Davuluri Rajayogesh, Jiang Wen, Fang Penny, Xu Cai, Komaki Ritsuko, Gomez Daniel R, Welsh James, Cox James D, Crane Christopher H, Hsu Charles C, Lin Steven H
Department of Radiation Oncology, The University of Arizona, Tucson, Arizona.
Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Int J Radiat Oncol Biol Phys. 2017 Sep 1;99(1):128-135. doi: 10.1016/j.ijrobp.2017.05.037. Epub 2017 Jun 1.
Host immunity may affect the outcome in patients with esophageal cancer. We sought to identify factors that influenced absolute lymphocyte count (ALC) nadir during chemoradiation therapy (CRT) for esophageal cancer (EC) and looked for clinically relevant associations with survival.
504 patients with stage I-III EC (2007-2013) treated with neoadjuvant or definitive CRT with weekly ALC determinations made during treatment were analyzed. Grade of lymphopenia from ALC nadir during CRT was based on Common Terminology Criteria for Adverse Events version 4.0. Associations of ALC nadir with survival were examined using multivariate Cox proportional hazards analysis (MVA) and competing risks regression analysis.
The median follow-up time was 36 months. The incidences of grade 1, 2, 3, and 4 ALC nadir during CRT were 2%, 12%, 59%, and 27%, respectively. The impact was lymphocyte-specific because this was not seen for monocyte or neutrophil count. On MVA, grade 4 ALC nadir (G4 nadir) was significantly associated with worse overall and disease-specific survival outcomes. Predictors of G4 nadir included distal tumor location, definitive CRT, taxane/5-fluorouracil chemotherapy, and photon-based radiation type (vs proton-based). Radiation type strongly influenced the mean body dose exposure, which was a strong predictor for G4 nadir (odds ratio 1.22 per Gray, P<.001).
G4 nadir during CRT for EC was associated with poor outcomes, suggesting a role of host immunity in disease control. This observation provides a rationale to prospectively test chemotherapeutic and radiation treatment strategies that may have a lower impact on host immunity.
宿主免疫可能会影响食管癌患者的预后。我们试图确定在食管癌放化疗（CRT）期间影响绝对淋巴细胞计数（ALC）最低点的因素，并寻找与生存相关的临床关联。
分析了504例I-III期食管癌患者（2007-2013年），这些患者接受了新辅助或根治性CRT，治疗期间每周测定ALC。CRT期间ALC最低点的淋巴细胞减少分级基于不良事件通用术语标准第4.0版。使用多变量Cox比例风险分析（MVA）和竞争风险回归分析检查ALC最低点与生存的关联。
中位随访时间为36个月。CRT期间1级、2级、3级和4级ALC最低点的发生率分别为2%、12%、59%和27%。这种影响是淋巴细胞特异性 的，因为单核细胞或中性粒细胞计数未出现这种情况。在MVA中，4级ALC最低点（G4最低点）与总体和疾病特异性生存结果较差显著相关。G4最低点的预测因素包括肿瘤远端位置、根治性CRT、紫杉烷/5-氟尿嘧啶化疗和光子放疗类型（与质子放疗相比）。放疗类型强烈影响平均身体剂量暴露，这是G4最低点的一个强预测因素（每格雷的优势比为1.22，P<.001）。
食管癌CRT期间的G4最低点与不良预后相关，提示宿主免疫在疾病控制中起作用。这一观察结果为前瞻性测试可能对宿主免疫影响较小的化疗和放疗策略提供了理论依据。
