INTRODUCTION: There has been a long-standing debate regarding the efficacy of single fraction radiotherapy (SFRT) compared to multiple fraction radiotherapy (MFRT); many systematic reviews and meta-analyses have been conducted to resolve the debate and suggested SFRT is equally as effective as MFRT. Given the adequate amalgamated sample size that exists, it is difficult to appreciate the need for further RCTs. The aim of this paper was to conduct a cumulative meta-analysis to determine whether further trials will be of value to the meta-conclusion. This paper also assessed publication quality.
METHODS: A total of 29 studies were used in our meta-analysis. Comprehensive Meta-Analysis (Version 3) by Biostat was used to conduct a cumulative meta-analysis. The Cochrane Risk of Bias assessment tool was employed to assess study quality of the included RCTs. Funnel plots were generated using Review Manager (RevMan 5.3) by Cochrane IMS, to visually assess for publication bias.
RESULTS: All but one endpoint, overall response rates in assessable patients, maintained the same meta-conclusion over publication time; published studies did not change the amalgamated scientific conclusion of existing literature. Additional studies have simply confirmed pre-existing conclusions and refined the point estimate of the efficacy estimate. The majority of included studies have low risk of bias.
CONCLUSION: In conclusion, the meta-conclusion has remained consistent over time - SFRT is equally as efficacious as MFRT. Recent studies have had little impact on the overall conclusion, and given the vast amount of resources to execute a randomized trial, future resources should not be used to repeat these studies, and can be better allocated to test other hypotheses.
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 a 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.
FUNDING: Ontario Institute for Cancer Research and London Regional Cancer Program Catalyst Grant.