Trial reportNeuro-oncology2021
Proton therapy reduces the likelihood of high-grade radiation-induced lymphopenia in glioblastoma patients: phase II randomized study of protons vs photons.
Trial report in Neuro-oncology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 85 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
85 citing papers in PubMed, 1 synthesis or guideline pooled it, 141 citations in OpenAlex.
- Prognostic Value and Risk Factors of Treatment-Related Lymphopenia in Malignant Glioma Patients Treated With Chemoradiotherapy: A Systematic Review and Meta-Analysis.Frontiers in neurology · 2021Pooled it
- Personalized machine learning-guided radiation dose escalation in newly diagnosed glioblastoma: prospective pilot study.Nature communications · 2026Trial
- Unlocking the therapeutic potential of immuno-radiotherapy: insights from preclinical and clinical research.Oncoimmunology · 2026Review
- Brain dose burden is associated with treatment-related lymphopenia in IDH-wildtype glioblastoma: dosimetric determinants and prognostic impact.Journal of neuro-oncology · 2026Article
- Challenges and opportunities in combining radiotherapy and immunotherapy for localized pancreatic cancer.Nature reviews. Gastroenterology & hepatology · 2026Review
- Impact of Proton versus Photon (Chemo)radiation on Circulating Immune Cells in Head and Neck Cancer.Cancer research communications · 2026Article
- Impact of dynamic beam delivery of intensity-modulated radiation therapy and volumetric modulated arc therapy on circulating immune cell exposure in glioma.Physics and imaging in radiation oncology · 2026Article
- Immune-sparing radiotherapy in solid tumors: radiation-induced lymphopenia, circulating immune-cell dose, and biomarker-guided optimization of radioimmunotherapy.Journal of cancer research and clinical oncology · 2026Review
- No Evidence for Depletion of Circulating Lymphocyte Populations in Primary Brain Tumor Patients Receiving Radiation Therapy Alone.International journal of radiation oncology, biology, physics · 2026Article
- Radiotherapy and Immune System Interactions Historical Perspectives and Clinical Advancements.Molecular carcinogenesis · 2026Review
- The global landscape of particle beam radiotherapy trials over the past 15 years.Cancer pathogenesis and therapy · 2026Article
- Clinical, molecular, and immunologic determinants of survival in WHO-defined IDH-wildtype glioblastoma treated with radiotherapy: a large real-world cohort study.Journal of neuro-oncology · 2026Article
- Review
- Clinical Considerations of Splenic Dose Constraints to Mitigate Radiation-Induced Lymphopenia.Cancer medicine · 2026Article
- Radiation-induced lymphopenia: A data compilation to unveil relevant factors and mitigation strategies.Clinical and translational radiation oncology · 2026Review
- Glioblastoma in adults: A Society for Neuro-Oncology (SNO) and European Society of Neuro-Oncology (EANO) consensus review on current management and future directions.Neuro-oncology · 2025Review
- Real-world survival and prognostic factors in WHO 2021 classified gliomas treated with chemo-radiotherapy.Scientific reports · 2025Article
- Assessment of prognostic value and development of predictive model for prolonged lymphopenia in patients with glioblastoma following chemoradiotherapy.Journal of radiation research · 2025Article
- Radiotherapy in Glioblastoma Multiforme: Evolution, Limitations, and Molecularly Guided Future.Biomedicines · 2025Review
- Comparative Outcomes of Standard Radiation Therapy and 5-Fraction Adaptive Stereotactic Radiation Therapy in Newly Diagnosed Glioblastoma: A Propensity Score-Matched Analysis.Advances in radiation oncology · 2025Article
25 more citing papers are in PubMed but not listed here.
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Authors and funding
20 authors at 7 institutions in 1 country.
Funding
Abstract
backgroundWe 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).
methodsPatients 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.
resultsRates 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.
conclusionsSex, 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.
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