Poumeaud F, Valentin T, Fares N, Segier B, Watson S, Verret B, Tlemsani C, Penel N, Lejeune S, Firmin N, Sabouret A, Thery J-C, Bonvalot S, Cottereau E, Cauchin E, Lancon A, Nambot S, Zattara H, Coudert M, Fourme E, Nogues C, Tougeron D, Prieur F, Collonge-Rame M-A, Denis C, Laurent-Puig P, Chieze-Valero S, Dreyfus H, Jaffrelot M, Vande Perre P, Rochaix P, Gomez-Mascard A, Rochefort P, Campoy S, Chibon F, Lasset C, Selves J, Guimbaud R
Department of Medical Oncology, Oncopole Claudius Regaud, Toulouse, France; Department of Digestive Medical Oncology, Toulouse University Hospital, Toulouse, France; Toulouse Cancer Research Centre, Toulouse, France.
Department of Medical Oncology, Oncopole Claudius Regaud, Toulouse, France; Toulouse Cancer Research Centre, Toulouse, France.
Eur J Cancer. 2025 Feb 5;216:115196. doi: 10.1016/j.ejca.2024.115196. Epub 2024 Dec 21.
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.
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.
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.
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.
肉瘤不属于林奇综合征（LS）相关肿瘤谱。越来越多的文献报道了LS患者发生肉瘤的情况。这些患者的临床和肿瘤特征尚不清楚。
我们开展了第一项全国性回顾性研究SarcLynch，描述LS患者发生的肉瘤的病理和临床特征。患者通过两个全国性网络识别，来自法国23个中心。
81例患者参与了SarcLynch研究。67例（83%）肿瘤为软组织肉瘤（STS），14例（17%）为骨肉瘤。在STS中，59例（88%）显示多形性成分，未分化多形性肉瘤（UPS）（36%）和多形性横纹肌肉瘤（pRMS）（21%）是最常见的亚型。肉瘤是32例患者（40%）的首个肿瘤事件。32例患者（40%）为MSH2种系致病性变异携带者。在通过免疫组化和/或分子生物学状态评估错配修复缺陷（dMMR）的患者中，75%通过免疫组化显示为dMMR，45%为微卫星高度不稳定（MSI-H）。8例患者接受了免疫检查点抑制剂治疗，4例（50%）出现客观缓解，其中3例为影像学完全缓解，包括1例病理完全缓解患者。缓解持续时间为6至20个月。
SarcLynch是描述LS患者发生肉瘤的最大多中心系列研究，显示多形性肉瘤患者富集，尤其是UPS和pRMS。这一发现有力支持对这些罕见组织学类型进行MMR状态评估筛查，以用于肿瘤发生学筛查和治疗。考虑到客观缓解率为50%，对于这些肿瘤应考虑给予免疫治疗。
