Intraoperative radiotherapy electron boost followed by moderate doses of external beam radiotherapy in resected soft-tissue sarcoma of the extremities

Abstract

Purpose: To analyze the patterns offailure and the toxicity profile of intraoperative electron beam radiotherapy (IOERT) after resection of soft tissue sarcomas of the extremities (STS). Patients and methods: Forty-five patients with extremity STS were treated with IOERT and moderate-dose postoperative radiotherapy (45-50 Gy). Twenty-six patients were treated for primary disease (PD) and 19 patients for an isolated recurrence (ILR). Tumor size was > 5 cm (maximum diameter) in 36 patients (80%), and high-grade histology in PD patients was present in 14 patients (54%). In nine patients, IOERT was used alone, due to previous irradiation or patient refusal. Chemotherapy (neoadjuvant and/or adjuvant) was mainly given to high-grade tumors. Results: Nine patients relapsed in the extremity (20%), and 12 patients in distant sites (28%). Actuarial local control at 5 years was 88% for patients with negative/close margins and 57% for patients presenting positive margins (P = 0.04). Five patients (11%) developed neuropathy associated with the treatment. Extremity preservation was achieved in 40 patients (88%). With a median follow-up of 93 months (range: 27-143 months) for the patients at risk, 25 patients remain alive (a 7-year actuarial survival rate of 75% for PD and 47% for ILR; P = 0.01). Conclusions: IOERT combined with moderate doses of external beam irradiation yields high local control and extremity preservation rates in resected extremity STS. Peripheral nerves in the IOERT field are dose-limiting structures requiring a dose compromise in the IOERT component to avoid severe neurological damage.

Excellent Local Control With IOERT and Postoperative EBRT in High-Grade Extremity Sarcoma: Results From a Subgroup Analysis of a Prospective Trial

“…These results seem to compare favourably with major retrospective series using similar combinations of intraoperative and external beam radiation therapy (see Table 6, [13][14][15][16][17][18], which reported consistently 5-year local control rates of 80-90%, although keeping in mind that the percentage of incomplete resections in our trial was lower than in most of these series (12% vs. 39-58%). This might be at least partly attributable to the use of neoadjuvant chemotherapy, although major responses according to RECIST criteria were rare.…”

“…In our study, one patient (3%) developed a fracture, which is in the range of reported rate (1-8%) with [14,38] or without IOERT [31,39,40] as part of radiation therapy. However, as fractures may occur many years after the end of radiation treatment as highlighted by a large analysis from Gortzak et al [40], it cannot be ruled out that the fracture rate is underestimated by our analysis due to the relatively short follow up.…”

“…Intraoperative radiation therapy is a treatment technique, which has been developed for dose escalation in body regions, where such doses are hardly achievable with external beam radiotherapy alone because of adjacent organs at risk which much lower tolerance than in extremity regions. However intraoperative radiation therapy has been introduced by several groups including ours also in the treatment of extremity tumors [13][14][15][16] to replace the external beam boost mainly because of its unique opportunity to guide a high single dose directly to the high risk region for close or positive margins under visual control during surgery. Further advantages in comparison to an external boost include at least theoretically smaller field sizes (because safety margins for daily positioning errors can be omitted), the possibility to exclude organ at risk like major nerves or skin from the irradiation field and the reduction of overall treatment time.…”

Risk Factors for Significant Wound Complications Following Wide Resection of Extremity Soft Tissue Sarcomas

“…Preoperative EBRT combined with IOERT increases the efficacy of radiation to the tumor bed, while ostensibly limiting morbidity to surrounding normal tissue, thus potentially minimizing the long-term adverse effects of radiation treatment [2,10,13]. Previous studies have focused largely on the timing of radiation as the main predictor of woundhealing problems after tumor resection [7,15].…”

“…Interstitial brachytherapy has been used as a primary adjuvant therapy or in combination with preoperative or postoperative EBRT. Intraoperative radiation therapy (IORT) is an alternative method to achieve targeted dose escalation while at the same time minimizing toxicity to normal tissue [2,10,13]. This technique, when combined with preoperative or postoperative EBRT, may improve local control and overall survival in many disease sites [17].…”