Dorman Klara, Auernhammer Christoph J, Spitzweg Christine, Schmidmaier Ralf, Nölting Svenja, Kroiss Matthias, Reincke Martin, Schulz Christian, Angele Martin, Werner Jens, Schmid-Tannwald Christine, Rauch Josefine, Zacherl Mathias, Knösel Thomas, Kumbrink Jörg, Jung Andreas, Klauschen Frederick, Tufman Amanda, Zhang Danmei, Weiss Lena, Böck Stefan, von Bergwelt-Baildon Michael, Heinemann Volker, Westphalen C Benedikt, Heinrich Kathrin
Department of Medicine III and Comprehensive Cancer Center, LMU University Hospital, LMU Munich, Marchioninistr. 15, 81377, Munich, Germany.
German Cancer Consortium (DKTK), Partner Site Munich, Munich, Germany.
Target Oncol. 2025 Jun 30. doi: 10.1007/s11523-025-01152-6.
Comprehensive genomic profiling (CGP) has become more generally accessible to patients with rare cancer, but data on the results and benefits are limited.
Our objective was to gain a real-world understanding of the molecular landscape and targeted treatment options in neuroendocrine tumors, neuroendocrine carcinomas, adrenocortical carcinomas, pheochromocytomas, and carcinoids.
In this retrospective cohort study, we analyzed CGP results and clinical data from patients with neuroendocrine tumors, neuroendocrine carcinomas, adrenocortical carcinomas, pheochromocytomas, and carcinoids who were discussed in the CCCMunich Molecular Tumor Board (MTB) between May 2017 and April 2023.
In total, 104 patients with endocrine and neuroendocrine neoplasms were discussed in the MTB. CGP was technically successful in 99 patients. The most commonly mutated genes were TP53 (29.3%), RB1 (11.1%), and KRAS (10.1%). The highest overall prevalence of pathogenic alterations was detected in neuroendocrine carcinomas (76.9%) and carcinoids (83.3%), and the lowest prevalence of pathogenic alterations was seen in adrenocortical carcinoma (37.5%). Of the 99 patients with successful CGP, 35 received a treatment recommendation from the MTB based on the CGP results. Of these, ten patients ultimately received the recommended treatment. Of the ten treated patients, four experienced a longer progression-free survival under the targeted treatment than under their previous treatment.
One-third of patients with rare endocrine and neuroendocrine neoplasms who underwent CGP had a druggable alteration and received a treatment recommendation from the MTB. However, only 28.6% of these patients were treated accordingly. Our experience highlights the unmet medical need for targeted treatment options in patients with rare cancers.
全面基因组分析（CGP）已越来越普遍地应用于罕见癌症患者，但有关结果和益处的数据有限。
我们的目的是对神经内分泌肿瘤、神经内分泌癌、肾上腺皮质癌、嗜铬细胞瘤和类癌的分子图谱和靶向治疗选择有一个真实世界的了解。
在这项回顾性队列研究中，我们分析了2017年5月至2023年4月在慕尼黑CCCM分子肿瘤委员会（MTB）讨论的神经内分泌肿瘤、神经内分泌癌、肾上腺皮质癌、嗜铬细胞瘤和类癌患者的CGP结果和临床数据。
MTB共讨论了104例内分泌和神经内分泌肿瘤患者。CGP在99例患者中技术上成功。最常发生突变的基因是TP53（29.3%）、RB1（11.1%）和KRAS（10.1%）。在神经内分泌癌（76.9%）和类癌（83.3%）中检测到的致病性改变总体患病率最高，而在肾上腺皮质癌（37.5%）中致病性改变的患病率最低。在99例CGP成功的患者中，35例根据CGP结果获得了MTB的治疗建议。其中，10例患者最终接受了推荐的治疗。在这10例接受治疗的患者中，4例在靶向治疗下的无进展生存期比之前的治疗更长。
接受CGP的罕见内分泌和神经内分泌肿瘤患者中有三分之一存在可靶向治疗的改变，并获得了MTB的治疗建议。然而，这些患者中只有28.6%接受了相应的治疗。我们的经验凸显了罕见癌症患者对靶向治疗选择的未满足医疗需求。
