Dataset Information

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

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.

SUBMITTER: Mohan R

PROVIDER: S-EPMC7906048 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature

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Publications

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

Mohan Radhe R Liu Amy Y AY Brown Paul D PD Mahajan Anita A Dinh Jeffrey J Chung Caroline C McAvoy Sarah S McAleer Mary Frances MF Lin Steven H SH Li Jing J Ghia Amol J AJ Zhu Cong C Sulman Erik P EP de Groot John F JF Heimberger Amy B AB McGovern Susan L SL Grassberger Clemens C Shih Helen H Ellsworth Susannah S Grosshans David R DR

Neuro-oncology 20210201 2

<h4>Background</h4>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).<h4>Methods</h4>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 (W ...[more]

PMID: 32750703

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Project description:PurposeTo assess possible differences in radiation-induced lymphocyte depletion for esophageal cancer patients being treated with the following 3 treatment modalities: intensity-modulated radiation therapy (IMRT), passive scattering proton therapy (PSPT), and intensity-modulated proton therapy (IMPT).Methods and materialsWe used 2 prediction models to estimate lymphocyte depletion based on dose distributions. Model I used a piecewise linear relationship between lymphocyte survival and voxel-by-voxel dose. Model II assumes that lymphocytes deplete exponentially as a function of total delivered dose. The models can be fitted using the weekly absolute lymphocyte counts measurements collected throughout treatment. We randomly selected 45 esophageal cancer patients treated with IMRT, PSPT, or IMPT at our institution (15 per modality) to demonstrate the fitness of the 2 models. A different group of 10 esophageal cancer patients who had received PSPT were included in this study of in silico simulations of multiple modalities. One IMRT and one IMPT plan were created, using our standards of practice for each modality, as competing plans to the existing PSPT plan for each patient. We fitted the models by PSPT plans used in treatment and predicted absolute lymphocyte counts for IMRT and IMPT plans.ResultsModel validation on each modality group of patients showed good agreement between measured and predicted absolute lymphocyte counts nadirs with mean squared errors from 0.003 to 0.023 among the modalities and models. In the simulation study of IMRT and IMPT on the 10 PSPT patients, the average predicted absolute lymphocyte count (ALC) nadirs were 0.27, 0.35, and 0.37 K/μL after IMRT, PSPT, and IMPT treatments using Model I, respectively, and 0.14, 0.22, and 0.33 K/μL using Model II.ConclusionsProton plans carried a lower predicted risk of lymphopenia after the treatment course than did photon plans. Moreover, IMPT plans outperformed PSPT in terms of predicted lymphocyte preservation.

Project description:PurposeTo evaluate whether reduction in glioblastoma radiation treatment volume can reduce risk of acute severe lymphopenia (ASL).Methods and materialsA total of 210 patients with supratentorial/nonmetastatic glioblastoma were treated with radiation therapy (RT) plus temozolomide from 2007 to 2016 and had laboratory data on total lymphocyte counts. Before 2015, 164 patients were treated with standard-field RT (SFRT), and limited-field RT (LFRT) was implemented thereafter for 46 patients to reduce treatment volume. Total lymphocyte counts were evaluated at baseline, during RT, and at approximately week 12 from initiating RT. Acute severe lymphopenia was defined as any total lymphocyte count < 500 cells/μL within 3 months (by week 12) of initiating RT. Multivariate analysis for overall survival (OS) was performed with Cox regression and with logistic regression for ASL. Propensity score matching was performed to adjust for variability between cohorts. Acute severe lymphopenia, progression-free survival (PFS), and OS were compared using the Kaplan-Meier method.ResultsLimited-field RT patients had higher gross tumor volume than SFRT patients yet lower brain dose-volume parameters, including volume receiving 25 Gy (V25 Gy: 41% vs 53%, respectively, P < .01). Total lymphocyte count at week 12 was significantly higher for LFRT than for SFRT (median: 1100 cells/μL vs 900 cells/μL, respectively, P = .02). On multivariate analysis, ASL was an independent predictor of OS, and brain V25 Gy was an independent predictor of ASL. The ASL rate at 3 months was 15.5% for LFRT and 33.8% for SFRT (P = .12). In a propensity-matched comparison of 45 pairs of LFRT and SFRT patients, PFS (median: 5.9 vs 6.2 months, respectively, P = .58) and OS (median: 16.2 vs 13.9 months, respectively, P = .69) were not significantly different.ConclusionsLimited-field RT is associated with less lymphopenia after RT plus temozolomide and does not adversely affect PFS or OS. Brain V25 Gy is confirmed as an important dosimetric predictor for ASL.

Dataset Information

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

Background

Methods

Results

Conclusions

Publications

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

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