Department of Translational Medical Oncology, National Center for Tumor Diseases (NCT) Heidelberg and German Cancer Research Center (DKFZ), Heidelberg, Germany.
German Cancer Consortium (DKTK), Heidelberg, Germany.
Cancer Discov. 2021 Nov;11(11):2780-2795. doi: 10.1158/2159-8290.CD-21-0126. Epub 2021 Jun 10.
The clinical relevance of comprehensive molecular analysis in rare cancers is not established. We analyzed the molecular profiles and clinical outcomes of 1,310 patients (rare cancers, 75.5%) enrolled in a prospective observational study by the German Cancer Consortium that applies whole-genome/exome and RNA sequencing to inform the care of adults with incurable cancers. On the basis of 472 single and six composite biomarkers, a cross-institutional molecular tumor board provided evidence-based management recommendations, including diagnostic reevaluation, genetic counseling, and experimental treatment, in 88% of cases. Recommended therapies were administered in 362 of 1,138 patients (31.8%) and resulted in significantly improved overall response and disease control rates (23.9% and 55.3%) compared with previous therapies, translating into a progression-free survival ratio >1.3 in 35.7% of patients. These data demonstrate the benefit of molecular stratification in rare cancers and represent a resource that may promote clinical trial access and drug approvals in this underserved patient population. SIGNIFICANCE: Rare cancers are difficult to treat; in particular, molecular pathogenesis-oriented medical therapies are often lacking. This study shows that whole-genome/exome and RNA sequencing enables molecularly informed treatments that lead to clinical benefit in a substantial proportion of patients with advanced rare cancers and paves the way for future clinical trials...
综合分子分析在罕见癌症中的临床相关性尚未确定。我们分析了德国癌症联合会前瞻性观察研究中 1310 名患者（罕见癌症患者占 75.5%）的分子谱和临床结局。该研究通过全基因组/外显子组和 RNA 测序为无法治愈的成年癌症患者提供护理信息，适用于该研究。基于 472 个单一和六个综合生物标志物，跨机构的分子肿瘤委员会提供了循证管理建议，包括诊断重新评估、遗传咨询和实验治疗，在 88%的病例中提供了这些建议。在 1138 名患者中的 362 名（31.8%）推荐了治疗方法，与之前的治疗方法相比，总体反应率和疾病控制率显著提高（23.9%和 55.3%），这转化为 35.7%的患者无进展生存率>1.3。这些数据表明了在罕见癌症中进行分子分层的益处，并且代表了一种资源，可能会促进这一未得到充分治疗的患者群体的临床试验和药物批准。意义：罕见癌症难以治疗；特别是，缺乏针对分子发病机制的医疗疗法。本研究表明，全基因组/外显子组和 RNA 测序能够实现分子信息治疗，在很大一部分晚期罕见癌症患者中带来临床获益，并为未来的临床试验铺平道路。
