Department of Oncology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, 70403, Taiwan.
Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
Target Oncol. 2023 Jul;18(4):611-623. doi: 10.1007/s11523-023-00974-6. Epub 2023 Jun 22.
RET plays an oncogenic role, and its aberrations are potentially actionable. However, they have seldom been reported in tumours other than lung or thyroid cancers. The correlation of RET aberrations with clinical characteristics, co-occurring aberrations, and responses to immune checkpoint inhibitors (ICPi) have not been explored in digestive tract tumours.
The aim of the study was to elucidate the clinical characteristics, frequently co-altered genes, and treatment responses in RET-aberrant digestive tract tumours.
We retrospectively evaluated patients with digestive tract cancers for RET-aberrant tumours via FoundationOne CDx tumour-based selected genome sequencing from Jan 2016 to Jan 2021.
In a median follow-up time of 51 months, a total of 453 patients were analysed. RET-aberrant tumours accounted for 4.4% in the studied population (n = 20), and 1.1% had an oncogenic fusion (n = 5). APC, KRAS, TP53, MSH6 and STK11 were the differentially co-altered genes (all false discovery rates <0.05). The presence of RET aberrations alone was not a significant prognostic factor. Eleven patients with RET-aberrant tumours received ICPi-based treatment and none achieved an objective response. In contrast, 47 patients with non-aberrant tumours received ICPi treatment and had an objective response rate of 27.7% and a significantly longer treatment duration (6.2 vs 2.8 months, p = 0.0008).
Albeit rarely, RET aberrations can be found in digestive tract tumours. Patients with RET-aberrant tumours have a blunted response to ICPi and a comparable prognosis as compared with RET-wild type tumours. Together, these results provide insights into this rare but potentially actionable target in digestive tract tumours.
RET 发挥致癌作用，其异常改变具有潜在的可操作性。然而，除了肺癌或甲状腺癌外，其他肿瘤中很少有报道。RET 异常与临床特征、共同改变的基因以及对免疫检查点抑制剂（ICPi）的反应之间的相关性尚未在消化道肿瘤中得到探索。
本研究旨在阐明 RET 异常的消化道肿瘤的临床特征、常共同改变的基因和治疗反应。
我们通过 2016 年 1 月至 2021 年 1 月的 FoundationOne CDx 基于肿瘤的选择性基因组测序，回顾性评估了患有消化道癌的患者是否存在 RET 异常肿瘤。
在中位随访时间为 51 个月时，共分析了 453 例患者。在研究人群中，RET 异常肿瘤占 4.4%（n=20），有致癌融合的占 1.1%（n=5）。APC、KRAS、TP53、MSH6 和 STK11 是差异共同改变的基因（所有假发现率<0.05）。单独存在 RET 异常并不是一个显著的预后因素。11 例 RET 异常肿瘤患者接受了 ICPi 为基础的治疗，但均未达到客观缓解。相比之下，47 例非异常肿瘤患者接受了 ICPi 治疗，客观缓解率为 27.7%，且治疗持续时间显著更长（6.2 个月 vs 2.8 个月，p=0.0008）。
虽然罕见，但 RET 异常可发生于消化道肿瘤中。与 RET 野生型肿瘤相比，RET 异常肿瘤患者对 ICPi 的反应较差，预后相似。这些结果共同为消化道肿瘤中这一罕见但具有潜在可操作性的靶点提供了新的见解。
