Background: Comprehensive genomic profiling (CGP) has become generally accepted practice in cancer care since CGP has become reimbursed by national healthcare insurance in Japan in 2019. However, its usefulness for cancer patients is insufficient for several reasons. Methods: In an observational clinical study of FoundationOne®CDx, potential biomarkers were explored and the cause of testing failure was investigated. A total of 220 cancer patients were enrolled in the study during the period from 2018 to 2019 at Kyushu University Hospital. Results: The primary tumor sites of the 220 cases were breast (115), colon (29), stomach (19), and pancreas (20). The present dataset suggested that homologous recombination repair (HRR) gene alterations were positively associated with tumor mutational burden-high (TMB-high) (p= 0.0099). A public dataset confirmed that patients with HRR gene alterations had a higher TMB and showed significantly longer survival of immunotherapy. In the present study, 18 cases failed sequencing. A lower percentage of tumor cell nuclei was the most common reason for testing failures (p= 0.037). Cases that received neoadjuvant chemotherapy before sampling tended to fail testing. Conclusions: HRR gene alterations can be a potential biomarker predicting TMB-high and a good response to immunotherapy. For successful sequencing, samples with lower percentages of tumor cell nuclei and previous neoadjuvant chemotherapy should be avoided.
背景：自2019年日本国家医疗保险开始覆盖全面基因组测序（CGP）费用以来，该技术已在癌症诊疗中成为普遍接受的临床实践。然而，由于多种原因，CGP对癌症患者的实际效用仍存在不足。方法：本研究通过开展FoundationOne®CDx观察性临床试验，探索潜在生物标志物并分析检测失败原因。2018年至2019年间，九州大学医院共纳入220例癌症患者。结果：220例患者的原发肿瘤部位分布为：乳腺（115例）、结肠（29例）、胃（19例）和胰腺（20例）。现有数据集显示同源重组修复（HRR）基因改变与高肿瘤突变负荷（TMB-high）呈正相关（p=0.0099）。公共数据集证实携带HRR基因改变的患者具有更高的TMB水平，且免疫治疗生存期显著延长。本研究中有18例样本测序失败，肿瘤细胞核占比过低是最常见的失败原因（p=0.037）。采样前接受过新辅助化疗的病例更易出现检测失败。结论：HRR基因改变可作为预测高TMB状态及良好免疫治疗反应的潜在生物标志物。为确保测序成功率，应避免使用肿瘤细胞核占比较低及曾接受新辅助化疗的样本。
肿瘤(癌症)患者之家