Original Article
COVID Collection
A Definitive Prognostication System for Patients With Thoracic Malignancies Diagnosed With Coronavirus Disease 2019: An Update From the TERAVOLT Registry

https://doi.org/10.1016/j.jtho.2021.12.015Get rights and content
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Abstract

Introduction

Patients with thoracic malignancies are at increased risk for mortality from coronavirus disease 2019 (COVID-19), and a large number of intertwined prognostic variables have been identified so far.

Methods

Capitalizing data from the Thoracic Cancers International COVID-19 Collaboration (TERAVOLT) registry, a global study created with the aim of describing the impact of COVID-19 in patients with thoracic malignancies, we used a clustering approach, a fast-backward step-down selection procedure, and a tree-based model to screen and optimize a broad panel of demographics and clinical COVID-19 and cancer characteristics.

Results

As of April 15, 2021, a total of 1491 consecutive eligible patients from 18 countries were included in the analysis. With a mean observation period of 42 days, 361 events were reported with an all-cause case fatality rate of 24.2%. The clustering procedure screened 73 covariates in 13 clusters. A further multivariable logistic regression for the association between clusters and death was performed, resulting in five clusters significantly associated with the outcome. The fast-backward step-down selection procedure then identified the following seven major determinants of death: Eastern Cooperative Oncology Group—performance status (ECOG-PS) (OR = 2.47, 1.87–3.26), neutrophil count (OR = 2.46, 1.76–3.44), serum procalcitonin (OR = 2.37, 1.64–3.43), development of pneumonia (OR = 1.95, 1.48–2.58), C-reactive protein (OR = 1.90, 1.43–2.51), tumor stage at COVID-19 diagnosis (OR = 1.97, 1.46–2.66), and age (OR = 1.71, 1.29–2.26). The receiver operating characteristic analysis for death of the selected model confirmed its diagnostic ability (area under the receiver operating curve = 0.78, 95% confidence interval: 0.75–0.81). The nomogram was able to classify the COVID-19 mortality in an interval ranging from 8% to 90%, and the tree-based model recognized ECOG-PS, neutrophil count, and c-reactive protein as the major determinants of prognosis.

Conclusions

From 73 variables analyzed, seven major determinants of death have been identified. Poor ECOG-PS was found to have the strongest association with poor outcome from COVID-19. With our analysis, we provide clinicians with a definitive prognostication system to help determine the risk of mortality for patients with thoracic malignancies and COVID-19.

Keywords

COVID-19
Cancer
Thoracic
NSCLC
TERAVOLT
Registry

Cited by (0)

Drs Whisenant and Baena contributed equally in this work.

Disclosure: Dr. Whisenant reports receiving support for this research from IASLC/Lung Ambition Alliance and personal royalties/licenses from Anasys Instruments. Dr. Baena reports receiving personal fees from AstraZeneca, Bristol-Myers Squibb, and Roche and nonfinancial support from Angelini. Dr. Cortellini reports receiving speaker fees/grant consultancies from AstraZeneca, Bristol-Myers Squibb, Merck Sharp & Dohme, Roche, Eisai, and Novartis. Dr. Lo Russo reports receiving personal fees from AstraZeneca, Italfarmaco, Lilly, Novartis, Pfizer, and Roche; support for attending meetings/travel from Bristol-Myers Squibb, Italfarmaco, Merck Sharp & Dohme, and Roche; and participation as a DSMB or advisory board member for AstraZeneca, Bristol-Myers Squibb, Merck Sharp & Dohme, and Sanofi. Dr. Porcu reports receiving personal fees from Ipsen and Italfarmaco. Dr. Bestvina declares receiving personal consulting fees from AstraZeneca, Bristol-Myers Squibb, CVS, Genentech, Jazz, Johnson & Johnson, Novartis, Pfizer, Regeneron/Sanofi, Seattle Genetics, and Takeda; speakers bureau for Merck; and institutional contracted research from AstraZeneca and Bristol-Myers Squibb. Dr. Monnet declares receiving travel support from Pfizer, Takeda, and Behringer Ingelheim. Dr. Rogado reports receiving personal fees from Roche, AstraZeneca, Merck, Ferrer, Persan Farma, and Fresenius Kabi; travel expenses from Merck Sharp & Dohme, Bristol-Myers Squibb, Roche, and AstraZeneca; and advisor consultancies from Fresenius Kabi. Dr. Arrieta reports receiving institutional grants and contracts from AstraZeneca, Merck, and Roche and personal payments from AstraZeneca, Boehringer Ingelheim, Lilly, Pfizer, and Roche. Dr. Unk reports receiving personal consulting fees and participation in a data safety monitoring board or advisory board from Amgen, AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Lilly, Merck Sharp & Dohme, Novartis, Pfizer, Roche, and Takeda. Dr. Zhumagaliyeva reports receiving support for the work of this manuscript from the Center for Nuclear Medicine and Oncology of Semey, Semy, Kazakhstan. Dr. Blaquier reports receiving payment for an educational event and travel support from Amgen. Dr. Mountzios reports receiving grants or contracts from AstraZeneca, Bristol-Myers Squibb, Amgen, Gilead Pharmaceuticals, GlaxoSmithKline, Immunomedics, Merck, Merck Sharp & Dohme, Novartis, Roche, and Sanofi; consulting fees from Amgen, AstraZeneca, Bristol-Myers Squibb, GlaxoSmithKline, Merck Sharp & Dohme, Novartis, Pfizer, Roche, Sanofi, and Takeda; and support for meetings/travel from AstraZeneca, Bristol-Myers Squibb, GlaxoSmithKline, Merck Sharp & Dohme, Roche, Sanofi, and Takeda. Dr. Marmarelis reports receiving consulting/honoraria from Boehringer Ingelheim, Novocure, AstraZeneca, Janssen, Takeda, Blueprint Pharmaceuticals, Bristol-Myers Squibb, and Ikena; research support from Eli Lilly, Trizell, Merck, and AstraZeneca; stock from Gilead, Merck, Portola Pharmaceuticals, Bluebird Biosciences, Novartis, Janssen, and Pfizer; and medical writing support for Novartis. Dr. Hirsch reports receiving personal consulting fees from Bristol-Myers Squibb, AstraZeneca/Daiichi, Sanofi/Regeneron, Novartis, Merck, Amgen, and OncoCyte. Dr. Garrido declared having advisory roles or receiving speakers fees from AbbVie, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, GlaxoSmithKline, Janssen, Lilly, Merck Sharp & Dohme, Medscape, Novartis, Pfizer, Roche, Takeda, and TouchIme; support for travel/meetings from AstraZeneca, Bristol-Myers Squibb, and Roche. Dr. Khan reports receiving study funding from the Bristol-Myers Squibb Foundation for Diversity in Clinical Trials and participated to advisory boards for Sanofi Genzyme. Dr. Mascaux reports receiving personal consulting fees from Amgen, AstraZeneca, Bristol-Myers Squibb, Kephren, Merck Sharp & Dohme, Pfizer, Roche, Sanofi, and Takeda; receiving support for travel from AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, and Roche; and having European Patent Application EP19305434.3. Dr. Ceresoli declared having consulting/advisory role for Novocure and speaker’s bureau from Novocure, Zai Laboratory, Merck Sharp & Dohme Oncology, AstraZeneca, and Bristol-Myers Squibb/Medarex. Dr. Fidler reports receiving consulting fees from Silverback, G1 Therapeutics AstraZeneca, Rakuten, Beigene, and Daiichi; speakers bureau from Beigene and Jazz; and research support from Biodesix, Pfizer/EMD Serono, AstraZeneca, Jounce, CytomX Therapeutics, Merck, Novartis, Rakuten, and Alkermes. Dr. Métivier reports receiving personal payment for expert testimony from Merck Sharp & Dohme, Novartis, and Takeda. Dr. Felip reports receiving research funding to the institution from Grant for Oncology Innovation, Merck Healthcare KGAa, and Fundacion Merck Salud; personal consulting fees from Amgen, AstraZeneca, Bayer, Beigene, Boehringer Ingelheim, Bristol-Myers Squibb, Eli Lilly, F. Hoffmann-LaRoche, GlaxoSmithKline, Janssen, Medical Trends, Merck Sharp & Dohme, Merck Serono, Peptomyc, Pfizer, Puma Biotechnology, Regeneron, Sanofi, and Takeda; serving in data safety and monitoring for Syneos Health; serving in the speakers bureau and participating in manuscript writing or educational events for Amgen, AstraZeneca, Bristol-Myers Squibb, Lilly, F. Hoffmann-La Roche, Janssen, Medscape, Merck Sharp & Dohme, Merck Serono, Peervoice, Pfizer, Springer, and Touch Medical; and serving as member of the board for Grifols. Dr. Genova reports receiving personal honoraria for presentations from AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Merck Sharp & Dohme, Roche, and Takeda. Dr. Julien Mazieres reports receiving personal fees from Merck, AstraZeneca, Bristol-Myers Squibb, Merck Sharp & Dohme, Roche, Novartis, Daiichi, and Pfizer and grants from Roche, AstraZeneca, Pierre Fabre. Dr. Bria reports receiving speakers’ and travels’ fees from Merck Sharp & Dohme, AstraZeneca, Pfizer, Eli Lilly, Bristol-Myers Squibb, Novartis, and Roche and institutional research grants from AstraZeneca and Roche. Dr. Puri reports receiving advising/consulting fees from AstraZeneca and G1 Therapeutics. Dr. Tapan declares receiving advisory fees from Sanofi and educational grant from Pfizer. Dr. Reckamp reports receiving personal consulting fees from Amgen, Calithera, AstraZeneca, Blueprint, Boehringer Ingelheim, Daiichi Sankyo, EMD Serono, Genentech, GlaxoSmithKline, Janssen, Lilly, Merck KGA, Mirati, Takeda, and Tesaro; nonfinancial support from Seattle Genetics; and research support to institution from Calithera, Blueprint, Daiichi Sankyo, Genentech, Elevation Oncology, and Janssen. Dr. Nadal reports receiving research support from Bristol-Myers Squibb, Merck Serono, Pfizer, and Roche; personal consulting fees or honoraria from Roche, Bristol-Myers Squibb, Merck Sharp & Dohme, Merck Serono, Pfizer, Lilly, Amgen, Boehringer Ingelheim, AstraZeneca, Takeda, Sanofi, and Bayer; and participation in data safety monitoring board for Apollomics. Dr. Mazzoni reports receiving personal fees for participation in an advisory board from Lilly, Roche, and Takeda. Dr. Grosso reports receiving personal fees for advisory role, speaker engagements, and travel and accommodation expenses from Merck Sharp & Dohme, Novocure, Bristol Meyer Squibb, Boehringer Ingelheim, Pharmamar, and Novartis. Dr. Grosso reports receiving personal fees and travel support from Bristol-Myers Squibb, Boehringer Ingelheim, Merck Sharp & Dohme, Novartis, Novocure, and Pharmamar; speakers bureau for Novocure; and honoraria for educational events from Bristol-Myers Squibb, Boehringer Ingelheim, Merck Sharp & Dohme, and Novartis. Dr. Gomes reports receiving personal payments for educational events from AstraZeneca, Merck, and Roche. Dr. Dingemans reports receiving research support from Amgen; consulting fees from Roche, Boehringer Ingelheim, AstraZeneca, Pharmamar, Bayer, Sanofi, and Amgen; payment for lectures or presentations from Eli Lily, AstraZeneca, Chiesi, Pfizer, Takeda, and Jansen; and participation in data safety monitoring board for Roche and Takeda. Dr. Wakelee reports receiving research funding to the institution from ACEA Biosciences, Arrys Therapeutics, AstraZeneca/Medimmune, Bristol-Myers Squibb, Clovis Oncology, Genentech/Roche, Merck, Novartis, Seattle Genetics, Xcovery, Eli Lilly, Pfizer, and Helsinn; compensated advisory board from AstraZeneca, Xcovery, Jannsen, Daiichi Sankyo, Blueprint, Mirati, and Helsinn; and uncompensated advisory board for Merck, Takeda, Genentech/Roche, and Cellworks. Dr. Peters reports serving as consultant/advisory board member for AbbVie, Amgen, AstraZeneca, Bayer, Beigene, Biocartis, Boehringer Ingelheim, Bristol-Myers Squibb, Clovis, Daiichi Sankyo, Debiopharm, ecancer, Eli Lilly, Elsevier, Foundation Medicine, Illumina, Imedex, IQVIA, Incyte, Janssen, Medscape, Merck Sharp and Dohme, Merck Serono, Merrimack, Novartis, OncologyEducation, Pharma Mar, Phosplatin Therapeutics, PER, Pfizer, PRIME, Regeneron, RMEI, Roche/Genentech, RTP, Sanofi, Seattle Genetics, and Takeda; receiving speaker fees from AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, ecancer, Eli Lilly, Illumina, Imedex, Medscape, Merck Sharp and Dohme, Novartis, PER, Pfizer, Prime, Roche/Genentech, RTP, Sanofi, and Takeda; and receiving grants/research supports from (sub)investigator in trials (institutional financial support for clinical trials) sponsored by Amgen, AstraZeneca, Biodesix, Boehringer Ingelheim, Bristol-Myers Squibb, Clovis, GlaxoSmithKline, Illumina, Lilly, Merck Sharp and Dohme, Merck Serono, Mirati, Novartis, Pfizer, Phosplatin Therapeutics, and Roche/Genentech (all to institution). Dr. Chiara Garassino reports receiving grants and research support to the institution from Eli Lilly, Merck Sharp & Dohme, Pfizer (MISP), AstraZeneca, Merck Sharp & Dohme, Bristol-Myers Squibb, Boehringer Ingelheim, Celgene, Eli Lilly, Ignyta, Incyte, MedImmune, Novartis, Pfizer, Roche, Takeda, Tiziana, Foundation Medicine, GlaxoSmithKline, Spectrum Pharmaceuticals; personal consulting fees from AstraZeneca, Merck Sharp & Dohme, Bristol-Myers Squibb, Boehringer Ingelheim, Celgene, Eli Lilly, Ignyta, Incyte, Inivata, MedImmune, Novartis, Pfizer, Roche, Takeda, Seattle Genetics, Mirati, Daiichi Sankyo, Regeneron, and Merck; speaker fees from AstraZeneca, Merck Sharp and Dohme, and Takeda; and travel and accommodation expenses from Roche. All the declared conflict of interests are outside the submitted work. The authors declare no conflict of interest.

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A complete list of investigators in the TERAVOLT registry that provided data for this analysis is provided in the Supplementary Appendix. With endorsement of the European Society of Medical Oncology, International Association for the Study of Lung Cancer, European Respiratory Society, and the European Thoracic Oncology Platform.