Radiation-Associated Lymphopenia and Outcomes of Patients with Unresectable Hepatocellular Carcinoma Treated with Radiotherapy

被引:25
|
作者
De, Brian [1 ]
Ng, Sweet Ping [1 ,2 ]
Liu, Amy Y. [1 ]
Avila, Santiago [1 ]
Tao, Randa [3 ]
Holliday, Emma B. [1 ]
Brownlee, Zachary [4 ]
Kaseb, Ahmed [5 ]
Lee, Sunyoung [3 ]
Raghav, Kanwal [5 ]
Vauthey, Jean-Nicolas [6 ]
Minsky, Bruce D. [1 ]
Herman, Joseph M. [1 ]
Das, Prajnan [1 ]
Smith, Grace L. [1 ]
Taniguchi, Cullen M. [1 ]
Krishnan, Sunil [7 ]
Crane, Christopher H. [8 ]
Grassberger, Clemens [9 ]
Hong, Theodore S. [9 ]
Lin, Steven H. [1 ]
Koong, Albert C. [1 ]
Mohan, Radhe [1 ]
Koay, Eugene J. [1 ]
机构
[1] Univ Texas MD Anderson Canc Ctr, Dept Radiat Oncol, Houston, TX USA
[2] Dept Radiat Oncol, Austin Hlth, Melbourne, Vic, Australia
[3] Univ Utah, Dept Radiat Oncol, Huntsman Canc Inst, Salt Lake City, UT USA
[4] Tufts Med Ctr, Dept Radiat Oncol, Boston, MA USA
[5] Univ Texas MD Anderson Canc Ctr, Dept Gastrointestinal Med Oncol, Houston, TX USA
[6] Univ Texas MD Anderson Canc Ctr, Dept Surg Oncol, Houston, TX USA
[7] Mayo Clin Jacksonville, Dept Radiat Oncol, Jacksonville, FL USA
[8] Mem Sloan Kettering Canc Ctr, Dept Radiat Oncol, New York, NY 10021 USA
[9] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA
基金
美国国家卫生研究院;
关键词
lymphocyte count; circulating lymphocytes; splenic dose; liver dose; overall survival; PROTON-BEAM THERAPY; SURVIVAL; CANCER; CHEMORADIOTHERAPY; PROGNOSIS;
D O I
10.2147/JHC.S282062
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Background: 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 and Methods: 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. Results: 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/mu L, 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. Conclusion: 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.
引用
收藏
页码:57 / 69
页数:13
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