Long-Term Results of a Phase 1 Dose Escalation Trial of Ablative Stereotactic Body Radiation Therapy.

Abstract

Stereotactic body radiation therapy is increasingly used for oligometastatic disease as well as palliation, but treatment protocols for nonspine bone and nodal metastases are lacking, with a wide variety of schedules applied. A prospective dose-escalation trial was initiated, involving 90 patients, among whom 52 (58%) had primary prostate tumors, 13 had breast tumors (14%), and 25 (28%) had other primary tumor types. All visible lymph node or nonspine bone oligometastases were treated in 3 consecutive cohorts: 5 × 7.0 Gy, 3 × 10.0 Gy, or 1 × 20.0 Gy. Initial results revealed no dose-limiting toxicity after a median follow-up of 17.2 months. This update provides information on long-term toxicity, local failure (LF), and progression-free survival (PFS). After a median follow-up of 50 months, no new safety signals were observed. Grade 2 toxicity was 13%, 7% and 10% in the respective cohorts (P = .9), without grade 3 to 5 toxicities. LF rates were 9%, 3%, and 6% (P = .5) for the respective treatment groups, with an overall cumulative risk of LF of 7% (95% CI, 2-12) at 4 years. Median PFS was 16.5 months (95% CI, 9.8-21.5), and 4-year PFS was 21% (95% CI, 14-32). Median overall survival across groups was not reached (95% CI, 52.8 - not reached), 4-year OS was 68% (95% CI, 59-78). A subset of patients (23%) remained long-term disease-free, 37% had oligoprogressive disease at first recurrence and 40% developed polymetastatic relapse. The safe and effective use of dose-escalated single-fraction stereotactic body radiation therapy for bone and lymph node metastases is supported by this trial, especially considering patient-convenience and cost-effectiveness. Caution is needed when generalizing these outcomes beyond breast and prostate cancer, given their underrepresentation in our study.