Harmonization of clinical practice guidelines for primary prevention and screening: actionable recommendations and resources for primary care.

BACKGROUND: Clinical practice guidelines (CPGs) synthesize high-quality information to support evidence-based clinical practice. In primary care, numerous CPGs must be integrated to address the needs of patients with multiple risks and conditions. The BETTER program aims to improve prevention and screening for cancer and chronic disease in primary care by synthesizing CPGs into integrated, actionable recommendations. We describe the process used to harmonize high-quality cancer and chronic disease prevention and screening (CCDPS) CPGs to update the BETTER program. METHODS: A review of CPG databases, repositories, and grey literature was conducted to identify international and Canadian (national and provincial) CPGs for CCDPS in adults 40-69 years of age across 19 topic areas: cancers, cardiovascular disease, chronic obstructive pulmonary disease, diabetes, hepatitis C, obesity, osteoporosis, depression, and associated risk factors (i.e., diet, physical activity, alcohol, cannabis, drug, tobacco, and vaping/e-cigarette use). CPGs published in English between 2016 and 2021, applicable to adults, and containing CCDPS recommendations were included. Guideline quality was assessed using the Appraisal of Guidelines for Research and Evaluation (AGREE) II tool and a three-step process involving patients, health policy, content experts, primary care providers, and researchers was used to identify and synthesize recommendations. RESULTS: We identified 51 international and Canadian CPGs and 22 guidelines developed by provincial organizations that provided relevant CCDPS recommendations. Clinical recommendations were extracted and reviewed for inclusion using the following criteria: 1) pertinence to primary prevention and screening, 2) relevance to adults ages 40-69, and 3) applicability to diverse primary care settings. Recommendations were synthesized and integrated into the BETTER toolkit alongside resources to support shared decision-making and care paths for the BETTER program. CONCLUSIONS: Comprehensive care requires the ability to address a person's overall health. An approach to identify high-quality clinical guidance to comprehensively address CCDPS is described. The process used to synthesize and harmonize implementable clinical recommendations may be useful to others wanting to integrate evidence across broad content areas to provide comprehensive care. The BETTER toolkit provides resources that clearly and succinctly present a breadth of clinical evidence that providers can use to assist with implementing CCDPS guidance in primary care.

The role of IGFBP-3 in tumor development and progression: enlightenment for diagnosis and treatment.

IGFBP-3 is aberrantly expressed in many tumor types, and its serum and tumor tissue levels provide auxiliary information for assessing the degree of tumor malignancy and patient prognosis, making it a potential therapeutic target for human malignancies and conferring it remarkable clinical value for determining patient prognosis. In this review, we provide a comprehensive overview of the aberrant expression, diverse biological effects, and clinical implications of IGFBP-3 in tumors and its role as a potential prognostic marker and therapeutic target for tumors. In addition, we summarize the signaling pathways through which IGFBP-3 exerts its effects. IGFBP-3 comprises an N-terminal, an intermediate region, and a C-terminal structural domain, each exerting different biological effects in several tumor cell types in an IGF-dependent/non-independent manner. IGFBP-3 shares an intricate relationship with the tumor microenvironment, thereby affecting tumor growth. Overall, IGFBP-3 is an essential regulatory factor that mediates tumor occurrence and progression. Gaining deeper insights into the fundamental characteristics of IGFBP-3 and its role in various tumor types will provide new perspectives and allow for the development of novel strategies for cancer diagnosis, treatment, and prognostic evaluation.

The effect of local hospital waiting times on GP referrals for suspected cancer.

INTRODUCTION: Reducing waiting times is a major policy objective in publicly-funded healthcare systems. However, reductions in waiting times can produce a demand response, which may offset increases in capacity. Early detection and diagnosis of cancer is a policy focus in many OECD countries, but prolonged waiting periods for specialist confirmation of diagnosis could impede this goal. We examine whether urgent GP referrals for suspected cancer patients are responsive to local hospital waiting times. METHOD: We used annual counts of referrals from all 6,667 general practices to all 185 hospital Trusts in England between April 2012 and March 2018. Using a practice-level measure of local hospital waiting times based on breaches of the two-week maximum waiting time target, we examined the relationship between waiting times and urgent GP referrals for suspected cancer. To identify whether the relationship is driven by differences between practices or changes over time, we estimated three regression models: pooled linear regression, a between-practice estimator, and a within-practice estimator. RESULTS: Ten percent higher rates of patients breaching the two-week wait target in local hospitals were associated with higher volumes of referrals in the pooled linear model (4.4%; CI 2.4% to 6.4%) and the between-practice estimator (12.0%; CI 5.5% to 18.5%). The relationship was not statistically significant using the within-practice estimator (1.0%; CI -0.4% to 2.5%). CONCLUSION: The positive association between local hospital waiting times and GP demand for specialist diagnosis was caused by practices with higher levels of referrals facing longer local waiting times. Temporal changes in waiting times faced by individual practices were not related to changes in their referral volumes. GP referrals for diagnostic cancer services were not found to respond to waiting times in the short-term. In this setting, it may therefore be possible to reduce waiting times by increasing supply without consequently increasing demand.

Mitochondria: A source of potential biomarkers for non-communicable diseases.

Mitochondria, as an endosymbiont of eukaryotic cells, controls multiple cellular activities, including respiration, reactive oxygen species production, fatty acid synthesis, and death. Though the majority of functional mitochondrial proteins are translated through a nucleus-controlled process, very few of them (∼10%) are translated within mitochondria through their own machinery. Germline and somatic mutations in mitochondrial and nuclear DNA significantly impact mitochondrial homeostasis and function. Such modifications disturbing mitochondrial biogenesis, metabolism, or mitophagy eventually resulted in cellular pathophysiology. In this chapter, we discussed the impact of mitochondria and its dysfunction on several non-communicable diseases like cancer, diabetes, neurodegenerative, and cardiovascular problems. Mitochondrial dysfunction and its outcome could be screened by currently available omics-based techniques, flow cytometry, and high-resolution imaging. Such characterization could be evaluated as potential biomarkers to assess the disease burden and prognosis.

Cancer literacy differences of basic knowledge, prevention, early detection, treatment and recovery: a cross-sectional study of urban and rural residents in Northeast China.

Background: Cancer literacy as a potential health intervention tool directly impacted the success of cancer prevention and treatment initiatives. This study aimed to evaluate the cancer literacy in Northeast China, and explore the factors contributing to urban-rural disparities. Methods: A cross-sectional survey was conducted in 14 cities across Liaoning Province, China, from August to October 2021, using the multistage probability proportional to size sampling (PPS) method. The survey comprised 4,325 participants aged 15-69 and encompassed 37 core knowledge-based questions spanning five dimensions. Associations between sociodemographic factors and the cancer literacy rate were evaluated using chi-square tests and multivariate logistic regression model. Results: The overall cancer literacy rate was 66.9% (95% CI: 65.6-68.2%). In the primary indicators, cancer literacy were highest in treatment (75.8, 95% CI: 74.2-77.4%) and early detection (68.2, 95% CI: 66.8-69.6%), followed by basic knowledge (67.2, 95% CI: 65.8-68.6%), recovery (62.6, 95% CI: 60.7-64.5%) and prevention (59.7, 95% CI: 58.2-61.3%). Regarding secondary indicators, the awareness rates regarding cancer-related risk factors (54.7, 95% CI: 52.8-56.5%) and early diagnosis of cancer (54.6, 95% CI: 52.7-56.6%) were notably inadequate. Rural participates exhibited lower cancer literacy across all dimensions compared to urban. Multi-factor analysis showed that factors such as advanced age, limited education or low household income were barriers to health literacy in rural areas. Conclusion: Strengthening awareness concerning prevention and early detection, particularly among key populations, and bridging the urban-rural cancer literacy gap are imperative steps toward achieving the Healthy China 2030 target.

[Cancer registration in Iceland for 70 years - incidence, mortality and survival].

INTRODUCTION: The Icelandic Cancer Registry (ICR) was founded seventy years ago by the Icelandic Cancer Society. In 2007 the ICR became one of the health registers of the Directorate of Health. In this paper we present cancer incidence, mortality, and survival in Iceland over 70 years. MATERIAL AND METHODS: The ICR receives information on cancer diagnoses from histopathological laboratories, the Hospital Discharge Registry and the Cause of Death Registry. Iceland participates in the Nordic cancer database NORDCAN. Because of the small population size, random variation in numbers is very prominent. Therefore, data from ICR are published as five-year averages. RESULTS: For all malignancies combined, age-standardized incidence (ASI) in men rose steadily until around 15 years ago when a decline started. This is in line with prostate- and lung cancer incidence trends. In women, the ASI was lower than in men, but it is still on the rise despite declining lung cancer incidence. ASI for breast cancer, the most common cancer in women, is increasing. Simultaneously, cancer mortality for both sexes has declined in recent years and cancer survival is improving. CONCLUSIONS: Population-based cancer registration for over 70 years makes it possible to monitor the epidemiology of cancer in Iceland and compare with other countries. The changes in trends in ASI are in line with changes of cancer risk factors and diagnostic policy. The decline in cancer mortality and improvement in survival reflects advances in cancer treatment as well as effects of early detection and prevention.

Sample-to-answer salivary miRNA testing: New frontiers in point-of-care diagnostic technologies.

MicroRNA (miRNA), crucial non-coding RNAs, have emerged as key biomarkers in molecular diagnostics, prognosis, and personalized medicine due to their significant role in gene expression regulation. Salivary miRNA, in particular, stands out for its non-invasive collection method and ease of accessibility, offering promising avenues for the development of point-of-care diagnostics for a spectrum of diseases, including cancer, neurodegenerative disorders, and infectious diseases. Such development promises rapid and precise diagnosis, enabling timely treatment. Despite significant advancements in salivary miRNA-based testing, challenges persist in the quantification, multiplexing, sensitivity, and specificity, particularly for miRNA at low concentrations in complex biological mixtures. This work delves into these challenges, focusing on the development and application of salivary miRNA tests for point-of-care use. We explore the biogenesis of salivary miRNA and analyze their quantitative expression and their disease relevance in cancer, infection, and neurodegenerative disorders. We also examined recent progress in miRNA extraction, amplification, and multiplexed detection methods. This study offers a comprehensive view of the development of salivary miRNA-based point-of-care testing (POCT). Its successful advancement could revolutionize the early detection, monitoring, and management of various conditions, enhancing healthcare outcomes. This article is categorized under: Diagnostic Tools > Biosensing Diagnostic Tools > Diagnostic Nanodevices.

The Application of Artificial Intelligence to Cancer Research: A Comprehensive Guide.

Advancements in AI have notably changed cancer research, improving patient care by enhancing detection, survival prediction, and treatment efficacy. This review covers the role of Machine Learning, Soft Computing, and Deep Learning in oncology, explaining key concepts and algorithms (like SVM, Naïve Bayes, and CNN) in a clear, accessible manner. It aims to make AI advancements understandable to a broad audience, focusing on their application in diagnosing, classifying, and predicting various cancer types, thereby underlining AI's potential to better patient outcomes. Moreover, we present a tabular summary of the most significant advances from the literature, offering a time-saving resource for readers to grasp each study's main contributions. The remarkable benefits of AI-powered algorithms in cancer care underscore their potential for advancing cancer research and clinical practice. This review is a valuable resource for researchers and clinicians interested in the transformative implications of AI in cancer care.

Magnetic beads and GO-assisted enzyme-free signal amplification fluorescent biosensors for disease diagnosis.

Cancer detection is still a major challenge in public health. Identification of oncogene is the first step toward solving this problem. Studies have revealed that various cancers are associated with miRNA expression. Therefore, the sensitive detection of miRNA is substantially important to solve the cancer problem. In this study, let-7a, a representative substance of miRNA, was selected as the detection target. With the assistance of magnetic beads commonly used in biosensors and self-synthesized graphene oxide materials, specificity and sensitivity detection of the target gene let-7a were achieved via protease-free signal amplification. The limit of detection (LOD) was as low as 15.015pM. The fluorescence signal intensity showed a good linear relationship with the logarithm of let-7a concentration. The biosensor could also detect let-7a in complex human serum samples. Overall, this fluorescent biosensor is not only simple to operate, but also strongly specificity to detect let-7a. Therefore, it has substantial potential for application in the early diagnosis of clinical medicine and biological research.

Protecting Caribbean patients diagnosed with cancer from compounding disasters.

Caribbean small island developing states are becoming increasingly vulnerable to compounding disasters, prominently featuring climate-related hazards and pandemic diseases, which exacerbate existing barriers to cancer control in the region. We describe the complexities of cancer prevention and control efforts throughout the Caribbean small island developing states, including the unique challenges of people diagnosed with cancer in the region. We highlight potential solutions and strategies that concurrently address disaster adaptation and cancer control. Because Caribbean small island developing states are affected first and worst by the hazards of compounding disasters, the innovative solutions developed in the region are relevant for climate mitigation, disaster adaptation, and cancer control efforts globally. In the age of complex and cascading disaster scenarios, developing strategies to mitigate their effect on the cancer control continuum, and protecting the health and safety of people diagnosed with cancer from extreme events become increasingly urgent. The equitable development of such strategies relies on collaborative efforts among professionals whose diverse expertise from complementary fields infuses the local community perspective while focusing on implementing solutions.

Considerations for using potential surrogate endpoints in cancer screening trials.

The requirement of large-scale expensive cancer screening trials spanning decades creates considerable barriers to the development, commercialisation, and implementation of novel screening tests. One way to address these problems is to use surrogate endpoints for the ultimate endpoint of interest, cancer mortality, at an earlier timepoint. This Review aims to highlight the issues underlying the choice and use of surrogate endpoints for cancer screening trials, to propose criteria for when and how we might use such endpoints, and to suggest possible candidates. We present the current landscape and challenges, and discuss lessons and shortcomings from the therapeutic trial setting. It is hugely challenging to validate a surrogate endpoint, even with carefully designed clinical studies. Nevertheless, we consider whether there are candidates that might satisfy the requirements defined by research and regulatory bodies.

Diagnosis rates, therapeutic characteristics, lifestyle, and cancer screening habits of patients with diabetes mellitus in a highly deprived region in Hungary: a cross-sectional analysis.

Introduction: Low socioeconomic status affects not only diagnosis rates and therapy of patients with diabetes mellitus but also their health behavior. Our primary goal was to examine diagnosis rates and therapy of individuals with diabetes living in Ormánság, one of the most deprived areas in Hungary and Europe. Our secondary goal was to examine the differences in lifestyle factors and cancer screening participation of patients with diagnosed and undiagnosed diabetes compared to healthy participants. Methods: Our study is a cross-sectional analysis using data from the "Ormánság Health Program". The "Ormánság Health Program" was launched to improve the health of individuals in a deprived region of Hungary. Participants in the program were coded as diagnosed diabetes based on diagnosis by a physician as a part of the program, self-reported diabetes status, and self-reported prescription of antidiabetic medication. Undiagnosed diabetes was defined as elevated blood glucose levels without self-reported diabetes and antidiabetic prescription. Diagnosis and therapeutic characteristics were presented descriptively. To examine lifestyle factors and screening participation, patients with diagnosed and undiagnosed diabetes were compared to healthy participants using linear regression or multinomial logistic regression models adjusted for sex and age. Results: Our study population consisted of 246 individuals, and 17.9% had either diagnosed (n=33) or undiagnosed (n=11) diabetes. Metformin was prescribed in 75.8% (n=25) of diagnosed cases and sodium-glucose cotransporter-2 inhibitors (SGLT-2) in 12.1% (n=4) of diagnosed patients. After adjustment, participants with diagnosed diabetes had more comorbidities (adjusted [aOR]: 3.50, 95% confidence interval [95% CI]: 1.34-9.18, p<0.05), consumed vegetables more often (aOR: 2.49, 95% CI: 1.07-5.78, p<0.05), but desserts less often (aOR: 0.33, 95% CI: 0.15-0.75, p<0.01) than healthy individuals. Patients with undiagnosed diabetes were not different in this regard from healthy participants. No significant differences were observed for cancer screening participation between groups. Conclusions: To increase recognition of diabetes, targeted screening tests should be implemented in deprived regions, even among individuals without any comorbidities. Our study also indicates that diagnosis of diabetes is not only important for the timely initiation of therapy, but it can also motivate individuals in deprived areas to lead a healthier lifestyle.

PET Imaging of Metabolism, Perfusion, and Hypoxia: FDG and Beyond.

ABSTRACT: Imaging glucose metabolism with [18F]fluorodeoxyglucose positron emission tomography has transformed the diagnostic and treatment algorithms of numerous malignancies in clinical practice. The cancer phenotype, though, extends beyond dysregulation of this single pathway. Reprogramming of other pathways of metabolism, as well as altered perfusion and hypoxia, also typifies malignancy. These features provide other opportunities for imaging that have been developed and advanced into humans. In this review, we discuss imaging metabolism, perfusion, and hypoxia in cancer, focusing on the underlying biology to provide context. We conclude by highlighting the ability to image multiple facets of biology to better characterize cancer and guide targeted treatment.

PET Imaging for Monitoring Cellular and Immunotherapy of Cancer.

ABSTRACT: Cancer immunotherapy, including checkpoint blockade and cellular therapy, has become a cornerstone in cancer treatment. However, understanding the factors driving patient response or resistance to these therapies remains challenging. The dynamic interplay between the immune system and tumors requires new approaches for characterization. Biopsies and blood tests provide valuable information, but their limitations have led to increased interest in positron emission tomography (PET)/computed tomography imaging to complement these strategies. The noninvasive nature of PET imaging makes it ideal for monitoring the dynamic tumor immune microenvironment. This review discusses various PET imaging approaches, including immune cell lineage markers, immune functional markers, immune cell metabolism, direct cell labeling, and reporter genes, highlighting their potential in targeted immunotherapies and cell-based approaches. Although PET imaging has limitations, its integration into diagnostic strategies holds promise for improving patient outcomes and accelerating drug development in cancer immunotherapy.

Analytical validation of a novel comprehensive genomic profiling informed circulating tumor DNA monitoring assay for solid tumors.

Emerging technologies focused on the detection and quantification of circulating tumor DNA (ctDNA) in blood show extensive potential for managing patient treatment decisions, informing risk of recurrence, and predicting response to therapy. Currently available tissue-informed approaches are often limited by the need for additional sequencing of normal tissue or peripheral mononuclear cells to identify non-tumor-derived alterations while tissue-naïve approaches are often limited in sensitivity. Here we present the analytical validation for a novel ctDNA monitoring assay, FoundationOne®Tracker. The assay utilizes somatic alterations from comprehensive genomic profiling (CGP) of tumor tissue. A novel algorithm identifies monitorable alterations with a high probability of being somatic and computationally filters non-tumor-derived alterations such as germline or clonal hematopoiesis variants without the need for sequencing of additional samples. Monitorable alterations identified from tissue CGP are then quantified in blood using a multiplex polymerase chain reaction assay based on the validated SignateraTM assay. The analytical specificity of the plasma workflow is shown to be 99.6% at the sample level. Analytical sensitivity is shown to be >97.3% at ≥5 mean tumor molecules per mL of plasma (MTM/mL) when tested with the most conservative configuration using only two monitorable alterations. The assay also demonstrates high analytical accuracy when compared to liquid biopsy-based CGP as well as high qualitative (measured 100% PPA) and quantitative precision (<11.2% coefficient of variation).

High-throughput molecular assays for inclusion in personalised oncology trials - State-of-the-art and beyond.

In the last decades, the development of high-throughput molecular assays has revolutionised cancer diagnostics, paving the way for the concept of personalised cancer medicine. This progress has been driven by the introduction of such technologies through biomarker-driven oncology trials. In this review, strengths and limitations of various state-of-the-art sequencing technologies, including gene panel sequencing (DNA and RNA), whole-exome/whole-genome sequencing and whole-transcriptome sequencing, are explored, focusing on their ability to identify clinically relevant biomarkers with diagnostic, prognostic and/or predictive impact. This includes the need to assess complex biomarkers, for example microsatellite instability, tumour mutation burden and homologous recombination deficiency, to identify patients suitable for specific therapies, including immunotherapy. Furthermore, the crucial role of biomarker analysis and multidisciplinary molecular tumour boards in selecting patients for trial inclusion is discussed in relation to various trial concepts, including drug repurposing. Recognising that today's exploratory techniques will evolve into tomorrow's routine diagnostics and clinical study inclusion assays, the importance of emerging technologies for multimodal diagnostics, such as proteomics and in vivo drug sensitivity testing, is also discussed. In addition, key regulatory aspects and the importance of patient engagement in all phases of a clinical trial are described. Finally, we propose a set of recommendations for consideration when planning a new precision cancer medicine trial.

A Red-Emission Fluorescent Probe with Large Stokes Shift for Detection of Viscosity in Living Cells and Tumor-Bearing Mice.

Abnormal viscosity is closely related to the occurrence of many diseases, such as cancer. Therefore, real-time detection of changes in viscosity in living cells is of great importance. Fluorescent molecular rotors play a critical role in detecting changes in cellular viscosity. Developing red emission viscosity probes with large Stokes shifts and high sensitivity and specificity remains an urgent and important topic. Herein, a novel viscosity-sensitive fluorescent probe (TCF-VIS1) with a large stokes shift and red emission was prepared based on the 2-dicyanomethylene-3-cyano-4,5,5-trimethyl-2,5-dihydrofuran (TCF) skeleton. Due to intramolecular rotation, the probe itself does not fluorescence at low viscosity. With the increase in viscosity, the rotation of TCF-VIS1 is limited, and its fluorescence is obviously enhanced. The probe has the advantages of simple preparation, large Stokes shift, good sensitivity and selectivity, and low cytotoxicity, which make it successfully used for viscosity detection in living cells. Moreover, TCF-VIS1 showed its potential for cancer diagnosis at the cell level and in tumor-bearing mice by detecting viscosity. Therefore, the probe is expected to enrich strategies for the detection of viscosity in biological systems and offer a potential tool for cancer diagnosis.

Survey of awareness and beliefs about cancer (ABC) in Tehran Province, Iran.

INTRODUCTION: Knowledge, attitudes, and practices are essential measures for planning and evaluating cancer control programs. Little is known about these in Iran. METHODS: We conducted a population-based interview survey of adults aged 30-70 using the Farsi version of the Awareness and Beliefs about Cancer questionnaire in the capital province of Tehran, Iran, 2019. We calculated weighted estimates of levels of cancer knowledge, attitudes, and practices to allow for different selection probabilities and nonresponse. We used multivariate logistic regression to understand demographic factors associated with bowel, cervix, and breast screening practices. RESULTS: We interviewed 736 men and 744 women. The mean number of recalled cancer warning signs was less than one; 57.7% could not recall any cancer warning signs. Participants recognized 5.6 out of 11 early cancer warning signs and 8.8 of 13 cancer risk factors. Most (82.7%) did not know that HPV infection was a cancer risk factor. Approximately, half had negative attitudes towards cancer treatment, but over 80% had positive attitudes towards the effectiveness of screening for improving survival. Colorectal, breast, and cervical screening rates were 24%, 42%, and 49%, respectively. Higher socioeconomic status increased the odds of taking up screening for cancer. Women aged 60-70 were less likely to report taking up breast and cervical screening than younger women. DISCUSSION: The Iranian population has poor awareness and negative attitudes about cancer, and participation in screening programs is low. Public awareness and early detection of cancer should be promoted in Iran.

Developmental surveillance and screening practices in a pediatric oncology clinic: Initial progress of a quality improvement study.

BACKGROUND: Pediatric cancer patients' oncology teams regularly take on a primary care role, but due to the urgent nature of cancer treatment, developmental screenings may be deprioritized. This leaves patients at risk of developmental diagnoses and referrals being delayed. AIMS: Clarify the current developmental surveillance and screening practices of one pediatric oncology team. MATERIALS AND METHODS: Researchers reviewed charts for patients (n = 66) seen at a pediatric oncology clinic in a suburban academic medical center to determine engagement in developmental screening (including functioning around related areas such as speech, neurocognition, etc.) and referrals for care in these areas. RESULTS: Developmental histories were collected from all patients through admission history and physical examination (H&P), but there was no routinized follow-up. Physicians did not conduct regular developmental screening per American Academy of Pediatrics guidelines for any patients but identified n = 3 patients with needs while the psychology team routinely surveilled all patients seen during this time (n = 41) and identified n = 18 patients as having delays. DISCUSSION: Physicians did not routinely screen for development needs beyond H&P and were inconsistent in developmental follow-up/referrals. Integrated psychologists were key in generating referrals for developmental-based care. However, many oncology patients were not seen by psychologists quickly or at all, creating a significant gap in care during a crucial developmental period. CONCLUSION: The case is made for further routinization of ongoing developmental screening in pediatric oncology care.