Bioinformatics and in-silico findings reveal medical features and pharmacological targets of biochanin A against colorectal cancer and COVID-19.

Severe mortality due to the COVID-19 pandemic resulted from the lack of effective treatment. Although COVID-19 vaccines are available, their side effects have become a challenge for clinical use in patients with chronic diseases, especially cancer patients. In the current report, we applied network pharmacology and systematic bioinformatics to explore the use of biochanin A in patients with colorectal cancer (CRC) and COVID-19 infection. Using the network pharmacology approach, we identified two clusters of genes involved in immune response (IL1A, IL2, and IL6R) and cell proliferation (CCND1, PPARG, and EGFR) mediated by biochanin A in CRC/COVID-19 condition. The functional analysis of these two gene clusters further illustrated the effects of biochanin A on interleukin-6 production and cytokine-cytokine receptor interaction in CRC/COVID-19 pathology. In addition, pathway analysis demonstrated the control of PI3K-Akt and JAK-STAT signaling pathways by biochanin A in the treatment of CRC/COVID-19. The findings of this study provide a therapeutic option for combination therapy against COVID-19 infection in CRC patients.

Lessons Learned in Managing Patients with Colorectal Cancer During the COVID-19 Pandemic.

OPINION STATEMENT: The COVID-19 pandemic forced us to rapidly and dramatically shift our medical priorities and decision making. With little literature or experience to rely on, the initial priority was to minimize patient exposure to the hospital and to others. It remains unclear whether cancer patients are at higher risk of infection or serious complications, or if it is our traditional therapies that place them to be at higher risk. By far, the greatest negative impact was on screening. Routine colonoscopies were considered elective, and as a result, delays in diagnosis will be felt for years to come. The most positive changes were the incorporation of tele-visits, increased use of oral therapies, alterations in treatment schedules of both chemotherapy and radiation, and an increased emphasis on neoadjuvant therapy. These too will be felt for years to come. The colorectal cancer medical community has responded collaboratively and effectively to maintain treatment and to optimize outcomes for our patients during the COVID-19 pandemic.

Modeling Strategies to Optimize Cancer Screening in USPSTF Guideline-Noncompliant Women.

Importance: In 2018, only half of US women obtained all evidence-based cancer screenings. This proportion may have declined during the COVID-19 pandemic because of social distancing, high-risk factors, and fear. Objective: To evaluate optimal screening strategies in women who obtain some, but not all, US Preventive Services Task Force (USPSTF)-recommended cancer screenings. Design, Setting, and Participants: This modeling study was conducted from January 31, 2017, to July 20, 2020, and used 4 validated mathematical models from the National Cancer Institute's Cancer Intervention and Surveillance Modeling Network using data from 20 million simulated women born in 1965 in the US. Interventions: Forty-five screening strategies were modeled that combined breast, cervical, colorectal, and/or lung cancer (LC) screenings; restricted to 1, 2, 3 or 4 screenings per year; or all eligible screenings once every 5 years. Main Outcomes and Measures: Modeled life-years gained from restricted cancer screenings as a fraction of those attainable from full compliance with USPSTF recommendations (maximum benefits). Results were stratified by LC screening eligibility (LC-eligible/ineligible). We repeated the analysis with 2018 adherence rates, evaluating the increase in adherence required for restricted screenings to have the same population benefit as USPSTF recommendations. Results: This modeling study of 20 million simulated US women found that it was possible to reduce screening intensity to 1 carefully chosen test per year in women who were ineligible for LC screening and 2 tests per year in eligible women while maintaining 94% or more of the maximum benefits. Highly ranked strategies screened for various cancers, but less often than recommended by the USPSTF. For example, among LC-ineligible women who obtained just 1 screening per year, the optimal strategy frequently delayed breast and cervical cancer screenings by 1 year and skipped 3 mammograms entirely. Among LC-eligible women, LC screening was essential; strategies omitting it provided 25% or less of the maximum benefits. The top-ranked strategy restricted to 2 screenings per year was annual LC screening and alternating fecal immunochemical test with mammography (skipping mammograms when due for cervical cancer screening, 97% of maximum benefits). If adherence in a population of LC-eligible women obtaining 2 screenings per year were to increase by 1% to 2% (depending on the screening test), this model suggests that it would achieve the same benefit as USPSTF recommendations at 2018 adherence rates. Conclusions and Relevance: This modeling study of 45 cancer screening strategies suggests that women who are noncompliant with cancer screening guidelines may be able to reduce USPSTF-recommended screening intensity with minimal reduction in overall benefits.

Association of Cancer Screening Deficit in the United States With the COVID-19 Pandemic.

Importance: The COVID-19 pandemic led to sharp declines in cancer screening. However, the total deficit in screening in the US associated with the pandemic and the differential impact on individuals in different geographic regions and by socioeconomic status (SES) index have yet to be fully characterized. Objectives: To quantify the screening rates for breast, colorectal, and prostate cancers associated with the COVID-19 pandemic in different geographic regions and for individuals in different SES index quartiles and estimate the overall cancer screening deficit in 2020 across the US population. Design, Setting, and Participants: This retrospective cohort study uses the HealthCore Integrated Research Database, which comprises single-payer administrative claims data and enrollment information covering approximately 60 million people in Medicare Advantage and commercial health plans from across geographically diverse regions of the US. Participants were individuals in the database in January through July of 2018, 2019, and 2020 without diagnosis of the cancer of interest prior to the analytic index month. Exposures: Analytic index month and year. Main Outcomes and Measures: Receipt of breast, colorectal, or prostate cancer screening. Results: Screening for all 3 cancers declined sharply in March through May of 2020 compared with 2019, with the sharpest decline in April (breast, -90.8%; colorectal, -79.3%; prostate, -63.4%) and near complete recovery of monthly screening rates by July for breast and prostate cancers. The absolute deficit across the US population in screening associated with the COVID-19 pandemic was estimated to be 3.9 million (breast), 3.8 million (colorectal), and 1.6 million (prostate). Geographic differences were observed: the Northeast experienced the sharpest declines in screening, while the West had a slower recovery compared with the Midwest and South. For example, percentage change in breast cancer screening rate (2020 vs 2019) for the month of April ranged from -87.3% (95% CI, -87.9% to -86.7%) in the West to -94.5% (95% CI, -94.9% to -94.1%) in the Northeast (decline). For the month of July, it ranged from -0.3% (95% CI, -2.1% to 1.5%) in the Midwest to -10.6% (-12.6% to -8.4%) in the West (recovery). By SES, the largest screening decline was observed in individuals in the highest SES index quartile, leading to a narrowing in the disparity in cancer screening by SES in 2020. For example, prostate cancer screening rates per 100 000 enrollees for individuals in the lowest and highest SES index quartiles, respectively, were 3525 (95% CI, 3444 to 3607) and 4329 (95% CI, 4271 to 4386) in April 2019 compared with 1535 (95% CI, 1480 to 1589) and 1338 (95% CI, 1306 to 1370) in April 2020. Multivariable analysis showed that telehealth use was associated with higher cancer screening. Conclusions and Relevance: Public health efforts are needed to address the large cancer screening deficit associated with the COVID-19 pandemic, including increased use of screening modalities that do not require a procedure.

The impact of COVID-19 on systemic anticancer treatment delivery in Scotland.

Understanding the impact of the COVID-19 pandemic on systemic anticancer therapy delivery (SACT) is crucial to appreciate the short- and long-term consequences for cancer patients and plan future care. Here, we report real-time national SACT delivery data from NHS Scotland. We demonstrate an initial rapid reduction in patient attendance of 28.7% with subsequent rapid recovery following service redesign. The smallest decrease was seen in breast cancer (19.7%), which also had the most rapid recovery and the largest decrease seen in colorectal cancer (43.4%). Regional variation in the magnitude of impact on SACT delivery was observed, but nadirs occurred at the same time and the rate of recovery was similar across all regions. This recovery reflected a coordinated national approach and associated patient and clinician support structures, which facilitated the creation of COVID-19-protected areas for SACT delivery in Scottish cancer centres enabling rapid sharing of successful and innovative strategies. The data show that these actions have limited the disadvantage to cancer patients.

The COVID-19 Pandemic: Identifying Adaptive Solutions for Colorectal Cancer Screening in Underserved Communities.

The 2019 novel coronavirus disease (COVID-19) pandemic has dramatically impacted numerous health and economic fronts. Because of the stay-at-home mandate and practice of physical distancing, nearly all preventive care measures have been halted, including colorectal cancer (CRC) screening. The health consequences of this temporary suspension are of great concern, particularly for underserved populations, who experience substantial CRC-related disparities. In this commentary, we describe challenges and opportunities to deliver COVID-19-adapted CRC screening to medically underserved populations receiving care in community health centers (CHC). This perspective is based on key informant interviews with CHC medical directors, teleconference discussions, and strategic planning assessments. To address the unprecedented challenges created by the COVID-19 pandemic, we identify 2 broad calls to action: invest in CHCs now and support equitable and adaptable telehealth solutions now and in the future. We also recommend 4 CRC-specific calls to action: establish COVID-19-adapted best practices to implement mailed fecal immunochemical test programs, implement grassroots advocacy to identify community gastroenterologists who commit to performing colonoscopies for CHC patients, assess cancer prevention priorities among individuals in underserved communities, and assess regional CRC screening and follow-up barriers and solutions. The COVID-19 pandemic may further exacerbate existing CRC screening disparities in underserved individuals. This will likely lead to delayed diagnosis, a shift to later-stage disease, and increased CRC deaths. To prevent this from happening, we call for timely action and a commitment to address the current extraordinary CRC screening challenges for vulnerable populations.