2062 - Peripheral Neuropathy following External Beam Plus Intraoperative Radiation Therapy in Extremity Soft Tissue Sarcoma
Presenter(s)
A. N. Elguindy1,2, K. N. Dibs1, R. Barve3, V. Yildiz4, D. Blakaj5, J. Mayerson6, K. E. Haglund7, D. D. Martin5, and D. J. Konieczkowski1; 1Department of Radiation Oncology, James Cancer Hospital/Wexner Medical Center, The Ohio State University, Columbus, OH, 2Department of Radiation Oncology, El-Demerdash Hospitals, Ain Shams university, Cairo, Egypt, 3Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, 4The Ohio State University Wexner Medical Center, Columbus, OH, 5Department of Radiation Oncology, The Ohio State University Wexner Medical Center, Columbus, OH, 6The James Cancer Hospital and Solove Research Institute, The Ohio State University Comprehensive Cancer Center, Columbus, OH, 7Department of Radiation Oncology, The Ohio State University Wexner Medical Center, Columbus, OH, Columbus, OH
Purpose/Objective(s): Achieving adequate margins for extremity soft tissue sarcomas (eSTS) can be challenging due to proximity to critical structures such as neurovascular bundles. Intra-operative radiotherapy (IORT) has been used to boost at-risk margins. We sought to investigate outcomes following external beam radiation therapy (EBRT) and IORT among eSTS patients with anticipated close/positive margins specifically along major peripheral nerves.
Materials/Methods: In this single institute retrospective analysis, 17 patients were identified with eSTS within 1 cm of a major peripheral nerve who were treated with EBRT and limb-sparing surgery (LSS) with IORT from May 2013 to October 2018.
Results: Median age was 68 years. Thirteen patients (76%) had lower extremity sarcomas, and 4 (24%) had upper extremity. Median tumor size on pre-treatment MRI was 9.7 cm. Eleven patients (65%) received chemotherapy for a median of 4 cycles. Fourteen patients (82%) had microscopically negative (R0) and 3 (18%) had positive (R1) margins. Fifteen patients (88%) received preoperative EBRT (50 Gy in 25 fractions), and two (12%) received postoperative EBRT (also 50 Gy in 25 fractions). Median IORT dose was 10 Gy (range: 10-15Gy). Assuming an A/B ratio of 2 for peripheral nerves, the median total BED and EQD2 were 160 Gy (range: 145.5- 227.5) and 80 Gy (range: 80-113.75 Gy), respectively.
With a median follow-up of 85 months among surviving patients, the 5-year overall survival (OS), local control (LC), and disease-free survival (DFS) were 81%, 93%, and 70%, respectively. Overall, eleven patients (65%) developed grade 2+ neuropathy (grade 3, n=8)), and Grade 3 neuropathy incidence rate after 5 years was 38%. Eleven patients (65%) had direct intra-operative manipulation of the nerve, of whom 9/11 (82%) had postoperative neuropathy. Median EQD2 value for patients with G3 neuropathy was 87.65 Gy (range: 80-113.75 Gy), which did not differ significantly from median EQD2 values among patients without G3 neuropathy (median 80 Gy (range: 80-95.3 Gy); HR= 1.06 (95% CI: 0.97-1.15) per Gy, p=0.18). Univariate and multivariate analysis showed significant association between development of grade 3 neuropathy and ECOG performance (p = 0.011), HR = 7.64 (95% CI: 1.58 - 37.02), but not with total EQD2 (p = 0.35), total BED (p= 0.27), or intraoperative nerve manipulation (p=0.71).Conclusion: While the combination of EBRT, IORT, and LSS yields excellent local control for eSTS with close proximity to critical neurovascular structures, we observed a high rate of peripheral neuropathy in our cohort. This observation likely relates to the specific use of IORT to target anticipated close/positive margins along the nerves, in the context of significant exposure to cytotoxic systemic therapy as well as intra-operative nerve manipulation. Caution appears to be warranted in applying this treatment paradigm to at-risk critical neurovascular margins.