III 期错配修复缺陷型结肠癌辅助化疗的生存结局。
Survival outcome of adjuvant chemotherapy in deficient mismatch repair stage III colon cancer.
机构信息
Department of Hematology and Oncology, Winship Cancer Institute, Emory University, Atlanta, Georgia.
Winship Research Informatics, Emory University, Atlanta, Georgia.
出版信息
Cancer. 2020 Sep 15;126(18):4136-4147. doi: 10.1002/cncr.33049. Epub 2020 Jul 22.
BACKGROUND
The prognostic impact of DNA mismatch repair (MMR) status remains controversial in patients with stage III colon cancer who are treated with adjuvant chemotherapy (AC). The aim of this study was to evaluate the survival outcome of AC in deficient mismatch repair (dMMR)/microsatellite instable (MSI) stage III CC.
METHODS
Patients with pathological stage III CC between 2010 and 2013 were identified from the National Cancer Database using International Classification of Diseases for Oncology (3rd Edition) morphology and topography codes 8140, 8480, and C18.0-18.8. Patients with pathologic stage T3N2, T4N1, or T4N were considered high risk; patients with stage T3N1 were considered low risk. Univariate and multivariable analyses were conducted, and Kaplan-Meier analysis and Cox proportional hazards models were used to identify the association between AC and overall survival (OS).
RESULTS
A total of 9226 patients with pathological stage III CC were identified, of which 2384 (25.8%) were MSI-high (MSI-H) and met the inclusion criteria of the final analysis. MSI-low (MSI-L) patients (n = 6842) were excluded. There was a preponderance of women (55.0% [n = 1311]), and 76.6% (n = 1825) of patients were non-Hispanic white. The median age was 65 years (range, 19-90 years). The primary sites were the cecum (29.7% [n = 707]), ascending colon (26.0% [n = 620]), sigmoid colon (17.2% [n = 410]), and transverse colon (10.8% [n = 257]). The most common tumor grade was moderately differentiated (n = 50.4% [1202]), followed by poorly differentiated (34.1% [n = 813]) and well differentiated (5.1% [n = 121]). High-risk pathologic stage III CC (T4N1, TxN2) constituted 51.0% (n = 1215) of the study population. High-risk stage III was associated with worse OS compared with low-risk stage III on univariate (P < .001) analysis and displayed a similar trend on multivariable analysis, without a statistically significant difference. Multiagent AC was associated with improved OS compared with no treatment on univariate (P < .001) and multivariable (P < .001) analysis. When stratified by risk status, multiagent AC was associated with improved OS compared with no treatment for high-risk (P < .001) and low-risk (P < .001) stage III disease.
CONCLUSION
Adjuvant chemotherapy is associated with better OS in stage III dMMR/MSI-H CC. An enhanced benefit was shown for high-risk stage III disease.
背景
在接受辅助化疗（AC）治疗的 III 期结肠癌患者中，DNA 错配修复（MMR）状态的预后影响仍存在争议。本研究旨在评估在缺陷性错配修复（dMMR）/微卫星不稳定（MSI）III 期 CC 中 AC 的生存结局。
方法
使用国际肿瘤疾病分类（第 3 版）形态学和解剖学代码 8140、8480 和 C18.0-18.8，从国家癌症数据库中确定 2010 年至 2013 年间患有病理 III 期 CC 的患者。病理 T3N2、T4N1 或 T4N 的患者被认为是高危；T3N1 期患者被认为是低危。进行了单变量和多变量分析，并使用 Kaplan-Meier 分析和 Cox 比例风险模型来确定 AC 与总生存期（OS）之间的关联。
结果
共确定了 9226 例病理 III 期 CC 患者，其中 2384 例（25.8%）为 MSI-高（MSI-H），符合最终分析的纳入标准。排除了 MSI-低（MSI-L）患者（n=6842）。女性居多（55.0%[n=1311]），76.6%（n=1825）的患者为非西班牙裔白人。中位年龄为 65 岁（范围 19-90 岁）。原发部位为盲肠（29.7%[n=707]）、升结肠（26.0%[n=620]）、乙状结肠（17.2%[n=410]）和横结肠（10.8%[n=257]）。最常见的肿瘤分级为中分化（n=50.4%[n=1202]），其次是低分化（34.1%[n=813]）和高分化（5.1%[n=121]）。高风险病理 III 期 CC（T4N1、TxN2）占研究人群的 51.0%（n=1215）。单变量分析（P<0.001）和多变量分析（P<0.001）均显示，高危 III 期与低危 III 期相比，OS 更差，且无统计学差异。与无治疗相比，多药 AC 与 OS 改善相关，无论单变量（P<0.001）还是多变量分析（P<0.001）。按风险状态分层时，与无治疗相比，多药 AC 与高危（P<0.001）和低危（P<0.001）III 期疾病的 OS 改善相关。
结论
在 III 期 dMMR/MSI-H CC 中，辅助化疗与更好的 OS 相关。高危 III 期疾病显示出更大的获益。
Zotero 插件