ORIGINAL RESEARCH article
Front. Oncol.
Sec. Cancer Epidemiology and Prevention
Volume 15 - 2025 | doi: 10.3389/fonc.2025.1585884
Sex differences in toxicity and outcomes in patients with sarcoma treated in the perioperative setting at a Comprehensive Cancer Center
Provisionally accepted
Ilaria Tortorelli1,2*
Benedetta Chiusole1
Fabio Murtas1,2
Antonella Galiano1Maital Bolshinsky1Selma Ahcene-Djaballah3Chiara De Toni1Salvatore Vizzaccaro1
Marco Maruzzo3
Umberto Basso1Alberto Banzato4Marina Coppola5
Sara Lonardi1Vittorina Zagonel1
Antonella Brunello1- 1Unit of Oncology 1, Veneto Institute of Oncology (IRCCS), Padua, Italy
- 2Department of Surgical, Oncological and Gastroenterological Sciences, School of Medicine and Surgery, University of Padua, Padua, Veneto, Italy
- 3Unit of Oncology 3, Veneto Institute of Oncology (IRCCS), Padua, Veneto, Italy
- 4Cardiology Unit, Veneto Institute of Oncology IOV - IRCCS, Padua, Italy, Padova, Italy
- 5Unit of Pharmacy, Veneto Institute of Oncology (IRCCS), Padua, Veneto, Italy
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There is an unmet need of personalized strategies taking into account the influence of sex on treatment. Toxicities commonly lead to dose reductions or delays, which may impact outcomes. The current retrospective study investigated the impact of sex on chemotherapy efficacy and toxicity, and evaluated the effect of Relative Dose Intensity (RDI) on survival in patients with sarcoma. Data of patients with localized high-grade sarcoma treated at the Veneto Institute of Oncology – IRCCS between 2010 and 2022 were analyzed. Dose reduction or delay were expressed as RDI. Sex differences in RDI, severe adverse events (AEs) and the impact of RDI on disease-free survival and overall survival were analyzed. A total of 215 patients (women, 46.5%; men, 53.5%) were eligible. Of these, 127 patients were affected by high-grade soft-tissue sarcoma and treated with anthracycline-based chemotherapy. Males were more likely to receive RDI ≥85%, with a lower risk of AEs compared to females. An RDI ≥85 was associated with improved survival outcomes. To the authors’ knowledge, this is the first study investigating the impact of sex on toxicity and efficacy of perioperative chemotherapy in patients with sarcomas. The increased toxicity in women suggests there is a sex difference in treatment delivery and outcome. Despite a lower RDI, survival outcomes for women were not worse than men. Future studies should aim to better optimize drug dosing according to the sex, with the ultimate goal of increasing therapeutic benefit while limiting toxicity.
Keywords: Sarcoma, Toxicity, Outcome, sex differences, Relative dose intensity
Received: 01 Mar 2025; Accepted: 09 Jun 2025.
Copyright: © 2025 Tortorelli, Chiusole, Murtas, Galiano, Bolshinsky, Ahcene-Djaballah, De Toni, Vizzaccaro, Maruzzo, Basso, Banzato, Coppola, Lonardi, Zagonel and Brunello. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Ilaria Tortorelli, Unit of Oncology 1, Veneto Institute of Oncology (IRCCS), Padua, Italy
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