(P 323) PERIPHERAL NEUROPATHY FOLLOWING INTRA-OPERATIVE RADIOTHERAPY FOR EXTREMITY SOFT TISSUE SARCOMA: A SINGLE INSTITUTION EXPERIENCE

Objective: Extremity soft tissue sarcomas (eSTS) frequently arise along critical/unresectable structures, leading to close or positive surgical margins. Close or positive surgical margins can raise concern for increased local recurrence risk, and methods to address this concern are of interest. Intra-operative radiation therapy (IORT) provides such a method by delivering a single fraction boost dose to the at-risk margin during surgery. Here, we sought to review treatment toxicity and outcomes for patients who received surgery with IORT for eSTS.

Methods: We performed a retrospective study of patients with eSTS treated between 2013-2018 with external beam radiation therapy (EBRT) and surgery with IORT. We analyzed clinicopathologic variables, outcomes, and toxicity according to CTCAE v4.0 guidelines.

Results: We identified 22 patients with extremity STS treated with surgery + IORT in the study timeframe. The lower extremity was involved in eighteen (82%) patients and the upper extremity in 4 (18%). Median age was 67 (range 35-88) and 41% were male. Ten patients (45%) patients had a > 10 pack years smoking history, and one (5%) had diabetes mellitus. None had previously received radiation therapy. Most common tumor histologies included pleomorphic sarcoma in 6 (27%), myxoid liposarcoma in 5 (23%), and myxoid fibrosarcoma in 4 (18%). All patients underwent surgical resection with IORT; of these, 16 (73%) received preoperative EBRT and 1 (5%) received post-operative EBRT. Thirteen (59%) patients received pre-op systemic therapy, most commonly with HD-AIM (40%); eight patients (36 %) received adjuvant chemotherapy, most commonly with pazopanib (18%). Surgical margins were microscopically negative (R0) in 18 patients (82%) and microscopically positive (R1) in 4 (18%). All patients received electron IORT with 6 MeV electrons; median IORT dose was 10 Gy (range 10-15). Eighteen patients (82%) had nerves in proximity or abutting the tumor that were included in the IORT field. Of these 18 patients, 6 (33%) developed grade 3 neuropathy (extremity weakness, foot drop, or use of AFO or cane). Neuropathy developed at a median of 10 months (range 7-12 months) after surgery+ IORT. All patients developing neuropathy had received pre-operative EBRT as well as chemotherapy. Mean BED was 131.9 vs 105.0 Gy in patients developing vs not developing neuropathy (p=0.0365). In all 6 patients, the nerve deficit was consistent with neuropathy arising in the IORT field. On follow up, 8 (36%) patients had distant recurrence in lungs and 1 (5%) patient had local recurrence requiring amputation. Sixteen (78%) patients were alive, five (23%) were dead, and one (5%) was lost to follow up.

Conclusion: Although the combination of surgery, and typically EBRT, with an IORT boost is an attractive approach in principle to address close or positive surgical margins in eSTS, this study describes a significant risk of neuropathy with this approach. Peripheral nerves are dose-limiting structures for IORT, and significant caution should be exercised in using IORT when major peripheral nerves are located within the treatment field.