Center for Experimental and Molecular Medicine, Amsterdam UMC, location University of Amsterdam, Amsterdam, the Netherlands.
Oncode Institute, Amsterdam, the Netherlands.
JAMA Netw Open. 2023 Feb 1;6(2):e230631. doi: 10.1001/jamanetworkopen.2023.0631.
Although small intestinal adenocarcinomas (SIAs) are rare, they have a poor prognosis, and the optimal treatment strategies are largely unknown. Because of the lack of high-quality evidence, guidelines for colorectal cancer are often followed in the treatment of SIAs.
To review the current evidence regarding survival benefit of systemic therapies, including chemotherapy, targeted agents, and immunotherapy, for patients with SIAs.
Following the Preferred Reporting Items for Systematic Reviews and Meta-analyses, MEDLINE and Embase were searched for articles published from January 1, 2005, until June 1, 2022.
Retrospective cohort studies and prospective phase 2 or 3 trials describing survival after systemic therapies for patients with SIAs were eligible for inclusion. Assessment of study eligibility was blinded and performed by 3 reviewers.
The reviewers independently extracted data. Random effects, inverse variance, pairwise meta-analyses were performed.
Primary outcomes were overall survival (OS) and progression-free survival (PFS) of patients with SIAs after systemic therapies. Measures of interest included hazard ratios for survival and median survival times.
Overall, 57 retrospective cohort and phase 2 studies of 35 176 patients were included. Adjuvant chemotherapy, generally fluoropyrimidine-based, was associated with increased OS in stage I to III SIAs (hazard ratio [HR], 0.60; 95% CI, 0.53-0.68), especially in stage III tumors (HR, 0.55; 95% CI, 0.48-0.64), irrespective of tumor localization. Palliative chemotherapy was also associated with an OS benefit (HR, 0.48; 95% CI, 0.40-0.58). Fluoropyrimidine-oxaliplatin combinations were superior to other regimens (OS: HR, 0.54; 95% CI, 0.30-0.99; PFS: HR, 0.46; 95% CI, 0.30-0.71). Furthermore, bevacizumab added to chemotherapy compared with chemotherapy alone was associated with significantly prolonged PFS (HR, 0.62; 95% CI, 0.43-0.89). Immunotherapy showed a 50% overall response rate in previously treated defective mismatch repair tumors.
In this systematic review and meta-analysis, adjuvant and palliative chemotherapy were both associated with improved survival of patients with SIAs, especially fluoropyrimidine-based regimens and fluoropyrimidine-oxaliplatin combinations. Adding bevacizumab to chemotherapy appears to prolong PFS and deserves further investigation. Immunotherapy seems beneficial and should be considered for patients with defective mismatch repair tumors. International collaborations should be undertaken to confirm and improve efficacy of systemic therapies for patients with SIAs.
尽管小肠腺癌（SIAs）较为罕见，但预后较差，且其最佳治疗策略仍知之甚少。由于缺乏高质量的证据，在治疗 SIAs 时通常遵循结直肠癌的指南。
回顾目前关于全身治疗（包括化疗、靶向药物和免疫疗法）对 SIAs 患者生存获益的证据。
根据系统评价和荟萃分析的首选报告项目，检索了 2005 年 1 月 1 日至 2022 年 6 月 1 日发表的文章，检索 MEDLINE 和 Embase。
纳入描述 SIAs 患者接受全身治疗后生存情况的回顾性队列研究和前瞻性 2 期或 3 期试验。
研究者独立提取数据。采用随机效应、倒数方差、成对荟萃分析进行分析。
主要结局为 SIAs 患者接受全身治疗后的总生存（OS）和无进展生存（PFS）。感兴趣的指标包括生存的风险比和中位生存时间。
共纳入 57 项 35176 例患者的回顾性队列和 2 期研究。辅助化疗，通常是氟嘧啶类药物，与 I 期至 III 期 SIAs 的 OS 增加相关（HR，0.60；95%CI，0.53-0.68），特别是在 III 期肿瘤中（HR，0.55；95%CI，0.48-0.64），与肿瘤定位无关。姑息性化疗也与 OS 获益相关（HR，0.48；95%CI，0.40-0.58）。氟嘧啶-奥沙利铂联合方案优于其他方案（OS：HR，0.54；95%CI，0.30-0.99；PFS：HR，0.46；95%CI，0.30-0.71）。此外，与单纯化疗相比，贝伐珠单抗联合化疗与显著延长 PFS 相关（HR，0.62；95%CI，0.43-0.89）。免疫治疗在先前治疗的错配修复缺陷肿瘤中显示出 50%的总缓解率。
在这项系统评价和荟萃分析中，辅助和姑息性化疗均与 SIAs 患者的生存改善相关，特别是基于氟嘧啶的方案和氟嘧啶-奥沙利铂联合方案。在化疗中加入贝伐珠单抗似乎延长了 PFS，值得进一步研究。免疫治疗似乎有效，应考虑用于错配修复缺陷肿瘤患者。应开展国际合作，以证实和提高 SIAs 患者全身治疗的疗效。
