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

2021-03-03

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

circulating lymphocytes

liver dose

lymphocyte count

overall survival

splenic dose

Journal Article

0000-0003-3468-3359

0000-0003-3633-4304

0000-0001-7675-3461

10.2147/JHC.S282062

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.

link

Journal of Hepatocellular Carcinoma 2021; 8: 57-69

Journal of Hepatocellular Carcinoma

2253-5969