Effect of Radiation Treatment Volume Reduction on Lymphopenia in Patients Receiving Chemoradiotherapy for Glioblastoma

Abstract

Purpose: To evaluate whether reduction in glioblastoma radiation treatment volume can reduce risk of acute severe lymphopenia (ASL).

Methods and materials: A total of 210 patients with supratentorial/nonmetastatic glioblastoma were treated with radiation therapy (RT) plus temozolomide from 2007 to 2016 and had laboratory data on total lymphocyte counts. Before 2015, 164 patients were treated with standard-field RT (SFRT), and limited-field RT (LFRT) was implemented thereafter for 46 patients to reduce treatment volume. Total lymphocyte counts were evaluated at baseline, during RT, and at approximately week 12 from initiating RT. Acute severe lymphopenia was defined as any total lymphocyte count < 500 cells/μL within 3 months (by week 12) of initiating RT. Multivariate analysis for overall survival (OS) was performed with Cox regression and with logistic regression for ASL. Propensity score matching was performed to adjust for variability between cohorts. Acute severe lymphopenia, progression-free survival (PFS), and OS were compared using the Kaplan-Meier method.

Results: Limited-field RT patients had higher gross tumor volume than SFRT patients yet lower brain dose-volume parameters, including volume receiving 25 Gy (V25 Gy: 41% vs 53%, respectively, P < .01). Total lymphocyte count at week 12 was significantly higher for LFRT than for SFRT (median: 1100 cells/μL vs 900 cells/μL, respectively, P = .02). On multivariate analysis, ASL was an independent predictor of OS, and brain V25 Gy was an independent predictor of ASL. The ASL rate at 3 months was 15.5% for LFRT and 33.8% for SFRT (P = .12). In a propensity-matched comparison of 45 pairs of LFRT and SFRT patients, PFS (median: 5.9 vs 6.2 months, respectively, P = .58) and OS (median: 16.2 vs 13.9 months, respectively, P = .69) were not significantly different.

Conclusions: Limited-field RT is associated with less lymphopenia after RT plus temozolomide and does not adversely affect PFS or OS. Brain V25 Gy is confirmed as an important dosimetric predictor for ASL.

Fig. 1.

(A) Box and whisker plot illustrating median and quartile distribution of total lymphocyte counts for standard-field radiation therapy (SFRT) and limited-field radiation therapy (LFRT) patients at baseline, week 2, week 6, and week 12. (B) Box and whisker plot illustrating median and quartile distribution of brain V25 Gy (brain volume receiving 25 Gy) for standard-field radiation therapy and limited-field radiation therapy patients.

Fig. 2.

(A) Acute severe lymphopenia (ASL) rate of glioblastoma (GBM) patients treated with standard-field radiation therapy (SFRT) and limited-field radiation therapy (LFRT). (B) Progression-free survival of GBM patients treated with SFRT and LFRT. (C) Overall survival of GBM patients treated with SFRT and LFRT. (D) Acute severe lymphopenia rate of propensity-matched patients treated with SFRT and LFRT. (E) Progression-free survival of propensity-matched patients treated with SFRT and LFRT. (F) Overall survival of propensity-matched patients treated with SFRT and LFRT.

Fig. 3.

(A) Dose—response plot of brain V25 Gy (brain volume receiving 25 Gy) and 3-month acute severe lymphopenia (ASL) rate. Number above each data point denotes the sample size of that dose range. Linear regression equation estimates the risk of ASL for any given brain V25 Gy. (B) ASL rate stratified by V25 Gy greater than or less than 40%. Abbreviation: RT = radiation therapy.