Proton therapy reduces the likelihood of high-grade radiation-induced lymphopenia in glioblastoma patients: phase II randomized study of protons vs photons

Radhe Mohan*, Amy Y. Liu, Paul D. Brown, Anita Mahajan, Jeffrey Dinh, Caroline Chung, Sarah Mcavoy, Mary Frances Mcaleer, Steven H. Lin, Jing Li, Amol J. Ghia, Cong Zhu, Erik P. Sulman, John F. De Groot, Amy B. Heimberger, Susan L. Mcgovern, Clemens Grassberger, Helen Shih, Susannah Ellsworth, David R. Grosshans

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Background: We investigated differences in radiation-induced grade 3+ lymphopenia (G3+L), defined as an absolute lymphocyte count (ALC) nadir of <500 cells/μL, after proton therapy (PT) or X-ray (photon) therapy (XRT) for patients with glioblastoma (GBM). Methods: Patients enrolled in a randomized phase II trial received PT (n = 28) or XRT (n = 56) concomitantly with temozolomide. ALC was measured before, weekly during, and within 1 month after radiotherapy. Whole-brain mean dose (WBMD) and brain dose-volume indices were extracted from planned dose distributions. Univariate and multivariate logistic regression analyses were used to identify independent predictive variables. The resulting model was evaluated using receiver operating characteristic (ROC) curve analysis. Results: Rates of G3+L were lower in men (7/47 [15%]) versus women (19/37 [51%]) (P < 0.001), and for PT (4/28 [14%]) versus XRT (22/56 [39%]) (P = 0.024). G3+L was significantly associated with baseline ALC, WBMD, and brain volumes receiving 5-40 Gy(relative biological effectiveness [RBE]) or higher (ie, V5 through V40). Stepwise multivariate logistic regression analysis identified being female (odds ratio [OR] 6.2, 95% confidence interval [CI]: 1.95-22.4, P = 0.003), baseline ALC (OR 0.18, 95% CI: 0.05-0.51, P = 0.003), and whole-brain V20 (OR 1.07, 95% CI: 1.03-1.13, P = 0.002) as the strongest predictors. ROC analysis yielded an area under the curve of 0.86 (95% CI: 0.79-0.94) for the final G3+L prediction model. Conclusions: Sex, baseline ALC, and whole-brain V20 were the strongest predictors of G3+L for patients with GBM treated with radiation and temozolomide. PT reduced brain volumes receiving low and intermediate doses and, consequently, reduced G3+L.

Original languageEnglish (US)
Pages (from-to)284-294
Number of pages11
JournalNeuro-oncology
Volume23
Issue number2
DOIs
StatePublished - Feb 1 2021
Externally publishedYes

Keywords

  • GBM
  • glioblastoma
  • lymphopenia
  • proton therapy

ASJC Scopus subject areas

  • Oncology
  • Clinical Neurology
  • Cancer Research

Fingerprint

Dive into the research topics of 'Proton therapy reduces the likelihood of high-grade radiation-induced lymphopenia in glioblastoma patients: phase II randomized study of protons vs photons'. Together they form a unique fingerprint.

Cite this