Phase I Dose Escalation Clinical Trial of Stereotactic Body Radiation Therapy (SBRT) for Limited Locoregional Recurrences of Ovarian Cancer.

Abstract

PURPOSE/OBJECTIVE(S)\nRadiation therapy is infrequently used in the treatment of advanced ovarian cancer due to the propensity for peritoneal spread and the dose limitations of large field techniques. However, for patients with limited sites of recurrence, advanced radiation techniques such as Stereotactic Body Radiation Therapy (SBRT) may offer an effective treatment option. There are many clinical trials supporting the safety and efficacy of SBRT for lung and liver tumors, but the role for abdominopelvic targets adjacent to gastrointestinal mucosa remains largely investigational, especially in this often heavily pretreated patient population.\n\n\nMATERIALS/METHODS\nA single institution Phase I dose escalation study was conducted to determine the maximum tolerated dose (MTD) of SBRT for patients with limited (≤ 3 sites) abdominopelvic recurrences of ovarian cancer. We utilized a 3+3 design with 3 dose levels: 8 Gy x 3 fractions (DL1), 9 Gy x 3 fractions (DL2), and 10 Gy x 3 fractions (DL3). Dose limiting toxicity (DLT) was defined as treatment-related grade 3 or higher adverse events and the DLT monitoring period was 12 weeks after completion of SBRT prior to escalating to the next dose level. Secondary endpoints included toxicity, one-year local control (LC), progression-free survival (PFS), overall survival (OS), and quality of life (QOL) utilizing the EORTC QLQ-C30 assessment tool. Patients underwent tumor perfusion imaging as an exploratory endpoint. The median of each perfusion metric in the gross tumor volume (GTV) was computed at baseline, immediately following fraction one, and six weeks after completion of SBRT, and compared with a paired t-test.\n\n\nRESULTS\nSixteen patients were enrolled; 9 in the initial dose escalation and 7 in an expansion cohort. The initial dose escalation cohort has completed 12-month follow-up. Patients were enrolled according to the 3+3 design, with a safety break between levels, and the dose was safely escalated to DL3 with no DLT. There were no serious adverse events or any Grade 2 or higher SBRT-related toxicities, including bowel complications or bowel surgery. One-year LC, PFS, and OS were 92%, 44%, and 100%, respectively. The majority of patients received SBRT on study in lieu of systemic therapy (67%), and one-half of these patients remained off systemic therapy at one-year follow-up. At one year after completion of SBRT, global health status/QOL patient reported outcomes were maintained from baseline values. In perfusion imaging, we observed increases in GTV median permeability (P < 0.01) and blood flow (P\u202f=\u202f0.03) after delivery of the first fraction of SBRT, and decreases in blood volume (P\u202f=\u202f0.01) six weeks after treatment.\n\n\nCONCLUSION\nThis Phase I clinical trial offers preliminary evidence that SBRT can be delivered safely and can be effective in controlling limited locoregional recurrences of ovarian cancer, while maintaining quality of life. SBRT offers another potential tool in the armamentarium of treatments for gynecologic cancers with limited site recurrences.