Gastrointestinal Tumor Patients Research Articles

Estimating prognosis of gastric neuroendocrine neoplasms using machine learning: A step towards precision medicine

Survival rates following radical surgery for gastric neuroendocrine neoplasms (g-NENs) are low, with high recurrence rates. This fact impacts patient prognosis and complicates postoperative management. Traditional prognostic models, including the Cox proportional hazards (CoxPH) model, have shown limited predictive power for postoperative survival in gastrointestinal neuroectodermal tumor patients. Machine learning methods offer a unique opportunity to analyze complex relationships within datasets, providing tools and methodologies to assess large volumes of high-dimensional, multimodal data generated by biological sciences. These methods show promise in predicting outcomes across various medical disciplines. In the context of g-NENs, utilizing machine learning to predict survival outcomes holds potential for personalized postoperative management strategies. This editorial reviews a study exploring the advantages and effectiveness of the random survival forest (RSF) model, using the lymph node ratio (LNR), in predicting disease-specific survival (DSS) in postoperative g-NEN patients stratified into low-risk and high-risk groups. The findings demonstrate that the RSF model, incorporating LNR, outperformed the CoxPH model in predicting DSS and constitutes an important step towards precision medicine.

Association of preoperative nutritional status with sarcopenia in patients with gastrointestinal malignancies assessed by GLIM criteria: a prospective cohort study.

The Global Leadership Initiative in Malnutrition (GLIM) consensus highlights the importance of using the GLIM criteria as a standardized approach to diagnosing malnutrition, particularly in patients with cachexia. Although many existing studies have utilized the GLIM criteria to assess the association between malnutrition and malignant tumor patients, there remains relatively little research exploring the specific relationship between malnutrition and sarcopenia. This study aimed to investigate the correlation between malnutrition under the GLIM criteria and preoperative sarcopenia in patients with gastrointestinal malignancies. By looking into the relationship, we hope to find better ways to prevent and treat sarcopenia in these patients, which will lead to better clinical outcomes. In this study, we selected 210 patients with gastrointestinal malignant tumors from Northern Jiangsu People's Hospital between June 2022 to July 2023. We diagnosed and graded the nutritional status of these patients using the GLIM criteria. At the same time, body composition analysis, calf circumference, and grip strength were detected in all patients to observe whether they had sarcopenia. According to GLIM criteria, 30.1% of the patients were diagnosed with malnutrition, of which 25.1% were classified as moderate malnutrition and 15% as severe malnutrition. The risk of sarcopenia in patients with severe malnutrition was 2.5 times that of patients with good nutrition, and 1.19 times that of patients with moderate malnutrition. Patients with BMI <18.5 kg/m2 were 9.12 times more likely to develop sarcopenia than those with BMI≥18.5 kg/m2. Due to inadequate nutrient intake and resultant malnutrition in patients with malignant tumors, muscle protein synthesis is affected, exacerbating muscle protein breakdown and leading to an overall decline in muscle strength and function. This study highlights the urgent need for nutritional screening in early gastrointestinal tumor patients, revealing a strong link between sarcopenia and malnutrition. Higher malnutrition levels, low BMI, and high nutritional risk significantly predict sarcopenia, with risk increasing alongside worsening malnutrition and disease stage.

Abstract CT213: Anlotinib plus chemotherapy as first-line therapy for gastrointestinal tumor patients with unresectable liver metastasis: Updated results from a multi-cohort, multi-center phase II trial ALTER-G-001-cohort C

Abstract Background Advanced gastrointestinal (GI) tumors, such as colorectal, gastric and pancreatic cancers (CRC, GC, and PC), and esophageal squamous cell carcinoma (ESCC), 20%-50% with liver metastases (LMs) have a poor prognosis. Previous trials showed that anlotinib plus chemotherapy has promising clinical activity and a tolerable safety profile for advanced CRC and ESCC, especially with LMs. In this phase II trial, we assessed the efficacy and safety of anlotinib plus chemotherapy as first-line treatment for LMs GI tumors. Methods Patients with unresectable LMs GI tumors and without previous systemic treatment would be divided into cohort A (CRC), cohort B (ESCC), and cohort C (other GI tumors, such as PC, GC, biliary tract cancer (BTC), etc.). In cohort C, patients received induction therapy: anlotinib plus standard chemotherapy. Patients without progressive disease (PD) and radical resection received anlotinib and metronomic capecitabine (500 mg, PO, BID, days 1-21, q3w) maintenance until PD or unacceptable toxicity. The primary endpoint was objective response rate (ORR) per RECIST v1.1. Secondary endpoints were duration of response (DoR), progression-free survival (PFS), overall survival (OS), disease control rate (DCR), time to response (TTR), depth of response (DpR), radical resection rate for LMs, and safety. Results As of November 13, 2023, 41 patients were enrolled in cohort C (29 PC, 6 GC, 5 BTC, and others), the median age was 64 years (34-74), 63.4% male, 92.7% ECOG-PS 1 and 56.1% had LMs only. The majority of the pancreatic cancer patients (26/29) received gemcitabine plus nab-paclitaxel chemotherapy combination with anlotinib as induction therapy. After induction therapy, 4 patients (1 PC, 2 GC, 1 BTC) received surgical resection. Of 38 evaluable patients in cohort C, 16 had partial response (PR), 17 had stable disease (SD) and 14 SD with reduced tumor size. The ORR was 42.1%, DCR was 86.8%. Of 26 evaluable pancreatic cancer patients, ORR and DCR were 42.3% (11/26) and 88.5%(23/26) respectively. 11 PRs and 10 SD- were observed with the median depth of response (DpR) of 37.6%. According to the Kaplan-Meier method, the median DoR was 4.1 (95%CI, 3.5-4.6) months and PFS was 5.8 (95%CI, 5.2-6.3) months. The median TTR was 1.7 (range, 0.8-3.5) months. 39 patients in cohort C had TEAEs and ≥ grade 3 TEAEs (53.7%) mainly included neutropenia (19.5%), white blood cell decreased (14.6%), and blood platelet decreased (9.8%). Conclusions Anlotinib plus chemotherapy as first-line treatment has shown promising efficacy and acceptable safety and maybe a favorable option for advanced LMs GI tumors, especially for pancreatic cancer. Clinical trial information: NCT05262335. Citation Format: Junwei Wu, Chenfei Zhou, Jun Yan, Zhengxiang Han, Chun Wang, Zhiquan Qin, Jinling Jiang, Chunbin Wang, Xinyu Tang, Lingjun Zhu, Jun Chen, Yong Mao, Xiaowei Wei, Chengfang Shangguan, Jun Zhang. Anlotinib plus chemotherapy as first-line therapy for gastrointestinal tumor patients with unresectable liver metastasis: Updated results from a multi-cohort, multi-center phase II trial ALTER-G-001-cohort C [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr CT213.

103P Anlotinib plus chemotherapy as first-line therapy for gastrointestinal tumor patients with unresectable liver metastasis: Updated results from a multi-cohort, multi-center phase II trial ALTER-G-001-cohort A

103P Anlotinib plus chemotherapy as first-line therapy for gastrointestinal tumor patients with unresectable liver metastasis: Updated results from a multi-cohort, multi-center phase II trial ALTER-G-001-cohort A

150P Anlotinib plus chemotherapy as first-line therapy for gastrointestinal tumor patients with unresectable liver metastasis: Updated results from a multi-cohort, multi-center phase II trial ALTER-G-001-cohort C

150P Anlotinib plus chemotherapy as first-line therapy for gastrointestinal tumor patients with unresectable liver metastasis: Updated results from a multi-cohort, multi-center phase II trial ALTER-G-001-cohort C

Gastrointestinal tumor-related perihepatic fluorouracil encapsulated lesions and liver metastases: a diagnostic imaging study based on contrast-enhanced computed tomography and magnetic resonance imaging.

Perihepatic fluorouracil encapsulated lesions (FELs) can result in potentially confusing computed tomography (CT) and magnetic resonance imaging (MRI) features in postoperative examinations of gastrointestinal tumors. This retrospective study aimed to summarize the typical imaging features of FELs and determine the best imaging modality to distinguish FELs from liver metastases for junior residents. Patients with FELs who had undergone gastrointestinal tumor surgery in Tongji Hospital from January 2016 to June 2022 were evaluated. The imaging features of FELs were summarized by two senior radiologists. Contrast-enhanced CT (CECT) was used as the primary follow-up tool for postoperative gastrointestinal tumor patients. Patients with FELs and available CECT and MRI examinations were matched with patients with liver metastases based on gender and age and presented in chronological order in a 2:1 ratio. Different imaging modality combinations were used for further evaluation, including a CECT group (modality Ⅰ), CECT and nonenhanced MRI group (modality Ⅱ) and CECT with all MRI sequences group (modality Ⅲ). Subsequently, two junior residents blindly evaluated three groups following a 4-week interval based on a 5-point scale (1= definite benign lesion, 2= probable benign lesion, 3= indeterminate, 4= probable liver metastasis, 5= definite liver metastasis). Imaging features of 33 patients with 36 FELs were analyzed. CECT and dynamic contrast-enhanced MRI (DCE-MRI) showed no enhancement in most lesions. Additionally, 20 patients with FELs meeting the requirements were matched with 40 patients with liver metastases. The highest sensitivity, specificity, and consistency for identifying liver metastases were achieved using a combination of CECT and MRI encompassing all sequences yielded, including modality Ⅰ (reader 1: 72.0% and 17.4%; reader 2: 62.0% and 17.4%; kappa value 0.295), modality Ⅱ (reader 1: 88.0% and 8.7%; reader 2: 92.0% and 34.8%; kappa value 0.259), and modality Ⅲ (reader 1: 98.0% and 34.8%; reader 2: 92.0% and 39.1%; kappa value 0.680). FELs are typically non-enhancing lesions. In our study, two junior residents could best distinguish FELs from liver metastases using CECT with all MRI sequences.

1628P Anlotinib plus chemotherapy as first-line therapy for gastrointestinal tumor patients with unresectable liver metastasis: Preliminary results from a multi-cohort, multi-center phase II trial (ALTER-G-001)

1628P Anlotinib plus chemotherapy as first-line therapy for gastrointestinal tumor patients with unresectable liver metastasis: Preliminary results from a multi-cohort, multi-center phase II trial (ALTER-G-001)

Survival and Response Outcomes for Gastrointestinal Neuroendocrine Tumor (GEP-NETs) Patients Treated with Lutetium-177-DOTATATE in a Brazilian Reference Center: A Six-Year Follow-Up Experience.

PRRT can be an option for all-grade GEP-NETs, but selecting patients is challenging. In this scenario, clinical-pathological and radiological characteristics, such as pre-treatment Ga-68 DOTA PET/CT, might have the potential to help. A retrospective chart review was conducted on advanced GEP-NETs treated with at least one PRRT dose. Overall survival (OS) and progression-free survival (PFS) were calculated using the Kaplan-Meier method. Krenning Score (KS), and the maximum standardized uptake value (SUVmax) were derived from the pre-treatment scans. A maximally selected rank statistics test was used for SUVmax simple cut point estimate. Among 36 patients, 19 had primary pancreatic tumors. The numbers of G1, G2, and G3 tumors were 10, 18, and 7, respectively. During a median follow-up of 90.5 months, 4 patients died. Median OS was not reached for G1 and G2 tumors, and it was 30 months for G3 (p = 0.001). Median PFS was 23 months, with G3 showing lower PFS compared to G1 [7 versus 30 months; HR 8.41 (95%CI 2.2-31.0; p = 0.001)]. PRRT provides long-term PFS in patients with G1/G2 GEP-NETs independent of clinical characteristics and primary site. G3 has worse survival, but selected patients may experience long OS after PRRT treatment.

Medical nursing care of gastrointestinal tumour patients during chemotherapy

Objectifs : La présente recherche menée auprès de patients atteints d’un cancer gastro-intestinal étudiait les effets escomptés des interventions infirmières sur a) le respect du traitement par les patients, b) leur satisfaction à l’égard des soins infirmiers et c) la santé physique, par exemple la fonction pulmonaire. Méthodologie : Tous les patients (60 personnes) ayant reçu de la chimiothérapie au service de médecine traditionnelle chinoise du First Affiliated Hospital of Soochow University, ont été répartis en deux groupes égaux. Aux patients du groupe 1, on a administré les soins usuels planifiés; les patients du groupe 2 ont bénéficié d’interventions infirmières fondées sur des données probantes. Résultats : Les résultats montrent que le respect du traitement était meilleur dans le groupe 2 que dans le groupe témoin (p=0,01). De plus, on a observé un degré de satisfaction plus élevé à l’égard des services infirmiers (p =0,01) et une amélioration de la fonction pulmonaire (p=0,01). Le respect du traitement a fait diminuer la proportion d’infections secondaires dans le groupe 2 (p =0,05). Conclusion : Les résultats montrent que des interventions infirmières de qualité permettent d’améliorer la fonction pulmonaire, de réduire le stress, de bonifier les plans de traitement et de réduire le nombre d’infections secondaires.

Medical nursing care of gastrointestinal tumour patients during chemotherapy.

This research with gastrointestinal cancer patients analyzed the expected outcomes of nursing interventions on a) patient adherence to treatment; b) patient satisfaction with nursing care; and c) health of body conditions such as lung function. All patients (60 individuals) who underwent chemotherapy at The First Affiliated Hospital of Soochow University, Department of Traditional Chinese Medicine, were divided into two equal groups. Group 1 received planned care and Group 2 received evidence-based nursing interventions. The results showed that treatment adherence was higher in Group 2 than in the control group (p = 0.01). In addition, there was a higher rating by patients for the quality of nursing care (p = 0.01), as well as a higher score obtained for lung function (p = 0.01). Treatment adherence resulted in a decrease in the secondary infection rate in Group 2 (p = 0.05). The results showed that quality nursing intervention is effective for lung function improvement, stress level reduction, treatment plans, and a reduction of secondary infections.

Mortality during or shortly after Curative-Intent Radio-(Chemo-)Therapy over the last decade at a large comprehensive cancer center.

Definitive surgical, oncological and radio-oncological treatment may result in significant morbidity and acute mortality. Mortality during or shortly after treatment in patients undergoing curative radio-(chemo)-therapy has not been studied systematically. We reviewed all curative radio-(chemo-)therapies at a large comprehensive cancer center over the last decade. The institutional record was screened for patients who received curative-intent radio-(chemo-)therapy and deceased during or within 30days after radiotherapy. Curative therapy was defined as prescribed dosage of EQD2≥50Gy for radiotherapy alone and EQD2≥40Gy for radiochemotherapies. Data on demographics, disease and treatment were assembled and assessed. Of 15,255 radiotherapy courses delivered at our center, 8,515 (56%) were performed with curative-intent. During or within 30days after radio-(chemo-)therapy, 78 patients died (0.9% of all curative-intent courses). Median age of the deceased patients was 70 (IQR, 62-78) years, and 36% (28/78) were female. Median pre-therapeutic ECOG-PS was 1 (IQR, 0-2) and Charlson-Comorbidity-Index was 3+ (IQR, 2-3+). The most common primary malignancies were head and neck cancer (33/78; 42%) and central nervous system tumors (13/78; 17%). Peritherapeutic mortality varied by primary tumor, with the highest prevalence observed in head and neck and gastrointestinal cancer patients with 2.9% (33/1,144) and 2.4% (8/332), respectively. Among patients with known cause of death (34/78; 44%), tumor progression (12/34; 35%) and pulmonary complications/causes (11/34; 35%) were most common. On multivariable regression analysis, a worse ECOG-PS was associated with a relatively earlier peri-radiotherapeutic death (p=0.014). Mortality during or within 30days of curative-intent radio-(chemo-)therapy was low, yet highest for head and neck (2.9%) and gastrointestinal tumor (2.4%) patients. Reasons for these findings include rapid tumor progression in some cancers, good patient selection, with ECOG-PS being most useful and predictive for avoiding early mortality. Future research should help refine predictors for peri-RT mortality.

P-104 Anlotinib plus chemotherapy as first-line therapy for gastrointestinal tumor patients with unresectable liver metastasis: Preliminary results from a multi-cohort, multi-center phase II trial (ALTER-G-001)

P-104 Anlotinib plus chemotherapy as first-line therapy for gastrointestinal tumor patients with unresectable liver metastasis: Preliminary results from a multi-cohort, multi-center phase II trial (ALTER-G-001)

Assessment of Tumor Necrosis Factor-α, Interleukin-17, and Vitamin D3 Levels on a Group of Gastrointestinal Tumor Patients in Babylon Provence, Iraq

Background: Gastrointestinal (GIT) tumors refer to collection of tumor including colorectal, gastric, liver, and pancreatic tumors and other. Objective: The current study aims to measure the serum level of tumor necrosis factor-α (TNF-α), interleukin-17 (IL-17), and vitamin D3 among GIT tumor patients comparing with irritable bowel disease (IBD) patients and healthy control. Materials and Methods: Serum samples were taken from 88 participants (42 from malignant GIT tumor, 29 from benign GIT tumor, 10 from IBD (as positive control), and 7 from health individual (as negative control)). All patients admitted in GIT center of Babylon in Merjan Medical city at April up to December 2020. The TNF-α, IL-17, and vitamin D3 level were measured by Enzyme-Linked Immunoassay (ELISA. Results: The result showed younger men are more prevalent with malignant GIT tumor with mean age (53.39 years) than benign GIT tumor as well as IBD. There is an significant increase in TNF-α (Least Significant Difference (LSD = 1.79) levels of malignant GIT tumor when compared with other groups (mean ± Standard Deviation (SD) = 23.7 ± 8.1, 20.4 ± 2.8, 18.9 ± 2.66, and 18.1 ± 2.78 pg/mL for malignant GIT, benign GIT, IBD, and healthy persons respectively). Results of IL-17 level also reveal a significant increase (LSD = 13.2) of malignant GIT tumor when compared with other groups (mean ± SD = 222.2 ± 73.5, 128.2 ± 35.5, 201.5 ± 39.4, and 164.2 ± 44.1 pg/mL for malignant GIT, benign GIT, IBD, and healthy persons, respectively). Inverse results were documented for vitamin D3 level, in which a significant decrease (LSD = 23.45) in the levels of malignant GIT tumor was observed when compared with other groups (mean ± SD = 204.2 ± 24.3, 306.1 ± 97.2, 453.2 ± 78.2, 368 ± 78.0 pg/mL for malignant GIT, benign GIT, IBD, and healthy persons, respectively). Conclusion: The current study concluded that early age men get affected with malignant GIT tumor in Iraqi population giving a hint to that the population at high risk to involved with such tumor as well as other tumor types with elevated level of TNF-α and IL-17 and decreased level of vitamin D3. More and more studies with large number of patients should be recommended to exclude the factors in which that may lead to such conditions.

Risk factors of preoperative myocardial injury in patients with gastrointestinal tumors

BackgroundRecent studies indicated that the prognosis of patients with gastrointestinal tumors is frequently influenced by its complications, notably myocardial injury. The main object is to investigate the occurrence and risk factors of myocardial injury in patients with gastrointestinal tumor.Methods1126 patients who received gastrointestinal tumor related surgery from May 2018 to June 2020 in the Sixth Affiliated Hospital of Sun Yat-sen University were retrospectively collected and divided into the non-myocardial injury group and the myocardial injury group (high-sensitive cardiac troponin I (hs-cTnI) ≥ 0.028 ng/ml). The occurrence and risk factors of myocardial injury in patients with gastrointestinal tumor are analyzed. The influence of myocardial injury on the ICU detention time in gastrointestinal tumor patients is also studied.ResultsIn total, 78 (6.93%) patients developed myocardial injuries. Compared with patients in the non-myocardial injury group, patients in the myocardial injury group have a higher prevalence of cardiovascular risk factors (including advanced age and higher smoking ratio), a higher prevalence of comorbidities (such as previous coronary artery disease, hypertension, atrium fibrillation and diabetes), and a higher rate of premedication (such as anticoagulation, β-blocker, Angiotensin-converting enzyme inhibitor/Angiotensin II receptor blocker, and diuretic) (all with P-value < 0.05). In addition, patients in the myocardial injury group also presented with a higher revised cardiac risk index (Lee index), higher neutrophil granulocyte ratio, lower hemoglobin, and higher likelihood of impaired cardiac structure and function (all with P-value < 0.05). There was a trend of statistical significance in the ICU detention time between the myocardial injury group and the non-myocardial injury group (1[1,3] vs. 2[1,10], P = 0.064). In this study, there were 7 patients presented with clinical symptoms in the myocardial injury group (chest discomfort in 4 cases, non-compressive precordial chest pain in 1 case, dyspnea in 2 cases). In the multivariate analysis, advanced age, increased Lee index score, increased neutrophil granulocyte ratio, decreased left ventricular ejection fraction (LVEF), increased interventricular septum were independent risk factors for myocardial injury.ConclusionIn conclusion, advanced age, increased Lee index, increased neutrophil granulocyte ratio, decreased left ventricular ejection fraction, and increased ventricular septum were independent risk factors for preoperative myocardial injury in patients with gastrointestinal tumors. The proportion of clinical symptoms in gastrointestinal tumor patients with myocardial injury was low, indicating the necessity to closely monitor the cardiac status of individuals with gastrointestinal tumors.

The evaluation of morbidity in gastrointestinal tumor patients underwent cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (HIPEC).

In this study, we aimed to determine the postoperative morbidity rate and identify demographic, clinical, and treatment-related variables that may be potential risk factors for morbidity in gastrointestinal tumor patients undergoing hyperthermic intraperitoneal chemotherapy (HIPEC) with or without cytoreductive surgery (CRS). In this retrospective study, 60 patients who had undergone HIPEC due to gastrointestinal tumor between October 2017 and December 2019 were included. Systemic toxicities were graded and evaluated according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 criteria. Mean age of the patients was 60.43 ± 12.83. Primary tumor localization was the stomach in 33 patients (55%), colon in 21 (35%), rectum in five (8.3%), and appendix in one patient (1.7%). PCI mean value was 9.51 ± 10.92. CC-0 was applied in 37 (61.7%) patients, CC-1 in 11 (18.3%), CC-2 in 6 (10%), and CC-3 in six patients (10%). Morbidity was observed in 50 (83.33%) of the 60 patients participating in the study according to NCI-CTCAE v3.0 classification. Mild morbidity rate was 46.6%, severe morbidity rate was 36.6%, and mortality rate was 11.66%. Enteric diversion application, length of stay in the ICU, and length of hospital stay were shown to have a statistically significant effect on the NCI-CTCAE morbidity score (p= 0.046, p= 0.004, p <0.001). With proven beneficial effects on survival in patients with locally advanced gastrointestinal tumors, CRC and HIPEC are acceptable in these patients despite their increased morbidity and mortality rate. With new studies on this subject, morbidity and mortality rates may be reduced.

Immunological Study of IFN-γ, ICAM-4, and Vitamin D3 Markers among Gastrointestinal Tumor Patients in Babylon Province, Iraq.

The current study was conducted to investigate the roles of ICAM-4, IFN-γ, and vitamin D3 markers among benign and malignant gastrointestinal stromal tumors (GISTs). Eighty-eight participants, admitted to the Babylon GIT Center, Merjan Medical City, Iraq from April to December 2020, were recruited for the study. Blood samples were collected from the participants, who were divided into four groups: malignant GIT tumor (N = 42), benign GIT tumor (N = 29), irritable bowel disease as a positive control (N = 10), and healthy individuals as a negative control (N = 7). Serum ICAM-4, IFN-γ, and vitamin D3 levels were determined using the blood samples. The younger males were more affected by malignant GIT tumors at a mean age of 53.39 years than benign GIT tumors, IBD, and healthy individuals. There is also an increase in ICAM-4, IFN-γ, and a decrease in vitamin D3 levels compared to healthy individuals. The vitamin D3 level decreased progressively with age and rose in ICAM-4 with a decrease in vitamin D3 level in patients, increasing the probability of infection with GIT tumor. ICAM-4 levels may grow and increase as interferon levels rise. The younger males are more prone to malignant GIT and the serum levels of ICAM-4, vitamin D3, and IFN-γ are high in malignant patients compared with benign GIT tumors and lower than the control.

Abstract B003: Cross-reacting antigens between the intestinal microbiome and tumor neoantigen are associated with immune checkpoint inhibitor response in a gastrointestinal tumor cohort

Abstract Background: Immune checkpoint inhibitor (ICI) is a revolutionary therapy that promotes the activation of effector T cells against tumors. Despite the potential for long-term benefit, a large proportion of patients does not respond to ICI therapy. One reason for this heterogenic response is due to the high variability in the intestinal microbiota among different patients. The abundance of certain bacteria has been associated with different responses and fecal meta transplant from responding donors was shown to rescue a beneficial phenotype in refractory patients. The presence of cross-reactive antigens (CRAgs) between the gut microbiome and tumor neoantigens has been proposed as a potential mechanism that could link the intestinal microbiota with ICI response. However, empirical evidence of CRAg’s role in ICI therapy is limited to a few studies. Methods: We investigated ICI response in a cohort of 22 stage IV gastrointestinal (GI) tumor patients in which whole-exome and gut metagenomic sequencing data were available. This cohort included patients with gastric cancer (n=11), esophageal carcinoma (n=6), and colon cancer (n=5). For each patient, we characterized the tumor neoantigen load based on epitopes that show high affinity and presentability in HLA molecules. Neoantigens were matched to the intestinal microbiome to identify corresponding CRAgs. CRAg quality, which ranks CRAgs according to their immunogenic potential, was defined based on matches in immunogenic protein or epitope databases. Results: We found the total number of CRAgs varied per tumor type, with a higher abundance in colon cancer (median µ=619) followed by esophageal (µ =287.5) and gastric (µ = 243). Interestingly, colon cancer patients showed a better progression-free survival (PFS) curve followed by esophageal and gastric cancer patients, respectively. We also observed that CRAg load was better associated with longer PFS (p=.03) than neoantigen load (p=0.07). Moreover, CRAg’s quality showed to be an important predictor of PFS. Patients with a high proportion of CRAgs matching at least one of the quality databases showed better PFS (p=0.02). Further, a taxa-specific analysis indicated that commensal CRAgs load was a better predictor of PFS (p&amp;lt;0.008) than relative abundance. Altogether, our work supports a mechanistic link between the microbiome, neoantigens, and immuno-therapy. Citation Format: Ravin Poudel, Die Dai, Fang Li, Xiaochen Yin, Yan Kou, Antonio L. C. Gomes. Cross-reacting antigens between the intestinal microbiome and tumor neoantigen are associated with immune checkpoint inhibitor response in a gastrointestinal tumor cohort [abstract]. In: Proceedings of the AACR Special Conference on Colorectal Cancer; 2022 Oct 1-4; Portland, OR. Philadelphia (PA): AACR; Cancer Res 2022;82(23 Suppl_1):Abstract nr B003.

Clinical Spectrum and Endoscopic Treatment of Gastrointestinal Carcinoid Tumour.

To analyse the clinical spectrum and endoscopic treatment outcome of patients diagnosed with gastrointestinal carcinoid tumours. Case series. The First Hospital of Putian City of Fujian Province, China from 2012 to 2019. Patients with gastrointestinal carcinoid tumours were searched on the gastrointestinal endoscopic database and the hospital medical records database. Patients who were evaluated and treated at other institutions or with insufficient clinical information were excluded. Data were extracted from the databases, including clinical presentation, tumour size and location, treatment, complications of treatment, and clinical and endoscopic follow-up. In 113 cases, 92 tumours were smaller than 1 cm, 16 tumours were between 1-2 cm, and 5 tumours were larger than 2 cm in size. Ninety-five (84.1%) tumours showed as nodules with smooth surface, and 4(3.5%) as neoplasms with malignant performance. The tumours were limited to the mucosa in 14 (12.4%) cases, invaded into the submucosa in 88 (77.9%) cases, and the muscularis propria in 6 cases (5.3%). Most of the tumours (87.6%) were located in the rectum. The Ki-67 index was more than 30% in cases with metastases. One hundred and eight (95.6%) gastrointestinal carcinoid tumour patients were treated with endoscopic resection including endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD), and 5 (4.4%) patients underwent surgical resection. All 108 patients including the 6 patients with positive margins had no relapse of carcinoid tumour on follow-up. The rectum may be the most common location of gastrointestinal carcinoid tumours in Asian people. Most small tumours located in the stomach, colon, and rectum are nonfunctional, especially in rectum. Endoscopic excision including EMR and ESD is effective and safe for the treatment of small-sized gastrointestinal carcinoid tumours. Ki-67 index can be a good predictor for malignant potency of gastrointestinal carcinoid tumours. Gastrointestinal carcinoid tumours, Neuroendocrine tumour, Clinical features, Endoscopic treatment.

Activation of MT1/MT2 to Protect Testes and Leydig Cells against Cisplatin-Induced Oxidative Stress through the SIRT1/Nrf2 Signaling Pathway.

There is growing concern that chemotherapy drugs can damage Leydig cells and inhibit the production of testosterone. Increasing evidence shows that melatonin benefits the reproductive process. This study mainly explores the protective effect and possible molecular mechanism of melatonin regarding cisplatin-induced oxidative stress in testicular tissue and Leydig cells. We found that there were only Leydig and Sertoli cells in the testes of gastrointestinal tumor patients with azoospermia caused by platinum chemotherapeutic drugs. Melatonin (Mel) receptor 1/melatonin receptor 2 (MT1/MT2) was mainly expressed in human and mouse Leydig cells of the testes. We also observed that the melatonin level in the peripheral blood decreased and oxidative stress occurred in mice treated with cisplatin or gastrointestinal tumor patients treated with platinum-based chemotherapeutic drugs. iTRAQ proteomics showed that SIRT1/Nrf2 signaling and MT1 proteins were downregulated in cisplatin-treated mouse testes. The STRING database predicted that MT1 might be able to regulate the SIRT1/Nrf2 signaling pathway. Melatonin reduced oxidative stress and upregulated SIRT1/Nrf2 signaling in cisplatin-treated mouse testes and Leydig cells. Most importantly, after inhibiting MT1/MT2, melatonin could not upregulate SIRT1/Nrf2 signaling in cisplatin-treated Leydig cells. The MT1/MT2 inhibitor aggravated the cisplatin-induced downregulation of SIRT1/Nrf2 signaling and increased the apoptosis of Leydig cells. We believe that melatonin stimulates SIRT1/Nrf2 signaling by activating MT1/MT2 to prevent the cisplatin-induced apoptosis of Leydig cells.

Next generation sequencing (NGS) to identify relapsed gastrointestinal (GI) solid tumor patients with human leukocyte antigen (HLA) loss of heterozygosity (LOH) for future logic-gated CAR T therapy to reduce on target off tumor toxicity.

190 Background: Metastatic colorectal (CRC), pancreatic (PANC), and gastroesophageal (GE) cancers are the leading causes of GI cancer–related mortality (5-yr survival rate, 14%, 3% and ̃5-6%, respectively). T-cell immunotherapy targeting GI-associated tumor antigens has been attempted, but efficacy has been constrained by on-target off-tumor toxicity, limiting the therapeutic window. The Tmod (TM) platform is an AND-NOT logic-gated CAR T modular system, versions of which have a CEA- or MSLN-targeting CAR activator and a separate HLA-A*02-targeting blocker receptor to protect normal cells. Tmod CAR T exploits HLA LOH, common in GI malignancies (10-33% in primary solid tumors [TCGA]) and can kill tumor cells without harming healthy cells in vitro and in vivo. However, the prevalence of HLA LOH across GI tumors is unknown in the real-world setting. We utilized the Tempus xT oncology NGS database of patients with multiple GI tumors. From a standard-of-care NGS assay, GI cancer patients can be readily identified for HLA LOH and future treatment with Tmod CAR T therapy. Methods: The occurrence of HLA LOH in GI tumors of 1439 patients was assessed using paired germline and somatic DNA sequencing using a research assay [6]. CRC, PANC and GE patients with ≥ stage 3 were then extracted, and rates of HLA LOH were identified (ie, whether loss occurred across high-frequency HLA-A alleles). In addition, mutations in KRAS and BRAF, as well as MSI status were stratified to determine any association with HLA-A LOH. Results: HLA-A LOH was detected in 830 (17.3%) of all solid tumor records, and a similar proportion when all GI cancer records were analyzed (17.0%). For GI subtypes, these values ranged from 13.5% to 23.1% (Table). No high-frequency HLA-A allele (A*01, A*02, A*03, A*11) was more likely to be lost. Clinical biomarkers ( KRAS, BRAF and MSI status) were not associated with HLA-LOH. Conclusions: The frequency of HLA LOH among advanced solid tumor cancers in this dataset is 17.3%, with a range of 13.5-23% between CRC, PANC and GE. The HLA LOH frequency observed in these GI tumors is consistent with that in primary tumors from TCGA, which also used germline-matched and tumor samples. Clinical biomarkers were not associated with HLA LOH. Tempus NGS was able to identify HLA LOH, which can be used for Tmod CAR T therapy to an enhanced therapeutic window. Identification of these patients in BASECAMP-1 (NCT04981119) will enable novel Tmod CAR T therapy. [Table: see text]