Re-irradiation of recurrent IDH-wildtype glioblastoma in the bevacizumab and immunotherapy era: Target delineation, outcomes and patterns of recurrence

Sebastian M Christ; Gilbert Youssef; Shyam K Tanguturi; Daniel Cagney; Diana Shi; J Ricardo McFaline-Figueroa; Ugonma Chukwueke; Eudocia Q Lee; Caroline Hertler; Nicolaus Andratschke; Michael Weller; David A Reardon; Daphne Haas-Kogan; Matthias Guckenberger; Patrick Y Wen; Rifaquat Rahman

doi:10.1016/j.ctro.2023.100697

Re-irradiation of recurrent IDH-wildtype glioblastoma in the bevacizumab and immunotherapy era: Target delineation, outcomes and patterns of recurrence

Clin Transl Radiat Oncol. 2023 Oct 30:44:100697. doi: 10.1016/j.ctro.2023.100697. eCollection 2024 Jan.

Authors

Sebastian M Christ^{1

2}, Gilbert Youssef³, Shyam K Tanguturi¹, Daniel Cagney¹, Diana Shi¹, J Ricardo McFaline-Figueroa³, Ugonma Chukwueke³, Eudocia Q Lee³, Caroline Hertler⁴, Nicolaus Andratschke², Michael Weller⁵, David A Reardon³, Daphne Haas-Kogan¹, Matthias Guckenberger², Patrick Y Wen³, Rifaquat Rahman¹

Affiliations

¹ Department of Radiation Oncology, Dana-Farber/Brigham and Women's Cancer Center, Harvard Medical School, Boston, MA, USA.
² Department of Radiation Oncology, University Hospital and University of Zurich, Zurich, Switzerland.
³ Center for Neuro-Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
⁴ Competence Center Palliative Care, University Hospital and University of Zurich, Zurich, Switzerland.
⁵ Department of Neurology, University Hospital and University of Zurich, Zurich, Switzerland.

Abstract

Introduction and background: While recurrent glioblastoma patients are often treated with re-irradiation, there is limited data on the use of re-irradiation in the setting of bevacizumab (BEV), temozolomide (TMZ) re-challenge, or immune checkpoint inhibition (ICI). We describe target delineation in patients with prior anti-angiogenic therapy, assess safety and efficacy of re-irradiation, and evaluate patterns of recurrence.

Materials and methods: Patients with a histologically confirmed diagnosis of glioblastoma treated at a single institution between 2013 and 2021 with re-irradiation were included. Tumor, treatment and clinical data were collected. Logistic and Cox regression analysis were used for statistical analysis.

Results: One hundred and seventeen recurrent glioblastoma patients were identified, receiving 129 courses of re-irradiation. In 66 % (85/129) of cases, patients had prior BEV. In the 80 patients (62 %) with available re-irradiation plans, 20 (25 %) had all T2/FLAIR abnormality included in the gross tumor volume (GTV). Median overall survival (OS) for the cohort was 7.3 months, and median progression-free survival (PFS) was 3.6 months. Acute CTCAE grade ≥ 3 toxicity occurred in 8 % of cases. Concurrent use of TMZ or ICI was not associated with improved OS nor PFS. On multivariable analysis, higher KPS was significantly associated with longer OS (p < 0.01). On subgroup analysis, patients with prior BEV had significantly more marginal recurrences than those without (26 % vs. 13 %, p < 0.01).

Conclusion: Re-irradiation can be safely employed in recurrent glioblastoma patients. Marginal recurrence was more frequent in patients with prior BEV, suggesting a need to consider more inclusive treatment volumes incorporating T2/FLAIR abnormality.

Keywords: New systemic therapies; Re-irradiation; Recurrent glioblastoma.

Grants and funding

K12 CA090354/CA/NCI NIH HHS/United States