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

Journal: Neuro-oncology 2021;23(2):284-294

PMID: 32750703

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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.

Address: Department of Radiation Physics, The University of Texas MD Anderson Cancer Center, Houston, Texas.; Department of Radiation Oncology, Mayo Clinic Hospital, Rochester, Minnesota.; Millennium Physicians Radiation Oncology, The Woodlands, Texas.; Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.; Department of Radiation Oncology, University of Maryland, Baltimore, Maryland.; Department of Radiation Physics, The University of Texas MD Anderson Cancer Center, Houston, Texas.; Department of Epidemiology, Human Genetics and Environmental Sciences, School of Public Health, The University of Texas Health Science Center, Houston, Texas.; Department of Radiation Oncology, NYU Grossman School of Medicine, New York, New York.; Department of Neuro-Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.; Department of Neurosurgery, The University of Texas MD Anderson Cancer Center, Houston, Texas.; Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts.; Department of Radiation Oncology, Indiana University School of Medicine, Indianapolis, Indiana.

DOI: 10.1093/neuonc/noaa182

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MeSH Terms: Female, Glioblastoma, Humans, Lymphopenia, Male, Photons, Proton Therapy, Protons, Radiotherapy Dosage