Imaging Changes in Pediatric Intracranial Ependymoma Patients Treated With Proton Beam Radiation Therapy Compared to Intensity Modulated Radiation Therapy

Gunther, Jillian R.; Sato, Mariko; Chintagumpala, Murali; Ketonen, Leena; Jones, Jeremy; Allen, Pamela K.; Paulino, Arnold C.; Okcu, M. Fatih; Su, Jack; Weinberg, Jeffrey S.; Boehling, Nicholas S.; Khatua, Soumen; Adesina, Adekunle M.; Dauser, Robert C.; Whitehead, William E.; Mahajan, Anita

doi:10.1016/j.ijrobp.2015.05.018

Cited by 119 publications

(76 citation statements)

References 17 publications

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“…Our group recently identified that, in comparison to patients treated with photon therapy, children with ependymoma treated with protons more often developed changes in normal brain parenchyma on MR images after treatment [22]. Although image changes do not always indicate permanent adverse neurological defects [22–25], they are still considered a grade 1 response according to the Common Terminology Criteria for Adverse Events (CTCAE) v4.0 [26] grading scale and may be a harbinger of more severe reactions [27,28].…”

Section: Introductionmentioning

confidence: 99%

“…Although image changes do not always indicate permanent adverse neurological defects [22–25], they are still considered a grade 1 response according to the Common Terminology Criteria for Adverse Events (CTCAE) v4.0 [26] grading scale and may be a harbinger of more severe reactions [27,28]. Imaging changes such as these are thought to reflect early tissue damage [25] and thus are important for studying the biological properties of protons as a function of dose and LET.…”

Section: Introductionmentioning

confidence: 99%

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Clinical evidence of variable proton biological effectiveness in pediatric patients treated for ependymoma

Peeler

Mirković

Titt

et al. 2016

Radiotherapy and Oncology

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Background and Purpose A constant relative biological effectiveness (RBE) is used for clinical proton therapy; however, experimental evidence indicates that RBE can vary. We analyzed pediatric ependymoma patients who received proton therapy to determine if areas of normal tissue damage indicated by post-treatment image changes were associated with increased biological dose effectiveness. Material and Methods Fourteen of 34 children showed T2-FLAIR hyperintensity on post-treatment magnetic resonance (MR) images. We delineated regions of treatment-related change and calculated dose and linear energy transfer (LET) distributions with Monte Carlo. Voxel-level image change data were fit to a generalized linear model incorporating dose and LET. Cross-validation was used to determine model parameters and for receiver operating characteristic curve analysis. Tolerance dose (TD50; dose at which 50% of patients would experience toxicity) was interpolated from the model. Results Image changes showed dependence on increasing LET and dose. TD50 decreased with increasing LET, indicating an increase in biological dose effectiveness. The cross-validated area under the curve for the model was 0.91 (95% confidence interval 0.88–0.94). Conclusions Our correlation of changes on MR images after proton therapy with increased LET constitutes the first clinical evidence of variable proton biological effectiveness.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Clinical evidence of variable proton biological effectiveness in pediatric patients treated for ependymoma

Peeler

Mirković

Titt

et al. 2016

Radiotherapy and Oncology

Self Cite

225

230

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“…In a recent retrospective study, an increased rate of neuroimaging changes was found in 37 ependymoma patients treated with proton beam RT when compared to 35 ependymoma patients treated with photon RT; both cohorts of patients had localized diseased only and treated with focal radiotherapy. Three patients in the proton beam cohort had persistent neurological deficits and 1 patient died of radiation necrosis, compared with no patients with persistent neurological deficits or death in the photon radiotherapy cohort 32 . Determination of the risks and benefits of proton compared with photon adjuvant radiotherapy for localized ependymoma requires further study.…”

Section: Prognosis and Treatmentmentioning

confidence: 90%

Investigating therapies in ependymoma

Theeler

Gilbert

2016

Expert Opinion on Orphan Drugs

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Introduction: Ependymomas are a heterogeneous group of primary central nervous system neoplasms with varied clinical characteristics, pathologic appearances, survival outcomes, cytogenetic, gene expression, and epigenetic profiles. The variable outcomes with adjuvant radiotherapy and the meager success of cytotoxic chemotherapies point to a need to develop personalized, targeted therapies. Areas Covered: This review provides an overview of clinical, pathologic, radiographic, prognostic, and treatment characteristics of ependymomas, summarizes recent discoveries in gene expression profiling, and future directions for the development of targeted and immunologic therapeutic strategies. Expert Opinion: Translating the quickly accumulating molecular data into an improved system of grading, classification, prognostication, and therapeutic development will be necessary to improve patient outcomes.

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“…Table 1 provides a summary of these papers. The rest of the articles reported multivariate analysis (using Cox model) applied to survival (or outcome) evaluation in pediatric brain tumors [16][17][18][19][20][21][22][23][24][25][26][27][28][29], which are summarized in Table 2.…”

Section: Resultsmentioning

confidence: 99%

Multivariate Analysis in Pediatric Brain Tumor

Zhang

2017

IJRRT

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Imaging Changes in Pediatric Intracranial Ependymoma Patients Treated With Proton Beam Radiation Therapy Compared to Intensity Modulated Radiation Therapy

Cited by 119 publications

References 17 publications

Clinical evidence of variable proton biological effectiveness in pediatric patients treated for ependymoma

Clinical evidence of variable proton biological effectiveness in pediatric patients treated for ependymoma

Investigating therapies in ependymoma

Multivariate Analysis in Pediatric Brain Tumor

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