High-Dose-Rate Intraoperative Radiation Therapy for Pediatric Sarcoma: Outcomes, Toxicity, and Practice Recommendations

Abstract

To evaluate outcomes and toxicity of high-dose-rate intraoperative radiation therapy (HDR-IORT) in the management of pediatric sarcoma. Seventy-three consecutive pediatric patients underwent HDR-IORT for sarcoma from May 1993-November 2012. The mean age was 10 years (34 patients ≤6 years). HDR-IORT was a component of the initial therapy in 35 (48.6%) patients and used for recurrent disease in 37 (51.4%). Forty (55.6%) patients received HDR-IORT and postoperative external beam radiation therapy (PORT), and 20 (27.8%) were previously treated with external beam radiation therapy to the IORT site. The median IORT dose was 12 Gy (range, 4-17.5 Gy). When used, the median dose of PORT was 36 Gy (range, 15-53.4 Gy), accounting for HDR-IORT dose to allow for dose reduction. Rates of local control (LC) and overall survival (OS) were estimated using Kaplan-Meier methods; all confidence intervals are 95%. Independent prognostic factors were identified using the Cox stepwise regression analysis. At a median follow-up of 23 months, the 2-year projected rates of LC and OS were 69% (56%-81%) and 60% (47%-72%), with a median survival of 37.4 months. For patients undergoing initial treatment, 2-year projected rates of LC and OS were 95.5% (87%-100%) and 66% (48%-83%); LC and OS for patients with recurrent disease were 50% (32%-67%) and 54% (37%-72%). The addition of PORT was associated with excellent LC for initial therapy (median LC not reached in either case) and improved LC for recurrent disease (median LC 21.9 months vs 16.5 months without PORT), but did not reach significance (p = .132). Improved median OS was also associated with PORT for both initial therapy (median survival 52.9 months vs 7.3 months without PORT) and for recurrent disease (median survival 34 months vs 17.9 months without PORT), p < .001. On multivariate analysis, PORT retained its significance in terms of improved OS (p = .006; HR for death 0.301 (0.13-0.71). Acute ≥ Grade 3 toxicity (< 90 days of HDR-IORT) occurred in 1 (1.3%) patient, consisting of delayed wound healing in an abdominal incision. Late ≥ Grade 3 toxicity (> 90 days of HDR-IORT) occurred in 3 (4.2%) patients, including peripheral neuropathy (1.4%), small bowel infarct (1.4%), and broncho-esophageal fistula (1.4%). The incidence of ≥ Grade 3 toxicity was not associated with HDR-IORT applicator size, HDR-IORT dose, prior RT or PORT, or prior or post-operative chemotherapy, but all ≥ Grade 3 toxicity occurred in patients ≤ 6 years treated with HDR-IORT doses ≥ 12 Gy. HDR-IORT is a well-tolerated component of multimodality therapy for pediatric sarcoma, with the greatest benefits associated with PORT, allowing additional local treatment while reducing external beam exposure. Doses between 8-12 Gy are appropriate for HDR-IORT treatment in pediatric populations’ ≤ 6 years of age.