D. Greto1, M. Loi1, M. Banini2, V. Salvestrini3, G. Francolini1, M. Mangoni4, I. Desideri2, C. Arilli5, C. Talamonti6, S. Calusi5, I. Meattini7, G. Simontacchi1, and L. Livi2; 1Radiation Oncology, Careggi University Hospital, University of Florence, Florence, Italy, 2Department of Experimental Clinical and Biomedical Sciences “Mario Serio”, University of Florence, Florence, Italy, 3Istituto Fiorentino di Cura e Assistenza (IFCA), CyberKnife Center, Florence, Italy, 4Department of Biomedical, Experimental and Clinical Sciences "Mario Serio", University of Florence, Florence, Italy; Medical Physics Unit, AOU Careggi Florence, Italy, Florence, Italy, 5Medical Physics, Careggi University Hospital, University of Florence, Florence, Italy, 6Department of Biomedical, Experimental and Clinical Sciences “Mario Serio", University of Florence, Florence, Italy, 7Department of Experimental and Clinical Biomedical Sciences “M. Serio”, University of Florence, Florence, Italy
Purpose/Objective(s): Management of locally advanced Soft Tissue Sarcoma (STS) is based on surgery and external beam radiation therapy (EBRT). Theoretical benefits of neoadjuvant EBRT include reduced volume and dose requirements and possible tumor shrinkage, particularly in association with concurrent chemotherapy (CT), that may facilitate clear margin resection, although at the price of increased wound complications rate in up to 35% of patients. The aim of this study is to evaluate outcome and toxicity results of neoadjuvant radiotherapy in STS patients candidate to surgical excision and to assess prognostic-related features to guide treatment personalization. Materials/
Methods: Clinical and treatment related data were retrospectively retrieved from a consecutive cohort of non-metastatic STS patients treated at our Institution with neoadjuvant RT followed by surgery from 1991 to 2023. CT consisted of an Epirubicin-Ifosfamide regimen for 3 cycles during EBRT delivery in selected candidates. Overall survival (OS), Distant-metastasis free survival (DMFS), Local control (LC) data were extrapolated using Kaplan-Meier method. Chi-square, log-rank test and Cox model were performed to identify factors related with outcome and toxicity. Results: 156 patients were included in our study. Median age was 55 years. Tumors were mostly located in the limbs (94%). Disease stage was T=3 in 71% of cases. Most represented histologic subtypes were liposarcoma (LPS) (34%), undifferentiated pleomorphic sarcoma (UPS) (24%) and synovial sarcoma (5%). Neoadjuvant EBRT was administered to a dose of 50 Gy in 25 daily fractions concurrently with CT in 82 % patients. IMRT was used in 34% of case. R0 and R1 resection were obtained in 93% and 7% of patients respectively. Wound complications were observed in 16% of patients. Grade (G) 3 disease was found in 70% patients. After a median follow-up of 32 months, 5-year OS, DMFS and LC rates were 72%, 57% and 82%, respectively. At multivariate analysis only R1 resection was significantly associated to worse LC rates (p=0.0214), while G3 disease was correlated with impaired DMFS (p=0.0029). UPS (p=0.0028), G3 (p=0.004) and R1 (p=0.05) correlated with poorer OS rates. None of the examined variables, particularly use of IMRT and CT, were associated with higher occurrence of wound complications. Conclusion: In this large STS cohort, neoadjuvant RT resulted in excellent RO rate and favorable outcomes. Wound complications rate was inferior to historical data from landmark trials. R1 resection and G3 disease correlated respectively with impaired LC and DMFS. Both factors were associated with poorer OS, as well as UPS subtype, suggesting an unmet need for treatment intensification in selected patients. Use of IMRT and concurrent CT were not correlated with wound complications occurrence.
