Liu Zhen, Liu Kun, Gao Jiale, Jing Chao, Ma Yanhong, Zheng Shu, Shan Jianzhen
Department of Oncology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Cancer Institute (Key Laboratory for Cancer Intervention and Prevention, China National Ministry of Education, Zhejiang Provincial Key Laboratory of Molecular Biology in Medical Sciences), The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Front Oncol. 2022 Mar 25;12:865745. doi: 10.3389/fonc.2022.865745. eCollection 2022.
Due to the lack of large-scale clinical trials, the treatment strategies of small bowel adenocarcinoma (SBA) are controversial, especially for stage II patients. According to the National Comprehensive Cancer Network (NCCN) guideline, few lymph nodes (LNs) examined (<5 for duodenum or <8 for jejunal/ileal primary location) are one of the high-risk features for stage II patients, for whom adjuvant chemotherapy is recommended. This consensus is originally drawn from data in the Surveillance, Epidemiology, and End Results Database (SEER) between 1988 and 2010. However, the surgical modalities and chemotherapy strategies changed a lot after 2004 for SBA patients. The previous data may not represent a true picture of current therapeutics. Thus, we reanalyzed the SEER database and updated the cutoff point of LN numbers resected with respect to cancer-specific survival (CSS) using the latest SEER information.
Patients diagnosed with stage II SBA and who underwent curative surgery between 2004 and 2018 were extracted from the SEER database. CSS was calculated using the Kaplan-Meier method and compared by log-rank test. Maximum survival differences based on total LNs examined for duodenal and jejunoileal tumors were determined separately with the cut-point analysis and maximum log-rank χ statistic. A nomogram model was constructed based on the multivariate Cox analysis to predict 5- and 10-year CSS and was then validated with an internal cohort.
A total of 935 stage II SBA patients met the inclusion criteria. The greatest difference in survival was found in patients who had removal of at least 5 LNs for duodenal and 12 LNs for jejunoileal tumors. Multivariate Cox analysis showed that age, T stage, histology grade, primary site, and LN numbers were independent prognostic factors for survival. The C index of nomogram model was 0.701 (95% CI, 0.661-0.741, p < 0.001).
The number of LNs harvested is an important prognostic factor for survival in stage II SBA patients. LN number examined <5 remains a high-risk factor for duodenum, but the cutoff point for jejunal/ileal tumors should rise from 8 to 12. Appropriate radical lymphadenectomy should be performed in stage II SBA surgery.
由于缺乏大规模临床试验，小肠腺癌（SBA）的治疗策略存在争议，尤其是对于II期患者。根据美国国立综合癌症网络（NCCN）指南，检查的淋巴结（LN）数量少（十二指肠少于5个或空肠/回肠原发部位少于8个）是II期患者的高危特征之一，推荐对这类患者进行辅助化疗。这一共识最初源自1988年至2010年监测、流行病学和最终结果数据库（SEER）中的数据。然而，2004年后SBA患者的手术方式和化疗策略发生了很大变化。先前的数据可能无法代表当前治疗的真实情况。因此，我们重新分析了SEER数据库，并使用最新的SEER信息更新了与癌症特异性生存（CSS）相关的切除LN数量的临界值。
从SEER数据库中提取2004年至2018年间被诊断为II期SBA且接受了根治性手术的患者。使用Kaplan-Meier方法计算CSS，并通过对数秩检验进行比较。分别通过切点分析和最大对数秩χ统计量确定十二指肠和空回肠肿瘤检查的总LN数量的最大生存差异。基于多变量Cox分析构建列线图模型，以预测5年和10年CSS，然后在内部队列中进行验证。
共有935例II期SBA患者符合纳入标准。十二指肠肿瘤切除至少5个LN、空回肠肿瘤切除至少12个LN的患者生存差异最大。多变量Cox分析显示，年龄、T分期、组织学分级、原发部位和LN数量是生存的独立预后因素。列线图模型的C指数为0.701（95%CI，0.661-0.741，p<0.001）。
收获的LN数量是II期SBA患者生存的重要预后因素。检查的LN数量<5仍然是十二指肠的高危因素，但空肠/回肠肿瘤的临界值应从8提高到12。II期SBA手术应进行适当的根治性淋巴结清扫。
