Prognostic value of circulating tumor DNA (ctDNA) detection during adjuvant chemotherapy in patients with stage III colorectal cancer: The interim report of a prospective, observational study.
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29 Background: Adjuvant chemotherapy (ACT) is the standard treatment for stage III colorectal cancers (CRC). However, optimal biomarker were still needed for individualized adjuvant strategies. Here, we conducted a prospective study in patients with stage III CRCs with combined ACT, to explore the prognostic effect of circulating tumor DNA (ctDNA) before and after ACT. Methods: The study enrolled 130 patients with stage III colon and rectal cancer (≥10cm from anal) who received curative resection without neoadjuvant therapy at Fudan University Shanghai Cancer Center. All patients received 3 or 6 months of ACT. The Roche AVENIO Surveillance Kit was used to assess somatic mutations by next-generation sequencing (NGS) in tissue, pre- and post-chemo plasma samples. The plasmas were collected 3-5 weeks after surgery and after last cycle of ACT, respectively. Patients were classified as ctDNA (+) or (-) based on the detection of SNVs identified in tumor tissue at an AF of at least 5%. Results: In the interim analysis, 116 tissues, 123 pre-chemo and 98 post-chemo plasmas were prospectively collected and detected, and a total of 86 matched samples were analyzed with a median follow-up of 12.0 months. ctDNA was detectable in 14 of 86 patients (16.3%) before ACT, and in 10 (11.6%) patients after ACT. After 1-year follow-up, longitudinal ctDNA analysis identified 6 of 12 early relapses (50.0%), while 6 in 69 patients (8.7%) who were both ctDNA (-) in pre- and post-chemo samples had early relapse. Before ACT, ctDNA(+) patients were 7 times more likely to relapse early than ctDNA(-) patients (HR, 7.372; 95% CI, 1.543-35.22; P = 0.012). Similarly, after ACT, ctDNA(+) patients were 13 times (HR, 13.37; 95% CI, 2.026-88.23; P = 0.007) more likely to relapse. Monitoring after ACT indicated that 7 of the 14 ctDNA(+) patients (50.0%) were cleared, and the early relapse rate decreased from 43.9% (3/7) to 28.6% (2/7) if ctDNA turned negative. Conclusions: ctDNA analysis can potentially change the postoperative management and surveillance strategies for stage III CRC by enabling risk stratification, monitoring ACT efficacy, and detecting early relapse. Clinical trial information: ChiCTR1800018754.Keywords:
Interim analysis
Circulating tumor DNA
Interim
Adjuvant Chemotherapy
Adjuvant Therapy
Supplementary Data from Circulating Tumor DNA in Stage III Colorectal Cancer, beyond Minimal Residual Disease Detection, toward Assessment of Adjuvant Therapy Efficacy and Clinical Behavior of Recurrences
Minimal Residual Disease
Adjuvant Therapy
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背景・目的: oxaliplatin base の化学療法が大腸癌腹膜播種症例に与える影響について検討した。対象・方法: 2006 年1月～2012 年11 月の間に，腹膜播種陽性Stage IV 大腸癌と診断され，oxaliplatin base の化学療法を導入した49 例（oxaliplatin施行群）と，それ以前に5─FU 系の全身化学療法を施行した26 例（control 群）を対象。oxaliplatin 導入前後のoverall survival（OS）を比較。また，oxaliplatin 施行群のOS に関して臨床病理学的因子を共変量とし，単変量，多変量解析を行い，予後因子を検討した。結果: oxalplatin 施行群はcontrol 群より有意に生存期間が延長していた（中央値 20.5 か月 vs 11.7 か月，p＝0.04）。oxaliplatin 施行群におけるOS に対するfavorable factor として，70 歳以下（p＝0.03），原発巣切除（p＝0.02）が同定された。結語: oxaliplatin base の化学療法は大腸癌腹膜播種症例においても生存期間を改善させた。腹膜播種の程度に関係なく原発巣切除を70 歳以下の症例に行い，速やかにoxaliplatin base の化学療法を導入することが予後向上につながることが示唆された。
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Supplementary Data from Circulating Tumor DNA in Stage III Colorectal Cancer, beyond Minimal Residual Disease Detection, toward Assessment of Adjuvant Therapy Efficacy and Clinical Behavior of Recurrences
Minimal Residual Disease
Adjuvant Therapy
Circulating tumor DNA
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Supplementary Data from Circulating Tumor DNA in Stage III Colorectal Cancer, beyond Minimal Residual Disease Detection, toward Assessment of Adjuvant Therapy Efficacy and Clinical Behavior of Recurrences
Minimal Residual Disease
Circulating tumor DNA
Adjuvant Therapy
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Supplementary Data from Circulating Tumor DNA in Stage III Colorectal Cancer, beyond Minimal Residual Disease Detection, toward Assessment of Adjuvant Therapy Efficacy and Clinical Behavior of Recurrences
Minimal Residual Disease
Adjuvant Therapy
Circulating tumor DNA
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Supplementary Data from Circulating Tumor DNA in Stage III Colorectal Cancer, beyond Minimal Residual Disease Detection, toward Assessment of Adjuvant Therapy Efficacy and Clinical Behavior of Recurrences
Minimal Residual Disease
Adjuvant Therapy
Circulating tumor DNA
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Adjuvant Therapy
Circulating tumor DNA
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