De Brian, Ng Sweet Ping, Liu Amy Y, Avila Santiago, Tao Randa, Holliday Emma B, Brownlee Zachary, Kaseb Ahmed, Lee Sunyoung, Raghav Kanwal, Vauthey Jean-Nicolas, Minsky Bruce D, Herman Joseph M, Das Prajnan, Smith Grace L, Taniguchi Cullen M, Krishnan Sunil, Crane Christopher H, Grassberger Clemens, Hong Theodore S, Lin Steven H, Koong Albert C, Mohan Radhe, Koay Eugene J
Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Department of Radiation Oncology, Austin Health, Melbourne, Victoria, Australia.
J Hepatocell Carcinoma. 2021 Mar 3;8:57-69. doi: 10.2147/JHC.S282062. eCollection 2021.
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.
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预后不良。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。
研究了2006年至2016年接受根治性放疗的HCC患者。根据CTCAE v4.0对连续的ALC进行分级。采用Kaplan-Meier法分析总生存期（OS）、无病生存期和无远处转移生存期。采用单变量和多变量Cox比例风险分析来确定OS的预测因素。进行了匹配治疗体积的队列分析，以研究光子治疗和质子治疗之间ALC动态变化的差异。
在143例确诊患者中，中位年龄为66岁（范围19 - 90岁）。治疗方式为光子放疗103例（72%），质子放疗40例（28%）。中位随访时间为17个月（95%置信区间，13 - 25个月）。放疗开始后ALC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中位ALC最低点较高（0.41 vs 0.32 k/µL，p = 0.002），中位OS较长（33 vs 13个月，p = 0.002），高于接受光子放疗的患者。匹配队列分析显示光子组低剂量肝脏体积更大，这与较低的ALC相关。多变量Cox分析显示，放疗前或放疗后3级或更高等级的淋巴细胞减少、门静脉肿瘤血栓、较大的计划靶体积、Child-Pugh（CP）B级以及放疗后CP评分增加与较高的死亡风险相关，而使用质子治疗与较低风险相关。
3级或更高等级的淋巴细胞减少可能与接受放疗的HCC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，这可能是由于造血部位的剂量暴露减少。
