Increase In Incidence Of Cancer Research Articles

Increased cancer incidence and mortality among people with opioid use-related disorders: A nation-wide cohort study.

Studies on cancer incidence and mortality among people with opioid use-related disorders are lacking. We aimed to measure cancer-specific incidence, mortality and survival among people diagnosed with opioid use-related disorders in Norway during 2010-18. This was a cohort study conducted in Norway during 2010-18. Individuals (n = 20710) diagnosed with opioid use-related disorders. We conducted a cohort study utilizing a data-linkage of national health and population registers. Information on opioid use-related disorders was extracted from specialized healthcare, malignancies from the Cancer Registry of Norway and deaths from Cause of Death Registry. Cancer incidence and mortality were compared with the general population by calculating sex-specific age-standardized incidence (SIR) and mortality (SMR) ratios. One-year survival rates were computed. Compared with the general population, people with opioid use-related disorders were at an increased risk of developing cancer overall [SIR = 1.2, 95% confidence interval (CI) = 1.1-1.3] with a higher than twofold cancer mortality rate (SMR = 2.3, 95% CI = 2.0-2.7). Excess risk was observed for liver (12.6, 95% CI = 9.1-17.0), larynx (4.7, 95% CI = 1.7-10.2), lung (3.5, 95% CI = 2.8-4.3) and pancreas cancer (2.6, 95% CI = 1.6-4.0), whereas reduced risk was found for melanoma (0.5, 95% CI = 0.3-0.9), breast (0.6, 95% CI = 0.4-0.9) and prostate cancers (0.3, 95% CI = 0.1-0.4). Site-specific SMRs were significantly elevated for liver (12.3, 95% CI = 8.5-17.2), lung (3.9, 95% CI = 3.0-5.0), pancreas (3.0, 95% CI = 1.7-4.8) and colon cancers (1.9, 95% CI = 1.1-3.1). The average 1-year survival rate after a cancer diagnosis was low in liver, pancreas and colon cancer, ranging from 10 to 15% less than that of the general population. In Norway, cancer incidence and cancer-related mortality appear to be elevated among individuals with opioid use-related disorders.

A population-based study on incidence trends of kidney and renal pelvis cancers in the United States over 2000-2020.

Cancers of the kidney and renal pelvis are among the most prevalent types of urinary cancers. We aimed to outline the incidence trends of kidney and renal pelvis cancers by age, sex, race/ethnicity, and histology in the United States (US) from 2000 to 2020. The data was obtained from the Surveillance, Epidemiology, and End Results (SEER) 22 database. The identification of patients with kidney and renal pelvis cancers with morphologies of renal cell carcinoma, nephroblastoma, sarcoma, and neuroendocrine tumor was conducted utilizing the International Classification of Diseases for Oncology version 3. The average annual percent change (AAPC) were presented. All estimates were given in the form of counts and delayed age-standardized incidence rates (ASIRs) per 100,000 people. From 2000 to 2019, a total of 490,481 cases of kidney and renal pelvic cancer were recorded across all age groups in the US. The majority of them were among Non-Hispanic Whites (NHWs) (69.75%) and those aged 55-69 years (39.96%). The ASIRs per 100,000 for kidney and pelvis cancers were 22.03 for men and 11.14 for women. Non-Hispanic Black men had the highest ASIR (24.53 [24.24, 24.81]), and increase in ASIR over the 2000-2019 period (AAPC: 2.19% [1.84, 2.84]). There was a noticeable increase in incidence of kidney and renal pelvis cancers. Individuals aged 70-84 years had the highest ASIR for kidney and renal pelvis cancers. The COVID-19 era has resulted in a significant reduction in incidence rates across all demographics.

Controversy and boundary in the diagnose and treatment of thyroid cancer

In recent years, the incidence of thyroid cancer has rapidly increased, whereas the mortality rate has not risen correspondingly. Therefore, scholars at home and abroad have proposed the view of overdiagnosis in thyroid cancer, sparking intense debates about the phenomenon of overdiagnosis and overtreatment. A historical review and discussion of the primary reasons for the increase in thyroid cancer incidence and the improvement in treatment outcomes are beneficial. It helps clarify that the real increase in thyroid cancer is primarily due to the higher incidence rate, rather than overdiagnosis. Additionally, it allows us to reevaluate which factors guarantee favorable efficacy in thyroid cancer.

A Calculating Model of the Need Radiotherapy Departments with Equipment and Personnel due to an Increase in the Incidence of Cancer

Currently, all over the world, in Russia and the Republic of Sakha (Yakutia), there continues to be a significant increase in the number of cancer diseases, the mortality rate from which is in second place. Existing models for determining the number of devices and employees of a medical institution are mainly based indirectly and directly on the total population of administrative units. However, against the backdrop of an increase in the incidence of malignant neoplasms, it is necessary in the field of providing medical care to the adult population for cancer when determining the equipment parameters of radiotherapy departments to take into account the growing importance of morbidity. This paper presents a model for calculating the quantity of a certain high-tech apparatus, taking into account the incidence of malignant neoplasms as a first approximation in conditions of negligible population growth. Using the example of the radiotherapeutic department of the Yakut Republican dispensary, the initial number of the equipment that satisfies the current needs for medical care for cancer patients of the republic are determined. Based on this an example is made of calculating the number of linear electron accelerators and medical physicists that should be in the department in the near future. The results show that models for calculating equipment and staffing needs need to take into account the increase in cancer incidence.

Bisphenol S enhances the cell proliferation ability of prostate cancer cells by regulating the expression of SDS

Recent times have witnessed an increase in both incidence and mortality rates of prostate cancer. While some individuals with localized or metastatic cancer may progress slowly with a lower mortality risk, those with intermediate or high-risk cancer often face a higher likelihood of death, despite treatment. Bisphenol A (BPA) has been linked to various cancers, including prostate and breast cancer, yet the relationship between bisphenol S (BPS) and human health remains underexplored. In our study, we employed ssGSEA analysis to evaluate the BPS-associated score in a prostate cancer cohort. Additionally, differential expression analysis identified BPS-related genes within the same group. Through COX and LASSO regression analyses, we developed and validated a BPS-related risk model using ROC curve and survival analyses. A nomogram, integrating clinical characteristics with this risk model, was established for improved predictive accuracy, further substantiated by calibration curve validation. Molecular docking analysis suggested potential binding between SDS and BPS. We also conducted cell proliferation assays on C4–2 and LNCaP prostate cancer cells, revealing increased cell growth at a BPS concentration of 10–7 M, as evidenced by CCK8 and EdU assays. In summary, our findings shed light on the BPS-prostate cancer linkage, identifying BPS-associated genes, establishing a validated risk model, exploring SDS-BPS binding potential, and assessing BPS's effect on prostate cancer cell growth. These insights underscore the need for further investigation into BPS and its impact on human diseases.

Increased cancer incidence among patients with hidradenitis suppurativa - a Danish nationwide register study 1977-2017.

The chronic, inflammatory skin disease hidradenitis suppurativa (HS) (prevalence: 0.5%-1%, diagnostic delay: 7-10 years) primarily arises in younger adults and frequently coincides with autoimmune comorbidities and unhealthy life-styles (smoking and obesity). These factors are known to increase cancer risk, but despite this, information on cancer occurrence among HS patients is scarce. A nationwide retrospective register-based study assessing relative risk of cancer-overall and by anatomical site - following HS diagnosis expressed as standardized incidence ratios (SIRs), which is ratios between observed cases among all Danes diagnosed with HS since 1977 and expected cases based on cancer incidence rates of the entire Danish population during the same period. Participants consisted of a cohort of 13,919 Danes with HS, who during an average of 14.2 years of follow-up developed a total of 1,193 incident cancers, corresponding to a 40% increased risk (SIR = 1.4, 95% CI: 1.3 to 1.4, p < 0.001). Increased risks were observed for cancers of the respiratory system, oral cavity and pharynx, digestive organs and peritoneum, urinary tract, and the lymphatic tissues. These findings underline an unmet need for health monitoring, lifestyle interventions and cancer screening if and when relevant.

Non-preventable cases of breast, prostate, lung, and colorectal cancer in 2050 in an elimination scenario of modifiable risk factors

Most Western countries have increasing number of new cancer cases per year. Cancer incidence is primarily influenced by basically avoidable risk factors and an aging population. Through hypothetical elimination scenarios of multiple major risk factors for cancer, we estimated the number of new cancer cases that are non-preventable in 2050. We compare numbers of new postmenopausal breast, prostate, lung, and colorectal cancer cases in 2021 to projected numbers of new cases in 2050 under prevention scenarios regarding smoking, overweight and obesity, and alcohol consumption: no intervention, 50%, and 100% instant reduction. Cancer incidence data were derived from NORDCAN, and risk factor prevalence data from the Danish National Health Survey. Cancer projections were calculated with the Prevent program. Hypothetical 100% instant elimination of major risk factors for cancer in Denmark in 2022 will result in unchanged numbers of new breast and colorectal cancers in 2050. The number of new prostate cancers will increase by 25% compared to 2021. Unchanged risk factor levels will result in noticeable increase in cancer burden. Increase in life expectancy and age will entail an increase in cancer incidence, despite maximum effect of preventive actions in the population. Our results are important when planning future health care.

Abstract SY38-01: Diverse effects of obesity on cancer immunology and therapy: Both the good and the bad

Abstract Obesity (BMI of 30 or higher) has reached pandemic proportions in the US and continues to rise. Obesity is associated with increased cancer incidence, progression, and mortality. Obesity is also associated with a meta-inflammation as well as general immune suppression. However, we and others have observed in both preclinical models involving diet-induced obese (DIO) mice as well as clinical cancer outcomes, that obesity can be associated with increased efficacy and T cell responses following immune checkpoint inhibition (ICI) targeting PD-1/PDL-1 (Wang Z et al, Nat Med 2019). This protective effect in preclinical models occurred despite marked increased tumor growth and progression in DIO mice. The results indicated that an “obesity paradox” existed regarding some cancer immune therapies. However, this increased efficacy did not apply to all immune therapy responses as we have also observed that following strong systemic immunostimulatory regimens such as with high dose cytokines (IL2) or following an allogeneic hematopoietic stem cell transplant (HSCT), that obesity was correlated with poorer outcomes due to increased cytokine release syndrome (CRS) due to macrophage dysregulation, reduction in gut microbiome diversity, and increased gut permeability, in both preclinical models and clinical outcomes (Khuat LT et al, Sci Trans Med 2020). These results indicated that a balance exists between the positive and negative effects of obesity which could be contingent on the particular type of cancer immunotherapy applied. With ICI, obesity is beneficial, but strong systemic immunostimulatory therapies can result in heightened proinflammatory responses and pathologies. It has also been reported that sex differences regarding the obesity paradox may also occur with high BMI males demonstrating increased anti-tumor efficacy (McQuade JL et al, Lancet Oncol 2018). The physiology of obesity regarding adiposity deposition and metabolic perturbations are also affected by sex hormones and obesity can also have marked effects on both androgen and estrogen production. We therefore assessed the role of sex on different cancer immunotherapy outcomes in obesity. Following systemic cytokine application or after allogeneic HSCT, no differences were observed between male and female DIO mice regarding the increased toxicities due to CRS. In marked contrast, following ICI targeting PD-1, increased anti-tumor effects were only observed in male and not female DIO mice. This was associated with immune differences in which female DIO mice had higher myeloid derived suppressor cells (MDSCs) and decreased T cell responses. However, when female mice were ovariectomized before placed on diet, application of ICI now resulted in increased anti-tumor efficacy comparable to DIO males. Importantly, metabolomics indicated that key metabolite changes could be correlated with the return of responsiveness. Similarly, clinical outcomes stratified on both sex and BMI also demonstrated the increased efficacy following ICI in high BMI males. These results demonstrate that sex-linked differences exist regarding the effects obesity has on cancer immunotherapy outcome following ICI but not other types of immune therapies. Further, these sex-based differences in obesity can be correlated with immunological alterations, and these can be reversed by estrogen inhibition suggesting that hormone modulation may offer immunological benefits in the context of obesity following cancer immunotherapy involving ICI. Citation Format: William J. Murphy, Logan Vick, Robert Canter, Spencer Rosario, Arta Monjazeb. Diverse effects of obesity on cancer immunology and therapy: Both the good and the bad [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr SY38-01.

'There is still a part of me that would love to be the old me again', how do adolescents and young adults (AYA) experience cancer-related bodily changes: a phenomenological interview study.

Due to the increase in both cancer incidence and overall survival rates, more adolescents and young adults (AYAs) have to live with the effects that their cancer diagnosis and following treatments have on their bodies. This qualitative phenomenological study aimed to gain more insight into the way AYAs experience these effects and how they respond to these effects. Semi-structured interviews with a sample of 11 AYAs with an age range of 25-41years at the time of the interview, who were diagnosed with different types of cancer, were conducted. Participants were recruited via social media and patient associations until data saturation was reached. A topic guide with open-ended questions about lived experiences was used. Interpretative phenomenological analysis (IPA) was performed to analyse the transcripts. We identified six Group Experiential Themes based on different ways AYAs experience their bodies: (1) self-conscious body, (2) vulnerable body, (3) adapting to the body, (4) uncontrollable body, (5) remembering the body and (6) shared bodies. This study offers in-depth insight into the bodily experiences of AYAs after cancer and how they respond to these changes from a phenomenological point of view. This knowledge could be beneficial to provide more guidance for AYAs during and after their illness, by focussing on personalised psychological (after)care.

An Integrated Cancer Prevention Strategy: the Viewpoint of the Leon Berard Comprehensive Cancer Center Lyon, France.

This article describes some of the key prevention services in the Leon Berard Comprehensive Cancer Center (CLB) Lyon, France, which are based on clinical prevention services, outreach activities, and collaboration with professional and territorial health communities. In addition, research is embedded at all stages of the prevention continuum, from understanding cancer causes through to the implementation of prevention interventions during and after cancer. Health promotion activities in the community and dedicated outpatient primary cancer prevention services for individuals at increased risk have been implemented. The CLB's experience illustrates how prevention can be integrated into the comprehensive mission of cancer centers, and how in turn, the cancer centers may contribute to bridging the current fragmentation between cancer care and the different components of primary, secondary, and tertiary prevention. With increasing cancer incidence, the shift toward integrated prevention-centered cancer care is not only key for improving population health, but this may also provide a response to the shortage of hospital staff and overcrowding in cancer services, as well as offer opportunities to reduce carbon emissions from cancer care.

Restricted access and advanced disease in post-pandemic testicular cancer

Introduction: Urologists observed reduced cancer consultations and surgeries during the SARS-CoV-2 pandemic, raising concern about treatment delays. Testicular cancer serves as a particularly sensitive marker of this phenomenon, as the clinical stage of testicular cancer at presentation is predictive of cancer-specific survival. We aimed to investigate whether COVID-related restrictions to primary care access resulted in increased incidence of metastatic germ cell testis cancer. Methods: A retrospective chart review was conducted on all cases of testicular cancer managed surgically at our center from March 1, 2018, to February 28, 2023. Patients were categorized into temporal cohorts, representing before, during, and following the implementation of COVID-19 public health restrictions in the province of Newfoundland and Labrador. Results: Forty-one cases of testicular germ cell tumors were identified during the study period. The mean age at diagnosis was 40.8 years (standard deviation ±13.7). Demographics did not vary across the cohorts. Clinical stage 3 disease remained stable before and during the pandemic at 10.5% and 9.1% of cases, respectively. In the post-pandemic period, there was an increase to 27.3% (p=0.617). Surgical wait times remained stable across the pandemic (p=0.151). Conclusions: There was a 16.8% rise in clinical stage III disease from the pre-pandemic to post-pandemic period. Our study failed to identify a statistically significant increase in metastatic testis cancer incidence upon lifting of pandemic restrictions. Further study is necessary to confirm suspicions that pandemic restrictions contributed to increased incidence of metastatic testis cancer.

The association between pre-existing heart failure and cancer incidence: A systematic review and meta-analysis

Introduction and objectivesCardiovascular diseases (CVD) and cancer are some of the most recognized causes of mortality and morbidity worldwide. Cancer is the second leading cause of death in heart failure (HF) populations. Recent studies have hypothesized that HF might promote the development and progression of cancer. We aim to analyze and discuss the most recent evidence on the relationship between HF and cancer development. MethodsFrom inception to November 2022, we searched PubMed, Web of Science and ClinicalTrials.gov for relevant articles on patients with HF and a subsequent cancer diagnosis that reported outcomes of overall and site-specific cancer incidence, or mortality. ResultsOf 2401 articles identified in our original search, 13 articles met our criteria. Studies reporting risk rate estimates were summarized qualitatively. Studies reporting hazard ratios (HRs), or relative risks were combined in a meta-analysis and revealed that HF was associated with an increased overall cancer incidence with a HR=1.30 (95% CI: 1.04–1.62) compared with individuals without HF. Subgroup analyses by cancer type revealed increased risk for lung cancer (HR=1.87; 95% CI: 1.28–2.73), gastrointestinal cancer (HR=1.22; 95% CI: 1.03–1.45), hematologic cancer (HR=1.60; 95% CI: 1.23–2.08) and female reproductive cancer (HR=1.67; 95% CI: 1.27–2.21). Mortality from cancer was higher in HF patients compared with non-HF subjects with a HR=2.17 (95% CI: 1.23–3.84). ConclusionsOur systematic review and meta-analysis revealed that HF may result in a subsequent increase in cancer incidence as well as in cancer-related mortality. The most common cancer subtypes in HF patients were lung, female reproductive system, and hematologic cancers. Further research is needed to understand this association better and to provide the best cardiological and oncological care.

Perspectives of healthcare workers on chemotherapy treatment in selected facilities in Kenya

Healthcare workers are better placed to recognize the drivers of the cancer health care experience by patients, an important ingredient in shaping the realization of the third pillar of the Kenya National Cancer Control Strategy. To adequately assess health systems and identify bottlenecks in cancer care, a triumvirate of factors including patient, health system, and health workforce need to be considered. For context, Kenya’s health ministry reports that 70-80% of cancer patients in Kenya are diagnosed at an advanced stage of the disease, a pointer to a gap in the detection and linkage of cancer patients to care. With increasing cancer incidence, cancer treatment centres will experience increased patient loads and will be overwhelmed in addressing individualized patient needs. Health workers can offer information on what the cancer care situation is currently like, and lessons drawn from their experience used to create adequate health systems. An adequate health system has been fashioned as one that not only address patients' needs but also generates adequate information needed to inform the transformation of those systems in line with the goals contemplated in quality healthcare. The aim of this study was to explore (i) the perspectives of health workers on the characteristics of cancer patients seen in treatment facilities and (ii) the capacity of cancer treatment facilities in the management of cancer. A key informant approach using semi-structured interviews was carried out with sampled respondents consisting of health workers (n=12) in selected facilities who were providing outpatient chemotherapy treatment. Data analysis involved transcribing the interviews into first-person narratives and then analysed using the three-dimensional framework. Subsequently, thematic analysis was applied to generate themes. Data analysis generated three main themes: characteristics of patients receiving chemotherapy treatment, capacity of the facility to manage cancer patients, and factors that hinder effective cancer care provision. Cancer care in Kenya is impeded by poverty, staff shortages, and lack of adequate cancer care. There is a need to reorient cancer care with an emphasis on integrated cancer care delivery modalities.

Effective vaccination strategies for human papillomavirus (HPV) infection and cervical cancer based on the mathematical model with a stochastic process.

Human papillomavirus (HPV) infection poses a significant risk to women's health by causing cervical cancer. In addition to HPV, cervical cancer incidence rates can be influenced by various factors, including human immunodeficiency virus and herpes, as well as screening policy. In this study, a mathematical model with stochastic processes was developed to analyze HPV transmission between genders and its subsequent impact on cervical cancer incidence. The model simulations suggest that both-gender vaccination is far more effective than female-only vaccination in preventing an increase in cervical cancer incidence. With increasing stochasticity, the difference between the number of patients in the vaccinated group and the number in the nonvaccinated group diminishes. To distinguish the patient population distribution of the vaccinated from the nonvaccinated, we calculated effect size (Cohen's distance) in addition to Student's t-test. The model analysis suggests a threshold vaccination rate for both genders for a clear reduction of cancer incidence when significant stochastic factors are present.

Abstract 4818: Cancer disparities in Chile: Unveiling the impact of educational disparities and regional variances on mortality rates

Abstract Differences in education not only influence our access to good-quality and timely healthcare but also impact our ability to make healthy decisions, access nutritious food, and inhabit healthy and safe physical and psychological environments. Consequently, these factors have contributed to an increase in cancer incidence and mortality among individuals with lower levels of education. To assess the mortality rate based on education, we utilized census data and the national mortality register, comparing the cancer mortality rate between those with more than 12 years of education and those with less than 8 years. We employed a Poisson regression model, with the number of deceased individuals as the dependent variable and age, along with gender, region of residence, and education level as covariates. The natural logarithm of the population served as an offset. The exponential of the estimated betas in this regression represents the Relative Index of Inequality (RII), comparing individuals with a low educational level to those with a high educational level. We conducted the analysis using SPSS version 17.0 and SAS version 9.4, considering values with p-values less than or equal to 0.05 as significant, with a confidence interval of 95%. Our findings indicate that two cancer sites are particularly affected by these educational differences, gallbladder (RII(95%CI): 5.43 (4.0-7.5)) and gastric (RII(95%CI): 4.09 (3.5-4.8)) with additional disparities when comparing by gender (RII gallbladder in women (95%CI): 7.06 (5.0-10.9)). Interestingly, even though Chile is a relatively small country, there are significant variations of mortality by geographical region (RII(95%CI): 1.3 (1.1-1.5) to 3.1 (2.3-4.0)), in terms of magnitude and cancer sites, suggesting the influence of environmental factors. The results of this study should serve as a basis for decentralization and the development of a cancer policy that considers territorial differences in resource allocation and plans specific screening and early detection strategies tailored to the epidemiologic and sociodemographic profile. We also conducted a mortality analysis comparing education levels across age intervals. Our findings reveal that, up to the age of 60, mortality is significantly higher among individuals with less than 8 years of schooling. However, beyond the age of 60, the group with higher mortality comprises individuals with 9-12 years of education. This suggests that they may be more capable of affording health services and accessing screening and diagnosis compared to the less educated group but are still diagnosed at later stages when curative treatment is not feasible. In addition, this group has the highest tobacco consumption in the country. Citation Format: Paz Cook, Fabio Paredes, Jorge Jimenez de la Jara. Cancer disparities in Chile: Unveiling the impact of educational disparities and regional variances on mortality rates [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 4818.

Abstract 4335: High-resolution characterization of age-specific cell type composition changes and signaling events in HPV-negative HNSCC tumors

Abstract This study is aimed at testing the hypothesis that increased patient age fosters conditions that are favorable for head and neck squamous cell carcinomas (HNSCC) of the oral cavity development. There is a well-documented increase in cancer incidence with age observed across diverse cancer types, where elderly patients exhibit diminished survival outcomes compared to their younger counterparts. While the convergence of aging and cancer hallmarks offers valuable insights, further work is needed to elucidate the age-specific mechanisms influencing HNSCC, beyond the shared characteristics of these biological processes. To this end, we have assembled a high-quality human single-cell RNA-sequencing HNSCC atlas profiling more than 230,000 cells across more than 50 patients with ages ranging between 18 and 89, which provides a resource to investigate age-associated changes in the disease heterogeneity. For this library, we integrated six publicly available single-cell RNAseq datasets from 54 HPV-negative patients to create the atlas. Cells were clustered, classified, characterized by gene set enrichment analysis, both in the epithelial cell compartment and in the tumor microenvironment (TME). Differential cell type proportion analysis was performed to identify cell types enriched in young (&amp;lt;49 years) or old (&amp;gt;70 years) patients. Cell-cell communication analysis was performed to identify signaling events occurring between different populations, and how these and specific ligand-receptor pairs differed in patients of different ages. CNV analyses were performed to identify cancer subclones and assess level of variation across tumors. Interestingly, we identified distinct cell populations and signaling events that associate with age, and we were able to compare, validate and recapitulate these observations in the 4MOSC1 OSCC isograft tumor model in old and young mice. Additional notable findings include a differential enrichment for cytotoxic CD8 T cells over dysfunctional CD8 T cells in young patients when compared to old, suggesting younger patients have a more effective immune TME. We also found an enrichment for cancer-associated fibroblast populations in old patients (myCAFs) that send collagen signals to malignant epithelial cells, a result we have recapitulated using the 4MOSC1 model, and hypothesize may play a role in ECM stiffening, EMT, and metastasis. Further analyses are ongoing, and we plan to validate the hypotheses generated, specifically the presence of differential abundance of specific cell populations, and age-specific ligand-receptor signaling events that lead to tumor growth. Citation Format: Lina Kroehling, Anthony Spinella, Maria Kukuruzinska, Xaralabos Varelas, Stefano Monti. High-resolution characterization of age-specific cell type composition changes and signaling events in HPV-negative HNSCC tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 4335.

Abstract 3935: Involvement of nanoscale physical communication in obesity-associated breast cancer severity

Abstract Obesity is a risk factor for several cancers, including breast cancer, and contributes up to 20% of cancer-related deaths. Growing evidence from both clinical and preclinical studies indicates that increased obesity is associated with increases in cancer incidence, progression, metastasis, and therapeutic resistance. According to the Centers for Disease Control and Prevention (CDC), more than 70% and 40% of American adults can be classified as overweight and obese, respectively. However, treatment strategies for dealing with cancer in obese patients have not advanced apart from lifestyle interventions. However, several signaling mechanisms have been proposed related to the inflammatory and metabolic impact of obese adipocytes in promoting cancer progression. However, a lack of mechanistic understanding led to no specific treatment strategies have been proposed which can specifically downregulate the key regulator by which obese adipocytes promote cancer progression. Thus, translational research initiatives are immediately needed to provide mechanistic justifications for these striking statistics in order to better serve this growing segment of the population. Here, we have shown the role of nanoscale physical communication between breast cancer cells and adipose tissue in promoting cancer progression. Using high-resolution optical and electron microscopy, we have found that breast cancer cells form nanoscale tubular communications with obese adipocytes. Moreover, the cancer cells hijack mitochondria from obese adipocytes. However, coculturing cancer cells and obese adipocytes in the Boyden chamber, allowing exosomal and paracrine communication but blocking direct physical communication, revealed negligible mitochondria transfer. This observation indicates an active transfer of mitochondria via nanotube. A significantly higher rate of mitochondria transfer from obese adipocytes to cancer cells has been observed than non-differentiated pre-adipocytes. The transfer of mitochondria results in an increase in the metabolism of the cancer cells. The mechanistic investigation of the nanotube formation revealed actin's presence as the major component in the nanotube. The exocyst-GTPase protein complex has a prime contribution in actin remodeling and nanotube formation. Inhibition of exocyst-GTPase using a pharmacological inhibitor results in a significant reduction in nanotube-mediated mitochondria transfer. Conclusion: Our goal is to (i) investigate the direct physical connection between adipocytes and cancer cells and the effect on cancer progression and (ii) eliminate mortality related to obesity-associated breast cancer severity by introducing a new therapeutic strategy. Here, we have shown how cancer cells communicate with obese adipocytes and receive additional metabolic power for proliferation. The in vivo investigation of the same is under progress. Citation Format: Tanmoy Saha, Balaaji Baanupriya Srinivasan, Shiladitya Sengupta. Involvement of nanoscale physical communication in obesity-associated breast cancer severity [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3935.

Overview of the Engagement Process to Develop the Future of Cancer Impact (FOCI) Report in Alberta: The Power of Collective Action.

This commentary provides a detailed overview of the extensive stakeholder engagement efforts critical to the development of the Future of Cancer Impact (FOCI) in Alberta report. The overarching aim of the FOCI report was to support informed and strategic discussions and actions that will help key stakeholders in the province prepare for a future with increasing cancer incidence and survival. Employing a comprehensive approach and a diverse range of engagement activities, insights from a wide spectrum of stakeholders were gathered and subsequently used to shape the content of the report. This inclusive process ensured broad representation of perspectives, contributing to a deeper understanding of the complexities in cancer care. The outcome is a robust, consensus-driven report with recommendations set to drive significant transformations within the healthcare system. These efforts highlight the critical role of extensive, inclusive, and collaborative engagement in shaping healthcare initiatives and advancing discussions crucial for the future of cancer care in Alberta.

Small Extracellular Vesicles Harboring PD-L1 in Obstructive Sleep Apnea.

Obstructive sleep apnea syndrome (OSA) has been associated with increased cancer incidence and aggressiveness. One hypothesis to support this association is the implication of immune response, particularly the programmed cell death pathway, formed by the receptor PD-1 and its ligand PD-L1. Recent studies have shown dysregulation of this pathway in severe OSA patients. It has also been shown that small extracellular vesicles (sEVs) carrying PD-L1 induce lymphocyte dysfunction. Thus, the aim of our study was to analyze the expression of PD-L1 on sEVs of OSA patients and to evaluate the role of sEVs on lymphocyte activation and cytotoxicity. Circulating sEVs were isolated from OSA patients and the control group. Lymphocytes were isolated from the control group. Circulating sEVs were characterized by western blot, nanotracking analysis, and flow cytometry and were incubated with lymphocytes. Our results show no differences in the quantity and composition of sEVs in OSA patients and no significant effects of sEVs in OSA patients on lymphocyte activation and cytotoxicity. These results suggest that OSA does not modify PD-L1 expression on sEVs, which does not contribute to dysregulation of cytotoxic lymphocytes.

PErspective and current status of Radiotherapy Service in IRan (PERSIR)-1 study: assessment of current external beam radiotherapy facilities, staff and techniques compared to the international guidelines

Background and purposeRadiotherapy (RT) is an essential treatment modality against cancer and becoming even more in demand due to the anticipated increase in cancer incidence. Due to the rapid development of RT technologies amid financial challenges, we aimed to assess the available RT facilities and the issues with achieving health equity based on current equipment compared to the previous reports from Iran.Materials and methodsA survey arranged by the Iran Cancer Institute's Radiation Oncology Research Center (RORC) was sent to all of the country's radiotherapy centers in 2022. Four components were retrieved: the reimbursement type, equipment, human resources, and patient load. To calculate the radiotherapy utilization rate (RUR), the Lancet Commission was used. The findings were compared with the previous national data.ResultsSeventy-six active radiotherapy centers with 123 Linear accelerators (LINACs) were identified. The centers have been directed in three ways. 10 (20 LINACs), 36 (50 LINACs), and 30 centers (53 LINACs) were charity-, private-, and public-based, respectively. Four provinces had no centers. There was no active intraoperative radiotherapy machine despite its availability in 4 centers. One orthovoltage X-ray machine was active and 14 brachytherapy devices were treating patients. There were 344, 252, and 419 active radiation oncologists, medical physicists, and radiation therapy technologists, respectively. The ratio of LINAC and radiation oncologists to one million populations was 1.68 and 4.10, respectively. Since 2017, 35±5 radiation oncology residents have been trained each year.ConclusionThere has been a notable growth in RT facilities since the previous reports and Iran's situation is currently acceptable among LMICs. However, there is an urgent need to improve the distribution of the RT infrastructure and provide more facilities that can deliver advanced techniques.