RT dose/volume and Evidence Every Site Flashcards

(359 cards)

1
Q

Indications/Dose for gastric and gastroesophageal adenocarcinoma adjuvant EBRT chemoradiation:

Rationale and key studies.
Bonus if you can guess the chemo

A

Concurrent with cisplatin and capecitabine.

Indications
1) Stage:
T3 (T3=through serosa) N+ OR
T3 N0 with positive margins OR
T4 OR N+

ECOG 0-2
2) Adequate nutritional intake
3) Suitable for combined therapy

TOPGEAR (ongoing) looking at NeoAdj 45/25
INT OS/PFS/DM benefit to adj CTRT

BUT CRITICS Trial Peri-op Epirubicin Etop Carboplatin (ECC) c4 then surg then c4 equivalent to ECC surg chemoRT

45/25 (INT Trial) + consider 5.4Gy/3# boost to GTV if can be visualised.
Notify surgeon if both ends of anastomosis likely to be in field.
Chemo

MAGIC (Epirubicin-Cisplatin-5FU), updated to FLOT-4 (5FU-leucovorin-oxaliplatin-docetaxel) (From Neoagis esophagus fame).

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2
Q

Thyroid RAI doses

A

Iodine 123 study = 2mCi
Ablative dose = 30mCi

ESMO guidelines (US tend to be less):

Adjuvant = 100mCi
micro residual = 150mCi
Metastatic = 200mCi

Retreatment can be considered up to cumulative 600mCi (or significantly more if only low volume lung Mets)

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3
Q

Dose EBRT for thyroid cancer and indications:

A

60-70Gy 1.8-2Gy/#

It is optimally used in a small subset of pts w/aggressive locoregional disease.

A single randomized prospective trial failed to recruit adequate patients and only 26 received EBRT. However, a mounting retrospective data showing significant benefit for EBRT in select patients: with gross residual or unresectable locoregional disease, except for patients <45 years old with limited gross disease that is RAI-avid.

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4
Q

High risk prostate cancer: Definitive Brachy + EBRT dose:

Urinary function requirements?

A

Definitive radiotherapy:
HDR brachytherapy boost, 15Gy/1#
Or 18/2. There is no clear evidence on which dose/fraction schedule is superior, except RCT data suggests multifraction has better local control.

and

46Gy/23# EBRT

and ADT 18-36months (typically 2 years)

HDR brachytherapy can be given before, concurrent with or after the external beam radiation therapy.
The optimal dose, fractionation and brachytherapy scheduling has yet to be defined.

(15 and 15 is easier to remember and is recommended by EVIQ, in US they are way less picky/more aggressive).
IPSS < 15. If IPSS > 15, then formal flow studies
Caution:
Peak urinary flow r< 15 mL/sec or post void residual > 100 mL

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5
Q

Dose for SABR to spine met (e.g. prostate).

Some indications:
Which tumours are excluded?

A

24Gy/2 fractions (there are a very wide range including 27/3). Range: from 24/1 to 30/5.

Some indications:
Oligigomet disease as defined by COMET-SABR = 4-10
ESTRO ASTRO = 1-5

Oligoprogressive disease

Spinal metastases from the solid primary tumour (excluding haem seminoma and SCLC).
Life expectancy >3months
SINS score<12, >7 get consult.

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6
Q

For Int Risk Prostate Cancer: Conventional dose vs Hypo#

Evidence for Hypo# dose?

A

78Gy/39#
vs
60Gy/20#

60gy/20# supported by multiple Phase III trials: PROFIT, CHHiP, RTOG - these demonstrate non-inferiority (either with or without ADT, low or intermediate risk) and 2 studies demonstate no increased bladder or bowel toxity, one suggests more grd II/III late toxiciy.

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7
Q

Extensive stage SCLC dose?

Trial?

A

IF: Any response to systemic therapy and residual thoracic disease.
Limited extra-thoracic metastatic disease burden.

Consolidative dose: 30Gy/10#

CREST Trial:
CTRT improved 2-year overall survival (13% vs 3%) and 6-month progression free survival.

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8
Q

Limited stage SCLC dose?

Ideally concurrent with?

The alternative approach:

Give a little Hx of this dose:

A

(Concurrent chemotherapy is preferred - ideally with earlier cycles of chemotherapy. Eg cisplayin and Etoposide). Aim start cycle 2.

Currently Tiurrisi (INT0096) 45/30 BD remains the standard
66/33 CONVERT Trial found not superior (with trend favouring Turrisis.
Further escalation 70/35 not superior, and potentially more toxic.

Early trials demonstrated an OS benefit w/RT, subsequently confirmed on meta-analysis.
Turrisi 1999 - 45Gy/30# (1.8Gy/#) vs 45Gy BID (1.5Gy/#) (!!!These doses are not BED equivalent!!!) w/concurrent cisplatin etop.

IF Unlikely to tolerate full treatment: 40/15 to 50/25 +/-chemo

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9
Q

Extensive stage Small cell lung cancer PCI dose:

Discuss evidence.

A

Japanese RCT suggests for extensive stage pts PCI can be omitted in favour of close (3monthly MR) surveillance - original data suggesting benefit defined no cranial disease on CT (not MR) therefore a number of pts who truly had brain mets were included..

BUT Now! An NRG RCT has demonstrated that hippocampus sparing is safe and leads to less neuro cognitive SEs.

Complete responders: 25Gy/5#

Partial responders: 20Gy/5#s

Doses “partly” supported by metaanalysis. Original data (1999) supported OS benefit. RCT data suggests 25/5 as effective as 36/18…

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10
Q

Extensive stage Small cell lung cancer PCI dose:

A

20/5 or 25/5 both employed, or 25/10 with hippocampus sparing. RCT data = Slotman 2007 - better OS and less symptomatic brain mets at 1 year.

Japanese RCT suggests for extensive stage pts PCI can be omitted in favour of close (3monthly MR) surveillance - original data suggesting benefit defined no cranial disease on CT (not MR) therefore a number of pts who truly had brain mets were included..

Now NRG 25/10 hippocampus sparing minimal neuro cog tox (treated both limited and extensive).

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11
Q

Dose: Oligo mets to lung?

Criteria?

A

All evidence is at best phase II

48/4 near (<2cm) chest wall.
54/3 if not central. Less radio resistant Mets consider 28/1.
SABR to ultra central appears dangerous (increased haemorrhage). Recent SUNSET trial for NSCLC 60/8, no haemorrhage from 30 pts..

Oligometastatic/oligoprogressive/oligopersistent peripherally located (defined as at least 2 cm from the bifurcation of the lobar bronchi) lung metastases (0-3 metastases).

Tumour/s ≤5 cm in maximum diameter.

Supported by Phase II data:

30/1 or 54/3 - away from chest wall/not central
(phase II study, efficacy of a 30 Gy single fraction was found to have lower 2-year LC compared to multi-fraction SABR (74% vs 91% respectively).

Despite the 30/1 data suggesting inferior to 54/3, fucking TROG (those turds) did a trial. 48/4 within 1cm of chest wall - Saffron II TROG (phase II) suggests 28/1 equivalent to 48/4 and may be more immunogenic. The only exception being colorectal mets, where multi fraction may be better.

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12
Q

Indication for SABR for NSCLC and dose:

Target volume objectives!!!????!!

Key Study and finding!?

A

The below is from CHISEL which found OS and LC benefit compared with 66/33 or 50/20

1) Stage I-IIa non small cell lung cancer (NSCLC).
2) Tumour ≤5 cm in maximum diameter.
3) Peripherally located tumour defined as at least 2 cm from the bifurcation of the lobar bronchi.6
4) Medically inoperable or declining surgery.

IF tumour GTV <1 cm from chest wall, consider 48 Gy in 4 fractions (12 Gy/fx).

54/3 or 30/1

Target volume objectives!!!
iGTV = DMax 125-143% of PD
PTV= D99% ≥100% of PD.

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13
Q

Non-small cell lung cancer stereotactic EBRT central tumours?

Define central:

Define Ultra-Central:

Target volume objectives!!!????!!

A

For 1-2 (≤5 cm maximum diameter) N0 M0 non-small cell lung cancer (NSCLC). Centrally located tumour defined as ≤2 cm around the proximal bronchial tree (PBT) - NB not “ultra central”

Ultracentral defined as: PTV touching or overlapping the central bronchial tree, oesophagus, pulmonary vein, or pulmonary artery.

Dose for central 50/5
Dose for Ultracentral 60/8 SUNSET (or 60/15 LUSTRE Trial)

iGTV should get DMax 125-140% of PD.

PTV should get D95-99% ≥100% of PD.

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14
Q

NSCLC adj dose in post op patients found to be node positive:

A

Its a bit of a trick: A meta-analysis demonstrates no clear evidence of an adverse or beneficial effect of PORT on survival in patients with pN2 disease. The applicability of this finding to current day practice is questionable. Data from four non-randomised studies suggest a survival benefit for PORT in pN2 disease.

N2 = mets in ipsilateral mediastinal/subcarinal nodes

N2 [R0] disease - 50/25
N2 R1 - 54/27
N2 R2 60/30

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15
Q

The non-SABR NSCLC curative intent dose:

Evidence?

A

60/30

Bradley (RCT) Trial 2015: for stage III dose escalation to 74Gy not supported. Better survival in 60gy arm

For node negative patients not suitable for SABR consider dose escalation e.g. 66Gy/33# or moderate hypofractionation

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16
Q

Definitive EBRT dose for FIGO stage IB-­IVA squamous, adenosquamous or adenocarcinoma of the cervix.

A

SIB:
Pelvis and elective nodes: 45/25
Boost nodes 55/25

(CCCMAC)

A dose prescription of 40 Gy in 20 fractions is also in clinical use.

Chemoradiation therapy superior to radiation therapy alone.

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17
Q

Brachy boost dose for FIGO stage IB-­IVA squamous, adenosquamous or adenocarcinoma of the cervix.

What do you prescribe to?

A

24/3 aim 1-2#s/week depending on timing of brachytherapy in relation to EBRT.

EBRT same as definitive: 45/25,

Prescribe to HR-CTVbrachy (D90)
= 90% of High risk CTV receives at least 100% of the dose.

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18
Q

Primary curative intent doses for Oral cavity SCC

A

70 to Gross (+5mm) + involved nodes (66/33 if superficial).
63 to High risk = CTV70+5mm, BOT if tongue involved, equivocal nodes.
56 to elective nodes I, II, III, IV
Bilateral i close to midline or within 1cm of tip of tongue or >2 nodes
(Nothing lower than this)

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19
Q

T1 glottic/larynx

T2?

A

60/25

70/35

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20
Q

When might TPF be considered in larynx cancer?

What is the study?

For preferred treatment, what is the expected outcome

A

GORTEC

Consider TPF if downstaging stage IV (i.e. through thyroid cartilage) to persue “Curative” intent ChemoRT and bulky tumour compromises airway.

Overall both induction and concurrent chemo have been studied for larynx cancer (RTOG) with both having favourable results and long-term options arguably in favour of induction.

After definitive Mx OS is 35%

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21
Q

For Stg III and lower Larynx cancer, what is the benefit of concurrent chemo?
When consider it?
NOt fit for chemo, what is an option?

A

Increases rates of organ preservation.
- T2+ (bulky - remeber staging doesn’t include this significant prog factor).
- N+
- Hypopharynx!!

Overgaard trial - 6#s/week accelerated RT

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22
Q

Doses and systemic Tx (where applicable) and key studies for esophagus RT (all the indications):

What is the alternative?

A

ESOPEC. CROSS vs perioperative FLOT. FLOT4 wins 3yr OS 57% vs CROSS 50%

ESOPEC confirms and improves on NeoAegis = Peri-operative MAGIC/FLOT 3yrs OS 56%.

Neoadj:
Neoadjuvant CROSS
- 41.4Gy/ 23#/5, 1.8Gy/#, 5#/week
CROSS (weekly x5 cycles) (CROSS better than FLOT/MAGIC):
- Carboplatin (AUC=2)
- Paclitaxel (50mg/m2)

Definitive RTOG94-05/ INT-0123
- 50.4Gy/28#/5, 1.8Gy/#, 5#/ week
RTOG94-05/ INT-0123 (week 1,5,8,11)
- Cisplatin (75mg/m2)
- 5FU (1000mg/m2/day D1-4)

Palliative 30-36Gy/ 10-12#/5 (36/12 if you can get away with it).

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23
Q

Preferred salvage option for locally recurrent esophagus Ca (POST multimodal therapy):

A

Esophagus HDR brachytherapy:
25/5 ti 5mm depth and 20mm above and below.
Supported by multple retrospective and institution reports

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24
Q

The standard of care for medulloblastoma is?

Key factors that decide treatment?

CTVs
VMAT Technique:

A

GTR (90% recur with GTR alone)
Followed by CSI 4 weeks post (evidence says longer time worse outcome).
Dose = 54Gy/30# 1.8Gy/#, with CSI dose determined by risk group:
Average Risk: CSI = 23.4/13, boost post fossa to 54Gy/30
High Risk: CSI 36/20, bring PF to 54.30.

Followed by x4c of CVP (cyclophos, Vincristin cisPlatinum)

All PTVs 3mm
CTVcranial = entire brain + optic nerves + cribiform plate

Boost = GTVpre-op + surgical cavity+gross residual
CTV54 = GTV+5mm, clipped to boundaries

CTV spine: thecal sac, including neural/intevertebral foramen to 1cm below sac (~S1/2)

VMAT: 3 PTVs Cranial, sup and inf spine.

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25
Critical in plan review of a CSI peads plan: 3DCRT technique for CSI
Homogenous cover of the entire vertebrae to avoid scoliosis
26
Role of radiation and dose in: Solitary plasmacytoma Multiple Myeloma:
Plasmacytoma: Radiation is the mainstay, with surgery indicated only where stability is a concern - SINS score >8, Mirrels>8. Data is retrospective only. Give 45/25 - ISRT - i.e whole involved vertebrae. Or 40/25 if <5cm. For Extramedullary consider 45/25 to primary and 40/25 ENI MM: 30/10 Rarely now (most given Mephalan) TBI prior to ASCT
27
Radiation dose and rationale for primary CNS lymphoma.
Evidence supports a PFS but not OS advantage to WBRT. The critical treatment is Autologous Stem Cell transplant (if pt can get to that): Fit young Pt: High-dose methotrexate, Ritux and alk agent - Progression = salvage 36/20. Partial 23.4/13 (These are the same as the CSI doses for medulloblastoma). complete may omit WBRT. Elderly/not ASCT candidate: Chemo as above -> Partial/complete = 23.4/13, or watch and wait or maintenance e.g tmz Progression = Individualised care, including WBRT up to salvage 36/20. Unfit: Curative intent WBRT40/22 Palliative: E.g. 30/10
28
Marginal lymphoma doses:
Nodal, splenic, MALT (90%, GI 60%, 85% gastric): Orbital (12% due to chlamydia psittaci - gross) 24/12 (same dose as??, Deb uses 4Gy/2 55% contol), CTV = whole bony orbit Late tox: epiphora, cataracts, Gastric MALT: If failure of triple therapy (Claire's Amplified esophagus) of t(18,11): 30/10 entire stomach (GIJ to duodenal bulb) Fast 4hrs (commonly overnight).
29
Kaposi Sarcoma dose and evidence and broad Tx options available: Key warning to patient about outcome after XRT? Likely Outcome of RT
Surveillance can be considered but indolent progression highly likely (with a larger lesion the to be treated). * Surgery: Excisional biopsy is an option for single symptomatic lesion. Can provide sustained local control * Radiotherapy: Wide variation of dose (20Gy/10- 30Gy/15#) – higher dose has improved and more durable response * Topical therapy – limited experience with imiquimod * Cryotherapy – mainly cosmetic, no documentation of LC rate * Intra-lesion therapy – painful, not generally recommended Like other sarcomas can take 4 months to regress XRT - 80-90% LCR but significant risk of progression outside of field.
30
A 63 year old man presents with extensive symptomatic Kaposi lesion on his right lower leg extending from just below the knee anteriorly, involving the calf posteriorly as well as both dorsal and plantar surface of his foot. c. Describe a suitable radiation therapy technique including a dose and fractionation schedule (4m)
I will offer this patient palliative radiotherapy to the right lower leg lesion to a total dose of 20Gy in 10 fractions, 2Gy/X, VMAT technique for local control * An alternative technique is with water-bath technique, this is cumbersome, with less accurate dosimetry calculation, and on the assumption that the entire ‘water-bath’ (including the leg) is of homogenous density Sim * Position: supine, arms on chest, leg towards gantry, left hip/ knee flex to move left leg out of treatment field * Immobilisation: cradle under right leg * Clinical mark-up the symptomatic lesion, or wire the most superior/ inferior/ lateral edge of lesion * Bolus: 5mm bolus inside cradle, and 1cm bolus on skin anterior to the cradle * Planning CT: 3mm slice from mid-thigh all the way down to cover the entire foot Target volume * CTV20 will be 1cm thickness from skin surface circumferentially from superior to inferior marker, clipped at bone/ muscle fascia, and spare at least one strip of soft tissue * PTV20 = CTV20 + 5mm expansion Technique: partial arc VMAT with 6MV photon Plan review: * Ensure PTV well-covered by 95% isodose line * Minimise hotspot outside of PTV * Minimal OAR at risk of concern; important to ensure contralateral leg is not receiving any dose Treatment verification: daily kV imaging, with 5mm tolerance
31
Dose, and rationale for adj XRT post node dissection for melanoma. Volumes: For whom should you consider it?
Burmeister study: Improve LC (lymph nodes) from 60-80% CTVprimary - 2cm margin around scar CTVnodal - 3cm prox-distal (like esophagus) and 0.5cm axial. EVIQ CTVs: Pre-operative disease + surgical bed (including scar) ± margin as appropriate for potential sub-clinical disease. Consider non-surgically perturbed at risk nodal basin Dose 48/20 UNLESS H&N, Groin lymphoedema - 50/25 Burm's criteria at least 1 RF: 1 or more parotids, 2 or more neck (pr>3cm), 3 or more groin (or >4cm), ENE
32
Dose technique for average risk meduloblastoma
Avg = age>3, GTR w<1.5cm, not mets I will offer this patient cranio-spinal irradiation to a dose of 23.4Gy in 13 fraction followed by tumour bed boost to total dose of 54Gy/30#) (1.8Gy/#, 5#/ week). VMAT technique with 6MV photon- 3 isocentres (cranial, upper spinal, lower spinal), junction at 4cm depth, no feathering. Pre-SIM * Ensure recovery from surgery (but within 4 weeks!!) SIM * Positioning: supine, arms on side, head towards gantry * Immobilisation: on vac bag/ body cradle, thermoplastic mask * CT simulation: 3mm slice planning CT from vertex to mid-thigh * Fusion: with pre-op MRI, post-op MRI Target volume: * Phase 1: CSI 23.4Gy/13# (entire intracranial/ spinal subarachnoid volume) o CTVcranial = Entire brain, covering cribriform plate, and optic nerve o CTVspine = Thecal sac expand laterally to intervertebral foramina; inferior level must be determined on MRI (usually ~ S1-2) o PTVcranial = CTVcranial + 3mm o PTVspine = CTVspine + 5mm lat + 10mm AP + 10mm SI * Phase 2: Tumour bed boost 30.6Gy/17# o GTV: surgical cavity + post-op residual disease o CTV30.6: GTV + 5mm o PTV30.6: CTV30.6 + 3mm
33
Describe a suitable radiation therapy technique and dose fractionation schedule for 3cm Merkel cell carcinoma completely excised (R0) from the upper right lateral arm (over the deltoid) Give benefit, T1 vs. T2
SEER database suggests likely OS benefit to PORT. T2 = 2-5cm (consider PET even in T1 - 25% T1 and T2 get upstaged). Definitive EBRT alone 54Gy in 27 fractions, 2Gy per fractions to the right deltoid primary and axillary node + supraclavicular fossa to improve local and distant control, and overall survival. Pre-SIM: - MDM discussion Simulation: - Position: supine, arms akimbo, head towards gantry - Immobilisation: vac bag, knee fix, ankle support - Addition: wire scar, bolus 3-5 cm around scar/ primary lesion - Planning CT: 3mm slice planning CT from upper cervical to below diaphragm (cover the entire lung for DVH) Fusion: pre-op MRI/ PET Target volume: - CTV54 = (pre-op GTV and scar) + 4cm radial margin, and 1.5cm DEEP to skin down to fascia, clipped at anatomical boundaries - CTV51.2 (50Gy EQD2) = CTV54 + at risk nodal group (level 1-3 axilla and supraclavicular fossa) - PTV = CTV + 1cm margin for setup uncertainties Technique: 5-7 field IMRT technique with 6MV photons Plan review - Target coverage, PTV D98>95% - Minimise hotspot PTV D2<107%, ensure no hotspot outside of PTV or in OAR - Ensure low dose (10%, 50%) reasonably distributed around PTV - Try to spare a strip of skin/ subcutaneous tissue - Review OAR DVH o Brachial plexus Dmax< 54Gy o Ipsilateral lung: V20Gy<30%, V30Gy<20% Treatment verification: daily CBCT, matched to bone, soft tissue review
34
Describe a suitable radiation therapy technique and dose fractionation schedule for TBI. Justify your answer
DOSE PRESCRIPTION * 12Gy in 6 fractions, 2 Gy per fraction, 2 fractions per day, over 3 days * Prescribed to a single point at midline of the patient (usually umbilicus) * (Other dose options: 2Gy/1#, 13.2Gy/11#, 4Gy/2#) Pre-SIM * MDM discussion * Fertility preservation referral SIMULATION * Position: supine, upper arms on side resting on 4cm polystyrene (maximise lung shielding from lateral beam), and hand resting on abdomen * Planning CT: 3mm slice covering the entire body length (from vertex to mid-thigh) TARGET VOLUME * Entire body contour TECHNIQUE * 4-field equally weighted MV photons AP/PA and opposing lateral, with extended SSD (4m) and largest practical field size * 6/10/18 MV (avoid 18MV if possible) Alternate APPA and oppose lateral for each fraction (e.g. APPA for fraction 1, 3, 5, lateral for fraction 2, 4, 6) Lateral field Position: * patient lie supine, small sponge under head, knee fix, * Upper arm resting on 4cm polystyrene (to reduce lung dose) * Hand resting on abdomen * Trolley turn around for the opposing lateral field treatment Compensator/ bolus (‘beam spoiler’) – (because of skin-sparing effect of photon) * Super-flab – on lateral and anterior surface of neck + chest (to reduce dose to lung) * Perspex – as head frame compensator, and from mid-thigh inferiorly (thicker from mid knee inferiorly)
35
Doses and presim for pituitary adenomas:
SRS (non-functional) 14-16 Gy/ 1# SRS (functional) 20 Gy/1# Functional needs higher dose Fractionated SRT 25 Gy/ 5# (5 Gy/#) (BED~ 11-13Gy / 1#) (FSRT if: lesion >3cm size, or <3mm from optic IMRT/ VMAT 40Gy/ 15# (1.8Gy/#) 50.4 Gy/ 28# (1.8Gy/#) PRE-SIM * Baseline ophthalmology, neurology, and endocrinology review
36
Spine SABR: Rationale Contraindications Dose Technique
24Gy/2# Rationale - Compared to multi# EBRT, multiple RCTs demonstrate higher complete response rates at 3 months, BUT higher vert body collapse 17% vs 10%. In oligomet setting - COMET SABR shows OS benefit, Contras: Previous radiation at site!! SIN Score > 12 (caution 8 or more). >3 spinal mets (i.e. much higher risk of collapse) Tumour indenting cord (Bilsky 2) Not: seminoma, SCLC, haem malig Non-oligo or life expect <3mths Technique: sim CT + MRI fusion 8-Field co-planar, non-opposed 6-10Mv photons Prescribe to covering isodose Volumes: GTV on fusion CTV = GTV + CTV defined by International Spine Radiation Consortium (ISRC) guidelines. E.g Well lateralised Vert body then CTV = whole vert body + ipsi pedicle. e.g 2. Diffuse vert body, CTV whole v.body bilateral peds. PTV = CTV +2mm, EXCEPT trimmed off spinal cord!!! Verification daily 3D CBCT to bone.
37
Dose, volumes and rationale for RT in soft tissue sarcoma: Key studies:
Key studies: O'sullivan = RCT of pre vs PORT STRASS = retroperitoneal dont do RT unless relapse (if you have to to 50.4/28) SEER database Rationale: For higher-grade STS SEER multistudy reterospective analysis supports a benefit to RT in conjunction with surgical resection. Both pre and post have equivalent OS but differ in their toxicities - E.g higher wound complications (reversible) in pre vs higher fibrosis rates in PORT (not reversible). RCT supports Brachytherapy as approx equivalent LCR. For reteroperitoneal tumours surgery alone (STRASS). PORT not recommended, consider if recurrence. For extremities: Pre-Op: 50.4/28 (Myxoid liposarcoma 36/12) Some data demonstrating equivalent outcomes with 30/5!! GTV as delineated on all imaging (MRI T1+C) CTV = GTV + 1.5cm radial, 4cm (or 3cm) sup-inf PTV= CTV +1cm PORT: CTV60= pre-op GTV/tumour bed +1.5cm radial (as above) + !2cm! sup inf CTV50= CTV60+2cm sup-inf PTV = CTV50+1cm Definitive: At least 70Gy required for local control
38
Dose and technique for Hodgkins (and rationale/evidence and clinical information used to decide dose). Key Chemos?
(except for popcorn cell nodular lymph prodominant HL) Relevant studies in order of disease severity: HD10/EORTC, HD11, RAPID, HD15 (Stag III/IV). Risk = AMEEN = Age>50, Mediastinum>1/3rd, ESR elevated, Extra Nodal, Nodes>3. (1 or more = HR stg I/II). ISRT: GTVp = residual, GTVpre = prechemo. CTV=GTVp+5mm axial, and cranio-caudal expansion to cover GTVpre. If no GTV pre then 1.5cm. Stg I/II and low risk (H10): 1) x2ABDV then ISRT 20Gy (10yr PFS 10%) is standard 2) PET direct RAPID (fav or Unfav) x3ABVD no need for RT if PET-ve post c3. IFF +ve then x1ABVD the 30Gy ISRT Stg I/II and HR (AMEEN>0) H11 (10yr PFS 85% same as fav): 1) x4ABVD the 30Gy ISRT (i.e 10Gy more) 2) PET direct RAPID (fav or Unfav) x3ABVD no need for RT if PET-ve post c3. IFF +ve then x1ABVD the 30Gy ISRT Stg III/IV (HD15): BEACOPPx6 (dose escalation to x8 kills more ppl than it helps). IFF PET +ve or residual >2.5cm then 30Gy. Exception: urgent debulking of initially bulky - 30/15. ABVD = Adriamycin, Bleomycin, vinBLASTine, Dacarbazine - 1 month cycles, 2 infusions/mth BEACOPP= Bleo, etoposide, Cyclophosphamise, Oncoven (vincristine), procarbazine, pred.
39
What are the subtypes of Hodgkins, give dose/approach for the exception to the group:
HL = RS cells (CD 15 and 30) or Popcorn cells (CD 19,20 like NHL, and neg CD 15/30) Classical has 4 types (2 are assoc w/EBV): 1) Nodular sclerosing (70%) often mediastinum M=F broad band of bifingent sclerosing collagen 2) Mixed Cellularity (20%) EBV associated, often abdo/Spleen, M>F, Diffuse effacement of node with mix of lympocytes/plasma/eosin and RS Cells. No sclerosis 3) Lymphocyte Rich (5%): best prognosis 4) Lymphocyte Depleted EBV associated. Nodular Lymphocyte Predominant HL (5%) CD 19 and 20 (Ritux target). Frequently transform into DLBCL Stage I/II get upfront ISRT 30Gy then R-CHOP if PET +ve III/IV get R-CHOP +/I ISRT
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Dose/schedule and rationale for bladder preservation approach. Evidence for chemo?
Bladder preservation approach offers chance of preservation (66% at 8 years) with comparable OS to neoAdj chemo + surgery (both in order of 75%). Combined analysis of 2 trials favours hypofractionated approach for better LCR ~60%. Concurrent chemo is supported by multiple phase II trials that demonstrate LC benefit, one trial had a trend for OS benefit EBRT, Vmat technique 55Gy/20#, 5#s/week, to bladder and tumour volume (no clear evidence for ENI), 6MV photons, prescribed to D50. Concurrent with weekly cisplatin 35mg/m.sqr.
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Dose, technique and volumes for bladder preservation approach.
EBRT, Vmat technique 55Gy/20#, 5#s/week, to bladder and tumour volume (no clear evidence for ENI), 6MV photons, prescribed to D50. Conc w/Day 1 MMC 12mg/msq, and D1 and D15 5-FU 2.5g/msq (DFS BENEFIT, trend to OS). Pre sim: EMPTY BLADDER and Rectum. Maximal TURBT. Sim: supine head, towards gantry, vac bag immobilisation, w/knee/ankle fix. 2mm Slice CT+contrast mid-abdomen to upper 1/3rd femur. Fuse w/pelvic MRI. GTV: Gross tumour volume on imaging/cystoscopy, or is complete TURBT than pre TURBT volume. CTV = GTV+5mm on gross extravesicular extension, whole bladder, IF: bladder neck/trigone, CIS, multi tumour do prostate, or females 2cm urethra. IF posterior tumours ant vag wall.
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Broad Mx approach to germ-cell ball cancer Name some factors in Stg 1 that may influence your choice.
(never Bx) Orchidectomy with high spermatic cord ligation The Mx based on seminoma vs NSGCT: NSGCT: Any residual then resect. Lmited role for RT, LVI is critical (relapse 50 vs 15%), LVI = BEPx1, LVI neg = Surveillance. Seminoma Mx based on Stg (Stg 1 = TanyN0, IIa=N<2cm = N1): Stg 1 = Surveillance (15% Recurrence, but no OS risk) vs 1-2 cycles of carboplatin (unclear data for 1vs2) vs Para-aortic 20/10. The TE19 study suggests Chemo is as effective as RT (relapse rate 5%), but less toxic. Factors that may make surveillance bad = tumour>4cm, involves scrotum, raised markers post surg, poor compliance with follow up Stg II - IIa (single node<2cm) consider dog-leg RT 20/10 (30/10 to dose). Otherwise BEPx3 (or EPx4 if cant do B): BEP = Bleomycin (pulmfibrosis risk) Etoposide
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Mx post chemo residual ball cancer
<3cm do surveillance, >3cm do PET at 6 weeks. If neg surveillance, if+ resection (preferred) or RT
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Suitable dose and broad techniques (and rationale) for Ball cancer: 1) Node -ve 2) Single small node (<2cm)
Rationale: Decrease relapse rate from 15% to 5% 1) EBRT VMAT technique treating para-ortic nodes to 20G/10#s, 6MV photons, prescribed to D50. CTV20= IVC and aorta, from 2cm below renal apex to aortic bifurcation, expanded by 2cm and trimmed to anatomical boundaries. PTV = 0.5cm 2) Dogleg: As above but include common, internal, external and iliac vein to UPPER-BORDER of acetabulum
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For pancreatic cancer give the: Benefit/evidence and doses of EBRT for each situation it may be used.
Inoperable panc cancer has 5yr OS of 5%, operable has 25% One key role therefore is in borderline inoperable - where metananlysis suggests neoAdj ChemoRT may make 1/3rd operable. BUT the specific role of RT is unclear (PREOPANC 2), with 36/15+ gemcitabine -> surg ->x4cycle gem = x6FOLFIRINOX (both approaches are highly toxic w/50% Pt having "serious adverse events"). Operable: Resecection - if +ve margin metanalysis supports a LC benefit to 45/25. Inoperable: Very limited evidence of OS benefit to the addition of RT to Chemo - 50.4/28 MASTERPLAN trial is looking at 4 cycles mFOLFIRINOX SABR with chemo: 40/5
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Target volumes for pre-op extremity soft tissue sarcoma:
Fusion: MRI and FDG PET Target volume: - GTV = visible disease based on planning CT, and fused MRI/ FDG PET (T1 and T2 sequence + contrast) - CTV = GTV + 1.5cm radial expansion + 4cm sup-inf expansion (include all oedema on T2 sequence) - PTV = CTV + 1cm expansion
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Role and doses for Osteosarcoma?
Free knowledge: Histological Dx - characterised by osteoid production, and classified by site (central = within = conventional = 90% high grade, Juxta cortical most low grade, Extraskeletal is rare). RT only if: 1) Cannot be resected - neoAdj Chemo->70Gy->Adj Chemo (3 agents including methotrexate) 2) Further resection not possible:
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Roles and doses of radiation for mesothelioma:
Main role Palliative 20Gy/5# low dose equivalent to HD Other: 1) Neoadjuvant - investigational 2) Adjuvant: NOT if Extra pleural pneumonectomy (EPP)! Consider but don’t for pneumonectomy and decortication. RO 50/25 R1 50/25 and boost to 56/28. Phase 2 (MARS) says no benefit and may cause harm after EPP May be tolerated, await IMPRINT trial to see if any benefit. * SABR for oligo-mets No role Prophylactic RT to procedural tract
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Partial breast: Who, dose, technique, rationale:
At least 7RCTs have shown non-inferiority to WBRT IMPORT LOW: Unifocal. Age>50, IDC grd1 to 3, <=3cm, <3nodes (N1) 40/15, 5#/week, 3Dplanned tangents with FIF, Prescribed to ICRU83, 100% PTV>95%. Sim: breath hold - all that shit Volumes: Tumour bed on imaging (clips, wired scar) CTV=TB + 15mm, trimmed 5mm off skin and lung interface. PTV=CTV+10mm.
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For lung SABR define the doses in terms of tumour location:
Peripheral: >2cm from proximal bronchial tree = 54Gy/3#s UNLESS <2cm from chestwall - then 48Gy/4#s Central: <=2cm around proximal bronchial tree, but not ultra central. 50Gy/5# Ultracentral: PTV overlaps: proximal bronchial tree, pulmonary artery/vein, or esophagus. Controversial whether to treat with SABR - some reports of fatal pulmonary haemorrhage. SUNSET Trial 2024. Prospective phase 1 - 30Pts good LCR and no haemorrhage with 60Gy/8#s.
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Curative approach (and rationale) to a pancoast tumour (AKA?):
Superior sulcus tumour: 2 phase II trials show pre-operative chemoRT has superior DFS and OS compared to historical controls. Approx 50% 5yrOS. But other phase II data suggests chemo alone may be sufficient... DO ONLY if resectable (
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Give a dose prescription for SABR (doesnt matter which dose, the main bits are prescribed to and aim):
Curative intent SABR 50Gy/5#s (using central tumour), 1#/day, prescribed to 100% isodose, 6MV photons, DCAT technique. Aim Dmax within PTV 125-140% of prescribed dose, CI-100; 1.2-1.3, CI-50<5. PTV D98>100%PD. CI-100 = Ratio of Volume getting 100% of prescribed dose to volume of PTV. Should be 1.2-1.3 CI-50 = Ratio of Volume getting 50% of prescribed dose to volume of PTV. Should be <5.
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Technique options for SABR For the moving target which may be better. Describe it in detail.
Technique options - Fixed beam >7 beam – fixed beam angle, converging on one isocentre, with open field, mixed coplanar/ non- coplanar - DCAT technique – modulated; open field; doesn’t allow MLC covering PTV at any stage; preferred for moving target - VMAT technique – static target DCAT (dynamic conformal arc therapy) - MLC only modulate field edge, and doesn’t cover the PTV at all time (compared to VMAT where MLC can cover PTV at some) - Avoid Interplay effect i.e. shielding of PTV with MLC during VMAT, leading to underdosage of PTV due to tumour motion - VMAT is ok on apex
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Primary Tx for a T2NOMO nasopharyngeal carcinoma: What 2 factors may change volumes?
EBRT (VMAT partial arc 6MV photons) **alone**: CTV_70Gy/35# = GTV+5mm CTV_63/35 (EQD2 60Gy) = Entire nasopharynx + Sup: Skull base w/ovale and rotundum, inf sphenoid sinus **if >=T3** - whole sphenoid and cavernous sinus Inf: Soft palate Ant: posterior 1/3 of max and nasal sinus Post: Bilateral retropharynx nodes, ant 1/3 of clivus (**whole clivus if involved - i.e. T3**) Lateral: Pterygoids and parapharyngeal space. CTV 56 (EQD2 50): CTV 63+ Levels II-V. **If node +ve include 1B.**
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Treatment approaches for Primary CNS Lymphoma (with doses).
Divide into, young, elderly, and fit and unfit. Then response based (Autologous stem cell or WBRT or more chemo). Evidence: post chemo WBT improves PFS but unclear OS benefit. Unfit (for chemo): 40/20 WBRT or less All fit (young n old) should get HDmethotrex + ritux + Alkylating agent (eg TMZ). +/- further chemo then: If response: ASCT (preferred in young) or WBRT 23.4/13 No response/prog: Isofosphamide vs 23.4/13 then boost residual to 45/25 Fit elderly - 3 options: WBRT Maintenance TMZ or Wait and Watch
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The OARS of head and neck and Dmax
Brain stem/ optic chiasm = Dmax <54Gy Optic nerve Spinal cord = Dmax <45Gy Temporal lobe/Brain = Dmax< 60Gy, V40Gy<5cc Brachial plexus= Dmax< 66Gy Retina/ eye = Dmax< 50Gy Lens = Dmax < 8Gy Lacrima = Dmax < 30Gy Manidble = Dmax < 70Gy Carotid = Dmax <100Gy Parodid is a mean dose = Dmean 26Gy
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Describe suitable follow up regimes for Anal SCC, and some key principles.
Most recurrence is locoregional, so the role of CT CAP is unclear. 6 weeks clinical review with Ex. 3 months: MRI and PET, Ex, DRE * residual/progression should be Bx and plan for APR. Year 1 3 monthly w/Ex DRE +/-anoscopy/endoscopy surveillance) * Consider annual CT C/A/P if T3-4 or N+ Year 2 - Ex review 6monthly. Year 4 - 5 anus ally
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Dose and volumes for Anal SSC, what is the chemo?
>T1, then chemo= MMC + (5-FU or Capecitabine) (MMC essential, substitute for cisplatin as last resort) for improved LC and CSS SIB technique: CTV50or54: primary + 2cm+ whole canal/sphincters CTVnodes: inguinal, mesorectal, ischiorectal, pre-sacral, internal (inc obturator and external ilacs - do not do common. Non bulky (<2cm = <=T2): 50.4Gy/28 and 42Gy/28 - COVID Dose 45/15 Bulky (T3): 54/30 and 45/30.
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Describe suitable follow up regimes Post rectal (stg I to III) Ca Mx.
1st year: 3monthly: Physical exam/Hx 6monthly: - CEA for 2 yrs then annually for 2 yrs - DRE and sigmoidoscopy CT CAP at 1 year. 2nd Year: 24month - Hx/Ex, DRE/Sigmoidoscopy 3rd-5th years: Annual Hx/Ex Coloscopy every 3-5year
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Key anal cancer studies: Key principles in the timing of anal SCC XRT:
Nigro (1974) Retrospective study 30/15 + CTx (MMC+5FU) ACT1: Chemo improves LC and CSS compared w/RT alone. Other trial says cant omit MMC. No benefit to induction chemo. ACT2: MMC+5FU = MMC+cis isoeffective/isotoxic PLATO recruiting=ACT3 (T1 surg +/- adj), ACT4 (<4cm de-escalation 41.4Gy/ 23 = butt hole CROSS), ACT 5 (N+ and/or T>=3, boost to 61Gy). OTT should be minimised (Not>6wks) Treatment breaks are shit for tumour control avoided - BD or treat on weekend if any missed #.
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Concurrent chemotherapy for butt SCC?
5FU/ MMC (MMC IV D1 12mg/m2 + 5FU infusion 1000mg/m2/day D1-4 week 1 and 5
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Rationale for radiotherapy and chemoradiotherapy in dick cancers:
The goal is organ preservation. Benefit of concurrent chemo is extrapolated from vulva/anal. For adj Pelvis RT retrospective data is mixed. Some suggests DSS and OS benefit, especially where multiple nodes. Therefore, adjuvant RT is recommended following a PLND with +ve nodes.
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Doses and volumes for penile cancers: And benefit for each. Also, indications for concurrent chemo
Use 2gy/# cisplatin 40mg. 1) Definitive local: - Primary <4cm and does not involve cavernosum local +/- cisplatin - 60Gy/30#s CTV = GTV+2cm (alternative is brachy 60/5). Surgery seems about equivalent for local - 5yr OS 75%, 80% LCR. 2) Definitive advanced (surg is the standard approach): >4cm, or >=T3 (meaning cavernosus invasion or worse): 50/25 whole penis and inguinal/pelvis, boost primary (+ve nodes, or ece and dissection) to 66/33Gy. This supported by UK RCR. (PORT is the same but adds 60/30 to micro) >4cm or >T2 should always get concurrent chemo: E.g. cisplatin or cisplain + MMC 3)PORT: 66/33 to residual, 60/30 to R1and ECE, then 50/25 to everything else. Chemo is R1, ECE or very advanced. Benefit extrapolated from anal/cervix. RT added to CT may increase PFS to 30% from 15% (multi-institutional anaylsis). 4) NeoAdj is investigational InPACT (45/25).
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Broad statement on penile SCC node status, general Mx of penile Ca and evidence. Indications for treating nodes with RT:
Approximately 20–30% of patients with positive inguinal nodes have positive pelvic nodes. Lymph node status is a major prognostic factor for penile cancer. Surgery is the mainstay of locoregional treatment. There is a lack of high-level evidence to guide management. ECE or >2 nodes
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What does Adj RT add to chemo for dick cancer after inguinal surgery?
A multi-institutional retrospective analysis was carried out to review the benefit of adj RT to Adj Ctx after inguinal surgery for penile cancer. Found longer cancer-specific survival with ChemoRT (29%) compared with adj chemoalone (16%)
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Role of chemo in dick cancer: What is the trigger point for neoAdj and the level of evidence.
NeoAdj: 1) Bulky: resectable disease rarely cured with a single modality; therefore, consider NACTx prior to Iliac LND. 2) >2 nodes or bilateral nodes - Phase 2 support OS benefit to TIP (paclitaxel, ifosfamide, and cisplatin) or "TIP PIC". Adj: No diff bet adjuvant versus neoadjuvant chemotherapy or adjuvant versus no intervention, OS was higher with neoadjuvant chemotherapy compared to no intervention and PFS was higher with adjuvant compared to neoadjuvant chemotherapy.
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Types of vaginal brachy applicators (and role of each):
Vaginal cylinder (often segmented) - best for symmetric brachy Multichannel cylinder - For asymmetric dose (also e.g. to avoid bowel loop 80Gy) Tandem and ovoid or ring applicator (or tandem or ring): Cervix cancer Combined interstitial intracavity devices. Rotte applicator (a 2 channel tandem thing where both channels can go into the uterine cavity) - in rare case of intact uterus.
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In general terms, list the steps in treatment planning LDR prostate implant (3 marks)
Free knowledge: contraindicated prostate >60cc. Planning: - Based on TRUS volume - Contouring o CTV = prostate; PTV = CTV + 3mm (except 0mm posterior) o Urethra and rectum - Placement of seed ~ 100 through the prostates - Review DVH o PTV: V100>98%, V150% ~50%, V200%~ 13-18% , D100%>95Gy o Urethra: D10<210Gy, no 150% isodose line encircling/ in urethra o Rectum: V100<1cc, 70% isodose line away from anterior rectal wall - Seed ordered from overseas
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In general terms, list the steps in treatment that are involved with delivering an LDR prostate implant (3 marks)
- GA, lithotomy position - Prep and drape - IDC and injection of ~120mL mixed normal saline/ contrast - TRUS probe per-rectum, ensure image closely resembles volume study - Interstitial needle inserted using template and under ultrasound guidance, and position checked - Stylet (with radioactive seed) deployed - Interstitial needles removed, leaving stylet (with radioactive seed) in situ - TRUS probe removed - Cystoscopy – to check bladder and urethra of any seed, trauma, obstruction
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For Ewing's give the indications for PORT and approach (dose/volumes). How does the PORT differ from definitive?
PORT dose = definitive (post chemo) dose. Post operative volumes based on degree of necrosis (<90% necrosis = bigger volume = pre chemo GTV). Indications for PORT: * Positive (R1/R2) or close margin <1cm * poor response to chemotherapy (<90% necrosis) * tumour spill * For tumour spill, boost pre-chemo volume 45Gy/25# to pre-chemo volume then boost to 54/30 as below (I.e the only thing that changes is bigger volume if worse/less necrosis): IF post CTx NECROSIS >90%, then boost 9Gy/5# (1.8Gy/#) to post-chemo GTV (smaller volume) IF NECROSIS <90%, then boost 9Gy/5# (1.8Gy/#) to pre-chemo GTV (bigger volume) = forget post-chemo GTV and simply treat 54/30 based on pre chemo GTV.
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For Ewing's XRT (PORT or curative), what are the planning considerations?
* Do not treat across a joint/ encompass an extremity circumferentially (i.e. need to spare a strip), unless absolutely necessary for tumour coverage * Reduce margins if there is no extension beyond joint space, but adjacent epiphysis is in volume * For diaphyseal lesion, exclude one epiphysis of the affected bone, if possible * If CR to chemo, boost post-chemo volume * If incomplete response then boost pre-chemo volume
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For Ewings, what is the chemo, and timing of chemo in relation to XRT in the following settings: Definitive Adjuvant With treatment what is the expected outcome?
VDCA-IE – VDCA+IE better than VDCA alone in CCG-7881 trial (5yr OS 72% vs 61%) Induction chemotherapy 6 cycles Q2W (=12 weeks) o Chemotherapy break for surgery (week 13) o Adjuvant chemotherapy (restarted as soon as possible) to 48 weeks (i.e. total of 24 cycles) o If definitive/ adjuvant RT, start with cycle continue chemotherapy (withhold doxorubicin during RT)
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Not a dose/technique question. But very high yield. For each tumour marker, state which tumours can elevate it (i.e. not all of these are routine by any means). 1) CEA 2) CA15.3 3) CA 125 4) CA19.9 5) AFP. Give half-life 6)Beta or just hCG. Give half-life 7) LDH 8) Calcitonin 9) NSE 10) S100
1) CEA: Colorectal Ca, colangiocarcinoma, medullary thyroid 2) CA15.3: Breast 3) CA 125: Ovarian 4) CA19.9: Pancreatic Ca 5) AFP: NSGCTs = yolk sac and embryonal, Liver HCC 6)Beta or just hCG: choriocarcinoma, some mixed NSGCTs, and approx 10%seminomas that express it. 7) LDH: Melanoma, Myeloma, Folicular lymphoma, DLBCL 8) Calcitonin: Medullary thyroid ca 9) NSE: can be a marker of SCLC 10) S100: melanoma - not routine at Dx/or ever
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Another high yield non Dose/technique question: Relate radiation (maximum) doses to fertility and ovarian/testes function:
Males: - Infertility if >6Gy - Reduced sperm count (and North Queensland quality sperm) 0.15-0.5Gy - Azoospermia 0.5-6Gy - Leydig dysfunction 10-15Gy Ladies: - Permanent: >12Gy prepubertal, >2Gy near menopause - Hormone insufficiency 10-15Gy (same as Leydig)
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Timing of adjuvant breast radiotherapy after chemo
4-6 weeks
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Dose/approach to endometrial Ca: State benefit and study
All get TAH+BSO+lymph node sampling + washings (peritoneal sampling if serous carcinoma). Stages: 1A = Observation (includes 1AmPOLEmut) 1B = VBT 28/4 (GOG99) consider ommitting 1C= Pelvic RT alone (45/25, SIB 55 to nodes) GOG249. VBT may be reasonable (PORTEC2) 2-IVa = ChemoRT (cisplatin 5mg D1 and D20) 45/25 pelvis and bed + VBT 10Gy/2#s (PORTEC 3) Definitive: EBRT 45/25 pelvis,SIB nodes 55Gy, VBT 21/3.+ Chemo. Or for IA definitive brachy: 27/3 Salvage (if no previous Rad): 45/25 (55 to nodes), 21/3 VBT - Observational data only. + Chemo. Whole abdo RT for IIIC/V 30/20 is shit compared to chemo alone.
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Broadly, staging (which determines dose) in endometrial ca is based on?
Stgs based on: Invasion, extensive LVI, fav (grd I-III) vs aggressive (III, serous, clear cell), local (stg III) regional (III) systemic. POLEmut, p53abn.
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In the setting of endometrial cancer - For VAGINAL BRACHYTHERAPY: Give doses and origin of dose:
Definitive: For IA in-operable: 27/3 PORTEC 2 - VBT adj alone. Stage IB 21Gy/ 3, 7Gy/ , 1-2 #/ week * Prescribed to 5mm from surface of cylinder * Dose to 5mm cranial from vaginal vault along the axis of cylinder should not vary more than 10% of prescribed dose PORTEC 3 - ChemoPelvis and VBT if stroma involved. * 10Gy/ 2, 5Gy/#, 1-2 #/ week * Prescribed to 5mm from surface of cylinder
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Stg II endometrial Ca what get brachy? outline the technique.
Stromal involvement: Vaginal vault brachytherapy * Position: supine, use largest vaginal cylinder that will fit comfortably to minimise air pocket * Target volume: upper half of vagina * Dose/fractionation: 10Gy/ 2#, 5Gy/#, 2#/ week * Technique: HDR brachytherapy with Iridium-192 radioactive source, prescribed to 5mm from surface.
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Approach to cranipharyngioma (and dose).
If GTR then >90% dont come back = observation. STR = 70% recurrence = Adj RT = 54/30.
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Indication for adjuvant therapy for heterotopic ossification? Timing? Dose/fraction? Benefit? Alternate treatment?
If recurrent. <24hrs pre-op, <72hrs post. Dose fractionation - 7Gy/1# , AP/PA dose to midline, spare a strip of soft tissue. Reduces risk of recurrence to 10%. Alternative - Surgery followed by NSAID (indomethacin 75-100mg/day) for 7-14 days post-op
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For pineal tumours what are the indications for CSI
Germinoma - do CSI if Mets NGGCT - do CSI IF Mets OR No response to induction chemo. After induction carbo-etop (4-6 cycles): Germinoma (always 1.5Gy#s): Mets = CSI (1.5Gy/#) 18/12 + GTV boost to total 45Gy/30#. NGGCT (always 1.8Gy#s): Mets or No response to induction CSI (1.8Gy/#) 36Gy/20# (1.8Gy/#) + 18Gy/10# boost to GTV (total dose of 54Gy/30#)
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Approach to pineal tumours (not ependymomas)
Always aim GTR. Pineal parancymal tumours if GTR then obs, if STR consider RT. Germ cell: InductionCT (carbo etop) x4 if germinoma, x6 NGGCT: Radiation based on class, and induction response (CT/PR/none) and mets. 1) Germinoma (always 1.5Gy/#, total 30 or 36Gy): CR: 30Gy total. WVRT 18Gy/12# + GTV boost 12Gy/8# PR: 36Gy total. WVRT 24Gy/16# + GTV boost 12Gy/8# Mets: 45Gy. CSI 24Gy/16# + GTV boost to 45Gy/30# 2)NGGCT (always 1.8Gy, total 54Gy) CR/PR: WVRT 30.6Gy/17# + GTV boost 23.4Gy/13# = 54Gy No-response or mets: 36Gy/20# (1.8Gy/#) CSI + 18Gy/10# boost to GTV (total dose of 54Gy/30#) + 9Gy/5# to bulky spinal met (total dose of 45Gy/25#)
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Brief epidemiology and associated risks for AVM. How are they graded? Indication for XRT? Relate to treatment options:
1/2000 people. 2-4% chance of bleed/year, At each bleed - 30%chance of morbidity, 10%chance of death. Biggest risk for bleed is a previous bleed. Present from birth, average age become clinically apparent is in 30s. Graded (Spetzler-Martin) score 1-5: based on Size (<3cm, 3-6,>6cm), location (eloquent/non-eloquent), Presence of deep venous drainage. Size >4cm attempt emobilisation to facilitate surgery/SRS Surgery Tx of choice where possible. Improves seizures indicated in S-M score 1-2 (may not be possible in eloquent brain or deep venous drainage). SRS - tumours <3cm Observation: may be only option, if previous, aneurysm or deep location should be avoided if possible.
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For AVM give indications dose and expected outcome.
SRS for tumours <3cm. with dose 16-20Gy/1# (GTV on angiogram). Outcome 80-90% at 3years (requires endothelial proliferation to cause obliteration), in latent period risk of bleeding is unchanged.
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Epidemiology of acoustic neuromas: Preferred approach and why? XRT dose and outcome:
8% Brain tumours, 96% of NF2 get them (often bilateral), 5%NF1 (also oft bilateral). M=F. Merlin is a Schwan cell tumour suppressor protein (gene on chromo 22), dsPyfunction ->proliferation. Note: While no RCT data, meta analysis of available data shows no diff in LC or tox bet SRS or SRT. Preferred Mx = surgery, especially in younger Pt - allows debulking and reduction of BS compression (but signif risk hearing loss if tumour >2cm) Observation=6-12month MR, if growth>2.5mm/year or hearing loss/worsening Sx need Tx. SRS: 12.5Gy/1# for tumours <3cm and PTV not on BS. Otherwise..... SRT: 25/5 Outcomes growth arrest (=LC) 85%@3yrs. It’s possible some crazy big tumours need VMAT 50/25.
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Gamma Knife based brain SRS, ???% is usually chosen as the prescription (marginal) dose. Typical prescription point for SRS
Gamma Knife based brain SRS, 50% is usually chosen as the prescription (marginal) dose. We (Hamilton) prescribe to 100%, other places prescribe to 60-80%, it’s apparently not an arbitrary choice. Lower dose point leads to faster dose fall off, remember radiation necrosis is partly a function of volume irradiated.
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Dose and technique for adjuvant SRS post resction of a brain met: Evidence?
You could do WBRT (e.g 30/10) isoefective control - but more neurotoxicity and time toxicity (2 phase 3 trials). Neither SRS or WBRT is better than observation in terms of OS. SRS 12-20Gy ALIANCE Trial SRT if <30cc 27Gy/3# If > 30cc 25Gy/5#s Adj SRT to the surgical cavity, VMAT technique, 6mV photons, Prescribed to 100% isodose line. Sim: patient supine, head towards gantry, arms by side, knee rests, comfort measures. Imo: thermoplastic mask. Contrast CT 1mm fine slice - vertex to C4. Planning MRI T1+C. HighRiskTumourVolume=HRTV=Surgical cavity CTV = HRCTV + any GTV + 2mm (may include tract and/or dural margin). PTV: =GTV +3mm OARS: in 2Gy/# (I would convert for SRT): Brain stem <45Gy, Brain Dmax<60Gy, V40Gy<5cc. Verification: daily CBCT matched to bone
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Volumes for adj cavity/brain SRT: Dose? When should you be cautious when using SRT? As an aside what should be done about asymtomatic brain mets (if possible)
GTV if any (though if residual present is technically post operative SRS) High Risk Tumour Volume=HRTV=Surgical cavity CTV = HRCTV + any GTV + 2mm (may include tract and/or dural margin). PTV: = CTV +2mm (1-3mm) DOSE: 30/5 (if >3cm). OR 27/3 IF<2cm Caution >5cm, Change to WBRT at about 5.5cm. Osimertinib only if Exon 19/21 EGFR mutations.
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Options for Liver HCC? SABR dose?
No RT or TACE if Childs C (caution in B) 1) Surgery: -Solitary tumour<2cm do Partial/hemihepatectomy -2-3 lesions or a single lesion <5cm (Milan criteria) aim liver transplant with bridging therapies while waiting (see below). 5yr OS70% (best chance survival) 2) Ablation: - Thermal = RFA if <3cm 90%CR, 2-5cm 50-70%, Microwave improved CR for tumours up to 5cm. - Non Thermal = Irreversible Electroporation: preserves structural integrity of. bile ducts and vessels (used more in pancreas). 3) Trans Arterial Embolisation - +Chemo (TACE) Yttium-90 microsphere (TARE). Local response 50% (TARE up to 70%) - For lesions too large for TACE (>5cm) - 85% post-embolisation syndrome 3-4days, 15% irrevesible liver injury. 4) XRT - preferred in patients w/vascular invasion, portal vein thrombosis: SABR 30 or 50 in 5# (LC up to 90%). Conventional 66/33 (French), Palliative whole liver 10/2 for 60%response rate 5) Systemic - no chemo, but Sorafenib increases OS 2-3 months 6) Sorafinib + SABR for disease unsuited to other treatments.
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Preferred liver mets SABR dose, and EVIQ range: Inter# interval? Indications
54/3. 3# doses range from 42/3 to 54. Large (i.e 5-6cm) consider 5# 40/5 up to 60/5. 36-96hrs apart Ideally 1-3 Maximum diameter 6 cm, or combined ≤10 cm, larger Solitary oligometastatic or oligoprogressive disease. No evidence of nodal or distant mets Unresectable mets or patient unfit/declines resection. If cirrhosis; Child Pugh score A/B maximum 7 points. Adequate liver function If close to kideny do split renal function.
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Role and doses for XRT for HCC:
Can be used in bridging prior to transplant. In combination with other therapies (e.g. TACE+RT reduces recurrence in tumours>3cm). Preferred in patients w/vascular invasion, portal vein thrombosis. Some retrospective data suggests better LC with SABR compared to RFA, SABR 30 or 50 in 5# (LC up to 90%). Conventional 66/33 (French), Palliative whole liver 10/2 for 60%response rate In patients unsuitable or refractory to TACE Sorafinib OS + SABR for disease unsuited to other treatments. SABR adds 3-5 Months OS = 16months.
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SABR doses and volumes for liver HCC
Rationale: Equivalent local control to historic RFA (90%<3cm, with better control than RFA for tumours >3cm). SABR: 30/5 to 50/5 1#/day 5#s week, prescribed to 100% isodose. 4DCT Contrast CT 1mm slice (HCC enhances on arterial phase only). + MRI Volumes contoured on MIP and checked across all phases of respiratory cycle. iGTV= All parenchymal (iGTVp) + vascular (iGTVv) on imaging. CTV=GTV PTV=CTV+5mm Motion management system. Mean liver dose <28Gy
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In what curative setting would you use RT for cholangiocarcinoma? What is the benefit? Dose?
Phase 2 SWOG trial for T2-T4 node positive resected Ro or R1: Adjuvant RT increases OS compared to historic data (Median OS=3yrs). 45/25 nodes 54/30 to bed 59/33 to R1.
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Approach to Inflammatory breast cancer: 5yr OS
NeoAdj chemo -> Mastectomy +ALND -> Adj RT + Receptor targeted therapy You need pre-treatment clinical photos. There will never be an RCT, but large retrospective studies demonstrate control benefit of escalation>60Gy. MDACC (largest study): 66/44, 1.5Gy/#BD, CTV 3cm beyond scar + Bolus until skin rxn too significant. Do this for age<45 or residual post chemo, otherwise can de-escalate - e.g. 60Gy. 5yr OS =40% If no residual post
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28F w/ Left inflammatory breast cancer, has neoAdj Chemo, mastectomy and ALND. 2cm CW residual, and 14/16 nodes. What do you do (dose, volume)?
MDACC suports dose escalation in this patient (up to 66Gy). I would treat chestwall and undissected nodes including IMC to 50Gy/25, then boost chest wall to 16Gy. VMAT, DIBH. Bolus as long as tolerated. CTV50= GTV+1cm (trimmed to boundaries) + whole chest wall and nodes (level III, SCF, IMC) PTV=CTV+5mm CTVboost= GTV+1cm (trimmed to boundaries) + whole chest wall
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Besides chemo, Surgery and RT, What adjuvant treatments need to be considered for pre-menopausal women with receptor positive breast cancer?
The SOFT-Text trial: Ovarian suppression (for 5 years, GnRH agonist=goserelin) added to either AI or tamoxifen improves DFS and OS. In particular women <35, T>2cm, or grd III, where an AI is preferred to Tamox due to improved DFS and decreased distant failure. Begin Ovarian suppression at start of chemo
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For limited stage SCLC Describe a suitable radiation therapy technique and discussion of organ at risk tolerances. What’s your CTV expansion on the primary? The chemo? Also Outcomes
5yr OS = 30% Curative intent EBRT 45Gy/30#s, 2#s/day, at least 6 hours apart, 10#s per week. VMAT technique, 6MV photons, prescribed to D50. Concurrent with chemotherapy = Carboplatin + Etopside. iCTV=iGTVp + 7mm, iGTVn+5mm PTV+7mm
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OARS and tolerances for chest XRT
LUNG: Mean lung dose <20Gy, V20gy<30% Heart: MHD<20Gy, Spinal cord DMax < 50Gy Esophagus Mean< 25Gy, Dmx<66Gy Brachial plexus DMax<66Gy
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Discuss the effects of ionising radiation on the foetus in the first trimester, and how these are known. What are the maligancy, retard and threshold risks?
Quick numbers. Malignancy 6% increase in absolute risk/Gy. IQ 25 points/Gy threshold hold dose for effects is 0.1Gy: During the organogenesis phase of foetal development the foetus is at most risk from radiation. Studies of atomic bomb survivors, and other disaster exposures, combined with animal studies demonstrate: A threshold dose of 0.1Gy W/general features of Interuterine growth restriction, Cognitive impairment, and future malignancy (6% increase absolute risk/Gy) risk being proportional to dose and also the phase of development at which exposure occurred: Exposure during (Germinal) pre-implantation phase (day 0-10) - often fatal/failed implantation. Organogenesis (Embryonic) phase (up to 6 weeks): Highest risk of congenital abnormalities, especially CNS (microencephaly). Severe intrauterine growth restriction (due to cellular depletion). Foetal period 6 weeks to 9 months: 1) Mental retardation - 25 IQ points per Gy, threshold 0.1Gy, due to failure of neurons to migrate peripherally. 2) Microcephaly 3) Eye, skeletal, genital abnormalities 4) Intrauterine growth restriction
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For salivary gland tumours, indications for XRT Approach to nodes
Benign (e.g. pleomorphic adenoma): Controversial - doses up to 60Gy Malignant: Low grade (e.g. Maligant mucoepithelial carcinoma): Surgery and observation. High grade PORT: 63/30 to R1, 60/30 to R0. 54Gy to nodes (1B II and III). All adenoid cystic carcinomas. Close margins (<2mm) PNI T3-T4 Node +ve/ENE ENI: All HG - But dont bother with ACC N0 = cover IB-III N+ = cover 1B, II-V PNI: Treat to BOS if: cPNI, rPNI, named nerve, extensive PNI, or adenoid cystic
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High-grade salivary cancer PORT dose:
63/30 to R1, 60/30 to R0. 54Gy to nodes (1B II and III, Unless node + then do 1B to V). Exception ACC don’t do nodes unless involved nodes (very rare).
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Indications thyroid EBRT and doses (and broadly, the targets)
Generally age>45. ENI: II-VII MTC: If extensive nodes, residual or extension beyond the thyroid. PTC/FTC: Poor I-131 (e.g. Hurtle cell), I-131 failure, >T3b (Extra thyroid/capsular extension), Gross residual post op. Anaplastic: Always do PORT, or start 70Gy ASAP if inoperable. Median OS 3months, 5yr OS 10%. 70Gy (or 66/30 to gross residual) 66/30 - to residual/gross 60
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A patient with
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Dose for Merkels: And principles of volumes Potential immunotherapy? Role of Chemo?
With RT - LC 75%, 5yr OS 50% (remember often elderly, immunesupressed). Definitive 60/30 SIB: CTV60 = GTV +4cm, and 1.5cm deep or to muscle fascia. CTV54 = CTV60 and a strip to at risk nodal groups. PORT: T1 (<2cm) dont need, but strongly consider nodes (but do need LNBx). 1) R0/no ECE: SIB to max 50/25. CTV50= scar +4cm + 1.5cm deep/dwn to fascia. CTV45= strip to at risk nodes + those nodes. 2) R1/R2/ECE Treat like definitive Avelumab is investigation Stg I-III Chemo: Consider in stg >I, But no clear role, carboplatin as radiosensitiser.
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Your exam doses for the Head and Neck sites PORT and Definitive
Definitive Naso: 3 dose clouds SIB in 35#s: 70GTV+5mm, 63Gy HR, 56Gy nodes II-V (include IB if node+ve). I.e clouds drop by 7Gy. Definitive: 70/35 GTV+5mm 63/35 = HR = equivocal nodes, Oral = entire BOT if tongue involved. Oropharynx = also entire BOT if tongue involved. Larynx = entire larynx. Hypo pharynx = entire hypopharynx. Glottic T1 (limited to vocal cords): RCT supports 55/20 for T1, with concurrent chemo improving preservation. 80% 10yrs. >T1, as above. PORT: in 30#s, 63Gy (if +ve margin/ECE, historic data from the Peters Trial for ECE), 60Gy to bed and +ve nodes, 57Gy to dissected neck, 54Gy to undissected neck.
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Subsites of the hypopharynx?
Subsites: 1) Piriform sinus, 2) posterior pharyngeal wall 3) Posterior cricoid
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For Larynx and hypopharynx when would you add level VI. What nodal group is the retropharynx? When would you include it
Level VI If: Larnyx - Include level VI for subglottic disease Hypopharynx: - Piriform sinus - All T4 (i.e. invading cricoid or carotid ect). Retrophaynx VIIa and VIIb. If posterior pharyngeal wall involved include at least 1 side. Also extensive level II involvement.
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Evidence and roll of adding chemo to RT for H&N PORT
Pooled analysis of 2 RCT demonstrates OS benefit IFF ENE or +ve margin. Interestingly no clear benefit for +Nodes even >5+,
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Options for voice restoration post total laryngopharyngetomy:
1) Preferred: Tracheo-oesophageal speech +/- one way valve. Best voice sound, less difficult to master than esophageal. 2) Electrolarynx: Easiest, but most mechanical voice. 3) Esophageal Speech: Most difficult to master (basically talking with burps).
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Endometrial cancer: What are the indications for vaginal brachytherapy in the post-operative setting? (2 marks) .
Curative intent stage 1A: Brachytherapy alone (not favoured approach) for inoperative/declined operative intervention. 27Gy/3# As part (adjuvant post surgery) curative intent treatment. 1) Stage 1B (>50% myometrial invasion, no LVSI, limited to uterus), without pelvic EBRT. E.g. 21Gy/3. (PORTEC2) 2) Stage II (extension beyond uterus where stromal invasion has occurred) in addition (brachy boost) to pelvic EBRT. 10Gy/2# 3) Stage III and IVa. In addition (brachy boost) to pelvic EBRT. e.g. 10Gy/2# (PORTEC3).
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ii. Discuss the use of chemotherapy in uterine cancer including in your answer the rationale for its use. (2)
RCT Data (PORTEC3) demonstrates at 5years concurrent chemo (weekly cisplatin) followed by adjuvant x4 cycles (Carboplatin Paclitaxel) can provide LC, FFS and OS benefit when concurrent with radiotherapy. It may be considered from grd 3 stg1. Sub-analysis of PORTEC3 shows the benefit of chemo is primarily in any of the following: Stage III (serosa or nodes involved), Papillary Serous or p53abn.
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Adjuvant brachy alone for endometrial cancer - give dose and technique:
Assume stage 1B: Adjuvant vaginal vault Brachytherapy (Ir-192 source, remote after loader technique), 21Gy/3# to the upper 1/2 of vaginal vault prescribed to 5mm from cylinder surface. Pre sim: Full discussion of procedure for consent. Analgesia, comfort measures as appropriate. Dilator education with educator (to begin 4 weeks post). Sim: Patient in lithotomy position. Manual examination and selection of appropriate vaginal cylinder/cylinder segments. Aim largest size that is comfortable to minimise air gaps. Plan selected from Plan library for applicator selected. Planning system to provide dwell times for after loader. OARS: Rectum, Bladder. Verification: External measurement from labia. Dose Delivery (in specialised bunker with video/audio monitoring, interlocks) via remote after loader.
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Discuss the role of systemic therapy in the management of metastatic prostate cancer. Include in your answer the class of agents used, duration of therapy and justification for use.
Anti-androgen medications - Typically non steroidal anti-androgens (e.g. Bicalutamide): In hormone naive pts: part of initial therapy + GnRH agonist +/- abiraterone (e.g.STAMPEDE) increases progression free survival, and OS. Alternatively can be used for 3-4 weeks as part of commencement of GnRH agonist - to prevent testosterone spike from initial LH surge. Can also be used when progression despite GnRH agonist (“total androgen blockade) to prolong PFS. ADT+ Apalutamide superior DMFS (SPARTAN). Used life-long or until significant progression. GnRH agonist (e.g Goserelin), provides an PFS, OS and Sx benefit in patients with newly Dx metastatic prostate cancer, and is part of multimodal therapy as above. Duration life-long, or until progression, or in the setting of stable disease intermittent (restart when >10ng/ml). Androgen synthesis inhibitor - Abiraterone: Improves OS and PFS (STOPCAT RCT)- used in the following contexts - as initial therapy for newly Dx metastatic disease (in combination with ADT but not ADT+Enzalutimide), or when progression on ADT. Chemo - Taxane chemotherapy - Docetaxel, improves PFS and OS (CHAARTED phase III RCT OS increase from 48 to 58months) when part of initial Mx of metastatic disease. Also increases OS for N+ and locally advanced (STAMPEDE). 75mg/m.sqr (65mg for Asians) until response (up to 10 cycles).
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In NeoAdj rectum, When may long-course be considered over SC
Traditionally, LC-CRT was preferred over SCRT in patients with locally advanced tumours whereby ‘downstaging’ is required to minimise the chance of a positive circumferential resection margin or maximise sphincter preservation. The lesser ‘downstaging’ effect of SCRT may be overcome with a longer delay to surgery or addition of pre-operative chemotherapy (i.eTNT approach).
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For rectal cancer: Neo-Adj long course RT is concurrent with? What is the evidence for chemo?
Capecitabine 825mg/M.sqr BD, or continuous 5-FU daily (better than bolus), dont 5-FU dMMR/MSI patients. Studies from the 1980 and 90s suggested a LC and OS benefit to chemo in post op setting, more significant in the concurrent setting. In the the neoadjuvant setting concurrent improves LC compared to LCRT alone. Recent trials have demonstrated that total neoadjuvant therapy may avoid TME (OPRA - 54Gy+cap -> FOLFOX/CAPOX, or FOLFOX/Capox->54Gy, radiation before better trend) can achieve 50% 5yr preservation rates, w/no change in 5yr DFS = 75% = historical control. Recently PROSPECT RCT trial demonstrated that neoAdj RT could be avoided (if >20% response on MRI to FOLFOXx6 AND followed by TME and more FOLFOX).
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A 45yro patient is clinically staged as having an adenocarcinoma of the mid rectum with tumour invading the prostate gland. Multiple mesorectal lymph nodes are present. (cT4N2M0). A decision is made to proceed with pre-operative, long course chemo-radiotherapy to the pelvis. Dose and technique including Chemo & Sim. (not volumes) only:
Neoadj long-course chemoRT, EBRT to a maximum of 50Gy/25#, 2Gy/#, 5#s/week. VMAT SIB technique, >=6MV photons, prescribed to D50. Concurrent with oral capecitabine 825mg/m.sqr BD. Pre-sim: consider if defunctioning indicated, fertility counseling, analgesia, anti-emetics. Comfortably full bladder, bowels empty (enema) prior to sim and each treatment.
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A 45yro patient is clinically staged as having an adenocarcinoma of the mid rectum with tumour invading the prostate gland. Multiple mesorectal lymph nodes are present. (cT4N2M0). A decision is made to proceed with pre-operative, long course chemo-radiotherapy to the pelvis. Volumes OARS
Volumes: GTVp= GTV on imaging and endoscopy GTVn= Positive nodes on imaging. CTVp50= GTV+1cm craniocaudally, + mesorectum and pre-sacral space at these axial levels. CTVn50 (if outside above volume) = GTVn +5mm. CTV45=CTV50 p and n, Entire mesorectum (+1cm anterior internal margin for bladder filling) and presacral space, external iliacs (as prostate involved), obturators, and internal iliacs to bifurcation. Entire prostate. PTV=CTV45+1cm OARS: Bladder V40Gy<40%, DMax <50Gy (ideally) Small bowel DMax<50Gy Large bowel V45Gy<195cc Femoral heads V40Gy<40%
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For rectal cancer volumes: 1. Give the T3NO volumes. 2. Invading anal canal (same as?) 3. Invading prostate, upper vag.
1. CTV50 = GTV+1cm craniocaudal, entire mesorectum and presacral space at those axial levels. CTV45= CTV50 + entire mesorectum, presacral space and internal iliacs. 1cm anterior expansion to account for variable bladder filing. 2) CTV50 = GTV+1cm craniocaudal + entire anal canal including sphincters and mesorectum and presacral space at those levels. CTV45=CTV50 NOW include inguinal and external iliacs. (same with lower 1/3 vag). 3) As above. CTV45 = as above, BUT include prostate/vag. External iliacs and obturators. If bladder, may reasonable to do entire bladder (in which case sim empty).
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A 44-year-old woman presents with vaginal bleeding. Clinical examination reveals a 5 cm ulcerative mass in the lower third of the vagina. Biopsy confirms a primary vaginal squamous cell carcinoma with no evidence of nodal or distant spread. The decision is made to treat the patient with curative intent. The first phase involves external beam radiotherapy with concurrent chemotherapy. What doses will each volume get?
Vaginal Vault brachy: GTV on imaging includiong MRI in Tx position + 5mm. 21Gy/3#. (same as endometrial). iCTVp=CTV50= GTV+5mm + entire vag+cervix, contoured on full and empty bladder and merged. CTV45= Inguinal, external, internal and pre-sacral nodes. Boost any + node to 55Gy and if internal iliac consider treating level above or 3cm above positive node.
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A 44-year-old woman presents with vaginal bleeding. Clinical examination reveals a 5 cm ulcerative mass in the lower third of the vagina. Biopsy confirms a primary vaginal squamous cell carcinoma with no evidence of nodal or distant spread. The decision is made to treat the patient with curative intent. The first phase involves external beam radiotherapy with concurrent chemotherapy. Describe a suitable radiation Dose and Pre sim and sim:
Curative intent EBRT to a total of 50Gy/25#, 2Gy/#. 5#s/week (see boost below). VMAT Technique, photons >= 6MV, prescribed to D50. Concurrent with weekly cisplatin 40mg/Msqr. Combined with brachytherapy (described below) in final week(s) of treatment. Pre-sim: Preg test, offer fertility counselling/service referral, analgesia, anti-emetics as required. Comfortably full bladder (also prior to each fraction). Sim: Supine, arms on chest, head towards gantry. Immobilization with vac bag, knee and ankle supports as needed. Bowel empty (enema at sim and prior to daily RT). 2mm slice CT+contrast, L4-mid femur. Fused with MRI and diagnostic PET.
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A 44-year-old woman presents with vaginal bleeding. Clinical examination reveals a 5 cm ulcerative mass in the lower third of the vagina. Biopsy confirms a primary vaginal squamous cell carcinoma with no evidence of nodal or distant spread. The decision is made to treat the patient with curative intent. The first phase involves external beam radiotherapy with concurrent chemotherapy. Describe Volumes and OARS
Volumes: For non-nodal volume contour on full and empty bladder and merge CTVs for ITV. GTV = Primary tumour on imaging and examination. iCTVp= GTV+5mm, Entire vaginal canal, and Cervix PTVp = iCTVp+7mm CTVn = Inguinal, external and internal iliacs (to bifurcation), obturator and presacral nodes (Pre sacral nodes if cervix involved). PTVn = CTVn+7mm. OARS: Bladder V40Gy<40% Rectum V40Gy<60% Hips V40Gy<40%
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For rectum, SHORT COURSE not appropriate in the following:
Patient - Sphincter preservation is considered important Tumour - cT4 tumour - N2 - Low rectal tumour (e.g. <5cm from anal verge) - Presence of EMVI (on MRI) - Threatened/ close/ positive CRM - Recurrent rectal cancer (even in patients without prior RT) Treatment - As adjuvant treatment - Re-irradiation in patient with previous RT - When non-operative approach is considered
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Which rectal patients can be considered for TNT? Expected outcomes:
OPRA: T3aN0 (invades subserosa)- to T4N2 (Stg II to III). No hx prior pelvis RT/recurrence/mets. Better organ pres seen in ChemoRT->FOLFOX/CAPOX, than FOLFOX/CAPOX->ChemoRT. 5yr 55% organ pres. 5Yr 80% OS 90% LC, with 90% recurrences within 2 yrs. BUT: grd III or IV tox in 20% Recent metaanalyis suggests for TNT any LR is associated with poorer outcomes (compared to TME <10% viable cells).
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Arguments for and against TNT:
For: improved chemo compliance by front‐loading this treatment resulting in improved disease‐free survival, Increased primary tumour complete response rates, Less time with a covering stoma. Chance (55% @ 5yrs) organ preservation and subsequent lower rates of permanent stoma. Good oncologic outcomes compared with historical controls. AGainst: How to interpret near complete Response on mrTRG (.e. grade 2 outcomnes same as 1?). Lack of definitive histo - while inter-operator mrTRG is good, less than TRG. Recent meta-analysis: Possible worse outcomes if LR (metanal compared to <10% TRG post TME). Still quite toxic - >20% GrdIII or IV toxicity. Direct (phase III) comparison of TNT v.s std approach is lacking. Promising toxicity and ocologic outcomes with s/cRT + NeoAdj + Adj chemo (STELLAR Trial). Less established than standard approach.
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After TNT when and how is treatment response ass (clue) essed?
At 6-8 weeks MRI Tumour Response Grade (mrTRG): Graded 1 to 5 (1 complete response - no tumour signal, fibrosis only). Based on fibrosis, residual tumor signal, mucin, and comparison with pre-treatment MR.
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Re-irradiation for rectal Ca (e.g. previous 50Gy)
Retrospective and prospective data suggest safe and associated with better outcomes. 45/25 concurrent with capecitabine or 5-FU (no if dMMR).
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Discuss the advantages and disadvantages of the different treatment strategies available for locoregionally advanced laryngeal carcinoma (Stages III and IV). (5 marks)
Surgery: 1) For stage III (T3 where thyroid cart not fully penetrated) - Larynx sparing surgery w/followed by PORT (no chemo). Advantage: Avoids chemo, equivalent to definitive ChemoRT (i.e VA study). Histology on resection provides more fine grained prognostic information/risk qualification and decisions on adjuvant therapies (e.g. the addition of chemo). Disadvantages: Worse reported QOL outcomes than definitive chemoRT, operative risks including failed organ preservation and dyspnonia/nerve injury. Does not avoid radiation. 2) For stage IV: Total laryngectomy and adjuvant PORT +/- Chemo. Advantage: Definitive operation, with en bloc resection and detailed pathological information, preferred option for advanced disease. Disadvantages: Offers no chance of organ preservation, highly morbid surgery with poor QOL, intraoperative and post operative risks and complications, despite intensity of intervention may not be curative. ChemoRT (note the role of induction chemo, e.g. VCF is controversial in terms of benefit vs toxicity, may consider for bulky disease where definitive chemoRT is treatment of choice). 1) Definitive For Stage III - 70Gy/35# with cisplatin (eg. 100mg/msqr) 2) as for 1, potential proceeded by induction chemo. Palliative: 1) Palliative radiation for local control and symptom MX (e.g. 20/5 or 30/10): Not curative (main disadvantage), can offer good durable local control and symptom relief. 2) In severe case IV - Best supportive care, with medical Mx of Sx, and social emotional and family support.
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For each of these OARS for pelvis (anal, cervix) Small bowel loop Large Bowel loops Rectum Bladder External genitalia Femoral head/neck Kidneys
Small bowel loop V30Gy<200c, Dmax<50Gy Large Bowel loops = same as small bowel. Rectum V40Gy <60%(e.g. cervix) Bladder: V40Gy< 30% (or 35%), V50Gy<5% External genitalia: V40Gy< 5% Femoral head/neck: V30Gy< 50% Kidneys: Mean dose <15Gy
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Indications: adjuvant nodal Tx Melanoma
Adjuvant treatment (nodal) – TROG 0201 * ≥1 parotid node, ≥ 2 cervical or axillary nodes, ≥3 inguinal nodes * Largest node ≥3cm (cervical nodes), or ≥4cm (axillary/ inguinal nodes) * ENE
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Evidence for nodal irradiation in pelvic node+ve Pr cancer
STAMPEDE - FFS benefit 85% vs 55% (compared to no irradiation). This is consistent witrh a number of prospective trials suggestive of significant benefit - including OS. Dose: 74/37 to prostate and SV + positive nodes. 55/37 to prostate.
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Give Degarelix MOA Degerelix vs conventional ADT?
Gonadotropin Releasing Hormone ANTAGONIST (as oppsed to the typical GnRH agonsist goserelin/leuporelin). Phase III open label data demonstrated superior PSA response, and mixed difference in toxicity. Degarelix has more injection site reactions. Monthly S/c Dose: Dose 1 =240mg. Dose 2-infinity = 80mg.
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OARS for prostate and nodes plan:
OARS (in EQD2): Rectum V50Gy<50% Bladder V50<50% (may compromise to V65<50), Femoral heads V50Gy<5%, V40<50 Small bowel V45<195cc, Large bowel - avoid hotspots.
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Node positive prostate cancer dose and technique: What’s a key rule for your nodal volume?
Curative intent EBRT with ADT (2-3 years) to maximum 60Gy/20#, 3Gy/#, 5#s/week. VMAT SIB technique, >=6MV photons, prescribed to D50. Aim PTV D95>98% prescribed dose, avoid plan hotspots over OARS (especially bowel), Dmax<107%. Pre sim: LUTSxt assessment and Mx as appropriate/if needed. Pre sim and each # - bowels empty (enema) and comfortably full bladder. Sim: Supine, hands on chest, knee/ankle supports, immob w/vac bag. 22mm slice CT+ con(L3 - upper 1/3rd femur), consider fusion with dx MRI/PSMA PET if +ve nodes small/reduced with ADT. STAMPEDE - Improves failure free survival. Volumes: CTV60p = Entire prostate + 1st 1cm of SVs GTVn = + nodes CTV60n= GTVn+3mm (depending on prox to bowel may reduce to 55/20). CTV44= CTV60 + remaining SVs, pre-sacral (always forget to write that) external iliacs+obturator nodes, internal and common iliac nodes to bifurcation or 2cm above highest positive node (whichever is higher).!!!!!!!!!!!1 PTV= CTV44+7mm. OARS (in EQD2): Rectum V40Gy<40% (ideal) may accept up to V50Gy<50% Bladder V40Gy<30%, Small bowel V45<195cc, femoral heads V40Gy<40%. Large bowel - avoid hotspots
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Evidence for SABR for liver mets: Give dose and volume.
No phase III data (i.e comparing SABR to RFA). Multiple retrospective and 2 phase II prospective trials. A HyTEC analysis of 13 studies found 1year LCR to be 90%. Outcomes were significantly better for lesions treated with BEDs exceeding 100 Gy (3-year local control 93%). Rule et. al "Rule" for dose response: LC rate at 2yrs - 100% at 60Gy years, 89% for the 50 Gy cohort, and 56% for 30 Gy. 54/3#, SABR with motion Mx, iGTV to 5mm PTV expansion (if GTV unclear consider 3mm CTV expansion). Contour on CT+contrast - late arterial phase if technically feasible with 4DCT
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In the treatment of thyroid eye disease with radiation therapy; what are the: (3) i. indications ii. contraindications iii. target volumes iv. radiation dose fractionation schedules and v. expected response rates to therapy?
i. indications - Clinical exophthalmus due to thyroid eye disease - Failed trial of steroids - Not suited to or declined other approaches (surgical decompression) ii. contraindications - Responsive to steroids/other Mx. - Connective tissue diseases (cautionary) - Eye diseases: e.g. glaucoma iii. target volumes CTV= preorbital tissues, PTV 3mm. E.g. with 5 × 5 cm lateral fields using 6 MV photons and 5° poste- rior tilt or half-beam block iv. radiation dose fractionation schedules and v. expected response rates to therapy? 20Gy/10#, recent evidence suggests that this dose may be reduced (Don’t ever hypofractionate benign). Local control in approximately 2/3rds.
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For Keloids: Indications Dose Timing Outcomes Other options
Local recurrence after surgery alone =50%. (25% post RT) 21 Gy/3 fx for most locations and 18 Gy/3 fx for earlobe 24–72 hrs after surgical excision. 37.5 Gy/5 fx if RT is used definitively. LC 75%. Other options include steroid injection, cryotherapy, pulsed-dye laser, interferon, or topical agents.
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Following surgery for cutaneous Squamous Cell Carcinoma (SCC) in the Head and Neck area, what high-risk factors would you consider when recommending adjuvant radiation therapy. (2)
Absolute indications = T4, +ve margin where further resection not available. PNI in large nerve. Recurrence where no previous RT given. Relative (if 2 or more then do): T21, 2 or T31. ≥6 mm depth of invasion. Close margins < 2 mm. Poorly differentiated. Pathological microscopic perineural invasion (PNI). Lymphovascular invasion. Immunosuppression. Higher risk sites, e.g. non-hair bearing lip, chin, ear, preauricular, periorbital, temple.
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Clinically the patient has a 12mm vertical scar in the midline lower eyelid. There is no obvious residual BCC. A decision is made to offer adjuvant radiation therapy. b. Describe an appropriate radiation therapy technique and dose fractionation schedule. (3)
Adjuvant RT to reduce risk of recurrence. SXR technique, 40Gy/15#, 5#s/week, 100% prescribed dose at skin surface, energy/filter/SSD selected for D90 cover at target depth (e.g. 3mm). Pre: Explain vision changes associated with topical anaesthetic (may need to arrange transport etc). Sim: Mark-up scar, make or select lead cutout and applicator appropriate to markup + 10mm margin (for CTV + setup error and penumbra). Make setup template from above + setup photos. Eyeshield fitted. Using departmental tables, select Energy/Filter/SSD e.g 20cmSSD 2mmAl, 100Kv for D90 ~3mm (consider contribution of scatter from eye shield to dose). Clinical setup photos. Volume: as above, Dmax at skin surface aim D90 based on path report. OARS (in EQD2, note SXR higher BED): Eye: lens DMax<8Gy, Eye <45Gy, lacrimal duct Dmax<30Gy. Verification via template match and setup photographs.
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Basic treatment principles for Rhabdo: - Sequence - Key variables for decisions - Dose options - Which sites inoperable?
COGS/ IRS (US/ Australia) Surgery → chemotherapy → RT SIOP Surgery → chemotherapy → no adjuvant RT * 50% will relapse – intensive therapy for relapse including exenteration + RT (reserve RT for salvage) Variables (that define risk): Site, Histo. Surgical/Post-op. Doses: Embryonal R0 - No Rt R0 Alveolar and all R1 - 36/20 N+ 41.4/23 Gross disease 50.4/28
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A 4-year-old girl presents with proptosis. A right orbital mass is identified on MRI. Biopsy confirms an embryonal rhabdomyosarcoma. Further staging investigations show no metastatic disease. Give dose and technique.
Definitive EBRT 50.4Gy/28#, 1.8Gy/#, 5#s/week to the right orbital mass with concurrent chemotherapy (vincristine and cyclophosphamide; and omitting actinomycin-D during RT) Pre-SIM: * Repeat MRI post chemotherapy * Consider GA if patient not able to remain still on RT SIM * Position: supine, arms down, head towards gantry, under GA * Immobilisation: thermoplastic mask, vac bag, neck support, * Marker: no specific * Planning CT: 2mm slice CT from vertex to lower cervical spine Fusion: pre-chemo and post-chemo MRI Targe volume: * GTV = pre-chemo gross disease * CTV = GTV + 1cm clipped at anatomical (i.e. bone) boundaries (no need to cover entire orbit) * PTV=CTV+5mm Technique: partial arc unilateral VMAT technique with 6MV photon Plan evaluation: * Tumour coverage PTV D98>95% * Minimise hotspot PTV D2<107%, ensure no hotspot outside of PTV/ over critical OAR * Ensure low dose (10% and 50%) reasonably distributed around PTV, with contralateral sparing * Review OAR DVH o Pituitary and temporal lobe ALARA o Lacrimal gland Dmax< 41.4Gy o Optic nerve/ chiasm/ brain stem: Dmax< 50.4Gy o Lens Dmax< 14Gy Verification: Daily kV, matched to bone, with 3mm tolerance
143
Immunotherapies (name targets and mechanism) for BRAF negative melanoma: What is the benefit?
If no BRAF than target T-Cell mediated cell death evasion: CTLA4 - Ipilumimab. Normal role is to downregulate T-Cell activation. Upregulated in cancer leading to immuncheckpoint evasion. Ipilumimab binds CTLA4 and inactivates it. By itself adds 3 months PFS. PD-1 - E.g. Nivolumab. Binds PD1 receptor on T-Cell preventing PDL-1 from binding and inactivating T-Cell, By itself adds 6Months Ipi + Nivo = 12months PFS 5Yr OS for metastatic BRAF negative is 45% 5Yr OS for +v is higher at 55%
144
Immunotherapies (name targets and mechanism) for BRAF positive melanoma: What is the benefit?
Best results combine BRAF and Mek targeted therapies: TKI signal transduction pathway RAS RAF MEK ERK Braf: Dabrafinib MEKtargeted by molecular inhibition = Trametinib. Get on the 'ol Dab Tram for 1yr OS 70% next stop death.
145
Doses for meningioma:
If optic nerve or being gentle - 50.4/28 Grd 1 R0 -observation Simpson 1-3 - Observation versus 54/30 STR/primary Mx - 54/30 SRS 14/1 SRT - 25/5 Grd II/III For grd II Observation is investigational (ROAM) Simpson I-III 54 to 60/30 or 59.4/33 (if big or young!!!) STR/residual - 60/30 or 59.4 SRS/SRT - 14G or 25/5 Note: 59.4Gy/33, 1.8 Gy# where large volume or young patient 1.8Gy/# - a common Exam trick question. Grd I-III Recurrence: Re-resection where possible Then doses as per relevant grade
146
Volumes for menigioma:
GTV = gross disease (T1 + contrast) [if no resection] GTV(post-op) = residual disease (post-op MRI) (T1 + contrast) Grade 1 - CTV = GTV + 0.5cm for WHO Grade, 5mm into brain, clipped at anatomical boundaries Grade 2 - CTV = GTV + 1 - 1.5cm along the dural for WHO Grade 2/3, 5mm into brain, clipped at boundaries PTV=CTV+5mm
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pathology demonstrates a WHO Grade 3 (anaplastic) meningioma. Post-operative imaging shows residual disease on the floor of the anterior cranial fossa. A decision is made to give post-operative radiation therapy. b. In this woman, describe the GTV, CTV, and PTV you would apply and explain how would you determine these? (2m) c. What dose would you prescribe? Justify your answer (1m)
Fuse pre-op and post-op MRI GTVpost-op = GTR based on fusion of PO MRI CTV = GTV + surgical cavity + 1.5cm along dural + 5mm into brain, clipped at anatomical boundaries PTV = CTV + 5mm expansion I will offer her adjuvant RT to a total dose of 59.4Gy/33, 1.8Gy#, 5#/ week - Large volume hence use more fractionated + young patient 1.8Gy/# (lower late effects than 2Gy/#)
148
Prostate: Is there a benefit to elective pelvic nodal RT (ENI) and which patients should be considered?
Historically trial data has been unclear or not supportive (e.g. GETUG, RTOG). More recently the POP RT trial, which studied a population of higher-risk of nodal involvement (>=20% by Roach) demonstrated a 5yr met free, disease free benefit but with higher late GU toxicity. WPRT = 90% 5yr disease free survival vs 75%. This study used a modern prostate dose (68/25), and 80% of pts had a PET. A new RTOG study 0924 is recruiting with an aim for higher-power than previous.
149
Which non-high risk prostate Ca patients should get ADT? Give duration and evidence.
Int risk Unfav - ADT 6mths = DFS, biochemical failure reduced from 20 to 10% at 5yrs. PrSpec survival and potential OS benefit: NCCN recommendation is for ADT beginning at intermediate unfavourable prostate cancer. Its is based on 2 phase 3 RTOG trials and meta-analysis. The 1st RTOG trial 9408 found 4 months ADT provided a DFS benefit to IR-U but not IR-F (on subanalys). A 2nd RTOG phase III trial found int risk PrCa in general benefit from 6 months ADT in terms of DMS and prostate specific survival. Meta-anlysis suggests a small OS benefit at around 9 years in int prostate cancer. Notably ADT effect is independent of radiation dose.
150
What is the optimal duration of hormone therapy for HR prostate cancer?
OS benefit has been demonstrated with long-term ADT (28–36 months) compared to short-term regimens (4–6 months), even in the dose-escalated era (DART trial). EORTC trial 3yrs ADT improved 10yr OS from 40%-58% One trial (PCS IV) found similar oncologic outcomes between 18 months and 36 months. The RADAR trial found that 18 months of ADT was superior to 6 months prCa spec OS 13vs10%
151
Ignoring more modern trials looking at nodes ect: In men with a detectable Prostate Specific Antigen (PSA) after prostatectomy for prostate cancer, salvage prostate bed alone yields what benefit?
In men with a detectable Prostate Specific Antigen (PSA) after prostatectomy for prostate cancer, salvage prostate bed radiotherapy (PBRT) results in about a 70% freedom from progression (FFP) at 5 years
152
What approach most significantly impacts outcomes in early salvage prostate cancer treatment. State the benefit of this approach.
Remember by treating the bed alone you achieve 70% freedom from progression benefit at 5yrs. The SPPORT trial (3-ARM) shows that with treatment of: Traditional arm = Bed RT = 71% Bed +6 months ADT benefit increases to 81% (a 10% gain) Bed+WPRT+ADT = 87% (16% gain!) Keep in mind OS at 5yrs is great regardless - 95% so no difference.
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PRIME II Criteria Key findings
Age>65, ER or PR +, node -ve, margin >1mm, THEN can have either LVI or grd 3 BUT not both. RT + tamoxifen = Tamoxifen alone for OS, and DM. ONLY benefit is a reduction in IBTR from 4% to 1%
154
For prostate cancer: Early Salvage vs Adjuvant(AKA?)? Key studies:
3 key proRCT studies: RAVES (failed to meet criteria), GETUG-AFU17, RADICAL suggest Salvage is non-inferior to Adjuvant radiotherapy in terms of event free survival - but is associated with less late GU toxicity, and some men may be spared radiation entirely. Salvage being defined as when PSA crosses a defined point (usually 0.2ng/ml).
155
Dose/prescription for salvage EBRT post RRP:
RAVES uses 64/32 to bed, SPORT (bed+nodes+ 6 months ADT) uses up to 70Gy to bed, 45Gy to nodes. As we are only treating microscopic disease - I would use 52.5/20 (2.75Gy/#) to the bed and 44Gy to the nodes. EQD2 68Gy (for prostata alpha/beta 1.1). This dose is in EVIQ.
156
When is RT indicated for neuroblastoma? Give the criteria:
For high risk (50% present as HR): Basically SANDS Surgical stage (R1,R2, unresectable) >= 2, mets, N-Myc amplification, Unfavourable Histo (as Per Shimada: Stroma poor, Differentiation poor, Mitosis/Karryohaxis high, Nodular).
157
For Neuroblastoma give the treatment sequence based on Risk:
Low - Risk - 4S - Observation. Spontaneously resolve 5yrOS 95% (4S = age<1, ipsilateral node negative, Age <1y/o with <10%bone marrows, even mets to skin or liver) Low risk: Surg alone for non-4S = GTR: No benefits for adj RT * If STR, or recurrence after GTR: consider chemo Int risk: Induction chemo then surg, RT only if progression. HR: Always need multimodality treatment Sequence: Induction chemotherapy → surgery → consolidative chemotherapy → autologous stem cell transplant → RT (primary + metastatic site + boost residual disease) → differentiation therapy and immunotherapy. Consolidative RT = 21.6Gy/ 12# (1.8Gy/#) to tumour bed, For unresectable bulky sites, metastatic site = Boost residual disease to total of 36Gy/20# OS 15% at 5yrs!
158
Define the following: Absolute Risk Reduction (ARR) Number needed to treat (NNT) Relative Risk (RR) Relative Risk Reduction (RRR)
ARR = I Experimental event rate - Control event rate I NNT = 1/ARR RR = Experimental Event rate/Control Event Rate RRR = ARR/Control event rate = 1-RR
159
When delivering post mastectomy radiation to the chest wall: i. What is the rationale for the use of bolus? (1) Ii. Which patients require bolus? (2)
i. What is the rationale for the use of bolus? (1) - to reduce dose to underlying lung - Increase skin and subcutaneous dose (most common site of recurrence post mastectomy) and - Smooth some post mastectomy tissue irregularities. Ii. Which patients require bolus? (2) - Pts with close/involved superficial/skin margin - Pts with highly irregular surface contour - Pts with shallow skin to lung interface depth,
160
An 80-year-old man is diagnosed with a 3cm squamous cell cancer near the hilum of his right lung (cT2N0M0). Investigations reveal no other sites of disease. A decision is made to treat with definitive SBRT using a linear accelerator. Describe a suitable radiation therapy technique and dose fractionation schedule. (4)
Curative intent (local control 90%, 2yr OS 75%, 50%5yr vs 50%3yr EBRT): SABR 50Gy/5#s (using central tumour), 1#/day, prescribed to PTV D95>100% prescribed dose, 6MV photons, DCAT technique. Aim Dmax within PTV 125-14% of prescribed dose, CI-100; 1.1-1.3, CI-50<5. Presim: Baseline lung function Sim: Supine arms above head, head towards gantry, knee/ankle rests, head support Immobilise with vac bag. Patient breathing freely. 4DCT + contrast, fusion with PET if available. Volumes: iGTV = tumour volume contoured on MIP and checked against all phases of breathing cycle and referenced against PET, PTV=iGTV+5mm OARS (in 2Gy#s, would convert or use published data - e.g. from CHISEL): Spinal cord Dmax<45Gy, brachial plexus Dmean<60Gy, Lung V20Gy<10%, oesophagus, heart MHD<2Gy.
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Locally recurrent nasopharynx Ca. A decision is made to retreat with radiation therapy. Discuss a suitable external beam radiation non-proton technique. (2.5)
Curative intent re-irradiation, hyperfractionated approach 60Gy/40, 2#s/day, 10#s/week, VMAT technique, 6MV photons, prescribed to D50. Aim PTV D98>100% prescribed dose. Avoid Dmax>107%. Pre-sim: Consent to include discussion of significant risk of potential severe toxities and death Sim: Supine, head towards gantry, arms by side, knee board, ankle supports. Immobilise with thermoplastic mask. 2mm fine slice CT+contrast, above vertex to T4, and fused with PET and planning MRI (T1+C). Volumes: GTV: defined on imaging and endoscopy. CTV: GTV+5mm trimmed to boundaries, PTV = CTV+5mm I would not include elective nodal regions. Verification: Daily CBCT matched to bone.
162
For nasopharygeal Ca, who should get NA chemo? What is the chemo?
Stage III to IV: III = Bilateral nodes or T3 (bone invasion) IVa = Intracranial extension. BUT: Only fit patients where NA wont compromise chances of tolerating definitive ChemoRT. Chemo: Cisplatin + Gem OR TPF (more toxic). Dont forget to include the entire pre-chemo GTV in CTV63.
163
Outcomes by stage for Nasophaygeal Ca:
5-year OS Stage I 90%, Stage II 75%, Stage III 60%, (bone invasion) Stage IV 30% Local control: Stage III/IV only a half to 1/3.
164
When treating a NSCLC to 60Gy/30: What is the expansion on iGTV? What is the Chemo? Compare that to SCLC
SCC - 8mm Adeno - 6mm Chem0 = Cisplatin Etop = both 50mg/msq SCLC = Carbo Etop = 5AUC!!! + 100mg/msq
165
When would you consider PORT for vulva cancer? What is the most important prognostic factor?
Node status is by far and away the most important - 1 inguinal node 50% 5yr OS, 1 pelvic 11%, node - 90% The Heaps study was one of the 1st to identify RFs. Critical are: Margin <8mm Depth >5mm LVSI/VSI Size>4cm Stage III = Node +ve (GOG37!! OS benefit when clinical node +ve, more than 1 node, ECE or ulcerated). Others from Heaps (but not critical to the answer): Keratin production, mitotic rate.
166
Benefit, evidence and role for Neo Adj Chemo RT for unresectable vulva cancer. Give dose and volumes.
GOG 205 - Phase II unresectable (T3-T4, N+): Pathological complete response in 50% with this dose escalated regimen: 45/25 to primary + nodes: Nodes and primary boosted to 59.4/33#s. Essential CTVprimary = GTV+1cm, Subcutaneous Mons bridge and whole vulva. - Add ons: Node volumes: If +ve treat bilateral level, treat the eschalon above bilaterally. Involvement of distal vagina, include: bilateral inguinofemoral, bilateral obturator, and internal and external iliac nodes. If proximal posterior vaginal involvement, include pre-sacral nodes (S1 to the bottom of S2/top of S3). If involvement of anal canal, include as per distal vagina and include perirectal, mesorectum and presacral nodes.
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Dose for PORT vulva: ?Adjuvant ChemoRT
+ve margin - advocate re-excision. Divide into >2cm solitary node negative (i.e Ib-II) : R1- 54/27, R0 - 50/25. “Indications” : Margin <8mm (or 5mm…), DOI >5mm, LVSI, lesion>4cm, “Spray” (diffuse) histology, Node +ve: Micromet <2mm on Bx can have nodal irradiation instead of dissection (GROINS VII) Post inguinal dissection – if >1 node +ve Or “less extensive” dissection (<12 nodes). 50Gy/25 +/- 10Gy boost to positive nodes ?Adjuvant ChemoRT – no prospective data. Some retro analysis suggests possible OS benefit. Extrapolate from Cx Ca and consider when bulky nodes, +ve margin
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Role of chemo in vulva Ca?
?Adjuvant ChemoRT – no prospective data. Some retro analysis suggests possible OS benefit. Extrapolate from Cx Ca and consider when bulky nodes, +ve margin
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Dose ranges vulva PORT:
i.e. when 2 or more nodes +ve Do SIB to a maximum of 2Gy/# either 56, or 60: Fully excised no ECE: Site +ve node 56/28 Everything else including TB 50.4/28. (prefer 1.8Gy#s to groin - NCCN) +ve margin/ECE: R1 = 60/30 (ECE, TB) + 2cm, surrounded by 56/30. Rescection bed (i.e. margins -ve ECE): 56/30. Everything else 46/30.
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Volumes for PORT vulva when >1node +ve fully excised margins neg,
Site of +ve node 56/28, everything else (TB uninvolved nodes) 50.4/28. CTV50nodes: 1) Treat echelon above highest involved node bilaterally. 2) If inguinofemoral node involved, treat contralateral inguinofemoral region and external iliac nodes. 3.1) Involvement of distal vagina, include: - bilateral inguinofemoral, - bilateral obturator- - internal and external iliac nodes. 3.2) If proximal posterior vaginal involvement, include pre-sacral nodes (S1 to the bottom of S2/top of S3). 4) Anal canal (same volumes as anal primary), include as per distal vagina: - bilateral inguinofemoral, - bilateral obturator- - internal and external iliac nodes & perirectal, mesorectum and presacral nodes.
171
What is pentoclo protocol for osteoradionecrosis?
PENTOCLO protocol: Pentoxifylline 400 mg, BD Tocopherol 500 mg, BD Clodronate BD 5 Days a week Continue til "acceptable clinical response"
172
Approach to PORT (or definitive) nodal irradiation for oral cavity SCC
1) Decide if unilateral or bilateral: - Unilateral only if single ipsilateral node & tumour well lateralised - at least 1cm from midline, BOT or tip of tongue. - Bilateral if >=2 ipsi nodes, close to midline. 2) Which nodes? IB, II and III always Any tumour close to midline or into oropharynx then include level IV. Obviously also if III involved. If bucal mucosae then level IX (buccal nodes) ipsilateral nodes.
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Posterior borders of the Oral cavity. Subsites of the oral cavity. Indications for PORT (Name a very important study about one histological RF).
Post border: Post edge hard palate, anterior to vallate papillae (which demarcates the BOT). Subsites: Lips, gum, hard palate, FOM, tongue excluding bass, retromolar trigone. PORT if: Absolute: positive margin (defined as <1mm), ECE o Positive margin: < 1mm o Close margin: < 5mm >=T3 IF pT1-2 AND one or more risk factors: PNI, LVI, close margin < 5mm * T2 with DOI >4mm if based on (Ganly) * pN2-3 * recurrence
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Approach to PORT (or definitive) nodal irradiation for Oropharynx SCC p16 negative.
Trick - p16+ may also be the same - unlear. 1) Decide if unilateral or bilateral (similar to oral cav): Unilateral if NO-N2a (single ipsilateral node <6cm). Tonsil fossa tumor NOT infiltrating the soft palate OR the BOT 2) Which nodes? If ipsilateral then: II, III, IVa', + 1B if oral cavity extension (e.g. into retromolar trigone) +VIla = retro pharyngeal nodes for posterior pharyngeal wall tumor If bilateral: Ib, II, III, IVa, Va,b, +VIla, +VIIb* only do bilateral retropharygeal nodes if posterior paryngeal wall tumour.
175
Definitive dose and volumes for a T1-T2 glottic larynx: Define T1 and T2.
T1 = vocal cords (a = uni, b=bi) T2= extension in supra/sub glottis. 60/25old school - T1 now 63/28 CTV= Entire larynx at level of GTV and 0.5-1.0 cm superiorly and inferiorly.
176
Compare volumes for larynx and hypopharynx
CTV70 = GTV + 5-10mm both sites. CTV63 = CTV70+ intermediate risk nodes +: If Larynx SCC: consider entire larynx If Hypopharynx: entire hypopharynx CTV56=Bilateral nodal levels II, III and IV. Consider levels Ib and/or V included on side(s) of lymphadenopathy. Consider VIIb and level V for extensive level II lymph node involvement. IF Larynx: VI if subglottis Hypopharynx: VI for apex of piriform sinus, post cricoid and/or oesophageal extension
177
When is chemo indicated in definitive RT for larynx and hypopharynx? Differnt approaches to chemo, their benefits and when might be considered?
Hypopharynx: Consider from T2 (invades more than 1 subsite, or adjacent region, or is 2-4cm big). Chemo: Consider induction for bulky disease (T3-T4), TPF or less effective/toxic cisplat+5FU. There is no OS benefit to induction -> ChemRT. Both chemotRT and induction->RT are better than RT alone. Induction ->RT: - Improves Laryngectomy Free Survival, Italian data had trend to OS benefit. - Worse LC than concurrent. ChemoRT (vs induction - RT) - Better LC
178
Define Stage I and II hypopharynx cancer: COmpare surgery vs RT for this
Stg I to II = T1 to T2 (2-4cm and or more than 1 site, or invasion into other area). Not directly compared but appear isoeffective, with RT better QoL. Surgery - distant mets more common RT - Local recurrence more common.
179
For H&N cancers define: Positive/involved margin: Close margin Clear margin. Large-calibre and small-calibre nerves
Positive/involved margin: <1mm Close margin: 1-5mm Clear margin: >5mm Large-calibre and small-calibre nerves: Large >0.1mm, small <0.1
180
Dose and rationale for SABR to RCC mets.
No phase III data, but pooled and meta-analysis suggests LCR>95% at 5yrs (potentially better than historic ablative controls). Phase II data SABR + pembro offeres excellent local control rates. Indication is inoperable and not suited to ablative techniques. (dont give concurrently with molecular therapy!!) Dose of SABR: 26/1 (smaller lesion <3), 42/3 (up to 10cm caution though).
181
Briefly give the argument for treating pelvic nodes in node negative prostate cancer:
There is no large randomised trial evidence (GETUG-01, RTOG 9413) supporting that PNRT improves oncological outcomes. A recent smaller phase III trial (POP- RT) showed improved biochemical control with PNRT 50Gy/25.
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For each of the following simply give doses, the study they cam from, a guideline supporting their use (and the evidence grade assigned by that guideline): Prostate-only RT: * EBRT only * EBRT + Brachy Stereotactic radiotherapy (SBRT): Pelvic nodal RT (node -): *The current gold standard. *Your approach Postoperative RT:
All the below doses are within UK-RCR Prostate-only RT: * 60 Gy/20 over 4 weeks CHIiP Trial (Grade A) EBRT+Brachy * 46 Gy in 23 fractions (prostate and pelvic nodes) over 4.5 weeks followed by 15 Gy HDR or 115 Gy LDR brachytherapy boost (Grade A) SBRT: * 36.25Gy/5(Grade A) - 2 trials: Hypo RT (42/7), PACE-B 36.25/5 (USE). Same outcomes as conventional, but possibly higher late grd II GU. Pelvic nodal RT node -ve: * 50Gy/25 over 5 weeks or equivalent (Grade A) - POP-RT current only trial for node-ve to show benefit - therfore this is current standard. *44-47/20 are in common use. 46/20 (2.3Gy/#) = 50Gy BED (Grade D) Node +: STAMPEDE - PFS benefit. 60/20 to Pr, 44/20 nodes, 55-60Gy to +ve nodes (OARS permitting). Postoperative RT: * I favour early salvage and treat nodes (SPORT Trial 64.8/36, 45/25 nodes), but dose I prefer 55/20 (60/20 is PSMA residual) and 44/20 to the nodes
183
Name a rectal spacer brand. How many mls of spacer? Evidence?
Barigel - 9 to 10mls. Results from 2 RCTs were varied; however, the use of rectal spacers showed improvement in rectal toxicity and quality of life at up to 36 months. More severe toxic effects were less common.
184
A decision is made to administer TBI using an opposed lateral technique. Describe this radiation technique and include an appropriate dose fractionation schedule. (5)
TBI delivered to a total of 12Gy/6#, 2#s/day treat over 3 days, opposed lateral photons (SSD 4m), aim energies below 6Mv, prescribed to midpoint (typically umbilicus). Alternating between lateral beams at each fraction. Aim for 7 days prior to transplant. Pre sim: Anti-nausea medication, other meds to consider are dexamethasone and anti-anxiety meds (e.g. Lorazepam). Fertility preservation (though they’re pretty fucked if not done by this point). Sim: Supine, small under head, knee fix, Upper arm resting on 4cm polystyrene (to reduce lung dose), Hand resting on abdomen. Compensator/ bolus (‘beam spoiler’) – (because of skin-sparing effect of photon): Bolus (E.g. flab) – on lateral and anterior surface of neck + chest (to reduce dose to lung) Perspex – as head frame compensator, and from mid-thigh inferiorly (thicker from mid knee inferiorly)Linac field typically at most open position/largest practical field size. Volume: Whole Body – Covered by light field. Aim homogenous dose +/-5% of PD. OAR: Lungs – Aim <12.6Gy, consider Lung shields. Verification: Patient position confirmed with laser matching. Whole body within light field, in vivo dosimetry (e.g. TLDs on skin surface) not routine.
185
Contraindications to bladder preservation approach:
Assess for relative contraindications: Tumour>5cm, multifocal/in-situ, incomplete TURBT, irreversible hydronephrosis.
186
A crusty as fuck elderly person wants curative intent treatment for their muscle invasive bladder Ca. What can you offer? ------------------------------------ Just to save a card: In a well younger patient what is preferred Mx node neg bladder SCC? Also for bladder ca in general, any role Adj RT?
Surgery too intense. The works: 55/20 + 35mg/msq cisplatin Phase 2 data: 50/20 with gemcitabine, similar outcomes to above. Cant have chemo: 55/20 with Nicotinomide and Carbogen. --------------------- Some evidence for surgery then adjuvant RT for SCC/grd III urothelial: Egyptian data (phase II random): 45/15 may improve LRC where N+ or grd III or macroscopic ijnvasion through serosa (T3b, a is micro). No OS benefit. BART trial 50.4Gy ongoing.
187
What is the expected 5-year overall survival following treatment for muscle invasive bladder cancer? Ii. Discuss the difficulties that arise when comparing survival outcomes between radical cystectomy and bladder preservation treatment approach.
Recent (2023) Pooled analysis of phase II data suggests 5rOS for treated bladder Ca is 60-70% (slightly higher than surgery despite being a more com-morbid cohort). 66% chance of bladder preservation. Difficulties when comparing survival outcomes between cystectomy and bladder preservation: - No direct, randomised trial exists to demonstrate superiority/ (non) inferiority. - Populations may not be directly comparable - Bladder preservation candidates may have more co-morbidities/tumour complications than those selected for radical surgery. Comparisons with historic data in terms of patient outcomes may be out of date due to new surgical (increased options for conduit) and radiation (VMAT vs planned) techniques. Planned technique may have treated nodes!!
188
Indications of breast boost - name who recommends? Key study and who benefits the most?
ASTRO (2018) Guidelines: 50 years or younger with any grade tumor, or in patients aged 51 to 70 years with high-grade tumors or positive margins. ***Consistent w/subgroup analysis of Bartelink (now 20yrs) - suggests greatest benefit age<50. Also those w/adjacent DCIS (at long term follow up) and grdIII
189
Who gets the most benefit to post mastectomy RT? What Study? Also define N1, N2 and relate to stage.
PMRT improves both loco­regional control and OS in both pre and post­-menopausal women w/locally advanced BrCa. A large EBCTG pooled analysis (which is pre Her-2 era, pre modern LND/Bx and RT techniques) but is the most comprehensive to date: 1) T1-T2 with 1-3 nodes (i.e N1, stage II) - LRR and BrCaS benefit 2) 4 or more nodes (Stage III) - LRR and BrCaS benefit. SUPREMO is ongoing looking in the modern era at the extent to which this benefit extends to: T2 grdIII, T2 LVSI, T1-2N1. RCR UK supports 26/5 (Fastforward had 90pts, only recurrence was in 40/15grp) as Grade A.
190
Early Breast: In general, what are the options for the further management of the axilla where one sentinel node is positive? Justify your answer (2m)
1) Observation (i.e. no further axillary treatment) Z0011 study, patients with 1-2 SLN + - Randomised to ALND vs. observation - no differences in nodal recurrence/ OS with between arms - higher risk of lymphoedema in patients who had ALND (13% vs. 2%) Also, given that she has endocrine therapy and targeted therapy options 2) Axillary RT AMAROS study – patients with SLN+ - randomised to level 1-3 ALND vs. axillary RT 50Gy/25# - no differences in axillary recurrence (primary endpoint) or OS between arms - less lymphoedema with axillary RT (23% vs. 11%) 3) ALND In AMAROS, ALND arm - 33% had further LN+, and 8% had 4 LN+ 4) MA20 also did IMC - demonstrated a DFS benefit and included high risk N0. 5)Clinical trial POST-NOC (1-2 SLN+, macro mets >2mm) - randomised to observation vs. axillary treatment (surgery or RT) 6) EBCTG meta-analysis 2023: 8 modern studies up to 20years out suggest BCS and OS extending down to node negative. Hopefully POSNOC clarifies.
191
Describe MA.20 RCT: Notable inclusion?
MA.20 (median follow-up was 9.5 years): Patient cohort: node+Ve or high-risk node-Ve breast treated w/BCS and adjSystemics: WBI+ plus RNI (including internal mammary, SCF, and axillary) (nodal-irradiation group) VS Whole-breast irradiation alone Notably, IM nodes were included. Found: RNI + WBRT did not improve OS but reduced the rate recurrence = 5% improvement in DFS at 10yrs (they talk up the "40% relative risk reduction")(But in general most pts did well so this number is small - pts w/>3 nodes tended to be excluded as they all had radiation- taking away the strength of the signal). Higher rates of grdII pneumonitis
192
Your position on IMN radiation (justify):
I would treat IMN if N2 (Thorsten prospective), or N1 and medial tumour (KROG). Major RNI studies (MA.20) have included IMN and demonstrated minimal added toxicity. The Thorsten prospective trial suggests an OS benefit to IMN (that studied included up to 9nodes+ve) for N+ Krog - DFS benefit in medial N+ tumours
193
32F completely excised left breast IDC tripple pos, grd II T2. She undergoes a left level II axillary dissection and is found to have a total of 4 macro-metastases from 15 nodes. She is referred for adjuvant radiation therapy. Provide justification for your choice of nodal volume (1m)
This pt with N2 disease following ALND would benefit from RNI to levels 3, SCF and IMN. I would boost the surgical bed for improved local control given age <50 (Barlelink 20yr data, Astro guidelines). As per MA.20 and EBCTG meta-analysis this is likely to improve DFS (in the order of 5% or more). MA.20 included IMN, and specific benefit is noted in prospective data (Thorsten) when N2 disease.
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32F completely excised left breast IDC T2. She undergoes a left level II axillary dissection and is found to have a total of 4 macro-metastases from 15 nodes. She is referred for adjuvant radiation therapy. d. Describe a suitable radiation therapy technique and dose fractionation schedule. (2m)
Adj EBRT for improved IBTR, and DFS to the left breast and level III, SCF and IMC nodes, 40.05Gy/15#, +10Gy boost to the tumour bed, 5#s/week. VMAT 6MV photons, breathhold technique, prescribed to D50. Pre sim: well-healed, assess for baseline lympoedema, Beta-HCG. Sim: the usual, DIBH. wire scar. no bolus. 2mm slice CT+contrast. CTV=all breast tissue on imaging, trimmed 5mm off skin, deep border fascia of pec major. Level III, SCF, and IMN intercostal space 1-3 (5mm expansion on internal mammary vessels trimmed to boundaries). PTV=CTV+5mm CTV boost= scar tissue on imaging, encompassing surgical clips PTVboost = CTVboost+5mm
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Relate surgery to stage of Wilms and indication for RT, what other criteria relate to this stage? What other factor is an indication for RT? What is stage V, how is it conceptualized?
Stg III is largely based on surgery events or non-events: Bx (i.e. causes seeding) Seeding LN +Ve Unresctable Ruptue Piecemeal rescetion B_SLURPP Unfav Histo (UH) = Diffuse anaplasia = 19.8Gy/11. Stage V is bilateral kidney disease at Dx - Stage each lesion separately!
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Simple principles for RT for Wilms:
Residual disease gets a boost - 10.8Gy/6# (i.e double the R0 port dose). Siop Dose is higher Stg III get at minimum 10.8/6 (i.e. +/- boost) UH get 19.8/11 NWTS: Upfront Nephrectomy -> RT if indicated - VACD-IE Siop: Upfront CTx (VA) - Delayed nephrectomy - Chemo Whole Abdo RT (10.5/7) if Spill, Peritoneal Seed, Ascites Cyto+, Rupture (SPAR). Whole Lung RT 12Gy/8: if lung mets (NWTS), incomplete path response to CTx (SIOP)
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Doses for Wilms (NWTS)
Whole Abdo RT (10.5/7) if Spill, Peritoneal Seed, Ascites Cyto+, Rupture (SPAR). Whole Lung RT 12Gy/8: if lung mets (NWTS), incomplete path response to CTx (SIOP) Stg III 10.8/6 to bed. UH 19.8/11 Boost 10.8/6
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The "not low risk" DCIS patients who should be considered for a boost:
"the big 3" trial is utter bullshit - they changed the definition of risk due to failure to recruit, they dont say, but the NNT is 24 (they sell the benefit as 40% risk reduction! But the control event rate IBTR was 7% the experimental rate 3%). 16Gy extra to the boob for that. Total nonsense. Age <50 or Grd II or higher, multifocal, margin<10mm, size >1.4cm, palpable or necrosis (so basically everyone. total BS). I would boost age <40, grd III, +margin (less than 2mm) or necrosis.
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WLE+RT vs Mastectomy (recurrence out comes)
Broadly: LRR 10-15% WLE+RT, 2%Mastectomy
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a. In general, what are the indications for adjuvant radiation therapy in the management of thymoma? (3m) b.Give doses and iCTV for definitive and adjuvant thymomas.
Indications for adjRt: - Stage II-IVA disease (Masaoaka Stage) - Residual disease (R1-R2) - Thymic cancer (i.e. WHO Grade C) b. Definitive - 60Gy (minimal evidence, but if higher-grade consider concurrent chemo carbo-pac) R0 - 45/25 (e.g. thymic carcinoma) R1 - 54/27. R2 - 60/30 iCTV = iGTV (if any)+5mm, entire thymic space.
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Post operative soft tissue sarcoma dose and volumes:
PORT: CTV60= pre-op GTV/tumour bed +1.5cm radial (as above) + !2cm! sup inf CTV50= CTV60+2cm sup-inf PTV = CTV50+1cm
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iii. In general, what is the goal and magnitude of the benefit from adjuvant radiation therapy for DCIS.
The goal of therapy is to reduce ipsilateral breast tumour recurrence (approximately 50% of recurrences are invasive disease). Broadly (depending on prognostic factors) recurrence at 10 years ranges between 10-30% (very significantly less if hormone therapy part of treatment), 50% or recurrences are with invasive disease. With adjuvant RT reducing by more than half (~60%) this risk.
203
Discuss the role of surgery in liver HCC (include and compare):
Surgery - offers highest chance of cure: - Partial/hemihepatectomy: Indications solitary tumour <2cm. Generally well tolerated, offer highest chance of cure >70%5yr OS, but most disease does not present when indicated. Contraindications= multiple tumours, size>2cm, invasion into vessels. Pt must be fit for surgery. - Liver transplant: Offers excellent survival (Os 70% 5 years), however has long wait times for suitable donor, and often requires bridging therapy, pt must also be fit enough for intensive surgery. Indications (UCSF): Solitary <6.5cm (or 5cm Milan), or up to 3 small lesions with cumulative size <8cm.
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Approach to a patient with a pacemaker getting RT:
2 types: Cardiac output dependent pacing or not dependent. At booking initiate pacemeker pathway )physic team, planners aware, device contoured). In general avoid >10Mv if possible, total dose <2Gy. - Dependent: Vitals monitoring during each #, Device function assessment during treatment and at end. - Independent: If above constraints not met then vitals during. If met then just device assessment at end of Tx.
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Outline the Hx of low grade glioma trials: Treatment approach to low grade glioma
1) Non-believers: Early adjuvant - better PFS but not OS 2) Believers: 45Gy=59.4Gy, No OS benefit. SATAN criteria: Size>6cm, Age>40, Tumour crosses midline, Astrocytoma, Neurology. 3-5 factors = high risk. 3) Shaw - adjuvant PCV (after 54Gy) significantly increases OS. Median OS 13years. On sub analysis benefit only in IDH mut (both deleted and co-deleted) - Greatest gain = codeleted. 4) Fisher - low grade IDHmut AND 3 SATAN risk factors, 54Gy w/TMZconcurrent + adj appears better than controls. 5) Catnon - no-codeleted gliomas (anaplastic astrocytoma) has been assessed in the CATNON trial - final results pending, but so far OS benefit to 59.4/33 and adjuvant (but not current tmz). 6) Indigo trial - Grd II - Vorasidinib - IDH mut inhibitor - buys 2 years progression free. Therefore: For lower risk (SATAN <2) oligo it may be reasonable to delay adjuvant treatment, potentially give chemo 1st (Non-belivers,Baumert Trial). Grd II - consider delaying RT with Vorasidinib (Indigo) Grd III - Oligo (co-deleted): 54/30 followed by PCV (Shaw trial) - Astro: 59.4/33 with adjuvant Tmz. (CATNON) (Grd 4 Astro - Stupp, as these used to be GBMs)
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Give the SATAN criteria. Give your doses and treatment approach for low grade gliomas:
SATAN criteria: Size>6cm, Age>40, Tumour crosses midline, astrocytoma, Neurology. 3-5 Factors considered high risk. For lower risk (SATAN <2) oligo it may be reasonable to delay adjuvant treatment, potentially give chemo 1st (Non-belivers, Baumert Trial). Grd II - consider delaying RT with Vorasidinib (Indigo) Grd III - Oligo (co-deleted): 54/30 followed by PCV (Shaw trial) - Astro: 59.4/33 with adjuvant Tmz. (CATNON (Grd 4 Astro - Stupp, as these used to be GBMs) Brainstem/gentle dose - 50.4/28 PORT: CTV= residual GTV + operative cavity based on post-operative imaging. Inoperable: GTV on fused T1!!!
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Dose and volumes for a grd III brainstem astrocytoma
50.4/28.!!!! GTV = fused T1 MRI CTV=GTV+1.5cm (trimmed to boundaries) PTV=CTV+3mm
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Give treatment volumes for: Low grade gliomas: GBM
Glioma: Inoperable: GTV on fused T1. CTV= GTV+1.5cm. PORT: Residual GTV + operative cavity based on post-operative imaging. Use contrast to better deliniate tumour bed (obviously tumour wont enhance). GBM: GTV Bx only: the entire tumour on T1+C. GTV post resection: T1+C residual GTV (including the MASS/tumour component on T2/FLAIR)+ tumour bed CTV=GTV + 1.5cm trimmed to boundaries. Checked against T2 FLAIR abnormality which may be included beyond this expansion.
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Compare and contrast the radiology findings for: Oligo, astro, GBM
CT: 1) Califications: Astro (20%), Oligo (80-90%!), GBM (rare) 2) GBM: hypodense centre if large due to necrosis, thickened (dense) irregular edges due to hypercellularity, oedema, marked mass effect. MRI: T1 - most tumours are hypointense. BUT astros may be iso. GBM hypo to iso. Contrast enhancing. T2 (high water content): Oligo HYPER Astro HYPER GBM HYPER T2/FLAIR mismatch suggests Astro. Contrast enhancing: Extra-axial tumours, GBM and PILOCYTIC ASTRO!! Give 60gy SIB to the contrast enhancing bit of an Astro.
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A 3 year-old girl presents with a biopsy confirmed primary neuroblastoma of the right adrenal gland. After the completion of all relevant staging investigations, she is found to have a poorly differentiated, MYCN amplified, INSS Stage IV disease Expected OS with this treatment? Dose and technique:
Consolidative radiotherapy to a total dose of 36Gy/20: pre-op GTV 21.6Gy/12#, boost surgical bed to total overall treatment dose of 36Gy/#, 1.8Gy/#, 5/#s/wk to reduce LRR Remember 1.5cm on pre-op and post op CTVs. Pre-SIM - Consider GA Position: supine, arms up, head towards gantry- Immobilisation: vac bag - Planning CT: 2mm slice CT from thoracic inlet to femoral head (overing entire lung, kidney for OAR DVH) Fusion: pre-op and post-op MRI Target volume - GTV(pre-op) = post-chemo and pre-op right adrenal tumour - GTV(boost) = post-op gross residual disease - CTV21.6 = GTV(pre-op) + 1.5cm, clipped at anatomical boundaries - CTV14.4 = GTV(boost) + 1.5cm, clipped at anatomical boundaries - PTV=CTV+5mm 5yr OS 5-10%!!!
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A 4 yro has a left nephrectomy + node dissection for a favourable histology Wilm’s tumour. Pathology shows R1 resection but involvement of some left para-aortic nodes. There was no spill, or peritoneal involvement. What are the indication for radiation therapy for a child with Wilm’s tumour? (2m)
Adjuvant RT to flank (to reduce risk of local recurrence): Stage 3 (includes all the surgical stuff, Eg biopsy only, rupture, partial resection) Unfavourable histo. R1.
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Roa NOA Nordic Roa Explain
Key RCT trials for older people w/GBM Roa = phase III RCT - 40/15 = 60/30 NOA & NORDIC = TMZ = RT if methylated Roa = Phase III - 25/5 = 40/15 IF - age >64 Or - age >50 and poor performance status (KPS 50-70)
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Evidence and dose for re-irradiation in: GBM LG-Glioma
GBM 35Gy/10#: Particularly in pts who have relapsed after a reasonable interval of local control (e.g>12mnths). 1 RCT phase II RTOG trial randomised pts to bevacizumab with or without reirradiation giving 35/10. No OS benefit but significant PFS benefit. UK RCR Grade A - 35/10 Sub analysis suggests OS benefit in methylated patients and ECOG0. LG: 45/25. UK RCR
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For cutaneous SCC PORT when would you consider treating nodes
2 or more node mets Parotid node (unless parotidectomy and full nodal dissection) Size: any lymph node >3 cm. ENE +Ve nodal margin or spillage Close margins <2 mm to facial nerve. Recurrent nodal disease.
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Right forehead 2.0cm x 1cm x 7mm thick poorly differentiated SCC. Peripheral margins are well clear, the deep margin is 0.3mm. There is evidence of perineural spread involving several nerves up to 0.2mm in diameter at the deep margin. There are no signs of further disease on examination or imaging. A decision is made to proceed with adjuvant radiation therapy. Describe a suitable radiation therapy tdose fractionation schedule.
This is very high risk disease with extensive PNI with multiple nerves >0.1mm involved, deep invasion (>=6mm), positive deep margin (0.3mm, unexcised <2mm treat as +ve). PNI spread beyond foramina is incurable. Therefore in 30#s: R1(surgical bed) should get 63Gy CTV63=bed + 1cm trimmed to boundaries. CTV60 = HR PNI disease = CTV63+1cm (i.e 2cm expansion for PNI) CTV56 (intermediate risk) = CTV60 + skin and subcutaneous tissues extending from inferior border of CTV60 to the supraorbital notch (course of V1 branches), and to the superior edge of preauricular nodes. CTV54n (nodes and extended to stylomastoid foramen): Preauricular nodes with inferior portion extended to stylomastoid foramen. CTV54elective - Discuss with patient: covering supraorbital course of nerve to potentially to fissure.
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What are considered adequate surgical margins for: BCC SCC
BCC 3-4mm SCC and at least 4 mm for a low-risk SCC. There are no published guidelines for a high-risk SCC. 6-10mm is accepted range.
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What are the controversies around the utility of adjuvant radiotherapy for thymoma?
There is overall a lack of trial data (no RCT) regarding radiation for thymoma. For at least stg >=II (Mazaoka stage) prospective database review suggests adjuvant radiotherapy is associated with improved OS. This extends to patients who have had an R0 resection - opening the question of whether adj RT is reasonable for most patients. Lower grade (less than B2) have excellent 20year OS >=90%, and the role of radiotherapy in this setting is controversial given the outcomes without it, and the toxicities of RT especially late (cardiac, and second malignancy) given 20yr survival data.
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ii. What are the indications for radiation therapy in thymoma? Doses and volumes
- Inoperable - as local control or palliative. - Neoadj - to downstage tumour prior to resection. - Adjuvant: R1 and R2 resection, consider in R0. Thymic carcinoma. - Palliative: radioresponsive, decrease mass effect. NeoAdj = 45/25 R0 thymic carcinoma = 45/25 to thymic space R1= 54/27 - bed and thymic space R2 = 54/27 thymic space and bed + 60Gy boost (to GTV + 5mm)
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Discuss the role of systemic therapy in the management of metastatic prostate cancer. Include in your answer the class of agents used, duration of therapy and justification for use. 5 marks
- Anti-androgen medications - Typically non steroidal anti-androgens (e.g. Bicalutamide): In hormone naive pts: part of initial therapy + GnRH agonist +/- abiraterone (STAMPEDE ADT+enzalutamide + abiraterone no benefit). Alternatively can be used for 3-4 weeks as part of commencement of GnRH agonist - to prevent testosterone spike from initial LH surge. Can also be used when progression despite GnRH agonist (“total androgen blockade) to prolong PFS. ADT+ Apalutamide superior DMFS (SPARTAN). Used life-long or until significant progression. - GnRH agonist (e.g Goserelin 10.8mg s/c q3monthly), provides a PFS, OS and symptomatic benefit in patients with newly Dx metastatic prostate cancer, and is part of multimodal therapy as above. Duration life-long, or until progression, or in the setting of stable disease intermittent (restart when >10ng/ml). -Androgen synthesis inhibitor - Abiraterone: Improves OS and PFS (STOPCAT meta-analysis)- used in the following contexts - as initial therapy for newly Dx metastatic disease (in combination with ADT but not ADT+Enzalutimide STAMPEDE), or when progression on ADT/disease progression. -Chemo - Typically Taxane chemotherapy - Docetaxel, improves PFS and OS (CHAARTED phase III RCT OS increase from 48 to 58months) when part of initial Mx of metastatic disease. Also increases OS for N+ and locally advanced (STAMPEDE). 75mg/m.sqr (65mg for Asians) until response (up to 10 cycles).
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For rectal Ca, when may organ preservation TNT be attempted? What is the outcome?
OPRA Phase 2.- Stg II-III up to T3bN1 (3 or less regional nodes), 4nodes=N2. They maxed out at 5cm T size. FOLFOX/CAPOX -> Chemo RT may not be as good as ChemoRT -> FOlfox Capox 5yr organ preservation 50%
221
In general, with patients being treated for rectal cancer with external beam radiation therapy, how would you manage: (3m) i. A hip replacement ii. Excess small bowel dose within the field in a patient requiring neoAdj RT.
i. A hip replacement - Avoid high energy beam (e.g. 18MV) - Avoid beam entry through hip prosthesis - Contour artefact from hip prosthesis on planning CT and adjust densities in RT planning dose calculation - Get physicist involved - Review proximity between tumour to prosthesis - Oblique kv imaging for treatment verification ii. Excess small bowel dose within the field in a patient requiring neoadjuvant radiation therapy. - Check persistent over more than 1 fraction. - Re-SIM with full bladder to push bowel further out of field - Most conformal technique (e.g. IMRT/VMAT) and prioritize dose constraints to bowel - Prone position - Trim superior PTV expansion, and consider compromise coverage more superiorly (if safe to do so) - Daily CBCT to monitor, re-plan if required - Monitor GI toxicity, pre-med ondansetron
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Options for T3a-b N0 Rectum Ca
"Good" prog on MRI pts with minimal extension into perirectal fat (<15) may be considered for surgery only. Short course Long course TNT.
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Broadly, what are the chances of stoma reversal after TME?
75% in 3 years - aim at 3 months.
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Doses and volumes for all brain mets (resected/cavity and un resecected). Key planning goal for modern WBRT Criteria for SRS/SRT:
WBRT 30Gy/10# with hippocampal sparing. Aim Hippocampus D100 <10Gy. This is the conventional dose, if no hippocampal sparing do 20/5 (no evidence this is less effective). If 4 or less tumours and size <4.5cm 1) Cavity: SRS 12-20Gy <30cc 27Gy/3 >30cc 25/5 (note this is only dose different from defitive where 30/5) HR CTV = residual, bed, tract. 2) Intact SRS 16Gy-20Gy <30cc 27/3 (single 27/1 is in use) >30cc to less than <4.5cm 30/5. Volumes CTV=GTV, PTV=CTV+2mm
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What is the go-to Watch and wait study for follicular lymphoma? What stages/grd? What outcomes? Compare that with other data?
Standford study 2/3 patients not need Tx at 7 years. 85% 10yr OS. Compare that with: Taking all grades <3 RT 24Gy in 12 fraction + CVP/ R-CVP - TROG 99.03 showed improved PFS with addition of CVP/ R-CVP From 50% 5yr RFS to 60%. I.e Stanford study shows RT alone gives you a 50% chance of relapse free survival.
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For cervix brachy: Define target volumes Give Aims (target dose dose coverage) Give key OARs
HRCTV := Disease on Ex and MRI at time of brachy + entire Cervix. Aim D90> 85Gy EQD2 IR HTV= HRCTV + 1cm Aim D90>65Gy OARS: Bladder Dmx (2cc) <90Gy Rectum Dmx <75Gy, (D40Gy<60% ideal)
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Dose and technique for adj Brachytherapy component of definitive Cervix:
24gy/3#s, 3days apart, 2#s/week. Timed with final 2 weeks of RT (aim OTT <49 days), no chemo on brachy days. HRCTV D90 to receive 100% of prescribed dose. Pre-treatment - Anaesthetic review Applicator insertion - Under GA - Lithotomy position - Examination under anaesthesia (EUA): to assessment of tumour response (from external beam radiotherapy), cervix and fornix anatomy (for selection of appropriate applicator/ ovoid size) - Prep and drape - 18F 3-way IDC catheter inserted, 7-10ml balloon, bladder filled to 300-400mL normal saline - Uterus sounded to determine length of tandem applicator - Cervical os dilated - Insert applicator (tandem and 2x ovoid) under ultrasound guidance - Vaginal packing with gauze to hold applicator in situ - Position checked with ultrasound Planning Imaging: MRI pelvis performed with applicator in situ Target volume - GTV = macroscopic tumour (based on EUA at applicator insertion and MRI) - HR-CTV = GTV + whole cervix - IR-CTV = HR-CTV + 1cm expansion Plan review - Aim HR-CTV D90 of EQD2 85-90Gy with / of 10 (with assuming the entire volume received 45Gy in 25 fraction on EBRT) - Aim IR-CTV EQD2 65-70Gy - Review OAR dosimetry o Bladder D2cc<90Gy o Rectum/ sigmoid/ bowel D2cc<75Gy Treatment delivery - Treatment delivery in bunker, with patient in supine position - Treat with Iridium-192 radiation source - Applicator removed after each brachytherapy fraction
228
Doses for unresectable and borderline resectable pancreatic cancer. Give key studies and benefit for both:
Unresectable Proper (note that the role of radiation is controversional, especially with modern chemo FOLFIRNOX nab-Paclitaxel): 50.4/28 (45/28 nodes)- LAP07 improves LC no OS benefit Consider MASTERPLAN Trial Borderline: Approximately 1/3 can be made resectable. 45/25 or 36/15.
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Give the VMAT broad technique (not volumes OARS ect) for an intermediate medulloblastoma. Also key parts of plan evaluation. Through treatment what do you have to monitor?
Cranio-spinal irradiation to a dose of 23.4Gy in 13 fraction followed by tumour bed boost to a dose of 30.6Gy/17# (to total dose of 54Gy/30#) (1.8Gy/#, 5#/ week). (NB HR is 36/20 see then boot to a total of 54Gy - i.e 18gy). RT Technique: VMAT technique with 6MV photon * 3 isocentres (cranial, upper spinal, lower spinal), junction at 4cm depth, no feathering Plan evaluation: * Ensure CTV D98>98%, and PTV D98>95%, * Minimise hotspot: D2<105% of prescribed dose * Homogenous 16Gy covering entire vertebra body Additional * Weekly FBE monitoring (given entire vertebral marrow irradiation)
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Endometrial Cancer concurrent chemo: Adj chemo: Evidence:
50mg/m.sq D1 of week 1 and 4 (i.e Not weekly!!!!!!!!) Adj is Carbo Pac. PORTEC 3: OS and PFS benefit - Especially stage III, serous and p53abn
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Give Dose and approach to inflammatory breast cancer in each curative setting
Neo-Adj = inoperable after chemo. MDACC 66/44, 1.5Gy/# BD. Breast and nodes 50.1Gy, GTV+1cm to 66Gy. Adjuvant Residual/R1 resection: MDACC 66/44, 1.5Gy/# BD. Breast and nodes 50.1Gy, GTV+1cm (or area of +ve margin) to 66Gy. Full mastectomy and otherwise all good: 50/25 to everything. Use Bolus!!
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Outline the relationship between dose and cardiac toxicity risk
The risk of cardiac event increases linearly 7.4% per Gy, with no threshold This will likely be higher with the use of anthracycline-based chemotherapy and Herceptin
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Respiratory Motion Management Techniques Pros & Cons
1) Expiratory breathold: most reproducible, least movement. Cons: dificult, loose the benefit of reduced dose to oars. 2) DIBH: Often protects critical normal tissues. Minimal additional equipment. Con: limited by patient compliance/participation/lung function 3) DIBH + Active Breathing control: Highly regulated breathing if tolerated. Con: may be poorly tolerated extra set up time/training. Some evidence further reduces heart dose. 4) Abdominal drape/Compression: -less dependent on pt participation. can support smaller margins (lower ITV). Con - uncomfortable, may effect dosimetry for caudal tumours. 5) Vacuum drape: Less dependent on pt. Con: uncomfortable,long set up. 6) Real-time target tracking (e.g. MR linac): Great, super expensive. 7) Respiratory gating: Objective way to ensure reproducible position, increased treatment time, relies on tracking equipment.
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Recent evidence suggests which subgroups of locally advanced patients benefit from XRT post mastectomy and NA chemo?
More recent analysis in B-27 suggests 10-year risk of LRR is significant after neoAdjCTx (>10%) for the following patients: tumor size >5 cm, positive axillary lymph nodes, younger age, and incomplete response to NACT portend a higher risk of LRR.
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For each of these systemic therapies give the side effects for which they are famous: Taxanes Cisplatin Carboplatin Oxaloplatin 5-FU Capecitabine Etoposide Doxorubicin Ritux Cetuxumab
Taxanes: Perif neuropathy - cardiomyopathy if used with Acanthracycline. Most common: Fatigue>N+V, hair loss and myalgia. Cisplatin: common = N&V, electrolyte disturbances (especially low Mg, but also low Ca/k/PO4). Nephropathy also not uncommon. Not uncommon and consequential = Neuropathy, ottotoxicity. Carboplatin: Fatigue, myalgia, electrolyte disturbances (less than common than cisplat) Myleosuppression Oxaloplatin (e.g adj rectal ca) famous for peripheral neuropathy - 90% peaks at 6months. 5-FU: Mucocitis, hand foot and mouth - like rash, coronary artery spasm Capecitabine: Is converted to 5-FU Etoposide: Well known for GIT Sx: N&V, annorexia, bleeding gums, maleana. Myleosuppression. Leukaemia 2ndry malignancy. Doxorubicin: Allopecia, N&V, stomatitis, mucocitis, fatigue, acute reversible cardiac tox 10%, late not reversible approx 2% (risk proportional to dose and age, cardiac risk factors) Ritux: Super COVID Cetuxumab: Skin rash - 95% of the time.
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Most radiosensitive soft tissue sarcoma and dose
Myxoid liposarcoma. Only needs 36/20.
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Give doses for complete concurrent and adj Temzolomide course:
Concurrent: Daily 75mg/M.sq One month post: Monthly cycles (conventionally 6 but more can be considered): Cycle 1: Day 1-5 = 150mg/M.Sq/day Cycle 2 onwards: If tolerated increase to 200mg.
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Describe a whole brain hippocampus sparing technique for multiple brain mets:
Whole brain RT 30Gy/10#s, 3Gy/# VMAT technique with hippocampal sparing. 6MV photons. Prescribed to D50. Would include down to C2 if post fossa mets. Pre sim: dex, analgesia, anti seizure as required. Sim: Supine, head towards gantry, knee and ankle supports. Immob with thermoplastic mask. 1mm Slice CT scalp vertex to C7. Planing MRI (T1) to help deliniate hippos. Volumes: CTV = whole brain. Hippocampal Avoidance Zone = bilateral hippos +5mm. PTV = CTV+5mm with the hippocampal avoidance zone subtracted from this volume. Goals: 1) Hippo: Aim max dose <16Gy Min dose <9Gy. Blah.
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For a pre-menopausal lady, what should you consider before offering WBRT +/- hippo sparing?
- Prego, or up the duff. - For small volume asymptomatic disease, consider central nervous system (CNS) penetrating systemic therapy, if available. - Previous radiation therapy to the same site. - Cardiac implantable electronic devices (CIEDs). - Concurrent cytotoxic therapy. - Non-rheumatoid collagen vascular disorders. - Degenerative neurological conditions e.g. MS - Possible hydrocephalus Patients with favourable prognosis (>4 months life expectancy). Consider Brain metastases palliative EBRT hippocampal avoidance whole brain to decrease the risk of neurocognitive decline.
240
For defitive skin cancer treatment - what is the lowest fraction (least visits) dose schedule?
35Gy/5#, 7Gy/#, 5#s/week. (EQD2 52Gy)
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Field margins for cutaneous SCC: With key modifications SXR PTV?
"Guidelines vary" 1cm radial (unless PD the 1.5cm), 0.5mm below estimated depth. If T3 or higher deep margin is 1cm. If PNI then 2cm expansion. This is trick question - The above margin should include sub clinical extension and margin for setup errors and penumbrum (which is 0.5mm for SXR)
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An example of an SXR setup to achieve a 5mm D90 for 2cm lesion.
Prescribed to surface. Select SSD 20cm, Beam energy 120KV, AL filter 5mm
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How would you verbally give a skin electron plan.
"I would prescribe to the 90% isodose." "6MEV and with 1cm bolus, I would expect 90% Isodose at 1cm" "9MEV and with 1cm bolus, I would expect 90% Isodose at 2cm"
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Rule of thumb for picking an electron MeV to cover target depth: Rule of thumb for shielding:
Mev x 3 = R90 ie. 6Mev x 3 = 18mm Thickness of lead alloy = Mev/2 I.e. 6MeV then 3mm of shielding.
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Prognostic factors for BCC: Efficacy of topical treatment (and dose of preferred topical)
Patient: Immunosupression, Gorlin syndrome Tumour: >5cm (50% 5yr LCR), location in "H zone", Morphoiec, infiltrative, basosquaromus, recurrent, PNI. Treatment: R1 30% 2yr recurrence.
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The QUARTZ trial:
Phase III NSCLC non-inferiority study. Best supportive care vs WBRT in patients unsuited to resction or SRT/SRS. No difference in OS, QOL, dex dose. Subanalysis suggestive of a survival benefit age <60 or >5mets.
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For each situation for which WBRT (+/- hippo spare) may be considered comment on the evidence/benefit:
WBRT alone (where not appropriate for SRS/T): Main goal is to palliate Sx of brain mets/oedema, and prevent deterioration of neurologic function. Despite much investigation/meta-analysis, little evidence for OS benefit. The QUARTZ trial (unresectable/not for SRS NSCLC): no better than best supportive care except Pts <60. Adj: Increased LC, No OS bene, worse cog and QOL. No benefit whatsoever for melanoma (Hong). SRS+WBRT -
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48F Left 28mm, poorly differentiated SCC of anterior tongue, x2 LEFT level 2 nodes. Lingual nerve invasion. Hemi-glossectomy: 1mm margin, left neck dissection nodes fully excised. What do you do?
(Note about +ve margins. NCCN: <1mm is positive, <5mm = close). Given lesion PD and node +ve I would consider 1mm +ve. Can consider concurrent Chemo. Therefore I would treat EBRT, VMAT SIB technique to a maximum dose of 63/30, 5#s/week. Prescribed to D50. Pre sim: Dental review and necessary work Consider PEG Analgesia/PRN/anxiolytics as needed. Dietician Smoking cessation and other allied health such as psychology as needed. Sim: Supine, head towards gantry, in neural position, arms by side shoulders lowered. Immobilisation with thermoplastic mask, knee and ankle supports. 2mm slice CT+contrast, vertex to upper thorax. Fused w/planning MRI and pre-operative imaging. Volumes: CTV63= Tumour bed based on imaging expanded by 5mm and trimed to boundaries. CTV60=CTV63+1cm trimmed to boundaries. CTV56=dissected nodal levels AND lingual nerve to the stylomastoid foramen - could consider path of V3 to foramen. CTV54 = CTV56 + undisected bilateral nodes: 1a, 1B, II, III and IV. I would treat level V on ipsilateral side and omit IIa on the contraleral side. PTV = CTV54+7mm Daily CBCT matched to bone with soft tissue review. OARS (in EQD2): Brain Dmax<60Gy, lens Dmax<6Gy, retina mean <45Gy, Lacrimal duct Dmean<30Gy, Parotid mean<26Gy, mandible avoid hotspots, cervical eso mean<30Gy,
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Indications for splenic radiation. Dose schedule:
Indications = symptomatic splenomegaly: - Malignant e.g. AML, NHL - Cirrhosis related - Extramedullary haematopoesis (e.g. due to myelodysplasia). - Many more. 0.5Gy/# every second day with bloods every 2nd fraction. Titrated to clinical effect, total dose 10Gy.
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Gastric and gastroesophageal adenocarcinoma adjuvant EBRT chemoradiation: Indications Dose, Trial, Volumes
Indications: Node+ OR, T3 with R1, OR, T4. Int trial - OS benefit, but role of RT debatable (CRITICS trial, success of FLOT). 45Gy/25#, 1.8Gy/#, 5#s/week, concurrent with capecitabine and cisplatin. Consider R1 boost to 50.4/33. VMAT technique Volumes: CTVboost = Tumour bed +1cm CTV = CTVboost + Using table from TROG trial include CTV structures based on tumour location (gastroeso, proximal 1/3, body, distal 1/3). As per that guideline I would include pergastric and coeliac nodes and other nodal groups based on that table for each tumour location. PTV = CTV+1cm.
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For whole breast RT give OARs. Not in EQD2, But: 1) 40/15 2) 26/5
2.67Gy#: Lung V15%<15Gy Heart V20 Gy <5% Mean Heart Dose (MHD): <4 Gy 5.2Gy#: Lung V15%<8Gy Heart V7Gy<5%
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For the vulva: What is included in the primary CTV (at minimum)
GTV+1cm Whole vulva Sub cutaneous mons bridge.
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OARS and constraints: 40/15 Boob
Lung V16Gy<15% Contralateral lung V5Gy<10% Heart V20Gy<5% MHD<2Gy or 4Gy Contra boob mean dose <1.5Gy
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OARS and constraints: 60/20 Prostate
Rectum V40Gy<40% Bladder V40Gy<50% Femur V40Gy<50% Small bowel Dmax<43Gy Large Dmax<44Gy
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Describe Lutetium-177 treatment:
Lutetium-177–PSMA-617: - Beta-emitter with a half life of 6.7 days - Appropriate patients = castrate resistant, met prostate ca, with PSMA avid disease (duh) and have already had at least one line of anti-androgen therapy AND one line of taxane chemo. - Improves OS by ~4 months compared to “standard of care” - no phase 3 RCT vs things like carbazitaxel or Radium-223 so the NICE group wasn’t impressed enough to fund it in the UK. - Given by IV infusion, 200mCi once every 6 weeks for 4-6 cycles. Not necessary to do a post treatment uptake scan in most cases. - Pretty well tolerated. SEs include dry mouth, nausea, fatigue. - Risk of acute grade 3 myelosuppression modest (7-10%).
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Up to what stage may surgery be considered for cervix cancer? Give the Peters criteria: Give the Sedlis Criteria:
Disease localised to the cervix AND less than 2cm (Stage IA and IB1) OR IIA (upper 2/3rds of vag) NB: 1B2 (limited to the cervix but big = 2 to 4cm) = Chemo RT Peters (for post op chemo) = 3Ps = Parametrial Invasion, Pos Margin, Pos Node Sedlis (for adj RT) = SDLvi = based on size, depth of stromal invasion, LVI
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Give the key decision variables for RT dose/approach for: 1) Rhabdo 2) Wilms 3) Ewings
Rhabdo (Surg->VAC-RT or not if SIOP): Site (H&N/GU = 50.8Gy), Histo (RO alveolar 36/20), N+ (41/.4), Resection (alveolar or Embryonal R1 both get 36/20, R = 50.4). Wilms (NWTS is upfront surg +/-RT +/-Chemo): Stg 3 = adjRT = surgical events - Bx (seeding), seeding, piecemeal resection, STR, Rupture. Fav Histo and Stg 3 = 10.8/6Gy Anaplasia = Unfav Histo = 19.8Gy/11#, R1/R2 = Boost 10.8/6 WART (10.5/7) if Spill, Peritoneal Seed, Ascites Cyto+, Rupture (SPAR). Whole Lung if Mets: 12/8 (do SIOP approach, if Cr no RT to lung) Ewings (VCDA-IE): Response to chemo (<90 or >90%) Surgical Events: R1/R2Spill rupture, Margin <1cm Unresctable - neoAdj 45/25 Poor (<90%) response to chemo = prechemo GTV to 54/30 Good = 45/25 to prechemo, boost postchemo to 54/30.
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Cervix Cancer: The local anatomy (narrow vaginal vault) prevents optimal geometry for a 3 channel intracavitary insertion
- Alternatives : 1. Tandem and ring (with smallest ring) + interstitial needle (shown in EMBRACE study to improve dose coverage and conformity as well) 2. Tandem and multichannel cylinder (but dosimetry may be suboptimal) 3. If not possible to insert brachytherapy applicator, consider external beam radiotherapy boost (e.g. 20Gy in 10 fractions), accepting inferior dosimetry compared to brachytherapy
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The PACE studies (A and B) famously did not use what intervention that is touted as reducing toxicity? Exclusion criteria: Ongoing relevant trial?
Did not use (banned) spacer. Exclusions: 1) ISUP 3 or higher (i.e. no 4+3) Confusingly allows for "Intermediate and select high-risk prostate adenocarcinoma" 2) Node positive 3) Unable to have fiducials UNLESS using planning MRI (ideally MRI linac) 4) Previous pelvic RT Caution: large prostate (>80cc) Urinary function poor (IPSS>15, flow<15) IBD Bilateral hip replacement Previous TURP High-Five - SBRT 40/5 to prostate, 25/5 to pelvis (30-40Gy to +ve nodes).
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Sim and Target volumes for ultra hypo prostate RT:
Pre sim: urinary function, fertility/counseling. Comfortably full bladder, empty rectum. Sim: Feet towards, vac bag immob, ankle/knee and comfort supports. Planning: MRI in tx position ideally flat top couch, and CT non-con mid femur to L5 2mm. Fusion with PSMA PET CTV= prostate +/- proximal 1cm of SV if risk>15% of involvement (Partin table). PTV = CTV+3mm uniform expansion Dominant intraprostatic lesion (DIL) on MRI T2, Diffusion-weighted imaging (DWI) and Dynamic contrast enhanced (DCE), and PSMA PET GTV = DIL PTV_DIL = PTV40!!! = GTV+2mm, exclude urethral PRV. Urethral_PRV = Urethra + 0.2- cm radial expansion
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For palliative RT to bone Mets, compare 8Gy to 20Gy. Expected outcomes to either:
Wong meta-anlysis suggest euivalent, with potentially higher retreatment rates at 1 year for 8Gy (but possible selection bias). Note RCT/phase 3 data shows superior pain control with SABR at 3 months. Outcomes: 3-4 weeks for full response (median 3 weeks) 25% CR 66% Some response 33% NO response 20% (to 30%) Acute pain flair (80% in 1st week). - Evidence for dex prophylaxis is mixed. Phase 3 data sugggests a small reduction.
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Absolute indications for adjRT post skin SCC excision
1) T4 2) Positive margins (when further surgery is contraindicated e.g. associated with significant functional or cosmetic impairment). 3) Large nerve perineural spread. 4) Recurrent disease in an area previously not irradiated.
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In addition to the absolute indications (T4, recurrence with no prior RT, large nerve PNI, +ve margins w/o further surg possible), what are the relative indications to adj RT post SCC skin excision?
Relative indications (consider PORT when 2 or more present) T2 or T3 ≥6 mm DOI Close margins < 2 mm. Poorly differentiated. Pathological microscopic PNI LVI Immunosuppression. Higher risk sites, e.g. non-hair bearing lip, chin, ear, preauricular, periorbital, temple.
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Give the range of doses of Rhabdo (Hint dont bog down in detail)
Low risk R0 = 0Gy Give 36/20 when either: LR R1 IR node neg (either R0 or R1) 41.4/23 only when: IR node +ve 50.4/28: Macroscopic disease - e.g orbital embryonal Bx only (they love that one).
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Outline the findings of FASTTRACK II Give dose…
Phase II - Outcomes for: 26/1 (<4cm) or 42/3 (>4cm) kidney SABR. 1yr LC 100% 3yr FFDF 97% 3yr OS 82%. GFR reduction at 1 year =10mL/min Dose constrain ipsilateral kidney outside of ITV v10Gy<1.5cc
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Kidney SABR Dose (Technique next card):
Curative intent EBRT SABR technique w/motion Mx for 100%1yr LC. 26Gy/1# (if tumour<4cm), 42Gy/3# (2-3/# week, non consecutive day), prescribed to covering isodose, >=6MV photons.
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Kidney SABR Technique (not dose- another card):
Presim: - Pre-sim planning session to decide best motion Mx strategy. - Prg test/Hb/antimetics ect - Split renal function - Fast 3 hours prior (and prior to each#) Sim: Sup, feet towards, arms above head, knee, ankle supports. Immob with vac bag. Assume FB technique w/resp gating: 2mm slice CT mid Thorax to pelvis, 4DCT fused with Dx imaging. Volumes: iGTV=GTV contoured on all slices of MIP (checked against all phases of cycle) PTV=iGTV+5mm OARS (in EQD2) (as per FASTTRACK II): include constraints on ipslateral kidney, aim contralat kidey V10Gy<33%, SC Dmax<45Gy, Bowel DMax<50Gy. Skin, liver. Verification = intrafraction 4DCT, match to tumour volume. Aims: DMax = 125-143% of PD PTVD99>100% PD
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Indications on contraindications/cautions for kidney SABR
Indications: Localised RCC not for resection ECOG <3 Life expectancy >3yrs Contraindications: Tumour extending into bowel Very Cautious: tumour>10cm3 GFR<30
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At what ISUP and Gleason score would you not consider ultrahypo?
Pace A/B did not include 4+3 (ISUP 3) At this point the roach score is probably high enough for POP RT-style RT to date and nodes
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Mesothelioma options and key studies:
Imprint (ongoing phase 3) 50.4/28Gy after pneumonectomy and decortication + chemo (NA or Adj) Italian Phase III (included all histo): Lung sparring surgery the 50Gy to pleural and 60Gy SIB to residual. Very high grd III tox, bit high 2yr OS. No RT SAKK - Phase II RCT = no benefit to RT if Pt has chemo->EPP and
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Criteria for partial boob.
A number of studies vary in criteria. IMPORT Low: age >50 Unifocal IDC (any grade) Node negative <3cm.
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Compare Roach formula and partin tables. Which is clinically useful for deciding approach to unfavourable int risk Pr Ca.
Roach are 3 formulas bnased on PSA and gleason score to determine: 1) Risk SV involved 2) Risk node + 3) Risk extracapsular extension. The Roach formula for N+ (2/3PSA + 10(GI-6)) was used in POP-RT - if >20% do elective nodes (even when PSMA neg). Gleason score does no differentiate 3+4 from 4+3 - but note PACE A and B cut off for ultrahypo is 3+4. Partin table: Nomogram based on PSA, GI and clinical stage to predict whether the tumor will be confined to the prostate NB: both approaches do not use ISUP, and suffer from the pitfalls of using an overall Gleason score.
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Definitive RT to bladder - Just the volumes.
Contoured on empty, 15mins and 30mins post void for plan of the day library. GTV= lesion on imaging and examination findings (cystoscopy). CTV=GTV+5mm (gross extra-vesical extension) + bladder. Extra conditions: If VUJ invloved consider including 1-2 cm of the distal ureter. Male: - Involved bladder neck/trigone = proximal 1 cm of the prostatic urethra - Involved proximal prostatic urethra then whole prostatic urethra Ladies: With bladder neck involvement, multiple tumours or CIS, consider including the proximal 1.5-2.0 cm of the urethra. If the anterior vaginal wall is involved, include in the any remaining uninvolved anterior vaginal wall in the CTV. For posterior tumours, the anterior vaginal wall can be included in the CTVPrimary. If the vagina is included, consider including the proximal urethra.
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Outline the benefit of current chemo for definitive cervix chemo RT. Dose? What other agents may be considered?
Meta-analysis suggests OS benefit with tumours >=IB While the SUNSET trial suggests adj chemo after RT has no benefit (in contrast to NeoAdj carboTax INTERLACE), recent KEYNOTE trial demonstrates from stage IB2 onwards there is an OS benefit to concurrent then adjuvant pembro.
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Follow up after definitive bladder cancer RT: 2011 exam "What follow-up regimen would you recommend and why? (1m)"
- Surveillance cystoscopy +/- TURBT + cytology, 3 monthly 2 years, then 6 monthly year 3-4, annually 5-10 years – high risk of recurrence - Staging CT C/A/P 6 monthly – for 1 year.
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In your view, who is the ideal patient with high grade muscle-invasive bladder cancer to receive bladder- conserving management? Justify your answer. (2 marks)
A well insured patient who isn’t chatty. Patient: - Unfit for surgery - Adequate bladder capacity/ function - Satisfactory renal function for concurrent chemo - Compliant with endoscopic surveillance - Patients who prefer organ preservation Tumour Relative C/I if: - Large tumour >5cm, multifocal tumour, hydronephrosis, widespread CiS And only after safe maximal TURBT
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Outcomes for bladder Preservation RT: 1) Oncologic 2) Organ Pres 3) Toxicity
5yr OS 60% 5yr LC 60% - 75% LR are non invasive, 25% invasive 30% have distant mets, only 10%nodal. 5yr bladder preservation 60% Tox - Grd III GU - 10% (cyctitis) GI - 2% (proctitis) Other tox Sexual dysfunction Pelvic insufficiency fracture Lower limb lymphoedema 2nd malignancy Fistula
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Patterns of recurrence following bladder preservation:
5yrs: (60% organ pres, 60%OS) 40% local recurrence: 75% are non-invasive 25% invasive (i.e only 10% of patients get an invasive recurrence) 30% get distant mets (10% nodal)
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For rectal TNT give: Organ preservation rates Oncologic outcomes Toxicity
OPRA: 5yr = 55% (Long course chemoRT Consolidation FOLFOX) 5yr 76% DFS 75% OS, Toxicity: TNT is pretty toxic with 40% patient experiencing Grd III toxicity (Same rate as significant LAR syndrome post resection) 1.5% Grd V (death)
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Outcome for patients suitable for RT to the prostate alone (hypofraction vs ultra hypo): Toxicity Oncologic
60/20 is slightly less late GU toxic than 40/5. GU late Tox >= grd 2 is 25% (27%Ultra) GI late Tox >= grd 2 is 10% For int favourable and unfav *w/GI 3+4 but not 4+3): 5yr 85% BPFS 5% DM
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Approach to locally recurrent prostate cancer post RT:
A range of options: Surg (RP), Cryo, High Intensity Focused Ultrasound, HDR, LDR, SABR. Recent metaanalysis (MASTER) of phase II or less data suggests, RT has less GU and GI tox compared to surg. HDR or SABR could achieve 60% freedom from progression at 5yr (the highest compared with resection, LDR, and cryo 50-54% FFP). HDR offered the lowest rates of severe GU 9% or GI tox 0% Therefore HDR offers good control, limiting re-irradiation to surrounding OARS and subsequent toxicity.
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Critical in deciding when to include brachytherapy in adjuvant chemoRT for endometrial cancer: Target volumes for the EBRT component and chemo
Parametrial involvement CTV= upper half vag and paravag tissues, parametrium. Contoured on full and empty blader and merged for iCTV. CTV nodes: obturator, internal iliac, external iliac, pre-sacral nodes, and common iliac + 3cm above the highest involved nodes. PTV=CTVnodes + iCTV+ 1cm. 2 cycles cisplatin 50mg/m2, week 1 and week 4 (as radiosensitizer) Adjuvant chemotherapy: 4 cycles carboplatin (AUC5) and paclitaxel (175mg/m2), every 3 weeks
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Describe the PROSPECT trial: Compare cohorts between this trial and OPRA.
PROSPECT RCT trial demonstrated that neoAdj RT could be avoided (if >20% response on MRI to FOLFOXx6 AND followed by TME and more FOLFOX). LC chemoRT->TME-> FOLFOX x8 Vs FOLFOXx6 assesses and if good -> TME -> FOLFOX x6 (Note 4 more cycles chemo) Long term toxicity may be worse in LC chemoRT->TME-> FOLFOX group (sex, fatigue, neuropathy). Roughly same cohort as OPRA. T3N0-T3N1.
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Conditions for resectable pancreatic cancer:
1. No arterial tumour contact of coeliac axis, SMA, and common hepatic artery 2. No radiographic evidence of SMV, or portal vein contact, or <180deg contact without vein contour irregularity
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Pancreatic cancer key trials for: Resectable:
Folfurinox superior (PRODIGE) ChemoRT equivalent to (older=gemcitabine) chemo alone but less toxic. RTOG: with improved resecability imaging criteria 50.4Gy+BD cap has good outcomes for N+ (same as PRODIGE = 5yr OS 45%).
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Pancreatic cancer key trials for: Borderline Resectable:
Unresctable 5yr OS 5%, resectable 20% (in PREOPANC). Surgery in the borderline group followed by gemcitabine is 7%5yr OS Gemcitabine + 36/15 starting on c2 of gem increases OS to 21% (PREOPANC 1) Pre-operative FOLFIRNOX alone is not superior (8 cycles then surg), with Chemo RT less toxic (PREOPANC2)
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Pancreatic cancer key trials for: UN-Resectable:
Some controversy but one high-level bit of evidence: LAP-07 (Phase III): No OS benefit to 54Gy + BD cap vs gemcitabine. Possible improved LC. The greater effectiveness of FOLFURINOX may further undermine any benefit to RT. BUT: Pooled analysis suggest may be some benefit to the addition of SABR to systemic therapy. MASTERPLAN ongoing = FOLFIRNOX+ 30-40Gy in 5#
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Preferred option metastatic pancreas.
FOLFIRNOX - much better OS than gemcitabine. Growing evidence for SABR in oligo mets. EXTEND trial - phase II. 1-5 mets 50/4 to 70/10 given (40/5 typical dose to primary) 1 year PFS 40% vs 9% systemic therapy alone.
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Options for resectable gastric cancer:
1) Preferred: Perioperative FLOT, superior to periop ECF (MAGIC). 4cycles pre, 4cycles post. 2) FLOT-ChemoRT -> Surg -> FLOT (NOt superior to FLOT alone or MAGIC), but may downstage, higher path complete response. TOPGEAR 3) NA chemo - Surg - ChemoRT. No better than MAGIC alone (which is inferior to FLOT), not superior to neoadj chemo. CRITICS 4) Surgery alone. Early work (pre D2 resection - MAcDonald) underlined OS benefit to additional modality (e.g. INT adj Chemo RT), ARTIST studies (1 and 5) show need for RT where less than D2 or R1 or higher resection.
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General Mx paradigm for ACUP:
If markers/IHC and Ix fail to identify: 1) Molecular cancer CLASSIFIER assay - can "predict" to some degree in in about 60% of cases. 2) Establish actionable mutations (Comprehesive Molecular Profile) and predictors of of response to immunotherapy - Tumour Mutational Burden (Mutations create neoantigens that the immune system may attack - e.g. T-cell directed Ipilumimab). Tx: If solitary met (much better prognosis) aim resection or ablative. If belongs to a clinicopathological subgroup (30-40%) e.g. Female with axillary mets (better prog), Female with peritoneal carcinomatosis, dude with bone mets and elevated PSA - then directed therapy has much better PFS. If target mut, or high TMB score, then directed therapy. If and only if none of the above "Empiric Chemo" doublet w/platinum: Classic combos Carbo Pac, Cis Gem.
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General treatment paradigm for ovarian cancer:
Most common (90% epithelial origin Ca125 marker, most common of which is serrous = better prog than others). 1) Surgical staging. TAHBSO + pelvic + PA node dissection. + Cytoreductive surgery (e.g. bowel rescection/hemi-hepatectomy) if indicated. 2) Adjuvant chemo = platinum doublet - typically carbPac. For minimal post op residual consider intra peritoneal chemo. 3) BRAC associated - maintenance PARP inhibitor 4) Recurrence = "platinum resistance". If fit Paclitaxel is common second line - docetaxel may be 3rd line.
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Discuss all the options for 1-3 brain mets:
1) Biologic therapy alone until symptomatic or progression. Common approach. Spares RT tox. But recent evidence (e.g. SINDAC) points to OS benefit in setting of oligmetastatic disease (e.g. TKIs are oncostatic, RT is oncoreductive). 2) Surgery preferred if possible in large or symptomatic disease. Older data suggests OS benefit, quicker reduction in Sx, quicker reduction in oedema (less steroids - commence earlier immuno). Adj SRS or WBRT for improved LC (possible decreased neurologic death). SRS adj preferred due to better cognitive outcomes (MDACC) 3) Primary SRS (unless >6cm, or 12, or very small) due to improved neurocog (MDACC). 4) WBRT w/hippocampal sparing (ideally with memantine) phase III data shows superior neurocog outcomes to WBRT. 5) WBRT - 20/5 less time toxicities better neuro PFS than observation 6) Observation/best supportive care. May in patients >60, or poor performance status offer equivalent OS and QoL. QUARTZ: WBRT benefit OS on subanalysis in mets >=5 or age <60. Trend to benefit if no extracranial disease, higher GPA.
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OARS/tolerances for prostate and nodes:
In EQD2: Rectum V40<40 ideal (accept up to V50Gy<50%) Bladder V40Gy<60% (may accept higher) Femoral heads V40Gy<50% Small bowel Dmax<54Gy V45<195cc.
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Which Desmoid tumour patients should be considered for local therapy? Give the options. Give some issues with the RT option.
For high-urgency patients = Significant Sx, high risk from mass effect, rapid recurrence or growth: Surgery gold standard: >20% Recurrence despite clear margins RT 54/30 (or 59.4/33): Limited retrospective data suggests LC 80-90%. Benefit appears independent of size. May take many months to years for significant regression - therefore may not be an option where life-impacting Sx. Chemo in cases of high-urgency/treatment failure/cant have surg or RT = doxorubicin = 75% RR Sorafinib has also been used
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For desmoid tumours. Give treatment options for mildly symptomatic patients, where minimal risks associated with mass effect:
1) Nirogacestat a targeted therapy. 40% 2) SOrafinib: 80%PFS (interseting 20% response in placebo group) 3) Tamoxifen: 50-60% CR/PR response +/- NSAID 4) NSAIDS: some limited data NB: if urgent debulking then chemo = Doxorubicin 70%RR
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Mx approach to operable cholangio carcinoma:
Intrahepatic: Hepatic resection +/- node dissection (opinions differ) Extra hepatic: - Perihilar resection (60% of cholangioCa's are perihilar). - Distal Whipple = pancredudenectomy (do same for Ampullar Vater Carcinoma). _______________________________________ Surg->Capecitabine has OS and DFS benefit (BILCAP) IF Extrahepatic & either N+ or R1 SWOG Trial (for N+) OS benefit compared to historic controls: 54/30 to bed 45 to nodes (boost R1 to 59.4/33).
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General approach to inoperable cholangiocarcinoma:
Chemo: Gemcitabine + Cisplatin. Some evidence for RT as consolidation (no progression): EBRT or SABR. If Metachronus: consider a COMET approach.
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Approach to unresectable (at most mets to liver) gallbladder carcinoma (also for the fuck of it give a sign of GB cancer on Ex)
Courvoisier's sign (he described it in himself): Painless (i.e. not gallstones) palpable GB mass + Jaundice = probable tumour (e.g. HOP, GB Ca) RACE-GB: Cisplatin + Gemcitabine x4. IF stable or PR 45/25+ 9Gy boost concurrent with capecitabine improves OS from 4 months to 10.
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Mx principles for DIPG
Dx does not require Bx. Enroll in trial if possible given 10month OS. Dex is critical Sx Mx step in initial Sx Mx, Bevacizumab reduces vasogenic oedema and can help substitute for Dex when long-term side effects become concern. RT is the only standard disease imapctful intervention: Doses: 59.4/33 to 54/30 (larger) Mindful of time tox 36/13 and 45/15 may also be suitable (and equally toxic) - a trial randomised to 54, 45 or 36Gy. CHemo: Tmz has no benefit and adds toxicity. Investigational: H3K27M vaccine looks promising as does CAR T cell.. Retreatment: Small prospective trial suggests not too toxic, may have clinical, QoL and radiologic befefits
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Glioma retreatment doses and benefit:
Best option is re-resection if possible. Grd III - 45G/25# - GBM 35Gy/10# (but size and ultimately goals of any irradiation should be considered - eg. SRS or SRT to small lesion, 45/25 to larger). A minimum dose above 36 EQD2Gy is needed (EANO) Both SRT and different EBRT fractionation schedules have been studied with similar OS of 7-10months. With genera; theme being a PFS benefit in the order of 2-4 months,. The use/benefit of concurrent systemic therapies is still an area of active investigation. Recent TROG phase II study shoed a 3 month PFS to Bevecuzumab + 35/10 (compared to Bev alone) with this sub analyis suggesting a small OS benefit to methylated and or good (KPS>90) function patients.
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Oral cavity: Besides location, when would you treat bilateral nodes? General "nodal formula"? What surgeries and the evididence surg V. RT
3 or more nodes. 1B,II, III. Bucal mucosa then parotid nodes. Include level above and below. e.g. IB then 1A (also if FOM). Surgeries (all with elective nodal dissection): Supported br D'Cruz study: better OS, and preserves function (taste ect) Hemiglossectomy with freeflap recon Retromolar surgery = marginal mandibulectomy +/-recon.
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For Larynx Ca: How common is verrocous Ca? What are its RFs? Bio Beh? Preferred Mx?
1-5% RFs: Chewing Beatle Nut or tobacco. BB: Locally invasive/destructive, mets rare. Prefeered Mx is surgery.
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Indications and dose/volumes for RT for neurblastoma:
High Risk defined as: IV= Distant mets or non-regional node(s) Stg II or III AND N-My Amplification N-Myc amplification is critical. Induction (chemo)->consolidadation (surgery, ASCT, RT) ->maintenance. Dose: Total of 36Gy: 21.6 to pre chemo GTV, 14.4 to post (1.8/#). Volumes (expand by 1.5cm!!): CTVpre = GTVpre+ 1.5cm CTVpost = GTV/bed + 1.5cm
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indications for PORT for vulva SCC
SLIM Size>5cm LVSI Invasion>5mm Margin <8mm Also Nodes and ECE. Other factors to consider from Heaphy study: Spray histology
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For advanced stage DLBCL what is the current state of RTs role? What is your approach?
Treat residual avidity to 40/15, with surrounding site (ISRT) to 30Gy SIB. For stage EBRT following systemic Rx. Recommendations largely based on retrospective and cohort data, with limited randomised data. In the era of accessible PET there is a trend towards PET adapted treatment and less weight given to bulky disease at Dx to identify patients who will most likely benefit from the addition of RT. Important patient and treatment factor to mention = whether pt is suitable for salvage therapy with transplant or not. Pre PET-directed studies: Ricover - 10% PFS benefit to RT in elederly pts w/bulky disease UNFOLDER:
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CROSS RT is concurrent with? Followed by what and when?
Weekly carboplatin 2AUC and paclitaxel 50mg/Mqr Followed by surgery at 4 weeks
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Volumes for CROSS
Consider tumour marker with lipidel fiducials for hard to see GTV iGTV on 4dCT. CTV = iGTV+5mm axial & 3cm sup-inf. PTV 7mm
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You want to give CROSS style RT to a distal esophagus SCC. What are the OARS?
In EQD2: Heart (is gonna be slammed so be realistic) = V40Gy<30% Kidneys V20Gy<20% - if one kidney >12Gy do split renal function. - consider protecting one kidney based on Mag3 study or dose to1 kidney>18Gy Liver - mean<30Gy Lung - V20Gy<15% SC - DMax<45Gy
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An asymptomatic 55-year-old man is diagnosed with non-small cell lung cancer (NSCLC). Staging investigations at diagnosis reveal a peri-hilar 4cm primary tumour with right hilar lymphadenopathy, and a solitary 13mm left cerebellar metastasis on MRI (T2aN1M1b). Lung function tests are within normal limits. General approach:
Treatment of the primary improves OS (Gomesz study). Treatment of oligomets in the setting of controlled primary disease may (phase II COMET) also improve survival. Therefore in addition to targeted molecular (LAURA) and immunotherapy (e.g. PACIFIC for stage "III" like disease): Treat primary 60/30 + chemo Treat brain met - surgery has OS benefit, so do that, then cavity 27/3. Acknoweldge that brain met is asymptomatic and if EGFR+ - may be reasonable to avoid aggressive Mx until progression.
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What are the Mx options for Ewings of the sacrum (2marks): The tumour is inoperable. Give dose and volumes (FTW)
Induction chemo -> local treatment -> Consolidation: Induction Ctx (6x VCD+IE 2-weekly) = consolidative Ctx (6x VCD + IE 2 weekly) Some extra info: Definitive dose= Total 54/30: GTV45=pre chemo bony+ pre chemo soft CTV45=GTV45+1cm. GTV54=pre chemo bony + post chemo soft. CTV54=GTV54+1cm.
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For stage I inoperable lung, what is the evidence for SABR vs Hypo#?
LUSTRE Trial 2024 (not well powered, and trend p=0.15 for SBRT): 48/4 (or central 60/8) (some evidence equivalent to 54/3 but I have doubts) vs 60/15 Equivalent - trend for better control with SBAR
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When does dick cancer become stage II and what does it imply? Approach to nodes in doodle cancer?
(T1 = below dermis but not corpus) T1b= LVI or PNI As soon as any lymphatic risk then stage II - needs comprehensive nodal assesment: N0 = SLNBX or modified ILND N1-2 = 1 st prove with initial FNA/core Bx then if confirmed - radical LND - different options (uni vs bi) Adjuvant Tx - pelvic node dissection, chemo, RT
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Describe the treatment options (including preffered) for stage III NSCLC:
Stage 3 is a heterogenous group. key is wherether any mediastinal nodes (N2). Break down into. 1) T3N1 (intra, pulmonary, hilar, peribronchial): Surgery (with induction systemic or perioper, or adj OSI) preferred where fit patient, resctable disease.. 2) N2 (mediastinal): Pacific trial approach preferred. Surgery may be considered in select cases: - Single station N2 disease. - Resctable with lobectomy rather than pneumonectomy, durvalumab (or LAURA trial)
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What stage is TanyN2MO lung cancer? What are the options?
Stg 3. N2 = ipsilateral mediastinal nodes. Pacific trial approach preferred. Surgery may be considered in select cases: - Single station N2 disease. - Resctable with lobectomy rather than pneumonectomy,
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Not that you would, but what are the key features of a prostatectomy pathology report that would suggest benefit to adjuvant (as opposed to salvage) RT
+Margins and Think T-Stage: Extracapsular extension = T3a SV involvement = T3b Invasion = T4 Node + Other risk factor for LR is PNI.
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A dude has a PSA of 3.141 1 year post RRP (initial PSA 0). PSMA and MRI demonstrate a nodular recurence 1cm in the tumour bed. No disease elsewhere. Outline approach with doses: What if also single pelvic boney met?
Treat as per SPORRT with 6 months ADT and: SIB in 20# GTV+5mm 55Gy (EQD2 68Gy), but consider OARS Bed 52.5Gy Nodes 44 Do the above, but ADT 2 years (treat like HR, with curative intent). SABR the met: 24/2 - if big consider 35/5.
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Breast cancer re-irradiation dose And benefit Should they all get some chemo?
45/30 BD PBI Phase II study suggests well-tolerated, w/low5yr Mastectomy rate ~10%. CALOR Study - OS benefit in ER-ve, otherwise benefit replaced by an aromatase inhibitor.
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For Rhabdo - give the definitive dose, treatment sequence. Outcomes from definitive RT
VAC, start RT week 9 of chemo. 1) 59.4Gy/33# post chemo IF: Incomplete response to chemo Unfavourable site (prostae/bladder, exteremity) Age >18 BUT parameningeal do 54/30. 2) 50.4/28: E.g. orbit 5yr LC = 75%, OS =70%
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Why is the Prodige 23 Trial your go-to rectal trial? Give the sequence/timing. Outcome? Who might you consider not for this approach?
Solidifies the role of NA chemo - in particular FOLFURINOX. Demonstrates an OS , DFS, MFS benefit (only trial to do so) for NA FOLFURINOX x6 -> 50/25+ cap -> TME (6-8 weeks post RT)->FOLFOX or just capecitabine. Better than 50/25+ Cap -> TME ->Chemo (FOLFOX or Cap). 82% at 7 years. ?Is this over-treatment for T2N1 (below lower limit of trial )? Yes consider OPRA (TanyN0-N1M0): Also where pat want to persue organ preservation and disease at most N1 (i.e. inside mesorectum) 50/25+ Cap FOLFOX and watchful waiting - 50% avoid surgery.
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Approach to cervical esophagus SCC: Dont forget the chemo!!!
Concurrent and adjuvant chemo are needed. A variety of approaches can be considered. I prefer 60/30 + cis and 5-FU. From only phase II trial (Japanese). Treat nodes 54/30 if large >3cm or through adventitia. Nodes= 3/4/SCF. Followed by more of the same chemo. Some may treat like H&N (very valid, some guidelines). But cervical eso then likely to stricture with very poor QoL. Also some data (ART-DECO) that dose escalation of eso Ca (including SCC) not needed. Treating as conventional eso is 50/25 (or 2Gy higher) and not treating nodes also not uncommon.
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A patient with dMMR colorectal cancer. What unique treatment option may they have?
A phase II trial has shown 100% cCR to Dostarlamab (PD-1 inhibitor alone)..... Same drug - very good results with Carbo Pac locally advanced endometrial
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PTV for liver SABR PTV for kidney SABR
5mm, except Sup-inf 8mm Kidney - 5mm
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Any evidence for prphylactic palliative RT to asymptomatic bone mets?
Yes. Can reduce skeletal related events. ` Recent phase II trial showed for HR lesions: "bulky" >2cm - Spine: if involved posterior elements or sacroiliac joint, or >1/3 bone. - Hip joint - Long bones with mets >1/3 cortical thickness (but obviously not needing nail.
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Dose for LDR brachytherapy is?
Dose for LDR: 144 to 145 Gy for I-125 (D90>145Gy) 125 Gy for Pd-103.
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Half life for the most common LDR source? Safety advice
I-125 1/2 life 59 Days. Minimise contact with: Preg ladies, kids. Strain urine Barrier contraception Dont get cremated (intentionally) in 1st year....
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Describe Ir-192
A common HDR brachy source. Strong Gamma emitter - with average energy around 370Kv. 74 Day half-life. Pliablbe material suited to brachy delivery system.
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Critical investigations if local prostate recurrence post RT: Detail your treatment approach:
Workup: PET, MRI, and biopsy - all to localise position of tumour. If unifocal CTV = tumour. BUT evidence suggest whole prostate RT is well tolerated. Multifocal - Tx whole prostate. Meta-analysis (MASTER) shows SABR and HDR offer 5yr relapse free survival of 60%, and 1/10 risl >=grd3 urinary tox, and very low late GI tox. Overall MASTER metanalysis suggests RT (SABR or HDR) associated with better DFS and toxicity than surgery.
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Folicullar lymphoma: Who may be considered for observation vs active Tx? General outcomes for treatment of early FL? Can RT be de-escalated further?
Low-grade (I-II) low stage (I to contiguous II) FL is an indolent disease, and in this group some patients elect for observation. A large population cohort study demonstrates however that RT may improve 10yr OS 70% vs 50%. At 10yrs RT affords 70% LC and 40%PFS. While 24/12 seems equiv to higher doses, 4Gy his much less PFS at 5 yrs (70% Vs 90%) FORT trial.
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Broadly discuss role of systemic therapy for endometrial cancer (not-retreatment/recurrence):
Maybe considered from mucle invasive grd 3/pap serrous (but not strong recommendation - NCCN 2B) PORTEC 3: Benefit from stg 3 to concurrent cisplatin -> 4 cycles Carbo PAC- OS benefit in stg 3 (mostly in pap serrous and p53abn on sub analysis). Carbo Tax is isoeffective to chemoRT+adjCarboPac (GOG258), but more tox. Lower distant mets, higher local rec. Advanced Stg III/IVa - adding Dorsalimab to carbo/Tax (no RT) increased PFS - larger benefit if dMMR
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Systemic approach to recurrent endometrial cancer:
1) PD-1/L1 directed + carbo pac. If dMMR consider Dorsalimab 2) Endocrine: E.g. alternating megestrol/Tamoxifen.
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Define locally advanced breast cancer: Not by coincidence, who should be considered (or defiitely have) NA chemo? Describe the chemo
Locally advanced = N2 (T<=3), N3 (=>10nodes or SCF), T4 NA: Young age and N+ or T3 (B-27 included T3N0) Tripple neg Inflammatory Aggressive subtype - e.g. medullary (young) or papilliary (old) AC (4 cycles) + T (give peruz+trast with T). A = doxorubicin C=cyclophos HR/inflamm consider dose dense = cycles of 2 weeks Tip neg - consider dose dense. Keynote supports pembro, phase III data for capecitamine if incomplete response.
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For patients with stg II-III NSCLC, who cant have chemo, is accelerated hypofractionation better?
Nope: Southwestern Trial (randomised): 60/15 is not superior to 60/30 (?inferior) but significantly more grade 2 esophagitis Non signif trend to better OS 2Gy/# 1yr OS 45 vs 38% (p=0.29).
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What is the preferred surgical approach to T1 NSCLC? Any evidence for a combined approach to T1-T2?
Sublobar resection and mediastinal sampling (Typically VATS) non-inferior to lobectomy. MISSILE Study: Phase II pre-op SABR-> resection, Undewheliming pCR at surgery Toxicity Ok Only phase II but outcomes seem comprable to giving immunotherapy in this group.
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Define SABR
Stereotactic ablative body radiotherapy (SABR) refers to the precise irradiation of an image-defined extra-cranial lesion with the use of high radiation dose in a small number of fractions (Typically less than 9). Its aim is to deliver an ablative dose of radiation to a tumour, while tightly limiting the volume of normal tissue exposed to a significant dose of radiation. (SABR Consortium UK - best to quote in case you miss something on their magical list).
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By stage give the Mx of seminomas:
Node -ve (stg I): Options: surveillance (15-20% recurrence), PA strip 20/10 = Carboplatin 1-2 cycles (TE19) - recurrence (not OS) improved to 4-5%. Node <2cm: Modified (no obturator) Dog-Leg 20/10, boost undissected node to 30/15. OR BEPx3 or EPx4 OR Craboplatin + RT OR Nerve-sparring RPLND Node 2-3cm: As above BUT higher boost to undissected node 36/18 Node 3-5cm: NCCN BEP3 or EP4 Stg IIc (>5cm) or non-local nodes: LR (at most pulm mets): BEP3 int Risk (non-pulm mets): BEP x4 (Note there is no such thing as HR seminoma)
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For non-sem GCTs outline the general treatment path:
Node neg: Surgery: If no RFs (LVI, scrotal/cord invasion, not predominantly embryonal) - surveillance preferred IF RFs: BEP1 or nerve sparring RPLND Node Pos: Markers -ve and local node only: BEP3 (or EP4) or nerve sparring RPLND. Positive: Consider re-resection then adjuvant as above. Non local: BEP 4
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- Pure Seminoma- Indications for Modified Dog-Leg? What makes it modified? Dose? Technique and volumes.
N+ where either: 1) Node <2cm: Then do 20/10 and boost undissected node to 30/15. 2) Node 2-3cm: 20/10, boost undissected node to 36/18. PA strip: from 2cm below superior pole to aortic bifurcation. expand VC+aorta by 1.5cm (PTV+7mm) The leg: from Bifurcation to superior margin acetabulum expand the following Arteries & Veins: Common, internal, external. VMAT or 3D Planned AP/PA 10-18MV.
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Describe image verification for lung SABR
For gated lung SABR treatments, 4D-CBCT should be used at each fraction to ensure that the tumour motion remains consistent with the planning 4D-CT and the associated gated window. Basically if it moves do 4DCT (especially if that is what you planned on). Intrafraction CBCT may be acquired between or during arcs or trigger imaging may be used to assess target/surrogate position during beam on time. Post treatment CBCT very optional.
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Give the toxicities for lung SABR:
Varies by site: Ultra central (SUNSET 30 patients): 60/8 (but consider 60/15 LUSTRE) - No pulmonary haemorrhage - 1 case signif dyspnoea - Life ending pneumonia. Central: Phase II data looking at dose/# found 50/5 very well tolerated. At higher doses: Dyspnoea, esophagitis, fatigue, chest pain. Consequential rare = pulmonary haemorrhage, cardiac (CHF, arrythmia), pneumonitis very rare. Mid (CHISEL): Cough, pneumonia/pneumonitis, chest pain. Rare: Dysponea, dysphagia, chronic chest pain. Possible: Brachial plexopathy, necrosis. Peripheral: 47% Risk chest wall Sx: 40% grd I/II, 7% grd >=3 6% risk of rib fractures. Pneumonitis 2% Rare: Grd 3 esophagitis, dyspnoea
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How does SABR compare to surgery for early NSCLC?
Data very limited, 1 phase II trial (STARS) and a VA study which is ongoing (but is threatened by descent into autocracy and subsequent funding withdrawal). STARS Trial: Prospective propensity matched, small N: No diff in OS, but trend towards surgery having better LC and less mets.
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Current approach to Iodine refractory Papillary or Follicular thyroid cancer:
Metastatic typical treatment is Levatinib - phase III against placebo, very large benefit. But Re-Differentiation therapy (restoration of tumoural 131I uptake) is common, though only limited data. This approach exploits the TKI pathway mutations common to PTC (Braf V600e in 50% - Debrafinib) and Follicular (NRAS/HRAS - Drabatinib). Consider enrollment in the I 1st trial
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For GBM: Elderly/low function RT doses: Re-irradiation For LG glioma: Re-rradiation
Old/crap: 40/15, 25/10 Re-irradiation: 35/10 LG: 45/25
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For salivary gland ACC with extensive large nerve PNI, what nerves to you cover and to where?
Gland innervation from hypoglossal nerve, V3 and mandibular branch of V. So: V3 to ovalis (ORO = V1orbit fiss, V2 Rotund V3 oval) Hypoglossal canal V = styolmastoid foramin
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A fit 70yro lady with an asymptomatic, unresectable solitary lung adenoCa brain met with EXON19+ EGFR mut. What is a relevant trial?
OUTRUN - RT then Osi Also consider SINDAS trial and the argument that Osi is more tumour static, so may work better when combined with a cytoreductive intervention..
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Compare (exact numbers) analgesia effects and local control of spine SABR vs palEBRT
At 3 months Phase III TROG data: SABR 1/3 have CR clinically 20/5 15% At 2yrs Local failure 15% in SABR vs 33%EBRT I Say: SABR at 1 yr >90%, EBRT 80%.
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Outcome of the INSEMA trial
For patients with T1, and T2 breast cancer, and WBRT Omission of SNBX not inferior to SNBx in terms of DFS. But 21% of T2 patients had +ve nodes... And evidence (e.g. MA20) supports a DFS benefit in this group.....
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Describe the SANO Trial
Phase III non-nferiority - Locally advanced esophagus cancer (adeno or SCC) with CR post CROSS. For CR: Active surveillance at 2 years is not inferior to surgery at 4 weeks. 2yr OS 75%.
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For unresectable liver HCC what drug is typically given in addition to SABR? What is the expected outcome?
Sorafinib + SABR (unsuited to or refractory to TACE) Median OS 16 months.
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Dupuytrens dose and evidence and outcomes. Beam energy
Now Phase III: 15/5 (5#/week) -> 10-12 week break -> 15/5 (5#/week) Optimal Orthovoltage 120Kv 25% symptom relief 85% local control at 5 years. 15% grd 2 dry skin
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Options for Early stage Hodgkins 1-2 sites:
In this setting the omission of RT is NOT non-inferior for PFS (H10 and RAPID). But options need to be considered in the setting of late toxicities. Informed by PET after Cycle 2 ("PET2, "ePET"): If PET +ve after c@ then 2 BEACOPP and 30Gy. Otherwise: 1-2 sites: ABVDx2 -> ISRT 20Gy - H10: benefit, less chemo, best PFS (highest chance to avoid toxic therapy if relapse) Avoid RT (RAPID): 3 ABVD (in practice often 4) if PET-ve No RT 3 sites: ABVDx3 -> ISRT 30Gy or ABVD 4-6 Unfavourable: 4ABVD then 30Gy 2ABVD then 2 BEACOPP (this is the only setting where PFS = RT!!!!!!)
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Key pre RAI bloods
TSH > 30mU/L Pre Tx baseline Tg (and Tg Ab) BetaHCG!
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A boozy old dude has capsular pain from a big'ol HCC, what dose of RT could you give, and what is the expected outcome?
10Gy/5#s. Well-tolerated 60% response rate.
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Options for uveal melanoma (also name the molecular features just for kicks):
(molecular: GNAQ and GNA11) RT is the definitive modality of choice. Options (besides enucleation): episcleral plaque brachytherapy or charged particle RT (protons) VMAT - 10Gy/5#s All appear to have LC in the order of 80-90% Eneucleation rates around 20%.
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Broad Options for Oropharynx SCC
1) Preferred = Definitive ChemoRT, Offers high rates of cure 85% 5yr OS, appears safer than transoral surgery (ORATOR). 2) Surgery +/- PORT - Transoral approach significantly reduces morbidity compared with other surgical techniques - but asociated with small risk death (ORATOR). 3) RT alone - for t1-t3 at most N1, may be acceptable, N2 disease without chemo is asociated with higher rates DM (Princess Margret). 4) RT with cetux: Cetux is not a substitute for chemo. 5) Palliative approach. NB: Recent metanalysis suggests that the role of pembro is as yet unclear in terms of OS/PFS. Despite this a number of recent papers continue to suggest otherwise.
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Prostate: When to include SV?
Intermediate: Include 1cm if Partin>15 All HR/VHR
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Expected oncologic outcomes with Lung SABR:
2yr OS 75% (only 50% with conventional!! CHISEL study) 2yr LC 90% (when in doubt always say SABR gives 90% LC..)
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For SABR give the interfraction interval range for the following: Kidney Lung Adrenal Renal Liver
They're all 2-3#s/week BUT Liver and prostate (the party organs) are >=36Hrs apart The others at least 24hrs apart.
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Without torturing yourself with details, give the evidence for SABR to adrenal mets: Very broadly whats you approach
The best local Tx modality is currently unknown (surg vs SABR). But recent metaanylsis has established a dose response relationship with BED 80Gy (e.g. 26Gy/1#) = 2yr LCR 80%, BED 100Gy >90%. Doses and setup are the same as FAST-TRACK II. Consider dose escalation to higher end of range (e.g.140%) for radioresitant tumours like Trump.
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You want to give a basic 60/20 to an int risk prostate. What value added feature would you consider? And to what dose.
ISO toxic boost to dominant lesion. Up to 67gy/20#s. Would require fiducials or MR linac, planning MRI.