History Of Cancer Research Articles

Integrating radiological and clinical data for clinically significant prostate cancer detection with machine learning techniques.

In prostate cancer (PCa), risk calculators have been proposed, relying on clinical parameters and magnetic resonance imaging (MRI) enable early prediction of clinically significant cancer (CsPCa). The prostate imaging-reporting and data system (PI-RADS) is combined with clinical variables predominantly based on logistic regression models. This study explores modeling using regularization techniques such as ridge regression, LASSO, elastic net, classification tree, tree ensemble models like random forest or XGBoost, and neural networks to predict CsPCa in a dataset of 4799 patients in Catalonia (Spain). An 80-20% split was employed for training and validation. We used predictor variables such as age, prostate-specific antigen (PSA), prostate volume, PSA density (PSAD), digital rectal exam (DRE) findings, family history of PCa, a previous negative biopsy, and PI-RADS categories. When considering a sensitivity of 0.9, in the validation set, the XGBoost model outperforms others with a specificity of 0.640, followed closely by random forest (0.638), neural network (0.634), and logistic regression (0.620). In terms of clinical utility, for a 10% missclassification of CsPCa, XGBoost can avoid 41.77% of unnecessary biopsies, followed closely by random forest (41.67%) and neural networks (41.46%), while logistic regression has a lower rate of 40.62%. Using SHAP values for model explainability, PI-RADS emerges as the most influential risk factor, particularly for individuals with PI-RADS 4 and 5. Additionally, a positive digital rectal examination (DRE) or family history of prostate cancer proves highly influential for certain individuals, while a previous negative biopsy serves as a protective factor for others.

Quantifying cell divisions along evolutionary lineages in cancer.

Cell division drives somatic evolution but is challenging to quantify. We developed a framework to count cell divisions with DNA replication-related mutations in polyguanine homopolymers. Analyzing 505 samples from 37 patients, we studied the milestones of colorectal cancer evolution. Primary tumors diversify at ~250 divisions from the founder cell, while distant metastasis divergence occurs significantly later, at ~500 divisions. Notably, distant but not lymph node metastases originate from primary tumor regions that have undergone surplus divisions, tying subclonal expansion to metastatic capacity. Then, we analyzed a cohort of 73 multifocal lung cancers and showed that the cell division burden of the tumors' common ancestor distinguishes independent primary tumors from intrapulmonary metastases and correlates with patient survival. In lung cancer too, metastatic capacity is tied to more extensive proliferation. The cell division history of human cancers is easily accessible using our simple framework and contains valuable biological and clinical information.

Development of a Microsimulation Model to Project the Future Prevalence of Childhood Cancer in Ontario, Canada.

Estimates of the future prevalence of childhood cancer are informative for health system planning but are underutilized. We describe the development of a pediatric oncology microsimulation model for prevalence (POSIM-Prev) and illustrate its application to produce projections of incidence, survival, and limited-duration prevalence of childhood cancer in Ontario, Canada, until 2040. POSIM-Prev is a population-based, open-cohort, discrete-time microsimulation model. The model population was updated annually from 1970 to 2040 to account for births, deaths, net migration, and incident cases of childhood cancer. Prevalent individuals were followed until death, emigration, or the last year of simulation. Median population-based outcomes with 95% credible intervals (CrIs) were generated using Monte Carlo simulation. The methodology to derive model inputs included generalized additive modeling of cancer incidence, parametric survival modeling, and stochastic population forecasting. Individual-level data from provincial cancer registries for years 1970 to 2019 informed cancer-related model inputs and internal validation. The number of children (aged 0-14 y) diagnosed with cancer in Ontario is projected to rise from 414 (95% CrI: 353-486) in 2020 to 561 (95% CrI: 481-653) in 2039. The 5-y overall survival rate for 2030-2034 is estimated to reach 90% (95% CrI: 88%-92%). By 2040, 24,088 (95% CrI: 22,764-25,648) individuals with a history of childhood cancer (diagnosed in Ontario or elsewhere) are projected to reside in the province. The model accurately reproduced historical trends in incidence, survival, and prevalence when validated. The rising incidence and prevalence of childhood cancer will create increased demand for both acute cancer care and long-term follow-up services in Ontario. The POSIM-Prev model can be used to support long-range health system planning and future health technology assessments in jurisdictions that have access to similar model inputs. This article describes the development of a population-based, discrete-time microsimulation model that can simulate incident and prevalent cases of childhood cancer in Ontario, Canada, until 2040.Use of an open cohort framework allowed for estimation of the potential impact of net migration on childhood cancer prevalence.In addition to supporting long-term health system planning, this model can be used in future health technology assessments, by providing a demographic profile of incident and prevalent cases for model conceptualization and budget impact purposes.This modeling framework is adaptable to other jurisdictions and disease areas where individual-level data for incidence and survival are available.

Malignant melanoma arising in a sebaceous naevus leading to the discovery of a pathogenic germline MUTYH mutation: a case report.

We report here the fourth case (to our knowledge) of malignant melanoma arising on a sebaceous nevus, in a context of parotid gland adenocarcinoma under treatment. The originality of this case is that genomic analysis revealed a germline bi-allelic MUTYH mutation despite no history of personal nor familial MUTYH spectrum cancer. Moreover, this condition is seldom associated with melanoma.

Testicular Germ Cell Tumors: A Review.

Testicular cancer is the most common solid malignancy among males aged 15 to 40 years in the US, with approximately 10 000 new cases diagnosed each year. Between 90% and 95% of testicular cancers are germ cell tumors (GCTs). The mean age at diagnosis for testicular cancer is 33 years. GCTs are categorized as seminomas and nonseminomatous GCTs (NSGCTs) based on their embryonic origins and path of differentiation. Risk factors include cryptorchidism, family history of testicular cancer, gonadal dysgenesis, infertility, cannabis use, and genetic conditions such as Klinefelter syndrome. The most common presenting symptom of testicular cancer is a painless testicular mass. History, physical examination, scrotal ultrasound, laboratory assessment of GCT-associated serum tumor markers (α-fetoprotein, β-human chorionic gonadotropin, and lactate dehydrogenase), and prompt referral to a urologist are indicated when testicular cancer is suspected. Early diagnosis and treatment, starting with a radical inguinal orchiectomy, are important to optimize outcomes. At diagnosis, GCT is stage I (localized to the testicle) in 70% to 75% of patients, stage II (metastatic only to the retroperitoneal lymph nodes) in 20%, and stage III (widely metastatic) in 10%. Treatment of GCTs is guided by histology, clinical staging, and risk classification, with 5-year survival rates of 99%, 92%, and 85% for those diagnosed at stages I, II, and III, respectively. Optimal treatment often involves a multidisciplinary team at high-volume, experienced medical centers and may include surveillance (serum tumor markers [α-fetoprotein, β-human chorionic gonadotropin, and lactate dehydrogenase] and imaging of the chest, abdomen, and pelvis), surgery (retroperitoneal lymph node dissection), chemotherapy, and/or radiation. Treatment decisions should consider long-term survivorship concerns, including body image, fertility, hypogonadism, mental health, financial cost, adherence to follow-up, and late adverse effects of therapy such as cardiovascular disease, secondary malignancies, and potential psychosocial effects such as anxiety, depression, and social isolation. Testicular cancer is the most common solid malignancy in young men in the US, and 90% to 95% are GCTs. Patients with testicular GCT have a 5-year survival rate of 99%, 92%, and 85% for stages I, II, and III, respectively. Prompt diagnosis and treatment are important to optimize outcomes, and treatment decisions should balance oncologic control with survivorship concerns to minimize long-term adverse effects of treatment.

The prevalence of Lynch syndrome and associated clinicopathologic features in patients with mismatch repair deficient gastric cancer.

380 Background: Approximately 2-4% of patients with primary colorectal cancer are estimated to be associated with Lynch syndrome. However, the prevalence of Lynch syndrome and associated clinicopathologic features in patients with mismatch repair-deficient (dMMR) gastric cancer (GC) is not well understood. In this study, we investigated the frequency of dMMR GCs in unselected GCs and the prevalence of Lynch syndrome, as well as associated clinicopathologic features and molecular alterations in dMMR GCs. Methods: A total of 847 cases of unselected GCs from 2010 to 2012 were collected at Jeju National University Hospital. Immunohistochemistry for mismatch repair proteins (MMR), including MLH1, MSH2, MSH6, and PMS2, and MSI analysis were performed on representative tumor sections of surgically resected specimens. Follow-up genetic counseling and genetic and/or epigenetic alterations of the MMR genes were also investigated. Results: Loss of one or more MMR proteins and microsatellite instability-high were observed in 72 patients; 67 patients showed loss of MLH1/PMS2, 2 patients showed loss of PMS2 alone, and 3 patients with MSH2/MSH6. Genetic counseling demonstrated that ten patients had a family history of LS-associated cancers and nine patients had a history of metasynchronous cancers. Of the 72 patients, 65 revealed hypermethylation of the promoter region of MLH1. The subsequent genetic germline tests demonstrated 2 patients with MLH1 mutation, 3 with MSH2 mutation, and 2 with PMS2 mutation. Conclusions: dMMR tumors were identified in 72 (8.5%) of 847 unselected primary GCs. This study estimated that 0.8% of patients with unselected GC and 9.7% of patients with dMMR GC fulfilled the revised Bethesda criteria and are associated with Lynch syndrome. The detection of dMMR GCs and necessary genetic counseling/tests based on revised Bethesda criteria would help find Lynch syndrome in patients with GC. Clinical and immunophenotypical features of patients with dMMR GC. Age ≤ 50 years 5 (6.9) > 50 years 67 (93.1) Other malignancy history except GAC No 63 (87.5) Yes 9 (12.5) History of metachronous cancers Esophageal cancer 1 (1.4) Maxillary sinus cancer 1 (1.4) Papillary thyroid cancer 1 (1.4) Colorectal cancer 1 (1.4) Pancreatic cancer 1 (1.4) Breast cancer 1 (1.4) Breast cancer and malignant GIST 1 (1.4) Multiple HCCs 2 (2.8) History of Family with LS related cancers No 62 (86.1) Yes 10 (13.9) Fulfillment of the rBG No 63 (87.5) Yes 9 (12.5) MMR proteins Loss of MLH1 and PMS2 67 (93.1) Loss of PMS2 2 (2.8) Loss of MSH2 and MSH6 3 (4.2) Germline mutation test MLH1 mutations 2 (2.8) MSH2 mutations 3 (4.2) PMS2 mutations 2 (2.8)

Sex-Stratified Prevalence of Classic Psychedelics Among Individuals With a History of Cancer in the United States: An Analysis of the National Survey on Drug Use and Health, 2015-2019

Sex-Stratified Prevalence of Classic Psychedelics Among Individuals With a History of Cancer in the United States: An Analysis of the National Survey on Drug Use and Health, 2015-2019

Do Patients With NASH-related Cirrhosis Have Better Overall Survival Compared With Other Etiologies of Cirrhosis? A Population-based Study.

Nonalcoholic steatohepatitis (NASH) is a leading cause of cirrhosis. We aim to explore the clinical outcomes of NASH cirrhosis compared with other etiologies of cirrhosis. We utilized an EHR-based database (TriNetX) to study the outcomes of NASH cirrhosis. Patients diagnosed with NAFLD or NASH and cirrhosis between January 2016 and December 2019 were identified utilizing appropriate ICD-10-CM codes. The primary outcome was 3-year overall survival. Secondary outcomes were decompensated cirrhosis, hepatocellular carcinoma, and liver transplantation. The Control group was patients with other etiologies of cirrhosis than NASH. Study and control groups were matched for demographic characters and comorbidities using propensity score matching. We identified 45,063 patients with NASH cirrhosis. The NASH cirrhosis cohort comprised older (61 vs. 59y) White (78% vs. 64%) women (58% vs. 38%) with more comorbidities (diabetes mellitus, obesity, ischemic heart disease, history of cancer, chronic kidney disease). After propensity score matching, patients with NASH cirrhosis had a better 3-year survival (78% vs. 74%, HR 0.79, 95% CI 0.77-0.82) compared with patients with non-NASH cirrhosis. Hepatocellular carcinoma was diagnosed less commonly in patients with NASH cirrhosis (6.7% vs. 10.6%, P <0.001), and liver transplantation was performed more often for NASH cirrhosis compared with non-NASH cirrhosis [Risk ratio 1.13 (1.08-1.18)]. Patients with NASH cirrhosis probably have better 3-year overall survival than other etiologies of cirrhosis. This is an interesting finding, as patients with NASH are older and have more comorbidities. Improved survival can be partly explained by a higher probability of liver transplantation and improvements in cardiovascular outcomes.

Being underweight or obese in adolescence may increase the risk of female infertility later in life: The Japan Nurses' Health Study.

Underweight or obesity is associated with infertility in women, but large cohort studies with a life course perspective are rare. We explored the association between body mass index (BMI) at age 18 and subsequent infertility among Japanese women. In total, 15,907 married women aged 30-44years who participated in a prospective cohort baseline survey during 2001-2007 were cross-sectionally analyzed. Those with a history of cancer, and those with a partner with infertility or missing data were excluded. All data were obtained from self-reported questionnaires. The main outcome measure was infertility, defined as a self-reported history of infertility for at least 2years. Age and cause of infertility were also recorded. Overall, 2825 participants (17.8%) reported being infertile. The proportions of women who were underweight (BMI <18.5kg/m2), overweight (BMI ≥25 and<30kg/m2), and obese (BMI≥30kg/m2) at age 18 were 12.8%, 4.5%, and 0.4%, respectively. Multiple logistic regression analysis revealed a 1.31-fold and a 1.82-fold increase in the rate of infertility in those women who were underweight or obese during adolescence, respectively, compared with those of normal weight. Further analysis by cause of infertility revealed no significant associations with overweight or obesity at age 18, but being underweight was positively associated with infertility of unknown cause. Being underweight or obese at adolescence is a potential risk factor for subsequent infertility among Japanese women. In particular, being underweight during adolescence may be a contributing factor to unexplained infertility later in life.

A 20-year population-wide cohort study on association of aspirin and risk of gastrointestinal and non-gastrointestinal cancer.

830 Background: Aspirin has been shown to reduce the risk of various gastrointestinal (GI) and non-GI cancers 1,2 . However, little was known about at what age aspirin should be started for maximal chemoprotective better on GI cancer. Furthermore, the randomised controlled trial on aspirin for primary prevention use in healthy elderly (ASPREE) showed no association between aspirin and cancer incidence despite the limitation of short follow-up duration 3 . The current study aims to investigate the 20-year risk of cancer using aspirin in a territory-wide Hong Kong population cohort. Methods: The study included all aspirin users from 2000 to 2019, and non-aspirin users matched by age and sex at a ratio of 1:2. Enrolled subjects with a history of cancer at enrolment, cancer incidence or death within 6 months were excluded. The incidence of individual GI and non-GI cancer was presented as the primary outcome. Baseline characteristics between aspirin and non-aspirin users were adjusted in the survival analysis by inverse probability of treatment weighting (IPTW). The fine-grey model has been used to address bias from competing risk of death. The sub-distribution hazard ratio was presented for the association of aspirin use and risk of GI and non-GI cancers. Results: The current study included 538,147 aspirin users and 968,378 non-users with a mean age of 64.8 years. A total number of 36,683 cases of GI cancer (2.4%) and 47,196 cases of non-GI cancers (3.1%) were observed. Aspirin was associated with a lower risk of several common individual GI cancers, including colorectal cancer (SHR 0.78, 95% CI 0.76-0.81), liver cancer (SHR 0.67, 95% CI 0.64-0.70), stomach cancer (SHR 0.79, 95% CI 0.75-0.84) and pancreatic cancer (SHR 0.85, 95% CI 0.79-0.91), but not oesophageal cancer. On the other hand, aspirin was associated with a lower risk of prostate cancer (SHR 0.95, 95% CI 0.91-1.00) and breast cancer (SHR 0.76, 95% CI 0.73-0.79), but not lung cancer and kidney cancer. In overall, aspirin was associated with a 24% lower risk of GI cancers (SHR 0.76, 95% CI 0.74-0.78) and a 3% lower risk of non-GI cancers (SHR 0.97, 95% CI 0.95-0.99). Conclusions: Aspirin was associated with a lower risk of most GI cancers, including colorectal cancer, liver cancer, stomach cancer and pancreatic cancer, but not most non-GI cancers. In general, results on the effect of aspirin on GI cancer prevention were consistent with the previously presented 10-year cohort. 1. Bosetti C, Santucci C, Gallus S, Martinetti M, La Vecchia C. Aspirin and the Risk of Colorectal and Other Digestive Tract Cancers: An Updated Meta-analysis through 2019. Ann Oncol. 2020;31(5):558-568. 2. Santucci C, Gallus S, Martinetti M, La Vecchia C, Bosetti C. Aspirin and the risk of nondigestive tract cancers: An updated meta-analysis to 2019. Int J Cancer. 2021;148(6):1372-1382. 3. McNeil JJ, Gibbs P, Orchard SG, et al. Effect of Aspirin on Cancer Incidence and Mortality in Older Adults. J Natl Cancer Inst. 2021;113(3):258-265.

Prevalence of extracolonic malignancies in patients with familial adenomatous polyposis.

103 Background: Familial adenomatous polyposis (FAP) is an autosomal-dominant inherited colorectal cancer syndrome resulting from mutations in the adenomatous polyposis coli ( APC ) gene. Patients with FAP have nearly 100% lifetime risk of colorectal cancer, typically managed with prophylactic colectomies. As patient survival has improved, the incidence of extracolonic tumors, including thyroid malignancies and desmoid tumors, has increased. However, limited research exists on the prevalence of extracolonic malignancies in FAP patients. Methods: We prospectively enrolled 219 patients with FAP in the Hereditary Gastrointestinal Cancers Cohort at the MD Anderson Cancer Center between December 2015 and July 2024. Inclusion criteria included either a clinical or molecular diagnosis of FAP. Data on demographics, cancer history (including cancers diagnosed both prior to and during the study period), BMI, tobacco use, medications, endoscopy results, thyroid ultrasound findings, and abdominal/pelvic CT results were collected. Screening for thyroid and desmoid tumors was provider-dependent, with additional screenings as deemed appropriate. Descriptive and inferential statistics were used to identify associations between demographic and clinical factors and the prevalence of extracolonic malignancies. Results: Among 219 patients, 20.5% developed desmoid tumors, 18.7% developed colorectal cancer, and 6.8% developed well-differentiated thyroid cancer (6.4% papillary thyroid cancer, 0.4% follicular thyroid cancer). Prophylactic colorectal surgery was performed in 151 patients (68.9%). Per chart review, benign thyroid disease and hypothyroidism were present in 21% and 11.4% of patients, respectively. Female sex was significantly associated with hypothyroidism (p=0.007) and thyroid cancer (p=0.009). BMI &gt; 30 was also linked to increased thyroid cancer risk (p=0.046). Desmoid tumors were found in 20.5% of patients, most commonly in the abdominal wall. Female sex, BMI &gt; 30, and history of colorectal surgery were significantly associated with desmoid tumor development (p=0.004, 0.0064, 0.0038). Conclusions: FAP patients exhibit a higher prevalence of benign thyroid disease, thyroid cancer, and desmoid tumors compared to the general population. Given these findings, adherence to existing surveillance guidelines, such as those outlined by the National Comprehensive Cancer Network (NCCN), is essential. Our findings further support the importance of these established surveillance strategies in the management of FAP patients.

First Case of Tracheobronchopathia Osteochondroplastica in an 82-Year-Old Patient From Saudi Arabia.

Tracheobronchopathia osteochondroplastica (TPO) is a benign tracheobronchial disorder characterized by the presence of osseous or cartilaginous nodules, typically affecting the proximal large airways while sparing the posterior membranous trachea. Around 600 cases has been documented worldwide for this rare disorder. While most cases are asymptomatic, some patients may exhibit symptoms such as dyspnea and chronic cough. These symptoms could be attributed to either the ulceration of the nodules or the onset of an acute infection. As it is a vague and rare disease, TPO goes undiagnosed in most cases. This case represents an 82-year-old male with ischemic cardiomyopathy and a history of colon cancer who presented with a six-month history of mild hemoptysis, occasional cough, and wheezing. Laboratory tests were normal except for a positive PPD test. Imaging showed tracheal thickening with nodularity and calcification, and bronchoscopy confirmed the diagnosis. The patient was managed with symptomatic treatment and close follow-up. Over 2 years, he remained stable, experiencing only two self-limiting hemoptysis episodes with resolution of other symptoms. This is the first case of TPO reported in Saudi Arabia. Given its nonspecific presentation, clinicians consider TPO as a differential diagnosis for patients with recurrent respiratory symptoms that do not respond to standard medical treatment. 4.

False-Negative Review from the Mammography Audit: Refining Breast Imaging Practice.

Annual review of false-negative (FN) mammograms is a mandatory and critical component of the Mammography Quality Standards Act (MQSA) annual mammography audit. FN review can help hone reading skills and improve the ability to detect cancers at mammography. Subtle architectural distortion, asymmetries (seen only on one view), small lesions, lesions with probably benign appearance (circumscribed regular borders), isolated microcalcifications, and skin thickening are the most common mammographic findings when the malignancy is visible at retrospective review of FN mammograms. Most FN mammograms are not due to radiologist error. There are common and predictable settings in which FN mammograms occur. Patient factors associated with elevated FN mammograms include dense breasts, elevated lifetime risk of breast cancer, and personal history of breast cancer treated with lumpectomy and radiation therapy. About half of FN cancers are detected by supplemental screening examinations and half manifest clinically. The most common manifesting symptoms for interval cancers are a palpable abnormality, nipple discharge, and skin changes. Interval cancers can have more aggressive pathologic features and higher rates of node positivity. The FN review includes Breast Imaging Reporting and Data System (BI-RADS) 3 cases that develop a cancer diagnosis during surveillance. Nonbreast malignancies diagnosed as interval cancers (most commonly lymphoma and metastatic disease) do not need to be counted as FNs for audit purposes. The FN review and annual audit are confidential processes that protect patient and radiologist information while allowing meaningful quality control and improvement. Although FN mammograms are rare, review of these cases is a valuable educational tool. The slide presentation from the RSNA Annual Meeting is available for this article. ©RSNA, 2025.

Refining colorectal cancer screening strategies using polygenic risk scores and classical risk factors: A proof-of-concept study in the UK Biobank cohort.

104 Background: While the rising incidence of CRC in younger populations has led to a push for lowering the screening age to 40, current clinical guidelines lack sufficient consideration of individual risk variations, raising concerns about the potential harms of over-diagnosis and false positives. Our proof-of-concept study evaluates the utility of risk stratification for multi-target stool DNA (mt-sDNA) testing by integrating polygenic risk scores and traditional clinical risk factors, addressing gaps in current clinical CRC screening guidelines. Methods: Our study utilized the UK Biobank prospective cohort, consisting of 311,544 unrelated individuals of White British ancestry, aged 40-69, excluding those with any prior malignant cancer diagnosis. We developed a sex-specific Cox proportional hazards model to estimate the risk of developing CRC, with the primary outcome being the first incidence of CRC. Three models were assessed: a polygenic risk score (PRS)-only model, a classical risk factors (RF)-only model, and a combined (PRS + RF) model. The traditional risk factors considered were BMI, smoking status, pack years of smoking, and family history of bowel cancer in first-degree non-adoptive relatives. Model performance was evaluated using the area under the curve (AUC), hazard ratios (HR), and the positive and negative predictive values of mt-sDNA across various risk profiles. Results: The combined model for early CRC screening using mt-sDNA demonstrated superior risk stratification (Table) and improved PPV compared to the risk factors-only model, with enhanced performance even among younger individuals at lower baseline risk. If risk stratification was not used, the average PPV for the test in the general population (ages 40-80) would be 2.13% for males and 1.44% for females. In contrast, individuals in the top 1% of risk would have significantly higher PPVs: 5.62% for males and 3.51% for females. If we limit testing to only the high-risk group, per 100,000 individuals, approximately 3,490 additional cases for males and 2,070 additional cases for females would be detected compared to the average-risk population without stratification. Conclusions: The findings suggest that risk stratification may enhance the effectiveness of screening by identifying high-risk individuals who would derive the greatest benefit. In contrast, broad application of the test across the general population may not achieve an optimal risk-benefit ratio, given the relatively low PPV in average-risk individuals. Model performance of the PRS-only, RF-only, and PRS + RF (Combined) models for females and males, respectively. Hazard Ratio (95% CI) C-index (SE) 5-Year AUC Female PRS-Only 1.50 (1.37 - 1.64) 0.62 (0.01) 0.61 RF + PRS 1.49 (1.36 - 1.63) 0.62 (0.01) 0.61 RF Only 1.09 (0.99 - 1.20) 0.53 (0.02) 0.51 Male PRS-Only 1.49 (1.38 - 1.61) 0.63 (0.01) 0.69 RF + PRS 1.49 (1.38 - 1.61) 0.64 (0.01) 0.71 RF Only 1.23 (1.15 - 1.31) 0.57 (0.01) 0.57

Outcomes of surveillance in patients with intraductal papillary mucinous neoplasms (IPMNs) who tested negative for high-risk mutations (HRMs) in next-generation sequencing (NGS).

704 Background: HRMs in NGS have demonstrated high sensitivity and specificity for predicting advanced neoplasia in patients with IPMNs. However, the outcomes of surveillance in patients who tested negative for these HRMs have not been investigated in prior studies. This study aimed to identify the predictors of progression in patients with negative NGS results for HRMs. Methods: We conducted a retrospective review of prospectively collected data from patients who underwent NGS testing between 2016 and 2023 in our pancreatic cancer prevention program. Patients without IPMNs (i.e., negative for KRAS/GNAS), with HRMs, and those without at least one follow-up imaging post-NGS were excluded from the study. Progression was defined as the development of new or additional worrisome features or high-risk stigmata (per Kyoto guidelines), or advanced neoplasia (HGD/PDAC) following NGS testing. A Cox proportional hazards regression model was used to identify predictors of progression. Results: A total of 543 patients underwent NGS testing during the study period, of which 210 patients met the inclusion criteria. The median follow-up duration was 22 months (IQR = 12-36). Of these, 72 patients developed progression following NGS testing. A total of 11 patients underwent surgical resection, and 5 of them had HGD. Factors predictive of progression included a history of smoking (HR = 1.74; 95% CI = 1.06 - 2.86), larger cyst size (HR = 1.09; 95% CI = 1.03 - 1.16), and the presence of a dilated main pancreatic duct (MPD) (HR = 2.56; 95% CI = 1.5 - 4.4) prior to NGS testing. The median time to progression for patients with worrisome features was 33 months, compared to 59 months for those without worrisome features at baseline. Similarly, the median time to progression for patients with cysts ≥ 2 cm was 38 months, compared to 57 months for those with cysts &lt; 2 cm. Conclusions: Patients who test negative for high-risk mutations in NGS are not exempt from the risk of progression. Any smoking history and presence of any worrisome features before NGS testing showed to be independent predictors of disease progression. For patients with smoking history, worrisome features or cysts ≥ 2 cm, frequent surveillance should be recommended following NGS testing. Results of Cox proportional hazards regression model for identifying the predictors of progression. Variables Hazards ratio (HR) 95% Confidence Interval P-value Age 0.99 0.96 – 1.01 0.257 Male sex 1.02 0.62 – 1.7 0.93 White race 1.07 0.63 – 0.83 0.8 Family history of pancreatic cancer 0.6 0.26 – 1.36 0.22 Personal history of other cancers 0.95 0.56 – 1.62 0.86 Diabetes 1.22 0.72 – 2.05 0.46 Any history of smoking 1.74 1.06 – 2.86 0.03* Pre-NGS cyst size (cm) 1.09 1.03 – 1.16 0.006* Pre-NGS dilated main pancreatic duct (≥5mm) 2.56 1.5 – 4.4 0.001* Pre-NGS presence of mural nodules 0.32 0.04 – 2.37 0.26 *Significant p-value.

A systematic review of the impact of artificial intelligence in pancreatic cancer detection.

685 Background: Pancreatic cancer is the fourth leading cause of cancer deaths in the United States, and early detection remains a significant challenge. Screening the general population is not feasible, but the rise of artificial intelligence (AI) has introduced new possibilities for improving early diagnosis and patient outcomes. Methods: A systematic literature search was conducted using PubMed, Google Scholar, and MEDLINE using MeSH terms Artificial intelligence or AI, and diagnosis and pancreatic carcinoma or pancreatic adenocarcinoma. Prisma guidelines were adhered to, and a total of 19 studies resulted, 6 of them were retrospective studies, 4 of them were literature reviews, and 4 of them were randomized trials. The rest were duplicates. The inclusion criteria for this study is AI being used in the diagnosis, only in pancreatic cancer, within the last 5 years, only in English, and only retrospective studies were included. Results: One study used Digital Imaging Processing (DIP) for analyzing Endoscopic ultrasound (EUS) images from 153 pancreatic cancer patients, yielding a sensitivity of 97.98% and a specificity of 94.32%. Two studies explored Computer Aided Diagnosis (CAD) models applied to PET/CT and EUS images, achieving a sensitivity of 95.23% and specificity of 97.51% in PET/CT scans and 83.3% and 93.3% in EUS images, respectively. Another study used a Faster R-CNN model to analyze CT images from 338 pancreatic cancer patients showed high diagnostic accuracy in much less time. Additionally, two studies utilized Natural Language Processing (NLP) for identifying family histories of pancreatic cancer and detecting pancreatic cysts, with the latter achieving sensitivity and specificity rates of 99.9% and 98.8%. Conclusions: The current strategies for early diagnosis of pancreatic cancer focus on serum biomarkers and EUS-guided Fine Needle Aspiration (EUS-FNA) and sensitivity varies but depends on the physician's expertise. AI is showing promise in improving pancreatic cancer diagnosis by enhancing early detection and accuracy. Techniques like deep learning, NLP-based models, Faster R-CNN, and CAD systems analyze medical data and images more effectively than manual methods. AI holds the potential to shape the future of pancreatic cancer diagnosis and improve patient outcomes.

Illness behavior and its predictors in young and middle-aged colorectal cancer patients: A latent profile analysis.

To describe the characteristics of sick role adaptation and understand the differences in young and middle-aged colorectal cancer (CRC) patients. 225 colorectal cancer patients aged 18-59 admitting to a specialized oncology hospital in Guangzhou, China were involved from January to April 2022. Socio-demographic characteristics, disease-related characteristics, scores of Illness Behavior Questionnaire, Hospital Anxiety and Depression Scale, the Brief Illness Perception Questionnaire, Mishel Uncertainty in Illness Scale and Medical Coping Modes Questionnaire were applied to collect quantitative data. Latent profile analysis (LPA) of illness behavior, analysis of variance (ANOVA) and multiple logistic regression were performed. Three latent classes of illness behavior were identified: low maladaptive illness behavior group, moderate maladaptive illness behavior group, and high maladaptive illness behavior group. Univariate analysis revealed statistically significant differences among the three latent classes with respect to education level, anxiety and depression, illness perception, uncertainty in illness and coping modes. Multiple logistic regression analysis revealed that marital status, family history of cancer, education level, family monthly income, anxiety and depression, illness perception, uncertainty in illness and coping modes were predictors of maladaptive illness behaviors among young and middle-aged CRC patients. The results of the study raise a concern of maladaptive illness behaviors in young and middle-aged colorectal cancer patients, highlighting the need for age-appropriate psychosocial care approaches to promote adjustment of the illness behaviors followed by the diagnosis and treatment of CRC.

Disparities and barriers in germline testing among patients with early-onset gastrointestinal cancers.

35 Background: Early-onset gastrointestinal cancers (EOGIC) are strongly associated with hereditary predisposition, making germline testing essential for treatment and familial risk management. Disparities in germline testing persist. This study investigates disparities and barriers to germline testing in EOGIC. Methods: This IRB-approved retrospective analysis included 864 patients aged 18-49 with GI cancers at the University of Chicago (2018-2023). Data collected included race, gender, age, insurance, family cancer history, and subtype. Outcomes were physician referrals for germline testing and completion. Chi-square tests and logistic regression models assessed predictors of recommendations and completion. Results: Of 864 patients, 473 (54.7%) received germline testing recommendations, and 323 (37.4%) completed testing. Completion rates: 30.2% for no insurance, 29.1% for Medicare/Medicaid, and 40.3% for private insurance (p=0.032). Patients with family history of cancer were more likely to be recommended for testing (62.9% vs. 39.5%, p&lt;0.001) and complete it (44.0% vs. 23.7%, p&lt;0.001). In our cohort, no significant racial disparities were observed (p=0.712 and p=0.358). Females were more likely to receive recommendations (59.1%) and complete testing (41.2%) than males (50.9% referral, 34.0% completion, p=0.016 and p=0.029). Patients under 30 had the highest rates of testing recommendation (66.1%) and completion (46.4%), followed by 30-39 (61.7%, 44.4%) and 40-49 (51.2%, 34.0%), p=0.006 and p=0.009. By cancer subtype, colorectal cancer (CRC) patients had the highest referral (66.1%) and completion (45.9%) rates, while anal cancer had the lowest (13.2% referral, 5.3% completion, OR 0.08, p&lt;0.0001). Gastric cancer (52.3% referral, 29.2% completion, OR 0.49, p=0.005) and esophageal cancer (36.9% referral, 20.0% completion, OR 0.31, p&lt;0.0001) also had lower testing rates. Liver cancer (35.4% referral, 27.1% completion, OR 0.38, p&lt;0.0001) and cholangiocarcinoma (45.5% referral, 22.7% completion, OR 0.28, p=0.016) showed similarly low rates. Conclusions: Disparities in germline testing were seen among uninsured patients, males, and those with public insurance. CRC had the highest testing rates, while anal, esophageal, liver, and cholangiocarcinoma had lower rates, likely due to lower suspicion of hereditary predisposition. Targeted interventions are needed to improve testing uptake and completion, especially among uninsured and underrepresented populations.

The Gastric Cancer Registry: A multi-omic cellular and molecular resource for cancer biomarker and therapeutic discovery.

491 Background: The Gastric Cancer Registry (GCR) is a comprehensive clinical and genomic data resource focused on gastric cancer (GC) patients and individuals with a family history of GC or a germline CDH1 mutation. As part of the GCR’s ongoing enrollment, patients contribute cancer history information, archival tumor samples and other biospecimens. The cancer samples undergo extensive molecular and cellular analysis that includes genomic sequencing and spatial analysis. We have generated a robust dataset, publicly accessible online through the GCR Genome Explorer (GCR-GE). This genomic, molecular and cellular resource provides a rich data set that accelerates multidisciplinary research aimed at improving detection and treatment strategies for GC. GC disproportionately affects Latin American populations - we have included new cohorts from Latin America. The GCR enables researchers, clinicians and patients to address specific questions about the molecular and cellular basis of GC. Methods: GC samples underwent whole genome, whole exome, and bulk RNA sequencing were conducted. The genomic features identified include copy number variation, gene mutations, gene expression, microbiome composition, estimation of tumor-infiltrating immune cells, tumor neoantigens, MSI/MSS status, and HLA subtypes. In addition to genomic data, clinical data was compiled from survey responses and pathology reports and integrated into the GCR-GE. We have incorporated single cell and spatial analysis that includes diverse cell types, single cell gene expression and cellular architecture in native tumor tissues. This data was released to the GCR Genome Explorer website. Results: A total of 817 subjects have enrolled in the GCR including 598 diagnosed with GC and 219 at high-risk for GC through family history of GC and/or a CDH1 mutation. Of the 598 with GC, some met multiple criteria including at least 40 with a family history of GC, 10 with a CDH1 mutation, and 18 with both a family history of GC and a CDH1 mutation. The GCR-GE includes data from 257 gastric tumors in addition to external datasets from TCGA. In the latest data release, clinical and genomic data from 78 gastric tumors from patients in Latin America were integrated into the GCR-GE. Conclusions: The GCR is a comprehensive database of crucial clinical and genomic data necessary for driving forward GC research. Through global expansion, the GCR has generated a more representative dataset by increasing racial diversity and including underrepresented populations that are at higher risk for GC.

Novel Breast Cancer Risk Assessment Tools for Pre- and Post-Menopausal Asian Women: Development and Validation in a Nationwide Mammographic Screening Cohort.

Widely used breast cancer risk-prediction tools are based on data from Western countries, but risk factors may differ for Asian women. Hence, we aimed to develop a risk assessment tool for breast cancer in Asian women using a nationwide, population-based mammographic screening cohort. Women aged ≥40 years who underwent breast cancer screening and general health examination in 2009 were included. Age, body mass index (BMI), breast density, lifestyle and reproductive factors, and comorbidities were used to develop 5-year breast cancer risk-prediction models for premenopausal (n=771,856) and postmenopausal (n=1,108,047) women at baseline. The best-fit risk prediction model was constructed using backward stepwise selection in a Cox proportional hazards model and was transformed into a risk score nomogram. The performance was assessed by discrimination and calibration. In premenopausal women, high BMI, low parity, short breastfeeding period, early age at menarche, high breast density, a history of benign breast masses, and family history of breast cancer contributed to the risk prediction of breast cancer. In postmenopausal women, age, diabetes mellitus, dyslipidemia, late-onset menopause, and hormone replacement therapy use were additional risk predictors of breast cancer. Our risk-prediction model showed a concordant statistic of 0.58 (0.57-0.59) for premenopausal women and 0.64 (0.63-0.65) for postmenopausal women. The calibration plot demonstrated good correlations for both models. Our breast cancer risk-prediction model demonstrated performance comparable to that of Western countries, especially among postmenopausal women. This provides a foundation for implementing risk-based screening recommendations in Asian women.