Deborah T Blumenthal1, Minhee Won2, Minesh P Mehta3, Mark R Gilbert4, Paul D Brown5,6, Felix Bokstein1, David G Brachman7, Maria Werner-Wasik8, Grant K Hunter9, Egils Valeinis10, Kirsten Hopkins11, Luis Souhami12, Steven P Howard13, Frank S Lieberman14, Dennis C Shrieve15, Merideth M Wendland16, Cliff G Robinson17, Peixin Zhang2, Benjamin W Corn1. 1. Tel Aviv Sourasky Medical Center, Tel Aviv, Israel. 2. NRG Oncology Statistics and Data Management Center, Philadelphia, Pennsylvania, USA. 3. Baptist Hospital of Miami, Miami, Florida, USA. 4. National Institutes of Health Clinical Center, Bethesda, Maryland, USA. 5. University of Texas-MD Anderson Cancer Center, Houston, Texas, USA. 6. Mayo Clinic, Rochester, Minnesota, USA. 7. Saint Joseph's Hospital and Medical Center ACCRUALS for Arizona Oncology Services Foundation, Phoenix, Arizona, USA. 8. Thomas Jefferson University Hospital, Philadelphia, Pennsylvania, USA. 9. Intermountain Medical Center, Murray, Utah, USA. 10. Paulus Stradins Clinical University Hospital-EORTC, Riga, Latvia. 11. Bristol Oncology Center-EORTC, Bristol, United Kingdom. 12. McGill University, Montreal, Quebec, Canada. 13. University of Wisconsin Hospital, Madison, Wisconsin, USA. 14. UPMC-Shadyside Hospital, Pittsburgh, Pennsylvania, USA. 15. University of Utah Health Science Center, Salt Lake City, Utah, USA. 16. Willamette Valley Cancer Institute, Eugene, Oregon, USA. 17. Washington University, St Louis, Missouri, USA.
Abstract
Background: We previously reported the unexpected finding of significantly improved survival for newly diagnosed glioblastoma in patients when radiation therapy (RT) was initiated later (>4 wk post-op) compared with earlier (≤2 wk post-op). In that analysis, data were analyzed from 2855 patients from 16 NRG Oncology/Radiotherapy Oncology Group (RTOG) trials conducted prior to the era of concurrenttemozolomide (TMZ) with RT. We now report on 1395 newly diagnosed glioblastomas from 2 studies, treated withRT and concurrent TMZ followed by adjuvant TMZ. Our hypothesis was that concurrent TMZ has a synergistic/radiosensitizing mechanism, making RT timing less significant. Methods: Data from patients treated with TMZ-based chemoradiation from NRG Oncology/RTOG 0525 and 0825 were analyzed. An analysis comparable to our prior study was performed to determine whether there was still an impact on survival by delaying RT. Overall survival (OS) was investigated using the Kaplan-Meier method and Cox proportional hazards model. Early progression (during time of diagnosis to 30 days after RT completion) was analyzed using the chi-square test. Results: Given the small number of patients who started RT early following surgery, comparisons were made between >4 and ≤4 weeks delay of radiation from time of operation. There was no statistically significant difference in OS (hazard ratio = 0.93; P = 0.29; 95% CI: 0.80-1.07) after adjusting for known prognostic factors (recursive partitioning analysis and O6-methylguanine-DNA methyltransferase methylation status). Similarly, the rate of early progression did not differ significantly (P = 0.63). Conclusions: We did not observe a significant prognostic influence of delaying radiation when given concurrently with TMZ for newly diagnosed glioblastoma. The effects of early (1-3 wk post-op) or late (>5 wk) initiation of radiation tested in our prior study could not be replicated.
RCT Entities:
Background: We previously reported the unexpected finding of significantly improved survival for newly diagnosed glioblastoma in patients when radiation therapy (RT) was initiated later (>4 wk post-op) compared with earlier (≤2 wk post-op). In that analysis, data were analyzed from 2855 patients from 16 NRG Oncology/Radiotherapy Oncology Group (RTOG) trials conducted prior to the era of concurrent temozolomide (TMZ) with RT. We now report on 1395 newly diagnosed glioblastomas from 2 studies, treated with RT and concurrent TMZ followed by adjuvant TMZ. Our hypothesis was that concurrent TMZ has a synergistic/radiosensitizing mechanism, making RT timing less significant. Methods: Data from patients treated with TMZ-based chemoradiation from NRG Oncology/RTOG 0525 and 0825 were analyzed. An analysis comparable to our prior study was performed to determine whether there was still an impact on survival by delaying RT. Overall survival (OS) was investigated using the Kaplan-Meier method and Cox proportional hazards model. Early progression (during time of diagnosis to 30 days after RT completion) was analyzed using the chi-square test. Results: Given the small number of patients who started RT early following surgery, comparisons were made between >4 and ≤4 weeks delay of radiation from time of operation. There was no statistically significant difference in OS (hazard ratio = 0.93; P = 0.29; 95% CI: 0.80-1.07) after adjusting for known prognostic factors (recursive partitioning analysis and O6-methylguanine-DNA methyltransferase methylation status). Similarly, the rate of early progression did not differ significantly (P = 0.63). Conclusions: We did not observe a significant prognostic influence of delaying radiation when given concurrently with TMZ for newly diagnosed glioblastoma. The effects of early (1-3 wk post-op) or late (>5 wk) initiation of radiation tested in our prior study could not be replicated.
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