Japan Clinical Oncology Group Data Center/Operations Office, National Cancer Center Hospital, Tokyo, Japan.
Translational Research Support Office, National Cancer Center Hospital East, Kashiwa, Japan.
BMJ Open. 2023 Aug 16;13(8):e073217. doi: 10.1136/bmjopen-2023-073217.
In locally recurrent rectal cancer (LRRC), surgery is a standard treatment for resectable disease. However, short-term and long-term outcomes are unsatisfactory due to the invasive nature of surgical procedures and the high proportion of local recurrence. Consequently, the identification of reliable prognostic and predictive biomarkers to guide treatment decisions may improve outcomes. The presence of circulating tumour DNA (ctDNA) in plasma after surgery may signify the presence of minimal residual disease (MRD) in various cancers. Therefore, we have launched a multi-institutional prospective observational study of ctDNA for MRD detection in conjunction with JCOG1801, a randomised, controlled phase III trial evaluating the efficacy of preoperative chemoradiotherapy (pre-CRT) compared with up-front surgery for LRRC (jRCTs031190076, NCT04288999).
JCOG1801A1 is the first correlative study that assesses ctDNA in LRRC patients enrolled in JCOG1801. Patients randomised to up-front surgery will provide whole blood samples at three time points (prior to surgery, after surgery and after postoperative chemotherapy); those to pre-CRT will provide at five time points (prior to pre-CRT, after pre-CRT, prior to surgery, after surgery and after postoperative chemotherapy). Cell-free DNA will be extracted from plasma and analysed by Guardant Reveal, a tumour tissue-agnostic assay that assesses both genomic alterations and methylation patterns to determine the presence or absence of ctDNA. We will compare the prognosis and treatment response of patients according to their ctDNA status after surgery and at other time points.
The study protocol received approval from the Institutional Review Board of National Cancer Center Hospital East on behalf of the participating institutions in February 2023. The study is conducted in accordance with the precepts established in the Declaration of Helsinki and Ethical Guidelines for Medical and Biological Research Involving Human Subjects. Written informed consent will be obtained from all eligible patients prior to registration.
在局部复发性直肠癌（LRRC）中，手术是可切除疾病的标准治疗方法。然而，由于手术的侵袭性和局部复发的高比例，短期和长期结果并不令人满意。因此，确定可靠的预后和预测生物标志物来指导治疗决策可能会改善结果。手术后血浆中循环肿瘤 DNA（ctDNA）的存在可能表明各种癌症存在微小残留疾病（MRD）。因此，我们与 JCOG1801 一起启动了一项多机构前瞻性观察性研究，以检测 ctDNA 用于 MRD 检测，JCOG1801 是一项随机对照 III 期试验，评估术前放化疗（pre-CRT）与 LRRC 的 upfront 手术（jRCTs031190076，NCT04288999）的疗效。
JCOG1801A1 是第一项评估 JCOG1801 入组的 LRRC 患者 ctDNA 的相关研究。随机分配至 upfront 手术的患者将在三个时间点提供全血样本（手术前、手术后和术后化疗后）；接受 pre-CRT 的患者将在五个时间点提供样本（pre-CRT 前、pre-CRT 后、手术前、手术后和术后化疗后）。从血浆中提取无细胞 DNA，并通过 Guardant Reveal 进行分析，这是一种肿瘤组织非特异性检测方法，评估基因组改变和甲基化模式，以确定是否存在 ctDNA。我们将根据手术后和其他时间点的 ctDNA 状态比较患者的预后和治疗反应。
该研究方案于 2023 年 2 月获得国立癌症中心医院东机构审查委员会的批准。该研究符合赫尔辛基宣言和涉及人体生物医学研究的伦理准则的规定。在登记之前，将从所有符合条件的患者获得书面知情同意。
