(P 278) NEOADJUVANT HYPOFRACTIONATED RADIOTHERAPY AND CHEMOTHERAPY IN EXTREMITY SOFT TISSUE SARCOMAS

Objective: To address the role of hypofractionated radiotherapy combined with chemotherapy in the neoadjuvant setting for extremity soft-tissue sarcomas, we report long-term results from a single-institution protocol.

Methods: Between 2015 and 2024, 23 patients with non-metastatic, histologically confirmed extremity soft-tissue sarcomas were treated with a protocol combining three neoadjuvant cycles of doxorubicin and ifosfamide, with hypofractionated radiotherapy (25 Gy in 5 fractions) delivered on day 1 of the second cycle. Primary endpoint was disease-free survival; secondary outcomes included pathologic response, wound complications, and morbidity.

Results: Median age was 54 years (range: 21–75), and median follow-up was 62 months (range: 6.7–93). At last follow-up, 17 patients (74%) were alive without local or systemic disease, three died from metastatic disease, and two (8.5%) experienced local recurrence.
Common chemotherapy-related adverse events included grade 1–2 nausea, vomiting, fatigue, mucositis, and alopecia. Febrile neutropenia occurred in 17.5%, leading to the suspension of the final chemotherapy cycle in one patient.
Acute skin toxicity was absent in 56.5%; grade 1 erythema occurred in 17.4%, and grade 2 or 3 reactions in 13% each. No grade 4 toxicity was reported. All patients completed radiotherapy, followed by surgery at a median of 7 weeks post-chemotherapy. Two patients (8.5%) had amputation as primary surgery.
According to EORTC-STBSG scoring, eight patients (35%) had no residual viable tumor. Eight had 10–49% viable cells, and seven had ≥50%.
Major wound complications occurred in nine patients (39%), all but one involving lower extremity lesions. Late toxicity included grade 1 fibrosis in 43.5%, grade 2 in 17.5%, and one case of femur fracture and necrosis with grade 4 joint stiffness. Nonetheless, 70% reported no joint stiffness or edema.

Conclusion: Despite elevated WC rates, this treatment approach is feasible, well-tolerated, and yields high rates of local control (91.5%), and pathologic complete response of 35%. Limitations include the small sample size and absence of correlation between pathologic findings and outcomes.