1. Breast SSG: SABR and Oligometastatic Disease
Charlie Comins
22/1/2016

2. SABR - the basics Stereotactic Ablative Body Radiotherapy A misnomer?
Extremely high dose
Body
As opposed to intracranial
Radiotherapy

3. SABR - History Stereotactic radiotherapy is an old technique
Developed at Karolinska Institute in 1960s for treatment of intracranial lesions
Use of multiple radiotherapy fields (7 or more) delivering a high dose to the target but low dose to surrounding structures
Taken up by Japanese to treat peripheral lung tumours

4. Why now? 2 main technical advances Compensation for tumour motion
4DCT
ABC
Respiratory gating
Image guided radiotherapy
Daily CT imaging of target to ensure accuracy

5. SABR platforms
Tomotherapy
Cyberknife

6. Linear Accelerator

8. Practicalities Patient attends for coaching session
4DCT scan (40 minutes)
Voluming by clinician (1 hours)
Planning by physicists
Day 0: dry run to ensure patient can tolerate and iron out problems (now dropped)
Day 1: first treatment

9. Practicalities 3 dose prescriptions: Toxicities 54Gy in 3 fractions
Minimum of 48 hours between treatments
Toxicities
Fatigue, skin reaction, cough, dysphagia
Chest wall pain, rib fracture, pneumonitis

10. No Fly Zone

11. Or this can happen…..

12. Oligometastatic disease
What is this?
The clinical state of oligometastatic disease was proposed in 1995 by Hellman and Weichselbaum. 
They hypothesized that, in some patients with a limited number of clinically detectable metastatic tumors, the extent of disease exists in a transitional state between localized and widespread systemic disease.
Is this a real entity?
Even if it isn’t, could ablative treatment be worthwhile?
Can we determine in which patients it might be beneficial?

13. Oligometastatic disease
PuLMICC – resection of lung mets in colorectal cancer
2 potential radiotherapy trials:
SARON for NSCLC patients
CORE for Breast, Lung, and prostate cancer patients
NHS England CtE
Commissioning through Evaluation
Bristol one of 17 centres to be selected to deliver SABR for oligometastatic disease
5 referrals; 1 patient treated to date

14. CORE Trial
Assessing the impact of SABR in patients 1-3 metachronous mets from breast, lung and prostate cancer primaries
Maximum 3 metastases and two different organs
Randomised trial: standard of care +/- SABR
Patients eligible for the CORE will not be able to receive SABR through CtE scheme

15. Background & Rationale
Emerging concept
Hellman and Weichselbaum 1995
No Level 1 evidence
Current PRTs on-going
SABR-COMET (CA & NL)
Randomised ph II (N=99) for any tumour type
Oligomets ≤ 5 including brain mets
SBRT vs Pall RT or systemic Rx
OS endpoint
STEREO-SEIN (IGR)
Randomised Ph III (N=280), Breast ca
SBRT + systemic Rx vs Pall RT or systemic Rx
PFS endpoint
Oligomets ≤ 5 & ≤ 10 cm

16. Why lung, breast and prostate?
Currently insufficient evidence to choose a single tumour site to investigate; no strong biological rationale why SBRT would be effective for some tumour sites and not others
Decision to include lung, breast and prostate cancer made following wide consultation with clinicians across the UK, including the relevant Clinical Studies Groups and CTRad – common cancers, size of patient pool
Increased heterogeneity with this approach is acknowledged; pragmatic design for phase II – signal finding

17. Phase II or phase III?
General agreement amongst protocol development group that there were too many uncertainties to commit to a large phase III trial on the data and experience available
Delivery of SBRT in this setting is novel across the UK
A staged design
will allow assessment of patient recruitment and feasibility of delivery in a multi-centre setting
enable an efficacy signal to be detected across the three tumour sites
If a positive signal is seen, expand to parallel phase III trials aiming to show superiority of SBRT over standard of care

18. Design
Multistage Phase II/III, international, multi-centre, non-blinded, parallel group randomised controlled trial: N = 206
Breast, non-small cell lung (NSCLC) or prostate cancer
Metachronous oligomets (≤ 3 lesions)
Standard of care (SoC) ± SBRT / SABR
SOC therapy is at the discretion of the local oncologist and will be defined (per patient) prior to randomisation. It may include any standard therapy that is clinically appropriate: chemotherapy, biological therapy, endocrine therapy, palliative radiotherapy or observation.
Multistage aspect (Emma Hall)

19. CORE trial schema Randomise (1:1) SBRT + Standard of Care
NSCLC, breast or prostate cancer patients
Completed radical treatment
≤3 extra cranial metachronous oligometastases
Suitable for SBRT
Randomise (1:1)
Standard of Care
SBRT +
Standard of Care
Standard of Care
defined prior to randomisation
May include further chemotherapy, hormone therapy, palliative radiotherapy or observation at PI discretion

20. Aims/Objectives Primary Secondary
To evaluate if the addition of SBRT to SoC improves PFS
Secondary

21. Secondary Aims/Objectives To demonstrate feasibility of recruitment
To demonstrate deliverability of SBRT within dosimetric constraints
To evaluate if the addition of SBRT to SoC improves OS
To evaluate the acute and late toxicity associated with the addition of SBRT to SoC
To evaluate the lesion local control rates in those receiving SBRT
To compare the quality of life (QoL) in patients receiving SBRT compared to those receiving SoC alone
To investigate and evaluate resource use and costs of SBRT and SoC therapy within the trial setting.

22. Development of SABR in Bristol
VMAT
Flattening –filter free
?Abdominal compression
Participation in trials

23. Conclusions Thank you for your support
Techniques and service continue to be improved
Will need continued support to recruit to current and future SABR trials
Other ablative techniques available but proper evaluation required