Current RT Developments - SABR

Question 1

What is SABR?

Answer 1

“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” (UK SABR Consortium)

Question 2

What does Sterotactic mean?

Answer 2

The precise positioning in 3D space.

Question 3

What does ablation mean?

Answer 3

When tissue/body part is removed or destroyed by surgery, radiation or photocoagulation.

Question 4

What are the characteristics of SABR?

Answer 4

1) low number of fractions (hypofractionated)
2) high dose per fraction
3) small volumes
4) Good immobilisation required
5) rigorous image guidance

Question 5

List some reports relating to SABR?

Answer 5

1) ICRU91

Question 6

Compared to 3DCRT plans, what are the advantages of using SABR?

Answer 6

1) smaller tissue volume irradiated due to
2) greater conformity to the tumour volume
3) steep dose drop-off from PTV
4) Inhomogeneous dose distribution within the PTV - requirement of steep dose drop off at PTV perimeter to spare healthy tissue (given high dose per fraction); can afford a higher max dose in PTV as ablating the tissue

Question 7

In SABR planning, what is used in NSCLC planning: MIP, AvIP or TavWP?

Answer 7

MIP

Question 8

What are the dose fractionation regimes for lung SABR that are recommended by the UK SABR Consortium?

Answer 8

1) PTV not abutting chest wall (standard fractionation) = 18Gy in 3# (54Gy) to give a BED of 154Gy
2) PTV abutting chest wall (conservative) = 11Gy in 5# (55Gy) or 60Gy in 5#, giving a BED of 115Gy
3) PTV abutting/within central zone but outside ultra-central zone (very conservative fractionation) = 7.5Gy in 8# (60Gy) with a BED of 108Gy
4) PTV within ultra-central zone = not recommended outside of clinical trials (from CHART study, 55Gy in 20# may be alternative treatment)

Question 9

What is the recommended inter-fraction gap for lung SABR treatments?

Answer 9

40 hours with a maximum gap of 4 days (therefore need to account for BHs, etc).

Question 10

Are the OAR dose constraints the same as for IMRT or VMAT?

Answer 10

No, separate OAR limits for SABR based on clinical experience. As the dose regime is different, i.e. greater dose per fraction, there are differing radiobiological responses from normal tissues. Therefore, differing patient outcomes.

Question 11

What can we improve inter-observer variation?

Answer 11

1) consistent windowing
2) Standard contouring guidelines (clinical protocols)
3) additional imaging info (e.g. PET, MRI)
4) Training
5) Peer review/independent checks/QA
6) Audit

Question 12

What does CHART stand for?

Answer 12

Continuous Hyperfractionated Accelerated Radiotherapy for non-small cell lung cancer radiotherapy treatment.

Question 13

Prescription dose - how are VMAT and SABR doses prescribed?

Answer 13

Conventional VMAT - Median dose (D50%) with dose being homogeneous within the PTV with a steep drop off on the DVH.

SABR:

1) dose prescribed to 95% of PTV receives at least 100% of the prescribed dose and inhomogeneous dose distribution within the PTV is expected
2) 99% of the PTV should receive at least 90% of the prescribed dose
3) Dmax should be between 110-140% of prescribed dose

Note: DVH has a shallower drop off as a consequence (higher max dose).

Question 14

Why is SABR thought to be more effective than conventional RT?

Answer 14

From meta anlysis, plotting BED vs TCP for SABR, single fraction delivery and > 10 fractions seems to show a greater TCP for SABR delivery.

However, radiobiology is uncertain and there are two trains of thought:

1) classical models (the LQ model,etc) are still applicable to SABR/hypofractionated treatments with increase in “clinical success” due to advances in delivery and technique allowing higher doses to be delivered without a much-increased toxicity
2) the LQ model is not applicable to SABR/hypofractionated treatments and that other radiobiological effects are at play (e.g. stem cells, vascular damage, etc)

Question 15

What body in the UK publishes SABR guidelines and what guidance do they give?

Answer 15

UK SABR Consortium gives site-specific guidance on:
1) patient selection
2) tumour and OAR delination
3) dose prescription and OAR constraints
4) treatment assessment and followup
It also provides literature reviews!

Question 16

What are the inclusion and exclusion criteria for patient selection for lung SABR?

Answer 16

INCLUSION

1) MDT diagnosis of NSCLC (positive histology, positive PET scan/high probability of malignancy
2) Clinical stage T1M0N0 or T2 (<5cm)M0No or chest wall invasion only T3 (<5cm)M0No
3) Not suitable for surgery
4) WHO performance status 0-2
5) Peripheral lesions outlise of IASLC ‘central zone’ - 2cm away from bronchial tree, heart, major vessels, oesophagus, spinal cord, brachial plexus, etc
6) aged 18+

EXCLUSION

1) Tumour not clinically definable on planning CT
2) Previous RT within planned volume
3) pregnancy or lactation
4) inability to give informed consent or comply with treatment requirements

Question 17

What are the IASLC ‘Central Zone’ and ‘ultra-central zones’?

Answer 17

Central zone is:
2cms away from major OAR and structures; namely: heart, bronchial tree, oesophagus, spinal cord, major blood vessels, brachial plexus, etc

Ultra-central zone is:
1cms away from the bronchial tree.

Question 18

What are the relative contraindications for patient selection for lung SABR?

Answer 18

1) target motion is >1cm, consider gating, compression, etc if >1cm
2) Presence of pulmonary fibrosis - consent for increased risk of significant toxicity

Question 19

List the volume definitions used in SABR.

Answer 19

GTV = radiolocally visible tumour in the lung, contoured on lung windows, using PET information (if available). Motion adapted GTV = CTV = ITV.

ITV = tumour volume delineated using 4DCT; options:
a) contour ITV on MIP
b) contour ITV on max inspiration and expiration scans
c) contour all individual phases of 4DCT then combine
OAR usually drawn on AvIP

PTV = ITV + margin (5mm isotropic margin used in most UK centres but dependent on immobilisation used at centre)

Note: UK SABR consortium guidelines recommend contours and plans should be reviewed by 2 clinicians and an additional review by a consultant radiologist is highly recommended.

Question 20

Outline the main differences you would expect between a 55Gy/20# VMAT plan and a lung SABR plan.

Answer 20

1) Less fractions for SABR; regime depends on the location of the tumour:
a) PTV no abutting chest wall (54Gy in 3#)
b) PTV abutting chest wall (55Gy in 5#)
c) PTV within central zone (60Gy in 8#)
d) PTV within ultra-central zone, not recommended outside clinical trials but CHART could offer 55Gy in 20#

2) SABR has much higher max dose than VMAT (recommended between 110% and 140% of the prescribed dose, UK SABR Consortium guidelines?), as the tumour is to be ablated
3) This allows for a much greater drop-off of dose at the edge of the PTV into normal tissue
4) This relates to a steep drop off of the PTV on the DVH for VMAT at the prescribed dose; for SABR, this drop off is slower and exceeds the prescribed dose at point of drop off and reaches 0% volume at a much higher maximum dose (between 110% and 140% of the prescribed dose)
5) a more uniform dose distribution for VMAT, a more heterogeneous dose distribution for SABR
6) dose is more conformal to the PTV with SABR than with VMAT

Question 21

Discuss the various treatment options available for NSCLC, including the patient cohorts they are suitable for and the expected outcomes.

Answer 21

1) Surgery - 5yr OS 60-70%; for patients fit enough (co-morbidities assessed) and with sufficient lung function to survive surgery; also the location of tumour needs to be logistically accessible for resection
2) Conventional RT - 5yr OS 10-30%; for patients not suitable for/unwilling to have surgery
3) SABR - RTOG trial showed 5yr OS at 40% and Japanese study showed 6yr OS at 70%, which is comparable to surgery (note the Japanese study was with the same patient cohort as Surgery…i.e. they opted for SABR rather than surgery. SABR can also be delivered to patients with COPD but lung fibrosis is a toxicity that needs consideration.

Note, it is more common to opt for surgery in younger patients as they are generally healthier (have less co-morbidities) and older patients can be frail and increased anesthetic risk.

NRIG Report provides recommendations for SABR treatment choices.

Question 22

How are 4DCT data sets typically processed for SABR?

Answer 22

Most SABR involves generating a Maximum Intensity Projection (MIT) from the 4DCT to delineate the ITV and the Average Intensity Projection (AvIP) to contour OAR.

The ITV can be directly drawn on the MIP (this will encompass all tumour positions); ITV could also be drawn using the maximum expiration and inhalation scans; ITV can also be drawn on each individual 4DCT scan and combined, however, this is sort of equivalent to the MIP and is more time consuming.

Note: PTV margins depend on the immobilisation (if any) used at the centre and UK SABR consortium guidelines are that the contours and plans should be reviewed by 2 clinicians with an addition review by a consultant radiologist being highly recommended.

Question 23

What is meant by ‘interplay’ and why it is a particular problem for SABR treatments?

Answer 23

Interplay effect refers to the interaction of constantly moving MLCs whilst delivering dose and a constantly moving target (such as a lung tumour during respiration). If these are not synchronized, the results will be incorrect dose deposition.

It is a particular issue for SABR given the large dose per fraction delivered; if the dose delivered is significantly different from that intended, there is more risk of causing patient harm (different radiobiological response) than a similar situation with conventional RT where there is less dose/fraction and more scope to compensate for the error in later fractions.

Question 24

Define the terms:

1) Metastatic disease
2) Oligometastatic disease
3) ‘oligoment’ and ‘oligoprogressive disease’

Answer 24

1) Metastatic disease has spread from the primary site to other parts of the body, usually lymph nodes, lung, bone, spine and liver.
2) Oligometastic disease is an intermediate stage between localised primary disease and widespread metastatic disease. i.e. has a few mets
3) Oligoment means a few metastasis (from greek ‘oligos’).

Oligoprogressive disease is a clincial concept describing progression of disease at only a few sites of metastasis in patients with otherwise controlled wide spread disease.

Question 25

For Oligometastses, what are the aims of SABR treatment?

Answer 25

1) achieve local control at metastatic site and prevent clinical sequelae of disease progression at that site
2) improve disease free survival, defer or delay system therapy and maximise QoL
3) improve overall survival

Question 26

What is the current dose constraint for ICDs and what issues do they present in terms of RT planning?

Answer 26

There is a 5Gy limit for ICDs.

They create artefacts which (depending on their position relative to the target volume) could add significant dosimetry uncertainty to the plan (even if densities are forced).

Can the ICD be deactivated (with cardiac support) to prevent damage if 5Gy limit cannot be achieved?

Question 27

What treatment planning issues could there be with a cavitating tumour of the lung?

Answer 27

1) thickness of tumour exterior - ideally want to be >1cm to be confident in dosimetry
2) the lack of tissue within adds uncertainty to dose modeling
3) stability of the cavity - will the material change (i.e. air vs fluid) over time, even if so is the material homogeneous in terms of electron density over time?

Question 28

List some details of the CORE phase 2/3 trial.

Answer 28

1) CORE is a UK mulitcentre randomised trial of conventional care vs SABR for extracranial oligomers
2) Does progression free survival (PFS) improve with standard care + SABR?
3) Breast, prostate or lung (NSCLC) primary controlled for 6 months, 3 or less oligomers in maximum of 2 different organ systems
4) aimed to recruit 230 patients over 3 years
5) opened in Oct 2016
6) once on CORE, patients not eligible for Commissioning through evaluation (CtE)

Question 29

What is Commissioning through Evaluation (CtE)?

Answer 29

CtE is a NHS England programme to evaluate the use of SABR for cancers other than lung (£15m over 3 years).

Question 30

What do CtE guidlines contain?

Answer 30

Guidance for:
Patient selection
dose prescription
OAR tolerances
imaging
planning
treatment
data collection
follow up

Specifies centres need permission to treat and this means they must have a rigorous QA programme (process docs, outlining WA, planning QA and dosimetry audits).

Training for clinicians for contouring, etc.

Specifies no brain mets and 3 or fewer oligomets in max of 2 organs in the following sites:
Lung
Liver
Adrenal
Lymph nodes
bone
spine

Question 31

What are the patient selection criteria for oligomer SABR?

Answer 31

1) metastatic carcinoma with proven primary
2) Not in CORE trial
3) 1-3 sites of metastatic disease (max 2 sites for spine)
4) max leison size 6cm (5cm for lung or liver)
5) Disease Free Survival (DFS) >6m
6) life expectancy >6months
7) Performance status less or equal to 2
8) Discussed at SABR MDT and with disease site-specific CCO
9) consent to follow-up + data collection for 2 or more years

Question 32

According to CtE criteria, can the treatment volume be within the no fly zone for lung oligomers?

Answer 32

Yes.

Question 33

If you were setting up a SABR service at your centre, what sources of information could you use?

Answer 33

1) Approach other centres which have the service for advice/benerfit of their experience
2) following from (1), mentoring - pair centres with one having experience in SABR
3) ICRU91
4) CtE Guidlines
5) UK SABR Consortium
6) NHSE SABR Commissioning policy

Question 34

Would you feel comfortable using experimental SABR treatments without published evidence of efficacy and safety?

Answer 34

Generally no; however, if a patient does not have any other treatment options, if the trust has a ‘compassionate use’ policy, (with associated REC approval?) the experimental treatment may be offered to the patient.

The example given in lectures is Cardiac SABR (given in Newcastle, Middlesborough and Sheffield).

Question 35

Cardiac SABR - Outline what is involved for Radiofrequency ablation for ventricular tachycardia.

Answer 35

1) Invasive electrophysical mapping using cathers
2) RF ablation of the VT circuit

ENCORE-VT trial - 19 patient with 94% response rate and 72% OS after 1 year (very good for these patients). Technique is experimental under the compassionate use policy.