Sarcomas developed in patients with Lynch Syndrome are enriched in pleomorphic soft-tissue sarcomas and are sensitive to immunotherapy

IF 7.6 1区医学 Q1 ONCOLOGY

European Journal of Cancer Pub Date : 2025-02-05 DOI:10.1016/j.ejca.2024.115196

F. Poumeaud , T. Valentin , N. Fares , B. Segier , S. Watson , B. Verret , C. Tlemsani , N. Penel , S. Lejeune , N. Firmin , A. Sabouret , J.-C. Thery , S. Bonvalot , E. Cottereau , E. Cauchin , A. Lancon , S. Nambot , H. Zattara , M. Coudert , E. Fourme , R. Guimbaud

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引用次数: 0

Abstract

Background

Sarcomas do not belong to the Lynch Syndrome (LS)-tumour spectrum. A growing body literature has reported sarcomas in patients with LS. Clinical and tumour characteristics of these patients remain unknown.

Patients and methods

We set up the first national retrospective study, SarcLynch, describing the pathological and clinical characteristics of sarcomas developed in patients with LS. Patients were identified from two national networks and included from 23 centres in France.

Results

Eighty-one patients participated in the SarcLynch study. Sixty-seven (83 %) tumours were soft-tissue sarcomas (STS) and 14 (17 %) bone sarcomas. Among STS, 59 (88 %) showed a pleomorphic component, with undifferentiated pleomorphic sarcoma (UPS) (36 %) and pleomorphic rhabdomyosarcoma (pRMS) (21 %) being the most represented subtypes. Sarcoma was the first neoplastic event in 32 patients (40 %). Thirty-two patients (40 %) were carriers of MSH2 germline pathogenic variants. Among patients who underwent an assessment of deficient mismatch repair (dMMR) by immunohistochemistry and/or molecular biology status, 75 % were dMMR by immunohistochemistry and 45 % were microsatellite instability high (MSI-H). Eight patients received immune checkpoint inhibitors and 4 (50 %) exhibited an objective response with 3 complete radiological response including 1 patient with pathological complete response. Duration of response ranged from 6 to 20 months.

Conclusions

SarcLynch, the largest multicentric series describing sarcomas developed in patients with LS, revealed an enrichment in patients with pleomorphic sarcomas – especially UPS and pRMS. This finding strongly supports screening for MMR status evaluation in these rare histotypes both for oncogenetic screening and therapeutic interest. Considering an objective response rate of 50 %, access to immunotherapy should be considered in these tumours.

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Lynch综合征患者的肉瘤多为多形性软组织肉瘤，对免疫治疗敏感。

背景：肉瘤不属于Lynch综合征（LS）肿瘤谱系。越来越多的身体文献报道了LS患者的肉瘤。这些患者的临床和肿瘤特征尚不清楚。患者和方法：我们建立了第一个全国性的回顾性研究sarlynch，描述了LS患者发生的肉瘤的病理和临床特征。患者从两个国家网络中确定，包括法国的23个中心。结果：81例患者参与了sarlynch研究。67例（83 %）为软组织肉瘤（STS）， 14例（17 %）为骨肉瘤。在STS中，59例（88 %）表现出多形性成分，其中未分化多形性肉瘤（UPS）（36 %）和多形性横纹肌肉瘤（pRMS）（21 %）是最具代表性的亚型。32例患者（40% %）中，肉瘤是第一肿瘤事件。32例患者（40 %）为MSH2种系致病变异携带者。在通过免疫组织化学和/或分子生物学状态评估缺陷错配修复（dMMR）的患者中，75% %通过免疫组织化学评估dMMR， 45% %为微卫星不稳定性高（MSI-H）。8例患者接受免疫检查点抑制剂治疗，4例（50% %）表现出客观反应，其中3例放射学完全缓解，1例病理完全缓解。反应持续时间为6至20个月。结论：sarlynch是描述LS患者中肉瘤的最大的多中心系列研究，揭示了多形性肉瘤（尤其是UPS和pRMS）患者中表达丰富。这一发现有力地支持了在这些罕见的组织类型中进行MMR状态评估的筛查，无论是用于癌基因筛查还是治疗目的。考虑到客观应答率为50% %，应考虑对这些肿瘤进行免疫治疗。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

European Journal of Cancer 医学-肿瘤学

CiteScore

11.50

自引率

4.80%

发文量

953

审稿时长

23 days

期刊介绍： The European Journal of Cancer (EJC) serves as a comprehensive platform integrating preclinical, digital, translational, and clinical research across the spectrum of cancer. From epidemiology, carcinogenesis, and biology to groundbreaking innovations in cancer treatment and patient care, the journal covers a wide array of topics. We publish original research, reviews, previews, editorial comments, and correspondence, fostering dialogue and advancement in the fight against cancer. Join us in our mission to drive progress and improve outcomes in cancer research and patient care.