Shehryar Sheikh1, Tom Radivoyevitch2, Jill S Barnholtz-Sloan3, Michael Vogelbaum4. 1. Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, OH, USA. 2. Department of Quantitative Health Sciences, Cleveland Clinic Foundation, OH, USA. 3. Department of Population and Quantitative Health Sciences, Case Western Reserve University School of Medicine, Cleveland, OH, USA. 4. Department of Neuro-Oncology, Moffitt Cancer Center, Tampa, FL, USA.
Abstract
BACKGROUND: Historical controls continue to be used in early-phase brain tumor trials. We aim to show that historical changes in survival trends for glioblastoma (GBM) call into question the use of noncontemporary controls. METHODS: We analyzed data from 46 106 primary GBM cases from the SEER database (1998-2016). We performed trend analysis on survival outcomes (2-year survival probability, median survival, and hazard ratios) and patient characteristics (age, sex, resection extent, and treatment type). RESULTS: In 2005-2016 (ie, the post-Stupp protocol era), fitting a parameter independently to each year, there was a demonstrable increase in median survival (R2 = 0.81, P < .001) and 2-year survival probability (R2 = 0.55, P = .006) for GBM. Trend analysis of the hazard ratio showed a significant time-dependent downward trend (R2 = 0.62, P = .002). When controlling, via multivariable Cox regression modeling, for age, sex, resection extent, and treatment type, there was a persistent downward trend in hazard ratios with increases in calendar time, especially in the most recent data. CONCLUSION: Contemporary GBM patients face a different overall hazard profile from their historical counterparts, which is evident in changes in measures of patient survival and parametric hazard modeling. Though there was a plateau in these measures before 2005 (pre-Stupp protocol), there is no evidence of a new plateau in recent years even when controlling for known prognostic factors (age, sex, resection extent, and treatment type), suggesting that it may be insufficient to match contemporary patients and noncontemporary controls on the basis of these factors.
BACKGROUND: Historical controls continue to be used in early-phase brain tumor trials. We aim to show that historical changes in survival trends for glioblastoma (GBM) call into question the use of noncontemporary controls. METHODS: We analyzed data from 46 106 primary GBM cases from the SEER database (1998-2016). We performed trend analysis on survival outcomes (2-year survival probability, median survival, and hazard ratios) and patient characteristics (age, sex, resection extent, and treatment type). RESULTS: In 2005-2016 (ie, the post-Stupp protocol era), fitting a parameter independently to each year, there was a demonstrable increase in median survival (R2 = 0.81, P < .001) and 2-year survival probability (R2 = 0.55, P = .006) for GBM. Trend analysis of the hazard ratio showed a significant time-dependent downward trend (R2 = 0.62, P = .002). When controlling, via multivariable Cox regression modeling, for age, sex, resection extent, and treatment type, there was a persistent downward trend in hazard ratios with increases in calendar time, especially in the most recent data. CONCLUSION: Contemporary GBM patients face a different overall hazard profile from their historical counterparts, which is evident in changes in measures of patient survival and parametric hazard modeling. Though there was a plateau in these measures before 2005 (pre-Stupp protocol), there is no evidence of a new plateau in recent years even when controlling for known prognostic factors (age, sex, resection extent, and treatment type), suggesting that it may be insufficient to match contemporary patients and noncontemporary controls on the basis of these factors.
Authors: John H Sampson; Amy B Heimberger; Gary E Archer; Kenneth D Aldape; Allan H Friedman; Henry S Friedman; Mark R Gilbert; James E Herndon; Roger E McLendon; Duane A Mitchell; David A Reardon; Raymond Sawaya; Robert J Schmittling; Weiming Shi; James J Vredenburgh; Darell D Bigner Journal: J Clin Oncol Date: 2010-10-04 Impact factor: 44.544
Authors: Matthew Koshy; John L Villano; Therese A Dolecek; Andrew Howard; Usama Mahmood; Steven J Chmura; Ralph R Weichselbaum; Bridget J McCarthy Journal: J Neurooncol Date: 2011-10-09 Impact factor: 4.130
Authors: Annick Desjardins; Matthias Gromeier; James E Herndon; Nike Beaubier; Dani P Bolognesi; Allan H Friedman; Henry S Friedman; Frances McSherry; Andrea M Muscat; Smita Nair; Katherine B Peters; Dina Randazzo; John H Sampson; Gordana Vlahovic; William T Harrison; Roger E McLendon; David Ashley; Darell D Bigner Journal: N Engl J Med Date: 2018-06-26 Impact factor: 91.245
Authors: Michael Weller; Nicholas Butowski; David D Tran; Lawrence D Recht; Michael Lim; Hal Hirte; Lynn Ashby; Laszlo Mechtler; Samuel A Goldlust; Fabio Iwamoto; Jan Drappatz; Donald M O'Rourke; Mark Wong; Mark G Hamilton; Gaetano Finocchiaro; James Perry; Wolfgang Wick; Jennifer Green; Yi He; Christopher D Turner; Michael J Yellin; Tibor Keler; Thomas A Davis; Roger Stupp; John H Sampson Journal: Lancet Oncol Date: 2017-08-23 Impact factor: 41.316
Authors: M Lacroix; D Abi-Said; D R Fourney; Z L Gokaslan; W Shi; F DeMonte; F F Lang; I E McCutcheon; S J Hassenbusch; E Holland; K Hess; C Michael; D Miller; R Sawaya Journal: J Neurosurg Date: 2001-08 Impact factor: 5.115
Authors: Stuart A Grossman; Xiaobu Ye; Marc Chamberlain; Tom Mikkelsen; Tracy Batchelor; Serena Desideri; Steven Piantadosi; Joy Fisher; Howard A Fine Journal: J Clin Oncol Date: 2009-07-27 Impact factor: 44.544
Authors: Roger Stupp; Monika E Hegi; Thierry Gorlia; Sara C Erridge; James Perry; Yong-Kil Hong; Kenneth D Aldape; Benoit Lhermitte; Torsten Pietsch; Danica Grujicic; Joachim Peter Steinbach; Wolfgang Wick; Rafał Tarnawski; Do-Hyun Nam; Peter Hau; Astrid Weyerbrock; Martin J B Taphoorn; Chiung-Chyi Shen; Nalini Rao; László Thurzo; Ulrich Herrlinger; Tejpal Gupta; Rolf-Dieter Kortmann; Krystyna Adamska; Catherine McBain; Alba A Brandes; Joerg Christian Tonn; Oliver Schnell; Thomas Wiegel; Chae-Yong Kim; Louis Burt Nabors; David A Reardon; Martin J van den Bent; Christine Hicking; Andriy Markivskyy; Martin Picard; Michael Weller Journal: Lancet Oncol Date: 2014-08-19 Impact factor: 41.316
Authors: Justin T Low; Quinn T Ostrom; Gino Cioffi; Corey Neff; Kristin A Waite; Carol Kruchko; Jill S Barnholtz-Sloan Journal: Neurooncol Pract Date: 2022-02-22
Authors: Toni Q Cao; Derek A Wainwright; Catalina Lee-Chang; Jason Miska; Adam M Sonabend; Amy B Heimberger; Rimas V Lukas Journal: Cancers (Basel) Date: 2022-08-20 Impact factor: 6.575