Nakata Eiji, Ennishi Daisuke, Osone Tatsunori, Ninomiya Kiichiro, Tomida Shuta, Itano Takuto, Fujiwara Tomohiro, Kunisada Toshiyuki, Ida Naoyuki, Yamamoto Hideki, Futagawa Mashu, Shimoi Tatsunori, Yanai Hiroyuki, Hirasawa Akira, Toyooka Shinichi, Tabata Masahiro, Ozaki Toshifumi
Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan.
Center for Comprehensive Genomic Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan.
Cancer Med. 2025 Aug;14(15):e71098. doi: 10.1002/cam4.71098.
Next-generation sequencing-based comprehensive cancer genomic profiling (CGP) tests are beneficial for refining diagnosis and personalized treatment of various cancers. However, the clinical impact of CGP, as covered by public health insurance in the management of sarcomas, remains unknown. Especially, the data on the utility of the newly emerging dual DNA-RNA panel compared to the conventional DNA-only panel in clinical settings is lacking. Therefore, we evaluated the utility of CGP in routine clinical practice for sarcoma treatment.
In this study, three types of DNA panel and one DNA-RNA panel, reimbursed by Japanese public health insurance, were utilized. We detected oncogenic and druggable gene mutations and genotype-matched therapies.
One hundred and thirty-six patients were included in this study. Based on the detection of highly histology-specific translocations in the sequencing results, 2.2% of patients were re-classified. In patients with translocation-related sarcomas, a DNA-RNA panel identified more histology-specific fusion genes than DNA panels (p = 0.0035). Specifically, 86.8% and 39.0% of patients had oncogenic and druggable genomic alterations, respectively. Of these, 9.6% underwent genotype-matched therapy, with a 36.3% response rate and an 81.8% disease control rate. Patients who were administered genomically matched therapy had better overall survival (OS) than those who did not in patients with metastatic or advanced sarcoma with no prior chemotherapy (3-year OS: 83.3% vs. 48.0%, p = 0.42). Patients with TP53 and RB1 mutations had worse OS than those without. Germline findings were detected in 11.0% of the patients, one of whom had a truly germline origin.
This study suggests that publicly reimbursed CGP tests, particularly the dual DNA-RNA panel, could be beneficial for refining diagnostic precision in selected sarcoma subtypes, treatment decisions, detecting the germline findings, and prognosis prediction in routine clinical settings for sarcoma. The implementation of genotype-matched therapies showed favorable clinical outcomes and improved the prognosis.
基于新一代测序的全面癌症基因组分析（CGP）检测有助于优化各种癌症的诊断和个性化治疗。然而，在肉瘤管理中，公共医疗保险所涵盖的CGP的临床影响尚不清楚。特别是，在临床环境中，与传统的仅DNA检测相比，新兴的双DNA-RNA检测的效用数据尚缺。因此，我们评估了CGP在肉瘤治疗常规临床实践中的效用。
在本研究中，使用了日本公共医疗保险报销的三种DNA检测和一种DNA-RNA检测。我们检测致癌和可靶向治疗的基因突变以及基因型匹配的治疗方法。
本研究纳入了136例患者。基于测序结果中高度组织学特异性易位的检测，2.2%的患者被重新分类。在与易位相关的肉瘤患者中，DNA-RNA检测比DNA检测鉴定出更多组织学特异性融合基因（p = 0.0035）。具体而言，分别有86.8%和39.0%的患者发生了致癌和可靶向治疗的基因组改变。其中，9.6%的患者接受了基因型匹配的治疗，有效率为36.3%，疾病控制率为81.8%。在未接受过先前化疗的转移性或晚期肉瘤患者中，接受基因组匹配治疗的患者总生存期（OS）比未接受治疗的患者更好（3年OS：83.3%对48.0%，p = 0.42）。TP53和RB1基因突变的患者OS比未发生突变的患者更差。11.0%的患者检测到胚系结果，其中1例具有真正的胚系起源。
本研究表明，公共报销的CGP检测，特别是双DNA-RNA检测，可能有助于提高特定肉瘤亚型的诊断精度、治疗决策、检测胚系结果以及在肉瘤常规临床环境中的预后预测。基因型匹配治疗的实施显示出良好的临床结果并改善了预后。
