Antonio Dono1,2, Ping Zhu1, Emma Holmes1, Takeshi Takayasu2, Jay-Jiguang Zhu1,3, Angel I Blanco1,3, Sigmund Hsu1,3, Meenakshi B Bhattacharjee2,3, Leomar Y Ballester2,3, Dong H Kim1,3, Yoshua Esquenazi1,3, Nitin Tandon4,5,6,7. 1. Vivian L. Smith Department of Neurosurgery, McGovern Medical School at UT Health, Houston, TX, USA. 2. Department of Pathology and Laboratory Medicine, McGovern Medical School at UT Health, Houston, TX, USA. 3. Memorial Hermann Hospital-TMC, Houston, TX, USA. 4. Vivian L. Smith Department of Neurosurgery, McGovern Medical School at UT Health, Houston, TX, USA. Nitin.Tandon@uth.tmc.edu. 5. Memorial Hermann Hospital-TMC, Houston, TX, USA. Nitin.Tandon@uth.tmc.edu. 6. Texas Institute for Restorative Neurotechnologies, UT Health, Houston, TX, USA. Nitin.Tandon@uth.tmc.edu. 7. Department of Neurosurgery, Texas Institute of Restorative Neurotechnology, McGovern Medical School at UT Health, 6400 Fannin Street, Suite 2800, Houston, TX, 77030, USA. Nitin.Tandon@uth.tmc.edu.
Abstract
INTRODUCTION: Recurrent glioblastoma (rGBM) prognosis is dismal. In the absence of effective adjuvant treatments for rGBM, re-resections remain prominent in our arsenal. This study evaluates the impact of reoperation on post-progression survival (PPS) considering rGBM genetic makeup. METHODS: To assess the genetic heterogeneity and treatment-related changes (TRC) roles in re-operated or medically managed rGBMs, we compiled demographic, clinical, histopathological, and next-generation genetic sequencing (NGS) characteristics of these tumors from 01/2005 to 10/2019. Survival data and reoperation were analyzed using conventional and random survival forest analysis (RSF). RESULTS: Patients harboring CDKN2A/B loss (p = 0.017) and KDR mutations (p = 0.031) had notably shorter survival. Reoperation or bevacizumab were associated with longer PPS (11.2 vs. 7.4-months, p = 0.006; 13.1 vs 6.2, p < 0.001). Reoperated patients were younger, had better performance status and greater initial resection. In 136/273 (49%) rGBMs undergoing re-operation, CDKN2A/B loss (p = 0.03) and KDR mutations (p = 0.02) were associated with shorter survival. In IDH-WT rGBMs with NGS data (n = 166), reoperation resulted in 7.0-month longer survival (p = 0.004) than those managed medically. This reoperation benefit was independently identified by RSF analysis. Stratification analysis revealed that EGFR-mutant, CDKN2A/B-mutant, NF1-WT, and TP53-WT rGBM IDH-WT subgroups benefit most from reoperation (p = 0.03). Lastly, whether or not TRC was prominent at re-operation does not have any significant impact on PPS (10.5 vs. 11.5-months, p = 0.77). CONCLUSIONS: Maximal safe re-resection significantly lengthens PPS regardless of genetic makeup, but reoperations are especially beneficial for IDH-WT rGBMs with EGFR and CDKN2A/B mutations with TP53-WT, and NF1-WT. Histopathology at recurrence may be an imperfect gauge of disease severity at progression and the imaging progression may be more reflective of the prognosis.
INTRODUCTION: Recurrent glioblastoma (rGBM) prognosis is dismal. In the absence of effective adjuvant treatments for rGBM, re-resections remain prominent in our arsenal. This study evaluates the impact of reoperation on post-progression survival (PPS) considering rGBM genetic makeup. METHODS: To assess the genetic heterogeneity and treatment-related changes (TRC) roles in re-operated or medically managed rGBMs, we compiled demographic, clinical, histopathological, and next-generation genetic sequencing (NGS) characteristics of these tumors from 01/2005 to 10/2019. Survival data and reoperation were analyzed using conventional and random survival forest analysis (RSF). RESULTS: Patients harboring CDKN2A/B loss (p = 0.017) and KDR mutations (p = 0.031) had notably shorter survival. Reoperation or bevacizumab were associated with longer PPS (11.2 vs. 7.4-months, p = 0.006; 13.1 vs 6.2, p < 0.001). Reoperated patients were younger, had better performance status and greater initial resection. In 136/273 (49%) rGBMs undergoing re-operation, CDKN2A/B loss (p = 0.03) and KDR mutations (p = 0.02) were associated with shorter survival. In IDH-WT rGBMs with NGS data (n = 166), reoperation resulted in 7.0-month longer survival (p = 0.004) than those managed medically. This reoperation benefit was independently identified by RSF analysis. Stratification analysis revealed that EGFR-mutant, CDKN2A/B-mutant, NF1-WT, and TP53-WT rGBM IDH-WT subgroups benefit most from reoperation (p = 0.03). Lastly, whether or not TRC was prominent at re-operation does not have any significant impact on PPS (10.5 vs. 11.5-months, p = 0.77). CONCLUSIONS: Maximal safe re-resection significantly lengthens PPS regardless of genetic makeup, but reoperations are especially beneficial for IDH-WT rGBMs with EGFR and CDKN2A/B mutations with TP53-WT, and NF1-WT. Histopathology at recurrence may be an imperfect gauge of disease severity at progression and the imaging progression may be more reflective of the prognosis.
Authors: Robert H Press; Jim Zhong; Saumya S Gurbani; Brent D Weinberg; Bree R Eaton; Hyunsuk Shim; Hui-Kuo G Shu Journal: Neurosurgery Date: 2019-08-01 Impact factor: 4.654
Authors: Johanna Quick; Florian Gessler; Stephan Dützmann; Elke Hattingen; Patrick N Harter; Lutz M Weise; Kea Franz; Volker Seifert; Christian Senft Journal: J Neurooncol Date: 2014-02-15 Impact factor: 4.130
Authors: Enrico Franceschi; Marco Bartolotti; Alicia Tosoni; Stefania Bartolini; Carmelo Sturiale; Antonio Fioravanti; Eugenio Pozzati; Renato Galzio; Andrea Talacchi; Lorenzo Volpin; Luca Morandi; Daniela Danieli; Mario Ermani; Alba A Brandes Journal: Anticancer Res Date: 2015-03 Impact factor: 2.480
Authors: Cyril Neftel; Julie Laffy; Mariella G Filbin; Toshiro Hara; Marni E Shore; Gilbert J Rahme; Alyssa R Richman; Dana Silverbush; McKenzie L Shaw; Christine M Hebert; John Dewitt; Simon Gritsch; Elizabeth M Perez; L Nicolas Gonzalez Castro; Xiaoyang Lan; Nicholas Druck; Christopher Rodman; Danielle Dionne; Alexander Kaplan; Mia S Bertalan; Julia Small; Kristine Pelton; Sarah Becker; Dennis Bonal; Quang-De Nguyen; Rachel L Servis; Jeremy M Fung; Ravindra Mylvaganam; Lisa Mayr; Johannes Gojo; Christine Haberler; Rene Geyeregger; Thomas Czech; Irene Slavc; Brian V Nahed; William T Curry; Bob S Carter; Hiroaki Wakimoto; Priscilla K Brastianos; Tracy T Batchelor; Anat Stemmer-Rachamimov; Maria Martinez-Lage; Matthew P Frosch; Ivan Stamenkovic; Nicolo Riggi; Esther Rheinbay; Michelle Monje; Orit Rozenblatt-Rosen; Daniel P Cahill; Anoop P Patel; Tony Hunter; Inder M Verma; Keith L Ligon; David N Louis; Aviv Regev; Bradley E Bernstein; Itay Tirosh; Mario L Suvà Journal: Cell Date: 2019-07-18 Impact factor: 41.582