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Temozolomide chronotherapy in patients with glioblastoma: a retrospective single-institute study
BACKGROUND: Chronotherapy is an innovative approach to improving survival through timed delivery of anti-cancer treatments according to patient daily rhythms. Temozolomide (TMZ) is a standard-of-care chemotherapeutic agent for glioblastoma (GBM). Whether timing of TMZ administration affects GBM pati...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8086242/ https://www.ncbi.nlm.nih.gov/pubmed/33959716 http://dx.doi.org/10.1093/noajnl/vdab041 |
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author | Damato, Anna R Luo, Jingqin Katumba, Ruth G N Talcott, Grayson R Rubin, Joshua B Herzog, Erik D Campian, Jian L |
author_facet | Damato, Anna R Luo, Jingqin Katumba, Ruth G N Talcott, Grayson R Rubin, Joshua B Herzog, Erik D Campian, Jian L |
author_sort | Damato, Anna R |
collection | PubMed |
description | BACKGROUND: Chronotherapy is an innovative approach to improving survival through timed delivery of anti-cancer treatments according to patient daily rhythms. Temozolomide (TMZ) is a standard-of-care chemotherapeutic agent for glioblastoma (GBM). Whether timing of TMZ administration affects GBM patient outcome has not previously been studied. We sought to evaluate maintenance TMZ chronotherapy on GBM patient survival. METHODS: This retrospective study reviewed patients with newly diagnosed GBM from January 1, 2010 to December 31, 2018 at Washington University School of Medicine who had surgery, chemoradiation, and were prescribed TMZ to be taken in the morning or evening. The Kaplan–Meier method and Cox regression model were used for overall survival (OS) analyses. The propensity score method accounted for potential observational study biases. The restricted mean survival time (RMST) method was performed where the proportional hazard assumption was violated. RESULTS: We analyzed 166 eligible GBM patients with a median follow-up of 5.07 years. Patients taking morning TMZ exhibited longer OS compared to evening (median OS, 95% confidence interval [CI] = 1.43, 1.12–1.92 vs 1.13, 0.84–1.58 years) with a significant year 1 RMST difference (−0.09, 95% CI: −0.16 to −0.018). Among MGMT-methylated patients, median OS was 6 months longer for AM patients with significant RMST differences at years 1 (−0.13, 95% CI = −0.24 to −0.019) to 2.5 (−0.43, 95% CI = −0.84 to −0.028). Superiority of morning TMZ at years 1, 2, and 5 (all P < .05) among all patients was supported by RMST difference regression after adjusting for confounders. CONCLUSIONS: Our study presents preliminary evidence for the benefit of TMZ chronotherapy to GBM patient survival. This impact is more pronounced in MGMT-methylated patients. |
format | Online Article Text |
id | pubmed-8086242 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-80862422021-05-05 Temozolomide chronotherapy in patients with glioblastoma: a retrospective single-institute study Damato, Anna R Luo, Jingqin Katumba, Ruth G N Talcott, Grayson R Rubin, Joshua B Herzog, Erik D Campian, Jian L Neurooncol Adv Clinical Investigations BACKGROUND: Chronotherapy is an innovative approach to improving survival through timed delivery of anti-cancer treatments according to patient daily rhythms. Temozolomide (TMZ) is a standard-of-care chemotherapeutic agent for glioblastoma (GBM). Whether timing of TMZ administration affects GBM patient outcome has not previously been studied. We sought to evaluate maintenance TMZ chronotherapy on GBM patient survival. METHODS: This retrospective study reviewed patients with newly diagnosed GBM from January 1, 2010 to December 31, 2018 at Washington University School of Medicine who had surgery, chemoradiation, and were prescribed TMZ to be taken in the morning or evening. The Kaplan–Meier method and Cox regression model were used for overall survival (OS) analyses. The propensity score method accounted for potential observational study biases. The restricted mean survival time (RMST) method was performed where the proportional hazard assumption was violated. RESULTS: We analyzed 166 eligible GBM patients with a median follow-up of 5.07 years. Patients taking morning TMZ exhibited longer OS compared to evening (median OS, 95% confidence interval [CI] = 1.43, 1.12–1.92 vs 1.13, 0.84–1.58 years) with a significant year 1 RMST difference (−0.09, 95% CI: −0.16 to −0.018). Among MGMT-methylated patients, median OS was 6 months longer for AM patients with significant RMST differences at years 1 (−0.13, 95% CI = −0.24 to −0.019) to 2.5 (−0.43, 95% CI = −0.84 to −0.028). Superiority of morning TMZ at years 1, 2, and 5 (all P < .05) among all patients was supported by RMST difference regression after adjusting for confounders. CONCLUSIONS: Our study presents preliminary evidence for the benefit of TMZ chronotherapy to GBM patient survival. This impact is more pronounced in MGMT-methylated patients. Oxford University Press 2021-03-02 /pmc/articles/PMC8086242/ /pubmed/33959716 http://dx.doi.org/10.1093/noajnl/vdab041 Text en © The Author(s) 2021. Published by Oxford University Press, the Society for Neuro-Oncology and the European Association of Neuro-Oncology. https://creativecommons.org/licenses/by-nc/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License (http://creativecommons.org/licenses/by-nc/4.0/ (https://creativecommons.org/licenses/by-nc/4.0/) ), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com |
spellingShingle | Clinical Investigations Damato, Anna R Luo, Jingqin Katumba, Ruth G N Talcott, Grayson R Rubin, Joshua B Herzog, Erik D Campian, Jian L Temozolomide chronotherapy in patients with glioblastoma: a retrospective single-institute study |
title | Temozolomide chronotherapy in patients with glioblastoma: a retrospective single-institute study |
title_full | Temozolomide chronotherapy in patients with glioblastoma: a retrospective single-institute study |
title_fullStr | Temozolomide chronotherapy in patients with glioblastoma: a retrospective single-institute study |
title_full_unstemmed | Temozolomide chronotherapy in patients with glioblastoma: a retrospective single-institute study |
title_short | Temozolomide chronotherapy in patients with glioblastoma: a retrospective single-institute study |
title_sort | temozolomide chronotherapy in patients with glioblastoma: a retrospective single-institute study |
topic | Clinical Investigations |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8086242/ https://www.ncbi.nlm.nih.gov/pubmed/33959716 http://dx.doi.org/10.1093/noajnl/vdab041 |
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