The impact of lag time to cancer diagnosis and treatment on clinical outcomes prior to the COVID-19 pandemic: a scoping review of systematic reviews and meta-analyses
Abstract
Background: The COVID-19 pandemic has disrupted cancer care, raising concerns regarding the impact of wait time, or 'lag time', on clinical outcomes. We aimed to contextualize pandemic-related lag times by mapping pre-pandemic evidence from systematic reviews and/or meta-analyses on the association between lag time to cancer diagnosis and treatment with mortality- and morbidity-related outcomes.
Methods: We systematically searched MEDLINE, EMBASE, Web of Science, and Cochrane Library of Systematic Reviews for reviews published prior to the pandemic (1 January 2010-31 December 2019). We extracted data on methodological characteristics, lag time interval start and endpoints, qualitative findings from systematic reviews, and pooled risk estimates of mortality- (i.e., overall survival) and morbidity- (i.e., local regional control) related outcomes from meta-analyses. We categorized lag times according to milestones across the cancer care continuum and summarized outcomes by cancer site and lag time interval.
Results: We identified 9,032 records through database searches, of which 29 were eligible. We classified 33 unique types of lag time intervals across 10 cancer sites, of which breast, colorectal, head and neck, and ovarian cancers were investigated most. Two systematic reviews investigating lag time to diagnosis reported different findings regarding survival outcomes among pediatric patients with Ewing's sarcomas or central nervous system tumours. Comparable risk estimates of mortality were found for lag time intervals from surgery to adjuvant chemotherapy for breast, colorectal, and ovarian cancers. Risk estimates of pathologic complete response indicated an optimal time window of 7-8 weeks for neoadjuvant chemotherapy completion prior to surgery for rectal cancers. In comparing methods across meta-analyses on the same cancer sites, lag times, and outcomes, we identified critical variations in lag time research design.
Conclusions: Our review highlighted measured associations between lag time and cancer-related outcomes and identified the need for a standardized methodological approach in areas such as lag time definitions and accounting for the waiting-time paradox. Prioritization of lag time research is integral for revised cancer care guidelines under pandemic contingency and assessing the pandemic's long-term effect on patients with cancer.
Funding: The present work was supported by the Canadian Institutes of Health Research (CIHR-COVID-19 Rapid Research Funding opportunity, VR5-172666 grant to Eduardo L. Franco). Parker Tope, Eliya Farah, and Rami Ali each received an MSc. stipend from the Gerald Bronfman Department of Oncology, McGill University.
Data availability
This is a scoping review of peer-reviewed scientific literature. Data used came from scientific manuscripts which can be accessed online. All relevant information is included in the manuscript.
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Author details
Funding
Canadian Institutes of Health Research (VR5-172666)
- Eduardo L Franco
McGill University, Gerald Bronfman Department of Oncology (MSc Stipend)
- Parker Tope
- Eliya Farah
- Rami Ali
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
© 2023, Tope et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Background:
Biological aging exhibits heterogeneity across multi-organ systems. However, it remains unclear how is lifestyle associated with overall and organ-specific aging and which factors contribute most in Southwest China.
Methods:
This study involved 8396 participants who completed two surveys from the China Multi-Ethnic Cohort (CMEC) study. The healthy lifestyle index (HLI) was developed using five lifestyle factors: smoking, alcohol, diet, exercise, and sleep. The comprehensive and organ-specific biological ages (BAs) were calculated using the Klemera–Doubal method based on longitudinal clinical laboratory measurements, and validation were conducted to select BA reflecting related diseases. Fixed effects model was used to examine the associations between HLI or its components and the acceleration of validated BAs. We further evaluated the relative contribution of lifestyle components to comprehension and organ systems BAs using quantile G-computation.
Results:
About two-thirds of participants changed HLI scores between surveys. After validation, three organ-specific BAs (the cardiopulmonary, metabolic, and liver BAs) were identified as reflective of specific diseases and included in further analyses with the comprehensive BA. The health alterations in HLI showed a protective association with the acceleration of all BAs, with a mean shift of –0.19 (95% CI −0.34, –0.03) in the comprehensive BA acceleration. Diet and smoking were the major contributors to overall negative associations of five lifestyle factors, with the comprehensive BA and metabolic BA accounting for 24% and 55% respectively.
Conclusions:
Healthy lifestyle changes were inversely related to comprehensive and organ-specific biological aging in Southwest China, with diet and smoking contributing most to comprehensive and metabolic BA separately. Our findings highlight the potential of lifestyle interventions to decelerate aging and identify intervention targets to limit organ-specific aging in less-developed regions.
Funding:
This work was primarily supported by the National Natural Science Foundation of China (Grant No. 82273740) and Sichuan Science and Technology Program (Natural Science Foundation of Sichuan Province, Grant No. 2024NSFSC0552). The CMEC study was funded by the National Key Research and Development Program of China (Grant No. 2017YFC0907305, 2017YFC0907300). The sponsors had no role in the design, analysis, interpretation, or writing of this article.