Prospective Randomized Phase 2 Trial of Hypofractionated Stereotactic Radiation Therapy of 25 Gy in 5 Fractions Compared With 35 Gy in 5 Fractions in the Reirradiation of Recurrent Glioblastoma

Andre Tsin Chih Chen; Alexandre Ruggieri Serante; Aline Sgnolf Ayres; Juliana Ono Tonaki; Raquel Andrade Moreno; Helen Shih; Gabriel Scarabotolo Gattás; Rossana Veronica Mendoza Lopez; Gabriela Reis Dos Santos de Jesus; Icaro Thiago de Carvalho; Rodrigo Carvalho Marotta; Gustavo Nader Marta; Olavo Feher; Hugo Sterman Neto; Iuri Santana Neville Ribeiro; Karina Gondim Moutinho da Conceição Vasconcelos; Eberval Gadelha Figueiredo; Eduardo Weltman

doi:10.1016/j.ijrobp.2024.01.013

Prospective Randomized Phase 2 Trial of Hypofractionated Stereotactic Radiation Therapy of 25 Gy in 5 Fractions Compared With 35 Gy in 5 Fractions in the Reirradiation of Recurrent Glioblastoma

Int J Radiat Oncol Biol Phys. 2024 Jan 15:S0360-3016(24)00026-9. doi: 10.1016/j.ijrobp.2024.01.013. Online ahead of print.

Authors

Andre Tsin Chih Chen¹, Alexandre Ruggieri Serante², Aline Sgnolf Ayres³, Juliana Ono Tonaki⁴, Raquel Andrade Moreno³, Helen Shih⁵, Gabriel Scarabotolo Gattás⁶, Rossana Veronica Mendoza Lopez⁷, Gabriela Reis Dos Santos de Jesus², Icaro Thiago de Carvalho², Rodrigo Carvalho Marotta², Gustavo Nader Marta², Olavo Feher⁸, Hugo Sterman Neto⁹, Iuri Santana Neville Ribeiro⁹, Karina Gondim Moutinho da Conceição Vasconcelos², Eberval Gadelha Figueiredo¹⁰, Eduardo Weltman¹¹

Affiliations

¹ Department of Radiation Oncology, Instituto do Câncer do Estado de São Paulo, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (FMUSP), Sao Paulo, Brazil. Electronic address: andre.chen@hc.fm.usp.br.
² Department of Radiation Oncology, Instituto do Câncer do Estado de São Paulo, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (FMUSP), Sao Paulo, Brazil.
³ Department of Radiology, Instituto do Câncer do Estado de São Paulo, Hospital das Clínicas da FMUSP, Sao Paulo, Brazil.
⁴ Division of Psychology, Instituto do Câncer do Estado de São Paulo, Hospital das Clínicas da FMUSP, Sao Paulo, Brazil.
⁵ Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts.
⁶ Department of Radiology, Institute of Radiology, Hospital das Clínicas da FMUSP, Sao Paulo, Brazil.
⁷ Oncology Translational Research Center, Instituto do Câncer do Estado de São Paulo, Hospital das Clínicas da FMUSP, Sao Paulo, Brazil.
⁸ Department of Clinical Oncology, Instituto do Câncer do Estado de São Paulo, Hospital das Clínicas da FMUSP, Sao Paulo, Brazil.
⁹ Department of Neurosurgery, Instituto do Câncer do Estado de São Paulo, Hospital das Clínicas da FMUSP, Sao Paulo, Brazil.
¹⁰ Department of Neurosurgery, Hospital das Clínicas da FMUSP, Sao Paulo, Brazil.
¹¹ Department of Radiation Oncology, FMUSP, São Paulo, Brazil.

PMID: 38232937
DOI: 10.1016/j.ijrobp.2024.01.013

Abstract

Purpose: The aim of this work was to investigate whether reirradiation of recurrent glioblastoma with hypofractionated stereotactic radiation therapy (HSRT) consisting of 35 Gy in 5 fractions (35 Gy/5 fx) compared with 25 Gy in 5 fractions (25 Gy/5 fx) improves outcomes while maintaining acceptable toxicity.

Methods and materials: We conducted a prospective randomized phase 2 trial involving patients with recurrent glioblastoma (per the 2007 and 2016 World Health Organization classification). A minimum interval from first radiation therapy of 5 months and gross tumor volume of 150 cc were required. Patients were randomized 1:1 to receive HSRT alone in 25 Gy/5 fx or 35 Gy/5 fx. The primary endpoint was progression-free survival (PFS). We used a randomized phase 2 screening design with a 2-sided α of 0.15 for the primary endpoint.

Results: From 2011 to 2019, 40 patients were randomized and received HSRT, with 20 patients in each group. The median age was 50 years (range, 27-71); a new resection before HSRT was performed in 75% of patients. The median PFS was 4.9 months in the 25 Gy/5 fx group and 5.2 months in the 35 Gy/5 fx group (P = .23). Six-month PFS was similar at 40% (85% CI, 24%-55%) for both groups. The median overall survival (OS) was 9.2 months in the 25 Gy/5 fx group and 10 months in the 35 Gy/5 fx group (P = .201). Grade ≥3 necrosis was numerically higher in the 35 Gy/5 fx group (3 [16%] vs 1 [5%]), but the difference was not statistically significant (P = .267). In an exploratory analysis, median OS of patients who developed treatment-related necrosis was 14.1 months, and that of patients who did not was 8.7 months (P = .003).

Conclusions: HSRT alone with 35 Gy/5 fx was not superior to 25 Gy/5 fx in terms of PFS or OS. Due to a potential increase in the rate of clinically meaningful treatment-related necrosis, we suggest 25 Gy/5 fx as the standard dose in HSRT alone. During follow-up, attention should be given to differentiating tumor progression from potentially manageable complications.