Kurt A Jaeckle1, Karla V Ballman2, Martin van den Bent3, Caterina Giannini4, Evanthia Galanis4, Paul D Brown4, Robert B Jenkins4, J Gregory Cairncross5, Wolfgang Wick6, Michael Weller7, Kenneth D Aldape8, Jesse G Dixon9, S Keith Anderson9, Jane H Cerhan10, Jeffrey S Wefel11, Martin Klein12, Stuart A Grossman13, David Schiff14, Jeffrey J Raizer15, Frederick Dhermain16, Donald G Nordstrom17, Patrick J Flynn18, Michael A Vogelbaum19. 1. Department of Neurology, Mayo Clinic Florida, Jacksonville, Florida, USA. 2. Alliance Statistics and Data Center, Weill Cornell Medicine, New York, New York, USA. 3. Brain Tumor Center, Erasmus MC Cancer Center, Erasmus University Medical Center, Rotterdam, Netherlands. 4. Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota, USA. 5. Department of Clinical Neurosciences, Arnie Charbonneau Cancer Institute, University of Calgary, Calgary, Alberta, Canada. 6. Neurologische Klinik, University of Heidelberg, Heidelberg, Germany. 7. Department of Neurology, University Hospital and University of Zurich, Zurich, Switzerland. 8. Department of Neuropathology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA. 9. Alliance Statistics and Data Center, Mayo Clinic, Rochester, Minnesota, USA. 10. Departments of Psychiatry and Psychology, Houston, Texas, USA. 11. Departments of Neuro-Oncology and Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA. 12. Department of Medical Psychology, VU University Medical Center, Amsterdam, Netherlands. 13. Department of Oncology, Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Baltimore, Maryland, USA. 14. Department of Neurology, University of Virginia, Charlottesville, Virginia, USA. 15. Department of Neurology, Northwestern University, Chicago, Illinois, USA. 16. Department of Radiation Therapy, Gustave Roussy Cancer Institute, Villejuif, France. 17. Medical Oncology, France Abben Cancer Center, Spencer, Iowa, USA. 18. Medical Oncology, Minnesota Oncology, Northfield, Minnesota, USA. 19. Department of Neurosurgery, Cleveland Clinic, Cleveland, Ohio, USA.
Abstract
BACKGROUND: We report the analysis involving patients treated on the initial CODEL design. METHODS: Adults (>18) with newly diagnosed 1p/19q World Health Organization (WHO) grade III oligodendroglioma were randomized to radiotherapy (RT; 5940 centigray ) alone (arm A); RT with concomitant and adjuvant temozolomide (TMZ) (arm B); or TMZ alone (arm C). Primary endpoint was overall survival (OS), arm A versus B. Secondary comparisons were performed for OS and progression-free survival (PFS), comparing pooled RT arms versus TMZ-alone arm. RESULTS: Thirty-six patients were randomized equally. At median follow-up of 7.5 years, 83.3% (10/12) TMZ-alone patients progressed, versus 37.5% (9/24) on the RT arms. PFS was significantly shorter in TMZ-alone patients compared with RT patients (hazard ratio [HR] = 3.12; 95% CI: 1.26, 7.69; P = 0.014). Death from disease progression occurred in 3/12 (25%) of TMZ-alone patients and 4/24 (16.7%) on the RT arms. OS did not statistically differ between arms (comparison underpowered). After adjustment for isocitrate dehydrogenase (IDH) status (mutated/wildtype) in a Cox regression model utilizing IDH and RT treatment status as covariables (arm C vs pooled arms A + B), PFS remained shorter for patients not receiving RT (HR = 3.33; 95% CI: 1.31, 8.45; P = 0.011), but not OS ((HR = 2.78; 95% CI: 0.58, 13.22, P = 0.20). Grade 3+ adverse events occurred in 25%, 42%, and 33% of patients (arms A, B, and C). There were no differences between arms in neurocognitive decline comparing baseline to 3 months. CONCLUSIONS: TMZ-alone patients experienced significantly shorter PFS than patients treated on the RT arms. The ongoing CODEL trial has been redesigned to compare RT + PCV versus RT + TMZ.
BACKGROUND: We report the analysis involving patients treated on the initial CODEL design. METHODS: Adults (>18) with newly diagnosed 1p/19q World Health Organization (WHO) grade III oligodendroglioma were randomized to radiotherapy (RT; 5940 centigray ) alone (arm A); RT with concomitant and adjuvant temozolomide (TMZ) (arm B); or TMZ alone (arm C). Primary endpoint was overall survival (OS), arm A versus B. Secondary comparisons were performed for OS and progression-free survival (PFS), comparing pooled RT arms versus TMZ-alone arm. RESULTS: Thirty-six patients were randomized equally. At median follow-up of 7.5 years, 83.3% (10/12) TMZ-alone patients progressed, versus 37.5% (9/24) on the RT arms. PFS was significantly shorter in TMZ-alone patients compared with RT patients (hazard ratio [HR] = 3.12; 95% CI: 1.26, 7.69; P = 0.014). Death from disease progression occurred in 3/12 (25%) of TMZ-alone patients and 4/24 (16.7%) on the RT arms. OS did not statistically differ between arms (comparison underpowered). After adjustment for isocitrate dehydrogenase (IDH) status (mutated/wildtype) in a Cox regression model utilizing IDH and RT treatment status as covariables (arm C vs pooled arms A + B), PFS remained shorter for patients not receiving RT (HR = 3.33; 95% CI: 1.31, 8.45; P = 0.011), but not OS ((HR = 2.78; 95% CI: 0.58, 13.22, P = 0.20). Grade 3+ adverse events occurred in 25%, 42%, and 33% of patients (arms A, B, and C). There were no differences between arms in neurocognitive decline comparing baseline to 3 months. CONCLUSIONS: TMZ-alone patients experienced significantly shorter PFS than patients treated on the RT arms. The ongoing CODEL trial has been redesigned to compare RT + PCV versus RT + TMZ.
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