Grimaudo Maria Susanna, D'Orazio Federico, Renne Salvatore Lorenzo, D'Incalci Maurizio, Maki Robert G, Colombo Piergiuseppe, Balzarini Luca, Laffi Alice, Santoro Armando, Bertuzzi Alexia Francesca
Medical Oncology and Hematology Department, IRCCS Humanitas Research Hospital, Via Alessandro Manzoni 56, 20089 Rozzano, MI, Italy.
Radiology Department, IRCCS Humanitas Research Hospital, Via Alessandro Manzoni 56, 20089 Rozzano, MI, Italy.
Cancers (Basel). 2025 Mar 13;17(6):976. doi: 10.3390/cancers17060976.
Liposarcoma (LPS) is one of the most frequent histotypes of soft tissue sarcoma (STS). Eribulin is a cytotoxic agent that has improved overall survival in patients with advanced LPS. Additionally, preclinical and clinical evidence suggests its influence on vascularization and cellular differentiation. Based on these data, we developed this study to investigate non-mitotic effects of eribulin in patients with advanced LPS. In this prospective monocentric observational study, we included patients with advanced LPS eligible to receive eribulin. An assessment with dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and a biopsy were planned before treatment and after four cycles of eribulin. DCE-MRI scans were elaborated to obtain perfusion and permeability maps. From September 2019 to January 2024, 11 patients were enrolled. Among them, 8/11 (73%) had successful pre- and post-treatment assessment. At the time of the analysis, 8/11 (73%) patients had disease progression and 4 (36%) had died, median progression-free survival (mPFS) was 3.3 months, and median overall survival (mOS) was 8.7 months. Among the evaluable patients, DCE-MRI perfusion decreased after eribulin treatment in patients with disease control (partial response or stable disease), while perfusion values increased in patients with progressive disease (PD). No significant change in permeability was found. Post-treatment histological changes were seen nearly in all patients, with decreased cellularity the most common change (50%), followed by vascularization modifications (20%). Eribulin appears to exhibit non-mitotic activity involving both vascularization and cell differentiation in LPS patients. Further studies are needed to better define these effects.
脂肪肉瘤（LPS）是软组织肉瘤（STS）最常见的组织学类型之一。艾瑞布林是一种细胞毒性药物，可改善晚期LPS患者的总生存期。此外，临床前和临床证据表明其对血管生成和细胞分化有影响。基于这些数据，我们开展了本研究，以调查艾瑞布林对晚期LPS患者的非有丝分裂作用。在这项前瞻性单中心观察性研究中，我们纳入了符合接受艾瑞布林治疗条件的晚期LPS患者。计划在治疗前和接受四个周期艾瑞布林治疗后，采用动态对比增强磁共振成像（DCE-MRI）进行评估并进行活检。对DCE-MRI扫描结果进行分析，以获得灌注和通透性图。2019年9月至2024年1月，共纳入11例患者。其中，8/11（73%）患者治疗前和治疗后的评估成功。在分析时，8/11（73%）患者出现疾病进展，4例（36%）患者死亡，中位无进展生存期（mPFS）为3.3个月，中位总生存期（mOS）为8.7个月。在可评估的患者中，疾病得到控制（部分缓解或病情稳定）的患者在接受艾瑞布林治疗后，DCE-MRI灌注降低，而疾病进展（PD）的患者灌注值升高。未发现通透性有显著变化。几乎所有患者治疗后均出现组织学改变，最常见的改变是细胞密度降低（50%），其次是血管生成改变（20%）。艾瑞布林似乎在LPS患者中表现出涉及血管生成和细胞分化的非有丝分裂活性。需要进一步研究以更好地明确这些作用。
