A multi-center prospective study of re-irradiation with bevacizumab and temozolomide in patients with bevacizumab refractory recurrent high-grade gliomas

Karan S. Dixit; Sean Sachdev; Christina Amidei; Priya Kumthekar; Tim J. Kruser; Vinai Gondi; Sean Grimm; Rimas V. Lukas; Martin Kelly Nicholas; Steven J. Chmura; Angela J. Fought; Minesh Mehta; Jeffrey J. Raizer

doi:10.1007/s11060-021-03875-8

A multi-center prospective study of re-irradiation with bevacizumab and temozolomide in patients with bevacizumab refractory recurrent high-grade gliomas

Karan S. Dixit^*, Sean Sachdev, Christina Amidei, Priya Kumthekar, Tim J. Kruser, Vinai Gondi, Sean Grimm, Rimas V. Lukas, Martin Kelly Nicholas, Steven J. Chmura, Angela J. Fought, Minesh Mehta, Jeffrey J. Raizer

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

8 Scopus citations

Abstract

Purpose: Survival is dismal for bevacizumab refractory high-grade glioma patients. We prospectively investigated the efficacy of re-irradiation, bevacizumab, and temozolomide in bevacizumab-naïve and bevacizumab-exposed recurrent high-grade glioma, without volume limitations, in a single arm trial. Methods: Recurrent high-grade glioma patients were stratified based on WHO grade (4 vs. < 4) and prior exposure to bevacizumab (yes vs. no). Eligible patients received radiation using a simultaneous integrated boost technique (55 Gy to enhancing disease, 45 Gy to non-enhancing disease in 25 fractions) with bevacizumab 10 mg/kg every 2 weeks IV and temozolomide 75 mg/m² daily followed by maintenance bevacizumab 10 mg/kg every 2 weeks and temozolomide 50 mg/m² daily for 6 weeks then a 2 week holiday until progression. Primary endpoint was overall survival. Quality of life was studied using FACT-Br and FACT-fatigue scales. Results: Fifty-four patients were enrolled. The majority (n = 36, 67%) were bevacizumab pre-exposed GBM. Median OS for all patients was 8.5 months and 7.9 months for the bevacizumab pre-exposed GBM group. Patients ≥ 36 months from initial radiation had a median OS of 13.3 months compared to 7.5 months for those irradiated < 36 months earlier (p < 0.01). FACT-Br and FACT-Fatigue scores initially declined during radiation but returned to pretreatment baseline. Treatment was well tolerated with 5 patients experiencing > grade 3 lymphopenia and 2 with > grade 3 thrombocytopenia. No radiographic or clinical radiation necrosis occurred. Conclusions: Re-irradiation with bevacizumab and temozolomide is a safe and feasible salvage treatment for patients with large volume bevacizumab-refractory high-grade glioma. Patients further from their initial radiotherapy may derive greater benefit with this regimen.

Original language	English (US)
Pages (from-to)	297-306
Number of pages	10
Journal	Journal of Neuro-Oncology
Volume	155
Issue number	3
DOIs	https://doi.org/10.1007/s11060-021-03875-8
State	Published - Dec 2021

Funding

We would like to thank all patients and caregivers. We would like to thank all of the clinical staff at the Robert H. Lurie Cancer Center of Northwestern University. We would like to thank Lyndsey Van for assistance with manuscript preparation. Finally, we would like to thank Dr. Roger Stupp for critical review of the manuscript.

Keywords

Bevacizumab
Glioblastoma
Radiation
Re-irradiation
Recurrent glioma
Temozolomide

ASJC Scopus subject areas

Oncology
Neurology
Clinical Neurology
Cancer Research

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1007/s11060-021-03875-8

Cite this

Dixit, K. S., Sachdev, S., Amidei, C., Kumthekar, P., Kruser, T. J., Gondi, V., Grimm, S., Lukas, R. V., Nicholas, M. K., Chmura, S. J., Fought, A. J., Mehta, M., & Raizer, J. J. (2021). A multi-center prospective study of re-irradiation with bevacizumab and temozolomide in patients with bevacizumab refractory recurrent high-grade gliomas. Journal of Neuro-Oncology, 155(3), 297-306. https://doi.org/10.1007/s11060-021-03875-8

@article{97e6a3f828844a18b574665413b67b2e,

title = "A multi-center prospective study of re-irradiation with bevacizumab and temozolomide in patients with bevacizumab refractory recurrent high-grade gliomas",

abstract = "Purpose: Survival is dismal for bevacizumab refractory high-grade glioma patients. We prospectively investigated the efficacy of re-irradiation, bevacizumab, and temozolomide in bevacizumab-na{\"i}ve and bevacizumab-exposed recurrent high-grade glioma, without volume limitations, in a single arm trial. Methods: Recurrent high-grade glioma patients were stratified based on WHO grade (4 vs. < 4) and prior exposure to bevacizumab (yes vs. no). Eligible patients received radiation using a simultaneous integrated boost technique (55 Gy to enhancing disease, 45 Gy to non-enhancing disease in 25 fractions) with bevacizumab 10 mg/kg every 2 weeks IV and temozolomide 75 mg/m2 daily followed by maintenance bevacizumab 10 mg/kg every 2 weeks and temozolomide 50 mg/m2 daily for 6 weeks then a 2 week holiday until progression. Primary endpoint was overall survival. Quality of life was studied using FACT-Br and FACT-fatigue scales. Results: Fifty-four patients were enrolled. The majority (n = 36, 67%) were bevacizumab pre-exposed GBM. Median OS for all patients was 8.5 months and 7.9 months for the bevacizumab pre-exposed GBM group. Patients ≥ 36 months from initial radiation had a median OS of 13.3 months compared to 7.5 months for those irradiated < 36 months earlier (p < 0.01). FACT-Br and FACT-Fatigue scores initially declined during radiation but returned to pretreatment baseline. Treatment was well tolerated with 5 patients experiencing > grade 3 lymphopenia and 2 with > grade 3 thrombocytopenia. No radiographic or clinical radiation necrosis occurred. Conclusions: Re-irradiation with bevacizumab and temozolomide is a safe and feasible salvage treatment for patients with large volume bevacizumab-refractory high-grade glioma. Patients further from their initial radiotherapy may derive greater benefit with this regimen.",

keywords = "Bevacizumab, Glioblastoma, Radiation, Re-irradiation, Recurrent glioma, Temozolomide",

author = "Dixit, {Karan S.} and Sean Sachdev and Christina Amidei and Priya Kumthekar and Kruser, {Tim J.} and Vinai Gondi and Sean Grimm and Lukas, {Rimas V.} and Nicholas, {Martin Kelly} and Chmura, {Steven J.} and Fought, {Angela J.} and Minesh Mehta and Raizer, {Jeffrey J.}",

note = "Funding Information: We would like to thank all patients and caregivers. We would like to thank all of the clinical staff at the Robert H. Lurie Cancer Center of Northwestern University. We would like to thank Lyndsey Van for assistance with manuscript preparation. Finally, we would like to thank Dr. Roger Stupp for critical review of the manuscript. Publisher Copyright: {\textcopyright} 2021, The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.",

year = "2021",

month = dec,

doi = "10.1007/s11060-021-03875-8",

language = "English (US)",

volume = "155",

pages = "297--306",

journal = "Journal of Neuro-Oncology",

issn = "0167-594X",

publisher = "Springer",

number = "3",

}

Dixit, KS , Sachdev, S, Amidei, C, Kumthekar, P, Kruser, TJ, Gondi, V, Grimm, S, Lukas, RV, Nicholas, MK, Chmura, SJ, Fought, AJ, Mehta, M & Raizer, JJ 2021, 'A multi-center prospective study of re-irradiation with bevacizumab and temozolomide in patients with bevacizumab refractory recurrent high-grade gliomas', Journal of Neuro-Oncology, vol. 155, no. 3, pp. 297-306. https://doi.org/10.1007/s11060-021-03875-8

TY - JOUR

T1 - A multi-center prospective study of re-irradiation with bevacizumab and temozolomide in patients with bevacizumab refractory recurrent high-grade gliomas

AU - Dixit, Karan S.

AU - Sachdev, Sean

AU - Amidei, Christina

AU - Kumthekar, Priya

AU - Kruser, Tim J.

AU - Gondi, Vinai

AU - Grimm, Sean

AU - Lukas, Rimas V.

AU - Nicholas, Martin Kelly

AU - Chmura, Steven J.

AU - Fought, Angela J.

AU - Mehta, Minesh

AU - Raizer, Jeffrey J.

N1 - Funding Information: We would like to thank all patients and caregivers. We would like to thank all of the clinical staff at the Robert H. Lurie Cancer Center of Northwestern University. We would like to thank Lyndsey Van for assistance with manuscript preparation. Finally, we would like to thank Dr. Roger Stupp for critical review of the manuscript. Publisher Copyright: © 2021, The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.

PY - 2021/12

Y1 - 2021/12

N2 - Purpose: Survival is dismal for bevacizumab refractory high-grade glioma patients. We prospectively investigated the efficacy of re-irradiation, bevacizumab, and temozolomide in bevacizumab-naïve and bevacizumab-exposed recurrent high-grade glioma, without volume limitations, in a single arm trial. Methods: Recurrent high-grade glioma patients were stratified based on WHO grade (4 vs. < 4) and prior exposure to bevacizumab (yes vs. no). Eligible patients received radiation using a simultaneous integrated boost technique (55 Gy to enhancing disease, 45 Gy to non-enhancing disease in 25 fractions) with bevacizumab 10 mg/kg every 2 weeks IV and temozolomide 75 mg/m2 daily followed by maintenance bevacizumab 10 mg/kg every 2 weeks and temozolomide 50 mg/m2 daily for 6 weeks then a 2 week holiday until progression. Primary endpoint was overall survival. Quality of life was studied using FACT-Br and FACT-fatigue scales. Results: Fifty-four patients were enrolled. The majority (n = 36, 67%) were bevacizumab pre-exposed GBM. Median OS for all patients was 8.5 months and 7.9 months for the bevacizumab pre-exposed GBM group. Patients ≥ 36 months from initial radiation had a median OS of 13.3 months compared to 7.5 months for those irradiated < 36 months earlier (p < 0.01). FACT-Br and FACT-Fatigue scores initially declined during radiation but returned to pretreatment baseline. Treatment was well tolerated with 5 patients experiencing > grade 3 lymphopenia and 2 with > grade 3 thrombocytopenia. No radiographic or clinical radiation necrosis occurred. Conclusions: Re-irradiation with bevacizumab and temozolomide is a safe and feasible salvage treatment for patients with large volume bevacizumab-refractory high-grade glioma. Patients further from their initial radiotherapy may derive greater benefit with this regimen.

AB - Purpose: Survival is dismal for bevacizumab refractory high-grade glioma patients. We prospectively investigated the efficacy of re-irradiation, bevacizumab, and temozolomide in bevacizumab-naïve and bevacizumab-exposed recurrent high-grade glioma, without volume limitations, in a single arm trial. Methods: Recurrent high-grade glioma patients were stratified based on WHO grade (4 vs. < 4) and prior exposure to bevacizumab (yes vs. no). Eligible patients received radiation using a simultaneous integrated boost technique (55 Gy to enhancing disease, 45 Gy to non-enhancing disease in 25 fractions) with bevacizumab 10 mg/kg every 2 weeks IV and temozolomide 75 mg/m2 daily followed by maintenance bevacizumab 10 mg/kg every 2 weeks and temozolomide 50 mg/m2 daily for 6 weeks then a 2 week holiday until progression. Primary endpoint was overall survival. Quality of life was studied using FACT-Br and FACT-fatigue scales. Results: Fifty-four patients were enrolled. The majority (n = 36, 67%) were bevacizumab pre-exposed GBM. Median OS for all patients was 8.5 months and 7.9 months for the bevacizumab pre-exposed GBM group. Patients ≥ 36 months from initial radiation had a median OS of 13.3 months compared to 7.5 months for those irradiated < 36 months earlier (p < 0.01). FACT-Br and FACT-Fatigue scores initially declined during radiation but returned to pretreatment baseline. Treatment was well tolerated with 5 patients experiencing > grade 3 lymphopenia and 2 with > grade 3 thrombocytopenia. No radiographic or clinical radiation necrosis occurred. Conclusions: Re-irradiation with bevacizumab and temozolomide is a safe and feasible salvage treatment for patients with large volume bevacizumab-refractory high-grade glioma. Patients further from their initial radiotherapy may derive greater benefit with this regimen.

KW - Bevacizumab

KW - Glioblastoma

KW - Radiation

KW - Re-irradiation

KW - Recurrent glioma

KW - Temozolomide

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U2 - 10.1007/s11060-021-03875-8

DO - 10.1007/s11060-021-03875-8

M3 - Article

C2 - 34689306

AN - SCOPUS:85117790797

SN - 0167-594X

VL - 155

SP - 297

EP - 306

JO - Journal of Neuro-Oncology

JF - Journal of Neuro-Oncology

IS - 3

ER -

A multi-center prospective study of re-irradiation with bevacizumab and temozolomide in patients with bevacizumab refractory recurrent high-grade gliomas

Abstract

Funding

Keywords

ASJC Scopus subject areas

UN SDGs

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