High-risk Cancer Research Articles

Feasibility of universal breast cancer risk assessment in a diverse, publicly insured obstetrician gynecology clinic.

e13759 Background: Breast cancer is the most diagnosed cancer among women in the United States. Established breast cancer risk assessment (BCRA) tools can estimate a woman’s lifetime risk and inform the need for enhanced breast screening which can improve cancer-associated morbidity and mortality. Currently, critical disparities exist both in breast cancer prognosis and screening uptake. We aimed to evaluate the feasibility of routine BCRA in a diverse, publicly insured obstetrician gynecology clinic. Methods: All patients presenting to the obstetrician gynecology clinic were offered a BCRA using the Tyrer Cuzick (TC) risk model. Patients completed paper surveys and the information was input into the TC model to generate lifetime risk estimates. Printed evidence-based management guidelines were reviewed with and provided to those at ≥ 20% lifetime breast cancer risk and shared with the patient’s provider. Results: Between June 2023 and February 2024, 300 patients were approached and 208 (69.3%) completed the survey. One hundred seven (51.4%) survey respondents were presenting for obstetrical care and 101 (48.6%) for gynecologic care. Respondents had a median age of 33 years (IQR: 12). Ninety-six (46.2%) responding patients self-identified as Hispanic, 45 (21.6%) as Black, 25 (12.0%) as Asian, 28 (13.5%) as Non-Hispanic White, and 14 (6.7%) did not identify in these categories. One hundred eighty-nine (90.9%) survey respondents were publicly-insured. Ten (4.8%) patients were assisted by an interpreter. Overall, 12 (5.8%) patients had an elevated lifetime breast of breast cancer, defined as ≥ 20% based on the TC model (6 (50.0%) among obstetrical patients and 6 (50.0%) among gynecology patients). All patients at elevated risk were referred to a genetics clinic for counseling on options for enhanced breast surveillance. Conclusions: As leaders in women’s cancer care, gynecologic oncologists can lead and support programs to identify those women at highest risk for cancer, especially among historically underserved populations. Our feasibility study demonstrated that 69.3% of patients were willing to complete a BRCA and this tool identified 5.8% of patients to have a significantly elevated lifetime breast cancer risk. Providers should consider incorporating such tools in gynecologic oncology and obstetrical/gynecology clinics.

Prognostic significance of serum Chemerin and neutrophils levels in patients with oral squamous cell carcinoma

ObjectivesChemerin, as a novel multifunctional adipokine, is proposed to be involved in high cancer risk and mortality. The present study was aimed to evaluate the prognostic value of serum Chemerin and neutrophils in patients with oral squamous cell carcinoma (OSCC). Materials and methods120 patients with OSCC were included in this prospective cohort study. The levels of serum Chemerin were measured by enzyme-linked immunosorbent assay (ELISA). We also explored the possible effects of Chemerin on neutrophils’ chemokines in OSCC using a real-time PCR, western blotting. ResultsLevels of serum Chemerin, neutrophils and NLR were significantly higher among non-survivors compared to survivors of OSCC (both P < 0.05). Higher serum Chemerin levels were associated with advanced TNM stage, lymph node metastasis, differentiation and tumor recurrence (both P < 0.05). Serum Chemerin levels correlated with neutrophils and NLR levels (r = 0.708, r = 0.578, both P < 0.05). Based on ROC analysis, Chemerin + NLR predicted OSCC patient mortality with 81.54 % sensitivity and 87.27 % specificity, with an AUC of 0.8898. In a Kaplan-Meier analysis, high serum Chemerin levels, high neutrophil levels and high NLR levels were associated with shorter overall and disease-free survival (both P < 0.05). A univariate and multivariate Cox regression analysis showed that serum Chemerin and neutrophils were independent risk factors for OSCC. (both P < 0.05). QRT-PCR and western blotting results showed that Chemerin upregulated the expression of chemokines IL-17 and CXCL-5 in neutrophils (both P < 0.05). ConclusionsOur study suggests that measurement of serum Chemerin and neutrophils might be a useful diagnostic and prognostic biomarker for OSCC patients. Chemerin may promote neutrophils infiltration in OSCC through upregulation of chemokines IL17 and CXCL-5.

Association of neighborhood-level superfund sites with atmospheric toxic exposures and increasing cancer risk in the United States: A proof-of-concept geospatial study.

10577 Background: Decades of underinvestment have disproportionately exposed several neighborhoods in the US to hazardous conditions. Superfund is the name given to the environmental program established by the US Congress in 1980, to address abandoned hazardous waste sites. The extent to which Superfund sites have contributed to differences in cancer risk remains unknown. We investigated atmospheric toxic exposures increasing cancer risk by proximity to Superfund sites at the neighborhood level. Methods: In this cross-sectional study of US neighborhoods, census-tract level air toxic cancer risk data from the Environmental Protection Agency for 2019 were linked with census-tract level geolocation data of ~1300 Superfund sites from the Superfund Enterprise Management System database. Linear regression models were utilized to explore association between cancer risk and proximity to Superfunds. Geographically Weighted Regression models explored spatial non-stationarity by modeling spatial relationships that vary across the study area. Bivariate Local Indicators of Spatial Association (LISA) cluster maps were created for superfund site proximity and cancer risk (high-high, low-low, low-high, high-low). Kruskal-Wallis testing compared the distributions of different variables across the four LISA cluster types. Results: Study explored 82,770 census tracts nationwide. For every 10 percentile increase in Superfund proximity, there was an increase of 4% in cancer risk (p &lt; 0.001). This association was strongest in the Intermountain West, South-Southeast, and Northeast regions. High-high clusters (high proximity to Superfund, high cancer risk) had higher percentage of non-White, low-income, unemployed and lower education attainment populations compared to low-low clusters (all p &lt; 0.001). Within high-high clusters, non-White population had the strongest correlation with proximity to Superfunds. Cancer risk was much higher for the top 10% than the bottom 10% of proximity to Superfunds (Table). Conclusions: Our study highlights higher clustering of cancer risk around neighborhoods with existing Superfund sites. Further, we demonstrate the closer a neighborhood is to a Superfund site, the greater the cancer risk is with associated sociodemographic changes. Using a novel approach to geospatial analytics, the results demonstrate the first clear evidence of a dangerous association between Superfunds and healthcare, and encourage the urgent prioritization of Congressional policies that optimize investment in Superfund site clean up for public health. [Table: see text]

Personalized 125I Seed Interstitial Brachytherapy for Patients Aged 80 Years and Over with Early Primary High-risk Non-melanoma Skin Cancer.

The aim of this study is to explore the safety and efficacy of iodine-125 seeds interstitial brachytherapy (PISI-BT) for patients aged 80 and above with early primary high-risk non-melanoma skin cancer (NMSC). In this retrospective single-center study, we collected and analyzed data from patients ≥ 80 years of age with early primary high-risk NMSC treated with PISI-BT between December 2003 and May 2020. Survival status, efficacy, adverse effects (AEs), cosmetic outcomes, and treatment cost were analyzed (data cut-off: November 20th, 2021). Only 9 patients met the inclusion criteria (median age, 86 years (81-90)). Five patients had an Eastern Cooperative Oncology Group (ECOG) score of 1, and allthe patients had at least one comorbidity. Six patients showed complete responseand three showed partial response, while none had stable or progressive disease. No recurrences, disease persistence, or AEs were detected during the follow-up period. After a median follow-up of 29.3 months (3-99), only two patients were alive, but the cause of death in the remaining patients was not related to NMSC. The cosmetic outcomes were excellent and good in two and four patients, respectively, while could not be evaluated in three patients. The cost (which was within the scope of medical insurance reimbursement) was acceptable. PISI-BT could be an alternative treatment option in patients above 80 years old with early primary high-risk NMSC and comorbidities.

Sequential Intravesical Chemotherapy for Treatment Naïve, High-Risk Non-Muscle Invasive Bladder Cancer: Oncologic Outcomes, Tolerance, and Comparison to Contemporary Controls

ObjectivesTo assess if receiving sequential intravesical chemotherapy (Gemcitabine-Docetaxel, Gem-Doce) therapy was associated with similar oncologic efficacy to bacillus Calmette-Guérin (BCG) in patients with treatment-naïve, high-risk non-muscle invasive bladder cancer (HR-NMIBC). MethodsSingle-center, retrospective cohort study of 80 patients with HR-NMIBC initiating first-line Gem-Doce or BCG between August 2020 and August 2023. Surveillance conducted with cystoscopy, urine cytology, and cross-sectional imaging. The primary oncologic outcome was high-grade bladder tumor recurrence during surveillance. Kaplan-Meier method applied to determine 12- and 24-month recurrence free survival (RFS) after initiation of therapy. Tolerance of each intravesical therapies was assessed. Results53/80 (66%) received Gem-Doce and 27/80 (34%) received BCG with overall 18-month median follow up. There were 10 recurrences after Gem-Doce and seven after BCG. The RFS at 12- and 24-months for Gem-Doce (12-months: 87%, 24-months: 75%) was not significantly different than BCG (12-months: 85%, 24-months: 81%). Lastly, Gem-Doce had significantly fewer patients with AEs compared to BCG (40% vs 74%). Limitations include retrospective design, small cohort size, and intermediate oncologic follow-up. ConclusionsOur data suggest that sequential intravesical Gem-Doce is an oncologically efficacious and, potentially better tolerated, alternative to BCG for treatment-naïve HR-NMIBC.

Bioinformatic analysis indicated that STARD4-AS1 might be a novel ferroptosis-related biomarker of oral squamous cell carcinoma

BackgroundOral squamous cell carcinoma (OSCC) stands as the predominant form of oral cancer, marked by a poor prognosis. Ferroptosis, a type of programmed cell death, plays a critical role in the initiation and progression of various cancers. Long non-coding RNAs (lncRNAs) are prominent in modulating cancer development. Nevertheless, the prognostic significance of ferroptosis-related lncRNAs (FRLs) in OSCC remains inadequately explored. This study aims to develop a predictive signature based on FRLs to forecast the prognosis of OSCC patients. MethodsWe gathered expression profiles of FRLs along with clinical data from The Cancer Genome Atlas (TCGA) and FerrDb databases. A prognostic model based on 10 FRLs were constructed using Cox regression analyses with LASSO algorithms, and their predictive power was evaluated. Then, the model was used to investigate functional enrichment, immune landscape, m6A genes, somatic variations, and drug response in different risk cohorts of patients. Finally, the expression and function of STARD4-AS1 (steroidogenic acute regulator protein-related lipid transfer domain containing 4-antisense RNA 1), a potential prognostic marker for OSCC screening based on our bioinformatics analysis, were investigated in vitro. ResultsWe developed a signature comprising 10 FRLs to stratify patients into two risk cohorts according to their calculated risk scores. Patients classified as high-risk exhibited significantly poorer prognoses compared to those in the low-risk cohort. Furthermore, survival analysis, patient risk heat plot, and risk curve verified the accuracy of the signature. The role of this signature in OSCC was well investigated using immune microenvironment, mutational, and gene set enrichment analysis (GSEA). Moreover, seven drugs, including cisplatin and docetaxel, were identified as potential treatments for patients with high-risk cancers. In addition, the knockdown of STARD4-AS1 in OSCC cell lines markedly inhibited cell proliferation and migration and induced ferroptosis. ConclusionUsing this signature may improve overall survival predictions in OSCC, throwing new light on immunotherapies and targeted therapies. Moreover, STARD4-AS1 might regulate the process of ferroptosis and could be used as a novel biomarker of OSCC.

Testosterone replacement therapy (TRT) in patients with locoregional prostate cancer (LPC) treated with prior androgen deprivation therapy (ADT): A single center review.

e24045 Background: In LPC, ADT may be combined with radiation therapy (RT) for 4-24 months. Post-ADT, a significant proportion of men experience prolonged hypogonadism. TRT can alleviate symptoms and improve metabolic outcomes. Contrary to longstanding concerns, there is no substantial evidence of increased prostate cancer recurrence in patients (pts) treated with single modalities (surgery or RT). However, sparse data ( &lt; 100 cases published to our knowledge) exist regarding recurrence risk of LPC with TRT after prior ADT, where baseline T levels may fall below the androgen receptor saturation point. Methods: We retrospectively abstracted clinical data from hospital records of men with stage I – IVA PC, treated with prior concurrent ADT and RT and subsequently received TRT between January 2014 and September 2023. Extracted data included demographics, cancer diagnosis/staging, ADT/TRT treatment details and PSA and clinical outcomes. The co-primary endpoints were change in PSA and incidence of PC recurrence. Results: 21 pts met criteria. Median age was 77. ISUP Grade Groups (GG) included: GG1: 2, GG2: 2, GG3: 8, GG4: 2, and GG5: 7. AJCC 8th ed. stages were: I: 2, II: 7, III: 7, IV-A: 5. The median duration of prior ADT was 8 months (IQR 5 – 17) and the median interval from RT to TRT was 19 months (IQR: 12 – 44). Prior to TRT, the median testosterone level was 30.5 ng/dL (IQR: 17-76). TRT formulations included: injection: 6, oral: 4, topical: 13. The median follow-up period from the start of TRT was 13 months, and the median duration on TRT was 10 months (IQR: 5-22). TRT was ongoing in 15 (71.4%) pts and discontinued in 6 (28.6%). Reasons for discontinuation included testosterone recovery (1), hospice (not PC related) (2), no perceived benefit (2), MD concern for PSA rise (1). After TRT, the median testosterone level was 336 ng/dL (IQR: 207-462). Median PSA pre- and post-TRT were undetectable and 0.08 ng/dL, respectively. None of the subjects experienced PC recurrence or PC-specific mortality. One pt showed PSA bounce without recurrence. Median BMI was unchanged before (28.3 kg/m2) and after (27.7 kg/m2) TRT (p = 0.48). Due to the nature of the study, quality of life measures and metabolic parameters could not be systematically abstracted. Conclusions: In men with LPC who remained hypogonadal long-term after prior ADT and RT, we found that TRT was not associated with a significant rise in median PSA and no cases of PC recurrence were documented. This included many with a history of very high-risk cancers (eg. GG ≥ 4, Stage ≥ III). This study adds to the sparse existing literature in this clinical setting and together they support the case for a prospective trial utilizing TRT in patients who remain hypogonadal after ADT and radiation.

Association between wildfire PM2.5 and genitourinary cancer survival in California.

10567 Background: Aerosolized particulate matter (PM) 2.5 (i.e., particles ≤ 2.5 µm in diameter or fine particles), including those that emanate from wildfires, has been previously associated with cancer risk and survival. While prior studies have focused primarily on etiology, little is known about the effects of wildfire PM2.5 on cancer prognosis. We sought to explore the effects of wildfire PM2.5 on genitourinary (GU) cancer survival in the state of California where episodic wildfires are considered a component of its climate. Methods: Using the California Cancer Registry, we identified incident prostate (n=81,261), urothelial (n=26,689), and kidney (n=26,303) cancers diagnosed between 2017-2020. Daily PM2.5 was estimated over the same period. Random forests regression was used to fuse diverse datasets (official air quality monitoring, satellite observations, meteorological modeling, predictive smoke modeling, and low-cost sensor networks [PurpleAir]) and produce a consensus estimate of PM2.5 for each centroid of a 1-square kilometer grid across California. We used home address at the time of cancer diagnosis to map each cancer case to the nearest centroid, and averaged PM2.5 exposures over the 6 months preceding cancer diagnosis for each case. Cox-proportional hazards regression was used to quantify the hazard ratio (HR) for death from any cause following cancer diagnosis associated with PM2.5, adjusting for key covariates including age, sex, race/ethnicity, neighborhood socioeconomic status, comorbidity, smoking status, rural/urban residence, and stage at diagnosis. Results: In patients with prostate cancer, a 10 µg/m³ increase in PM2.5 concentration was associated with an 18% increased hazard of death (HR=1.18; 95% confidence interval (CI)= 1.02-1.36, p=0.023). When stratified by stage at diagnosis, the association of PM2.5 and survival was limited to stages I, II, and III (HR=1.39; CI= 1.11-1.74, p=0.005) versus stage IV (HR=1.06; CI= 0.87-1.27, p=0.566). For urothelial cancer, a 10 µg/m³ increase in PM2.5 concentration was associated with a non-statistically significant 11% increased hazard of death (HR=1.11; CI= 0.96-1.29, p=0.151), which did not differ by stage at diagnosis. Kidney cancer survival was not associated with PM2.5 (HR= 0.94; CI= 0.79-1.11, p= 0.44). Conclusions: These findings suggest that higher PM2.5 exposure could influence prostate and urothelial cancer prognosis, perhaps through alteration of physiological pathways relevant to cancer aggressiveness or impairing response to treatment, including cellular immune response, inflammation, angiogenesis, or cell-signaling pathways. Further studies should look into the mechanisms and design mitigating strategies in patients diagnosed with these high-risk cancers who have been exposed to wildfire PM2.5.

Tamoxifen for breast cancer prevention among survivors of pediatric lymphoma previously treated with chest radiation: Clinical benefits, harms and tradeoffs.

10025 Background: Survivors of pediatric lymphoma previously treated with chest radiation are at high risk for subsequent breast cancer. Although early initiation of breast cancer screening is recommended, the clinical benefits and harms of adding tamoxifen to reduce breast cancer deaths among these women are unknown. Methods: We adapted a Cancer Intervention and Surveillance Modeling Network (CISNET) breast model using data from the Childhood Cancer Survivor Study (CCSS) to reflect the elevated risks for breast cancer and competing mortality for 5-year survivors previously treated with chest radiation (RT). Breast cancer risk was based on age, chest RT field, timing of RT relative to menarche, menopause status, anthracycline exposure, and family history. Premature menopause risk varied by cumulative ovarian RT and alkylator dose. Based on the US Preventive Services Task Force 2019 Evidence Summary, we assumed tamoxifen (20mg daily for 5 years) reduced estrogen receptor positive (ER+) breast cancer risk by 42% (RR = 0.58 [0.42-0.81]) for 20 years and increased risks for venous thromboembolism, deep vein thrombosis, coronary heart disease, stroke and endometrial cancer during treatment. Strategies included no screening or tamoxifen, annual screening with mammography and MRI starting at age 25, annual screening with mammography and MRI starting at age 25 with the addition of tamoxifen at ages 25, 30 or 35. Model outcomes included cumulative breast cancer risk, number of childbearing years before age 45 (defined as years menstruating without tamoxifen use or a breast cancer diagnosis or having survived breast cancer for at least 3 years), and number of tamoxifen-related side-effects. Results: Among a cohort of 20-year-old 5-year lymphoma survivors previously treated with mediastinal RT without primary ovarian failure, an estimated 20% were projected to develop breast cancer and 2.6% would die from the disease before age 50 in the absence of screening or tamoxifen use. Survivors would have on average 22 childbearing years before age 45. Early initiation of breast cancer screening at age 25 would reduce breast cancer deaths before age 50 by 56.3%. Depending on age at initiation, tamoxifen would further reduce breast cancer deaths by 8.0 to 9.6 percentage points for an overall 64.3% to 65.9% reduction and reduce the average number of childbearing years by 17% to 21%. For each breast cancer death averted, a reduction of 1950 to 3740 childbearing life years and 11 to 20 side-effects would occur and varied by the tamoxifen start age compared to mammography and MRI screening. Conclusions: Tamoxifen use for primary breast cancer prevention among pediatric lymphoma survivors may further reduce breast cancer deaths but decisions might depend on survivor preferences for side effects vs. avoiding breast cancer and consideration of timing for childbearing.

Overall and non‐lung cancer incidence and mortality in the National Lung Screening Trial: Opportunities for multi‐cancer early detection

AbstractBackgroundCurrently recommended cancer screening programs address only part of the overall population cancer burden. Even populations deemed high‐risk for certain individual cancers experience a considerable potential burden of other cancers. However, few published cancer screening trials report the incidence of untargeted cancers.MethodsThe National Lung Screening Trial (NLST), initiated in 2002–2004, was a randomized controlled trial of lung cancer screening in adults with ≥30 pack‐years of smoking. Active follow‐up for incident invasive cancers continued through 2009.ResultsAmong 53,229 NLST subjects (median follow‐up 6.5 years after randomization), the incidence of lung cancer was 615 per 100,000 person‐years (32% of 6142 overall first primary incident invasive cancers), and that of non‐lung cancer was 1327 per 100,000 (68%). Non‐lung cancer incidence exceeded that for lung cancer in all 5‐year age categories and all quintiles of smoking pack‐years. Besides lung cancer, the most common cancers were prostate, breast, colon/rectum, bladder, and head/neck; 23% were smoking‐related cancers, and 54% were cancer types lacking recommended population‐based screening modalities (32% excluding prostate). Non‐lung cancer comprised 48% of 1793 cancer deaths.ConclusionsIn the NLST, only 32% of first primary cancer incidence after study entry was lung, compared with 68% non‐lung. Even in a population at high risk for lung cancer, a single‐cancer screening test misses most cancers. Thus, in combination with existing single‐cancer screening modalities, multi‐cancer screening tests—which address many of the incident non‐lung cancers in this trial—have potential to address a currently inaccessible portion of cancer morbidity and mortality.

The Knowledge, Attitudes, and Practices of Parents Regarding Sun Protection for Their Children.

To evaluate the knowledge, attitudes, and practices of parents toward protecting their children against skin cancer and the sun. This cross-sectional study was performed in Turkey from March through October 2022. The authors used a questionnaire investigating the parents' and children's characteristics, attitudes, and practices toward sun protection and the Skin Cancer and Sun Knowledge (SCSK) scale to collect data. Of 465 parents, 60.2% were women, 83.2% were light-skinned, 20.2% perceived their children as risk-free, 43.8% perceived their children as low risk in terms of skin cancer, 14.6% examined their children from head to foot, 62.3% applied sunscreen to their children, 9.7% made them wear long-sleeved clothing, 60.0% made them wear headgear, 61.1% made them remain in the shade or under a sunshade, and 32.3% made them wear sunglasses. The mean parental SCSK scale score was 14.3 ± 4.1. Scale scores were higher among those who perceived their children as being at high risk for skin cancer (P = .000), whose children had not experienced red or painful sunburn in the previous year (P = .000), and who informed their children about sun protection (P = .000). Although knowledge of skin cancer and solar protection was high, parental perception of the risk of skin cancer was very low, and attitudes toward skin examination were also very relaxed.

Associations of systemic immune‐inflammation index with high risk for prostate cancer in middle‐aged and older US males: A population‐based study

AbstractBackgroundSystemic immune‐inflammation index (SII) provides convincing evaluation of systemic immune and inflammatory condition in human body. Its correlation with prostate cancer (PCa) risk remains uncharted. The principal objective of this investigation was to elucidate the association between SII and the risk for PCa in middle‐aged and elderly males.Materials and MethodsAnalysis entailed multivariate linear and logistic regression, generalized additive model, and smoothing curve fitting using resource from 2007 to 2010 National Health and Nutrition Examination Survey (NHANES). To ascertain robustness and consistency of this association across different demographic strata, we conducted rigorous subgroup analyses and interaction tests.ResultsAmong 3359 participants, those with elevated SII displayed higher total prostate‐specific antigen (tPSA) levels, higher risk for PCa, and lower free/total PSA (f/t PSA) ratio. Specifically, each unit increase of log2 (SII) was associated with a 0.22 ng/mL increase in tPSA (β: 0.22, 95% confidence intervals [CI] 0.05–0.38), a 2.22% decline in f/t PSA ratio (β: −2.22, 95% CI −3.20 to −1.23), and a 52% increased odds of being at high risk for PCa (odds ratio [OR]: 1.52, 95% CI 1.13–2.04). People in the top quartile of log2 (SII) exhibited 0.55 ng/mL increased tPSA (β: 0.55, 95% CI 0.19–0.90), 4.39% reduced f/t PSA ratio (β: −4.39, 95% CI −6.50 to −2.27), and 168% increased odds of being at high risk for PCa (OR: 2.68, 95% CI 1.32–5.46) compared to those in the bottom quartile.ConclusionSystemic immune and inflammatory condition, as represented by SII, is independently and positively associated with tPSA levels and the risk for PCa, as well as independently and negatively associated with f/t PSA ratio among middle‐aged and older US males. These findings may enhance the effectiveness of PCa screening in predicting positive biopsy results.

Artificial intelligence–aided lung cancer screening in routine clinical practice: A pilot of LungFlag at Geisinger.

e13604 Background: Use of low-dose computed tomography (LDCT) in lung cancer screening is recommended for early detection and can reduce mortality. LungFlag (Medial-EarlySign) is a machine-learning risk prediction model that identifies individuals at high risk of non-small cell lung cancer so their care team may recommend LDCT screening. The LungFlag model was developed using data from Kaiser Permanente Southern California and is being implemented in a pilot at Geisinger. Here we provide an overview of the clinical workflow for the LungFlag pilot. Methods: Geisinger has implemented LungFlag into routine clinical practice via integration with the electronic medical record system. This pilot is examining the performance and clinical impact of LungFlag in the first year. LungFlag runs every month to provide risk evaluation for individuals 50 to 80 years old who are eligible for annual lung cancer screening according to US Preventive Services Task Force recommendations. Eligible individuals have a 20 pack-year smoking history, no lung cancer history, and currently smoke or quit within the past 15 years. Patients with cancer history in the past 5 years and those screened or scheduled for screening in the past year are excluded. LungFlag identifies the top 30 individuals with the highest LungFlag scores per month (high-risk patients) and refers them for targeted outreach from a lung cancer screening program nurse navigator. A positive LungFlag result prompts nurse navigator chart review, patient outreach, and coordination with the primary care provider. Flagged individuals are contacted (up to 3 phone calls) and encouraged to receive lung cancer screening. Individuals not flagged by the model (non–high-risk patients) receive usual care consisting of reminders for lung cancer screening during primary care visits without additional targeted outreach and high-risk prioritization. Results: The LungFlag pilot was initiated in August 2023 and will continue until August 2024. As of January 2024, risk profiles of &gt;12,000 patients were analyzed and 180 high-risk patients were identified. Conclusions: This pilot is the first evaluation of the implementation process for the LungFlag model in routine clinical practice. After the pilot, a retrospective observational study is planned to further assess the impact of LungFlag and the associated clinical workflow in identifying high-risk individuals and increasing compliance with LDCT screening among high-risk individuals.

Clinical Characteristics of Patients With Previous Helicobacter pylori Infection-Induced Atrophic Gastritis.

Patients with atrophic gastritis unrelated to autoimmune gastritis (AIG) and without active Helicobacter pylori (H.pylori)infection or previous eradication therapy are considered to have previous Helicobacter pylori infection-induced atrophic gastritis (PHIG). This study aimed to clarify the clinical characteristics of patients with PHIG. Consecutive patients who underwent upper gastrointestinal endoscopy during the study period were enrolled in the study. Pepsinogen and gastrin levels, H. pylori serology, and endoscopic atrophic grade were assessed. Patients were divided into five groups based on their H. pylori status and disease history (PHIG, without H. pylori infection, with active H. pylori infection, with successful H. pylori eradication, and AIG). Their gastric cancer risk status was classified according to the ABC method of serological gastric cancer screening. Of 536 consecutive patients who underwent upper gastrointestinal endoscopy during the study period, 318 were included (31 with PHIG, 77 without H. pylori infection, 101 with active H. pylori infection, 80 with successful H. pylori eradication, and 29 with AIG). Of the 31 patients with PHIG, 21 (68%) were H. pylori-seronegative,and 20 (65%) were classified as group A (normal pepsinogen, H. pylori-seronegative). Patients with PHIG accounted for 90.1% of the patients at high risk for gastric cancer misclassified as group A. The pepsinogen and H. pylori serological profiles of patients with PHIG were similar to those of patients with successful H. pylori eradication more than six years previously. A receiver-operating characteristic curve (ROC) analysis that included 13 patients with AIG and without active H. pylori infection and no previous eradication therapy and 31 patients with PHIG revealed that an endoscopic atrophy grade of O-III or greater according to the Kimura-Takemoto classification can predict AIG. Two-thirds of the patients with PHIG were misclassified as being at low risk (group A) according to the ABC method, suggesting that endoscopy is necessary for group A patients. The results of the serological evaluation of PHIG indicated that patients with PHIG may have experienced spontaneous H. pylori eradication, possibly because of the use of antibiotics for other conditions. Autoimmune gastritis should be considered in the presence of grade 0-III or greater gastric mucosal atrophy in patients with suspected PHIG, even if the autoantibody and histological findings are not available.

Assessment of toxic elements in selected fish species in the marine water at Jamestown, Ghana

Fish is an excellent source of low-fat protein. Fish contains a lot of omega-3 fatty acids, as well as vitamins D and B2 (riboflavin). The daily consumption of contaminated food, especially fish, is among the primary cause of heavy metals pollution to human health. The aim of the research was to determine the concentration of heavy metals in selected species of fish from the Gulf of Guinea at James Town in Ghana. In tandem with the study's objective, samples of different forms of fish, Cassava fish, Flatfish, Redfish, Kingfish, and Silverfish, and sediment were obtained and analyzed for the presence of heavy metals using atomic absorption spectrometer (PerkinElmer®, PinAAcle 900T). The analysis indicated a high concentration of Pb, Cd, and Cr concentrations in fish gills, muscles, and sediment. High lead concentration in Silverfish gills (5.9 mg/kg) and Flatfish gills (2.29 mg/kg) above WHO levels. Cadmium was found in all fish species and sediment except Kingfish. Chromium concentrations were high n Cassava fish (3.10 mg/kg) and Silverfish (4.01 mg/kg) and copper concentrations were absent in the fish species. Arsenic and mercury were also not detected in all fish species and sediment. Manganese concentrations were found in fish and sediment. High cadmium target hazard quotient (0.17–11.60 for adults and 0.24 to 16.24 for children) and cancer risk (0.00–0.04) values in fish samples indicated potential health concerns. The Hazard Index (HI) for the analyzed samples ranged from 0.00 to 12.48 for adults and 0.00 to 17.47 for children. The study suggests that eliminating pollution and other sources of waterbody pollution is crucial to protecting the marine environment and the health of seafood consumers.

Phase II trial of intravesical camrelizumab in BCG-unresponsive high-risk non-muscle invasive bladder cancer.

Phase II trial of intravesical camrelizumab in BCG-unresponsive high-risk non-muscle invasive bladder cancer.

Practice patterns of high-risk non-muscle invasive bladder cancer (HR-NMIBC) in real-world Canadian practice.

Practice patterns of high-risk non-muscle invasive bladder cancer (HR-NMIBC) in real-world Canadian practice.

Exploration and prognostic analysis of two types of high-risk ovarian cancers: clear cell vs. serous carcinoma: a population-based study

BackgroundOvarian clear cell carcinoma (OCCC) is a rare pathological histotype in ovarian cancer, while the survival rate of advanced OCCC (Stage III-IV) is substantially lower than that of the advanced serous ovarian cancer (OSC), which is the most common histotype. The goal of this study was to identify high-risk OCCC by comparing OSC and OCCC, with investigating potential risk and prognosis markers.MethodsPatients diagnosed with ovarian cancer from 2009 to 2018 were identified from the Surveillance, Epidemiology, and End Results (SEER) Program. Logistic and Cox regression models were used to identify risk and prognostic factors in high-risk OCCC patients. Cancer-specific survival (CSS) and overall survival (OS) were assessed using Kaplan-Meier curves. Furthermore, Cox analysis was employed to build a nomogram model. The performance evaluation results were displayed using the C-index, calibration plots, receiver operating characteristic (ROC) curve, and decision curve analysis (DCA). Immunohistochemically approach was used to identify the expression of the novel target (GPC3).ResultsIn the Cox analysis for advanced OCCC, age (45–65 years), tumor numbers (total number of in situ/malignant tumors for patient), T3-stage, bilateral tumors, and liver metastases could be defined as prognostic variables. Nomogram showed good predictive power and clinical practicality. Compared with OSC, liver metastases had a stronger impact on the prognosis of patients with OCCC. T3-stage, positive distant lymph nodes metastases, and lung metastases were risk factors for developing liver metastases. Chemotherapy was an independent prognostic factor for patient with advanced OCCC, but had no effect on CSS in patients with liver metastases (p = 0.0656), while surgery was significantly related with better CSS in these patients (p < 0.0001) (p = 0.0041). GPC3 expression was detected in all tissue sections, and GPC3 staining was predominantly found in the cytoplasm and membranes.ConclusionAdvanced OCCC and OCCC with liver metastases are two types of high-risk OCCC. The constructed nomogram exhibited a satisfactory survival prediction for patients with advanced OCCC. GPC3 immunohistochemistry is expected to accumulate preclinical evidence to support the inclusion of GPC3 in OCCC targeted therapy.

A targeted panel of actionable high-risk hereditary cancer predisposition genes to identify patients with pathogenic/likely pathogenic variants (PVs) irrespective of meeting established NCCN testing criteria.

10596 Background: Current germline cancer testing guidelines are limited to patients who meet specific personal and family cancer history (PH, FH) criteria. Our objective was to determine if differences in PV rates exist based on meeting National Comprehensive Cancer Network (NCCN) testing criteria in patients who underwent testing for known actionable genes. Methods: 29 genes with actionable NCCN management guidelines were evaluated. Consecutive patients (N=195,615) aged 18 to 100 years had hereditary cancer testing at a commercial laboratory at the ordering clinician’s discretion that included at least the 29 genes between June 2020 and August 2023. Per clinician-reported patient features (e.g. FH, PH, age), patients were categorized as meeting or not meeting current NCCN testing criteria for breast/ovarian/pancreatic (BOP v2.2024), and colorectal cancer (v1.2023). PV rates were calculated for all genes associated with breast, endometrial, ovarian, prostate, pancreatic, and colorectal cancer risk. Results: PVs were reported in 6634/105,194 (6.3%) patients that met the testing criteria and 5134/90,421 (5.7%) that did not. Of patients with a PV, 5134/11,768 (43.6%) did not meet NCCN testing criteria. When comparing patients with PVs based on NCCN testing criteria, patients were similar in age (median [Q1, Q3], 43.6 [35.0, 56.1] v 42.5 [34.7, 56.6] years) and sex (female 91.5% v 91.3%). While PH and FH were comparable, a PH of cancer (31.5% v 36.1%, OR=0.81, 95% CI 0.75-0.88, p&lt;0.001) and/or a FH of cancer (83.9% v 97.1%, OR=0.16, 95% CI [0.13-0.18], p&lt;0.001) were slightly lower in patients who did not meet criteria compared to those who met testing criteria. On evaluating results in genes associated with individual cancer types, similar PV rates between the groups were observed (Table). Among all patients with PVs, the most common genes were CHEK2, BRCA1, BRCA2, and ATM. Most patients had only 1 PV reported (met: 96.5%, not met: 97.5%). Conclusions: In this cohort of patients who underwent germline testing, approximately 40% of patients with PVs in this study did not meet existing NCCN testing criteria. PV rates were similar between patients that met criteria and those that did not. Broadening existing testing criteria may reduce the number of patients who would otherwise be missed, thereby allowing for treatment decision-making and cascade testing of family members. [Table: see text]

Phase II/III study of paclitaxel/carboplatin alone or combined with either trastuzumab and hyaluronidase-oysk or pertuzumab, trastuzumab, and hyaluronidase-zzxf in HER2 positive, stage I-IV endometrial serous carcinoma or carcinosarcoma (NRG-GY026).

TPS5641 Background: Uterine serous carcinoma and uterine carcinosarcoma are rare, high-risk uterine cancer subtypes that overexpress HER2 in up to 40% and 10% of cases, respectively. Phase II data demonstrated a benefit in adding trastuzumab in HER2 positive advanced and recurrent uterine serous carcinoma. Dual anti-HER2 therapy has the potential for further improvement in survival. Methods: This is a non-blinded, three-arm randomized phase II/III study. The primary objective is to evaluate the efficacy of trastuzumab and hyaluronidase-oysk (HERCEPTIN HYLECTA) or a fixed dose combination of pertuzumab, trastuzumab, and hyaluronidase-zzxf (PHESGO) in combination with paclitaxel/carboplatin in patients with HER2 positive uterine serous carcinoma or carcinosarcoma. The primary outcome of the phase II component is PFS. Depending on the phase II results, the study will progress to a phase III study of either two or three study arms. Patients in the control arm (Arm 1) receive carboplatin and paclitaxel every 3 weeks for 6 cycles. Patients on Arm 2 receive carboplatin and paclitaxel with trastuzumab and hyaluronidase-oysk every 3 weeks for 6 cycles plus one year of maintenance trastuzumab and hyaluronidase-oysk. Patients enrolled on Arm 3 receive carboplatin and paclitaxel with trastuzumab, pertuzumab, and hyaluronidase-zzxf every 3 weeks for 6 cycles plus one year of maintenance trastuzumab, pertuzumab, and hyaluronidase-zzxf . Those with an ongoing partial response may continue maintenance therapy for up to three years. Patients are eligible if they are diagnosed with chemo-naïve, non-recurrent stage IA-IVB myoinvasive uterine serous or carcinosarcoma. All tumors must be HER2 positive as defined by the ASCO/CAP Breast Cancer 2018 guidelines (testing performed locally). Tumors may also be HER2 positive based on next generation sequencing testing. Patients may have measurable, non-measurable, or no measurable disease and may have a plan for vaginal brachytherapy . Key exclusion criteria include severe heart disease or interstitial lung disease. The phase II portion of this study is open and enrolling. Clinical trial information: NCT05256225 .