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结直肠癌患者的分子残留疾病与辅助化疗疗效。

Molecular residual disease and efficacy of adjuvant chemotherapy in patients with colorectal cancer.

机构信息

Department of Gastroenterology and Gastrointestinal Oncology, National Cancer Center Hospital East, Kashiwa, Japan.

Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.

出版信息

Nat Med. 2023 Jan;29(1):127-134. doi: 10.1038/s41591-022-02115-4. Epub 2023 Jan 16.

DOI:10.1038/s41591-022-02115-4
PMID:36646802
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9873552/
Abstract

Despite standard-of-care treatment, more than 30% of patients with resectable colorectal cancer (CRC) relapse. Circulating tumor DNA (ctDNA) analysis may enable postsurgical risk stratification and adjuvant chemotherapy (ACT) treatment decision-making. We report results from GALAXY, which is an observational arm of the ongoing CIRCULATE-Japan study (UMIN000039205) that analyzed presurgical and postsurgical ctDNA in patients with stage II-IV resectable CRC (n = 1,039). In this cohort, with a median follow-up of 16.74 months (range 0.49-24.83 months), postsurgical ctDNA positivity (at 4 weeks after surgery) was associated with higher recurrence risk (hazard ratio (HR) 10.0, P < 0.0001) and was the most significant prognostic factor associated with recurrence risk in patients with stage II or III CRC (HR 10.82, P < 0.001). Furthermore, postsurgical ctDNA positivity identified patients with stage II or III CRC who derived benefit from ACT (HR 6.59, P < 0.0001). The results of our study, a large and comprehensive prospective analysis of ctDNA in resectable CRC, support the use of ctDNA testing to identify patients who are at increased risk of recurrence and are likely to benefit from ACT.

摘要

尽管采用了标准治疗，但仍有 30%以上的可切除结直肠癌（CRC）患者复发。循环肿瘤 DNA（ctDNA）分析可能有助于术后风险分层和辅助化疗（ACT）治疗决策。我们报告了正在进行的 CIRCULATE-Japan 研究（UMIN000039205）的观测臂 GALAXY 的结果，该研究分析了可切除 II-IV 期 CRC 患者的术前和术后 ctDNA（n=1039）。在该队列中，中位随访时间为 16.74 个月（范围 0.49-24.83 个月），术后 ctDNA 阳性（术后 4 周）与更高的复发风险相关（风险比（HR）10.0，P<0.0001），并且是与 II 期或 III 期 CRC 患者复发风险最显著的相关预后因素（HR 10.82，P<0.001）。此外，术后 ctDNA 阳性可识别出从 ACT 中获益的 II 期或 III 期 CRC 患者（HR 6.59，P<0.0001）。我们的研究结果是对可切除 CRC 中 ctDNA 的一项大型和全面的前瞻性分析，支持使用 ctDNA 检测来识别复发风险增加且可能从 ACT 中获益的患者。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/226c/9873552/bd8e9bae17f0/41591_2022_2115_Fig12_ESM.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/226c/9873552/cfabdd3b6537/41591_2022_2115_Fig7_ESM.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/226c/9873552/b38a56feac32/41591_2022_2115_Fig8_ESM.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/226c/9873552/d18127d4072b/41591_2022_2115_Fig9_ESM.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/226c/9873552/412dce3dfacc/41591_2022_2115_Fig10_ESM.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/226c/9873552/57d4b2a8c071/41591_2022_2115_Fig11_ESM.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/226c/9873552/bd8e9bae17f0/41591_2022_2115_Fig12_ESM.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/226c/9873552/2caed5570687/41591_2022_2115_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/226c/9873552/f22ac400d32b/41591_2022_2115_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/226c/9873552/382564e8edb5/41591_2022_2115_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/226c/9873552/aee14fbf52b4/41591_2022_2115_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/226c/9873552/12503b3cf59a/41591_2022_2115_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/226c/9873552/dcd38c2bf00e/41591_2022_2115_Fig6_ESM.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/226c/9873552/cfabdd3b6537/41591_2022_2115_Fig7_ESM.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/226c/9873552/b38a56feac32/41591_2022_2115_Fig8_ESM.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/226c/9873552/d18127d4072b/41591_2022_2115_Fig9_ESM.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/226c/9873552/412dce3dfacc/41591_2022_2115_Fig10_ESM.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/226c/9873552/57d4b2a8c071/41591_2022_2115_Fig11_ESM.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/226c/9873552/bd8e9bae17f0/41591_2022_2115_Fig12_ESM.jpg

相似文献

[1]
Molecular residual disease and efficacy of adjuvant chemotherapy in patients with colorectal cancer.

Nat Med. 2023-1

[2]
Circulating tumor DNA dynamics and recurrence risk in patients undergoing curative intent resection of colorectal cancer liver metastases: A prospective cohort study.

PLoS Med. 2021-5

[3]
Circulating Tumor DNA as a Minimal Residual Disease Assessment and Recurrence Risk in Patients Undergoing Curative-Intent Resection with or without Adjuvant Chemotherapy in Colorectal Cancer: A Systematic Review and Meta-Analysis.

Int J Mol Sci. 2023-6-16

[4]
CIRCULATE-Japan: Circulating tumor DNA-guided adaptive platform trials to refine adjuvant therapy for colorectal cancer.

Cancer Sci. 2021-7

[5]
Circulating Tumor DNA Analyses as Markers of Recurrence Risk and Benefit of Adjuvant Therapy for Stage III Colon Cancer.

JAMA Oncol. 2019-12-1

[6]
Postoperative circulating tumor DNA as markers of recurrence risk in stages II to III colorectal cancer.

J Hematol Oncol. 2021-5-17

[7]
Early Detection of Molecular Residual Disease and Risk Stratification for Stage I to III Colorectal Cancer via Circulating Tumor DNA Methylation.

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[8]
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Clin Cancer Res. 2024-8-15

[9]
Circulating tumor DNA is a prognostic marker of tumor recurrence in stage II and III colorectal cancer: multicentric, prospective cohort study (ALGECOLS).

Eur J Cancer. 2021-12

[10]
ctDNA-based molecular residual disease and survival in resectable colorectal cancer.

Nat Med. 2024-11

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