Hempel Louisa, de Oliveira Julia Veloso, Gaumann Andreas, Milani Valeria, Schweneker Katrin, Schenck Kristina, Fleischmann Bastian, Philipp Patrick, Mederle Stefanie, Garg Arun, Piehler Armin, Gandorfer Beate, Schick Cordula, Kleespies Axel, Sellmann Ludger, Bartels Marius, Goetze Thorsten Oliver, Stein Alexander, Goekkurt Eray, Pfitzner Lucia, Robert Sebastian, Hempel Dirk
Medical School, Sigmund Freud University, 1090 Vienna, Austria.
Fraunhofer Institute of Optronics System Technologies, and Image Exploitation IOSB, 76131 Karlsruhe, Germany.
Cancers (Basel). 2021 Sep 3;13(17):4453. doi: 10.3390/cancers13174453.
After several years of negative phase III trials in gastric and esophageal cancer, a significant breakthrough in the treatment of metastatic adenocarcinomas of the gastroesophageal junction (GEJ) and stomach (GC) is now becoming evident with the emerging of precision oncology and implementation of molecular targets in tumor treatment. In addition, new generation studies such as umbrella and basket trials are focused on these molecular targets, which makes an early molecular diagnosis based on IHC/ISH and NGS necessary. The required companion diagnostics of Her2neu overamplification or PD-L1 expression is based on immunohistochemistry (IHC) or additionally in situ hybridization (ISH) in case of an IHC Her2neu score of 2+. However, there are investigator-dependent differences in the assessment of Her2neu amplification and different PD-L1 scoring systems obtained by IHC/ISH. The use of high-throughput technologies such as next-generation sequencing (NGS) holds the potential to standardize the analysis and thus make them more comparable. In the presented study, real-world multigene sequencing data of 72 Caucasian patients diagnosed with metastatic adenocarcinomas of GEJ and stomach were analyzed. In the clinical companion diagnostics, we found ESCAT level I molecular targets in one-third of our patients, which directly determined the therapy. In addition, we found potential targets in 14/72 patients (19.4%) who potentially qualify for precision therapies in corresponding molecular studies. The study highlights the importance of comprehensive molecular profiling for precision treatment of GEJ/GC and indicates that a biomarker evaluation should be performed for all patients with metastatic adenocarcinomas before the initiation of first-line treatment and during second-line or subsequent treatment.
在针对胃癌和食管癌进行了数年的阴性III期试验后，随着精准肿瘤学的兴起以及分子靶点在肿瘤治疗中的应用，胃食管交界（GEJ）和胃（GC）转移性腺癌的治疗取得了重大突破。此外，伞式试验和篮子试验等新一代研究聚焦于这些分子靶点，这使得基于免疫组化（IHC）/原位杂交（ISH）和二代测序（NGS）进行早期分子诊断成为必要。针对Her2neu过扩增或PD-L1表达所需的伴随诊断基于免疫组化（IHC），若IHC Her2neu评分为2+，则需额外进行原位杂交（ISH）。然而，在Her2neu扩增评估以及通过IHC/ISH获得的不同PD-L1评分系统方面，存在因研究者而异的差异。使用下一代测序（NGS）等高通量技术有可能使分析标准化，从而使其更具可比性。在本研究中，分析了72例被诊断为GEJ和胃转移性腺癌的白种患者的真实世界多基因测序数据。在临床伴随诊断中，我们发现三分之一的患者存在ESCAT I级分子靶点，这些靶点直接决定了治疗方案。此外，我们在14/72例患者（19.4%）中发现了潜在靶点，这些患者在相应的分子研究中可能符合精准治疗的条件。该研究强调了全面分子谱分析对GEJ/GC精准治疗的重要性，并表明在一线治疗开始前以及二线或后续治疗期间，应对所有转移性腺癌患者进行生物标志物评估。
