Gastrointestinal Malignancies Research Articles

Quantification of treatment-related time toxicity in patients with advanced stage cancer.

12137 Background: Treatment-related Time Toxicity (TrTT) in cancer patients is a recently proposed metric to describe the burden of time spent in pursuing medical care, including office/hospital visits, side effect management, lab tests, imaging scans, and travel time. Time toxicity is a valuable concept in patient-centered shared-decision making, especially in the palliative management of end-stage cancer patients with limited life expectancy. Despite tremendous progress in cancer treatment, most of the guideline-recommended treatment options convey short survival benefits of around 3-6 months when compared to supportive care. While medication toxicities are meticulously reviewed with patients, the cumulative burden and impact of time are rarely included in the discussion, partly due to the lack of standardized measurement of TrTT, and the absence of data from clinical trials. Thus, there is a compelling need for the quantification of time toxicity to guide clinical practice and patient preference. Methods: This was an observational analysis of the time toxicity from palliative treatment for patients with incurable solid tumors at a regional safety-net oncology office that focuses on underserved communities. Time toxicity is calculated as the number of days a patient spent with any healthcare-related encounters during a 3-month period from our medical record system. Results: The median age of the total 94 included patients was 57. 54% of the population were Hispanic. The ratios for mild, moderate, and severe time toxicity were 38%, 44%, and 18%, respectively. Immunotherapy was associated with significantly less time toxicity (TrTT = 8.5 days, 95% CI = 6.3-9.7) compared to chemotherapy (26.3 days, 95% CI = 18.3-34.4, P < 0.001), while targeted therapy (13.4, 95% CI = 7.0-19.8, P = 0.01) and hormone therapy (11.9, 95% CI = 4.1-19.7, P < 0.01) also has lower TrTT than chemotherapy. Patients with a worse performance status (ECOG PS 3-4, 30.1 days, 95% CI = 18.3-41.9) experienced higher time toxicity than fitter patients (PS 0-2, 16.7 days, 95% CI = 13.2-20.2, P < 0.05). Among different cancer types, gastrointestinal malignancies were associated with the highest time toxicity with average TrTT of 30.2 days/3 months (95% CI =22.5-37.2). Conclusions: This is the first comprehensive study to quantify real-world Treatment-Related Time Toxicity across multiple cancer and therapy types in an underserved population. We found 18% of patients with incurable solid malignancies experienced severe time toxicity (> 1 in 3 days). Higher TrTT was associated with cytotoxic chemotherapies, GI malignancies, and poor performance status. Time toxicity should be taken into account with other quality-of-life outcomes in treatment pathways and patient-centered oncology care.

529P Development and validation of a high-throughput drug screen (HTDS) from patient-derived tumor organoids (PDTO) from gastrointestinal malignancies: Clinical and genomic correlations

529P Development and validation of a high-throughput drug screen (HTDS) from patient-derived tumor organoids (PDTO) from gastrointestinal malignancies: Clinical and genomic correlations

Accurate parent-of-origin variant assignment for multiple hereditary cancer syndromes using proband-only blood sample analysis.

10516 Background: Predicting which side of the family a germline variant comes from is a critical gap in current clinical practice, vital for risk management, variant curation, and cascade genetic testing. Assignment of any autosomal variant to either parent with 99% accuracy is now possible with only a blood sample from the proband. Parent-of-Origin-Aware genomic analysis (POAga) is achieved by combining methylation and sequence data from Oxford Nanopore long-read sequencing with chromosome-length haplotypes generated from Strand-seq to infer parent of origin of any variant along the length of a chromosome, due to accurate phasing of imprinted differentially methylated regions that occur on each autosome. We sought to validate POAga in common, high penetrant hereditary cancer conditions such as hereditary breast and ovarian cancer (HBOC) and Lynch syndrome, rarer syndromes with parent-of-origin-effects and other genes predisposing to breast cancer and gastrointestinal malignancies that are associated with genes across multiple chromosomes. Methods: Blood samples from carriers of pathogenic variants in ATM, BRCA1, BRCA2, CDH1, MLH1, MSH2, MSH6, PMS2, EPCAM, PALB2, SDHD and SDHAF2, with known parental segregation, are currently being ascertained to determine the analytic validity of POAga in real world samples of differing age, sex, ethnicity, and cancer status. Samples are undergoing whole genome analysis by long and short read sequencing. Parent-of-origin of the pathogenic or likely pathogenic variant or variant of uncertain significance is predicted according to previously described methods (Akbari V, Hanlon VCT, et al. Cell Genom. 2022 Dec 21;3(1):100233.) under an REB approved protocol. Results: To date, analysis is complete for 100 individuals with a total of 107 rare or pathogenic germline variants with known or presumed parental segregation. Germline variants are in SDHD (n = 18), BRCA2 (n = 17), BRCA1 (n = 14), MLH1 (n = 10), PALB2 (n = 9), PMS2 (n = 8), MSH2 (n = 9), MSH6 (n = 7), ATM (n = 5), CDH1 (n = 5), SDHAF2 (n = 1), DICER1 (n = 1), MUTYH (n = 1), RET (n = 1), and EPCAM (n = 1). Of variants able to be assigned a parent-of-origin (n = 104 of 107, 97%), there was complete concordance between the predicted parent-of-origin and known clinical segregation (n = 104, 100%). Conclusions: Results to date support the ability of POAga to accurately infer parent-of-origin of rare or pathogenic variants with known parental segregation using only a blood sample from carriers of diverse hereditary cancer syndromes. Ongoing validation of POAga will continue to test its feasibility in real-world samples and inform its path towards clinically translation. Parent-of-Origin-Aware genomic analysis is a powerful technology that could improve our understanding of hereditary cancer syndromes and transform our ability to conduct genetic cancer risk assessments for patients and families.

Impact of bowel ischemia on mortality in gastrointestinal malignancies: A nationwide analysis.

e16370 Background: Bowel ischemia, characterized by reduced blood supply to the gastrointestinal (GI) tract, critically influences the pathogenesis and outcomes of GI malignancies through complex interactions involving vascular compromise, tumor biology, and systemic consequences. Despite this, the link between bowel ischemia and increased mortality in GI cancers remains unknown. This study aims to evaluate the impact of bowel ischemia on in-hospital mortality in GI cancer patients in the United States. Methods: This retrospective analysis utilized the 2016-2020 National Inpatient Survey (NIS) database. Adults aged 18 and above with esophageal, gastric, colon, cholangiocarcinoma, hepatocellular carcinoma, and pancreatic cancers were identified using the International Classification of Disease-10 (ICD-10) code. The cohort was stratified into patients with and without bowel ischemia. Hospital mortality was analyzed using STATA 18, adjusting for age, gender, race, insurance, Charlson’s index, baseline hospital characteristics, and comorbidities. Multivariate logistic regression analysis was performed, with all P values ≤ 0.05 considered statistically significant. Results: Among 2,133,465 adults with GI malignancies, 3,240 were hospitalized with bowel ischemia. Patients with bowel ischemia were older (mean age 68.10 vs. 67.07 years, P = 0.033), predominantly from the Southern region (33.49%, P = 0.019), and urban and teaching hospitals (76.83%; P = 0.006). Bowel ischemia was most associated with Pancreatic cancer (37.35%), Colon cancer (35.49%), and Hepatocellular carcinoma (11.57%). Within the cohort of patients with bowel ischemia, gastric cancer patients had the highest mortality rates of 45.83%. After adjusting for potential confounders, patients with gastric, esophageal, colon, and pancreatic cancers had significantly higher odds of in-hospital mortality of 11.90, 6.45, 4.14, 4.08, and 2.71, respectively. Conclusions: This study reveals an association between outcomes in hospitalized GI cancer patients and bowel ischemia, leading to increased mortality despite adjusting for potential confounders. Bowel ischemia significantly heightens the mortality risk in GI cancers through impaired nutrient and oxygen delivery, enhanced tumor aggressiveness, systemic inflammation, immune suppression, and compromised treatment efficacy. Understanding the intricate interplay between vascular compromise and cancer biology is crucial to improving patient care and outcomes in the face of these challenging malignancies.

Characterization of social determinants of health in patients considered for participation in treatment clinical trials at a community cancer center serving the Great Plains.

e13704 Background: Avera Cancer Institute, a community-based cancer network comprised of six rural cancer centers in SD and MN, provides care to a five-state region in the upper mid-west covering 72,000 square miles and offers several clinical trials to patients to offer access to advanced treatment for malignancies. Malignances are known to disproportionally affect patients that are older, rural, minorities, and have lower socioeconomic status, which are all less likely to enroll into clinical trials. Methods: Patients evaluated for participation in clinical trials from 2018-2022 were identified in an institutional database. Trial type was designated as either a treatment or nontreatment trial. Status of trial involvement was designated between enrolled or screened. Their demographic information was obtained from the electronic health record (EHR). Demographic information obtained from the EHR includes race, ethnicity, language spoken, gender, employment status, insurance type, and if they live in an urban or rural area as defined by the US Census Bureau. Clinical trial portfolio during this time includes trials for breast, gynecological, gastrointestinal, lung, and hematologic malignancies. Results: 4,397 patients were considered for participation in a clinical trial at our institution in the studied timeframe. Of these patients, 1887 were screened for treatment trials and of that group, 773 were enrolled. 35% of participants considered for clinical trials were from urban areas while 65% considered were rural. 48% of the urban population ultimately were enrolled on a clinical trial while 44% of rural population participated. Participants who lived in an urban area 25-50 miles from our study site had an enrollment rate of 49% compared to rural enrollment of 33%, from 50-100 miles rates of 53% and 37%, from 100-250 miles rates of 29% and 41%, and from greater than 250 miles rates of 44% and 33%, respectively. 99.5% of the population was non-Hispanic, 97% were White, and 99% were English speaking. 74% of the total population were female and 26% were male. Females had an enrollment rate of 51% while males had an enrollment of 29%. Patients with no insurance enrolled in trial 62% compared to 36% of those with commercial insurance The average national Area Deprivation Index percentile for screened patients was 57 vs 59 for enrolled patients. Conclusions: This retrospective study demonstrates a greater likelihood for females, urban patients, and white, English-speaking patients to enroll into clinical trials. Our data also demonstrate a preference for uninsured patients to enroll into clinical trials, possibly due to the financial benefits they may provide. Further directions include comparing our patients considered for clinical trials to all patients treated at our institution to identify potential disparities in care.

A nationwide analysis of demographic and treatment patterns in admissions for malignant pleural effusions from 2016-2020.

1618 Background: Malignant pleural effusions are an indicator of metastatic malignancy, with poor survival and need for palliative procedures to alleviate symptoms. Our study aims to identify the disparities in the utilization of these procedures and their effects on hospitalization outcomes. Methods: The Nationwide Inpatient Sample (NIS) was used to identify all adult hospitalizations with malignant pleural effusion (MPL) between the years 2016-2020. We studied patient demographics and treatment modalities during admission. The study's primary outcome measure was to identify the difference in the total length of stay (LOS) and total healthcare cost (THC)incurred during admission. The secondary outcome was mortality rates among patients undergoing these procedures. Statistical analysis was done using multivariate linear and logistic regression models. Results: A total of 439,245 admissions for MPL were identified, constituting 0.2% of all U.S. admissions. Among these, 59.6% were females and mean age was 67.3 years. There were 68% Whites, 15% Blacks, 8% Hispanics, 4% Asians or Pacific Islanders, 0.4% Native Americans, and 2.9% others. About 61% had Medicare, 11.2% Medicaid, 25.7% Private insurance, and 1.9% Self-pay. Most admissions occurred in teaching hospitals (76.3%), urban settings (94.5%), and hospitals with larger bed strength (56.1%). The most common primary admission diagnosis was sepsis (8.3%). The most common primary malignancies were Lung (39.9%), breast (27.9%), gastrointestinal (9%), and hematopoietic malignancies (7.1%). We studied rates of thoracocentesis, Pleurodesis, Decortication, and intrapleural chemotherapy. The mean LOS and THC increased in admissions where procedures were performed, highest for decortication (12.1 days, p<0.01). However, the odds of death in hospitals significantly reduced. When compared to primary lung cancer causing malignant effusions, primary G.I., renal, urinary, and upper aerodigestive malignancies with MPL had significantly higher mortality rates (p<0.05). Disparities were observed in procedures performed, with women having 29% lower odds of undergoing decortication (p<0.001). African Americans had lower odds of undergoing any procedures for MPL when adjusted for age, sex insurance status, compared to whites. Teaching hospitals had 10.9 times higher odds of performing thoracocentesis but lower odds of performing pleurodesis and decortication (p<0.05). Conclusions: This investigation provides insights into the favorable impact of invasive procedures on in-hospital mortality for malignant pleural effusions, suggesting a possibility that patients with better performance status underwent such interventions. We also noted racial and sex-based disparities in the performance of these procedures. Further studies are essential to identify the reasons for this disparity to help promote equitable care.

FOLFOX as a therapeutic option in patients with hepatic failure due to liver metastasis of gastrointestinal (GI) system malignancies: A case series.

e16378 Background: The treatment options for patients with hepatic metastasis presenting with liver dysfunction, particularly those experiencing severe hyperbilirubinemia, are limited. The oxaliplatin and fluorouracil/folinic acid regimen, known as FOLFOX, stands out as a viable option based on its pharmacokinetics. However, clinical data regarding the specific dosage and tolerability of this regimen are limited, and clear recommendations are not currently available. Patients and Methods: Patients who presented with severe hyperbilirubinemia immediately after the diagnosis of GI adeno cancer, and who were not eligible for drainage options, were prospectively observed in our clinic in Turkey throughout the year 2023. Severe hyperbilirubinemia was defined as a bilirubin level > 5mg/dL. The FOLFOX regimen was administered every two weeks, and the fluorouracil dose was initially reduced by 50% for the first two cycles. Subsequently, the dose was increased to the total amount if no toxicity occurred. Results: Six cases of GI cancer patients meeting the criteria were identified. Subsequent laboratory data for these six patients were collected after initiating the FOLFOX regimen. All six patients underwent the FOLFOX regimen with dose reduction for the first two cycles. Following the first cycle of chemotherapy, bilirubin levels dropped and normalized (Table 1), leading to an improvement in the patients' clinical condition. Conclusions: While our series is limited by a small number of patients, treatment with FOLFOX has proven to be feasible and may yield significant benefits in patients with severe liver dysfunction caused by GI cancer, especially when no further drainage options are available. [Table: see text]

316P Primary gallbladder cancer and the risk of gastrointestinal multiple primary malignancies

316P Primary gallbladder cancer and the risk of gastrointestinal multiple primary malignancies

Global interest in podcasts designed for medical oncology trainees.

9019 Background: Audio podcasts allow for medical education to be disseminated in an on-demand format and are globally accessible. There are currently a limited number of trainee-directed medical oncology podcasts and their global impact has not been shown. “Talking about Tumors with Ryann and Ryan” is an English language, evidence-based, free-to-use podcast that was initiated in April 2022 with a focus on education of trainees new to the field. Methods: Geographic statistics were collected for podcast episodes with greater than 30 days of availability. The proportion of listeners from different regions was compared between episodes. Trends in listeners from North America and global audiences were descriptively analyzed. Results: 34 episodes were included in this analysis, with content in gastrointestinal, breast, thoracic and cutaneous malignancies. Episodes had a median of 115 downloads, with consistently >30% from outside of Canada and the United States (median 37.3 +/- 6.4%). Twenty-four countries had greater than 10 downloads. The largest audience beyond North America was Australia (13%), Israel (4%), United Kingdom (3%), Pakistan (3%), Sweden (2%), India (1%), and Hong Kong (1%). A review of individual cities within countries was relatively constant, suggestive of persistent listenership. Conclusions: There is a global interest for introductory medical oncology education. Presentation in an evidence-based format and awareness of variation in regional approaches to systemic therapy can increase the impact of podcasts, which by their design can reach a global audience. The development of an index for early education oncology podcasts may improve visibility and access to those interested in this medium.

Analysis of the fecal metagenome in pelvic radiation survivors with or without chronic gastrointestinal toxicity.

e24041 Background: Whole pelvis radiation therapy (WPRT) is often used as a definitive or adjuvant treatment in patients with genitourinary, gynecologic, and gastrointestinal (GI) malignancies. Irradiation of nearby bowel can cause acute and chronic GI symptoms, which can affect patients’ quality of life. Radiation therapy has been shown to alter the microbial flora and may select for pathogenic species, which may enhance toxicity. Characteristics of the fecal metagenome in patients with or without chronic GI toxicity is unknown. Severity of GI symptoms can vary between patients who receive a similar radiation dose to normal bowel; therefore, there is a critical need to evaluate the interaction of RT and microbial species in the development of toxicity. Methods: An institutional database was used to identify survivors that completed WPRT for prostate, gynecologic, and anal cancer within the last 5 years. Patients were excluded if they had evidence of recurrent disease requiring additional therapy. Eligible patients were asked to participate via telephone. Consenting patients provided a stool sample and completed a customized PRO-CTCAE form (scale 1-5) assessing chronic GI symptoms. Comprehensive shotgun metagenomics were performed on stool. Stool was sequenced using an Illumina NextSeq500. The fecal metagenome in patients with or without chronic GI symptoms were compared. Patients were dichotomized by PRO-CTCAE diarrhea score (0-1 [mild] vs ≥2 [moderate-severe]). Raw reads were processed with Kneaddata for trimming, Kracken2 for taxonomic profiling, and Bracken for abundance estimation for bacterial, fungal and viral genomes using sequences from the National Center for Bioinformatics to determine quantitative genus and species differences. For microbial diversity assessments, estimated inverse Simpson and Shannon indices were performed. Results: Fecal metagenome and PRO-CTCAE results were available for 13 survivors. Thirty percent (n = 4) of patients reported moderate to severe diarrhea. The mean age was 66 years, 38% were male, 46% received concurrent or adjuvant chemotherapy, and the mean time from completion of WPRT to stool analysis was 34 months (range 14-62 months). Conventional radiation bowel constraints were met for each patient. Several species were enriched in patients with mild GI toxicity. Notably, Akkermansia muciniphilia had the largest differential enrichment in patients with without chronic GI toxicity. Conclusions: In this cohort of patients, A. muciniphilia, a mucin-degrading bacteria that modulates the gut barrier integrity and mucin layer thickness, was enriched in patients with no to mild diarrhea compared to patients with moderate to severe diarrhea. A. muciniphilia supplementation has been shown to decrease systemic inflammation in Western diet-fed mice. Evaluation of A. muciniphilia as a radioprotective gut bacterium warrants further evaluation.

Small bowel adenocarcinoma: A SEER database analysis.

e16383 Background: Small bowel malignancies (SBM) account for about 3% of all gastrointestinal malignancies. Small bowel adenocarcinoma (SBA) accounts for the majority of the SBM. SBA is associated with poor prognosis and treatment options are limited in patients with advanced cancer. We analyzed SEER data to study the factors that impacted survival in patients with SBA. Methods: We reviewed data on the SEER database (version Stat 8.4). We extracted data to include patients with adenocarcinoma with labeled primary site as small bowel diagnosed between 2000-2019. We excluded other histology. Variables included were age at diagnosis, race, gender, stage at diagnosis, and grade of malignancy. Chi-square test was used to analyze the association between each variable and survival. Results: We identified 3415 cases of SBA that met our inclusion criteria. The number of annual cases increased from 2000-2019. The mean age was 65.3 years (range 57-75 years). The Male to Female ratio was 11:9. 76% were white, 13.7% were black, 13% were others. Duodenum was the most common primary site with 58%, jejunum at 15.5%, ileum at 13%, and 13.5% overlapped sites or unknown. SEER combined summary stage at diagnosis was 32% regional, 18% localized, 29% distant, and 23% unknown. 6% was grade I, 37% grade II, 27% grade III, 1% grade IV, and 28% unknown. Median survival in patients with SBA was 13 months. The median survival for patients less than or equal to 60 years was 24 months compared to 11 months in patients over 60 years of age (p < 0.0001). Median survival in males was 13 months vs 12 months in females, (p = 0.548). There was no significant difference in survival per race (p = 0.5849). In this cohort, jejunal adenocarcinoma had better outcomes with a survival of 27 months (p < 0.0001). Grade I and II were associated with better outcomes with survival of 21.5 months and 24 months (p < 0.0001). Multivariate analysis showed that age less than 60, early-stage disease, jejunal primary site, and low-grade disease were associated with a better outcome. Conclusions: The number of cases of SBA in the SEER database has increased over the last few decades. SBA is associated with poor outcomes and our analysis shows that patients with early-stage disease, and younger age have better outcomes. Management of SBA is based on retrospective data and data extrapolated from management of colon adenocarcinoma, due to sparsity of prospective data. Clinical trials are needed to identify appropriate therapeutic options for the management of SBA.

Developing behavioral intervention to support molecular testing of patients with biliary tract cancer.

TPS1641 Background: Biliary tract cancer (BTC) represents 7% of gastrointestinal malignancies in the United States, with an incidence of 0.5 to 2.0 cases per 100,000 individuals. Standard care involves systemic chemotherapy, predominantly gemcitabine and cisplatin. Recent advancements in immunotherapy, as evidenced by the TOPAZ-1 trial and KN966, support the use of durvalumab, and pembrolizumab as treatment options. Genetic tumor testing identifies up to 40% of BTC patients with targetable mutations, leading to recent FDA approvals for FGFR2 inhibitors - pemigatinib, infigratinib, futibatinib, and IDH1 inhibitor ivosidenib. The emerging data on inhibitors targeting the BRAF mutation, together with HER2 amplification, underscore the importance of understanding the tumor's molecular profile. Navigating this evolving treatment landscape emphasizes an unmet need for patients to comprehend the pivotal significance of tumor molecular profiling in formulating effective and personalized treatment plans. Identifying knowledge gaps among BTC patients concerning tumor genetic testing and precision medicine, along with strategies to address these gaps, holds promise for improving the management and the outcome of patients with BTC. Methods: This is a behavioral intervention study where participants will undergo two in-person survey interviews before and after an educational intervention. The initial survey aims to establish baseline knowledge about the BTC diagnosis and treatment and ascertain preferences for various educational interventions. Patients’ knowledge gap will be determined by comparing their responses to the initial survey and medical history documented by their treating physicians. They will then be provided with a 10-minute educational video. Participants will have the flexibility to access the video multiple times. Within 6 weeks from enrollment, they will have a post-education survey to determine the effectiveness of the education intervention. Following completion of baseline surveys, collaboration with key stakeholders including medical oncology and community perspectives will be initiated to identify knowledge gaps and inform the design of an educational intervention. The study enrollment will be targeted at BTC patients receiving systemic therapy at Georgetown University Hospital, Fox Chase Cancer Center, and Hackensack Meridian Health. Ten participants are enrolled and have completed the first survey and intervention. This study is currently enrolling participants: GUIRB: STUDY00007119.

Global trends and projections of colorectal, esophageal and stomach cancer burden among youth associated with diet: A analysis of 204 countries and territories from 1990 to 2019 and until 2040

BackgroundUnhealthy diets significantly contribute to stomach, colorectal and esophageal cancer burden globally. Western diets high in processed and red meats promote carcinogenesis in these gastrointestinal cancers. However, adolescent and young adult (AYA) patients' unique needs regarding these cancers have been neglected. MethodsData from the 2019 Global Burden of Disease study was used to quantify stomach, colorectal and esophageal cancer burden among AYAs from 1990 to 2040 across 204 countries. Correlations between the burden of these cancers and the Socio-demographic Index were examined. ResultsHigh SDI locations experienced the largest reduction in cancer DALY rate change from 1990 to 2019 (-22% [-12 to -33]), compared to a small increase in low-middle SDI regions. Middle SDI areas saw the largest reduction in DALY rate change from 1990 to 2019 (-62% [-32 to -75]), compared to a small decrease in low-middle SDI locations (-9% [-27 to 10]) in esophageal cancer. From 1990–2019, stomach cancer deaths and DALYs declined across all SDI regions, with the largest reductions in high SDI locations (-61% [-57 to -69]) and smallest in low-middle SDI areas (-25% [-13 to -34]). Colorectal cancer deaths and DALYs rose across all SDI regions except high SDI locations, which showed a slight decrease. ConclusionThis study demonstrates the evolving global burden of stomach, colorectal and esophageal cancers among AYAs. The highest burden was in high-middle and high SDI regions, underscoring the need to prioritize initiatives targeting these gastrointestinal malignancies in youth.

Contrasting comprehensive genomic profiles of adenocarcinomas of the appendix in younger versus older patients.

3626 Background: Adenocarcinoma of the appendix (AAC) is a rare form of intestinal malignancy that can pursue an aggressive clinical course. Little is known about the clinical and biologic features of this disease when it presents in young patients under 40. Methods: 1,840 cases of clinically advanced AAC were selected and analyzed by hybrid capture based comprehensive genomic profiles (CGP) to evaluate all classes of genomic alterations (GA). MSI high status and tumor mutation burden (TMB) were determined from sequencing results and PD-L1 was measured by immunohistochemistry (Dako 22C3). Results: 135 (7.3%) of the AAC were identified in patients of 39 years of age or younger (“younger”). The mean age of the younger patients was 32.9 years and for the 40 and over (“older”) patients it was 60.4 years. The slight female gender preponderance was higher in the older patients than the younger patients (Table). The GA per sample were similar. The younger patients had a significantly higher frequency of KRAS GA (71.1% vs 60.4%; p=.017) and TP53 GA (56.3% vs 41.3%; p=.0008). The KRAS G12C mutation frequency was similarly low in both cohorts. Targetable GA in BRAF and ERBB2 were infrequent in both groups as were GA in PIK3CA, PTEN and FBXW7. GA in the APC gene was significantly more frequent in the older patients (10.8% vs 3.7%; p=.007). Biomarkers of immune-oncology (IO) drug efficacy were infrequently identified in both groups including MSI-High status, TMB levels and PD-L1 expression. Conclusions: At a 7.3% incidence, AAC is a relatively infrequent form of gastrointestinal malignancy in young patients. The data analysis shows significant differences in the genomics found in younger and older patients suffering from this disease. These results can have a crucial impact on current and future clinical trials used to design novel treatments. Further exploration into this subject can change the overall approach and even treatment guidelines for this type of cancer. [Table: see text]

The heavy implications of racial and socioeconomic factors affecting cachexia incidence at gastrointestinal malignancy diagnosis: A single-institution study.

e13694 Background: Cachexia, a complicated metabolic syndrome often related to cancer, is associated with anorexia, decreased quality of life, and increased mortality in advanced disease. The overall prevalence of cachexia ranges from 40% at cancer diagnosis to 70% in advanced disease. Our team aimed to determine whether racial and socioeconomic factors are associated with incidence of cachexia or being underweight at diagnosis (UAD) in patients with gastrointestinal (GI) tract cancer in a diverse, multiethnic urban medical center with high Asian-American representation. Methods: Using ICD-10 codes, adult (age ≥18) patients with diagnosis of primary GI carcinoma between 1/1/2013 to 12/31/2022 were identified. Those with secondary GI involvement from non-GI malignancies were excluded. Patient height, weight at time of diagnosis (weight measured within 4-week window from pathologic diagnosis date), and highest weight within 6 months preceding diagnosis date were recorded. Demographic data included: race, primary language, tumor origin, cancer stage and social deprivation index (SDI). Cachexia was defined as weight loss within a 6-month period of >5% of initial body weight, or weight loss >2% if body mass index (BMI) was <20kg/m2. UAD was defined as BMI <18.5kg/m2 at the time of diagnosis. Results: Of 718 patients with newly diagnosed GI cancer, 366 were analyzable for weight change. 61.2% were male. Race distributions were: 62.0% White, 23.8% Asian, 11.5% Black, and 2.7% Other. The primary languages spoken were: 76.5% English, 19.4% Asian-language, and 4.1% Other. The tumor originated from the following areas: 63.7% lower GI tract, 27.0% upper GI tract, and 8.5% hepato-pancreaticobiliary. 8.5% were UAD and 26.4% met criteria for cachexia at the time of diagnosis. Race and UAD had a significant association; Asians (p=.002) and those speaking Asian languages (p<.001) were more likely to present UAD. However, no significant relationship existed between race (p=.780) or language group (p=.656) on cachexia incidence. Tumor origin groups trended towards differences in cachexia incidence (p=.061). Mean SDI was significantly higher in those who were UAD (p=.026). The SDI was slightly higher among those who had cachexia, but this was not statistically significant (p=.244). Conclusions: GI cancer patients of Asian race, who primarily speak an Asian language, and those with higher SDI are more likely to present UAD, but these same factors are not associated with incidence of cachexia at diagnosis. Additional research is needed to determine if being UAD is associated with development of cachexia later in the illness trajectory or affects clinical outcomes for patient with GI cancer.

Endoscopic Ultrasound-Guided Tissue Sampling for the Cytohistological Diagnosis of Focal Liver Lesions.

Focal liver lesions (FLL) often require cytohistological evaluation. Endoscopic Ultrasound (EUS)-guided tissue acquisition (EUS-TA) is highly accurate in diagnosing pancreatic and gastrointestinal malignancies. The aim of our study was to evaluate the role of EUS-TA in the characterization of FLL. A retrospective analysis of a prospective database of patients who underwent EUS-TA for the evaluation of FLL. Diagnostic yield, adverse events and factors associated with diagnostic yield were evaluated as endpoints. The effect of variables such as needle size, lesion size, rapid on-site evaluation (ROSE) and the use of cytological or histological needles were analyzed. A total of 114 cases were included (mean age 68.05 ± 11.35 years, 64 male). A correct diagnosis was made using EUS-TA in 100 of the 114 cases (diagnostic yield of 88%). The EUS-TA of additional extrahepatic lesions during the same EUS procedure increased the diagnostic yield to 94%. No adverse events were reported. Multivariate analysis did not identify any factor influencing the diagnostic yield. EUS-TA is a highly accurate and safe technique for the differential diagnosis of FLL and could be considered as the primary approach in this setting.

Exploring the potential of thiophene derivatives as dual inhibitors of β-tubulin and Wnt/β-catenin pathways for gastrointestinal cancers in vitro

BackgroundGastrointestinal cancer poses a considerable global health risk, encompassing a heterogeneous spectrum of malignancies that afflict the gastrointestinal tract. It is significant to develop efficacious therapeutic agents, as they are indispensable for both the treatment and prevention of this formidable disease. MethodsIn this study, we synthesized a novel thiophene derivative, designated as compound 1312. An assessment was performed to investigate its anti-proliferative activity in several cancer cell lines (GES-1, EC9706, SGC7901, and HT-29). Furthermore, we performed molecular biology techniques to investigate the inhibitory impact of compound 1312 on gastrointestinal cell lines SGC-7901 and HT-29. ResultsOur findings reveal that compound 1312 exhibits significant efficacy in suppressing colony formation of cancer cells. Notably, it triggers cell cycle arrest at the G2/M phase in gastrointestinal cell lines SGC7901 and HT-29. Compound 1312 was confirmed to exert inhibitory effects on cell migration and invasion in SGC7901. Additionally, the compound elicits apoptotic cell death through the activation of the DNA repair enzyme poly (ADP-ribose) polymerase (PARP) and the caspase signaling cascade. Furthermore, in vitro experiments revealed that compound 1312 effectively suppresses both the β-tubulin cytoskeletal network and the Wnt/β-catenin signaling pathway. These multifaceted anti-cancer activities highlight the potential of compound 1312 as a promising therapeutic agent for the treatment of gastrointestinal malignancies. ConclusionThis study indicates the promising potential of compound 1312 as a prospective candidate agent for gastrointestinal cancer treatment. Further comprehensive investigations are needed to explore its therapeutic efficacy in greater detail.

Identification of octyl gallate, a novel apoptosis-inducing compound for colon cancer therapy, from Sanguisorba officinalis L. by cell membrane chromatography and UHPLC-(Q)TOF-MS/MS

Colon cancer is a common gastrointestinal malignancy that ranks third in incidence among gastrointestinal cancers. Therefore, screening bioactive compounds for treatment of colon cancer is urgently needed. Sanguisorba officinalis L. (SO) has been demonstrated that the extractions or monomers possess potential anti-tumor effect. In this study, we firstly used cell membrane chromatography (CMC) and ultra-performance liquid chromatography coupled with (quadrupole) time-of-flight mass spectrometry (UHPLC-(Q) TOF-MS/MS) to identify a novel active ingredient, octyl gallate (OG), from SO methanol extract (SO-MtOH). HCT116 and SW620 cells lines were used for in vitro research, which showed OG presents great anti-colon cancer effect by inhibiting proliferation, inducing apoptosis, and repressing the migration and invasion. Furthermore, SW620 bearing athymic nude mice was used to investigate the potential antitumor activity in vivo, which exhibited OG treatment remarkably lessened the tumor volume. Mechanism studies showed that OG downregulated the PI3K/AKT/mTOR signaling axis and induced apoptosis by upregulating the Bax/Bcl-2 protein and the cleaved caspase-3, caspase-9. In conclusion, our research innovatively applied the method of CMC to intriguingly unearth the potential anti-colon cancer ingredient OG and demonstrated its the great antineoplastic activity, which provide a new insight for researchers efficiently developing the novel apoptosis-inducing compound for colon cancer therapy.

CircRNA6448-14/miR-455-3p/OTUB2 axis stimulates glycolysis and stemness of esophageal squamous cell carcinoma.

Esophageal squamous cell carcinoma (ESCC) is a gastrointestinal malignancy with high incidence. This study aimed to reveal the complete circRNA-miRNA-mRNA regulatory network in ESCC and validate its function mechanism. Expression of OTU Domain-Containing Ubiquitin Aldehyde-Binding Protein 2 (OTUB2) in ESCC was analyzed by bioinformatics to find the binding sites between circRNA6448-14 and miR-455-3p, as well as miR-455-3p and OTUB2. The binding relationships were verified by RNA Immunoprecipitation (RIP) and dual-luciferase assay. The expressions of circRNA6448-14, miR-455-3p, and OTUB2 were detected by quantitative real-time polymerase chain reaction (qRT-PCR). MTT assay measured cell viability, and the spheroid formation assay assessed the ability of stem cell sphere formation. Western blot (WB) determined the expression of marker proteins of stem cell surface and rate-limiting enzyme of glycolysis. The Seahorse XFe96 extracellular flux analyzer measured the rate of extracellular acidification rate and cellular oxygen consumption. Corresponding assay kits assessed cellular glucose consumption, lactate production, and adenosine triphosphate (ATP) generation. In ESCC, circRNA6448-14 and OTUB2 were highly expressed in contrast to miR-455-3p. Knocking down circRNA6448-14 could prevent the glycolysis and stemness of ESCC cells. Additionally, circRNA6448-14 enhanced the expression of OTUB2 by sponging miR-455-3p. Overexpression of OTUB2 or silencing miR-455-3p reversed the inhibitory effect of knockdown of circRNA6448-14 on ESCC glycolysis and stemness. This research demonstrated that the circRNA6448-14/miR-455-3p/OTUB2 axis induced the glycolysis and stemness of ESCC cells. Our study revealed a novel function of circRNA6448-14, which may serve as a potential therapeutic target for ESCC.

Research advances on TIL therapy for colorectal cancer.

Colorectal cancer (CRC) is a prevalent gastrointestinal malignancy. Tumor-infiltrating lymphocyte (TIL) therapy, a form of adoptive cellular therapy (ACT), involves isolating T lymphocytes from tumor tissues, in vitro expansion, and reintroduction into the body to target and eliminate tumor cells. This article presents an overview of the development and application of TIL therapy in CRC, as well as the associated challenges.