Phase I Trial of Stereotactic MRI-guided Online Adaptive Radiation Therapy (SMART) for the Treatment of Oligometastatic Ovarian Cancer.

ABSTRACT Objective SBRT is increasingly used to treat a variety of oligometastatic histologies, but few data exist for ovarian cancer. Ablative SBRT dosing is challenging in sites like the abdomen, pelvis, and central thorax due to proximity and motion of organs-at-risk. A novel radiation delivery method, stereotactic magnetic-resonance-guided online-adaptive radiotherapy (SMART), may improve SBRT's therapeutic index through enhanced soft-tissue visualization, real-time non-ionizing imaging, and ability to adapt to the anatomy-of-the-day, with the goal of producing systemic-therapy-free intervals. This Phase I trial assessed feasibility, safety, and dosimetric advantage of SMART to treat ovarian oligometastases. Methods Ten patients with recurrent oligometastatic ovarian cancer underwent SMART for oligometastasis ablation. Initial plans prescribed 35 Gy/5 fractions with goal 95% planning target volume coverage by 95% of prescription, with dose escalation permitted, subject to strict organ-at-risk dose constraints. Daily adaptive planning was used to protect organs-at-risk and/or increase target dose. Feasibility (successful delivery of >80% of fractions in the first on-table attempt) and safety of this approach was evaluated, in addition to efficacy, survival metrics, quality-of-life, prospective timing and dosimetric outcomes. Results Ten women with seventeen ovarian oligometastases were treated with SMART. 100% of treatment fractions were successfully delivered. Online adaptive plans were selected at time of treatment for 58% of fractions, due to initial plan violation of OAR constraints (84% of adapted fractions) or observed opportunity for PTV dose escalation (16% of adapted fractions), with a median on-table time of 64 minutes. A single Grade ≥3 acute (within 6 months of SMART) treatment-related toxicity (duodenal ulcer) was observed. Local control at 3 months was 94%; median progression-free survival was 10.9 months. Median Kaplan-Meier estimated systemic-therapy-free survival following radiation completion was 11.5 months, with concomitant quality-of-life improvements. Discussion SMART is feasible and safe for high-dose radiotherapy ablation of ovarian oligometastases of the abdomen, pelvis, and central thorax with minimal toxicity, high rates of local control, and prolonged systemic-therapy-free survival translating into improved quality-of-life.