Chemoradiation-Induced Lymphopenia in Glioblastoma Patients and the Influence of Total Radiation Exposure Time

Abstract

There is a clear relationship between the adaptive immune response and solid tumor control. However, many of our effective cancer therapies are delivered at the cost of treatment-induced lymphopenia. It has been shown that patients with glioblastoma (GBM) treated with standard post-operative chemoradiation develop a significant, lasting treatment-induced lymphopenia. Others have shown in this patient population that severe CD4-postive T-cell depletion (<200cells/mm3) significantly reduces overall survival. We hypothesized that dosimetric and treatment planning parameters, including the cumulative time a patient is exposed to radiation (beam-on-time, BoT) and total monitor units (MU) delivered, increase lymphocyte toxicity and degree of lymphopenia. Here, we report a single institutional retrospective analysis of 128 patients with pathologically-proven WHO grade IV GBM treated with surgical resection followed by the standard 6000cGy of IMRT in 30 fractions with concurrent and adjuvant temozolomide from 2007-2016. In our cohort, the mean pre-treatment absolute lymphocyte count (ALC) was 1,528 cells/uL. Over the 6-week course of radiation therapy, patient’s ALC dropped by 47% (mean 811 cells/uL) immediately after completion of treatment and remained reduced by 38% (mean 950 cells/uL) and 36% (mean 980 cells/uL) 1- and 2-months post treatment, respectively. Furthermore 20.3% (26/128) developed severe lymphopenia (ALC < 500 cells/uL) immediately after treatment. The mean BoT was 42.3 minutes (13.6 – 116.1 minutes) and mean MU delivered per patient was 15787 MU (7904 – 39805 MU). Both BoT and MU did not correlate with post-treatment ALC or absolute reduction in ALC at the end of treatment (R2 < 0.01). The general neuroanatomic location of each tumor was included in the analysis and was also found not influence the degree of lymphopenia (p > 0.1), while pre-treatment ALC was indeed correlated with post-treatment ALC (p<0.001). These data suggest that the complexity of an IMRT plan that may increase a patient’s BoT and/or total MU delivered does not increase a patient’s risk of treatment-induced lymphopenia. Instead, our data confirmed that a low pre-treatment ALC is a risk factor for more severe post-treatment lymphopenia.