Stereotactic ablative radiation therapy to all lesions in patients with oligometastatic cancers: a phase I dose-escalation trial.

Abstract Purpose Increasing evidence suggests that patients with a limited number of metastases benefit from stereotactic ablative radiation therapy (SABR) to all lesions. However, the optimal dose and fractionation remain unknown. This is particularly true for bone and lymph node metastases. Therefore, a prospective single-center dose-escalation trial was initiated. Methods XXXX was an open-label phase I trial evaluating SABR to non-spine bone and lymph node lesions in patients with up to three metastases. Patients with European Cooperative Oncology Group performance status ≤ 1, an estimated life expectancy of at least 6 months, and histologically confirmed non-hematological malignancy were eligible. Three SABR fractionation regimens, i.e. 5 fractions of 7.0 Gy vs. 3 fractions of 10.0 Gy vs. a single fraction of 20.0 Gy, were applied in three consecutive patient cohorts. The rate of ≥ grade 3 toxicity, scored according to the Common Toxicity Criteria for Adverse Events v. 4.03, up to 6 months after SABR, was the primary endpoint. The trial was registered on clinicaltrials.gov (NCTXXXX). Results Between July 2017 and December 2018, 90 patients were enrolled. In total 101 metastases were treated. No ≥ grade 3 toxicity was observed in any of the enrolled patients (95% CI 0.0-12.3% for the first cohort with 28 analyzable patients, 95% CI 0.0-11.6% for the second and third cohort with 30 analyzable patients each). Treatment-related grade 2 toxicities occurred in 4/30 vs. 2/30 vs. 2/30 patients for the five, three and one fraction schedule, respectively. Actuarial local control rate at 12 months was 94.5%. Conclusion All three treatment schedules were feasible and effective with remarkably low toxicity rates and high local control rates. From a patient and resource point of view, the single-fraction schedule is undoubtedly most convenient.