Cancer and COVID-19: On the Quest for Effective Vaccines.

Cancer vaccine development has been historically fraught with difficulty, but tremendous progress has been made over the past 5 years. In this In Focus article, we reflect on the progress and challenges with vaccine development for cancers in general and for hematologic malignancies in particular, and suggest how our cancer vaccine experience can offer insight into COVID-19 vaccination.

Interplay of Vitamin D and SIRT1 in Tissue-Specific Metabolism-Potential Roles in Prevention and Treatment of Non-Communicable Diseases Including Cancer.

The importance of the prevention and control of non-communicable diseases, including obesity, metabolic syndrome, type 2 diabetes, cardiovascular diseases, and cancer, is increasing as a requirement of the aging population in developed countries and the sustainability of healthcare. Similarly, the 2013-2030 action plan of the WHO for the prevention and control of non-communicable diseases seeks these achievements. Adequate lifestyle changes, alone or with the necessary treatments, could reduce the risk of mortality or the deterioration of quality of life. In our recent work, we summarized the role of two central factors, i.e., appropriate levels of vitamin D and SIRT1, which are connected to adequate lifestyles with beneficial effects on the prevention and control of non-communicable diseases. Both of these factors have received increased attention in relation to the COVID-19 pandemic as they both take part in regulation of the main metabolic processes, i.e., lipid/glucose/energy homeostasis, oxidative stress, redox balance, and cell fate, as well as in the healthy regulation of the immune system. Vitamin D and SIRT1 have direct and indirect influence of the regulation of transcription and epigenetic changes and are related to cytoplasmic signaling pathways such as PLC/DAG/IP3/PKC/MAPK, MEK/Erk, insulin/mTOR/cell growth, proliferation; leptin/PI3K-Akt-mTORC1, Akt/NFĸB/COX-2, NFĸB/TNFα, IL-6, IL-8, IL-1ß, and AMPK/PGC-1α/GLUT4, among others. Through their proper regulation, they maintain normal body weight, lipid profile, insulin secretion and sensitivity, balance between the pro- and anti-inflammatory processes under normal conditions and infections, maintain endothelial health; balance cell differentiation, proliferation, and fate; and balance the circadian rhythm of the cellular metabolism. The role of these two molecules is interconnected in the molecular network, and they regulate each other in several layers of the homeostasis of energy and the cellular metabolism. Both have a central role in the maintenance of healthy and balanced immune regulation and redox reactions; therefore, they could constitute promising targets either for prevention or as complementary therapies to achieve a better quality of life, at any age, for healthy people and patients under chronic conditions.

Effect of non-pharmaceutical interventions on the incidence of respiratory viruses at a tertiary cancer care center.

BACKGROUND: In March 2020, nonpharmaceutical interventions (NPIs) including face coverings and social distancing were adopted to curb the spread of SARS-CoV-2. Over the course of the pandemic, adherence to these NPIs has varied and eventually became optional in most non healthcare settings. We investigated the impact of relaxation of NPI on the incidence of respiratory viruses other than SARS-CoV-2 at a tertiary cancer care hospital. METHODS: This was a retrospective cohort study of respiratory viral panel results performed at between 08/01/2014-07/31/2022. Only one viral target result per patient per year was included. Poisson regression models were used to compare 2019-2020, 2020-2021, and 2021-2022 incidence of respiratory viruses to those of 2014-2019. Interrupted time series analysis was performed using autoregressive integrated moving average models in order to compare expected and observed positivity rates. RESULTS: A large reduction in the odds of testing positive for a respiratory virus was observed for most respiratory viruses when comparing results from 2019 to 2020 group to the corresponding period in 2014-2019. Subsequent seasons showed ongoing reductions in the odds of testing positive while slowly increasing over time back toward pre-pandemic levels. A time interrupted series analysis showed that the monthly positivity rate for all respiratory pathogens were reduced after 03/01/2020, when compared to the expected values forecast, except for adenovirus. CONCLUSIONS: This study provides valuable data that could be used to guide public health practices and support the efficacy of NPIs in curtailing the spread of novel and endemic respiratory viruses.

An umbrella review of systematic reviews on the impact of the COVID-19 pandemic on cancer prevention and management, and patient needs.

The relocation and reconstruction of health care resources and systems during the coronavirus disease 2019 (COVID-19) pandemic may have affected cancer care. An umbrella review was undertaken to summarize the findings from systematic reviews on impact of the COVID-19 pandemic on cancer treatment modification, delays, and cancellations; delays or cancellations in screening and diagnosis; psychosocial well-being, financial distress, and use of telemedicine as well as on other aspects of cancer care. Bibliographic databases were searched for relevant systematic reviews with or without meta-analysis published before November 29th, 2022. Abstract, full- text screening, and data extraction were performed by two independent reviewers. AMSTAR-2 was used for critical appraisal of included systematic reviews. Fifty-one systematic reviews were included in our analysis. Most reviews were based on observational studies judged to be at medium and high risk of bias. Only two reviews had high or moderate scores based on AMSTAR-2. Findings suggest treatment modifications in cancer care during the pandemic versus the pre-pandemic period were based on low level of evidence. Different degrees of delays and cancellations in cancer treatment, screening, and diagnosis were observed, with low- and- middle- income countries and countries that implemented lockdowns being disproportionally affected. A shift from in-person appointments to telemedicine use was observed, but utility of telemedicine, challenges in implementation and cost-effectiveness in cancer care were little explored. Evidence was consistent in suggesting psychosocial well-being of patients with cancer deteriorated, and cancer patients experienced financial distress, albeit results were in general not compared to pre-pandemic levels. Impact of cancer care disruption during the pandemic on cancer prognosis was little explored. In conclusion, substantial but heterogenous impact of COVID-19 pandemic on cancer care has been observed.

The onset of the COVID-19 pandemic disrupted many aspects of human life, not least healthcare. As resources were redistributed towards the crisis, social isolation rules also limited access to medical professionals. In particular, these measures may have affected many aspects of cancer care, such as early detection or treatment. Many studies have aimed to capture the impact of these changes, but most have been observational, with researchers recording events without trying to impose a controlled design. These investigations also often faced limitations such as small sample sizes, or only focusing on one aspect of cancer care. Systemic reviews, which synthetize and assess existing research on a topic, have helped to bypass these constraints. However, they are themselves not devoid of biases. Overall, a clear, unified picture of the impact of COVID-19 on cancer care is yet to emerge. In response, Muka et al. carried an umbrella analysis of 51 systematic reviews on this topic. They used a well-known critical appraisal tool to assess the methodological rigor of each of these studies, while also summarising their findings. This work aimed to capture many aspects of the patients' experience, from diagnosis to treatment and the financial, psychological, physical and social impact of the disease. The results confirmed that the pandemic had a substantial impact on cancer care, including delays in screening, diagnosis and treatment. Throughout this period cancer patients experienced increased rates of depression, post-traumatic stress and fear of their cancer progressing. The long-term consequences of these disruptions remain to be uncovered. However, Muka et al. also showed that, overall, these conclusions rely on low-quality studies which may have introduced unaccountable biases. In addition, their review highlights that most of the data currently available has been collected in high- and middle-income countries, with evidence lacking from regions of the world with more limited resources. In the short-term, these results indicate that interventions may be needed to mitigate the negative impact of the pandemic on cancer care; in the long-term, they also demonstrate the importance of rigorous systematic reviews in guiding decision making. By shining a light on the ripple effects of certain decisions about healthcare resources, this work could also help to shape the response to future pandemics.

Vaccine hesitancy in cancer patients: A rapid review.

INTRODUCTION: Vaccination is a key strategy to limit the impact of the COVID-19 pandemic, among vulnerable groups such as cancer patients. However, COVID-19 vaccine hesitancy is limiting vaccination uptake in this population as in others. This study aimed to synthesise the emerging literature on vaccine hesitancy in this population and in Oncology health professionals, reasons for and factors associated with hesitancy, and interventions that address hesitancy. METHODS: A rapid review was undertaken PubMed, Ovid and Google across all years up to October 2021 for articles in English, from any country or region, addressing the above issues. Individual case studies, opinion pieces, commentary articles and conference abstracts were excluded. Article screening, data extraction and bias assessment were conducted by two authors. A narrative synthesis of the data was undertaken. RESULTS: Eighteen eligible articles were identified. Reported COVID-19 vaccine hesitancy rates varied from 76.7 % to 3.9 %, with a mean of 38.4 %. A large international study (n > 20,000) reported a more conservative hesitancy rate of 19 %. Six broad, common reasons for hesitancy were identified. Oncologist advice was valued by patients. DISCUSSION: Vaccine hesitancy remains a significant concern in the oncology context. Oncologists are key to addressing hesitancy and providing tailored advice to cancer patients. PRACTICE IMPLICATIONS: Where possible, patients appreciate personalised, tailored information about vaccination which addresses its interaction with cancer and its treatment. Education programmes for oncologists to support effective communication in this context are needed. Webinars and peer-to-peer counselling may be useful but remain to be proven.

Use of digital technologies to support cancer screening in community health promotion interventions: scoping review.

The scoping review investigated how digital technologies have helped to increase cancer screening uptake in communities including adolescents, adults and elderly people during the COVID-19 outbreak between January 2020 and June 2021. Thirteen studies were identified as being relevant, mostly addressing underserved or minority communities with the purpose to increase screening uptake, delivering health education or investigating social and cultural barriers to cancer screening. The interventions effectively used digital technologies such as mobile apps and messengers mobile apps, messaging and Web platforms. The limitations imposed by COVID-19 on social interaction can be supported with digital solutions to ensure the continuity of cancer screening programs. However, more research is needed to clarify the exact nature of effectiveness, especially in large-scale interventions.

Letter to the Editor: Perspectives on mRNA Vaccine Development for Cancer.

Recently, messenger ribonucleic acid (mRNA) vaccine research and development became a hotspot in the field of prevention and treatment of Corona Virus Disease 2019 (COVID-19) and some other disorders. mRNA vaccine shows many advantages over other vaccines, including cost-effectiveness, safety, and rapid optimization of antigen-specific sequences and shorter development cycle. Cancer progression is significantly associated with immune response, and mRNA vaccine also shows obvious advantages for cancer immunotherapy. In this study, we briefly summarize the recent advances and discuss the perspectives on tumor mRNA vaccine development; particularly, these findings pave an avenue for effective cancer prevention and treatment.

Everything causes cancer? Beliefs and attitudes towards cancer prevention among anti-vaxxers, flat earthers, and reptilian conspiracists: online cross sectional survey.

OBJECTIVE: To evaluate, using an online non-probability sample, the beliefs about and attitudes towards cancer prevention of people professing vaccination scepticism or conspiracy theories. DESIGN: Cross sectional survey. SETTING: Data collected mainly from ForoCoches (a well known Spanish forum) and other platforms, including Reddit (English), 4Chan (English), HispaChan (Spanish), and a Spanish language website for cancer prevention (mejorsincancer.org) from January to March 2022. PARTICIPANTS: Among 1494 responders, 209 were unvaccinated against covid-19, 112 preferred alternative rather than conventional medicine, and 62 reported flat earth or reptilian beliefs. MAIN OUTCOME MEASURES: Cancer beliefs assessed using the Cancer Awareness Measure (CAM) and Cancer Awareness Measure Mythical Causes Scale (CAM-MYCS) (both validated tools). RESULTS: Awareness of the actual causes of cancer was greater (median CAM score 63.6%) than that of mythical causes (41.7%). The most endorsed mythical causes of cancer were eating food containing additives or sweeteners, feeling stressed, and eating genetically modified food. Awareness of the actual and mythical causes of cancer among the unvaccinated, alternative medicine, and conspiracy groups was lower than among their counterparts. A median of 54.5% of the actual causes was accurately identified among each of the unvaccinated, alternative medicine, and conspiracy groups, and a median of 63.6% was identified in each of the three corresponding counterparts (P=0.13, 0.04, and 0.003, respectively). For mythical causes, medians of 25.0%, 16.7%, and 16.7% were accurately identified in the unvaccinated, alternative medicine, and conspiracy groups, respectively; a median of 41.7% was identified in each of the three corresponding counterparts (P<0.001 in adjusted models for all comparisons). In total, 673 (45.0%) participants agreed with the statement "It seems like everything causes cancer." No significant differences were observed among the unvaccinated (44.0%), conspiracist (41.9%), or alternative medicine groups (35.7%), compared with their counterparts (45.2%, 45.7%, and 45.8%, respectively). CONCLUSIONS: Almost half of the participants agreed that "It seems like everything causes cancer," which highlights the difficulty that society encounters in differentiating actual and mythical causes owing to mass information. People who believed in conspiracies, rejected the covid-19 vaccine, or preferred alternative medicine were more likely to endorse the mythical causes of cancer than their counterparts but were less likely to endorse the actual causes of cancer. These results suggest a direct connection between digital misinformation and consequent erroneous health decisions, which may represent a further preventable fraction of cancer.

Social Distancing to Avoid SARS-CoV-2 Infection in Cancer and Noncancer Patients.

BACKGROUND: Social distancing has been recommended by the Centers for Disease Control and Prevention to avoid exposure to SARS-CoV-2 ( Epidemiol Prev 2020;44:353-362).Cancer patients on or after active therapy seem to be more prone to COVID being symptomatic and life-threatening. When evaluating cancer patients' risk of acquiring COVID, it is essential to know the behavior of cancer patients that will affect their risk of exposure. However, it is not known to what degree social distancing is practiced by cancer patients compared with noncancer patients and what factors lead to the decision to distance oneself. METHOD: After a pilot phase using patients' MyChart messaging, links to the electronic questionnaires were texted to patients using Twillio. Responses were stored on REDCap (Vanderbilt University, Nashville, TN). Six questions about their social distancing behavior and mask wearing were posed and responses were compared between cancer and noncancer patients. Demographics, comorbidities, and a questionnaire about anxiety (Generalized Anxiety Disorder 7-item scale) were recorded. To assess differences between cancer and noncancer groups, Bonferroni-corrected χ 2 tests and proportions confidence intervals were used. RESULTS: The pilot survey was sent in mid-2020 and the full survey followed in January 2021 during a high community COVID incidence. Three hundred eighty-seven cancer patients (32.4% responded) and 503 noncancer patients (22.9% responded) completed the survey. Questions about leaving their houses, driving, shopping, friends, and family indicated that patients with cancer are more cautious ( P < 0.001). Cancer patients were up to 20% more likely to distance themselves. No difference was seen in wearing a mask-both groups wore approximately 90% of the time. Most respondents were female (63% versus 71%). Cancer patients were older (>60 y, 69% versus 45%) and less likely to work (52% versus 31%) or less likely to be White collar workers (21% versus 38%). In both groups, 54% marked "not at all anxious." CONCLUSIONS: Cancer patients' responses revealed a distancing behavior that would likely lower the risk exposure to SARS-CoV-2. It is unclear which of the demographic differences would account for this behavior, although remarkably anxiety was not a clear motivating factor. The high acceptance of masks is encouraging. Early publications during the pandemic and patient education suggesting a higher COVID risk for cancer patients may have reduced risk prone behavior. Considering COVID's impact on the vulnerable cancer population and uncertainty in immunosuppressed patients about clearing the virus or adequately responding to a vaccine, further studies about health behavior and health promotion during the pandemic are needed.

Evaluation of community outreach feasibility programmes on improving cancer-related, preventive, health behaviour.

BACKGROUND: The COVID-19 pandemic had a negative impact on cancer services and will have likely led to delayed early detection and diagnosis. In response, the Irish Cancer Society (ICS) planned and delivered seven cancer roadshow events run on 15 days across seven shopping centres in four deprived areas based on Trinity National Deprivation Index, 2016, in Limerick, Cork, Waterford and Dublin regions in Ireland to educate and promote awareness about cancer signs and symptoms, importance of screening, positive lifestyle changes, and encourage medical care-seeking behaviour. METHODS: ICS nurses and trained ICS volunteers conducted health checks such as blood pressure, BMI, and CO2, monitoring (one health check per person maximum), provided health information and conducted motivational interviews in aforementioned regions. Data were collected via an anonymous questionnaire from participants and volunteers. SPSS was used for descriptive and pre-post event comparative analysis. FINDINGS: 98 people, all adults (54 men and 44 women) participated; 88% (n=86) found the information provided useful, 85% (n=83) approved of the health check and 73% (n=71) stated that they would probably make changes to their current lifestyle to reduce their cancer risk. Moderate or high understanding of cancer signs and symptoms (from 62% to 82%; p<0·0001) and moderate or high awareness of cancer risk factors (from 49% to 61%; p<0·0001) both rose after the events. If symptomatic for cancer, 78% (n=76) of participants would probably visit their general practitioner and 74% (n=72) would probably contact ICS. Younger people (aged ≤40 years) were more likely to consider consulting a health-care professional if symptomatic (p=0·0270) and to contact the ICS (p=0·0070) for more information. High numbers of participants (99%; n=97) and volunteers (95%; n=42) recommended a nationwide roll out. INTERPRETATION: With moderate to high levels of public engagement, volunteers reported people discussed cancer screening, information on making lifestyle changes, and ICS services. Such community outreach programmes to promote cancer-related health are feasible and acceptable and might lead to improved knowledge of cancer prevention, early detection, and improved intention to seek help for health concerns. Determination of effectiveness in preventive behaviour, early diagnosis, and cost effectiveness would require longer term follow up. FUNDING: Irish Cancer Society.

Evaluation of a National Quality Improvement Collaborative for Improving Cancer Screening.

Importance: Cancer screening deficits during the first year of the COVID-19 pandemic were found to persist into 2021. Cancer-related deaths over the next decade are projected to increase if these deficits are not addressed. Objective: To assess whether participation in a nationwide quality improvement (QI) collaborative, Return-to-Screening, was associated with restoration of cancer screening. Design, Setting, and Participants: Accredited cancer programs electively enrolled in this QI study. Project-specific targets were established on the basis of differences in mean monthly screening test volumes (MTVs) between representative prepandemic (September 2019 and January 2020) and pandemic (September 2020 and January 2021) periods to restore prepandemic volumes and achieve a minimum of 10% increase in MTV. Local QI teams implemented evidence-based screening interventions from June to November 2021 (intervention period), iteratively adjusting interventions according to their MTVs and target. Interrupted time series analyses was used to identify the intervention effect. Data analysis was performed from January to April 2022. Exposures: Collaborative QI support included provision of a Return-to-Screening plan-do-study-act protocol, evidence-based screening interventions, QI education, programmatic coordination, and calculation of screening deficits and targets. Main Outcomes and Measures: The primary outcome was the proportion of QI projects reaching target MTV and counterfactual differences in the aggregate number of screening tests across time periods. Results: Of 859 cancer screening QI projects (452 for breast cancer, 134 for colorectal cancer, 244 for lung cancer, and 29 for cervical cancer) conducted by 786 accredited cancer programs, 676 projects (79%) reached their target MTV. There were no hospital characteristics associated with increased likelihood of reaching target MTV except for disease site (lung vs breast, odds ratio, 2.8; 95% CI, 1.7 to 4.7). During the preintervention period (April to May 2021), there was a decrease in the mean MTV (slope, -13.1 tests per month; 95% CI, -23.1 to -3.2 tests per month). Interventions were associated with a significant immediate (slope, 101.0 tests per month; 95% CI, 49.1 to 153.0 tests per month) and sustained (slope, 36.3 tests per month; 95% CI, 5.3 to 67.3 tests per month) increase in MTVs relative to the preintervention trends. Additional screening tests were performed during the intervention period compared with the prepandemic period (170 748 tests), the pandemic period (210 450 tests), and the preintervention period (722 427 tests). Conclusions and Relevance: In this QI study, participation in a national Return-to-Screening collaborative with a multifaceted QI intervention was associated with improvements in cancer screening. Future collaborative QI endeavors leveraging accreditation infrastructure may help address other gaps in cancer care.

The Role of Epigenetic Regulator SIRT1 in Balancing the Homeostasis and Preventing the Formation of Specific "Soil" of Metabolic Disorders and Related Cancers.

SIRT1 was discovered in 1979 but growing interest in this protein occurred only 20 years later when its overexpression was reported to prolong the lifespan of yeast. Since then, several studies have shown the benefits of its increased expression in preventing or delaying of many diseases. SIRT1, as a histone deacetylase, is an epigenetic regulator but it has wide range of non-histone targets which are involved in metabolism, energy sensing pathways, circadian machinery and in inflammatory regulation. Disturbances in these interconnected processes cause different diseases, however it seems they have common roots in unbalanced inflammatory processes and lower level or inactivation of SIRT1. SIRT1 inactivation was implicated in coronavirus disease (COVID-19) severity as well and its low level counted as a predictor of uncontrolled COVID-19. Several other diseases such as metabolic disease, obesity, diabetes, Alzheimer's disease, cardiovascular disease or depression are related to chronic inflammation and similarly show decreased SIRT1 level. It has recently been known that SIRT1 is inducible by calorie restriction/proper diet, physical activity and appropriate emotional state. Indeed, a healthier metabolic state belongs to higher level of SIRT1 expression. These suggest that appropriate lifestyle as non-pharmacological treatment may be a beneficial tool in the prevention of inflammation or metabolic disturbance-related diseases as well as could be a part of the complementary therapy in medical practice to reach better therapeutic response and quality of life. We aimed in this review to link the beneficial effect of SIRT1 with those diseases, where its level decreased. Moreover, we aimed to collect evidences of interventions or treatments, which increase SIRT1 expression and thus, open the possibility to use them as preventive or complementary therapies in medical practice.

Critique of Public Health Guidance for Vitamin D and Sun Exposure in the Context of Cancer and COVID-19.

Official public health pronouncements about sun exposure and vitamin D can be summarized as follows: First, there is no such thing as a safe tan. Therefore, avoid exposing the skin to sunshine. Second, in the absence of sunshine, a daily intake of 800 IU/day (20 mcg/d) vitamin D or less is sufficient for the health needs of almost all members of the population. However, exposure of the skin to sunlight induces multiple mechanisms that lower blood pressure, while also initiating production of vitamin D, which is needed to produce a hormone that regulates multiple systems including the cellular biology that affects cancer mortality. Disease-prevention relationships point to a beneficial threshold for serum 25-hydroxyvitamin D [25(OH)D; the index of vitamin D nutrition] that is at least 75 nmol/l (30 ng/ml). To ensure the threshold for all adults, an average per-day minimum total input of vitamin D3 from sunshine/UVB exposure, and/or from food (natural food like fish or fortified food like milk), and/or vitamin supplementation of at least 4,000 IU/d (100 mcg/d) is required. Strong, although not Level-1, evidence indicates that the maintenance of that threshold will lower mortality overall, lower mortality from cancer, and lower the risk of certain other diseases such as respiratory infection and COVID-19.

The role of AMPK-dependent pathways in cellular and molecular mechanisms of metformin: a new perspective for treatment and prevention of diseases.

Metformin can suppress gluconeogenesis and reduce blood sugar by activating adenosine monophosphate-activated protein kinase (AMPK) and inducing small heterodimer partner (SHP) expression in the liver cells. The main mechanism of metformin's action is related to its activation of the AMPK enzyme and regulation of the energy balance. AMPK is a heterothermic serine/threonine kinase made of a catalytic alpha subunit and two subunits of beta and a gamma regulator. This enzyme can measure the intracellular ratio of AMP/ATP. If this ratio is high, the amino acid threonine 172 available in its alpha chain would be activated by the phosphorylated liver kinase B1 (LKB1), leading to AMPK activation. Several studies have indicated that apart from its significant role in the reduction of blood glucose level, metformin activates the AMPK enzyme that in turn has various efficient impacts on the regulation of various processes, including controlling inflammatory conditions, altering the differentiation pathway of immune and non-immune cell pathways, and the amelioration of various cancers, liver diseases, inflammatory bowel disease (IBD), kidney diseases, neurological disorders, etc. Metformin's activation of AMPK enables it to control inflammatory conditions, improve oxidative status, regulate the differentiation pathways of various cells, change the pathological process in various diseases, and finally have positive therapeutic effects on them. Due to the activation of AMPK and its role in regulating several subcellular signalling pathways, metformin can be effective in altering the cells' proliferation and differentiation pathways and eventually in the prevention and treatment of certain diseases.

Cancer vaccines.

Given the renewed interest in vaccine development sparked by the COVID-19 pandemic, we are revisiting the current state of vaccine development for cancer prevention and treatment. Experts discuss different vaccine types, their antigens and modes of action, and where we stand on their clinical development, plus the challenges we need to overcome for their broad implementation.