BACKGROUND:
The oligometastatic paradigm suggests that some patients with a limited number of metastases might be cured if all lesions are eradicated. Evidence from randomised controlled trials to support this paradigm is scarce. We aimed to assess the effect of stereotactic ablative radiotherapy (SABR) on survival, oncological outcomes, toxicity, and quality of life in patients with a controlled primary tumour and one to five oligometastatic lesions.
METHODS:
This randomised, open-label phase 2 study was done at 10 hospitals in Canada, the Netherlands, Scotland, and Australia. Patients aged 18 or older with a controlled primary tumour and one to five metastatic lesions, Eastern Cooperative Oncology Group score of 0-1, and a life expectancy of at least 6 months were eligible. After stratifying by the number of metastases (1-3 vs 4-5), we randomly assigned patients (1:2) to receive either palliative standard of care treatments alone (control group), or standard of care plus SABR to all metastatic lesions (SABR group), using a computer-generated randomisation list with permuted blocks of nine. Neither patients nor physicians were masked to treatment allocation. The primary endpoint was overall survival. We used a randomised phase 2 screening design with a two-sided α of 0·20 (wherein p<0·20 designates a positive trial). All analyses were intention to treat. This study is registered with ClinicalTrials.gov, number NCT01446744.
FINDINGS:
99 patients were randomised between Feb 10, 2012, and Aug 30, 2016. Of 99 patients, 33 (33%) were assigned to the control group and 66 (67%) to the SABR group. Two (3%) patients in the SABR group did not receive allocated treatment and withdrew from the trial; two (6%) patients in the control group also withdrew from the trial. Median follow-up was 25 months (IQR 19-54) in the control group versus 26 months (23-37) in the SABR group. Median overall survival was 28 months (95% CI 19-33) in the control group versus 41 months (26-not reached) in the SABR group (hazard ratio 0·57, 95% CI 0·30-1·10; p=0·090). Adverse events of grade 2 or worse occurred in three (9%) of 33 controls and 19 (29%) of 66 patients in the SABR group (p=0·026), an absolute increase of 20% (95% CI 5-34). Treatment-related deaths occurred in three (4·5%) of 66 patients after SABR, compared with none in the control group.
INTERPRETATION:
SABR was associated with an improvement in overall survival, meeting the primary endpoint of this trial, but three (4·5%) of 66 patients in the SABR group had treatment-related death. Phase 3 trials are needed to conclusively show an overall survival benefit, and to determine the maximum number of metastatic lesions wherein SABR provides a benefit.
Lancet. 2019 Apr 10. pii: S0140-6736(18)32487-5. doi: 10.1016/S0140-6736(18)32487-5. [Epub ahead of print]
Palma DA1, Olson R2, Harrow S3, Gaede S4, Louie AV4, Haasbeek C5, Mulroy L6, Lock M4, Rodrigues GB4, Yaremko BP4, Schellenberg D7, Ahmad B4, Griffioen G5, Senthi S8, Swaminath A9, Kopek N10, Liu M11, Moore K3, Currie S3, Bauman GS4, Warner A4, Senan S5.
1London Health Sciences Centre, London, ON, Canada.
2British Columbia Cancer, Centre for the North, Prince George, BC, Canada.
3Beatson West of Scotland Cancer Centre, Glasgow, UK.
4London Health Sciences Centre, London, ON, Canada.
5Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, Netherlands.
6Nova Scotia Cancer Centre, Halifax, NS, Canada.
7British Columbia Cancer, Surrey Centre, Surrey, BC, Canada.
8Alfred Health Radiation Oncology, Melbourne, VIC, Australia.
9Juravinski Cancer Centre, Hamilton, ON, Canada.
10McGill University Health Centre, Montreal, QC, Canada.
11British Columbia Cancer, Vancouver Centre, Vancouver, BC, Canada.