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ctDNAを用いた大腸癌化学療法効果判定法と転移巣切除適応症例層別化の確立

ctDNA结直肠癌化疗疗效评价方法的建立及转移性肿瘤切除患者分层

基本信息

批准号：
22K08855
负责人：
八重樫瑞典
金额：
$ 2.66万
依托单位：
Iwate Medical University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2022
资助国家：
日本
起止时间：
2022-04-01 至 2025-03-31
项目状态：
未结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-22K08855/
关键词：
circulating tumor DNA digital PCR RECIST 大腸癌 ctDNA

项目摘要

Circulating tumor DNA (ctDNA)を用いた癌診断が注目されている。我々の大腸癌先行研究では、原発巣変異スクリーニングにより検出された症例特異的変異に対してdigital PCR (dPCR)によるctDNAモニタリングを用い、早期再発診断、治療に伴うctDNA dynamics、無再発状態の確認が可能であった。ctDNAモニタリングは術後の遺残・再発診断だけでなく、進行癌における治療効果の評価や予測のツールとしても期待されている。画像診断による効果判定はRECIST (Response Evaluation Criteria in Solid Tumors)に準じ評価されることが多いが、複数または微小転移・再発、播種など評価困難となる病態も多いため、本研究ではctDNAモニタリングを用いて、再発及び切除不能大腸癌患者における化学療法期間中のctDNAの変動とRECISTの評価と比較検証を行う。また、化学療法の治療経過や薬剤変更に伴う時間的なheterogeneityやctDNAが検出しにくいとされている肺転移や腹膜播種のctDNAモニタリングの臨床的な課題ともされているため、検証を行った。大腸癌は遠隔転移症例でも転移巣切除により予後改善が得られるため、切除可能であれば積極的に切除を行うケースは多いが、肝転移切除後の再々発は60%以上と高率である。しかし再々発例でも切除により完治する症例も存在することから切除効果の予測因子の同定は重要である。本研究では、遠隔転移症例のうちctDNA陰性症例は切除後長期予後が得られるという仮説のもと、根治切除後の再発症例や切除不能症例の治療経過中に遠隔転移巣切除可能になった症例において、転移巣切除後の再々発リスク因子や予後予測因子をctDNAによる層別化を検証する。

Circulating tumor DNA (ctDNA) uses cancer to stop paying attention to cancer. We were asked to study the cancer first, so that we could find out that the digital PCR (dPCR) of the special case of the disease had been studied first, and that the ctDNA had been used in the first place, and then cut off in the early stage. The treatment had been accompanied by ctDNA dynamics, and the status of the disease had confirmed that it was possible. After ctDNA treatment, the patients were cut off for further treatment of the cancer. The results showed that the patients were suffering from the disease. In this study, RECIST (Response Evaluation Criteria in Solid Tumors) was used to determine whether there was a significant increase in the number of samples, the number of complex particles, the number of symptoms, the number of patients who could not be resected. The results of this study were compared with those of patients who could not be resected during the period of chemical treatment of large cancer. the results of ctDNA test RECIST were compared with those of patients who could not be resected. Treatment and chemical methods are used to treat the problems caused by the use of heterogeneity ctDNA in the treatment of lung cancer, lung transfer and peritoneal surgery. The problem is that the peritoneum is sown in the peritoneum. In the case of septal metastases of large cancers, resection is necessary to improve the incidence of septal metastasis. resection may lead to active resection, multiple resection, and liver transfer after hepatectomy. the rate is more than 60%. The results of resection were similar to those of the same factors as those of important factors. In this study, patients with septal metastases, patients with ctDNA's symptoms, patients with recurrent symptoms after radical resection, patients with refractory symptoms after radical resection, patients with recurrent symptoms after radical resection, patients with recurrent symptoms after radical resection, patients with recurrent symptoms after long-term resection, patients with recurrent symptoms after radical resection, patients with recurrent symptoms after radical resection, patients with severe septal metastases, patients with severe septal metastases, and patients with severe septal metastasis. in this study, patients with septal metastases, patients with ctDNA syndrome, patients with recurrent symptoms after resection, patients with recurrent symptoms after radical resection, patients with refractory symptoms after radical resection, patients with refractory symptoms after radical resection, patients with recurrent symptoms after radical resection, patients with recurrent symptoms after radical resection, patients with recurrent symptoms after radical resection, patients with severe septal metastasis. in this study, there were two cases of septal metastasis. in this study, patients with septal metastases were treated long after resection. long-term follow-up after excision,