Phase 2 Study of a Temozolomide-Based Chemoradiation Therapy Regimen for High-Risk, Low-Grade Gliomas: Long-Term Results of Radiation Therapy Oncology Group 0424

Barbara J. Fisher; Stephanie L. Pugh; David R. Macdonald; Arnab Chakravatri; Glenn J. Lesser; Sherry Fox; C. Leland Rogers; Maria Werner-Wasik; Thomas Doyle; Jean Paul Bahary; John B. Fiveash; Joseph A. Bovi; Steven P. Howard; Hsiang Hsuan Michael Yu; David D'Souza; Nadia N. Laack; Igor J. Barani; Young Kwok; Daniel R. Wahl; Jon F. Strasser; Minhee Won; Minesh P. Mehta

doi:10.1016/j.ijrobp.2020.03.027

Phase 2 Study of a Temozolomide-Based Chemoradiation Therapy Regimen for High-Risk, Low-Grade Gliomas: Long-Term Results of Radiation Therapy Oncology Group 0424

Barbara J. Fisher, Stephanie L. Pugh, David R. Macdonald, Arnab Chakravatri, Glenn J. Lesser, Sherry Fox, C. Leland Rogers, Maria Werner-Wasik, Thomas Doyle, Jean Paul Bahary, John B. Fiveash, Joseph A. Bovi, Steven P. Howard, Hsiang Hsuan Michael Yu, David D'Souza, Nadia N. Laack, Igor J. Barani, Young Kwok, Daniel R. Wahl, Jon F. StrasserMinhee Won, Minesh P. Mehta

Radiation Oncology

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

4 Scopus citations

Abstract

Purpose: To report the long-term outcomes of the RTOG 0424 study of a high-risk, low-grade glioma population treated with concurrent and adjuvant temozolomide (TMZ) and radiation therapy (RT). Methods and Materials: For this single-arm, phase 2 study, patients with low-grade gliomas with ≥3 risk factors (age ≥40 years, astrocytoma, bihemispheric tumor, size ≥6 cm, or preoperative neurologic function status >1) received RT (54 Gy in 30 fractions) with TMZ and up to 12 cycles of post-RT TMZ. The initial primary endpoint P was overall survival (OS) at 3 years after registration. Secondary endpoints included progression-free survival (PFS) and the association of survival outcomes with methylation status. The initial 3-year report of this study was published in 2015. Results: The study accrued 136 patients, of whom 129 were analyzable. The median follow-up for surviving patients was 9.0 years. The 3-year OS was 73.5% (95% confidence interval, 65.8%-81.1%), numerically superior to the 3-year OS historical control of 54% (P <.001). The median survival time was 8.2 years (95% confidence interval, 5.6-9.1). Five- and 10-year OS rates were 60.9% and 34.6%, respectively, and 5- and 10-year PFS rates were 46.8% and 25.5%, respectively. Conclusions: The long-term results confirmed the findings from the initial report for efficacy, suggesting OS and PFS outcomes with the RT-TMZ regimen exceeded historical control groups treated with radiation alone. Toxicity was acceptable.

Original language	English (US)
Pages (from-to)	720-725
Number of pages	6
Journal	International Journal of Radiation Oncology Biology Physics
Volume	107
Issue number	4
DOIs	https://doi.org/10.1016/j.ijrobp.2020.03.027
State	Published - Jul 15 2020

ASJC Scopus subject areas

Radiation
Oncology
Radiology Nuclear Medicine and imaging
Cancer Research

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Fisher, B. J., Pugh, S. L., Macdonald, D. R., Chakravatri, A., Lesser, G. J., Fox, S., Rogers, C. L., Werner-Wasik, M., Doyle, T., Bahary, J. P., Fiveash, J. B., Bovi, J. A., Howard, S. P., Michael Yu, H. H., D'Souza, D., Laack, N. N., Barani, I. J., Kwok, Y., Wahl, D. R., ... Mehta, M. P. (2020). Phase 2 Study of a Temozolomide-Based Chemoradiation Therapy Regimen for High-Risk, Low-Grade Gliomas: Long-Term Results of Radiation Therapy Oncology Group 0424. International Journal of Radiation Oncology Biology Physics, 107(4), 720-725. https://doi.org/10.1016/j.ijrobp.2020.03.027

Phase 2 Study of a Temozolomide-Based Chemoradiation Therapy Regimen for High-Risk, Low-Grade Gliomas : Long-Term Results of Radiation Therapy Oncology Group 0424. / Fisher, Barbara J.; Pugh, Stephanie L.; Macdonald, David R. et al.

In: International Journal of Radiation Oncology Biology Physics, Vol. 107, No. 4, 15.07.2020, p. 720-725.

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

Fisher, BJ, Pugh, SL, Macdonald, DR, Chakravatri, A, Lesser, GJ, Fox, S, Rogers, CL, Werner-Wasik, M, Doyle, T, Bahary, JP, Fiveash, JB, Bovi, JA, Howard, SP, Michael Yu, HH, D'Souza, D, Laack, NN, Barani, IJ, Kwok, Y, Wahl, DR, Strasser, JF, Won, M & Mehta, MP 2020, 'Phase 2 Study of a Temozolomide-Based Chemoradiation Therapy Regimen for High-Risk, Low-Grade Gliomas: Long-Term Results of Radiation Therapy Oncology Group 0424', International Journal of Radiation Oncology Biology Physics, vol. 107, no. 4, pp. 720-725. https://doi.org/10.1016/j.ijrobp.2020.03.027

@article{b336fd8232b04f4a940fe8f314d322ef,

title = "Phase 2 Study of a Temozolomide-Based Chemoradiation Therapy Regimen for High-Risk, Low-Grade Gliomas: Long-Term Results of Radiation Therapy Oncology Group 0424",

abstract = "Purpose: To report the long-term outcomes of the RTOG 0424 study of a high-risk, low-grade glioma population treated with concurrent and adjuvant temozolomide (TMZ) and radiation therapy (RT). Methods and Materials: For this single-arm, phase 2 study, patients with low-grade gliomas with ≥3 risk factors (age ≥40 years, astrocytoma, bihemispheric tumor, size ≥6 cm, or preoperative neurologic function status >1) received RT (54 Gy in 30 fractions) with TMZ and up to 12 cycles of post-RT TMZ. The initial primary endpoint P was overall survival (OS) at 3 years after registration. Secondary endpoints included progression-free survival (PFS) and the association of survival outcomes with methylation status. The initial 3-year report of this study was published in 2015. Results: The study accrued 136 patients, of whom 129 were analyzable. The median follow-up for surviving patients was 9.0 years. The 3-year OS was 73.5% (95% confidence interval, 65.8%-81.1%), numerically superior to the 3-year OS historical control of 54% (P <.001). The median survival time was 8.2 years (95% confidence interval, 5.6-9.1). Five- and 10-year OS rates were 60.9% and 34.6%, respectively, and 5- and 10-year PFS rates were 46.8% and 25.5%, respectively. Conclusions: The long-term results confirmed the findings from the initial report for efficacy, suggesting OS and PFS outcomes with the RT-TMZ regimen exceeded historical control groups treated with radiation alone. Toxicity was acceptable.",

author = "Fisher, {Barbara J.} and Pugh, {Stephanie L.} and Macdonald, {David R.} and Arnab Chakravatri and Lesser, {Glenn J.} and Sherry Fox and Rogers, {C. Leland} and Maria Werner-Wasik and Thomas Doyle and Bahary, {Jean Paul} and Fiveash, {John B.} and Bovi, {Joseph A.} and Howard, {Steven P.} and {Michael Yu}, {Hsiang Hsuan} and David D'Souza and Laack, {Nadia N.} and Barani, {Igor J.} and Young Kwok and Wahl, {Daniel R.} and Strasser, {Jon F.} and Minhee Won and Mehta, {Minesh P.}",

note = "Funding Information: This project was supported by grants U10CA180868 ( NRG Oncology Operations ) and U10CA180822 ( NRG Oncology Statistical and Data Management Center ), and grant U24CA196067 ( NRG Biospecimen Bank ). Funding Information: Disclosures: J.A.B. discloses consulting fees from Elekta, outside the submitted work. J.B.F. discloses research and education contracts with Varian Medical Systems, outside the submitted work. G.J.L. discloses the role of data and safety monitoring board chair with Stemline Therapeutics, consulting roles with BTG and Monteris, and being a clinical trial site for Incyte, NewLink Genetics, Vascular Biogenics, and Novartis, outside the submitted work. D.R.M. discloses nonfinancial clinical trial support to his cancer center for the Tg-511-15-01 study from Tocagen, Inc, and nonfinancial clinical trial support to his cancer center for the Radiation Therapy Oncology Group 3508/AbbVie M13-18 (Intellance 1) study from AbbVie, Inc, outside the submitted work. M.P.M. discloses consultant roles with Insys, Remedy, IBA, Varian, Celgene, AbbVie, AstraZeneca, Tocagen, and Blue Earth and serves on the board of directors of Oncoceutics, with stock options, outside the submitted work. S.L.P. discloses salary support paid to her institution from Pfizer-Astellas and Millenium, and grant salary support paid to her institution from the Patient-Centered Outcomes Research Institute and a PA CURE grant. J.F.S. discloses personal speaker{\textquoteright}s bureau fees from AstraZeneca, Bristol Myers Squibb, and Genomic Health, outside the submitted work. D.R.W. discloses grants from Agioes, Inc, and Innocrin, Inc, outside the submitted work. In addition, D.R.W. has a patent for a transcription-based algorithm to predict therapy response in glioblastoma pending. Publisher Copyright: {\textcopyright} 2020 Elsevier Inc.",

year = "2020",

month = jul,

day = "15",

doi = "10.1016/j.ijrobp.2020.03.027",

language = "English (US)",

volume = "107",

pages = "720--725",

journal = "International Journal of Radiation Oncology Biology Physics",

issn = "0360-3016",

publisher = "Elsevier Inc.",

number = "4",

}

TY - JOUR

T1 - Phase 2 Study of a Temozolomide-Based Chemoradiation Therapy Regimen for High-Risk, Low-Grade Gliomas

T2 - Long-Term Results of Radiation Therapy Oncology Group 0424

AU - Fisher, Barbara J.

AU - Pugh, Stephanie L.

AU - Macdonald, David R.

AU - Chakravatri, Arnab

AU - Lesser, Glenn J.

AU - Fox, Sherry

AU - Rogers, C. Leland

AU - Werner-Wasik, Maria

AU - Doyle, Thomas

AU - Bahary, Jean Paul

AU - Fiveash, John B.

AU - Bovi, Joseph A.

AU - Howard, Steven P.

AU - Michael Yu, Hsiang Hsuan

AU - D'Souza, David

AU - Laack, Nadia N.

AU - Barani, Igor J.

AU - Kwok, Young

AU - Wahl, Daniel R.

AU - Strasser, Jon F.

AU - Won, Minhee

AU - Mehta, Minesh P.

N1 - Funding Information: This project was supported by grants U10CA180868 ( NRG Oncology Operations ) and U10CA180822 ( NRG Oncology Statistical and Data Management Center ), and grant U24CA196067 ( NRG Biospecimen Bank ). Funding Information: Disclosures: J.A.B. discloses consulting fees from Elekta, outside the submitted work. J.B.F. discloses research and education contracts with Varian Medical Systems, outside the submitted work. G.J.L. discloses the role of data and safety monitoring board chair with Stemline Therapeutics, consulting roles with BTG and Monteris, and being a clinical trial site for Incyte, NewLink Genetics, Vascular Biogenics, and Novartis, outside the submitted work. D.R.M. discloses nonfinancial clinical trial support to his cancer center for the Tg-511-15-01 study from Tocagen, Inc, and nonfinancial clinical trial support to his cancer center for the Radiation Therapy Oncology Group 3508/AbbVie M13-18 (Intellance 1) study from AbbVie, Inc, outside the submitted work. M.P.M. discloses consultant roles with Insys, Remedy, IBA, Varian, Celgene, AbbVie, AstraZeneca, Tocagen, and Blue Earth and serves on the board of directors of Oncoceutics, with stock options, outside the submitted work. S.L.P. discloses salary support paid to her institution from Pfizer-Astellas and Millenium, and grant salary support paid to her institution from the Patient-Centered Outcomes Research Institute and a PA CURE grant. J.F.S. discloses personal speaker’s bureau fees from AstraZeneca, Bristol Myers Squibb, and Genomic Health, outside the submitted work. D.R.W. discloses grants from Agioes, Inc, and Innocrin, Inc, outside the submitted work. In addition, D.R.W. has a patent for a transcription-based algorithm to predict therapy response in glioblastoma pending. Publisher Copyright: © 2020 Elsevier Inc.

PY - 2020/7/15

Y1 - 2020/7/15

N2 - Purpose: To report the long-term outcomes of the RTOG 0424 study of a high-risk, low-grade glioma population treated with concurrent and adjuvant temozolomide (TMZ) and radiation therapy (RT). Methods and Materials: For this single-arm, phase 2 study, patients with low-grade gliomas with ≥3 risk factors (age ≥40 years, astrocytoma, bihemispheric tumor, size ≥6 cm, or preoperative neurologic function status >1) received RT (54 Gy in 30 fractions) with TMZ and up to 12 cycles of post-RT TMZ. The initial primary endpoint P was overall survival (OS) at 3 years after registration. Secondary endpoints included progression-free survival (PFS) and the association of survival outcomes with methylation status. The initial 3-year report of this study was published in 2015. Results: The study accrued 136 patients, of whom 129 were analyzable. The median follow-up for surviving patients was 9.0 years. The 3-year OS was 73.5% (95% confidence interval, 65.8%-81.1%), numerically superior to the 3-year OS historical control of 54% (P <.001). The median survival time was 8.2 years (95% confidence interval, 5.6-9.1). Five- and 10-year OS rates were 60.9% and 34.6%, respectively, and 5- and 10-year PFS rates were 46.8% and 25.5%, respectively. Conclusions: The long-term results confirmed the findings from the initial report for efficacy, suggesting OS and PFS outcomes with the RT-TMZ regimen exceeded historical control groups treated with radiation alone. Toxicity was acceptable.

AB - Purpose: To report the long-term outcomes of the RTOG 0424 study of a high-risk, low-grade glioma population treated with concurrent and adjuvant temozolomide (TMZ) and radiation therapy (RT). Methods and Materials: For this single-arm, phase 2 study, patients with low-grade gliomas with ≥3 risk factors (age ≥40 years, astrocytoma, bihemispheric tumor, size ≥6 cm, or preoperative neurologic function status >1) received RT (54 Gy in 30 fractions) with TMZ and up to 12 cycles of post-RT TMZ. The initial primary endpoint P was overall survival (OS) at 3 years after registration. Secondary endpoints included progression-free survival (PFS) and the association of survival outcomes with methylation status. The initial 3-year report of this study was published in 2015. Results: The study accrued 136 patients, of whom 129 were analyzable. The median follow-up for surviving patients was 9.0 years. The 3-year OS was 73.5% (95% confidence interval, 65.8%-81.1%), numerically superior to the 3-year OS historical control of 54% (P <.001). The median survival time was 8.2 years (95% confidence interval, 5.6-9.1). Five- and 10-year OS rates were 60.9% and 34.6%, respectively, and 5- and 10-year PFS rates were 46.8% and 25.5%, respectively. Conclusions: The long-term results confirmed the findings from the initial report for efficacy, suggesting OS and PFS outcomes with the RT-TMZ regimen exceeded historical control groups treated with radiation alone. Toxicity was acceptable.

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JO - International Journal of Radiation Oncology Biology Physics

JF - International Journal of Radiation Oncology Biology Physics

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ER -

Phase 2 Study of a Temozolomide-Based Chemoradiation Therapy Regimen for High-Risk, Low-Grade Gliomas: Long-Term Results of Radiation Therapy Oncology Group 0424

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