Stereotactic radiosurgery for glioblastoma considering tumor genetic profiles: an international multicenter study

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  • 1 Department of Neurosurgery, University of Virginia, Charlottesville, Virginia;
  • | 2 Department of Neurosurgery, NYU Langone Health, New York, New York;
  • | 3 Department of Radiation Oncology, NYU Langone Health, New York, New York;
  • | 4 Department of Neurosurgery, Neurological Institute, Taipei Veteran General Hospital, Taipei, Taiwan;
  • | 5 School of Medicine, National Yang-Ming University, Taipei, Taiwan;
  • | 6 Division of Neurosurgery, Université de Sherbrooke, Centre de recherche du CHUS, Sherbrooke, Quebec, Canada;
  • | 7 Department of Neurosurgery, West Virginia University, Morgantown, West Virginia;
  • | 8 Department of Radiation Oncology, West Virginia University, Morgantown, West Virginia;
  • | 9 Gamma Knife Radiology Department, Dominican Gamma Knife Center and CEDIMAT, Santo Domingo, Dominican Republic;
  • | 10 Department of Neurosurgery, Postgraduate Institute of Medical Education and Research, Chandigarh, India;
  • | 11 Department of Radiotherapy, Postgraduate Institute of Medical Education and Research, Chandigarh, India; and
  • | 12 Gamma Knife Center, Jewish Hospital, Mayfield Clinic, Cincinnati, Ohio
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OBJECTIVE

Molecular profiles, such as isocitrate dehydrogenase (IDH) mutation and O 6-methylguanine-DNA methyltransferase (MGMT) methylation status, have important prognostic roles for glioblastoma patients. The authors studied the efficacy and safety of stereotactic radiosurgery (SRS) for glioblastoma patients with consideration of molecular tumor profiles.

METHODS

For this retrospective observational multiinstitutional study, the authors pooled consecutive patients who were treated using SRS for glioblastoma at eight institutions participating in the International Radiosurgery Research Foundation. They evaluated predictors of overall and progression-free survival with consideration of IDH mutation and MGMT methylation status.

RESULTS

Ninety-six patients (median age 56 years) underwent SRS (median dose 15 Gy and median treatment volume 5.53 cm3) at 147 tumor sites (range 1 to 7). The majority of patients underwent prior fractionated radiation therapy (92%) and temozolomide chemotherapy (98%). Most patients were treated at recurrence (85%), and boost SRS was used for 12% of patients. The majority of patients harbored IDH wild-type (82%) and MGMT-methylated (62%) tumors. Molecular data were unavailable for 33 patients. Median survival durations after SRS were similar between patients harboring IDH wild-type tumors and those with IDH mutant tumors (9.0 months vs 11 months, respectively), as well as between those with MGMT-methylated tumors and those with MGMT-unmethylated tumors (9.8 vs. 9.0 months, respectively). Prescription dose > 15 Gy (OR 0.367, 95% CI 0.190–0.709, p = 0.003) and treatment volume > 5 cm3 (OR 1.036, 95% CI 1.007–1.065, p = 0.014) predicted overall survival after controlling for age and IDH status. Treatment volume > 5 cm3 (OR 2.215, 95% CI 1.159–4.234, p = 0.02) and absence of gross-total resection (OR 0.403, 95% CI 0.208–0.781, p = 0.007) were associated with inferior local control of SRS-treated lesions in multivariate models. Nine patients experienced adverse radiation events after SRS, and 7 patients developed radiation necrosis at 59 to 395 days after SRS.

CONCLUSIONS

Post-SRS survival was similar as a function of IDH mutation and MGMT promoter methylation status, suggesting that molecular profiles of glioblastoma should be considered when selecting candidates for SRS. SRS prescription dose > 15 Gy and treatment volume ≤ 5 cm3 were associated with longer survival, independent of age and IDH status. Prior gross-total resection and smaller treatment volume were associated with superior local control.

ABBREVIATIONS

ARE = adverse radiation event; FRT = fractionated radiotherapy; IDH = isocitrate dehydrogenase; IRRF = International Radiosurgery Research Foundation; MGMT = O6-methylguanine-DNA methyltransferase; OS = overall survival; PFS = progression-free survival; RANO = Response Assessment in Neuro-Oncology; RTOG = Radiation Therapy Oncology Group; SRS = stereotactic radiosurgery.

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