Central Nervous System

PD 03 - CNS 1 - Poster Discussion - Toxicity and Quality of Life

1025 - One-Week Chemoradiotherapy is Associated With Less Treatment-Related Lymphopenia Compared to a Standard?Treatment?Course for Newly Diagnosed Glioblastoma

Sunday, October 21
5:27 PM - 5:33 PM
Location: Room 217 A/B

One-Week Chemoradiotherapy is Associated With Less Treatment-Related Lymphopenia Compared to a Standard Treatment Course for Newly Diagnosed Glioblastoma
D. K. Fujimoto1, K. Sborov1, R. Von Eyben1, E. C. Osmundson2, R. Thomas3, S. Nagpal3, and S. G. Soltys1; 1Department of Radiation Oncology, Stanford Cancer Institute, Stanford, CA, 2Department of Radiation Oncology, Vanderbilt University School of Medicine, Nashville, TN, 3Department of Neurology, Stanford Cancer Institute, Stanford, CA

Purpose/Objective(s): Treatment-related lymphopenia is associated with worse overall survival (OS) in patients with newly diagnosed glioblastoma (GBM), possibly due to immunosuppression (Grossman et al. 2011). We hypothesized that patients with GBM treated with a shorter 1-week chemoradiation (chemoRT) course had less lymphopenia compared to a conventional longer course of chemoRT.

Materials/Methods: With IRB approval, we retrospectively identified 79 patients with GBM treated with 4-6 weeks of conventional radiation therapy (RT), 40-66 Gy in 15-33 fractions to the target with a 2-3 cm margin, with concurrent/adjuvant temozolomide (TMZ) and compared them to 30 patients treated on an institutional, prospective, dose escalation trial of 1-week hypofractionated stereotactic radiosurgery (SRS), 25-40 Gy in 5 fractions to the target with a 0.5 cm margin, with concurrent/adjuvant TMZ. We collected the total lymphocyte (TLC), neutrophil, monocyte, hematocrit, and platelet counts before, during, and after chemoRT. Patients were excluded from analysis if treated with less than 40 Gy in the RT cohort or without concurrent TMZ. The relationship between treatment and TLC values over time was analyzed in a generalized estimation equation model to account for the within patient correlation. Time to lymphopenia was summarized using cumulative incidence curves with death as a competing risk, compared using Gray’s test. Time to OS was summarized using Kaplan-Meier curves, compared with log-rank tests.

Results: With a median follow-up of 11.1 months for SRS and 14.1 months for RT patients, a total of 19,306 blood values were analyzed. With no difference at the pre-treatment baseline (p=0.09), the TLC trend lines over time were significantly higher for SRS compared to RT (p<0.0001). The cumulative risk of CTCAE grade 2-4 lymphopenia (<0.8/cm3) was 0% vs 21% at 30 days, 4% vs 43% at 60 days, and 9% vs 56% at 90 days for SRS vs RT patients, respectively (p=0.0015). Table 1 lists the median TLC for each group. No significant difference in OS was seen between SRS vs RT, lymphopenia grade level, or when considering both factors together. OS was 16 months for both G0-1 and G2-4 lymphopenia for both SRS and RT groups (p=0.52). Table 1: TLC Medians
Time from RT start (days) SRS (count per cm3) Conventional RT (count per cm3) p value
Baseline 1.3 1.2 0.09
30 1.4 1.1 <0.0001
60 1.5 1.0 <0.0001
90 1.5 0.9 <0.0001
120 1.5 0.9 <0.0001
180 1.5 0.8 <0.0001

Conclusion: SRS in 1 week is associated with less severe treatment-induced lymphopenia than 4-6 weeks conventional RT for GBM. Further data are needed to determine which variable (e.g., 1 week of RT, 1 week of concurrent TMZ or smaller target volumes) of this protocol is most associated with immune-cell sparing. Shortened treatment courses such as this 1-week prospective trial may be less immunosuppressive than traditional treatment and a better radiation therapy paradigm to combine with immunotherapy.

Author Disclosure: D.K. Fujimoto: Independent Contractor; MYnd Analytics. K. Sborov: None. R. Von Eyben: None. E.C. Osmundson: None. S.G. Soltys: Consultant; Inovio Pharmaceuticals, Inc.

Dylann Fujimoto, BS

Disclosure:
Employment
MYnd Analytics: Research Coordinator: Independent Contractor; Stanford University: Assistant Clinical Research Coordinator: Employee

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