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

Abstract

Acute severe lymphopenia (ASL) occurs frequently in glioblastoma (GBM) patients receiving radiation therapy and concurrent temozolomide (CRT). Previous studies have demonstrated correlation between ASL and overall survival (OS) in GBM patients as well as between ASL and the brain dose-volume histogram (DVH). Our study aims to evaluate whether reduction in radiation treatment volume in GBM patients influences total lymphocyte counts (TLCs) within the first 3 months of radiation therapy (RT). A total of 230 patients with supratentorial/nonmetastatic GBM were treated with standard-fractionated CRT from January 2007 to December 2016 and had laboratory data to evaluate TLC. Before January 2015, patients were treated with standard-field RT. After January 2015, strategies to minimize treatment volumes were implemented at our institution (limited-field RT): reduction of clinical treatment volume (CTV) margin, elimination of routine inclusion of the entire T2 abnormality, minimizing brain DVH without sacrificing coverage through optimization with intensity-modulated RT. TLCs were retrospectively compared between patients who were treated with standard-field vs. limited-field RT during the first 3 months after beginning RT. The Mann-Whitney U test was used to compare week 6, week 12, and nadir (lowest TLC within 3 months of RT) lymphocyte counts. ASL was defined as TLC of <500 cells/μL within 3 months of starting RT. ASL rate, Progression-free survival (PFS), and OS between two treatment periods were compared using Kaplan-Meier analysis. One-hundred seventy patients were treated with standard-field RT while 60 patients were treated with limited-field RT. Age, surgery type, MGMT methylation status, and IDH mutation status were not significantly different between the two groups. Median TLCs of standard-field and limited-field RT were 1400 cells/μL vs. 1500 cells/μL at baseline before RT, 800 cells/μL vs. 900 cells/μL at week 6 (p = 0.182), 900 cells/μL vs. 1100 cells/μL at week 12 (p = 0.049), and 650 cells/μL vs. 800 cells/μL at nadir (p = 0.043), respectively. Rates of ASL were 30.6% for standard-field and 18.2% for limited field (p = 0.103). After a median follow-up of 11 months, median PFS was 8 versus 6 months (p = 0.95) and median OS was 14 versus 15 months (p = 0.28) between the standard-field and limited-field RT groups. Limited-field RT appears to be associated with reduced TLC at week 12 and at nadir for GBM patients receiving CRT. Reduction of treatment volume does not appear to adversely affect PFS and OS. With increasing development of immunotherapy for GBM, limited-field RT may warrant further investigation prospectively.