Camandaroba Marcos Pedro Guedes, de Araujo Raphael Leonardo Cunha, Silva Virgílio Souza E, de Mello Celso Abdon Lopes, Riechelmann Rachel P
Department of Clinical Oncology, A.C. Camargo Cancer Center, Sao Paulo, SP, Brazil.
Department of Digestive Surgery, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, SP, Brazil.
J Gastrointest Oncol. 2019 Feb;10(1):48-60. doi: 10.21037/jgo.2018.10.08.
Definitive chemoradiation (CRT) is the standard treatment for localized squamous cell carcinoma of the anus (SCCA). Because most phase III trials in SCCA have excluded patients with HIV, the evidence on treatment outcomes of these patients is lacking. We performed a systematic review and meta-analysis on the efficacy and toxicity profiles of HIV-positive SCCA patients treated with definitive CRT.
The systematic search was conducted Embase, Medline, Cochrane Libary, Scopus, Lilacs and Opengrey, from inception until September 2017. Eligible studies were clinical trials, prospective or retrospective cohort studies. The main outcome variables were 3-year disease-free survival (DFS) and overall survival (OS) rates and frequency of grade 3 or 4 (G3/4) treatment-related toxicities, according to HIV status. Meta-analyses using pooled risk ratios were performed for binary outcomes from comparative studies from the antiretroviral therapy (HAART) era with the fixed effects model.
Out of 3,951 studies, 40 were deemed eligible, with a total of 3,720 patients. One third (N=1,298; 34%) were HIV-positive and their median pre CRT CD4 count was 347 µm/L. HIV-positive patients presented higher risk of G3/4 cutaneous toxicities [risk ratio (RR) =1.34; 95% CI, 1.10-1.64; P=0.004; I=77.7%], worse 3-year DFS rate (RR =1.32; 95% CI, 1.01-1.74; P=0.043; I=52.19%), and 3-year OS rate (RR =1.77; 95% CI, 1.35-2.32; P<0.001; I=6%).
Patients with localized SCCA and HIV infection treated with CRT tend to experience higher risk of toxicities and worse DFS and OS rates. Our findings suggest that future trials should be tailored to HIV-positive patients.
根治性放化疗（CRT）是局部肛管鳞状细胞癌（SCCA）的标准治疗方法。由于大多数SCCA的III期试验排除了HIV患者，因此缺乏这些患者治疗结果的证据。我们对接受根治性CRT治疗的HIV阳性SCCA患者的疗效和毒性特征进行了系统评价和荟萃分析。
从数据库建立至2017年9月，在Embase、Medline、Cochrane图书馆、Scopus、Lilacs和Opengrey中进行系统检索。符合条件的研究为临床试验、前瞻性或回顾性队列研究。主要结局变量为根据HIV状态的3年无病生存率（DFS）、总生存率（OS）以及3/4级（G3/4）治疗相关毒性的发生率。对来自抗逆转录病毒治疗（HAART）时代的比较研究中的二元结局，采用固定效应模型进行汇总风险比的荟萃分析。
在3951项研究中，40项被认为符合条件，共有3720例患者。其中三分之一（N = 1298；34%）为HIV阳性，其CRT前CD4细胞计数中位数为347个/微升。HIV阳性患者出现3/4级皮肤毒性的风险更高[风险比（RR）= 1.34；95%置信区间（CI），1.10 - 1.64；P = 0.004；I² = 77.7%]，3年DFS率更差（RR = 1.32；95% CI，1.01 - 1.74；P = 0.043；I² = 52.19%），3年OS率也更差（RR = 1.77；95% CI，1.35 - 2.32；P < 0.001；I² = 6%）。
接受CRT治疗的局部SCCA合并HIV感染患者往往毒性风险更高，DFS和OS率更差。我们的研究结果表明，未来的试验应针对HIV阳性患者进行调整。
