zzTreatment Summaries Flashcards
Management of GBM and WHO G3 Astrocytoma
ATX SUM:
GBM or WHO G4 Astrocytoma
Curative:
* Max safe resection
* Adj ChemoRT as per STUPP protocol 60Gy/30F with TMZ 75mg/m2
* Adj Chemo TMZ 150-200mg/m2 for 6mo
Elderly/Palliative:
* Check MGMT Status
* Depending on PTT factors- mainly ECOG and Age
* Options (in decreasing order of toxicity)
○ 40Gy/15F with concurrent TMZ (only if excellent PS)
○ 40Gy/15F alone If > 60yo and good ECOG<2/KPS >70
○ 25Gy/5F alone If >60yo and poor ECOG>2/KPS 50-70
* If MGMT methylated: ○ TMZ alone is a reasonable alternative ○ Addition of concurrent TMZ with RT will preferentially benefit this population
Recurrence MX
* Re-resection +/- chemotherapy w/ carmustine
* Chemo:
○ Metronomic TMZ
○ CCNU-proCarbazine
○ Avastin + Lomustine
○ Re-challenge with TMZ if MGMT meth’d
* Re-Irradiation only if Time-Interval >6mo
○ Aim: decrease Steroid dependence and improve PFS
○ Dose: 30Gy/10F, 35Gy/10F (Siew), or 40Gy/15F
○ FSRT, Volume: PTV= GTV+5mm
* Tumour Treating Field (TTF)- not available in AUS
* Clinical trial
WHO Grade 3 Astrocytoma
* Tx Paradigm: Max safe resection—> Adj RT 59.4Gy/33F—> adj chemo TMZ
○ Should receive SEQUENTIAL radiotherapy and chemotherapy
§ Upfront radiotherapy is associated with improved time to failure only (lower need for salvage treatment at 54mo)
○ Adjuvant radiotherapy = 59.4Gy/33F ○ Adjuvant chemotherapy = 12 months of TMZ at 150-200mg/m2
WHO G3 Oligodendroglioma
* Tx Paradigm: Max safe resection—> Adj RT 59.4Gy/33F—> adj chemo (PCV EORTC or TMZ extrapolate CATNON)
○ Should receive SEQUENTIAL radiotherapy and chemotherapy
§ Upfront radiotherapy is associated with improved time to failure only
§ However, If young patient, consider delay RT until salvage (French POLCA trial)- Not evidence to support this still under investigation. Based on NOA-04, upfront chemo might worse TTF (more need for salvage treatment at 54mo)
○ Adjuvant radiotherapy = 59.4Gy/33F Adjuvant chemotherapy = PCV (or TMZ as more tolerable- extrapolated from CATNON)
Management of Low grade Glioma
SUM of RCTs showed:
* Adj RT improve seizure control
* improve mPFS 3.5- 5yrs but not OS benefit
* Not for dose escalation to 64.8Gy as increase G3+ toxicity and necrosis
* Dose 45-50.4Gy is adequate
* Criteria for High risk features: SATAN
○ Size <5cm was predictive of outcome
* Adj PCV post RT improve mOS, 10yr OS andd PFS but inly if IDH mut (regardless of 1p19q codeletion), NOT in IDH WT
○ better in Oligo than Astrocytoma
* TMZ monotherapy vs RT alone
○ RT = TMZ (no diff in PFS) in IDH WT and Oligo
○ But in Astro RT > TMZ
○ PFS is inferior to PCV
* STUPP protocol using 54Gy vs Historical (RT -> PCV)
○ STUPP improved mOS and 3yr OS
○ STUPP decreased mPFS and 3yr PFS at 3yr, but improved 10yr PFS
§ mOS improved IF IDH mut and IDH WT, and IF Co-deletion > non Co-deleted
§ MGMT methylation improved mOS
§ IDH WT without MGMT do poorly
○ IDH and 1p19q codeletion is more prognostic than MGMT
Overview:
-EORTC Nonbelievers compared early Adj RT vs delayed RT and shows PFS benefit with early RT. High risk “SATAN” criteria outlined in Believer’s trial
-Believers and INT/NCCTG - assessed the role of dose escalation for Adj RT. showed that 45-50.4 Gy is adequate over higher dose
-RTOG 9802. New era. PCV gives large OS benefit in high risk (STR or age≥40), especially for oligo and IDH mutant
-RTOG 0424 phase II shows TMZ is also effective. TMZ has never been compared to PCV, but many prefer TMZ for its ease of use
Radiotherapy:
* All pts should receive XRT at some point
* Observe initial for best prognostic category dt significance of late effects (neurocognitive, radn necrosis)
Moderate dose XRT 50-54Gy is adequate. Usually 54Gy for Grade 2 and 59.4Gy for Grade 3
Management of Meningioma
Tx SUM
> Small+ Asymptomatic- Observe until sx or rapid growth
> Large+ symptomatic -> upfront treatment
Resectable ○ Maximal safe resection, aim for GTR - Simpson criteria ○ Adj RT: depends on the histo, recurrence and GTR/STR § GTR+G1- Observe § GTR+ rec G1- Adj RT § STR+G1- Adj RT vs salvage RT- controversial § GTR+G2- obs and salvage RT- controversial § GTR + rec G2- Adj RT § STR+G2- Adj RT § GTR/STR + G3- Adj RT Dose: G1: □ 50.4Gy/28F if R0 □ 54Gy/30F If bulky residual, rec or adverse radiological feat § G2: □ 54Gy if R0 □ 60Gy/30F If bulky residual, rec or adverse radiological feat § G3: 60Gy/30F Unresectable ○ SRS 13-15Gy/1F or FSRS 25Gy/5F (Use FSRS for larger lesions) § Criteria for SRS: □ G1, <3cm, >3mm from optic apparatus and brainstem, <10cc volume □ distinct margin, little/no oedema ○ Conventional Fractionation § Low grade: □ 50.4Gy/28F □ 54Gy/30F If bulky or adverse radiological feat § High grade: 60Gy/30F
Note: Adverse imaging characteristics suggestive of higher grade
* Peri-tumoural oedema
* Bone invasion
* Lack of calcification
* Lack of intra-tumoural calcification
> Recurrence
* No OS benefit with RT
* IF NO prior RT, >3cm, close to optic apparatus/brainstem, and prior surgery
○ Re-resect, then offer adj RT
○ If unresectable, then EBRT
* IF PRIOR RT, <3cm, not near optic apparatus, no prior surgery
○ SRS 12-14Gy to 50% isodose line
Special sites:
§ Optic sheath -> Def RT 50.4Gy/28F
OR
Surgery, Surg+Adj RT, or observation-> all likely to result in worse vision
Outcome: LC >90%, stabilization of vision in 90%
§ Cavernous sinus-> Def or Adj RT
Outcome: 5yr PFS > 90%. (30% improved neurological function, 60% reduced progression and 10% continued to progress)
Management of Pituitary tumour
Mx SUM
Observation
* non functioning microadenoma and asymptomatic
Medical management-for functioning adeomas
* as either primary or adjunct Tx to other modalities depending on the subtype
* 70% functioning, 30# non functioning
○ Most common functioning Prolactin > Somastotatin> ACTH
○ Prolactin- bromocriptine
○ Somatostatin- Octreotide. Lanreotide
○ ACTH- KEtoconazole
○ Thyrotroph- Ostreotide,/ bromocriptine, b blocker
Surgery +/- Adj/ salvage RT
* Adj RT indicated if:
○ incomplete resection/ R2 resection and unable to re-resect
○ High risk pathology. eg carcinoma
○ Recurrence after Surgery
Def RT
* SRS/ FSRS-> IF size < 3cm and >3mm from optic apparatus/brainstem. NOT for carcinoma
* Fractionated EBRT-> IF size >3cm and <3mm from optic apparatus/brainstem
Adjuvant head and neck RT
Post operative radiotherapy
* Low risk (No PORT - 5y LRR 10%): T1-2, N0-1, no PNI/LVSI.
* Intermediate Risk (PORT): SM < 1-5 mm ([ECOG 3311] uses 3 mm), 2+ LN, > 3 cm LN, PNI, T3-4, < 1 mm ECE (OP). Grade and LVSI have been identified as possible risk factors for LRR, but individual significance remains unclear.
* High Risk (POCCRT): ECE and/or SM+. May consider for 3+ LN, low neck nodes, re-resect if SM+.
○ Beadle ASTRO abstract: High-risk groups have 30% LRF and DM (need chemo).
Indications for PORT to primary:
○ pT3-4, LVI, PNI, Close margin (≤ 5 mm - whether or not is a true indication for PORT is controversial because not listed on NCCN, but is entry criteria for [RTOG 09-20], so take into account how close margin is and other factors).
○ PORT for glottic LX if: pT4 (not pT3 like non-glottic LX, OPX and HPX), pN2-3, LVSI, PNI, SM < 5 mm (controversial).
Indications for PORT to nodes:
○ N2 or N3 (e.g. nodes > 3 cm), nodal disease in levels 4 or 5.
○ Generally, always treat primary and nodes together except for parotid or skin primary.
○ No neck dissection in high-risk patients.
○ DOI oral tongue primary > 3-4 mm [Ganly Cancer ‘12].
○ If only one + node and no adverse features, NCCN says “Consider RT”.
Adding Chemo to PORT:
○ Absolute indications: ECE or SM+.
○ Relative indications: Multiple positive nodes, PNI/LVSI, T4a primary, or OC primary with level IV nodes.
Nodal volume coverage for H&N RT
Management for early larynx and hypopharynx
TREATMENT SUMMARY
Carcinoma in situ
- Laser ablation, VC stripping, micro-excision
- RT for recurrent or widespread dx.
Stage 1-2 (T1-2N0) ->prospective data only no RCT for Sx Vs. RTx
Supraglottis
- Rich lymphatics: T1-2 (30-40% N+) and T3-4 (55-65% N+)
- Definitive RTx alone to 70/56Gy primary + bilateral neck nodes (preferred dt voice preservation, less morbid, surgical salvage option of recurrence).
○ LC T1 90%, T2 80-90%
- Surgery - Laser excision or Supraglottic laryngectomy + bilateral ELND (retention of vocal and swallowing function, but high aspiration risk)- not suitable if poor lung function
○ LC T1 100%, T2 81%
○ Alternative - Total laryngectomy + bilateral ELND
Glottis
- Definitive small field RT (Hypofn 2.25Gy/#) –> 63Gy/28F (T1) or 65.25Gy/29 (T2) ↑ LC (15%) vs. 2 Gy/F. NO neck ENI needed
○ LC: T1 90%, T2 75-80%.
○ Organ preservation - 80-90%. Surgery salvageable in 90-95%
○ LVH uses 60Gy/25F for T1
- Surgery- Laser excision - T1 or T2 non-bulky.
○ LC: same as RT
○ Contraindication for laser: deep pre-epiglottic space extension, infiltration of the cricoarytenoid joint leading to vocal cord fixation, paraglottic space encroachment, anterior commissure infiltration and inadequate exposure of the larynx.
○ Alternative- Partial/hemilaryngectomy or total laryngectomy (based on anatomic considerations, poor voice quality).
- Note:
○ Data suggest similar oncological and vocal preservation outcomes between options
○ Decision making is as per institutional experience and patient preference
○ Salvage laryngectomy is the ultimate treatment for failure after either approach
Management of Sinonasal cancers
Management:
General:
* Always establish relevant supportive care early
* Smoking cessation
* Dietician and speech pathology input
○ Consideration of prophylactic gastrostomy
* Dental input
○ Pre-RT OPG
* Social & psychological supports as appropriate
- T1-T2 N0:
- Surgery
- Consider observation in nasal cavity/ethmoid sinus for G1, SM-, T1.
- Maxillary sinus: PORT for SM+, T3/4, PNI, LVSI or adenoid cystic. *Always ask surgeons to re-resect positive margins.
- RT alone is uncommon
Caveat: - Adj concurrent chemoRT for pt with close/pos margin and ENE
- Elective nodal treatment in neck neg is controversial. But high rate LN relapse if LNs not electively treated (controversial).
○ Cover node IF ENB , SqCC, SNUC, or adenocarcinoma (higher neck mets 30%), T3/4, PNI+, LVI+, or clinically involved LN
- T3-T4 or N+:
- Consider CCRT for intracranial extension (>R0), high grade.
- Ipsilateral neck only, unless the tumor crosses the midline.
- Coverage of node-negative neck is controversial: Consider if G3, ENB, pT3-4, maxillary sinus or invasion of palate, NPX, skin of cheek or maxillary alveolar ridge.
- Volume:
○ Cover RP and IB-IV, IF node positive.
○ Consider elective coverage of RP and IB-II, IF maxillary T3-4 or undifferentiated histology. - If adenoid cystic, you do not need to cover neck due to a low probability of nodal spread.
Management of endometrial cancer - Adjuvant - Low and Int risk
Management of endometrial cancer - Adjuvant - High-int risk
Management of endometrial cancer - Adjuvant - High risk
Management of ovarian cancer
Tx SUM
Stage 1- LR (complete staging, G1-2, encapsulated, good margin)- observe
* If incomplete staging, may benefit from 3x carbo+ paclitaxel
Stage 1-2 HR (St1c-2, incomplete surg staging, HG serous or clear cell)- benefit from 6x Carbo/Paclitaxel
Stage 3-4:
* If unresectable
○ Induction chemo 3x carbo/taxol+/- avastin -> Surg-> HIPEC with Cis-> Adj chemo x6
○ optimal cytoreduction-> IV/IP chemo with carbo/taxol+/- avastin
Maintenance Treatment
* PARPi if BRCA pos
* Avastin if BRCA neg
Recurrence
* Assess Platinum free interval
○ If <6mo, trial of other agents- topotecan, caelyx, AI, VEGFi, TKI or PARPi
IF >6mo, then rechallenege with chemo.
Management of vulva cancer - primary
Management of vulva cancer - Nodal (negative)
Management of vulva cancer - Nodal (Positive)
Management of Vaginal cancer
Vagina ca Treatment Paradigm SUM
w VIS/VAIN: WLE, topical 5-FU or imiquimod, laser vaporization. 1 Rx course and req close and extended FU
○ Rarely RT - 42.5Gy/5F HDR to surface/ 0.5cm depth; entire length
w Stage I (vagina only):
○ Superficial tumours (<5mm thick) → brachytherapy alone
○ Definitive RT alone (EBRT + BT) - very select cases may do surgery in small, superficial, resectable locations.
§ Surgical options are morbid:
□ Radical upper vaginectomy + LND ± Rad Hys.
® Upper vaginal lesions = conservative excision or upper vaginectomy.
□ Exenteration.
® Distal vaginal lesions include total excision and inguinal LND.
® Esp if rectovaginal/ vesicovaginal fistula
Note: Adj RT undesirable as increase toxicity. But can be considered if close/ pos margin, or node +. Use concurrent Chemo if node +
w Stage II+ (Paravaginal tissue+):
○ Definitive CCRT + Boost (Concurrent Cisplatin 40 mg/m2 x6 - extrapolated from cervix data and US NCDB data showed OS better with CCRT vs RT)
§ Combination of EBRT and brachy (or EBRT boost)
□ Whole pelvis 40-50Gy
□ Boost to gross residual of 20-30Gy
○ After EBRT:
* IF disease is < 5 mm deep by exam and MRI, can do Cylinder/ Intracavitary brachy
* IF >5mm, hybrid intracavitary + interstitial boost or free hand needles.
○ Contraindications to brachy.->Then use EBRT boost 14-20Gy
§ extensive residual disease
§ deeply infiltrating disease
§ Poorly defined margins
§ involvement of rectovaginal septum/bladder
w Stage IVA:
○ Brachy can cause fistula! Consider exenteration (provided clear margin possible)
○ If Fistula- urinary diversion or colostomy
Note:
○ Excision of bulky node prior to Definitive RT
○ Ovarian Transposition prior to RT for premenopausal women
Recurrence
w Isolated local recurrence - no prior RT
○ High dose palliation for local control (esp if long DFII)
○ Exanteration if clear margin feasible
w Isolated local recurrence - prior RT
○ Salvage Exenteration if clear margin possible
○ urinary diversion or colostomy
w Isolated pelvic recurrence (previous RT)
○ limited options
○ IMRT/ IGBT - high risk of complications and tox
w +/- concurrent cisplatin (depending on P/T/T factors)
Metastatic disease
w systemic metastatic disease - poor response rates
w consider clinical trial
Management of Stage I+II Melanoma
Stage I + II (clinically LN negative)
Management of primary:
- Surgical excision with adequate margins
○ Melanoma in situ: 0.5mm
○ ≤1mm: 1cm
○ 1-4mm: 1-2cm
○ >4mm: 2-3cm
- Definitive radiotherapy (60Gy/30F or 50Gy/20F)
○ Indications:
§ Unresectable
§ Medically inoperable
§ Mucosal site
§ Lentigo maligna or lentigo maligna melanoma (50Gy/25F IF >5cm or 45Gy/10F if <5cm field size)
Management of LNs:
- SLNBx if: as per MSLT-I
○ 1-4mm thick; or
○ >0.75mm with 1 other risk factor (mitotic rate, ulceration)
- ⇒Positive SLNBx:
○ Completion LNDx MSLT-I- improved 10yr DFS 65-71% , DMFS, and CSS 42->63% ; or
○ Close ultrasound FU (if small deposit <1mm) with salvage LND MSLT-II: Immediate LN Dx small improvement in 3yr DFS 68 vs. 63% but no difference in OS significant morbidity (lymphoedema),DeCOG-SLT
Adjuvant RT to primary IF: 48Gy/20F ***** or 30Gy/5 twice weekly
- Desmoplastic histology, esp. neurotropic
- Inadequate surgical margins, where further surgery difficult (e.g. Face, H&N area)
- PNI/Extensive LVSI 90% relapse with in-transit / satellite lesions
- Recurrence
- +Margin
- DOI >4mm, ulceration, satellosis
Evidence: No RCT data, but Ph2 TROG and MDACC showed improved LC with Adj PORT to High risk melanoma (>1 node, ENE, recurrent, tumour spill, Clark 4). For desmoplastic, 2 retrospective study (MIA and NCDB) showed improve OS and LC with Adj PORT
Management of early Hodgkin’s Lymphoma
General Approach
Many patients are young, and so treatment should be considered in this context
1) Discussion and consideration of late toxicities 2) Fertility a. Referral/Consultation for fertility preservation b. bHCG for all female patients of appropriate age 3) Smoking cessation 4) Psychosocial input a. Preferably within the context of a AYA service
Long-term follow-up (late effects clinic) is required
- Primary cancer surveillance
- Secondary cancer surveillance
Late effects surveillance
Management of Nodular lymphocyte predominant hodgkin’s lymphoma
Nodular Lymphocyte Predominant Hodgkin Lymphoma
All treatment decisions need to be made in the context of natural history:
- Indolent progression
- Excellent prognosis (even with advanced disease)
Typically asymptomatic at most stages
Management of Early stage DLBCL
Management of cervical oesophagus cancers
Management of resectable thoracic oesophagus/ GOJ tumours
Management of unresectable thoracic oesophagus/ GOJ tumours
Describe neoadjuvant management for Gastric cancer
Describe adjuvant management for Gastric cancer
Management for resectable and Borderline resectable pancreatic cancer
Management for borderline resectable pancreatic cancer
Management of metastatic/ palliative pancreatic cancer
Management of rectal cancer
○ Indications for LCRT and TNT:
§ CRM+ ( involved or <2mm)
§ Low-rectal tumour (view to sphincter preservation) - DO NOT give SCRT for low rectal cancer
§ cT3/4 or cN2 disease (especially if extramesorectal LN)
§ Bulky or borderline un-resectable tumour
§ Uncertain if patient will proceed to surgery (i.e. possible definitive RT)
§ Young age (easily tolerate treatment and typically have worse disease)
NOTE: CRM/MRF – considered + if direct invasion or <=1mm between primary tumour and MRF □ Old ‘threatened’ MRF 1-2mm definition should be discarded
