Article
Proton radiation therapy is associated with decreased incidence of radiation-induced necrosis in IDH-mutant gliomas
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Authors
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Franziska Loebel
- Department of Neurosurgery, Harvard Medical School, Boston, MA, USA; Massacusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA, USA
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Brent S. Rose
- Department of Radiation Oncology, Harvard Medical School, Boston, MA, USA; Massacusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA, USA
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Nina Lelic
- Department of Neurosurgery, Harvard Medical School, Boston, MA, USA; Massacusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA, USA
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Andrew S. Chi
- Department of Neurology, Harvard Medical School, Boston, MA, USA; Massacusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA, USA
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Helen A. Shih
- Department of Radiation Oncology, Harvard Medical School, Boston, MA, USA; Massacusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA, USA
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Daniel P. Cahill
- Department of Neurosurgery, Harvard Medical School, Boston, MA, USA; Massacusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA, USA
| Published: | May 13, 2014 |
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Outline
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Objective: Recurrent mutations in IDH1/2 have been found in a subset of human gliomas, characterized by a younger age and favorable prognosis. We previously demonstrated that receipt of radiation therapy is associated with an improved progression-free survival (PFS) in these patients. Since IDH-mutants are often long-term survivors, late-toxicity effects are an important consideration. In contrast to conventional photon therapy, proton beam radiation has been shown to effectively target tumor while reducing the dose to surrounding healthy tissues, potentially minimizing late-toxicity. We hypothesized that proton therapy would be associated with a lower rate of radiation-induced necrosis in IDH-mutants.
Method: We retrospectively examined a cohort of 172 IDH-mutant glioma patients (grade II/III/IV: 74/75/23), of which 131 had been treated in the adjuvant setting with either proton (n=34, median dose: 54Gy) or conventional photon radiotherapy (n=97, median dose: 59Gy). A total of 65 patients underwent re-resection for recurrence; presence or absence of radiation necrosis was determined by histopathological review. Time-to-progression (TTP) was calculated from date of initial surgery and date of re-resection.
Results: The overall PFS of the cohort was 5.42yrs; 6.22yrs in patients receiving adjuvant radiotherapy vs. 4.22yrs for patients without radiation (p=0.0124). Baseline clinical factors (age, histological grade), TTP and the frequency of re-resection did not differ between radiation subgroups. Proton-receiving patients underwent 16 (47%) re-resections at a median TTP 48.3 months vs. 49 re-resections (51%) at a median TTP 52.23 months in photon-receivers. Radiation necrosis was identified in 16 cases (24.62%), only one of which had received proton-therapy. Statistical analysis revealed a significant association between presence of radiation necrosis and treatment with conventional photon-therapy (p=0.03, log-rank).
Conclusions: Radiation therapy is an effective treatment option for IDH-mutant gliomas. While upfront radiation offers progression-free survival benefits in this distinct subgroup, concerns about late-toxicity effects have been raised. Our results show that proton-therapy is associated with a significantly lower presence of radiation necrosis on re-resection compared to conventional photon therapy. While other factors might account for differences seen, this exploratory data suggests that proton therapy might be employed to minimize late-toxicity for IDH-mutant glioma patients.
