Möhrmann L, Werner M, Oleś M, Knol L, Arnold J S, Mundt T, Paramasivam N, Richter D, Fröhlich M, Hutter B, Hüllein J, Jahn A, Scheffold C, Möhrmann E E, Hanf D, Kreutzfeldt S, Heilig C E, Teleanu M-V, Lipka D B, Beck K, Baude-Müller A, Jelas I, Rieke D T, Klotz L V, Shah R, Herold T, Boerries M, Illert A L, Allgäuer M, Stenzinger A, Kerle I A, Horak P, Heining C, Schröck E, Hübschmann D, Fröhling S, Glimm H
Department of Translational Medical Oncology, National Center for Tumor Diseases (NCT), NCT/UCC Dresden, a partnership between DKFZ, Faculty of Medicine and University Hospital Carl Gustav Carus, TUD Dresden University of Technology, and Helmholtz-Zentrum Dresden-Rossendorf (HZDR), Dresden, Germany; Translational Medical Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, TUD Dresden University of Technology, Dresden, Germany; German Cancer Consortium (DKTK), Dresden, Germany; Computational Health Informatics Program, Boston Children's Hospital, Harvard Medical School, Boston, USA.
Department of Translational Medical Oncology, National Center for Tumor Diseases (NCT), NCT/UCC Dresden, a partnership between DKFZ, Faculty of Medicine and University Hospital Carl Gustav Carus, TUD Dresden University of Technology, and Helmholtz-Zentrum Dresden-Rossendorf (HZDR), Dresden, Germany; Translational Medical Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, TUD Dresden University of Technology, Dresden, Germany; German Cancer Consortium (DKTK), Dresden, Germany; Department of Internal Medicine I, University Hospital Carl Gustav Carus, TUD Dresden University of Technology, Dresden, Germany.
ESMO Open. 2025 Apr;10(4):104532. doi: 10.1016/j.esmoop.2025.104532. Epub 2025 Apr 1.
Peritoneal, pericardial and pleural mesothelioma (PeM/PcM/PM) are rare and aggressive diseases with limited survival. Molecularly guided therapy is currently not part of standard care.
This study integrates molecular and clinical data from 51 patients (among them 28 PM, one PcM, 21 PeM and one synchronous PeM/PM) enrolled in the National Center for Tumor Diseases and the German Cancer Consortium (NCT/DKTK) Molecularly Aided Stratification for Tumor Eradication Research (MASTER), a multicenter precision oncology registry trial addressing adults with rare advanced-stage cancers. Analysis comprised both somatic and germline whole exome sequencing/whole genome sequencing and transcriptome analysis leading to personalized treatment recommendations issued by a dedicated molecular tumor board. To assess clinical efficacy, progression-free survival (PFS) ratios comparing molecularly informed therapies (PFS2) to preceding systemic therapies (PFS1) were calculated. Efficacy of immune checkpoint inhibition applied during the observation period was assessed accordingly.
Cancer-related genes altered in more than 5 out of 44 assessable patients were BAP1, CDKN2A, NF2, SETD2 and TP53. Somatic (n = 23) or germline (n = 9) alterations in homologous recombination-related genes were detected in 27/44 patients. In 21/44 cases, they were supported by positive combined homologous recombination deficiency scores or BRCAness signature. Following American College of Medical Genetics and Genomics guidelines, (likely) pathogenic germline variants in autosomal dominant cancer predisposition genes were found in 8/51 patients. Molecular tumor board recommendations were issued in 46 cases and applied in 6 cases. Mean PFS ratio was 2.45 (n = 5). Median PFS2 was 6.5 months (n = 6), median PFS1 was 4.0 months (n = 5). A total of 27 patients received immune checkpoint inhibition during the observation period leading to a mean PFS ratio of 1.69 (n = 19).
In mesothelioma, comprehensive molecular analysis can provide valuable clinically actionable information. Molecularly informed therapy recommendations can lead to clinical benefit.
腹膜、心包和胸膜间皮瘤（PeM/PcM/PM）是罕见的侵袭性疾病，生存期有限。分子导向治疗目前并非标准治疗的一部分。
本研究整合了来自51例患者（其中28例PM、1例PcM、21例PeM和1例同步PeM/PM）的分子和临床数据，这些患者参加了德国国家肿瘤疾病中心和德国癌症联盟（NCT/DKTK）的肿瘤根除研究分子辅助分层（MASTER），这是一项针对患有罕见晚期癌症的成年人的多中心精准肿瘤登记试验。分析包括体细胞和种系全外显子测序/全基因组测序以及转录组分析，由专门的分子肿瘤委员会给出个性化治疗建议。为评估临床疗效，计算了将分子指导治疗（PFS2）与先前全身治疗（PFS1）相比较的无进展生存（PFS）比率。相应地评估了观察期内应用免疫检查点抑制的疗效。
在44例可评估患者中，超过5例发生改变的癌症相关基因有BAP1、CDKN2A、NF2、SETD2和TP53。在27/44例患者中检测到同源重组相关基因的体细胞（n = 23）或种系（n = 9）改变。在21/44例病例中，它们得到了阳性联合同源重组缺陷评分或BRCAness特征的支持。按照美国医学遗传学与基因组学学会的指南，在8/51例患者中发现了常染色体显性癌症易感基因中的（可能）致病种系变异。分子肿瘤委员会给出了46例建议并应用于6例。平均PFS比率为2.45（n = 5）。PFS2中位数为6.5个月（n = 6），PFS1中位数为4.0个月（n = 5）。共有27例患者在观察期内接受了免疫检查点抑制，导致平均PFS比率为1.69（n = 19）。
在间皮瘤中，全面的分子分析可提供有价值的临床可操作信息。分子指导的治疗建议可带来临床益处。
