High-risk Cancer Research Articles

8722 Sodium-Glucose Cotransporter 2 Inhibitors And The Risk Of Kidney Cancer Among Patients With Type 2 Diabetes: A Population-Based Cohort Study

Abstract Disclosure: M. Lee: None. H. Kim: None. R. Kim: None. Y. Yang: None. S. Lee: None. E. Kang: None. There is an important need to develop clinical strategies to reduce the risk of incident kidney cancer, especially in patients with type 2 diabetes (T2D) and concomitant chronic kidney disease. Here, we investigated kidney cancer risk associated with sodium-glucose cotransporter 2 (SGLT2) inhibitor use in patients with T2D, using a nationwide cohort of the Korean National Health Insurance claims and health examination database. After 1:1 propensity score matching, 83,531 SGLT2 inhibitor users and 83,531 non-users on other oral glucose-lowering drugs were selected from 814,685 cancer-free participants, aged 20 to 79 years, who started oral glucose-lowering drugs for T2D from 2014 to 2018. During 559,738 person-years of follow-up, 143 (25.5 per 100,000 person-years) new kidney cancer events occurred. SGLT2 inhibitor use was associated with a 37% reduced risk of kidney cancer compared with other oral glucose-lowering drug use (18.1 vs. 29.9 per 100,000 person-years; hazard ratio [HR], 0.63; 95% CI, 0.43 to 0.92). The reduced kidney cancer risk by SGLT2 inhibitor use was consistent even after additional adjustment for all variables composing the propensity scores (HR, 0.64; 95% CI, 0.43 to 0.93) and regardless of age, sex, BMI, comorbidities, or diabetic complications including nephropathy (all p > 0.1 for interaction). SGLT2 inhibitor use may be a preferable option for patients with T2D at high risk of kidney cancer. Presentation: 6/3/2024

Cancer risk assessment of premalignant breast tissues from patients with BRCA mutations by genome profiling

Patients with germline pathogenic variants of BRCA1/2 genes have a particular predisposition to develop breast cancer. No clinical test has been developed to accurately and quantitatively evaluate their risk of developing breast cancer. We hypothesized that aberrant cell clonal expansion may be initiated in normal breast tissues without manifesting pathologic changes. To assess the prevalence of clonal expansion in the normal breast, we collected normal breast tissue from 24 breast cancer patients who had undergone surgical resection and 5 carriers of pathogenic BRCA1/2 variant who had undergone prophylactic mastectomy. Whole-exome sequencing (WES) was conducted in 97 specimens from 14 individuals, and TOP panel, a gene panel targeting 464 genes, was conducted in 321 specimens from 26 individuals, including 8 individuals with germline pathogenic variants of BRCA1/2 genes. Recurrent oncogenic mutations within PIK3CA, ARHGAP35, HRAS, and NF1 were identified in normal breast tissue at considerable variant allelic frequencies (VAF), suggesting clonal expansion. In addition, 937 normal breast tissues were evaluated using the Breast Cancer Panel (BCP) targeting 25 genes to determine the exact prevalence and distribution of clonal expansion. To assess the clonal expansion, we developed the clonality score, which is the mean value of clonal cell fractions for samples obtained from a given breast. The average clonality score in macroscopically normal breast tissue was 0.95 (0–2.46), with a significant difference between cases with and without a history of breast cancer of stage 2 or more advanced stage (p = 0.01). Additional WES on 42 samples with relatively large clone size (VAF > 3%) confirmed that these cell clones harbored multiple mutations (10.7 mutations/sample), and the number of existing mutations was consistent with the clone size (R = 0.50). The results suggest that clonal changes occur in normal breast tissue of women at high risk for breast cancer even before cancer is detected pathologically and/or radiologically, and the clonality score shows the potential to be a valid method of evaluating clonal expansion for cancer-risk assessment that provides appropriate preventive options for patients at high risk for breast cancer.

Prevention and treatment of cancer-associated thrombosis during chemotherapy

In patients with malignant neoplasms, the incidence of symptomatic venous thromboembolism (VTE) is 4–7 times higher than in the general population. The presence of distant metastases of solid tumors increases the risk of VTE. Most often, VTE develops in pancreatic and stomach cancers. Chemotherapy increases the risk of VTE development. Low-molecular-weight heparin and direct oral anticoagulants are used for the treatment of VTE in patients receiving chemotherapy.Prior to the start of chemotherapy, it is necessary to assess the risk of VTE development using the Khorana risk score. Outpatient patients with high-risk cancer (Khorana score >3 before the start of a new systemic chemotherapy regimen) may be prescribed thromboprophylaxis.

A ten-year overview of cancer genetic family history screening in Georgia's Latina population.

Population-based cancer genetic family history (FH) screening to identify families at high risk for BRCA-associated cancers has been endorsed by national public health policies. This report aimed to describe the utilization of FH screening services from 2013 to 2022 according to rurality and socioeconomic deprivation among Latinas in Georgia. Women who attended a medical appointment at participating Georgia Public Health Clinics were invited to complete FH screening. Screening results and participant zip code were reviewed. Area deprivation index (ADI) was measured at the census block group level and dichotomized (more deprived and less deprived). Rurality was measured through Rural-Urban Commuting Area (RUCA) codes and dichotomized (urban and rural). The ADI and RUCA codes were linked to participant data by zip code to characterize FH utilization among the Latina community. Of the 9,330 adult Latinas in Georgia that completed cancer genetic FH screening, 9,066 (97.17%) women screened negative, and 264 (2.83%) screened positive (i.e., FH suggestive of higher risk for carrying BRCA1/2 mutations compared to the general population). Screening completion was higher among Latinas in urban areas (n = 7,871) compared to rural areas (n = 1,459). Screening completion was also higher in more socially deprived areas (n = 5,207) compared to less socially deprived areas (n = 4,123). Georgia's FH screening program reached Latinas across Georgia, particularly those living in urban, socially deprived areas. To ensure equitable cancer genetic screening dissemination, future efforts should prioritize tailored outreach in rural regions and comprehensive evaluations to identify key determinants of screening trends among Georgia's Latina population.

Is an Electronic Nose Able to Predict Clinical Response following Neoadjuvant Treatment of Rectal Cancer? A Prospective Pilot Study.

Introduction: A watch-and-wait strategy for patients with rectal cancer who achieve a clinical complete response after neoadjuvant (chemo) radiotherapy is a valuable alternative to rectal resection. In this pilot study, we explored the use of an electronic nose to predict response to neoadjuvant therapy by analyzing breath-derived volatile organic compounds. Materials and Methods: A pilot study was performed between 2020 and 2022 on patients diagnosed with intermediate- or high-risk rectal cancer who were scheduled for neoadjuvant therapy. Breath samples were collected before and after (chemo) radiotherapy. A machine-learning model was developed to predict clinical response using curatively treated rectal cancer patients as controls. Results: For developing the machine-learning model, a total of 99 patients were included: 45 patients with rectal cancer and 54 controls. In the training set, the model successfully discriminated between patients with and without rectal cancer, with a sensitivity and specificity of 0.80 and 0.65, respectively, and an accuracy of 0.72. In the test set, the model predicted partial or (near) complete response with a sensitivity and specificity of 0.64 and 0.47, respectively, and an accuracy of 0.58. The AUC of the ROC curve was 0.63. Conclusions: The prediction model developed in this pilot study lacks the ability to accurately differentiate between partial and (near) complete responders with an electronic nose. Machine-learning studies demand a substantial number of patients and operate in a rapidly evolving field. Therefore, the prevalence of disease and duration of a study are crucial considerations for future research.

Syndemic Geographic Patterns of Cancer Risk in a Health-Deprived Area of England

ObjectivesThis study aims to analyse the geographical co-occurrence of cancers and their individual and shared risk factors in a highly deprived area of the North West of England to aid the identification of potential interventions. Study DesignAn ecological study design was employed and applied at postcode sector level. MethodsA novel spatial joint modelling framework designed to account for large frequencies of left-censored cancer data was employed. Nine cancer types (breast, colorectal, gynaecology, haematology, head and neck, lung, skin, upper gastrointestinal, urology) alongside demographic, behavioural factors and socio-economic variables were included in the model. Explanatory factors were selected by employing an accelerated failure model with lognormal distribution. Post-processing included principal components analysis and hierarchical clustering to delineate geographic areas with similar spatial risk patterns of different cancer types. Results15,506 cancers were diagnosed from 2017 to 2022, with the highest incidence in skin, breast and urology cancers. Factors such as age, ethnicity, frailty and comorbidities were associated with cancer risk for most of the cancer types. A positive geographical association was found mostly between the colorectal, haematology, upper GI, urology and head and neck cancer types. That is, these cancers had their largest risk in the same areas, similarly to their lowest risk values. The spatial distribution of the risk and cumulative risk of the cancer types revealed regional variations, with five clusters identified based on cancer type risk, demographic and socio-economic characteristics. Rural areas were the least affected by cancer and the urban area of Barrow-in-Furness was the area with the highest cancer risk, three times greater than the risk in the surrounding rural areas. ConclusionsThis study emphasizes the utility of joint disease mapping by geographically identifying common or shared factors that, if targeted, could lead to reduced risk of multiple cancers simultaneously. The findings suggest the need for tailored public health interventions, considering specific risk factors and socio-economic disparities. Policymakers can utilize the spatial patterns identified to allocate resources effectively and implement targeted cancer prevention programmes.

438 (PB426): Precision-guided treatment improves outcomes for children with highrisk cancers

438 (PB426): Precision-guided treatment improves outcomes for children with highrisk cancers

Artificial Intelligence Algorithm for Subclinical Breast Cancer Detection

Early breast cancer detection is associated with lower morbidity and mortality. To examine whether a commercial artificial intelligence (AI) algorithm for breast cancer detection could estimate the development of future cancer. This retrospective cohort study of 116 495 women aged 50 to 69 years with no prior history of breast cancer before they underwent at least 3 consecutive biennial screening examinations used scores from an AI algorithm (INSIGHT MMG, version 1.1.7.2; Lunit Inc; used September 28, 2022, to April 5, 2023) for breast cancer detection and screening data from multiple, consecutive rounds of mammography performed from September 13, 2004, to December 21, 2018, at 9 breast centers in Norway. The statistical analyses were performed from September 2023 to August 2024. Artificial intelligence algorithm score indicating suspicion for the presence of breast cancer. The algorithm provided a continuous cancer detection score for each examination ranging from 0 to 100, with increasing values indicating a higher likelihood of cancer being present on the current mammogram. Maximum AI algorithm score for cancer detection and absolute difference in score among breasts of women developing screening-detected cancer, women with interval cancer, and women who screened negative. The mean (SD) age at the first study round was 58.5 (4.5) years for 1265 women with screening-detected cancer in the third round, 57.4 (4.6) years for 342 women with interval cancer after 3 negative screening rounds, and 56.4 (4.9) years for 116 495 women without breast cancer all 3 screening rounds. The mean (SD) absolute differences in AI scores among breasts of women developing screening-detected cancer were 21.3 (28.1) at the first study round, 30.7 (32.5) at the second study round, and 79.0 (28.9) at the third study round. The mean (SD) differences prior to interval cancer were 19.7 (27.0) at the first study round, 21.0 (27.7) at the second study round, and 34.0 (33.6) at the third study round. The mean (SD) differences among women who did not develop breast cancer were 9.9 (17.5) at the first study round, 9.6 (17.4) at the second study round, and 9.3 (17.3) at the third study round. Areas under the receiver operating characteristic curve for the absolute difference were 0.63 (95% CI, 0.61-0.65) at the first study round, 0.72 (95% CI, 0.71-0.74) at the second study round, and 0.96 (95% CI, 0.95-0.96) at the third study round for screening-detected cancer and 0.64 (95% CI, 0.61-0.67) at the first study round, 0.65 (95% CI, 0.62-0.68) at the second study round, and 0.77 (95% CI, 0.74-0.79) at the third study round for interval cancers. In this retrospective cohort study of women undergoing screening mammography, mean absolute AI scores were higher for breasts developing vs not developing cancer 4 to 6 years before their eventual detection. These findings suggest that commercial AI algorithms developed for breast cancer detection may identify women at high risk of a future breast cancer, offering a pathway for personalized screening approaches that can lead to earlier cancer diagnosis.

Recent Insight into Herbal Bioactives-based Novel Approaches for Chronic Intestinal Inflammatory Disorders Therapy.

Inflammatory bowel disease (IBD) is a life-threatening complex disease. It causes chronic intestinal inflammation in GIT. IBD significantly affects people's lifestyles and carries a high risk of colon cancer. IBD involves the rectum, ileum, and colon, with clinical manifestations of bloody stools, weight loss, diarrhea, and abdominal pain. The prevalence of inflammatory disease is increasing dramatically worldwide. Over 16 million people are affected annually in India, with an economic burden of $6.8- $8.8 billion for treatment. Modern medicine can manage IBD as immunosuppressive agents, corticosteroids, tumor necrosis factor antagonists, integrin blockers, and amino-salicylates. However, these approaches are allied with limitations such as limited efficacy, drug resistance, undesired side effects, and overall cost, which cannot be ignored. Hence, the herbal bioactives derived from various plant resources can be employed in managing IBD. Science Direct, PubMed, Google, and Scopus databases have been searched for conclusively relevant herbal plant-based anti-inflammatory agent compositions. Studies were screened through analysis of previously published review articles. Eminent herbal bioactives, namely curcumin, resveratrol, ellagic acid, silybin, catechin, kaempferol, icariin, glycyrrhizin acid, berberine, quercetin, rutin, and thymol are reported to be effective against IBD. Herbal leads are promising treatment options for IBD; they have been shown to display antiinflammatory and antioxidant properties by targeting enzymes and regulating the expressions of various inflammatory mediators. Natural products have been reported to have anti-inflammatory properties in various clinical and preclinical studies, and some are available as herbal preparations. Herbal medicine would be promising in association with the implication of a novel drug delivery system for managing IBD.

A Decade of Contrast-enhanced Mammography: Expanding Screening to Women at Intermediate or High Risk for Breast Cancer.

A Decade of Contrast-enhanced Mammography: Expanding Screening to Women at Intermediate or High Risk for Breast Cancer.

Gastric Mucosal Status and Risk of Gastric Cancer in High-Risk Individuals: A Population-Based, Multicenter Prospective Study in China.

This study explored the distributions of gastric mucosal status and their links to gastric cancer within urban high-risk individuals in China. From 2014 to 2015, a questionnaire survey was administered among individuals aged 40 to 69 years, residing for over 3 years in seven selected cities across China. Utilizing the questionnaire data, high-risk individuals for gastric cancer were screened. These identified high-risk individuals were invited to undergo endoscopy, followed by pathological examinations conducted for those with suspicious lesions. Prior cancer patients and those newly diagnosed with gastric cancer were excluded, and the remaining endoscopic participants were prospectively followed up until December 2021. The prospective study followed 8911 individuals at high risk of gastric cancer for a median duration of 6.77 years. The incidence density of gastric cancer was 58.55 per 100,000 person-years. At baseline, the distributions of subjects across normal gastric mucosa, gastritis/ulcer/polyp, atrophic gastritis/intestinal metaplasia, and intraepithelial neoplasia groups were 47.09%, 36.27%, 9.57%, and 7.07%, respectively. Compared with normal gastric mucosa, the hazard ratios (HRs) for gastric cancer in the other groups were 0.89 [95% confidence interval (95%CI): 0.38-2.08], 1.52 (95%CI: 0.50-4.66), and 4.63 (95%CI: 1.98-10.82). When using the 40-54 age group as the reference, the HR for 55-69 age group was 3.49 (95%CI: 1.52-7.98). Among high-risk individuals with gastric cancer, the proportions of individuals exhibiting different gastric mucosal status inversely correlated with the severity of mucosal lesions, whereas the risk of gastric cancer progressively escalated with the increasing severity of mucosal lesions and advancing age.

Defining the Need for Services for Patients at High Risk of Breast Cancer at a Safety-Net Hospital: An Approach to Narrowing the Disparities Gap.

The National Accreditation Program for Breast Cancer (NAPBC) standards were recently revised to promote breast cancer (BC) risk assessment and subsequent referral for high-risk services. This project sought to estimate the proportion of patients at high risk for BC in the authors' safety-net hospital system, gauge patient interest in high-risk services, and define resources for program development. Women presenting for breast imaging during 2 weeks in 2023 were surveyed. Thirty-five patients with a history or diagnosis of BC were excluded. The Tyrer-Cuzick (TC) model version 8 was used to calculate BC risk. High/intermediate risk was defined as a 10-year risk of 5% or more, a lifetime risk of 15% or more, or both. The criteria for genetic counseling and testing referral were based on National Comprehensive Cancer Network guidelines. A total of 257 patients had a TC risk assessment showing 14.8% (n = 38) with a 10-year BC risk of 5% or more (consideration of endocrine therapy), 6.2% (n = 16) with a lifetime BC risk of 20% or more (qualifying for annual screening MRI), and 10.5% (n = 27) with a lifetime BC risk of 15% or more (consideration of high-risk screening). The criteria for genetic counseling/testing were met by 61 (23.7%) of the 257 patients. Overall, 31.5% (n = 81) qualified for high/intermediate-risk screening, risk reduction, and/or genetic assessment/testing, 92.8% of whom were interested in referrals for additional information and care. In the authors' community, almost one third of patients undergoing breast imaging qualify for BC high-risk assessment and services. The majority of the patients expressed interest in pursuing such services. These data will be used in financial planning and resource allocation to develop a high-risk program at the authors' institution in line with NAPBC guidelines. They are hopeful that these efforts will improve oncologic outcomes and survival from BC in their community.

Cost-Effectiveness of 9-Valent HPV Vaccination for Patients Treated for High-Grade Cervical Intraepithelial Neoplasia in the UK

Patients who have been treated for high-grade cervical intraepithelial neoplasia (CIN grade ≥2) are at a high risk for subsequent CIN and other cancers and diseases related to human papillomavirus (HPV). HPV vaccination can reduce the risk of subsequent disease in patients surgically treated for grade 2 or greater CIN; however, there is no formal recommendation for prophylactic HPV vaccination in this high-risk population, and the cost-effectiveness is unknown. To assess the incremental lifetime outcomes, costs, and cost-effectiveness of integrating peritreatment 9-valent HPV (9vHPV) vaccination in combination with posttreatment surveillance for the prevention of cervical cancer and other HPV-attributable diseases in patients surgically treated for grade 2 or greater CIN vs posttreatment surveillance alone from a UK payer perspective. This economic evaluation used 3 independent Markov model structures. Model inputs for vaccine efficacy, utilities, and costs were obtained from published sources, and cervical cancer screening data were obtained from the National Health Service Cervical Screening Program. Costs were adjusted to 2022 to 2023 reference years. Data were analyzed from October 2022 to September 2023. Peritreatment vaccination with 9vHPV in combination with posttreatment surveillance compared with posttreatment surveillance alone. Clinical outcomes included grade 1, 2, or 3 CIN; cervical cancer; vaginal cancer; vulvar cancer; anal cancer; head and neck cancer; genital warts; and recurrent respiratory papillomatosis. Incremental cost-effectiveness ratios (ICERs) using a willingness-to-pay threshold (WTP) of £20 000 (US $26 200) per quality-adjusted life-year (QALY) were estimated. Deterministic sensitivity analysis and probabilistic sensitivity analysis were performed. Vaccination with 9vHPV in conjunction with posttreatment surveillance was cost-effective, with a favorable ICER of £13 789.07 (US $18 064.68) per QALY gained (ie, below the WTP of £20 000 per QALY) vs posttreatment surveillance alone. The resulting ICER was £52 358.01 (US $68 588.99) per HPV-related cancer averted and £64 090 (US $83 958.18) per HPV-related cancer death averted. The ICER was most sensitive to discount rate, incidence of HPV infection, vaccine price, and age at initial treatment for grade 2 or greater CIN. Results of the probabilistic sensitivity analysis showed peritreatment 9vHPV vaccination was cost-effective at the WTP recommended by the UK's Joint Committee on Vaccination and Immunisation (90% of iterations <£30 000 [US $39 300] per QALY) in 100% of iterations. These findings suggest that peritreatment prophylactic 9vHPV vaccination is a cost-effective option for preventing subsequent HPV-attributable diseases in patients surgically treated for grade 2 or greater CIN.

Exploring the use of health information technology in the awareness of genetic testing among individuals with a family history of cancer.

416 Background: Genetic testing plays a critical role in identifying individuals at high risk for certain cancers. Despite its significance, recent studies have demonstrated a lack of genetic testing awareness in the general population. This study aimed to illuminate potential avenues for improving the understanding of cancer genetic testing,specifically the association between health information technology (HIT) use and genetic testing awareness. Methods: In this cross-sectional study, we analyzeddata from the 2020 Health Information National Trends Survey (HINTS). Respondents ≥18 years with a family history of cancer were eligible. We excluded respondents without an electronic device or with a prior cancer diagnosis. HIT use (yes vs. no) was defined as having used electronic devices to look up health information, fill prescriptions, schedule medical appointments, or communicate with a health provider. The outcome measure was awareness of cancer genetic testing (yes vs. no). Descriptive statistics was used to compare baseline characteristics by HIT use. Multivariable logistic regression models were fit to calculate adjusted odds ratios (AOR) with 95% CIs. Results: Among a total of 2,075 respondents, 1,772 (85.4%) used one form of HIT and only 830 (40.0%) were aware of cancer genetic testing. The median age of the study population was 47 years. Patients who used HIT were younger, female, insured, married, had a relatively higher level of education and better access to a primary care provider. On multivariable analysis, overall HIT use was associated with increased awareness of cancer genetic testing, though not statistically significant (AOR 1.76; 95% CI: 0.82, 3.75). Stratifying by subgroups, having used HIT to communicate with doctors (AOR 0.83; 95% CI: 0.66, 1.05), check test results (AOR 0.91; 95% CI: 0.77, 1.08), look up health information online (AOR 0.78; 95% CI: 0.51, 1.22), or make health appointments (AOR 0.90; 95% CI: 0.77, 1.05) was not significantly associated with increased awareness of cancer genetic testing. Conclusions: Our study demonstrates a high prevalence of HIT use, with no statistically significant associations with awareness of genetic testing among individuals with a family history of cancer. Findings prompt a reevaluation of other targeted health educational strategies to close the knowledge gap of cancer genetic testing for this high-risk population.

Defining the complex needs of families with rare diseases-the example of telomere biology disorders.

Families with rare diseases, such as telomere biology disorders (TBDs), may have extensive unmet needs given the heterogeneity, chronicity, and potential severity of illness. TBDs are rare inherited syndromes associated with high risk of bone marrow failure, cancer, pulmonary fibrosis, and other severe, chronic complications. To identify gaps in clinical care, we aimed to ascertain the perceived unmet needs of adults and family caregivers, current or bereaved, of individuals with TBDs. Participants were aged ≥18 years with a self-reported TBD diagnosis and/or ever caregivers to one or more family members with a TBD. Participants completed an online survey (N = 35) and/or an audio-recorded telephone interview (N = 32). We calculated descriptive statistics in SPSS and thematically analyzed interview transcripts. Quantitative and qualitative data were analyzed concurrently. Most participants were aged ≥35 years, female, highly educated, and medically insured. Survey respondents reported numerous unmet needs in psychosocial, medical, financial, and daily activity domains. In interviews, participant descriptions validated and contextualized the salience of these unmet needs. Both qualitative and quantitative data identified critical shortfalls in addressing chronic family distress and specialty care coordination. Adults and caregivers of individuals with TBDs have a high risk of adverse psychosocial sequelae given extensive unmet needs. These findings provide a foundation for understanding the range and extent of gaps in care for families with rare diseases, especially TBDs but that are likely applicable to others. Tailored multi-disciplinary interventions involving patients, families, clinicians, researchers, and patient advocacy communities are required to appropriately address care needs for all rare diseases.

Implementation of the updated Sydney system biopsy protocol improves the diagnostic yield of gastric preneoplastic conditions: Results from a real-world study

BackgroundThe updated Sydney system biopsy protocol (USSBP) standardizes the sampling of gastric biopsies for the detection of preneoplastic conditions (e.g., gastric intestinal metaplasia [GIM]), but the real-world diagnostic yield is not well-described. AimTo determine whether regular application of USSBP is associated with higher detection of chronic atrophic gastritis (CAG), GIM and autoimmune gastritis (AIG). MethodsWe performed a real-world retrospective study at an academic urban tertiary hospital in Chile. We manually reviewed medical records from consecutive patients undergoing esophagogastroduodenoscopy (EGD) from January to December 2017. Seven endoscopists who performed EGDs were categorized into two groups (USSBP ‘regular’ and USSBP ‘infrequent’) based on USSBP adherence, using minimum 20% adherence as the prespecified threshold. Multivariable logistic regression models were used to estimate the odds ratios (aOR) and 95% confidence intervals (CI) for the association between endoscopist groups and the likelihood of diagnosing CAG, GIM or AIG. Results1206 patients were included in the study (mean age: 58.5; 65.3% female). The USSBP regular group demonstrated a higher likelihood of detecting CAG (20% vs. 5.3%; aOR 4.03, 95%CI: 2.69–6.03), GIM (12.2% vs. 3.4%; aOR 3.91, 95%CI: 2.39–6.42) and AIG (2.9% vs. 0.8%; aOR 6.52, 95%CI: 1.87–22.74) compared to infrequent group. Detection of advanced-stage CAG (Operative Link for Gastritis Assessment stage III/IV) was significantly higher in the USSBP regular vs. infrequent group (aOR 5.84, 95%CI: 2.23–15.31). ConclusionsRoutine adherence to USSBP increases the detection rates of preneoplastic conditions, including CAG, GIM and AIG. Standardized implementation of USSBP should be considered in high gastric cancer risk populations.

Real-world performance of integrative clinical genomics in pediatric precision oncology

Despite significant improvement in the survival of pediatric cancer patients, treatment outcomes for high-risk, relapsed, and refractory cancers remain unsatisfactory. Moreover, prolonged survival is frequently associated with long-term adverse effects due to intensive multimodal treatments. Accelerating the progress of pediatric oncology requires both therapeutic advances and strategies to mitigate the long-term cytotoxic side effects, potentially through targeting specific molecular drivers of pediatric malignancies. In this report, we present the results of integrative genomic and transcriptomic profiling of 230 patients with malignant solid tumors (the “primary cohort”) and 18 patients with recurrent or otherwise difficult-to-treat nonmalignant conditions (the “secondary cohort”). The integrative workflow for the primary cohort enabled the identification of clinically significant single-nucleotide variants, small insertions/deletions, and fusion genes, which were found in 55% and 28% of patients, respectively. For 38% of patients, molecularly informed treatment recommendations were made. In the secondary cohort, known or potentially driving alteration was detected in 89% of cases, including a suspected novel causal gene for patients with inclusion body infantile digital fibromatosis. Furthermore, 47% of findings also brought therapeutic implications for subsequent management. Across both cohorts, changes or refinements to the original histopathological diagnoses were achieved in 4% of cases. Our study demonstrates the efficacy of integrating advanced genomic and transcriptomic analyses to identify therapeutic targets, refine diagnoses, and optimize treatment strategies for challenging pediatric and young adult malignancies and underscores the need for broad implementation of precision oncology in clinical settings.

Long-term oncologic outcomes and complications of robot-assisted radical cystectomy for the treatment of urothelial carcinoma of the bladder

IntroductionTo report the long-term outcomes of robot-assisted radical cystectomy (RARC) for the treatment of muscle invasive and high-risk non-muscle invasive bladder cancer. MethodsWe reviewed a single tertiary center database of RARC from 2004 to 2020. Concomitant extended pelvic lymph node dissection and extracorporeal urinary diversion were performed. Cox regression analysis and the Kaplan-Meier method were used to identify factors associated with and report time-to-event estimations of recurrence-free survival and overall survival. Clavien-Dindo complications were identified, categorized, and substratified by time from surgery within 90-days and between 90-days and >5-years postoperatively. ResultsA total of 510 patients with median follow-up of 57.1 months (IQR 21.8–103.6) were included. Continent diversion was performed in 259 (51%) patients. Of the 340 (67%) ≥cT2 patients, 153 (45%) received cisplatin-based neoadjuvant chemotherapy. Recurrence was identified in 157 (31%) patients, and 118 (23%) died from bladder cancer. The overall complication rate was 52% with 267 (41%) major grade ≥ III events. Infectious (25%) and genitourinary (22%) complications were the most common irrespective of the time interval beyond 90-days. The risk of recurrence or death were increased by extravesical disease (HR 1.91 and 1.97, respectively) and lymph node positivity (HR 4.58 and 2.42, respectively) in multivariable analysis (all, P < 0.001). The estimated 5-, and 10-year recurrence-free and overall survival rates were 69% and 64% and 61% and 44%, respectively. ConclusionsRARC is a durable treatment that optimizes the probability of cure for patients requiring extirpation for bladder cancer. Targeting the modifiable complications of radical surgery may further improve the risk/benefit ratio of RARC.

S511 Direct Genetic Screening Approach in Hereditary Nonpolyposis Colorectal Cancer: A Health Economics Analysis in High-risk Colorectal Cancer Population; Perspective from Middle-Income Country

S511 Direct Genetic Screening Approach in Hereditary Nonpolyposis Colorectal Cancer: A Health Economics Analysis in High-risk Colorectal Cancer Population; Perspective from Middle-Income Country

Assessing capacity for hereditary cancer risk assessment in metro Chicago.

307 Background: Since 2005, the United States Preventive Services Task Force (USPSTF) recommends that primary care (PC) clinicians identify and refer adults with a high-risk cancer family history to cancer genetic services (CGS), yet hereditary cancer risk assessment (HCRA) continues to be underutilized in PC. A population-based approach to HCRA in PC settings can expand access to cancer prevention and early detection to vulnerable populations and reduce disparities in cancer outcomes. The Chicago Cancer Screening and Testing Access Coalition (CCSTAC) is developing strategies to integrate HCRA in PC settings. We conducted an environmental scan to assess current capacity to deliver 1) HRCA in Federally Qualified Health Centers (FQHCs) and 2) follow-up CGS for high risk patients. Methods: In 2023, we administered two surveys to assess HCRA practices in Metro Chicago. We invited 22 FQHCs to complete a 21-item survey of current practices, readiness to implement, and barriers to HCRA. We also invited 21 CGS sites to complete a 25-item survey to understand staffing, utilization, referral patterns, and barriers to access. Surveys were administered electronically via Qualtrics. We conducted a descriptive analysis of survey data. Results: Twenty FQHCs (91%) completed the survey on HCRA in PC; 85% reported familiarity with USPSTF guidelines for HCRA. The majority (75%) reported no plans to implement HCRA. Clinic workflow, paucity of follow-up resources, cost, lack of provider knowledge, and absence of HCRA as a mandatory performance measure were cited as the most significant barriers to implementation. Genetic counselors (GCs) from 19 CGS hospital-based sites (90%) completed the survey on availability of genetic services. CGS were most often located in a cancer center (47%); no CGS were located in PC. Most referrals originated from oncology, surgery, or gastroenterology, with the lowest rate of referrals from community-based PC. Nearly half of CGS clinics (47%) reported capacity for at least a small increase in patient volume. Wait-time at the majority of CGS clinics was less than a month. GCs cited patient logistics (e.g. transportation, time off work), lack of referral information from providers, and systemic racism as significant barriers in patient access to CGS. Conclusions: After almost 20 years of evidence-based guidelines, use of HCRA is still very limited in the community-based PC setting. Our findings point to a need to bridge the gap between hospital-based CGS and FQHCs to ensure patients in vulnerable communities have access to guideline-concordant cancer prevention and screening strategies. Based on these findings, CCSTAC is designing strategies to integrate HCRA in primary care at FQHCs focused on provider education, well-designed clinic workflows, connections with existing CGS, and advocacy to align UDS and HEDIS measures with USPSTF guidelines.