203: IORT for Neuroblastoma: Outcome and Morbidity

Abstract

Local control for patients with neuroblastoma remains a formidable challenge. Intraoperative radiation therapy (IORT) has been explored as a vehicle to potentially improve local control while minimizing side effects of external beam radiation. In this study we aim to assess the clinical outcome and morbidities of IORT as part of a multimodality treatment in a historical cohort of children with neuroblastoma. Between 1986 and 2004, 41 patients with neuroblastoma received IORT at a single institution. Two patients were lost to follow-up soon after surgery and were therefore excluded from this analysis. Mean age at diagnosis was 4 years (range 9 months-20.3 years), and mean age at time of IORT was 4.4 years (range 11 months-20.6 yrs). 32 had stage 4 disease, six stage 3, and one stage 2. IORT was delivered at the time of surgical resection using a linear accelerator with beam energies ranging from 4 MeV to 16 MeV. The median dose per field was 10 Gy (range 7-15 Gy). One to four separate fields were used in each case (1 field = 25, 2 fields=7, 3 fields =2, 4 fields =5). All sites of IORT were intraabdominal. Thirty five patients received IORT as part of initial therapy and 4 patients received IORT both at initial diagnosis and recurrence. Sixteen patients had external beam radiation to the primary tumor site and five patients had total body irradiation (TBI) as part of an autologous bone marrow transplant (ABMT). Median follow up time was 46 months (range 6 months-16.6 years), and, 67% of patients were alive at last follow up. Sixty-four percent of patients were without evidence of disease and of the 13 patients who died, five died without evidence of disease. Six patients had locally recurrent disease after initial surgery with IORT. Two of these patients had successful salvage after local recurrence with a second surgery and IORT in addition to chemotherapy. The overall local control rate with this multimodality treatment is 90%. Of the 39 patients, 10 (26%) were known to have hypertension, vascular stenosis or middle aortic syndrome. Two of the patients who are alive without evidence of disease have had vascular bypasses for stenotic vessels. Two patients died without evidence of disease from mesenteric ischemia due to stenotic vessels. Of the 10 patients with these clinical findings, 50% had multiple fields treated using IORT, and had aggressive surgeries with a goal of gross total resection. The mean ages at the time of IORT and surgery were 48 months and 58 months respectively for those who did and did not experience vascular consequences. Patients treated with IORT as part of multimodality therapy for neuroblastoma have excellent local disease control. In this group of patients, serious complications such as hypertension, vessel stenosis and death are reported for the first time. It remains unclear whether these vascular complications are due to the disease process, treatment factors, or both. The influence of patient age, number of IORT fields, and addition of EBRT are being assessed.