Radiation-Associated Lymphopenia and Outcomes of Patients with Unresectable Hepatocellular Carcinoma Treated with Radiotherapy.
Radiation-Associated Lymphopenia and Outcomes of Patients with Unresectable Hepatocellular Carcinoma Treated with Radiotherapy.
复制标题
放疗相关的淋巴细胞减少与不可切除肝细胞癌患者放疗后的结局
DOI：
10.2147/jhc.s282062
复制
发表时间：
2021
影响因子：
4.1
通讯作者：
Koay EJ
中科院分区：
文献类型：
--
作者：
De B;Ng SP;Liu AY;Avila S;Tao R;Holliday EB;Brownlee Z;Kaseb A;Lee S;Raghav K;Vauthey JN;Minsky BD;Herman JM;Das P;Smith GL;Taniguchi CM;Krishnan S;Crane CH;Grassberger C;Hong TS;Lin SH;Koong AC;Mohan R;Koay EJ
免疫系统在癌症监测中起着至关重要的作用。先前的研究表明，与放疗（RT）相关的淋巴细胞减少预示着不良预后。我们试图区分质子放疗和光子放疗对肝细胞癌（HCC）患者绝对淋巴细胞计数（ALC）变化的影响。
对2006年至2016年接受根治性放疗的肝细胞癌患者进行了研究。连续的ALC根据CTCAE v4.0进行分级。采用卡普兰 - 迈耶方法分析总生存期（OS）、无病生存期和无远处转移生存期。使用单变量和多变量考克斯比例风险分析来确定OS的预测因素。进行了一项针对治疗体积匹配的队列分析，以研究光子治疗和质子治疗之间ALC动态的差异。
在确定的143名患者中，中位年龄为66岁（范围为19 - 90岁）。治疗方式为光子放疗的有103例（72%），质子放疗的有40例（28%）。中位随访时间为17个月（95%置信区间为13 - 25个月）。放疗开始后ALC降至最低点的中位时间为17天，中位相对下降率为67%。接受质子放疗的患者ALC最低点的中位数更高（0.41对0.32×10³/μL，p = 0.002），中位总生存期更长（33对13个月，p = 0.002），相比接受光子放疗的患者。匹配队列分析显示光子组的低剂量肝脏体积更大，这与较低的ALC相关。在多变量考克斯分析中，放疗前或放疗后3级或更高级别的淋巴细胞减少、门静脉肿瘤血栓、更大的计划靶体积、Child - Pugh B级以及放疗后Child - Pugh评分升高与更高的死亡风险相关，而使用质子治疗与较低风险相关。
3级或更高级别的淋巴细胞减少可能与接受肝细胞癌放疗的患者预后较差有关。与光子相比，质子可能减轻淋巴细胞减少，这可能是由于淋巴细胞生成部位的剂量暴露减少。
The immune system plays a crucial role in cancer surveillance. Previous studies have shown that lymphopenia associated with radiotherapy (RT) portends a poor prognosis. We sought to differentiate the effects of proton and photon RT on changes in absolute lymphocyte count (ALC) for patients with hepatocellular carcinoma (HCC). Patients with HCC treated with definitive RT from 2006 to 2016 were studied. Serial ALCs were graded according to CTCAE v4.0. Overall survival (OS), disease-free survival, and distant metastasis-free survival were analyzed using the Kaplan–Meier method. Univariable and multivariable Cox-proportional hazards analyses were used to identify predictors of OS. A cohort analysis matched for treatment volume was performed to investigate differences in ALC dynamics between photon and proton therapy. Of 143 patients identified, the median age was 66 (range, 19–90) years. The treatment modality was photon in 103 (72%) and proton in 40 (28%). Median follow-up was 17 months (95% confidence interval, 13–25 months). The median time to ALC nadir after initiation of RT was 17 days with a median relative decrease of 67%. Those who received proton RT had a higher median ALC nadir (0.41 vs 0.32 k/µL, p=0.002) and longer median OS (33 vs 13 months, p=0.002) than those who received photon RT. Matched cohort analyses revealed a larger low-dose liver volume in the photon group, which correlated with lower ALC. On multivariable Cox analysis, Grade 3 or higher lymphopenia prior to or after RT, portal venous tumor thrombus, larger planning target volumes, Child-Pugh (CP) Class B, and increased CP score after RT were associated with a higher risk of death, whereas the use of proton therapy was associated with lower risk. Grade 3 or higher lymphopenia may be associated with poorer outcomes in patients receiving RT for HCC. Protons may mitigate lymphopenia compared with photons, potentially due to reduced dose exposure of sites of lymphopoiesis.