tbuckley/cabot-search huggingface dataset:
Gastric juice piR-1245: A promising prognostic biomarker for gastric cancer.
Authors: Wei Peng, Linghua Sun, Ting Qian, Ping Gong, Bo Shen, Guoren Zhou
Journal: Journal of Clinical Oncology (2025)

e16095 Background: Emerging reports demonstrated that PIWI-interacting RNAs (piRNAs) played an indispensable role in tumorigenesis. However, it still remains elusive whether piR-1245 in gastric juice specific in stomach could be employed as a biomarker for gastric cancer (GC). The present work is aiming at exploring the possibility of piR-1245 in gastric juice as a potential marker to judge for diagnosis and prognosis of gastric cancer. Methods: Gastric juice was collected from 66 GC patients and 66 healthy individuals. Quantitative real-time reverse transcriptase polymerase chain reaction (qRT-PCR) was employed to measure the levels of piR-1245 expression. Then, the pattern of piR-1245 expression in gastric juice was determined between GC patients and healthy individuals. A receiver operating characteristic (ROC) curve was constructed for distinguishing GC from healthy individuals. Results: Gastric juice piR-1245 levels in GC were higher than those of controls (P &lt; 0.0001). The value of area under ROC (AUC) was 0.885 (sensitivity, 90.9%; specificity, 74.2%; 95% confidence interval, 0.8286 to 0.9414). High gastric juice piR-1245 expression was signally correlated with tumor size (P = 0.013) and TNM stage (P = 0.001). GC patients with high piR-1245 expression in gastric juice exerted a poorer overall survival (OS) (P = 0.0152) and progression-free survival (PFS) (P = 0.013). COX regression analysis verified that gastric juice piR-1245 expression was an independent prognostic risk variable for OS (P &lt; 0.05). Conclusions: The current study suggested that piR-1245 in gastric juice had the potential to be a useful biomarker for GC detection and prognosis prediction.
The role of ADAR1-mediated A-to-I RNA editing and non-editing functions in radioresistance of esophageal squamous cell carcinoma.
Authors: Liangchao Sun, Xue Meng
Journal: Journal of Clinical Oncology (2025)

e16099 Background: Radiotherapy (RT) is a critical treatment for esophageal squamous cell carcinoma (ESCC), but radioresistance poses a significant challenge. Previous research has indicated that Adar1-null tumors exhibit enhanced radiotherapy response in melanoma, suggesting that ADAR1 loss could improve RT efficacy. This study aims to investigate the role of ADAR1, including both its A-to-I RNA editing and non-editing functions, in the regulation of radioresistance in ESCC. Methods: ADAR1 expression was quantified in six ESCC tissue samples and adjacent normal tissues using qRT-PCR. A radiotherapy-resistant KYSE410 cell line was developed through serial irradiation. ADAR1 was downregulated in KYSE410 and TE-1 cell lines using siRNA, and recombinant plasmids were used to overexpress both the wild-type and edited forms of C16orf46. Cell proliferation and radiotherapy sensitivity were evaluated using the MTT assay and clonogenic assay. Pyroptosis was assessed using Annexin V staining, LDH release, and measurements of interleukin 1β (IL-1β) and interleukin 18 (IL-18). Transcriptome sequencing was performed on ADAR1-silenced cells to analyze changes in signaling pathways and RNA editing sites. Western blot experiments was used to detect alterations in the pyroptosis pathway and NF-κB signaling pathway. Results: ADAR1 expression was significantly higher in cancerous tissues compared to adjacent normal tissues (P &lt; 0.05). Downregulation of ADAR1 significantly inhibited the proliferation of esophageal tumor cells, increased sensitivity to radiotherapy, and promoted radiotherapy-induced pyroptosis. Transcriptome analysis revealed that ADAR1 silencing activates the NF-κB signaling pathway. Inhibition of NF-κB with BAY 11-7082 reduced cell death following RT in ADAR1-knockdown KYSE410 cells, indicating a key role for NF-κB in pyroptosis triggered by ADAR1 loss. Western blot analysis demonstrated that ADAR1 activates cIAP2 in an RNA editing-independent manner, thereby regulating the NF-κB/GSDME pathway. A &gt; G RNA editing events, particularly in the C16orf46 transcript, were identified in ADAR1-silenced cells, resulting in a Y335H amino acid change in the C16orf46 protein. The edited form of C16orf46 (edit-C16orf46) was found to enhance esophageal tumor cell proliferation and radiotherapy resistance. Conclusions: Our study underscores the potential of ADAR1 as a therapeutic target for overcoming radioresistance in ESCC through the modulation of pyroptosis, offering a new perspective for the development of targeted therapies.
Gender disparities in major adverse cardiovascular and cerebrovascular events among gastric cancer patients: A nationwide analysis (NIS 2016–2021).
Authors: Siddharth Pravin Agrawal, Kanishka Uttam Chandani, Sharan Jhaveri, Niti Chokshi, Darshilkumar Maheta, Dev Lotia, Pragya Jain
Journal: Journal of Clinical Oncology (2025)

e16096 Background: Gastric cancer remains a leading cause of cancer mortality, with gender disparities in outcomes influenced by cardiovascular risk factors, resource utilization, and mortality rates. This study examines gender differences in MACCE, mortality, and healthcare costs among hospitalized gastric cancer patients using NIS data from 2016–2021. Methods: A retrospective cohort analysis was conducted using the NIS database to identify adult gastric cancer patients. Patients were stratified by gender, and demographic, clinical, and socioeconomic characteristics were compared. The primary outcomes included in-hospital mortality, myocardial infarction (MI), stroke, atrial fibrillation (A-fib), sudden cardiac arrest, and other MACCEs. Secondary outcomes included length of stay (LOS) and total hospital charges (TOTCHG). Multivariable logistic regression models adjusted for potential confounders were used to assess gender disparities in these outcomes. Results: Among 248,580 gastric cancer patients, 63.1% were male, &amp; 36.9% were female. Males had a significantly higher prevalence of dyslipidemia (35.91% vs. 31.38%, p &lt; 0.001), chronic obstructive pulmonary disease (16.54% vs. 15.25%, p = 0.0003), &amp; atrial fibrillation (14.24% vs. 10.21%, p &lt; 0.001), while females had a higher prevalence of obesity (9.38% vs. 7.17%, p &lt; 0.001). Males had a lower risk of in-hospital mortality (OR 0.919, p = 0.019) &amp; sudden cardiac arrest (OR 0.799, p = 0.015), but a higher risk of stroke (OR 1.296, p = 0.001) compared to females. Additionally, males had a lower likelihood of developing MI (OR 0.842, p = 0.009) and arrhythmias (OR 0.609, p &lt; 0.001). Length of stay was similar between genders (p = 0.878). However, total hospital charges were significantly higher for males ($91,785.70 vs. $87,387.09, p &lt; 0.001). Conclusions: This study reveals significant gender disparities in gastric cancer outcomes. Males had lower mortality and MI risk but higher stroke and atrial fibrillation risk. Despite similar LOS, males faced higher healthcare costs, emphasizing the need for gender-specific risk stratification and management. Outcome Odds Ratio 95% confidence P value Death 0.919 0.857 0.986 0.019 MI 0.842 0.74 0.958 0.009 Cerebral Artery Stenosis 0.876 0.69 1.111 0.276 Stroke 1.296 1.105 1.519 0.001 Sudden Cardiac 0.799 0.667 0.957 0.015 A Fib 0.619 0.582 0.659 &lt;0.001 Arrhythmia 0.609 0.522 0.711 &lt;0.001 ICH 0.82 0.608 1.107 0.196 Acute CHF 0.979 0.623 1.539 0.93 LOS 0.0112 -0.133 0.155 0.878 Total Health Charges -5296.334 -7620.04 -2972.62 &lt;0.001
Bridging gaps: Evaluating the impact of urban lung cancer screening on diverse populations.
Authors: Ana S Salazar, Subul Malik, Kyle Rowley, Helena F. Bruzzi, Kyle Edwards, Dan Morgenstern, Jose Noy, Zully Moreno, Nicole Ann Gay, Coral Olazagasti, Estelamari Rodriguez
Journal: Journal of Clinical Oncology (2025)

e13835 Background: Lung cancer (LC) screening reduces mortality in high-risk populations, yet disparities persist, particularly among Hispanic individuals who are often diagnosed at advanced stages and less likely to meet screening criteria. In 2024, Florida’s LC screening rate for high-risk individuals reached 15.8%, aligning with the national average of 16% and marking an improvement from previous years. This study evaluates the effectiveness of an LC screening program in a predominantly urban setting, focusing on follow-up outcomes among underserved populations disproportionately impacted by LC. Methods: A retrospective analysis was conducted on LC screening data from the University of Miami’s screening program between January 2022 and April 2024. Demographic variables, Lung-RADS classifications, and follow-up rates (defined as completed within 1 year and 90 days after an initial scan) were analyzed to assess program performance. Associations between screening adherence and demographic characteristics were examined using multivariate analysis. Results: The cohort included 661 patients, predominantly male (55%), with 85.9% identifying as White, 8.8% as Black, and 5% as Other. Nearly half (50.9%) were Hispanic, while 44% were non-Hispanic. Most patients (88.4%) had Lung-RADS categories 1–2, while 7.1% had category 3, and 4.5% had category 4. Multivariate analysis revealed that older age significantly increased the likelihood of follow-up visits (OR = 1.04 per year, p = 0.014). Although non-Hispanic patients had slightly higher odds of follow-up, the difference was not statistically significant (OR = 1.26, p = 0.199). However, White patients were significantly more likely than Black patients to repeat imaging for both Lung-RADS 3 (OR = 1.57; 95% CI: 1.10–2.23; p = 0.012) and Lung-RADS 4 (OR = 1.72; 95% CI: 1.23–2.42; p = 0.003). Conclusions: LC screening programs in urban, predominantly Hispanic populations face unique challenges, including lower adherence and socioeconomic barriers. Tailored, culturally competent interventions are essential for improving follow-up rates and ensuring equitable access to early detection and treatment. Expanding these efforts can contribute to broader public health goals of reducing disparities in LC screening and outcomes.
TRENT-002: A prospective, multicenter, randomized controlled phase II study to evaluate the efficacy and safety of salvage preoperative PD-1 inhibitor combined with chemotherapy neoadjuvant therapy in recurrent laryngeal/hypopharyngeal squamous cell carcinoma (L/HPSCC).
Authors: Xiaohong Chen, Yixin Jing, Yiming Ding
Journal: Journal of Clinical Oncology (2025)

TPS6119 Background: Salvage surgery is considered the standard of care for patients with resectable recurrent L/HPSCC. However, salvage surgery achieves durable disease control in only 20% to 50% of patients. The PATHWay study showed that the subgroup that received salvage therapy indicated that adjuvant pembrolizumab could significantly improve PFS compared with placebo, but there is no OS data. This muti-center, prospective, randomized controlled phase II study will evaluate efficacy and safety of PD-1 inhibitors plus chemotherapy as neoadjuvant therapy in recurrent L/HPSCC. Methods: Patients who meet the inclusion criteria will be divided into groups according to whether they had received radiotherapy in the past. Arm 1 and Arm 2 are the groups that had not received radiotherapy in the past (N=100), and Arm 3 and Arm 4 are the groups that had received radiotherapy (N=160). Arm 1 and Arm 2 will be randomly assigned at a 1:1 ratio. Arm 1 will receive 3 cycles of pembrolizumab + nab-paclitaxel + cisplatin, followed by surgery. After surgery, patients will be stratified according to the presence or absence of high-risk factors (extranodal extension or positive margins). The high-risk group will receive concurrent chemoradiotherapy + pembrolizumab maintenance therapy (up to 15 cycles), and the low-risk group will receive radiotherapy + pembrolizumab maintenance therapy (up to 15 cycles). Arm 2 will undergo surgery directly, followed by concurrent chemoradiotherapy/radiotherapy. The total radiation dose is 60-66 Gy, 2.0 Gy/fraction for high-risk group and 44-50 Gy, 2.0 Gy/fraction for low-risk group. Similarly, Arm3 and Arm4 will be randomly assigned in a 1:1 ratio. Arm 3 will receive 3 cycles of pembrolizumab + nab-paclitaxel + cisplatin, followed by surgery, and pembrolizumab maintenance treatment after surgery. Arm 4 will be directly given surgery, and after surgery, the doctor will choose observation / re-radiotherapy or chemoradiotherapy. Eligibility criteria will include patients with squamous cell carcinoma of the larynx and hypopharynx confirmed by histology and/or cytology; patients with recurrence of primary tumor or second primary tumor after receiving curative treatment; At least 6 months after the last platinum-containing treatment; ECOG performance status 0-1. Primary end points is 2y-PFS. Secondary end points include ORR, pCR, 3y-OS, safety. Recruitment is ongoing and will continue until 260 patients are enrolled. Clinical trial information: NCT06793761 .
21-gene expression assay in postpartum vs non-postpartum breast cancer and correlation with outcomes in young women with breast cancer.
Authors: Shiliang Zhang, Marla Lipsyc-Sharf, Kelly Elizabeth McCann, Mediget Teshome, Aditya Bardia, Nimmi S. Kapoor
Journal: Journal of Clinical Oncology (2025)

e12538 Background: The incidence of breast cancer (BC) in young women is rising and noted for more aggressive features and worse prognosis. Concurrently, increasing maternal age in the United States has led to a higher incidence of pregnancy-associated BC, known for worse survival outcomes. Specifically, post-partum BC (PPBC), characterized by mammary gland involution and remodeling after lactation, exhibits unique molecular characteristics thought to contribute to its poor prognosis. A higher prevalence of PPBC in YWBC may partly explain their worse outcomes, however genomic profiles of PPBC and non-PPBC are not well understood. We hypothesized that YWBC with PPBC may have higher 21-gene expression assay scores—Oncotype DX Recurrence Scores (RS)—and worse outcomes compared to YWBC with non-PPBC. Methods: A retrospective chart review was conducted, pooling data from three cohorts of YWBC with ER+HER2- BC over different time periods between 2011-2024 including patients (pts) with PPBC, pts with node positive BC, and a contemporary cohort of pts. YWBC were defined as women ≤45 years old. PPBC was defined as BC diagnosed ≤5 years postpartum and excluded cases diagnosed during pregnancy. Clinical outcomes, including 5-year distant recurrence-free survival (DRFS), overall survival (OS), and RS, were analyzed and compared between PPBC and non-PPBC using descriptive statistics, two proportion z-test, student’s t-test, Kaplan-Meier curves and log-rank test. Results: From the pooled cohorts, there were 43 YWBC with ER+HER2- BC. 44.2% of pts had stage I BC, 39.5% of pts had lymph node metastasis, and 58.1% were treated with systemic chemotherapy. 24 YWBC had non-PPBC while 19 had PPBC. Of these pts, 54.2% of non-PPBC had stage I disease compared to 31.6% of PPBC (p=0.128). 45.8% of non-PPBC had lymph node involvement compared to 73.7% of PPBC (p=0.066) and 45.8% of non-PPBC were treated with systemic chemotherapy compared to 68.4% of PPBC (p=0.128). 24 (55.8%) pts had RS available for review including 16 non-PPBC and 8 with PPBC. Average RS was 18.9 in the non-PPBC and 19.3 in the PPBC group (p=0.919). A higher proportion of PPBC pts had RS ≥16—75% in PPBC vs. 50% in non-PPBC (p=0.242). With a median follow-up of 66.1 months, distant recurrence rates were 8.33% and 21.1% in the non-PPBC and PPBC groups, respectively. The 5-year DRFS was 88.8% in non-PPBC and 80.3% in PPBC pts (p=0.26), with corresponding OS rates of 100% and 94.1% (p=0.55). Conclusions: From this pooled cohort, YWBC with PPBC have more lymph node involvement, higher chemotherapy use, and worse RFS than those with non-PPBC. However, differences in RS between these groups were less pronounced. Ongoing work will expand our cohorts to confirm these findings, while further studies are needed to better elucidate the biology lending to worse outcomes for pts with ER+ PPBC.
Disparities in GLP-1 receptor agonist prescriptions among breast cancer survivors with type 2 diabetes.
Authors: Jasmin Hundal, Omer Ashruf, Karen Basen-Engquist, David Kaelber, Jasmine S Sukumar
Journal: Journal of Clinical Oncology (2025)

e13831 Background: GLP-1 receptor agonists (GLP-1RA) improve glycemic control, promote weight loss, and reduce cardiovascular risks in patients with type 2 diabetes mellitus (DM2). Breast cancer survivors face increased recurrence risk and cardiovascular disease related to obesity and DM2 and thus can have substantial benefits from these agents. However, challenges in access to GLP-1RA exist, and this may exacerbate cancer survivorship care disparities. This study evaluated sociodemographic and geographic disparities in GLP-1RA prescription rates. Methods: We conducted a retrospective cohort analysis utilizing TriNetX, a de-identified electronic health record data platform. Breast cancer patients with DM2 (2005–2024) were included, excluding those with GLP-1RA contraindications (type 1 diabetes, pancreatitis, gastroparesis, thyroid cancer). Patients were stratified by race (Asian, Black, White, Other [American Indian or Pacific Islander] and age (18-64 or ≥65 years) and 1:1 propensity-matched for multiple covariates such as BMI and body weight, cardiometabolic conditions (hypertension, dyslipidemia, ischemic heart disease, obstructive sleep apnea), bariatric surgery, HbA1c, and prior antidiabetic agents. Sensitivity analysis included patients with overweight/obesity (BMI ≥ 25 kg/m2). The primary outcome was the rate of GLP-1RA prescription (lixisenatide, albiglutide, dulaglutide, semaglutide, liraglutide, exenatide, tirzepatide). Cox proportional hazards model estimated Hazard Ratios (HR) to assess time-to-event outcomes. Results: A total of 130,228 patients met eligibility (mean [SD] age: 67.2 [11.9] years; 61.6% White, 21.0% Black, 5.2% Asian, 12.1% Other). The mean follow-up time was 5.7 ± 4.2 years. Amongst the entire study population and those with overweight/obesity, White patients were more likely to be prescribed GLP-1RA compared to Asian, Black, and Other patients (HRs in Table 1). Those aged &gt; 65 were less likely to receive GLP-1RA than younger patients (HR 0.44, 95% CI 0.42–0.46). The most common geographic regions by race were the South for White (38%) and Black (62%) patients, the West for Asian patients (45%), and the Northeast for others (43%). Conclusions: Significant disparities in GLP-1RA prescription rates were identified among breast cancer survivors with DM2, particularly among older adults and non-White racial groups. This emphasizes the need for targeted interventions to improve equitable access to these classes of pharmaceutics with important health benefits in cancer survivors. GLP-1RA prescription disparities by racial subgroups. Race Race Hazard Ratio [95% CI] All Patients (n=130,228) White Ref Asian 0.64 [0.58–0.71] Black 0.78 [0.75–0.81] Other 0.84 [0.75–0.95] Patients with Overweight/Obesity (n=70,716) White Ref Asian 0.78 [0.68–0.88] Black 0.78 [0.74–0.81] Other 0.83 [0.72–0.95]
Ethnic differences in nonalcoholic fatty liver disease (NAFLD) among women with early-stage breast cancer receiving endocrine therapy.
Authors: Mengni Guo, Darren Wijaya, Kevin R Bera, Adam Hagele, Man Kit Ho, Andreas Lau, Riyan Bittar, Michael Borecky, Ami Patel, Roshni Narurkar, Gayathri Nagaraj
Journal: Journal of Clinical Oncology (2025)

e12524 Background: NAFLD is a metabolic comorbidity increasingly recognized in oncology populations.Hormone receptor-positive (HR+) breast cancer (BC) is typically treated with endocrine therapy (ET). Both aromatase inhibitors (AIs) and tamoxifen are linked to metabolic side effects, including NAFLD, which complicate treatment outcomes and impact long-term health. Ethnic differences in the prevalence of NAFLD among women receiving ET for BC remain underexplored. Methods: We conducted a retrospective single-center analysis of adult female patients with HR+ early-stage BC (carcinoma in situ to stage III) between January 2012 and December 2022. Baseline demographic and clinicopathologic characteristics were collected. All patients received adjuvant ET for at least 6 months. Patients with baseline NAFLD, viral/autoimmune/alcoholic hepatitis, heavy alcohol use, or concurrent malignancies were excluded. Incidence and time to onset of NAFLD by imaging was measured. Primary analysis was restricted to patients who self-identified as Hispanic (H) or Non-Hispanic (NH). Chi-square or Fisher’s exact tests were used for categorical variables, and Mann-Whitney U tests for continuous variables. Multivariate Cox regression models were used to identify risk factors for NAFLD and analyze its impact on patient outcomes. Results: A total of 246 patients were analyzed, comprising 54 (22%) H and 192 (78%) NH. H patients were younger (median age 51.5 vs. 61 years, p &lt; 0.0001), more frequently pre-menopausal (42.6% vs. 20.8%, p = 0.001) with lower prevalence of hypertension (27.8% vs. 44.8%, p = 0.025). No differences were noted between the two groups in BMI (median 29.1 vs. 27.4, p = 0.52), diabetes (14.8% vs. 12.5%, p = 0.66), or hyperlipidemia (31.5% vs. 36.4%, p = 0.5).Cancer stage at diagnosis and pathologic tumor characteristics did not significantly differ between the two groups.Treatment patterns showed more ovarian suppression (27.8% vs. 8.9%, p = 0.0003) and less chemotherapy use (14.8% vs. 33.3%, p = 0.008) in H vs. NH. No significant differences in recurrence-free survival ( p = 0.28) or overall survival ( p = 0.41) were noted. NAFLD incidence post-ET was significantly higher in H (22.2% vs. 11.5%, p = 0.043). Time to onset of NAFLD was also shorter in H compared to NH patients (HR 2.46, 95% CI 1.21–5.00, p = 0.01), with median durations not reached in either group. Multivariate analysis identified Hispanic ethnicity (HR 2.34, 95% CI 1.06–5.19; p = 0.036) and BMI (HR 1.10, 95% CI 1.04–1.17; p = 0.0015) as independent NAFLD risk factors. Conclusions: This study highlights the higher incidence and early onset of NAFLD in Hispanic women with early-stage breast cancer receiving ET, underscoring the unmet need for targeted screening, hepatic monitoring, and early lifestyle interventions for this high-risk population.