Stereotactic ablative radiotherapy for the comprehensive treatment of 1–3 Oligometastatic tumors (SABR-COMET-3): study protocol for a randomized phase III trial

Abstract

Background: A recent randomized phase II trial evaluated stereotactic ablative radiotherapy (SABR) in a group of patients with a small burden of oligometastatic disease (mostly with 1-3 metastatic lesions), and found that SABR was associated with a significant improvement in progression-free survival and a trend to an overall survival benefit, supporting progression to phase III randomized trials. Methods: Two hundred and ninety-seven patients will be randomized in a 1:2 ratio between the control arm (consisting of standard of care [SOC] palliative-intent treatments), and the SABR arm (consisting of SOC treatment + SABR to all sites of known disease). Randomization will be stratified by two factors: histology (prostate, breast, or renal vs. all others), and disease-free interval (defined as time from diagnosis of primary tumor until first detection of the metastases being treated on this trial; divided as ≤2 vs. > 2 years). The primary endpoint is overall survival, and secondary endpoints include progression-free survival, cost effectiveness, time to development of new metastatic lesions, quality of life (QoL), and toxicity. Translational endpoints include assessment of circulating tumor cells, cell-free DNA, and tumor tissue as prognostic and predictive markers, including assessment of immunological predictors of response and long-term survival. Discussion: This study will provide an assessment of the impact of SABR on survival, QoL, and cost effectiveness to determine if long-term survival can be achieved for selected patients with 1-3 oligometastatic lesions.

Cost-Effectiveness Analysis of Stereotactic Ablative Body Radiotherapy for the Treatment of Oligometastatic Tumors versus Standard of Care

“…While our approach used appropriate and robust modeling techniques consistent with Canadian guidelines for the conduct of economic evaluation, it must be acknowledged that the estimates of the effectiveness of SABR result from a phase II clinical trial. As such, the real-world effectiveness of SABR remains yet to be fully understood and could benefit from a subsequent phase III trial to reduce uncertainty; this trial is currently underway [27]. Importantly, various aspects of SABR-COMET could be enhanced to aid decision-making, such as specification of a comparator that would more accurately reflect treatment decisions, additional sample size, and a longer follow-up period.…”

Personalized Image-Guided Therapies for Local Malignencies: Interdisciplinary Options for Interventional Radiology and Interventional Radiotherapy

“…The oligometastatic paradigm hypothesizes that patients with a limited burden of metastases may achieve long-term disease control, survival benefit, or even cure, if the sites of disease can be removed. Although surgery was historically the primary modality used to remove metastases, newer and less-invasive modalities are now available, including stereotactic ablative radiotherapy (SABR) and image-guided ablations ( 4 ). Therapies are called minimally invasive if the success of the treatment is achieved in a way that is particularly gentle on the patient.…”

“…According to the results of the CLOCC trial mOS at 8 years was significantly improved in the combined LAT and SCT-therapy arm versus the SCT-arm (36% versus 8%) ( 1 ). Analogous the SABR-COMET trial analyzed the impact of SABR in the treatment of different oligometastatic cancers (breast, lung, colorectal and prostate) ( 4 ). The 5-year OS was 42.3% in the combined therapy arm (SABR combined with standard-of-care SOC treatment) versus 17.7% in the SOC treatment arm.…”

“…Studies have shown that especially in oligometastasized situations and a less aggressive tumor biology, the use of minimally invasive procedures can significantly extend overall survival with a good quality of life - sometimes by years ( 1 , 4 ). MIT are taken into consideration by many oncologists only in the salvage situation.…”

“…At the same time, minimally invasive, image-guided procedures (Minimal Invasive Therapies, MIT) are playing an increasingly important role in multimodal cancer therapy ( 1 – 3 ). In the last years, the concept of local tumor control has established itself as another pillar of modern oncology, not instead of, but complementary to the classical disciplines of systemic chemotherapy and surgery ( 1 , 4 ). In addition to local tumor and symptom control, the proven immunomodulating effect of MIT will play an important, perhaps even a more decisive role than we suspect today, especially in the newly dawning age of checkpoint inhibitor therapy ( 2 ).…”