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Re-irradiation for malignant glioma: Toward patient selection and defining treatment parameters for salvage

PURPOSE: Reirradiation for recurrent glioma remains controversial without knowledge of optimal patient selection, dose, fractionation, and normal tissue tolerances. We retrospectively evaluated outcomes and toxicity after conventionally fractionated reirradiation for recurrent high-grade glioma, alo...

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Autores principales: Shen, Colette J., Kummerlowe, Megan N., Redmond, Kristin J., Martinez-Gutierrez, Juan Carlos, Usama, Syed Muhammad, Holdhoff, Matthias, Grossman, Stuart A., Laterra, John J., Strowd, Roy E., Kleinberg, Lawrence R.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6200913/
https://www.ncbi.nlm.nih.gov/pubmed/30370358
http://dx.doi.org/10.1016/j.adro.2018.06.005
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author Shen, Colette J.
Kummerlowe, Megan N.
Redmond, Kristin J.
Martinez-Gutierrez, Juan Carlos
Usama, Syed Muhammad
Holdhoff, Matthias
Grossman, Stuart A.
Laterra, John J.
Strowd, Roy E.
Kleinberg, Lawrence R.
author_facet Shen, Colette J.
Kummerlowe, Megan N.
Redmond, Kristin J.
Martinez-Gutierrez, Juan Carlos
Usama, Syed Muhammad
Holdhoff, Matthias
Grossman, Stuart A.
Laterra, John J.
Strowd, Roy E.
Kleinberg, Lawrence R.
author_sort Shen, Colette J.
collection PubMed
description PURPOSE: Reirradiation for recurrent glioma remains controversial without knowledge of optimal patient selection, dose, fractionation, and normal tissue tolerances. We retrospectively evaluated outcomes and toxicity after conventionally fractionated reirradiation for recurrent high-grade glioma, along with the impact of concurrent chemotherapy. METHODS AND MATERIALS: We conducted a retrospective review of patients reirradiated for high-grade glioma recurrence between 2007 and 2016 (including patients with initial low-grade glioma). Outcome metrics included overall survival (OS), prognostic factors for survival, and treatment-related toxicity. RESULTS: Patients (n = 118; median age 47 years; median Karnofsky performance status score: 80) were re-treated at a median of 28 months (range, 5-214 months) after initial radiation therapy. The median reirradiation dose was 41.4 Gy (range, 12.6-54.0 Gy) to a median lesion volume of 202 cm(3) (range, 20-901 cm(3)). The median cumulative (initial radiation and reirradiation combined) potential maximum brainstem dose was 76.9 Gy (range, 5.0-108.3 Gy) and optic apparatus dose was 56.0 Gy (range, 4.5-90.9 Gy). Of the patients, 56% received concurrent temozolomide, 14%, bevacizumab, and 11%, temozolomide plus bevacizumab; 19% had no chemotherapy. The planned reirradiation was completed by 90% of patients. Median OS from the completion of reirradiation was 9.6 months (95% confidence interval [CI], 7.5-11.7 months) for all patients and 14.0, 11.5, and 6.7 months for patients with initial grade 2, 3, and 4 glioma, respectively. On multivariate analysis, better OS was observed with a >24-month interval between radiation treatments (hazard ratio [HR]: 0.3; 95% CI, 0.2-0.5; P < .001), reirradiation dose >41.4 Gy (HR: 0.6; 95% CI, 0.4-0.9; P = .03), and gross total resection before reirradiation (HR: 0.6, 95% CI, 0.3-0.9; P = .02). Radiation necrosis and grade ≥3 late neurotoxicity were both minimal (<5%). No symptomatic persistent brainstem or optic nerve/chiasm injury was identified. CONCLUSIONS: Salvage reirradiation, even at doses >41.4 Gy in conventional fractionation, along with chemotherapy, was safe and well tolerated with meaningful survival duration. These data provide information that may be useful in implementing safe reirradiation treatments for appropriately selected patients and guiding future studies to define optimal reirradiation doses, maximal safe doses to critical structures, and the role of systemic therapy.
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spelling pubmed-62009132018-10-26 Re-irradiation for malignant glioma: Toward patient selection and defining treatment parameters for salvage Shen, Colette J. Kummerlowe, Megan N. Redmond, Kristin J. Martinez-Gutierrez, Juan Carlos Usama, Syed Muhammad Holdhoff, Matthias Grossman, Stuart A. Laterra, John J. Strowd, Roy E. Kleinberg, Lawrence R. Adv Radiat Oncol Central Nervous System PURPOSE: Reirradiation for recurrent glioma remains controversial without knowledge of optimal patient selection, dose, fractionation, and normal tissue tolerances. We retrospectively evaluated outcomes and toxicity after conventionally fractionated reirradiation for recurrent high-grade glioma, along with the impact of concurrent chemotherapy. METHODS AND MATERIALS: We conducted a retrospective review of patients reirradiated for high-grade glioma recurrence between 2007 and 2016 (including patients with initial low-grade glioma). Outcome metrics included overall survival (OS), prognostic factors for survival, and treatment-related toxicity. RESULTS: Patients (n = 118; median age 47 years; median Karnofsky performance status score: 80) were re-treated at a median of 28 months (range, 5-214 months) after initial radiation therapy. The median reirradiation dose was 41.4 Gy (range, 12.6-54.0 Gy) to a median lesion volume of 202 cm(3) (range, 20-901 cm(3)). The median cumulative (initial radiation and reirradiation combined) potential maximum brainstem dose was 76.9 Gy (range, 5.0-108.3 Gy) and optic apparatus dose was 56.0 Gy (range, 4.5-90.9 Gy). Of the patients, 56% received concurrent temozolomide, 14%, bevacizumab, and 11%, temozolomide plus bevacizumab; 19% had no chemotherapy. The planned reirradiation was completed by 90% of patients. Median OS from the completion of reirradiation was 9.6 months (95% confidence interval [CI], 7.5-11.7 months) for all patients and 14.0, 11.5, and 6.7 months for patients with initial grade 2, 3, and 4 glioma, respectively. On multivariate analysis, better OS was observed with a >24-month interval between radiation treatments (hazard ratio [HR]: 0.3; 95% CI, 0.2-0.5; P < .001), reirradiation dose >41.4 Gy (HR: 0.6; 95% CI, 0.4-0.9; P = .03), and gross total resection before reirradiation (HR: 0.6, 95% CI, 0.3-0.9; P = .02). Radiation necrosis and grade ≥3 late neurotoxicity were both minimal (<5%). No symptomatic persistent brainstem or optic nerve/chiasm injury was identified. CONCLUSIONS: Salvage reirradiation, even at doses >41.4 Gy in conventional fractionation, along with chemotherapy, was safe and well tolerated with meaningful survival duration. These data provide information that may be useful in implementing safe reirradiation treatments for appropriately selected patients and guiding future studies to define optimal reirradiation doses, maximal safe doses to critical structures, and the role of systemic therapy. Elsevier 2018-07-10 /pmc/articles/PMC6200913/ /pubmed/30370358 http://dx.doi.org/10.1016/j.adro.2018.06.005 Text en © 2018 The Authors on behalf of the American Society for Radiation Oncology http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Central Nervous System
Shen, Colette J.
Kummerlowe, Megan N.
Redmond, Kristin J.
Martinez-Gutierrez, Juan Carlos
Usama, Syed Muhammad
Holdhoff, Matthias
Grossman, Stuart A.
Laterra, John J.
Strowd, Roy E.
Kleinberg, Lawrence R.
Re-irradiation for malignant glioma: Toward patient selection and defining treatment parameters for salvage
title Re-irradiation for malignant glioma: Toward patient selection and defining treatment parameters for salvage
title_full Re-irradiation for malignant glioma: Toward patient selection and defining treatment parameters for salvage
title_fullStr Re-irradiation for malignant glioma: Toward patient selection and defining treatment parameters for salvage
title_full_unstemmed Re-irradiation for malignant glioma: Toward patient selection and defining treatment parameters for salvage
title_short Re-irradiation for malignant glioma: Toward patient selection and defining treatment parameters for salvage
title_sort re-irradiation for malignant glioma: toward patient selection and defining treatment parameters for salvage
topic Central Nervous System
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6200913/
https://www.ncbi.nlm.nih.gov/pubmed/30370358
http://dx.doi.org/10.1016/j.adro.2018.06.005
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