Individual Cancer Research Articles

Cancer care for transgender and gender-diverse people: Practical, literature-driven recommendations from the Multinational Association of Supportive Care in Cancer.

In the United States, over 2 million individuals openly identify with a gender that differs from their sex assigned at birth. A cancer diagnosis is physically and psychologically taxing-and, in some, traumatic. However, for transgender and gender-diverse (TGD) people, many of whom have experienced discrimination in myriad health care settings, the challenges may be even greater. These recommendations focus on how best to deliver quality cancer care to transgender men (individuals who identify as men but were assigned female sex at birth), transgender women (individuals who identify as women but were assigned male sex at birth), and people who identify somewhere beyond this gender spectrum as nonbinary or using other terms, based on the available, albeit sparse, literature. This review broaches: (1) the epidemiology of cancer in TGD individuals, including the incidence of cancer and cancer-related mortality; (2) cancer center practices that are welcoming and affirming to TGD patients; (3) the need for awareness and intentionality in the spaces of diagnosis and treatment for cancer; (4) the inevitable conclusion that gender differences exist but much more needs to be learned about the impact of gender-affirming therapy, consisting of gender-affirming surgeries and gender-affirming hormone therapy, on cancer therapy; and (5) the efficacy and perceived safety of antineoplastic therapy and gender-affirming hormone therapy.

Identifying Factors Associated With Heightened Anxiety During Breast Cancer Diagnosis Through the Analysis of Social Media Data on Reddit: Mixed Methods Study.

More than 85% of patients report heightened levels of anxiety following breast cancer diagnosis. Anxiety may become amplified during the early stages of breast cancer diagnosis when ambiguity is high. High levels of anxiety can negatively impact patients by reducing their ability to function physically, make decisions, and adhere to treatment plans, with all these elements combined serving to diminish the quality of life. This study aimed to use individual social media posts about breast cancer experiences from Reddit (r/breastcancer) to understand the factors associated with breast cancer-related anxiety as individuals move from suspecting to confirming cancer diagnosis. We used a mixed method approach by combining natural language processing-based computational methods with descriptive analysis. Our team coded the entire corpus of 2170 unique posts from the r/breastcancer subreddit with respect to key variables, including whether the post was related to prediagnosis, diagnosis, or postdiagnosis concerns. We then used Linguistic Inquiry and Word Count (LIWC) to rank-order the codified posts as low, neutral, or high anxiety. High-anxiety posts were then retained for deep descriptive analysis to identify key themes relative to diagnostic progression. After several iterations of data analysis and classification through both descriptive and computational methods, we identified a total of 448 high-anxiety posts across the 3 diagnostic categories. Our analyses revealed that individuals experience higher anxiety before a confirmed cancer diagnosis. Analysis of the high-anxiety posts revealed that the factors associated with anxiety differed depending on an individual's stage in the diagnostic process. Prediagnosis anxiety was associated with physical symptoms, cancer-related risk factors, communication, and interpreting medical information. During the diagnosis period, high anxiety was associated with physical symptoms, cancer-related risk factors, communication, and difficulty navigating the health care system. Following diagnosis, high-anxiety posts generally discussed topics related to treatment options, physical symptoms, emotional distress, family, and financial issues. This study has practical, theoretical, and methodological implications for cancer research. Content analysis reveals several possible drivers of anxiety at each stage (prediagnosis, during diagnosis, and postdiagnosis) and provides key insights into how clinicians can help to alleviate anxiety at all stages of diagnosis. Findings provide insights into cancer-related anxiety as a process beginning before engagement with the health care system: when an individual first notices possible cancer symptoms. Uncertainty around physical symptoms and risk factors suggests the need for increased education and improved access to trained medical staff who can assist patients with questions and concerns during the diagnostic process. Assistance in understanding technical reports, scheduling, and patient-centric clinician behavior may pinpoint opportunities for improved communication between patients and providers.

Challenging Situations in the Treatment of Cancer-Associated Thrombosis.

Cancer-associated thrombosis (CAT) is a common clinical problem in the treatment of cancer patients posing some unique challenges. These include the need to balance between the risk of recurrent thromboembolic events and bleeding complications in the individual cancer patient. A frequently encountered dilemma is the need for long-term anticoagulation in the setting of active malignancy. Until now, optimal duration, intensity, and type of anticoagulation in cancer patients remain an area of ongoing debate. In this case-based review, we present several challenging clinical scenarios and provide guidance on management. For optimal treatment results, CAT generally requires a multidisciplinary approach including specialists for thrombosis and hemostasis as well as hematology and oncology. Individual patient preferences should always be taken into account, especially in clinical situations with weak treatment evidence.

Genetic and environmental risks for clonal hematopoiesis and cancer.

Somatic variants accumulate in all organs with age, with a positive selection of clonal populations that provide a fitness advantage during times of heightened cellular stress leading to clonal expansion. Easily measured within the hematopoietic compartment, clonal hematopoiesis (CH) is now recognized as a common process in which hematopoietic clones with somatic variants associated with hematopoietic neoplasms exist within the blood or bone marrow of individuals without evidence of malignancy. Most cases of CH involve a limited number of genes, most commonly DNMT3A, TET2, and ASXL1. CH confers risk for solid and hematopoietic malignancies as well as cardiovascular and numerous inflammatory diseases and offers opportunities for cancer prevention. Here, we explore the genetic and environmental factors that predispose individuals to CH with unique variant signatures and discuss how CH drives cancer progression with the goals of improving individual cancer risk stratification, identifying key intervention opportunities, and understanding how CH impacts therapeutic strategies and outcomes.

Alpha-1 antitrypsin deficiency associated with increased risks of skin cancer, leukemia, and hepatic cancer: A nationwide cohort study.

α1-Antitrypsin deficiency is characterized by elevated elastase activity and excessive elastin degradation, which may impact cancer development and progression. We tested the hypothesis that individuals with α1-antitrypsin deficiency have increased susceptibility to cancer in the Danish population. In a nationwide nested study, we identified 2702 individuals with α1-antitrypsin deficiency and 26,750 control subjects without α1-antitrypsin deficiency matched on age, sex, and municipality. We recorded admissions due to cancer as outcomes during a median follow-up of 62 years. Individuals with α1-antitrypsin deficiency versus control subjects had an increased hazard of skin cancer (2.18, 95%CI: 1.81-2.63), leukemia (1.76, 1.12-2.79), liver cancer (3.91, 2.23-6.85), and cancer overall (1.25, 1.13-1.38). Corresponding hazard ratios when the entire Danish population was used as control group were 3.02 (2.55-3.58), 1.83 (1.19-2.81), 4.46 (2.74-7.28), and 1.45 (1.31-1.59). When the analysis was stratified according to comorbidities, the hazard for skin cancer was higher in those with chronic obstructive pulmonary disease (COPD) (3.59, 2.60-4.95) and skin disease (2.93, 2.19-3.92) but remained elevated in those without any of these diseases. Hazards for skin cancer in individuals with α1-antitrypsin deficiency were similar when stratified by liver cirrhosis and ischemic heart disease (ps for interaction: ≥0.76). Hazards for liver cancer in individuals with α1-antitrypsin deficiency versus control subjects were similar when stratified according to liver cirrhosis, COPD, skin disease, and ischemic heart disease (ps for interaction: ≥0.13). Individuals with α1-antitrypsin deficiency have increased risks of skin cancer, leukemia, and liver cancer in the Danish population.

Association between plasma-glycosylated hemoglobin A1c/high-density lipoprotein cholesterol ratio and urinary albumin-creatinine ratio in Chinese adults

Objective: To explore the relationship between glycosylated hemoglobin A1c/high-density lipoprotein cholesterol ratio (HbA1c/HDL-C) and urinary albumin-creatinine ratio (UACR) in Chinese adults. Methods: In this cross-sectional study, the clinical data of 43 820 community residents (age>40 years) from the Risk Evaluation of Cancers in Chinese Diabetic Individuals (REACTION study; March-December 2012) across eight centers (Liaoning, Guangdong, Shanghai, Gansu, Guangxi, Henan, Hubei, and Sichuan) in China were collected and analyzed. Participants were divided into three groups based on UACR levels:<10 mg/g, 10-30 mg/g, and >30 mg/g. The HbA1c/HDL-C ratio was divided into four groups according to quartile division of the subjects: 1st quartile (Q1<3.79), 2nd quartile (3.79≤Q2<4.59), 3rd quartile (4.59≤Q3≤5.66), and 4th quartile (Q4>5.66). Multivariate ordinal logistic regression model was used to analyze the relationship between HbA1c/HDL-C and UACR. Receiver operating characteristic (ROC) analysis was used to explore the predictive value of HbA1c/HDL-C to UACR. Results: The 43 820 subjects included 13 452 (30.70%) male and 30 378 (69.30%) female patients, with an average age of (58.00±0.05) years. According to results of one-way analysis of variance analysis, the HbA1c/HDL-C ratio was significantly associated with the risk of increased UACR (F=495.73, P<0.001). After adjusting for clinically relevant confounding variables in logistic regression model, compared with participants with the lowest HbA1c/HDL-C ratio (Q1), women with the highest HbA1c/HDL-C ratio (Q4) had a 1.483-fold (95%CI 1.376-1.598, P<0.001) and men had a 1.161-fold (95%CI 1.019-1.323, P<0.001) increased risk of UACR. The ROC curve analysis showed that the area under the curve of HbA1c/HDL-C for predicting increased UACR was 0.623 (95%CI 0.597-0.606), with a sensitivity of 60.18% and a specificity of 54.91%. The HbA1c/HDL-C ratio showed the highest predictive value of all glycemic and lipidemic parameters. In individuals with well-controlled blood glucose (HbA1c<6.5%) or lipid levels (HDL-C≥1.0 mmol/L), the HbA1c/HDL-C ratio was still independently associated with the risk of increased UACR after adjusting for confounding variables [OR(95%CI) of quartile 4: 1.563 (1.210-2.019, P=0.001) in participants with HbA1c<6.5% and 1.822 (1.687-1.968, P<0.001) in participants with HDL-C≥1.0 mmol/L]. Conclusion: As a novel compound indicator for evaluating glucose homeostasis and dyslipidemia, the HbA1c/HDL-C ratio was independently associated with increased UACR in the general population aged>40 years in China, which was superior to both glycemic and lipid parameters alone.

Evaluation of some physicochemical parameters and health risks associated with potentially toxic elements (PTEs) in agricultural soils from the southwest region of Ethiopia

In this study, soil samples collected from Burusa and Bure agricultural sectors were analyzed for their physicochemical parameters and potentially toxic elements (Fe, Mn, Zn, Cu, Co, B, Se, Ni, Cr, Pb, Cd, As, and Hg). Physicochemical parameters were analyzed according to AOAC methods. For quantification of PTEs, the soil samples were digested by using aquaregia (HCl: HNO3; 3:1) and 5 mL of H2O2 (30%) at a digestion temperature of 250°C for 3 hours prior to ICP-OES analysis. The percent recoveries (%R) and relative standard deviation (%RSD) of this method ranged from 83 to 106% and 0.39 to 9.2%, respectively. The LODs and LOQ values were in the range of 4.3 × 10-4-5.3 × 10-2 mg/L and 1.4 × 10-3-1.76 × 10-1 mg/L, respectively. The analyzed mean values of physicochemical parameter including pH, temperature, electrical conductivity, moisture, organic matter and nitrogen content were found in the range of 4.85-6.47, 20.5-21.4°C, 101.6-230.7 µS/cm, 8.67-20.7%, 0.677-1.81% and 5.81-6.85%, respectively. The average amount of potentially toxic elements found in the soil samples were ranged as 57073-81279, 1185-3255, 41.0-72.2, 12.6-29.2, 18.8-50.8, 25.0-40.5, 42.2-60.8, 13.6-34.5, 41.9- 67.2, 25.0-59.4, 9.92-13.3, 0.933-1.12 and 4.97-8.63 in mg/kg for Fe, Mn, Zn, Cu, Co, B, Se, Ni, Cr, Pb, Cd, As and Hg, respectively. The highest concentrations of among the entire PTEs were recorded for Fe, followed by Mn, in the analyzed soil samples. All the studied elements are below the FAO/WHO permissible limit except Fe, Se, Cd, and Hg for all analyzed soil samples and Mn for the Bure soil sample. The target hazard quotient (THQ) and hazard index (HI) values are <1, suggesting an insignificant non-carcinogenic risk of the heavy metals to the adults via ingestion, inhalation, and dermal contact exposure of agricultural soils. Likewise, the individual element incremental lifetime cancer risk (ILCR) occurrence for all studied soil samples is below 1 × 10-4. The total ILCR of potentially toxic heavy metals (Ni, Cr, Pb, Cd and As) resulting from ingestion, inhalation, and dermal contact exposure of agricultural soil by an adult population indicate a slightly higher potential cancer risk (> 1 × 10-4) for soil samples obtained from Bure S1, Bure S2, and Bure S3. Therefore, continuous monitoring of these harmful elements should be made by agricultural sectors and responsible government regulatory authorities are crucial to prevent PTEs related to agricultural soils in Ethiopia.

A stochastic population model for the impact of cancer cell dormancy on therapy success

Therapy evasion – and subsequent disease progression – is a major challenge in current oncology. An important role in this context seems to be played by various forms of cancer cell dormancy. For example, therapy-induced dormancy, over short timescales, can create serious obstacles to aggressive treatment approaches such as chemotherapy, and long-term dormancy may lead to relapses and metastases even many years after an initially successful treatment.In this paper, we focus on individual cancer cells switching into and out of a dormant state both spontaneously as well as in response to treatment. We introduce an idealized mathematical model, based on stochastic agent-based interactions, for the dynamics of cancer cell populations involving individual short-term dormancy, and allow for a range of (multi-drug) therapy protocols. Our analysis – based on simulations of the many-particle limit – shows that in our model, depending on the specific underlying dormancy mechanism, even a small initial population (of explicitly quantifiable size) of dormant cells can lead to therapy failure under classical single-drug treatments that would successfully eradicate the tumour in the absence of dormancy. We further investigate and quantify the effectiveness of several multi-drug regimes (manipulating dormant cancer cells in specific ways, including increasing or decreasing resuscitation rates or targeting dormant cells directly). Relying on quantitative results for concrete simulation parameters, we provide some general basic rules for the design of (multi-)drug treatment protocols depending on the types and processes of dormancy mechanisms present in the population.

Multiomics biomarkers were not superior to clinical variables for pan-cancer screening

BackgroundCancer screening tests are considered pivotal for early diagnosis and survival. However, the efficacy of these tests for improving survival has recently been questioned. This study aims to test if cancer screening could be improved by biomarkers in peripheral blood based on multi-omics data.MethodsWe utilize multi-omics data from 500,000 participants in the UK Biobank. Machine learning is applied to search for proteins, metabolites, genetic variants, or clinical variables to diagnose cancers collectively and individually.ResultsHere we show that the overall performance of the potential blood biomarkers do not outperform clinical variables for collective diagnosis. However, we observe promising results for individual cancers in close proximity to peripheral blood, with an Area Under the Curve (AUC) greater than 0.8.ConclusionsOur findings suggest that the identification of blood biomarkers for cancer might be complicated by variable overlap between molecular changes in tumor tissues and peripheral blood. This explanation is supported by local proteomics analyses of different tumors, which all show high AUCs, greater than 0.9. Thus, multi-omics biomarkers for the diagnosis of individual cancers may potentially be effective, but not for groups of cancers.

Burden of gastrointestinal cancers among adolescent and young adults in Asia-Pacific region: trends from 1990 to 2019 and future predictions to 2044

Background Gastrointestinal cancer is a significant cause of cancer incidence and mortality. Nevertheless, the epidemiology of the burden among adolescents and young adults (AYAs, aged 15–39 years) remains limited in the Asia-Pacific region, despite the region’s significant population. This study aims to explore the gastrointestinal cancer burden among AYAs in the Asia-Pacific region for the year 2019, while also analysing trends from 1990 to 2019 and projecting future trends up to 2044. Methods Annual case numbers, age-standardized rates of incidence, death, and disability-adjusted life-years (DALYs) and their estimated annual percentage changes (EAPCs) for gastrointestinal cancers were derived from the Global Burden of Disease, Injuries, and Risk Factors Study 2019. Trends over the next 25 years have also been predicted. Results In 2019, there were 117,714 incident cases, 61,578 deaths and 3,483,053 DALYs due to gastrointestinal cancers in the Asia-Pacific region, accounting for 68.5%, 67.6% and 72.4%, respectively, of global gastrointestinal cancers in this population. The highest age­standardized rates occurred in countries with a middle Socio-demographic Index. From 1990 to 2019, there was a decline in the age-standardized rates of incidence, death and DALY attributed to gastrointestinal cancers, with EAPC of −1.10, −2.48 and −2.44, respectively. These rates are expected to stabilize over 25 years, with notable variations in individual gastrointestinal cancers. Conclusions Gastrointestinal cancers among AYAs in the Asia-Pacific region have posed a significant burden over the past 30 years and are expected to persist in the coming years.

Breaking barriers: improving mammography screening accessibility and quality of care for breast cancer women with disabilities in Saudi Arabia

IntroductionBreast cancer screening remains pivotal in early detection and intervention. However, disparities persist, particularly among women with disabilities, necessitating a comprehensive understanding of their screening practices. This study aims to investigate breast cancer screening behaviours in Saudi women with disabilities.MethodsA cross-sectional study conducted in Saudi Arabia surveyed 307 women with disabilities, evaluating their screening frequency, knowledge of mammography, disability types, and duration. The Statistical Package for the Social Sciences (SPSS) was employed for data analysis.ResultsThe study found that 70.4% of participants had irregular breast cancer screenings, and 92.5% lacked tailored information on breast cancer screening. The primary sources of information were support groups (59.3%) and healthcare professionals (25.4%). Significant associations were observed between education levels and awareness of the importance of mammography and the increased risk of breast cancer in individuals with disabilities. Notably, participants with higher education levels demonstrated greater awareness.ConclusionThe findings highlight substantial gaps in breast cancer screening practices and knowledge among Saudi women with disabilities. There is a critical need for tailored educational programs, accessible information, and targeted awareness campaigns to address these disparities. Enhancing the accessibility of screening services and information for this demographic is essential for improving healthcare equity and outcomes.

Current Challenges and Potential Strategies in CAR-T Cell Therapy

Abstract. CAR-T therapy, involves modifying the patient's immune T cells in a laboratory setting to recognize antigens on tumor cells. Significant progress has been made in the treatment of hematologic malignancies, thanks to advancements in cancer treatment, namely the discovery of immunotherapies. Nevertheless, the therapy encounters obstacles such as antigen evasion, effects that target both tumor and non-tumor cells, restricted penetration into tumors, a tumor microenvironment that suppresses immune response, and adverse effects such as CRS and neurotoxicity. This paper analyzes the complexities of CAR-T treatment, its fundamental principles, and potential uses for many forms of cancer, including solid tumors. The primary objective is to improve the effectiveness and safety of the therapy by the manipulation of CAR-T cells, alteration of CAR structures, and investigation of combined treatment approaches. Although CAR-T therapy shows promise in transforming cancer treatment, additional refinement is necessary to optimize its therapeutic efficacy and decrease undesirable side effects. This will facilitate the development of more efficient and individualized cancer treatments.

Abstract A024: Assessing Mitondiral Priming in Leukemia Using BH3 Complex Specific Antibodies (PRIMABS): Prediciting Patient Response to Apoptosis Inducing Drugs

Abstract Diagnostic tools for cancer therapy that enable oncologists to inform patients about the likely benefits of their treatment versus toxicity will empower patients to make evidence-based decisions about the management of their disease, and in some cases, their last phase of life. Here we provide a novel approach that measures key drug response features of individual cancer cells with the potential for providing prognostic/predictive diagnostic utility for practicing precision medicine. Most cancer treatments work though activation of the cell suicide program of apoptosis. This process is tightly regulated by the BCL-2 family of proteins whose members either prevent or promote cell death. The relative levels of, and the specific interactions between the pro-survival and pro-apoptotic family members that dictates the fate of all cells and determines their propensity to undergo apoptosis. Cells that more readily die in response to various stimuli are referred to as “primed”. Hence, the degree of priming of a tumor sample can be predictive of responses to anti-cancer drugs and can be established using a technique called “BH3 profiling”. The relevance of this method has been demonstrated but it has had only limited application. To address this limitation a unique panel of antibody-based reagents that are mitochondrial PRIMing state detecting Antibodies (PRIMABS), have been developed by our lab, as a novel approach to implementing personalized medicine and developing predicative diagnostic tests. These antibodies enable the degree of tumor cell priming to be determined directly, unlike BH3 profiling which is an indirect measure. The key innovation lies in the approach taken to determine the presence (or absence) of the critical pro-survival : pro-apoptotic protein complexes , as these are the principal determinants of cell priming.. Such PRIMAB reagents have hitherto not been available. Here we provide data outlining the methodology development as well as evidence demonstrating feasibility of PRIMABTM Dx platform for predicting AML and CLL patient response in retrospective studies. Our platform provides a PD biomarker that will become a clinical predictor of cancer cell response to treatments tat are intended to induce apopstosis in tumor cells. The PRIMABTM -DX platform will enable heretofore hard to achieve clinical applicability of priming measurements. This will be significant due to the important prognostic implications of PRIMAB-DxTM readouts and will provide insights into drug resistance and sensitivity mechanisms and lead to new treatment options for cancer patients. Citation Format: Michael Cardone. Assessing Mitondiral Priming in Leukemia Using BH3 Complex Specific Antibodies (PRIMABS): Prediciting Patient Response to Apoptosis Inducing Drugs [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: RNAs as Drivers, Targets, and Therapeutics in Cancer; 2024 Nov 14-17; Bellevue, Washington. Philadelphia (PA): AACR; Mol Cancer Ther 2024;23(11_Suppl):Abstract nr A024.

MS O08 - HPB Biomarkers for risk stratification of Intraductal Papillary Mucinous Neoplasm of the pancreas: A systematic review

Abstract Background Intraductal Papillary Mucinous Neoplasm (IPMN) of the pancreas is the precursor lesion from which pancreatic ductal adenocarcinoma (PDAC) arises in 10% of individuals. IPMNs may be associated with low-grade or high-grade dysplasia or an associated adenocarcinoma. Accurately determining low-risk from high-risk IPMN is crucial for early detection initiatives for PDAC, so treatment can be offered before invasive cancer in high-risk individuals but without causing harm to low-risk individuals. Currently, imaging forms the basis for stratification but this is costly, resource intense and is limited in accuracy. There is a need to develop biomarkers to improve the risk stratification of IPMN. Method A systematic review was conducted according to PRISMA-DTA guidelines by screening EMBASE, MEDLINE, CENTRAL and bibliographic reference lists for comparative studies. Studies were excluded if they were based on non-human subjects, not specific to IPMN, or determined IPMN from PDAC rather than low-grade from high-grade dysplasia in IPMN. Data extracted included study design, cohort demographics, specimen type, biomarker type, methodology for biomarker discovery, positive predictive value, negative predictive value, sensitivity, specificity or AUC value and were evaluated against the STARD checklist. Study quality was evaluated using the QUADAS-2 tool. Results We identified 1761 studies of which 88 were selected for analysis. Twenty-six studies identified biomarkers derived from serum/plasma, 25 from biopsy specimens, 18 from cystic fluid, 13 from radiological findings, 4 from pancreatic juice, 3 from clinical risk stratification and 1 urinary biomarker. Markers were based on proteins (43%), mRNA (1%), miRNA (14%), lncRNA (2%), DNA (16%), metabolites (1%), radiomics (19%), glycans (5%), inflammatory markers (5%) and clinical history (5%). We observed discriminatory values ranging from AUC 0.58-1, specificity 64-100% and sensitivity 56-90.9%. Conclusion This systematic review outlines the current evidence-base for potential biomarkers to determine low-risk from high-risk IPMNs of the pancreas. Current studies are limited by retrospective sample collection, limited cohort sizes and lack of external validation of candidate biomarkers. There is a need to develop and validate biomarkers in a longitudinal prospective cohort study of individuals undergoing IPMN screening with the ability to characterise low-risk to high-risk transformation which after external validation would be suitable for adoption into clinical practice.

Cancer Information Seekers' Comprehension Level and the Association With Preventable Cancer Risk Factors: A Cross-Sectional Analysis From a Nationally Representative U.S. Adult Survey.

To examine the association between U.S. adult cancer information seekers' comprehension level and preventable cancer risk factors. Cross-sectional analysis. Health Information National Trends Survey-6, 2022. 2,453 cancer information seekers. Four cancer risk factors were dichotomized: cigarette smoking (have smoked ≥100 cigarettes and currently smoke every day/some days); experiencing sunburn (≥1 times/past 12 months); being overweight/obese (≥25 body mass index [kg/m2]); and binge drinking (≥5 [male] or ≥4 [female] alcoholic drinks on one occasion/past 30 days). Individuals who reported that cancer information was hard to understand were considered having comprehension difficulties. Binomial and multinomial logistic regression analyses were conducted to examine the association of cancer information comprehension level with individual and cumulative cancer risk factors, adjusting for sex, race/ethnicity, age, annual household income, education level, metropolitan status, depressed mood, and cancer diagnosis history. Cancer information seekers with comprehension difficulties had higher odds of binge drinking (aOR: 1.66, 95% CI: 1.12, 2.46), being overweight/obese (aOR: 1.46, 95% CI: 1.09, 1.96), and experiencing sunburn (aOR: 1.61, 95% CI: 1.23, 2.11), as well as having ≥3 (aOR: 3.38, 95% CI: 1.87, 6.09) cancer risk factors concurrently than cancer information seekers without comprehension difficulties. Dissemination of easy-to-understand cancer information would help better prevent cancer risk factors for cancer information seekers with comprehension difficulties.

Reversal Potentials of Tween 20 in ABC Transporter-Mediated Multidrug-Resistant Cancer and Treatment-Resistant Depression Through Interacting with Both Drug-Binding and ATP-Binding Areas on MDR proteins

Drug efflux transporters, especially those belonging to the ATP-binding cassette (ABC) transporter superfamily, play a crucial role in various drug resistance issues, including multidrug resistance (MDR) in cancer and treatment-resistant depression (TRD) in individuals with major depressive disorder. Key transporters in this context include P-glycoprotein (P-gp), multidrug resistance protein 1 (MRP1), and breast cancer resistance protein (BCRP). This study aimed to investigate the modulatory effects of polyoxyethylene (20) sorbitan monolaurate (Tween 20) on these efflux transporters in vitro and to evaluate its potential for overcoming drug resistance in two models: an in vitro cancer MDR model and an in vivo TRD model. The findings indicated that 0.001% Tween 20 significantly inhibited the efflux actions of all three transporters. Additionally, 0.005% Tween 20 effectively reversed resistance to paclitaxel, vincristine, doxorubicin, and mitoxantrone in various cancer MDR cell lines. In the in vivo depression-like behavior model, 0.01% Tween 20 markedly enhanced the antidepressant and anxiolytic effects of fluoxetine. Given its strong inhibitory effects on P-gp, MRP1, and BCRP, along with its capacity to reverse drug resistance both in vitro and in vivo, Tween 20 is a compelling candidate for tackling transporter-mediated drug resistance.

Association between within-target risk factors and life expectancy free from cardiovascular disease, cancer, and dementia in individuals with type 2 diabetes in New Zealand between 1994 and 2018: a multi-ethnic cohort study

BackgroundThe extent to which type 2 diabetes (T2D) reduces life expectancy depends on the risk of complications. We aimed to characterise the relationship between risk factors for diabetes complications and life expectancy, in individuals with T2D, free from major chronic disease, in a regional database linked with national New Zealand health databases.MethodsA prospective cohort study design was employed, analysing data from individuals with T2D drawn from the comprehensive Diabetes Care Support Service database (1994–2018). Participants with known values for all five within-target risk factors (WTRF +) including blood pressure, glycaemia, and LDL cholesterol, alongside being non-smoking with normal renal function at baseline, were included. Life expectancy free from cardiovascular disease (CVD), cancer, and dementia at age 50 years was estimated using multistate life tables, adjusting for demographics and clinical metrics.ResultsWomen and men with no WTRF + at enrolment had a life expectancy free from CVD, cancer, or dementia of 13.1 (95% confidence interval: 9.1–19.0) and 11.2 (6.7–18.6) years, respectively. For the most socioeconomically deprived groups or Māori with no WTRF + at baseline, life expectancies were markedly lower. Life expectancies were 23.7 (18.9–29.7) years for women and 23.2 years (17.2–31.4) years for men with four or five WTRF + at baseline, respectively. While an increasing number of WTRF + at baseline was significantly associated with improved outcomes in men and certain subgroups (e.g. Other ethnicity group), this trend was not statistically significant for women overall or in most subgroups.ConclusionsHaving multiple WTRF + at baseline is associated with a considerable increase in life expectancy free from major chronic disease among individuals with T2D. This highlights the importance of lifestyle and clinical interventions in the management of T2D and in the prevention and management of associated chronic conditions.

TMET-27. MACHINE LEARNING-BASED IDENTIFICATION OF METABOLIC FLUXES IN PATIENT BRAIN TUMORS

Abstract Personalized oncology aims to match effective treatments for individual cancer patients based on the biology of an individual tumor. This approach is not possible for metabolic therapies due to our inability to quantify metabolic activity in patient tumors, even when patients are infused with 13C-glucose. We overcame this challenge by generating training data with a prior knowledge of 13C-glucose infused patient data and implementing a machine learning model to predict fluxes. We trained a convolutional neural network (CNN) to predict flux ratios. To validate our model, we compared predicted flux ratios to the experimental 13C-glucose-infused mouse models to predict treatment responses for: (1) pharmacologic inhibition of de novo GMP synthesis and (2) environmental serine restriction. Our GMP synthesis model predicted elevated GMP synthesis in GBM compared to cortex in a mouse model and discriminated between sources of GMP synthesis in patients. These findings allow prediction of potential responders to mycophenolate mofetil (MMF), which inhibits de novo but not salvage GMP synthesis. Furthermore, we previously showed that circulating serine uptake is higher in GBM than normal cortex, and a serine- and glycine-restricted diet slows tumor growth in mice. While de novo serine synthesis, circulating and microenvironmental-derived serine could account for serine sources in GBM, our model can distinguish between serine sources in patients, hence potentially predict response to dietary serine depletion. Thus, we have shown that our model may identify patients who will benefit from MMF treatment or a serine- and glycine-restricted diet, potentially enabling administration of highly effective personalized metabolic treatments for GBM patients.

N-NOSE Proves Effective for Early Cancer Detection: Real-World Data from Third-Party Medical Institutions.

Cancer remains a leading cause of mortality in Japan, yet participation in conventional screening programs is low due to invasiveness, cost, and accessibility. Non-invasive, affordable, and accurate methods for early cancer detection in asymptomatic individuals are urgently needed. This opinion manuscript evaluates nematode cancer testing, a novel urine-based screening test using the nematode Caenorhabditis elegans, for its potential to improve early cancer detection rates, based on real-world data published in a Japanese journal. Nematode cancer testing leverages the nematode's ability to detect cancer-associated volatile compounds in urine, offering a highly sensitive, non-invasive screening approach. We analyzed data from a nationwide survey of PET-equipped medical institutions in Japan, comparing cancer discovery rates between nematode cancer testing-triggered and standard PET screenings. In nematode cancer testing-triggered PET screenings, the cancer discovery rate was 2.96%, significantly higher than the 1.31% observed in standard PET screenings. The apparent positive predictive value (PPV) of nematode cancer testing was calculated at 2.09%; when adjusted for PET/CT sensitivity, the actual PPV increased to approximately 11.7%. This reflects a screening efficiency 14.6 times higher than the general population's cancer incidence. These findings indicate that nematode cancer testing successfully detects cancer in high-risk individuals and may encourage participation in further diagnostic evaluations. The recently published nationwide survey of PET-equipped medical institutions in Japan highlights the good performance of nematode cancer testing in cancer detection. As an opinion-type manuscript based on real-world data from Japan, this paper shows that nematode cancer testing has substantial potential as a cost-effective, minimally invasive primary cancer screening tool for asymptomatic populations. By enhancing early detection rates and screening efficiency, it addresses the limitations of traditional screening methods. Implementing nematode cancer testing could lead to improved cancer outcomes, particularly in populations with low participation in standard screening programs and resource-limited settings.

COVID-19 infection in children with blood cancer: A systematic review.

Blood cancer is the most common type of cancer and the leading cause of death by disease past infancy among children. Children with blood cancer are vulnerable population to viral infections such as coronavirus disease 2019 (COVID-19). To estimate the incidence of COVID-19 in children with blood cancer and analyse the demographic parameters, clinical characteristics and treatment outcomes in children with blood cancer with COVID-19 illness. We adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline and searched ProQuest, Medline, Embase, PubMed, CINAHL, Wiley online library, Scopus and Nature for studies on the development of COVID-19 in children with blood cancer, published from December 1, 2019 to April 30, 2023, with English language restriction. Of the 3077 papers that were identified, 155 articles were included in the systematic review (83 case report, 54 cohort and 18 case-series studies). Studies involving 1289 children with blood cancer with confirmed COVID-19 were analysed. Leukaemias (1141 cases) were the most frequent types of blood cancer observed in children who developed COVID-19, followed by non-Hodgkin's lymphomas (59 cases), Hodgkin's lymphomas (36 cases), Langerhans cell histiocytosis (7 cases), myelodysplastic syndrome (7 cases) and myeloid neoplasm (1 case). Among all 1289 blood cancer paediatric cases who transmitted severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), some children were documented to be admitted to the intensive care unit (ICU) (n = 175, 13.6%), intubated and placed on mechanical ventilation (MV) (n = 111, 8.6%), suffered acute respiratory distress syndrome (ARDS) (n = 144, 11.2%) or died (n = 111, 8.6%). Overall, COVID-19 in children with different types of blood cancer resulted in no or low severity of disease in 78.6% of all included cases (COVID-19 severity: asymptomatic = 238, mild = 601, or moderate = 171). Treatment for COVID-19 was not necessary in a small number of children with blood cancer (n = 94, 7.3%). Fatality in children with blood cancer with COVID-19 was reported in any of the included blood cancer categories for leukaemias (n = 99/1141, 8.7%), non-Hodgkin's lymphomas (n = 7/59, 11.9%), Hodgkin's lymphomas (n = 2/36, 5.5%), myelodysplastic syndrome (n = 1/7, 14.3%) or myeloid neoplasm (n = 1/1, 100%). Fatality rate in children with blood cancer infected with SARS-CoV-2 was the highest in patients with Hispanic ethnicity (n = 44/111, 39.6%) and COVID-19-related fatality was highest in male patients (76.5% of deceased patients). Most studies reported to alter the intensity and regimen of anticancer treatment in children with blood cancer during course of SARS-CoV-2 infection, however, many studies have reported to successfully treat COVID-19 without any changes to the anticancer treatment. Globally, leukaemias were the most prevalent and myeloid neoplasms were the least prevalent blood cancer types in children who developed SARS-CoV-2 infection. Children with blood cancer infected with SARS-CoV-2 may experience higher rates of ICU admission and mortality in comparison with the healthy pediatric populations. Mortality in children with blood cancer and infected with SARS-CoV-2 was highest in cases belonging to male gender and Hispanic ethnicity. However, children with blood cancer tend to have milder COVID-19 symptoms and are less likely to be hospitalized and have better prognosis when compared to adults. Continuation of anticancer treatment in individual paediatric blood cancer patients with COVID-19 seems to be possible.