Faculty Bibliography

PURPOSE: Retroperitoneal sarcomas represent a formidable challenge to the treating oncologist due to their location, large size, and poor prognosis. The purpose of this study was to determine if the addition of high-dose-rate intraoperative radiation therapy (HDR-IORT) to surgery and external beam radiotherapy (EBRT) would improve the outcome in these patients. METHODS AND MATERIALS: Thirty-two patients with retroperitoneal soft tissue sarcoma were prospectively treated according to a protocol that included maximal tumor resection, HDR-IORT, and postoperative EBRT when feasible. Twelve patients presented with primary and 20 with locally recurrent disease. The tumors were high-grade in 20 patients and low-grade in 12 patients. Complete gross resection was achieved in 30 patients. HDR-IORT was given to a dose of 12-15 Gy. Additional EBRT was given to 78% of patients to a dose of 45-50.4 Gy. The two patients with gross residual disease received an additional I-125 permanent implant to a median peripheral dose of 140-160 Gy. The median follow-up was 33 months (range 1-77 mo). RESULTS: The 5-year actuarial local control rate for the whole group was 62%. For patients with primary disease, the local control rate was 74% compared to 54% in patients with recurrent disease (p = 0.4). The overall 5-year distant metastasis-free survival rate was 82%. In patients with high-grade tumors the rate was 70% vs. 100% in those with low-grade tumors. This difference was statistically significant, p = 0.05. The 5-year disease-free and overall survival rates were 55% and 45%, respectively. The most common type of post-treatment complication was gastrointestinal obstruction (18%) followed by fistula formation (9%), peripheral neuropathy (6%), hydronephrosis (3%), and wound complication (3%). CONCLUSIONS: We are encouraged by the favorable local control rate and the acceptable morbidity with this new technique applied to a challenging patient population.

Intra-operative radiation therapy (IORT) can benefit patients with pelvic tumors by delivering a high dose of radiation with precise delineation of tumor bed and maximal protection of surrounding normal tissues. The IORT experience has been particularly promising for locally advanced primary or recurrent rectal cancers in which a gross total resection is achieved. However, its potential benefit must be weighed against added toxicity. The main dose-limiting toxicity of pelvic IORT is peripheral neuropathy and ureteral stenosis. We will review the techniques for optimal IORT delivery, the results of the major studies investigating IORT treatment of rectal cancer, and the pelvic complications associated with combining surgery and IORT. A team of surgeons and radiation oncologists providing close multidisciplinary coordination is essential to integrate IORT with combined modality regimens in a safe and effective manner.

Purpose. The purpose is to review the natural history, the clinicopathological prognostic factors, and the role of adjuvant radiation therapy with particular attention to the limited but favorable experience with IORT.Methods. Retroperitoneal sarcomas present a continuing therapeutic challenge to the oncologist. In contrast to sarcomas of the extremity and superficial trunk in which complete resection plus radiation therapy results in excellent local control, sarcomas of the retroperitoneum are difficult to resect and even if completely resected, demonstrate high rates of local relapse, the primary pattern of failure. Due to the proximity of normal organs, the delivery of therapeutic doses of adjuvant external beam radiation therapy is problematic.To deliver adequate doses (>60 Gy) of external beam to most patients would result in unacceptable toxicity. The therapeutic dilemma is unfortunate and better strategies are needed. One attractive approach has been to incorporate intraoperative radiation therapy (IORT) with maximal resection and external beam radiation. Results and Discussion. A number of institutions have explored this approach with encouraging preliminary results.

Several altered fractionation schemes have evolved to exploit different aspects of head and neck cancer growth kinetics and normal tissue repair. Hyperfractionation schedules exploit the differential repair abilities of tumor and normal tissue, whereas accelerated fractionation regimens minimize the time of tumor repopulation. Significant clinical data have accumulated that indicate an improvement between 15% and 20% in locoregional control from altered fractionation. Preliminary analysis of a randomized Radiation Therapy Oncology Group trial testing four fractionation schemes confirms the benefit of one altered fractionation approach. Several promising concurrent chemoradiation treatments involving altered fractionation have been reported. Future trials will determine whether the addition of chemotherapy to altered fractionation schemes is warranted in light of the factor of added toxicity.