Efficacy and Safety of Anthracyclines Combined with Temozolomide Regimens for the Treatment of Advanced Leiomyosarcoma: A Retrospective Study

Background: Leiomyosarcoma (LMS) is an aggressive soft tissue sarcoma with high rates of hematogenous metastasis and recurrent relapse, with a 5-year survival rate of 17.0%. This study evaluated the clinical efficacy of an anthracycline plus temozolomide (ATEM) regimen in advanced LMS and explored the feasibility of dynamic circulating tumor DNA (ctDNA) monitoring for early detection of disease progression. Methods: This retrospective study included patients with advanced LMS who received ATEM between September 2018 and December 2024. The efficacy, including complete response (CR), partial response (PR), stable disease (SD), or progressive disease (PD), objective response rate (ORR), and disease control rate (DCR), as well as safety, were assessed. The median progression-free survival (mPFS) and median overall survival (mOS) were calculated using Kaplan-Meier survival curves. A subset of patients treated with TEM-containing regimens between December 2023 and December 2024 underwent longitudinal ctDNA monitoring. Results: Forty-seven patients were included, with a median follow-up of 39.5 months. The mPFS was 12.0 months and mOS was 37.5 months. One patient achieved clinical CR, 9 achieved PR, 33 had SD and 4 experienced PD. The ORR was 21.3% (10/47), and DCR was 91.5% (43/47). The most common adverse events were leukopenia (42.6%), neutropenia (32.0%), and thrombocytopenia (14.9%). Grade 4 neutropenia occurred in three patients, including one case complicated by febrile neutropenia. All cases were managed successfully with supportive treatment. No treatment-related deaths were observed. In this pilot investigation of 7 patients, ctDNA levels consistently reflected clinical disease status and treatment response. Conclusion: ATEM regimen demonstrated promising efficacy in advanced LMS, with survival outcomes comparable to or better than in prior first-line treatments. ctDNA monitoring showed promise as a non-invasive biomarker for disease monitoring and treatment guidance. Prospective, multi-center studies are warranted to validate these findings.