George Shenouda1, Luis Souhami2, Kevin Petrecca3, Scott Owen4, Valerie Panet-Raymond2, Marie-Christine Guiot5, Andrea Gomez Corredor6, Bassam Abdulkarim2. 1. Department of Radiation Oncology, McGill University Health Centre, Montréal, Québec, Canada. Electronic address: george.shenouda@muhc.mcgill.ca. 2. Department of Radiation Oncology, McGill University Health Centre, Montréal, Québec, Canada. 3. Department of Neurosurgery, Montreal Neurological Institute, Montréal, Québec, Canada. 4. Department of Medical Oncology, McGill University Health Centre, Montréal, Québec, Canada. 5. Department of Pathology, Montreal Neurological Institute, Montréal, Québec, Canada. 6. Core Molecular Diagnostic Laboratory, McGill University, Montréal, Québec, Canada.
Abstract
PURPOSE: We performed a phase 2 trial of neoadjuvant temozolomide (TMZ), followed by hypofractionated accelerated radiation therapy (HART) with concurrent TMZ, and adjuvant TMZ in patients with newly diagnosed glioblastoma to determine whether neoadjuvant TMZ would safely improve outcomes in this group of patients prior to subsequent cytotoxic therapy. METHODS AND MATERIALS: Adult patients with newly diagnosed glioblastoma and a Karnofsky Performance Status >60 were eligible. Neoadjuvant TMZ administration started 2 to 3 weeks from surgery at a daily dose of 75 mg/m2 for 2 weeks prior to delivery of HART (60 Gy in 20 daily fractions) with concurrent and adjuvant TMZ. The primary endpoints were feasibility and toxicity. The secondary endpoints included overall survival (OS) and progression-free survival. RESULTS: Fifty patients were accrued. The median follow-up period was 44.0 months for patients at risk and 22.3 months for all 50 patients. Except for 1 patient in whom infection developed and another patient with progression during HART, all patients completed protocol therapy as planned. The median OS and progression-free survival were 22.3 months (95% confidence interval, 14.6-42.7 months) and 13.7 months (95% confidence interval, 8.0-33.3 months), respectively. The 4-year OS rates were 30.4% for the entire cohort and 53.3% and 14.0% for patients with methylated (n=21) and unmethylated (n=27) MGMT gene promoter tumors, respectively. One patient had grade 5 pancytopenia during HART, and another patient had transient grade 4 hepatotoxicity. A second surgical procedure was performed in 13 patients: 2 had intracranial infection, 3 had recurrences, 4 had recurrences and radiation-induced damage, and 4 had only radiation-induced damage. CONCLUSIONS: This novel approach of neoadjuvant TMZ is associated with an encouraging favorable long-term survival with acceptable toxicity. A future comparative trial of the efficacy of this regimen is warranted.
PURPOSE: We performed a phase 2 trial of neoadjuvant temozolomide (TMZ), followed by hypofractionated accelerated radiation therapy (HART) with concurrent TMZ, and adjuvant TMZ in patients with newly diagnosed glioblastoma to determine whether neoadjuvant TMZ would safely improve outcomes in this group of patients prior to subsequent cytotoxic therapy. METHODS AND MATERIALS: Adult patients with newly diagnosed glioblastoma and a Karnofsky Performance Status >60 were eligible. Neoadjuvant TMZ administration started 2 to 3 weeks from surgery at a daily dose of 75 mg/m2 for 2 weeks prior to delivery of HART (60 Gy in 20 daily fractions) with concurrent and adjuvant TMZ. The primary endpoints were feasibility and toxicity. The secondary endpoints included overall survival (OS) and progression-free survival. RESULTS: Fifty patients were accrued. The median follow-up period was 44.0 months for patients at risk and 22.3 months for all 50 patients. Except for 1 patient in whom infection developed and another patient with progression during HART, all patients completed protocol therapy as planned. The median OS and progression-free survival were 22.3 months (95% confidence interval, 14.6-42.7 months) and 13.7 months (95% confidence interval, 8.0-33.3 months), respectively. The 4-year OS rates were 30.4% for the entire cohort and 53.3% and 14.0% for patients with methylated (n=21) and unmethylated (n=27) MGMT gene promoter tumors, respectively. One patient had grade 5 pancytopenia during HART, and another patient had transient grade 4 hepatotoxicity. A second surgical procedure was performed in 13 patients: 2 had intracranial infection, 3 had recurrences, 4 had recurrences and radiation-induced damage, and 4 had only radiation-induced damage. CONCLUSIONS: This novel approach of neoadjuvant TMZ is associated with an encouraging favorable long-term survival with acceptable toxicity. A future comparative trial of the efficacy of this regimen is warranted.
Authors: Delphine Garnier; Brian Meehan; Thomas Kislinger; Paul Daniel; Ankit Sinha; Bassam Abdulkarim; Ichiro Nakano; Janusz Rak Journal: Neuro Oncol Date: 2018-01-22 Impact factor: 12.300
Authors: Tomas Kazda; Adam Dziacky; Petr Burkon; Petr Pospisil; Marek Slavik; Zdenek Rehak; Radim Jancalek; Pavel Slampa; Ondrej Slaby; Radek Lakomy Journal: Radiol Oncol Date: 2018-06-06 Impact factor: 4.214
Authors: Harold W Davis; Subrahmanya D Vallabhapurapu; Zhengtao Chu; Michael A Wyder; Kenneth D Greis; Venette Fannin; Ying Sun; Pankaj B Desai; Koon Y Pak; Brian D Gray; Xiaoyang Qi Journal: Cells Date: 2020-08-25 Impact factor: 6.600