Barbara J Fisher1, Stephanie L Pugh2, David R Macdonald3, Arnab Chakravatri4, Glenn J Lesser5, Sherry Fox6, C Leland Rogers7, Maria Werner-Wasik8, Thomas Doyle9, Jean-Paul Bahary10, John B Fiveash11, Joseph A Bovi12, Steven P Howard13, Hsiang-Hsuan Michael Yu14, David D'Souza3, Nadia N Laack15, Igor J Barani16, Young Kwok17, Daniel R Wahl18, Jon F Strasser19, Minhee Won2, Minesh P Mehta20. 1. London Regional Cancer Program, London, Ontario, Canada. Electronic address: barbara.fisher@lhsc.on.ca. 2. NRG Oncology Statistics and Data Management Center, Philadelphia, Pennsylvania. 3. London Regional Cancer Program, London, Ontario, Canada. 4. Ohio State University Comprehensive Cancer Center, Columbus, Ohio. 5. Comprehensive Cancer Center of Wake Forest University, Winston-Salem, North Carolina. 6. Cullather Brain Tumor Quality of Life Center, Richmond, Virginia. 7. Arizona Oncology Services Foundation, Scottsdale, Arizona. 8. Thomas Jefferson University Hospital, Philadelphia, Pennsylvania. 9. Henry Ford Hospital, Detriot, Michigan. 10. Centre Hospitalier de l'Universite de Montreal, Montreal, Quebec, Canada. 11. University of Alabama at Birmingham Medical Center, Birmingham, Alabama. 12. Froedtert and the Medical College of Wisconsin, Milwaukee, Wisconsin. 13. University of Wisconsin Hospital, Madison, Wisconsin. 14. H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida. 15. Mayo Clinic, Rochester, Minnesota. 16. UCSF Medical Center - Mount Zion, San Francisco, California. 17. University of Maryland Marlene and Stewart Greenebaum Comprehensive Cancer Center, Baltimore, Maryland. 18. University of Michigan Medical Center, Ann Arbor, Michigan. 19. Christiana Care Health Services, Inc, Wilmington, Delaware. 20. Miami Cancer Institute, Kendall, Florida.
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.
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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