Re-irradiation for recurrent high-grade glioma: an analysis of prognostic factors for survival and predictors of radiation necrosis

Daniel Moore-Palhares; Hanbo Chen; Julia Keith; Michael Wang; Sten Myrehaug; Chia-Lin Tseng; Jay Detsky; James Perry; Mary Jane Lim-Fat; Chris Heyn; Pejman Maralani; Nir Lipsman; Sunit Das; Arjun Sahgal; Hany Soliman

doi:10.1007/s11060-023-04340-4

Re-irradiation for recurrent high-grade glioma: an analysis of prognostic factors for survival and predictors of radiation necrosis

J Neurooncol. 2023 Jul;163(3):541-551. doi: 10.1007/s11060-023-04340-4. Epub 2023 May 31.

Authors

Affiliations

¹ Department of Radiation Oncology, Odette Cancer Centre, Sunnybrook Health Sciences Centre, University of Toronto, 2075 Bayview Ave, Toronto, ON, M4N 3M5, Canada.
² Department of Laboratory Medicine and Molecular Diagnostics, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON, Canada.
³ Division of Neurology, Department of Medicine Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON, Canada.
⁴ Department of Medical Imaging, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON, Canada.
⁵ Division of Neurosurgery, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON, Canada.
⁶ Division of Neurosurgery, St. Michael's Hospital, University of Toronto, Toronto, ON, Canada.
⁷ Department of Radiation Oncology, Odette Cancer Centre, Sunnybrook Health Sciences Centre, University of Toronto, 2075 Bayview Ave, Toronto, ON, M4N 3M5, Canada. hany.soliman@sunnybrook.ca.

PMID: 37256526
DOI: 10.1007/s11060-023-04340-4

Abstract

Purpose: Recurrent high-grade glioma (rHGG) is a heterogeneous population, and the ideal patient selection for re-irradiation (re-RT) has yet to be established. This study aims to identify prognostic factors for rHGG patients treated with re-RT.

Methods: We retrospectively reviewed consecutive adults with rHGG who underwent re-RT from 2009 to 2020 from our institutional database. The primary objective was overall survival (OS). Secondary endpoints included prognostic factors for early death (< 6 months after re-RT) and predictors of radiation necrosis (RN).

Results: For the 79 patients identified, the median OS after re-RT was 9.9 months (95% CI 8.3-11.6). On multivariate analyses, re-resection at progression (HR 0.56, p = 0.027), interval from primary treatment to first progression ≥ 16.3 months (HR 0.61, p = 0.034), interval from primary treatment to re-RT ≥ 23.9 months (HR 0.35, p < 0.001), and re-RT PTV volume < 112 cc (HR 0.27, p < 0.001) were prognostic for improved OS. Patients who had unmethylated-MGMT tumours (OR 12.4, p = 0.034), ≥ 3 prior systemic treatment lines (OR 29.1, p = 0.022), interval to re-RT < 23.9 months (OR 9.0, p = 0.039), and re-RT PTV volume ≥ 112 cc (OR 17.8, p = 0.003) were more likely to die within 6 months of re-RT. The cumulative incidence of RN was 11.4% (95% CI 4.3-18.5) at 12 months. Concurrent bevacizumab use (HR < 0.001, p < 0.001) and cumulative equivalent dose in 2 Gy fractions (EQD2, α/β = 2) < 99 Gy₂ (HR < 0.001, p < 0.001) were independent protective factors against RN. Re-RT allowed for less corticosteroid dependency. Sixty-six percent of failures after re-RT were in-field.

Conclusion: We observe favorable OS rates following re-RT and identified prognostic factors, including methylation status, that can assist in patient selection and clinical trial design. Concurrent use of bevacizumab mitigated the risk of RN.

Keywords: Corticosteroid dependence; Glioblastoma; Pattern of failure; Radiation necrosis; Re-irradiation; Recurrent high-grade glioma.

MeSH terms

Adult
Bevacizumab / therapeutic use
Brain Neoplasms* / pathology
Glioma* / pathology
Humans
Necrosis / drug therapy
Neoplasm Recurrence, Local / pathology
Prognosis
Re-Irradiation*
Retrospective Studies

Substances

Bevacizumab