Clinical utility of comprehensive genomic profiling test for colorectal cancer: a single institution prospective observational study.

IF 2.8 3区 医学 Q3 ONCOLOGY
Hiroki Tanabe, Katsuyoshi Ando, Keitaro Takahashi, Tomomi Kamanaka, Sayaka Yuzawa, Junko Kikuchi, Yoshihito Ohhara, Shin Ariga, Tatsuya Shonaka, Chikayoshi Tani, Shin Otake, Takaaki Sasaki, Kenji Takahashi, Nobuhiro Ueno, Kentaro Moriichi, Mishie Tanino, Ichiro Kinoshita, Yusuke Mizukami, Mikihiro Fujiya
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Abstract

Purpose: Next-generation sequencing (NGS) has revolutionized cancer treatment by enabling comprehensive cancer genomic profiling (CGP) to guide genotype-directed therapies. While several prospective trials have demonstrated varying outcomes with CGP in patients with advanced solid tumors, its clinical utility in colorectal cancer (CRC) remains to be evaluated.

Methods: We conducted a prospective observational study of CGP in our hospital between September 2019 and March 2024. Overall survival (OS) of the patients who received CGP-based therapy and those did not was compared, and genomic variables associated with OS were evaluated.

Results: A total of 100 patients with CRC underwent CGP using four platforms. The median patient age was 67 years, and most had a good performance status. The most frequent genomic alterations were TP53 (82%), APC (82%), and KRAS (55%). Actionable mutations such as ERBB2 amplification and BRAF V600E were identified in some patients, and 9% received CGP-based therapy, including immune checkpoint inhibitors for tumor mutational burden-high or microsatellite instability-high tumors. Patients receiving CGP-based therapy had longer OS from expert panel discussion (16.0 vs. 10.8 months) compared to those who did not. Alterations in TP53, SMAD4, and NF1 were associated with worse OS. Interestingly, PTEN mutations were linked to improved survival. TP53 alterations were more common in left-sided CRC.

Conclusion: Although some patients with CRC received CGP-guided therapy, a statistically significant survival benefit was not observed. However, TP53 and SMAD4 mutations were identified as negative prognostic markers, indicating their potential as targets for future drug development.

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结直肠癌综合基因组谱检测的临床应用:一项单机构前瞻性观察研究。
目的:下一代测序(NGS)通过使全面的癌症基因组分析(CGP)指导基因型导向治疗,彻底改变了癌症治疗。虽然几项前瞻性试验已经证明CGP在晚期实体瘤患者中的疗效不同,但其在结直肠癌(CRC)中的临床应用仍有待评估。方法:于2019年9月至2024年3月在我院开展CGP前瞻性观察研究。比较接受和未接受基于cgp治疗的患者的总生存期(OS),并评估与OS相关的基因组变量。结果:共有100例CRC患者采用4种平台进行了CGP。患者中位年龄为67岁,多数表现良好。最常见的基因组改变是TP53(82%)、APC(82%)和KRAS(55%)。在一些患者中发现了ERBB2扩增和BRAF V600E等可操作突变,9%的患者接受了基于cgp的治疗,包括针对肿瘤突变负担高或微卫星不稳定性高的肿瘤的免疫检查点抑制剂。从专家小组讨论来看,接受cgp治疗的患者比未接受cgp治疗的患者有更长的OS(16.0个月对10.8个月)。TP53、SMAD4和NF1的改变与更差的OS相关。有趣的是,PTEN突变与生存率的提高有关。TP53改变在左侧结直肠癌中更为常见。结论:虽然一些结直肠癌患者接受了cgp引导治疗,但没有观察到统计学上显著的生存获益。然而,TP53和SMAD4突变被确定为阴性预后标志物,这表明它们有可能成为未来药物开发的靶点。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
CiteScore
4.00
自引率
2.80%
发文量
577
审稿时长
2 months
期刊介绍: The "Journal of Cancer Research and Clinical Oncology" publishes significant and up-to-date articles within the fields of experimental and clinical oncology. The journal, which is chiefly devoted to Original papers, also includes Reviews as well as Editorials and Guest editorials on current, controversial topics. The section Letters to the editors provides a forum for a rapid exchange of comments and information concerning previously published papers and topics of current interest. Meeting reports provide current information on the latest results presented at important congresses. The following fields are covered: carcinogenesis - etiology, mechanisms; molecular biology; recent developments in tumor therapy; general diagnosis; laboratory diagnosis; diagnostic and experimental pathology; oncologic surgery; and epidemiology.
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