Patients with a limited number of metastases may have a survival benefit if all disease sites are eradicated. We performed a randomized trial to study the impact of stereotactic ablative radiotherapy (SABR) in patients presenting with metachronous oligometastases.
Eligible patients had a controlled primary malignancy with 1-5 metastatic lesions, all of which were suitable for SABR, had an ECOG performance status 0-1, and life expectancy >6 months. Stratification was by number of metastases (1-3 vs. 4-5). Randomization was in a 1:2 ratio between palliative standard of care (SOC) [Arm 1] vs. SOC plus SABR to all metastatic lesions [Arm 2]. The primary endpoint was overall survival (OS). A randomized phase II screening design was employed with a two-sided alpha of 0.20 (wherein a p-value <0.20 designates a positive trial) to provide an initial comparison of the two treatment strategies. Secondary endpoints included progression-free survival (PFS), toxicity, and QOL (assessed using the FACT-G).
Between 2012-2016, 99 patients were randomized (33 in Arm 1, 66 in Arm 2) at centres in Canada, Europe and Australia. Median age was 68 (range 43-89) and the commonest primary tumor types were breast (n = 18), lung (n = 18), colorectal (n = 18) and prostate (n = 16). Most patients (n = 92) had 1-3 metastases. Median follow-up was 26 months. Median OS was 28 months in Arm 1 (95% CI 19-33 months) vs. 41 months in Arm 2 (95% CI: 26 months to ‘not reached’; stratified log-rank p = 0.09). Median PFS was 6.0 months in Arm 1 (95% CI: 3.4-7.1 months) vs. 12 months in Arm 2 (95% CI: 6.9-30 months; stratified log-rank p = 0.001). Grade ≥2 treatment related adverse events occurred in 9% in Arm 1, and 29% in Arm 2 (p = 0.026). No differences in overall FACT-G scores were seen at 6 months (mean 82.5 vs. 82.6 respectively; p = 0.992). Rates of related grade ≥ 2 toxicity after SABR were 25% for lung lesions, 31% for bony lesions, 33% for liver and 57% for adrenals (p = 0.45). Lesional control rates after SABR ranged from 100% (in adrenals), 76% (bone), 75% (liver) and 70% (lung), p = 0.56.
SABR for oligometastases was associated with an improvement in OS, and a doubling in PFS. Future studies should evaluate techniques to improve lesional control rates.
NCT01446744.
Ontario Institute for Cancer Research.
Ontario Institute for Cancer Research, and a London Regional Cancer Program Catalyst Grant.
S. Senan: Departmental research Funding ViewRay Inc, Varian Medical Systems; Advisory boards: AstraZeneca, Celgene, MSD. R. Olson, D. Schellenberg: Research Funding Varian Medical Systems. All other authors have declared no conflicts of interest.