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为肉瘤患者实施精准肿瘤学:CCCMolecular肿瘤委员会的经验。

Implementing precision oncology for sarcoma patients: the CCCmolecular tumor board experience.

作者信息

Berclaz Luc M, Burkhard-Meier Anton, Lange Philipp, Di Gioia Dorit, Schmidt Michael, Knösel Thomas, Klauschen Frederick, von Bergwelt-Baildon Michael, Heinemann Volker, Greif Philipp A, Westphalen C Benedikt, Heinrich Kathrin, Lindner Lars H

机构信息

Department of Medicine III, University Hospital, Ludwig-Maximilians-University (LMU) Munich, Marchioninistr. 15, 81377, Munich, Germany.

Department of Psychology, Philipps-Universität Marburg, Marburg, Germany.

出版信息

J Cancer Res Clin Oncol. 2023 Nov;149(15):13973-13983. doi: 10.1007/s00432-023-05179-y. Epub 2023 Aug 5.

Abstract

PURPOSE

Due to poor outcomes and limited treatment options, patients with advanced bone and soft tissue sarcomas (BS/STS) may undergo comprehensive molecular profiling of tumor samples to identify possible therapeutic targets. The aim of this study was to determine the impact of routine molecular profiling in the setting of a dedicated precision oncology program in patients with BS/STS in a German large-volume sarcoma center.

METHODS

92 BS/STS patients who received comprehensive genomic profiling (CGP) and were subsequently discussed in our molecular tumor board (MTB) between 2016 and 2022 were included. Patient records were retrospectively reviewed, and the clinical impact of NGS-related findings was analyzed.

RESULTS

89.1% of patients had received at least one treatment line before NGS testing. At least one molecular alteration was found in 71 patients (82.6%). The most common alterations were mutations in TP53 (23.3% of patients), followed by PIK3CA and MDM2 mutations (9.3% each). Druggable alterations were identified, and treatment recommended in 32 patients (37.2%). Of those patients with actionable alterations, ten patients (31.2%) received personalized treatment and six patients did benefit from molecular-based therapy in terms of a progression-free survival ratio (PFSr) > 1.3.

CONCLUSION

Our single-center experience shows an increasing uptake of next-generation sequencing (NGS) and highlights current challenges of implementing precision oncology in the management of patients with BS/STS. A relevant number of patients were diagnosed with clinically actionable alterations. Our results highlight the potential benefit of NGS in patients with rare cancers and currently limited therapeutic options.

摘要

目的

由于晚期骨与软组织肉瘤(BS/STS)患者预后不佳且治疗选择有限,可能会对肿瘤样本进行全面分子分析以确定潜在治疗靶点。本研究旨在确定在德国一家大型肉瘤中心针对BS/STS患者开展的精准肿瘤学专项计划中,常规分子分析的影响。

方法

纳入了92例在2016年至2022年间接受全面基因组分析(CGP)并随后在我们的分子肿瘤委员会(MTB)进行讨论的BS/STS患者。对患者记录进行回顾性审查,并分析与NGS相关结果的临床影响。

结果

89.1%的患者在进行NGS检测前至少接受过一线治疗。71例患者(82.6%)发现至少一种分子改变。最常见的改变是TP53突变(占患者的23.3%),其次是PIK3CA和MDM2突变(各占9.3%)。确定了可靶向治疗的改变,并为32例患者(37.2%)推荐了治疗方案。在这些有可采取行动的改变的患者中,10例患者(31.2%)接受了个性化治疗,6例患者在无进展生存率(PFSr)>1.3方面从基于分子的治疗中获益。

结论

我们的单中心经验表明下一代测序(NGS)的应用越来越多,并突出了在BS/STS患者管理中实施精准肿瘤学的当前挑战。相当数量的患者被诊断出具有临床可采取行动的改变。我们的结果突出了NGS在罕见癌症且目前治疗选择有限的患者中的潜在益处。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/93db/11797633/076ac7c38390/432_2023_5179_Fig1_HTML.jpg

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