Gastrointestinal Cancer Patients Research Articles

Symptom experiences and influencing factors in patients undergoing chemotherapy for gastrointestinal cancers: a qualitative study

ObjectiveTo explore the symptom experiences and influencing factors of gastrointestinal (GI) cancer patients on chemotherapy (CTX) in China.MethodsSemi-structured interviews were conducted with 13 GI cancer patients undergoing CTX. Following the Colaizzi 7-step analysis method, the interview data were read carefully, meaningful statements related to the research questions were extracted, coded, collected, and described in detail, and the authenticity of the theme was verified.ResultsNine themes were grouped into two main areas including the characteristics of symptom experiences and influences on symptom experiences.ConclusionThe symptom experiences of patients undergoing CTX for GI cancer is poor and influenced by multiple factors. Nurses need to pay attention to the assessment and monitoring of CTX-related symptoms, improve symptom recognition, enhance doctor-patient communication and social support, explore intelligent management methods, and increase the efficiency of healthcare services to improve patients’ symptom experience.

UMobileNetV2 model for semantic segmentation of gastrointestinal tract in MRI scans.

Gastrointestinal (GI) cancer is leading general tumour in the Gastrointestinal tract, which is fourth significant reason of tumour death in men and women. The common cure for GI cancer is radiation treatment, which contains directing a high-energy X-ray beam onto the tumor while avoiding healthy organs. To provide high dosages of X-rays, a system needs for accurately segmenting the GI tract organs. The study presents a UMobileNetV2 model for semantic segmentation of small and large intestine and stomach in MRI images of the GI tract. The model uses MobileNetV2 as an encoder in the contraction path and UNet layers as a decoder in the expansion path. The UW-Madison database, which contains MRI scans from 85 patients and 38,496 images, is used for evaluation. This automated technology has the capability to enhance the pace of cancer therapy by aiding the radio oncologist in the process of segmenting the organs of the GI tract. The UMobileNetV2 model is compared to three transfer learning models: Xception, ResNet 101, and NASNet mobile, which are used as encoders in UNet architecture. The model is analyzed using three distinct optimizers, i.e., Adam, RMS, and SGD. The UMobileNetV2 model with the combination of Adam optimizer outperforms all other transfer learning models. It obtains a dice coefficient of 0.8984, an IoU of 0.8697, and a validation loss of 0.1310, proving its ability to reliably segment the stomach and intestines in MRI images of gastrointestinal cancer patients.

Untargeted metabolomics in gastric and colorectal cancer patients – preliminary results

IntroductionRecent years, microbiota-associated aspects have been analysed in multiple disorders regarding cancers. Existing evidence pints that gut microorganisms might take part in tumour origin and therapy efficacy. Nevertheless, to date, data on faecal metabolomics in cancer patients is still strongly limited. Therefore, we aimed to analyse gut untargeted metabolome in gastrointestinal cancer patients (i.e., gastric and colorectal cancer).Patients and methodsThere were 12 patients with either gastric (n=4) or colorectal cancer (n=8) enrolled and 8 analysed (n=4 each). Stool samples were collected prior to anti-cancer treatments. Untargeted metabolomics analyses were conducted by means of mass spectrometry.ResultsA plethora of metabolites in cancer patients we analysed were noted, with higher homogenity in case of gastric cancer patients. We found that the level of Deoxyguanosine,m/z 266.091,[M-H]-, Uridine,m/z 245.075,[M+H]+, Deoxyguanosine,m/z 268.104,[M]+, 3-Indoleacetic acid,m/z 176.07,[M+H]+, Indoxyl,m/z 132.031,[M-H]-, L-Phenylalanine,m/z 164.073,[M-H]-, L-Methionine,m/z 150.058,[M+NH4]+, was significantly higher in colorectal cancer patients and Ethyl hydrogen malonate,m/z 133.031,[M+H]+ in gastric cancer.ConclusionThe overall insights into untargeted metabolomics showed that most often higher levels of analysed metabolites were detected in colorectal cancer patients compared to gastric cancer patients. The link between gut metabolome and both local and distal metastasis might exist, however it requires confirmation in further multi-centre studies regarding larger sample size.

The psychological distress of gastrointestinal cancer patients and its association with quality of life among different genders

BackgroundPsychological distress is a prevalent unpleasant experience faced by many cancer patients. However, the psychological distress among gastrointestinal (GI) cancer patients is scarcely explored. Moreover, the association between psychological distress and quality of life in different genders has yet to be explored.AimsTo explore the psychological distress among GI cancer patients and examine its association with quality of life among different genders.MethodsThis study was a cross-sectional study. A total of 237 gastrointestinal cancer patients completed the distress thermometer and the Functional Assessment of Chronic Illness Therapy-General.ResultsThe mean score of psychological distress of the participants was 3.04 (SD = 2.90). A greater proportion of female gastrointestinal cancer patients (52.8%) had clinically relevant psychological distress compared to males (35.9%). The quality of life was negatively associated with their psychological distress (B =  − 1.502, 95%CI: − 2.759 to − 0.245, p = 0.019) among gastrointestinal cancer patients. Such association was stronger among males compared to females in gastrointestinal cancer patients (Interaction term, B =  − 1.713, 95%CI: − 3.123 to − 0.303, p = 0.017).ConclusionsThese findings suggest that healthcare providers should attach their attention to gastrointestinal cancer patients’ psychological distress, especially females. Longitudinal studies could adopted to track the changes in psychological distress and its association with quality of life over time among different genders. In future intervention studies, the focus of psychological interventions needs to be gender-specific.

Molecular study of KRAS mutations in Iraqi patients with gastrointestinal tract cancer

Molecular study of KRAS mutations in Iraqi patients with gastrointestinal tract cancer

Effects of Adjuvant Exercise and Nutrition Therapy on Muscle Fibre Biomechanics in Gastrointestinal Cancer Patients.

Patients with aggressive cancer, e.g., gastrointestinal cancer, are prone (≥50% chance) to developing cancer cachexia (CC). Little is known about the effects of CC on the biomechanical function of muscle. A promising prevention strategy was found in the form of a multi-modal therapy combining mild resistance exercise (e.g., whole-body electro-myostimulation, WB-EMS) and a protein-rich diet. In a previous study of ours, this was effective in counteracting the loss of muscle mass, yet a systematic and comprehensive assessment of active and passive single muscle fibre functions was so far absent. This pilot study investigated the biomechanical function of single muscle fibres (rectus abdominis) from the biopsies of conventionally treated (pre-)cachectic cancer ((pre-)CC) patients (m = 9), those receiving the multi-modal therapy comprising WB-EMS training and protein-rich nutrition (m = 3), and a control group (m = 5). Our findings not only align with previous findings showing the absolute force loss in CC that is accelerated by atrophy but also speak in favour of a different, potentially energy- and Ca2+-homeostasis-related effect that compromises muscle contraction (F ~0.9 mN vs. F ~0.6 mN in control patients). However, myofibrillar Ca2+ sensitivity and the quality of contraction were unaltered (pCa50: 5.6-5.8). Single fibres from the (pre-)CC patients receiving WB-EMS training and protein supplementation were significantly more compliant (p < 0.001 at ≥130% of resting length L0). Those fibres displayed a similar softness to the ones from the control patients (axial compliance ~15 m/N at ≥130% L0), while single fibres from the patients with (developing) cachexia were significantly stiffer (axial compliance ~7 m/N, p < 0.001 at ≥130% L0). Adjuvant multi-modal therapy (WB-EMS training and nutritional support) contributes to maintaining the axial compliance of single fibres and potentially improves the quality of life for patients at risk of developing CC.

68Ga-NC-BCH Whole-Body PET Imaging Rapidly Targets Claudin18.2 in Lesions in Gastrointestinal Cancer Patients.

68Ga-labeled nanobody (68Ga-NC-BCH) is a single-domain antibody-based PET imaging agent. We conducted a first-in-humans study of 68Ga-NC-BCH for PET to determine its invivo biodistribution, metabolism, radiation dosimetry, safety, and potential for quantifying claudin-18 isoform 2 (CLDN18.2) expression in gastrointestinal cancer patients. Methods: Initially, we synthesized the probe 68Ga-NC-BCH and performed preclinical evaluations on human gastric adenocarcinoma cell lines and xenograft mouse models. Next, we performed a translational study with a pilot cohort of patients with advanced gastrointestinal cancer on a total-body PET/CT scanner. Radiopharmaceutical biodistribution, radiation dosimetry, and the relationship between tumor uptake and CLDN18.2 expression were evaluated. Results: 68Ga-NC-BCH was stably prepared and demonstrated good radiochemical properties. According to preclinical evaluation,68Ga-NC-BCH exhibited rapid blood clearance, high affinity for CLDN18.2, and high specific uptake in CLDN18.2-positive cells and xenograft mouse models. 68Ga-NC-BCH displayed high uptake in the stomach and kidney and slight uptake in the pancreas. Compared with 18F-FDG, 68Ga-NC-BCH showed significant differences in uptake in lesions with different levels of CLDN18.2 expression. Conclusion: A clear correlation was detected between PET SUV and CLDN18.2 expression, suggesting that 68Ga-NC-BCH PET could be used as a companion diagnostic tool for optimizing treatments that target CLDN18.2 in tumors.

Employment status in cancer patients the first five years after diagnosis-a register-based study.

Work is important for identity formation, social status, and economic independency. Although some evidence within the field of work and cancer survivorship exists, no study has so far investigated employment status across all cancer diagnoses. Thus, the aim of the present study was to investigate the impact of all cancer diagnoses on employment status. Danish cancer patients aged 20-60years, diagnosed between 2000 and 2015, were identified through Danish registers and matched 1:5 with cancer-free controls. Logistic and linear regression was performed separately in 11 cancer types to assess and compare work status and work participation between cancer patients and cancer-free controls one, three, and five years after diagnosis. A total of 111,770 cancer patients and 507,003 cancer-free controls were included. All cancer types had lower chances of working one year after diagnosis (ORs between 0.05 and 0.76), with lung, colorectal, upper gastrointestinal, and blood cancer patients having the lowest chances. After three years, 10 of 11 cancer types had lower chances (ORs between 0.39 and 0.84). After five years, there were minimal differences between cancer patients and controls among most cancer types (ORs between 0.75 and 1.36). Most cancer patients had lower chances of working compared with the general population until five years after diagnosis. However, patients with certain cancer types experienced lower chances of working all years, despite improvement over time. The knowledge will help increase awareness on challenges regarding work-life after cancer. Furthermore, the distinguishing between diagnoses can inform to more targeted vocational rehabilitation.

Malnutrition screening with Nutritional Risk Screening 2002 prior to assessment as part of GLIM criteria in patients undergoing major abdominal surgery for gastrointestinal cancer.

For diagnosing malnutrition as an important modifiable risk factor in surgical cancer patients, GLIM criteria offer a standardised diagnostic pathway. Before assessing malnutrition it is suggested to screen for malnutrition with an implemented screening tool, i.e. the NRS-2002. Validated data regarding the applied screening tool and its relevance for predicting outcome parameters in surgical patients is sparse. 260 patients undergoing major abdominal surgery for cancer were retrospectively analysed. Between January 2017 and December 2019, patients were prospectively screened for malnutrition with the Nutritional Risk Score 2002 (NRS). Irrespective of their screening result malnutrition was assessed with GLIM criteria using CT scan at lumbar level 3 for measuring skeletal muscle mass (GLIM MMCT). Patients with negative screening results (NRS ≤ 2) were analysed regarding their malnutrition assessment and outcome parameters. 34 of 67 patients with NRS ≤ 2, posing no risk for malnutrition, were diagnosed malnourished according to GLIM MMCT (n=34, 50.7%). 19 patients (55.9%) with NRS ≤ 2 and malnutrition according to GLIM had at least one complication, 12 patients (35.3%) had a severe complication (Clavien-Dindo Grade ≥ 3a), in 26.5% re-laparotomy was necessary, re-admission within one month in 20.6% of patients, and length of hospital stay was 18.76 ± 12.66, which was in total worse in outcome compared to the whole study group (n=260). Patients with NRS ≤ 2 but diagnosed malnourished by GLIM were at significant higher risk to develop a severe complication (OR 2.256, 95% CI 1.038 - 4.9095, p=0.036) compared to patients with NRS ≤ 2 but not being diagnosed malnourished. The risk for overall complications was significantly increased in patients with malnutrition diagnosed by the GLIM criteria using MMCT (OR 2.028, 95% CI 1.188-3.463, p= 0,009). Patients screened at risk with NRS ≥ 3 and diagnosed malnourished by GLIM were also at significant higher risk for developing complications (OR 1.728, 95% CI 1.054 - 2.832, p=0.029). GLIM MMCT is suitable for diagnosing malnutrition and estimating postoperative risk in gastrointestinal cancer patients. Nutritional assessment only in patients with NRS > 2 may bear the risk to miss malnourished patients with high risk for poor clinical outcome. In every patient undergoing major cancer surgery regular assessment of nutritional status regardless of screening result should be performed exploiting CT body composition analysis.

Cell cycle associated protein 1 associates with immune infiltration and ferroptosis in gastrointestinal cancer

BackgroundCell Cycle-Associated Protein 1 (CAPRIN1) play an important role in cell proliferation, oxidative stress, and inflammatory response. Nonetheless, its role in tumor immunity and ferroptosis is largely unknown in gastrointestinal cancer patients. MethodsThrough comprehensive bioinformatics, we investigate CAPRIN1 expression patterns and its role in diagnosis, functional signaling pathways, tumor immune infiltration and ferroptosis of different gastrointestinal cancer subtypes. Besides, immunohistochemistry (IHC) and immune blot were used to validate our esophagus cancer clinical data. The ferroptotic features of CAPRIN1 in vitro were assessed through knockdown assays in esophagus cancer cells. ResultsCAPRIN1 expression was significantly upregulated, correlated with poor prognosis, and served as an independent risk factor for most gastrointestinal cancer. Moreover, CAPRIN1 overexpression positively correlated with gene markers of most infiltrating immune cells, and immune checkpoints. CAPRIN1 knockdown significantly decreased the protein level of major histocompatibility complex class I molecules. We also identified a link between CAPRIN1 and ferroptosis-related genes in gastrointestinal cancer. Knockdown of CAPRIN1 significantly increased the production of lipid reactive oxygen species and malondialdehyde. Inhibition of CAPRIN1 expression promoted ferroptotic cell death induced by RAS-selective lethal 3 and erastin in human esophagus cancer cells. ConclusionCollectively, our results demonstrate that CAPRIN1 is aberrantly expressed in gastrointestinal cancer, is associated with poor prognosis, and could potentially influence immune infiltration and ferroptosis.

Comparison of Goal Achievement during an Early, Intensive Nutrition Intervention Delivered to People with Upper Gastrointestinal Cancer by Telephone Compared with Mobile Application.

This study is aimed at exploring whether the mode of nutrition intervention delivery affected participant goal achievement in a three-arm randomised controlled trial of early and intensive nutrition intervention delivered to upper gastrointestinal cancer patients. Newly diagnosed upper gastrointestinal cancer patients were recruited from four tertiary hospitals in Melbourne, Australia. Participants in the intervention groups received a regular nutrition intervention for 18 weeks from an experienced dietitian via telephone or mobile application (app) using behaviour change techniques to assist in goal achievement. Univariate and multiple regression models using STATA determined goal achievement, dose, and frequency of contact between groups. A p value <0.05 was considered statistically significant. The telephone group (n = 38) had 1.99 times greater frequency of contact with the research dietitian (95% CI: 1.67 to 2.36, p < 0.001) and 2.37 times higher frequency of goal achievement (95% CI: 1.1 to 5.11, p = 0.03) compared with the mobile app group (n = 36). The higher dose (RR 0.03) of intervention and more behaviour change techniques employed in the telephone group compared with the mobile app group increased participant goal achievement (95% CI: 0.01 to 0.04, p < 0.001). Discussion. Telephone nutrition intervention delivery led to a higher frequency of goal achievement compared to the mobile app intervention. There was also a higher number of behaviour change techniques employed which may have facilitated the greater goal achievement. Mobile app-based delivery may have poorer acceptance in this population with high levels of withdrawal. Practice Implications. We need to ensure that specifically designed technologies for our target populations are fit for purpose, efficacious, and acceptable to both patients and healthcare providers. This trial is registered with ACTRN12617000152325.

[Malnutrition in advanced gastrointestinal cancer patients and nutritional support therapy].

The advancement of comprehensive treatment has allowed an increasing number of patients with gastrointestinal tumor to achieve long-term survival. In current clinical practice, there is a growing population of patients with advanced gastrointestinal tumor. Due to various factors, such as tumor burden, treatments including chemotherapy and radiation therapy, as well as underlying diseases, patients with advanced gastrointestinal tumor often experience malnutrition, which negatively impacts their clinical outcomes. The mechanism of malnutrition in patients with advanced gastrointestinal tumor is complex, and conventional nutritional support therapy has shown limited effectiveness. With the continuous progress in the concept and technique of nutritional support therapy, the diversification of treatment strategies, and the strengthening of multidisciplinary collaboration, the nutritional management for patients with advanced gastrointestinal tumor tends to be standardized and rational, leading to effective improvement in patients' nutritional status and clinical outcomes. Based on the latest evidence-based medicine, combined with the author's practical experience and insights, this article aims to explore nutritional support therapy for patients with advanced gastrointestinal tumor.

Abstract 944: Pre-clinical activity of the Wnt pathway inhibitor RXC004 in combination with MAPK pathway inhibitors in GI cancer models

Abstract Background: Gastrointestinal (GI) cancers cause more cancer deaths than any other body system, with 3.4 million related deaths in 2018. Wnt pathway activation is common in GI cancers, with the pathogenic upstream Wnt pathway variant sub-population (RNF43 loss of function/RSPO gain of function) showing a combined prevalence of 4.7% in GI cancer patients; pre-clinically this sub-population shows exquisite sensitivity to RXC004, a small molecule Porcupine inhibitor. A striking co-occurrence of upstream Wnt pathway variants with MAPK pathway driver mutations (KRAS, BRAF, NRAS) was detected in 77% of Microsatellite stable (MSS) GI cancers, suggesting co-inhibiting these pathways could enhance clinical activity in these patients. Methods: In vitro proliferation assays were performed in pre-clinical models of upstream Wnt pathway mutated MSS GI cancer (SNU-1411, HPAF-II and AsPC-1) using Wnt (RXC004) or MAPK (Trametinib) pathway inhibitors at multiple concentrations as single agents or in combination. Control cells with downstream Wnt pathway mutations (WiDr and HCT116) were also tested. Synergistic combination effects were detected by BLISS scores. RXC004 (1.5mg/kg QD) and Trametinib (0.3mg/kg QD) were evaluated in an RSPO-fusion xenograft model (SNU-1411) as single agents or in combination. Efficacy was measured by tumour volume and weight; PD markers were assessed in end of study tumour samples. Relative AXIN2 and DUSP6 gene expression changes were determined upon inhibitor treatment by quantitative Polymerase Chain Reaction (qPCR). Results: RXC004 in combination with Trametinib demonstrated strong anti-proliferative synergy in SNU-1411 cells and moderate synergy/additivity in HPAF-II and AsPC-1 cells; no synergy was observed in control cells. In vivo, RXC004 and Trametinib monotherapy led to significant moderate tumour growth control (p&amp;lt;0.05) at the doses tested, whereas their combination led to significantly enhanced efficacy (p&amp;lt;0.05). Gene expression analysis demonstrated a reciprocal Wnt/MAPK signaling mechanism; RXC004 strongly suppressed Wnt signaling (AXIN2) but increased MAPK signaling (DUSP6), whilst Trametinib strongly suppressed MAPK signaling (DUSP6) but increased Wnt signaling (AXIN2). Combination of RXC004 and Trametinib sustained inhibition of both Wnt and MAPK signalling. Similar effects were observed with inhibitors of other MAPK pathway components. Conclusion: Wnt and MAPK pathways are frequently co-activated in GI cancers, particularly in the upstream Wnt pathway mutated sub-population. Pre-clinically we show that Wnt and MAPK pathways act as potential reciprocal resistance mechanisms following single agent inhibition of either pathway; co-inhibition of these pathways leads to synergistic effects in vitro and enhanced efficacy in vivo. This provides a clear rationale to assess this combination approach in the clinic. Citation Format: Simon A. Woodcock, Dorottya Keppel, Catherine Eagle, James Kelly, Eimear Flanagan, Emma Bishop, Inder Bhamra, Clifford D. Jones, Richard Armer, Jane Robertson, Caroline Phillips. Pre-clinical activity of the Wnt pathway inhibitor RXC004 in combination with MAPK pathway inhibitors in GI cancer models [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 944.

Abstract 6458: Clinical significance of cancer genome profiling tests for gastrointestinal cancer patients with liver metastasis

Abstract Introduction: Distant metastasis is one of critical prognostic factors for patients with gastrointestinal cancer. Especially, liver metastasis shows high effects on prognosis of patients with gastrointestinal cancer. In Japan, cancer genome profiling (CGP) testing have been available for patients who have no selective standard treatment options since 2019. Based on the genetic mutations by CGP test, therapeutic drugs with evidence have been discussed at expert panels. CGP data has been accumulated in around 60,000 cases. It is necessary to evaluate the clinical significance of CGP tests for gastrointestinal cancer patients with liver metastasis to receive high benefits of CGP testing through C-CAT. Aims: We aimed to analyze the clinical significance CGP tests for gastrointestinal cancer patients with liver metastasis. Materials and methods: A total of 3,738 patients of gastrointestinal cancer with liver metastases including 215 cases of esophageal cancer, 347 cases of gastric cancer, and 3,176 cases of colorectal cancer, was enrolled in this study. Three types of CGP tests, including NCC Oncopanel, FoundationOne CDx, and FoundationOne Liquid, were performed, and the CGP data was collected to Center for Cancer Genomics and Advanced Therapeutics in Japan (C-CAT) database. Adequate treatment for each patient was discussed at the expert panel meeting according to the results from the CGP tests. Results: A total of 2,882 cases (77.1%) in 3,176 cases have been revealed druggable. However, only 216 cases (13.3%) were medicated by anti-cancer treatments. In the 216 treated cases, disease control case, complete response (CR), partial response (PR), or stable disease (SD) was only 52 cases. In 52 cases, six cases (4 of SD cases and 2 of PR cases) was administered encorafenib-based chemotherapies based on BRAF gene mutation. Five genes, ZNF217, SRC, ARFRP1, BARD1, FGF10, were significantly more frequently expressed on liver metastasis cases, in compared to other metastasis cases in gastrointestinal cancer. Conclusion: Around 13% of gastrointestinal cancer patients with liver metastasis might have a druggable benefit by CGP testing. BRAF mutation might be promising target for patients with liver metastasis. ZNF217, SRC, ARFRP1, BARD1, FGF10 might be associated with metastatic process to liver in gastrointestinal cancer. Citation Format: Takashi Sakuma, Masakazu Yashiro, Yasuhiro Fukui, Koji Maruo, Gen Tsujio, Yurie Yamamoto, Hiroaki Kasashima, Kiyoshi Maeda. Clinical significance of cancer genome profiling tests for gastrointestinal cancer patients with liver metastasis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6458.

Abstract 6470: Real-world analysis of insurance status and survival in patients with selected GI cancers

Abstract Background: Health insurance is a critical determinant of healthcare access and outcomes in gastrointestinal (GI) cancers. Epidemiological data have shown that insurance-associated healthcare outcomes vary by diagnosis, geographic location, and demographics. Thus, it is critical for cancer providers to understand local impacts of insurance status on patient outcomes. Here, we present real-world outcomes for pancreatic, hepatobiliary, and colorectal cancer (CRC) patients in 11 Midwest hospitals based on insurance status. Methods: We identified patients diagnosed with colorectal, pancreatic, and hepatobiliary cancers within 11 Midwest hospitals from 2011-2021 with North American Association of Central Cancer Registries data. Health insurance was defined as private, Medicaid, Medicare, and uninsured. Effect of insurance status at diagnosis on overall survival (OS) in selected cancers combined and by cancer type were calculated using a Cox proportional hazard (CoxPH) model controlling for age, sex, race, stage, time to treatment initiation (TTI), and Charlson Comorbidity Index (CCI). We evaluated differences in TTI by insurance status using t-tests. We analyzed stage and treatment modality by insurance status using chi-square tests. Post-hoc analysis of TTI by OS used CoxPH. Results: Relative to private insurance, Medicaid and Medicare insurance status significantly reduced OS for all selected GI cancers combined (HR 1.38, 95% CI 1.17 - 1.62 and HR 1.25, 95% CI 1.11 - 1.40, respectively; p&amp;lt;0.001) and for CRC (HR 1.49, 95% CI 1.12 - 1.98 and HR 1.28, 95% CI 1.06 - 1.54, respectively; p&amp;lt;0.01). Uninsured patients had significantly reduced OS only for pancreas cancer (HR 6.36, 95% CI 2.56 - 15.8; p&amp;lt;0.001). No significant associations between insurance status and OS were noted in Hepatobiliary cancer. TTI was significantly associated with insurance status (p&amp;lt;0.001) and mean TTI for Medicaid (35.8 days) and Medicare (27.9 days) patients was longer than mean TTI for privately insured patients (23.3 days; p&amp;lt;0.01). TTI for uninsured patients was not significantly different than for privately insured. Analysis of TTI and OS showed no increased hazard for patients with TTI of 36 days versus 23 days (HR 0.87, 95% CI 0.75 - 1.02; p=0.085). Treatment modality and stage did not differ as a function of insurance status in this dataset. Discussion: Our results expand previous work by demonstrating a survival impact for GI cancer patients with Medicaid or Medicare insurance. This disparity persists despite controlling for known prognostic factors such as age, stage, CCI, and TTI. Notably, TTI varied by insurance suggesting it may account for a portion of this disparity but did not independently drive survival. Further work is required to identify and develop targeted interventions to address other drivers of reduced survival in those without private insurance. Citation Format: Rebecca AbuAyed, Joshua Schwanke, Brooke Patterson, McKenzie White, Schelomo Marmor, Eric Jensen, Christopher Tignanelli, Emil Lou, Ajay Prakash. Real-world analysis of insurance status and survival in patients with selected GI cancers [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6470.

Abstract 4955: An analytic pipeline of neoantigen selection for both MHC-I and MHC-II pathways

Abstract Background: Accurate neoantigen selection is pivotal for assessing mutation burden and optimizing cancer vaccine formulation thereby playing a crucial role in cancer immunotherapy. The concurrent activation of CD4+ and CD8+ T cells engenders a robust immune response, which is key to effective treatment. However, currently analytic tools predominantly focus on the MHC-I pathway, typically relying on metrics such as gene expression level and MHC-binding affinity of mutated peptides. To address this gap, our study presents a comprehensive pipeline that encompasses both MHC-I and MHC-II pathways and integrates three critical dimensions of immune response: neoantigen abundance, presentation, and immunogenicity. Methods: We estimated mutated peptide abundance by analyzing genomic allelic frequency, transcriptomic allelic frequency, and RNA expression level. Antigen presentation was assessed using the patient harmonic binding rank (PHBR, a composite binding score for all potential MHC-peptide pairs) and MHC diversity (the variety of MHC alleles involved in peptide binding), with additional consideration for the loss of heterozygosity of MHC-I alleles, potentially indicative of immune escape. For immunogenicity, we factored in agretopicity (comparison of MHC-binding affinity between mutated and wild-type peptides), foreignness (similarity to immunogenic foreign antigens), and dissimilarity (sequence disparity with self-peptides, reflecting T cell negative selection process). Results: Implementing our pipeline on a dataset from Parkhurst et al. (2019), we analyzed immune reactivity in relation to 11,537 somatic mutations from 75 gastrointestinal cancer patients. Key metrics—RNA expression, transcriptomic allelic frequencies, PHBR, and MHC diversity—demonstrated significant correlations with both CD4+ and CD8+ activity (p&amp;lt;0.05). Notably, genomic allelic frequency was a significant factor in CD8+ reactivity, whereas agretopicity was crucial for CD4+ reactivity. Conclusion: Our pipeline elucidates the necessity for implementing both MHC-I and MHC-II pathway analyses to effectively select neoantigen candidates for CD8+ and CD4+ T cells respectively. The study confirms that abundance and antigen presentation metrics are robust indicators of neoantigen immunogenicity, supporting their use as potential markers in crafting more effective cancer vaccines. The findings highlight the critical role of this dual-pathway selection approach in generating a comprehensive immune response through neoantigen vaccination. Citation Format: Ko-Han Lee, Timothy Sears, Andrea Castro, Maurizio Zanetti, Hannah Carter. An analytic pipeline of neoantigen selection for both MHC-I and MHC-II pathways [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 4955.

Abstract 5180: Pharmacodynamic biomarker analysis of gastrointestinal cancer patients treated with metronomic chemotherapy in the Italian COMET Trial

Abstract Metronomic, or continuous low-dose, chemotherapy produces antitumor effects through multiple mechanisms. These include inhibition of angiogenesis and activation of the immune system. At AACR 2017 we presented a small, proof-of-concept, multiplex analysis of 14 cytokines specifically chosen by their association with activation of the immune system. The 14 cytokines were evaluated in 31 out of 38 patients with advanced refractory gastrointestinal tumors, enrolled in a phase II clinical trial of metronomic UFT (a 5-fluorouracil prodrug; 100 mg/twice per day p.o.) and cyclophosphamide (500 mg/mq2 i.v. bolus on day 1 and then 50 mg/day p.o.) plus celecoxib (200 mg/twice a day p.o.); the Italian COMET trial (Clinical Trial ID NCT02926911; Allegrini et al. Angiogenesis 2012: 15(2):275-86). We evaluated baseline (day 0) plasma levels with levels at days 28 and 56, and tested for correlations with observed Progression Free Survival, which we then reported (Valenzuela et al. Clin Exp Med. 2021: 21(1):149-159). We now present a comprehensive analysis of 75 cytokines in 34 of the 38 patients. Furthermore we extend the analysis to include baseline (day 0), days 28 and 56, and days 84 and 112 of the COMET trial, and we also correlated specific cytokines levels with Overall Survival. After an estimation of optimal cut-off points of plasma levels of the cytokines, survival analysis was performed, and log-rank tests and cox regression analyses were applied. We show that pre-treatment plasma level &amp;lt;435.46pg/ml of macrophage-derived chemokine (MDC), was a predictive marker for those patients with better progression-free survival at 3 and 6 months (log-rank test p=0.0046; Cox regression analysis p=0.016). Moreover, baseline plasma levels of three cytokines, including monocyte chemoattractant protein 2 (MCP-2), monocyte chemoattractant protein 4 (MCP-4) and TNF-related apoptosis-inducing ligand (TRAIL), were associated with an improved overall survival. MCP-2 values &amp;gt;26.21pg/ml (log-rank test p=0.0012; Cox regression analysis p=0.007), MCP-4 &amp;gt;72.97pg/ml (log-rank test p=0.012; Cox regression analysis p=0.019) and TRAIL &amp;gt;60.73pg/ml (log-rank test p=0.0059; Cox regression analysis p=0.011) were predictive markers for subjects with a better overall survival at 6 and 9 months. These results indicate that a methodology based on the detection of optimal cut-off points and survival analysis allowed the selection of potential biomarkers, such as MDC or MCPs. We propose that the systematic use of these statistical strategies, aimed at detecting potential biomarkers, could help to identify those patients that are likely to benefit from metronomic chemotherapy schedules. This would allow the stratification of such patients for future metronomic chemotherapy trials, and the potential identification of patients that should instead be offered alternative therapeutic strategies. Citation Format: Maria L. Manca, Diana Prospero, Saeedeh Darvishi, Arianna Bandini, Marta Banchi, Paola Orlandi, Hector Padilla, Alejandro Sanchez, Claire E. Perucho, Nydia de Avila, Hazel Padilla, Brianna E. Ortega, Ryley D. Stewart, Magdiel Santillan, Valeria Lopez, Robert Kirken, Giacomo Allegrini, Guido Bocci, Giulio Francia. Pharmacodynamic biomarker analysis of gastrointestinal cancer patients treated with metronomic chemotherapy in the Italian COMET Trial [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 5180.

Double role of depression in gastric cancer: As a causative factor and as consequence

In this editorial we comment on the article “Hotspots and frontiers of the relationship between gastric cancer and depression: A bibliometric study”. Gastric cancer (GC) is a common malignancy in the digestive system with increased mortality and morbidity rates globally. Standard treatments, such as gastrectomy, negatively impact patients' quality of life and beyond the physical strain, GC patients face psychological challenges, including anxiety and depression. The prevalence of depression can be as high as 57%, among gastrointestinal cancer patients. Due to the advancements in treatment effectiveness and increased 5-year overall survival rates, attention has shifted to managing psychological effects. However, the significance of managing the depression doesn’t lie solely in the need for a better psychological status. Depression leads to chronic stress activating the sympathetic nervous system and the hypothalamus-pituitary-adrenal axis, leading release of catecholamines inducing tumor proliferation, migration, and metastasis, contributing to GC progression. The dysregulation of neurotransmitters and the involvement of various signaling pathways underscore the complex interplay between depression and GC. Comprehensive strategies are required to address the psychological aspects of GC, including region-specific interventions and increased monitoring for depression. Understanding the intricate relationship between depression and GC progression is essential for developing effective therapeutic strategies and improving overall outcomes for patients facing this complex disease. In this Editorial we delve into double role of depression in the pathogenesis of GC and as a complication of it.

The impact of SARS-Cov-2 Omicron infection on short-term outcomes after elective surgery in patients with gastrointestinal cancer.

With the emergence of novel variants, Omicron variant caused a different clinical picture than the previous variants and little evidence was reported regarding perioperative outcomesafter Omicron variants. The aim of the study was to evaluate the postoperative outcomes of gastrointestinal cancer patients following Omicron variants infection and also to determine the timing of surgery after infection recovery. A total of 124 patients who underwent gastrointestinal cancer surgery with prior SARS-CoV-2 infection between December 2022 and February 2023 were retrospectively reviewed. 174 cases underwent the same operation during December 2018 and February 2019 as control group. SARS-CoV-2-infected patients were further categorized into three groups based on infected time (1-3weeks; 4-6weeks; and ≥ 7weeks). 90.3% of SARS-CoV-2-infected patients had mild symptoms. The COVID-19 vaccination rate was 71.0%, with a full vaccination rate of 48.4%. There were no significant differences in 30-day morbidity and mortality. There was also no significant difference in pulmonary complications, cardiovascular complications, and surgical complications between the three different diagnosis time groups. In conclusion, reducing waiting time for elective surgery was safe for gastrointestinal cancer patients in the context of an increasedtransmissibility and milder illness severity with Omicron variant.

Health-related quality of life among patients with esophageal, gastric, and colorectal cancer at Kenyatta National Hospital.

Despite the advancement of modern treatment approaches, several studies indicated a diminished health-related quality of life (HRQoL) in patients with gastrointestinal cancer. However, there is insufficient data about the HRQoL of gastrointestinal cancer patients in Kenya. The study aimed to investigate HRQoL and its determinants in gastrointestinal cancer patients at Kenyatta National Hospital. A cross-sectional study was employed among 160 esophageal, 103 gastric, and 96 colorectal cancer patients. The patient list, identified by unique hospital identification numbers, was obtained from records. Eligibility was assessed based on predetermined criteria, and the hospital identification numbers were reshuffled. Study participants were then randomly selected daily during the data collection period. Data were collected using a researcher-administered European Organization for Research and Treatment of Cancer quality of life questionnaire. The data entry and analysis were carried out using Statistical Package for the Social Sciences 26.0 statistical software. A bivariate and multivariate binary logistic regression analysis was employed to investigate determinants of HRQoL at a 0.05 level of significance. Most esophageal (N = 118, 73.7%), gastric (N = 75, 72.8%), and colorectal (N = 72, 75%) cancer patients had poor overall HRQoL. In the social (p = .04) and cognitive (p = .02) domain of HRQoL, esophageal cancer patients had a significantly lower mean score as compared to gastric cancer patients. Colorectal cancer patients had the highest mean score in physical functioning (p = .01) as compared with gastric cancer patients. Nonetheless, gastric cancer patients had the highest mean score in emotional functioning domains of quality of life as compared to esophageal (p = .04) and colorectal (p < .001) cancer patients The study revealed a low mean HRQoL score in the majority of the symptom domains of quality of life. A statistically significant difference in all domains of HRQoL was not observed in various treatment modalities of gastrointestinal cancer. Advanced-stage (stages III and IV) and co-morbidities were significant determinants of poor HRQoL. The overall HRQoL of gastrointestinal cancer patients was poor. Advanced-stage cancer and co-morbidities were significant determinants of poor HRQoL. Therefore, intensification of routine monitoring of the disease and the treatments should be actively implemented to improve the HRQoL.