Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2020 Apr 27;22(7):918-927.
doi: 10.1093/neuonc/noaa111. Online ahead of print.

A Quantitative Framework for Modeling COVID-19 Risk During Adjuvant Therapy Using Published Randomized Trials of Glioblastoma in the Elderly

Shervin Tabrizi  1   2 , Lorenzo Trippa  3 , Daniel Cagney  2 , Shyam Tanguturi  2 , Steffen Ventz  3 , Geoffrey Fell  3 , Patrick Y Wen  4 , Brian M Alexander  2 , Rifaquat Rahman  2
Affiliations

A Quantitative Framework for Modeling COVID-19 Risk During Adjuvant Therapy Using Published Randomized Trials of Glioblastoma in the Elderly

Shervin Tabrizi et al. Neuro Oncol. .

Abstract

Background: During the ongoing COVID-19 pandemic, contact with the healthcare system for cancer treatment can increase risk of infection and associated mortality. Treatment recommendations must consider this risk for elderly and vulnerable cancer patients. We re-analyzed trials in elderly glioblastoma (GBM) patients, incorporating COVID-19 risk, in order to provide a quantitative framework for comparing different radiation (RT) fractionation schedules on patient outcomes.

Methods: We extracted individual patient-level data (IPLD) for 1,321 patients from Kaplan-Meier curves from five randomized trials on treatment of elderly GBM patients including available subanalyses based on MGMT methylation status. We simulated trial data with incorporation of COVID-19 associated mortality risk in several scenarios (low, medium, and high infection and mortality risks). Median overall survival and hazard ratios were calculated for each simulation replicate.

Results: Our simulations reveal how COVID-19-associated risks affect survival under different treatment regimens. Hypofractionated RT with concurrent and adjuvant temozolomide (TMZ) demonstrated the best outcomes in low and medium risk scenarios. In frail elderly patients, shorter courses of RT are preferable. In patients with methylated MGMT receiving single modality treatment, TMZ-alone treatment approaches may be an option in settings with high COVID-19-associated risk.

Conclusions: Incorporation of COVID-19-associated risk models into analysis of randomized trials can help guide clinical decisions during this pandemic. In elderly GBM patients, our results support prioritization of hypofractionated RT and highlight the utility of MGMT methylation status in decision-making in pandemic scenarios. Our quantitative framework can serve as a model for assessing COVID-19 risk associated with treatment across neuro-oncology.

Keywords: COVID-19; Glioblastoma; elderly; randomized controlled trials.

PubMed Disclaimer

Figures

Fig. 1
Fig. 1
Survival curves from simulations of the Nordic trial with low risk, medium risk, and high risk COVID-19 pandemic scenarios. One thousand replicates were generated for each scenario, and the shaded bands represent the upper and lower 95% CI bounds for Kaplan–Meier estimates across the replicates.
Fig. 2
Fig. 2
Survival curves from simulations for MGMT methylated patients enrolled in the CCTG/EORTC hypofractionated chemoradiation trial and the Nordic trial, under low risk, medium risk, and high risk COVID-19 pandemic scenarios.
See this image and copyright information in PMC

References

    1. WHO Director-General’s Opening Remarks at the Media Briefing on COVID-19, 11 March 2020. https://www.who.int/dg/speeches/detail/who-director-general-s-opening-re.... Accessed March 28, 2020.
    1. Kamboj M, Sepkowitz KA. Nosocomial infections in patients with cancer. Lancet Oncol. 2009;10(6):589–597. - PubMed
    1. Liang W, Guan W, Chen R, et al. . Cancer patients in SARS-CoV-2 infection: a nationwide analysis in China. Lancet Oncol. 2020;21(3):335–337. - PMC - PubMed
    1. Braunstein LZ, Gillespie EF, Hong L, et al. . Breast radiotherapy under COVID-19 pandemic resource constraints—approaches to defer or shorten treatment from a comprehensive cancer center in the United States. Adv Radiat Oncol. 2020;0(0). doi:10.1016/j.adro.2020.03.013 - DOI - PMC - PubMed
    1. Zaorsky NG, Yu JB, McBride SM, et al. . Prostate cancer radiotherapy recommendations in response to COVID-19. Adv Radiat Oncol. 2020;0(0). doi:10.1016/j.adro.2020.03.010 - DOI - PMC - PubMed