Gastrointestinal Malignancies Research Articles

COL8A1 Regulates Esophageal Squamous Carcinoma Proliferation and Invasion Through PI3K/AKT Pathway.

Esophageal squamous carcinoma (ESCC) is a gastrointestinal malignancy with a high mortality, but the tumorigenesis is still unclear, restricting the target therapy development of ESCC. We explored the role of COL8A1 in ESCC development. Tissue microarrays were used to investigate the expression level of COL8A1 in ESCC tissues. The association between COL8A1 and the overall survival of ESCC patients was assessed. The effect of differential COL8A1 expression on tumor growth was investigated by the xenograft model. The regulation of COL8A1 on tumor growth, migration, and invasion was studied by using ESCC cell lines. The signal transduction pathways involved in COL8A1 were bioinformatically profiled and validated. The COL8A1 was significantly expressed in cancerous tissues and was associated with poor prognosis in patients with ESCC. In vivo, the tumor growth obviously declined after inhibition of the COL8A1 expression. The abilities of cell proliferation and invasion were both decreased when the expression of COL8A1 was knockdown in ESCC cell line. Furthermore, we found the inactivation of the PI3K/AKT pathway that was mediated by knockdown of COL8A1 in ESCC cells, which was reversed with COL8A1 overexpression, whereas the cell proliferation and invasion ability were restored. This is the first report that COL8A1 promote ESCC progression, which hopefully will provide a theoretical basis for clinical targeting of ESCC.

Phase 1 trial of same day cytology to guide the use of HIPEC.

Peritoneal metastases from gastrointestinal or gynecologic malignancy are a prominent part of the natural history of these diseases. Peritoneal metastases, if not effectively treated, will result in a decreased survival and cause an impaired quality of life. Hyperthermic intraperitoneal chemotherapy (HIPEC) is a treatment specifically designed to combat peritoneal metastases. A group of patients who, from a theoretical perspective, may benefit from HIPEC are those patients with a positive peritoneal cytology. In order to identify these patients at the time of a surgical intervention, a same day cytology is to be performed. The result of this test is to be available at or before the completion of the cancer resection. If the cytology is positive, the patient immediately becomes a candidate for HIPEC. The HIPEC will be of maximal value if a complete cytoreduction, as judged by the surgeon, has been possible. This phase 1 trial is to demonstrate that the Surgical Oncology Service, the Department of Pathology, the Pharmacy and the Operating Room personnel can co-ordinate a phase 1 protocol to successfully complete the same day cytology with an efficient delivery of HIPEC. A standardized plan for consent, cytology collection, preparation of the specimen, reading of the specimen, reporting the results in a timely manner facilitates the administration of HIPEC in peritoneal cytology positive patients. Successful completion of these requirements is a positive result for this study and allows for future protocols to be generated. Successful completion of the same day cytology phase 1 protocol will allow the efficacy, safety, and efficiency of this plan of patient management to be evaluated.

Detection of Upper Gastrointestinal Disorders in Patients with Positive Fecal Immunochemical Test (FIT) and Normal Colonoscopy: A Cross-Sectional Study

Abstract Introduction Colorectal cancer (CRC) is the second most prevalent cancer in the world, and the fecal immunochemical test (FIT) can be mentioned among the CRC screening methods based on the detection of occult blood in the feces, which may indicate upper gastrointestinal (UGI) malignancies; therefore, patients with a positive FIT but normal colonoscopy may be considered for a UGI endoscopy. Materials and Methods The present study was conducted on patients with a positive FIT who were submitted to colonoscopy with normal results. They subsequently underwent endoscopy for the detection of UGI disorders. Results We included 121 patients (64.5% of women and 35.5% of men; average age: 58.85 ± 12.93 years), 72.7% of whom were positive for Helicobacter pylori. The predominant result of the UGI endoscopy was normal, followed by erythema of the gastric mucosa, and anemia and dyspepsia were the most common clinical findings. The most common pathological result was chronic gastritis, followed by acute gastritis. Only one patient presented stomach cancer (adenocarcinoma). Conclusion Considering the small prevalence of cancer in the UGI endoscopies of patients with positive FIT and normal colonoscopy, to the performance of UGI endoscopy in these patients may not be necessary.

Identification and analysis of prognostic metabolic characteristics in colon adenocarcinoma

Colon adenocarcinoma (COAD) is a highly lethal gastrointestinal malignancy. The five-year survival rate of metastatic colorectal cancer remains low, at 14 percent. Numerous publications have suggested a role for peroxisome proliferator-activated receptors (PPARs) in malignancy. Recent studies have shown that PPARs, as nuclear transcription factors, may serve as potential targets for the treatment of metabolic syndrome tumors and their associated complications. However, the molecular mechanism has not been thoroughly investigated. Hence, in order to enhance the prediction of personalized medicine for PPAR-associated modulators in malignancy treatment, a timely review becomes essential. Utilizing TCGA-COAD expression profile data and patient overall survival (OS) information, this study systematically conducted investigations to identify and develop Hub stem cell-related diagnostic and prognostic identification models, aiming to enhance the multi-gene markers for COAD. Utilizing the differential expression profiles of stem cell-related genes, an 11-gene (SLC27A4, CPT1C, CPT1B, CPT2, CYP4A11, FABP3, FABP7, AQP7, MMP1, ACOX1, ANGPTL4) diagnostic and prognostic model was developed. This model demonstrated precise diagnostic and prognostic capabilities and holds the potential to characterize the clinicopathologic features of COAD. Univariate and multivariate Cox proportional hazards regression analyses were conducted to ascertain the independent factors influencing OS outcomes in COAD. The results revealed that CPT1B, SLC27A4, and FABP3 were identified as independent risk prognostic factors for OS in COAD, whereas ACOX1 and CPT2 served as independent protective prognostic factors. The hub genes associated with PPARs were identified through the differential expression of contrast agent COAD and normal tissues. Finally, the investigation of variations in immune infiltration and the analysis of relevant biological pathways validate the prognostic significance of the independent post-factors within this molecular model. This research aims to provide references for comprehending the mechanism of post-transcriptional regulation of COAD and molecular therapy.

Gastrointestinal Malignancies: Actionable Takeaways from the 2023 Precision Oncology Summit

The 2023 Precision Oncology Summit was held in San Francisco on October 7th and 8th, focusing on actionable strategies addressing personalized treatment to improve patient outcomes. This manuscript summarizes the discussion and key learning points from the precision medicine clinical science symposium in gastrointestinal (GI) malignancies.

Updates in Diagnosis and Endoscopic Management of Cholangiocarcinoma.

Cholangiocarcinoma (CCA) is an adenocarcinoma originating from the epithelial cells of the bile ducts/hepatocytes or peribiliary glands. There are three types of cholangiocarcinoma: intrahepatic, perihilar and distal. CCA represents approximately 3% of the gastrointestinal malignancies. The incidence of CCA is higher in regions of the Eastern world compared to the Western countries. There are multiple risk factors associated with cholangiocarcinoma such as liver fluke, primary sclerosing cholangitis, chronic hepatitis B, liver cirrhosis and non-alcoholic fatty liver disease. Endoscopy plays an important role in the diagnosis and management of cholangiocarcinoma. The main endoscopic methods used for diagnosis, biliary drainage and delivering intrabiliary local therapies are endoscopic retrograde cholangiopancreatography and endoscopic ultrasound. The purpose of this review is to analyze the current data found in literature about cholangiocarcinoma, with a focus on the actual diagnostic tools and endoscopic management options.

The Many Hidden Faces of Gallbladder Carcinoma on CT and MRI Imaging-From A to Z.

Gallbladder carcinoma represents the most aggressive biliary tract cancer and the sixth most common gastrointestinal malignancy. The diagnosis is a challenging clinical task due to its clinical presentation, which is often non-specific, mimicking a heterogeneous group of diseases, as well as benign processes such as complicated cholecystitis, xanthogranulomatous cholecystitis, adenomyomatosis, porcelain gallbladder or metastasis to the gallbladder (most frequently derived from melanoma, renal cell carcinoma). Risk factors include gallstones, carcinogen exposure, porcelain gallbladder, typhoid carrier state, gallbladder polyps and abnormal pancreaticobiliary ductal junction. Typical imaging features on CT or MRI reveal three major patterns: asymmetric focal or diffuse wall-thickening of the gallbladder, a solid mass that replaces the gallbladder and invades the adjacent organs or as an intraluminal enhancement mass arising predominantly from the gallbladder fundus. The tumor can spread to the liver, the adjacent internal organs and lymph nodes. Depending on the disease stage, surgical resection is the curative treatment option in early stages and adjuvant combination chemotherapy at advanced stages. The purpose of this scientific paper is to fully illustrate and evaluate, through multimodality imaging findings (CT and MRI), different presentations and imaging scenarios of gallbladder cancer in six patients and thoroughly analyze the risk factors, patterns of spread and differential diagnosis regarding each particular case.

Occupational exposure to silica and risk of gastrointestinal cancers: a systematic review and meta-analysis of cohort studies.

Although silica is a proven lung carcinogen, there is no convincing evidence linking crystalline silica to gastrointestinal malignancies. We detailedly searched studies on the link between gastrointestinal malignancies and occupational silica exposure. Studies published between 1987 and 2023 were found by searching PubMed, Scopus, Cochrane Library, and Web of Science databases. Further studies were included from reference searching. We conducted a meta-analysis of the incidence and mortality of gastrointestinal malignancies and occupational silica exposure. We computed pooled-risk estimates using random effects models. Egger's regression asymmetry test and a funnel plot were used to identify publication bias. Moreover, sensitivity analysis and subgroup analysis were out. We identified 40 research with individuals from 13 different countries. The results indicate that occupational silica exposure raises the risk of gastric and esophageal cancer incidence, with pooled standardized incidence ratio of 1.35 (95% CI 1.21-1.51, p < 0.001), 1.31 (95% CI 1.04-1.65, p = 0.023), respectively, but there was a lack of statistically significant relationship between standardized mortality ratio. In addition, we found that silica exposure did not increase the risk of colorectal and pancreatic cancers. Occupational silica exposure was found to increase the risk of liver cancer, with pooled SIR and SMR of 1.19 (95% CI 1.04-1.35, p = 0.009), 1.24 (95% CI 1.03-1.49, p = 0.026), respectively. We discovered a link between occupational silica exposure and gastrointestinal malignancies, with cancers of the liver, stomach, and esophagus being the most prevalent. Colorectal and pancreatic cancer were not linked to occupational silica exposure.

Impact of prior cancer history on survival in brain malignancy: A propensity score-adjusted, population-based study.

Individuals with a Prior Cancer History (PCH) are often excluded from clinical trials. However, a growing body of evidence suggests that prior cancer history does not present adverse outcomes on cancer patients. The evidence on the survival of brain cancer patients in this regard remains widely unknown. We conducted a retrospective cohort study to estimate the prevalence and impact of prior cancer on survival of patients diagnosed with brain cancer. Data of patients who were diagnosed with brain cancer as their first or second primary malignancy between 2000 and 2019 were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. Propensity Score Matching (PSM) was used to ensure comparable baseline characteristics among the patients. Survival analysis was conducted using the Kaplan-Meier method, as well as multivariate Cox proportional hazard and multivariate competing risk models. Out of 42 726 patients, 1189 (2.78%) had PCH. Genitourinary (40.4%), Breast (13.6%), Hematologic and Lymphatic (11.4%), and Gastrointestinal malignancies (11.3%) were the most common types of prior cancer. PCH served as a significant risk factor for Overall Survival (OS) (Adjusted Hazard Ratio [AHR] 1.26; 95% CI [1.15-1.39]; p < .001) but did not have a statistically significant impact on Brain Cancer-Specific Survival (BCSS) (AHR 0.97; 95% CI [0.88-1.07]; p = .54). Glioblastoma exhibited the most substantial and statistically significant impact on survival as compared to other histological types. Of all the organs systems, only prior Gastrointestinal and Hematologic and Lymphatic malignancies had a statistically significant impact on OS of patients. Our findings indicate that PCH does not exert a substantial impact on the survival of brain cancer patients, except in cases involving gastrointestinal or hematologic and lymphatic PCH, or when the brain cancer is glioblastoma.

The role of microbiomes in gastrointestinal cancers: new insights.

Gastrointestinal (GI) cancers constitute more than 33% of new cancer cases worldwide and pose a considerable burden on public health. There exists a growing body of evidence that has systematically recorded an upward trajectory in GI malignancies within the last 5 to 10 years, thus presenting a formidable menace to the health of the human population. The perturbations in GI microbiota may have a noteworthy influence on the advancement of GI cancers; however, the precise mechanisms behind this association are still not comprehensively understood. Some bacteria have been observed to support cancer development, while others seem to provide a safeguard against it. Recent studies have indicated that alterations in the composition and abundance of microbiomes could be associated with the progression of various GI cancers, such as colorectal, gastric, hepatic, and esophageal cancers. Within this comprehensive analysis, we examine the significance of microbiomes, particularly those located in the intestines, in GI cancers. Furthermore, we explore the impact of microbiomes on various treatment modalities for GI cancer, including chemotherapy, immunotherapy, and radiotherapy. Additionally, we delve into the intricate mechanisms through which intestinal microbes influence the efficacy of GI cancer treatments.

Hemospray® (hemostatic powder TC-325) as monotherapy for acute gastrointestinal bleeding: a multicenter prospective study.

Hemostatic powders are used as second-line treatment in acute gastrointestinal (GI) bleeding (AGIB). Increasing evidence supports the use of TC-325 as monotherapy in specific scenarios. This prospective, multicenter study evaluated the performance of TC-325 as monotherapy for AGIB. Eighteen centers across Europe and USA contributed to a registry between 2016 and 2022. Adults with AGIB were eligible, unless TC-325 was part of combined hemostasis. The primary endpoint was immediate hemostasis. Secondary outcomes were rebleeding and mortality. Associations with risk factors were investigated (statistical significance at P≤0.05). One hundred ninety patients were included (age 51-81 years, male: female 2:1), with peptic ulcer (n=48), upper GI malignancy (n=79), post-endoscopic treatment hemorrhage (n=37), and lower GI lesions (n=26). The primary outcome was recorded in 96.3% (95% confidence interval [CI]: 92.6-98.5) with rebleeding in 17.4% (95%CI 11.9-24.1); 9.9% (95%CI 5.8-15.6) died within 7 days, and 21.7% (95%CI 15.6-28.9) within 30 days. Regarding peptic ulcer, immediate hemostasis was achieved in 88% (95%CI 75-95), while 26% (95%CI 13-43) rebled. Higher ASA score was associated with mortality (OR 23.5, 95%CI 1.60-345; P=0.02). Immediate hemostasis was achieved in 100% of cases with malignancy and post-intervention bleeding, with rebleeding in 17% and 3.1%, respectively. Twenty-six patients received TC-325 for lower GI bleeding, and in all but one the primary outcome was achieved. TC-325 monotherapy is safe and effective, especially in malignancy or post-endoscopic intervention bleeding. In patients with peptic ulcer, it could be helpful when the primary treatment is unfeasible, as bridge to definite therapy.

Gastrointestinal malignancies in Zambia: a scoping review

Background&#x0D; Gastrointestinal (GI) malignancies account for greater than one-third of cancer-related deaths worldwide. In Zambia, there is a lack of data on epidemiology, diagnosis, management, and outcomes. We sought to review existing literature to determine the extent of research and identify gaps in knowledge pertaining to GI malignancies in Zambia.&#x0D; Methods&#x0D; We systematically searched databases including Ovid MEDLINE, CINAHL, Web of Science Core Collection, Cochrane Library via Ovid, Embase, Africa Wide Information via Ebsco, African Index Medicus and African Journals Online, to identify studies on GI malignancies including colorectal (CRC), pancreatic (PC), gastric (GC), esophageal (EC) and liver cancers (LC) in Zambia. &#x0D; Results&#x0D; Of 323 studies screened, 27 were included in the final analysis. The included studies assessed an individual GI cancer or more than one GI cancer as follows: GC only (n=10, 37%), EC only (n=5, 18%), LC only (n=5, 18%), CRC only (n=2, 7%), PC only (n=1, 4%), PC, CRC, EC, GC, LC combined (n=1, 4%), CRC, EC, GC, LC combined (n=1, 4%), CRC, EC, GC combined (n=1, 4%) and EC, GC combined (n=1, 4%). Gastric cancer was the most studied (n =14 articles), followed by esophageal (n=9 articles), liver cancer (n=7 articles), colorectal (n=5 articles) and pancreatic cancer (n=2 articles). &#x0D; Conclusion&#x0D; There is paucity of published data. Existing studies have focused mainly on prevalence and risk factors. Longitudinal studies examining incidence, prognosis and survival are needed. &#x0D; &#x0D; Keywords: Gastrointestinal cancer, Zambia, risk factors, management, clinical outcomes.&#x0D;

Nomogram for predicting neutropenia in patients with esophageal, gastric, or colorectal cancer treated by chemotherapy in the first cycle.

Development and validation of a predictive model including serum vitamin concentration to estimate the risk of chemotherapy-induced grade 3/4 neutropenia in esophageal cancer, gastric cancer, or colorectal cancer patients who receive the first cycle of chemotherapy. Data from 535 patients treated at the Affiliated Fuyang People's Hospital of Anhui Medical University from January 1, 2020, to March 2, 2022, were used to derive the predictive model. Least absolute shrinkage and selection operator regression analysis was performed to screen potential risk characteristics, and multivariate logistic regression was utilized to investigate efficient factors associated with chemotherapy-induced neutropenia. A nomogram was constructed using this logistic model. This nomogram was then tested on a temporal validation cohort containing 212 consecutive patients. In the cohort of all 747 eligible patients, grade 3/4 neutropenia incidence was 45.2%. Age, Eastern Cooperative Oncology Group-performance status, neutrophil count, serum albumin, and hemoglobin data were entered into the final model. The performance of the final predictive nomogram was assessed by the area under the receiver operating characteristic curve in both the development and validation datasets. The calibration curves indicated that the estimated risks were accurate. Decision curve analysis for the predictive model exhibited improved clinical practicality. In the present study, we established an accessible risk predictive model and identified valuable serum vitamin concentration parameters associated with chemotherapy-induced neutropenia. The predictive model may improve the grade 3/4 neutropenia risk prediction in patients with gastrointestinal malignancies who receive oxaliplatin- and fluoropyrimidine-based chemotherapy and help physicians make appropriate decisions for disease management.

A New Era for Cholangiocarcinoma Therapy – Targeting Metabolic Enzymes

Cholangiocarcinoma (CCA) is a malignancy of the biliary tract epithelium and is the second most common primary liver tumor following hepatocellular carcinoma (HCC): it accounts for ~15% of primary liver cancers and ~3% of gastrointestinal malignancies. Due to late diagnoses, poor prognoses, and limited treatment strategies, CCA shows a dismal outcome with a less than 5% overall 5-year survival and only a median overall survival of ~7months. Moreover, epidemiological data show that the incidence (0.3–6 per 100,000) and mortality (1 -6 per 100,000) of CCA is increasing globally over recent decades. Cholangiocarcinoma (CCA) is associated with approximately 3,500 new cases, the second most common primary liver tumor in Germany. Cholangiocarcinoma (CCA) is classified into anatomic subtypes including intrahepatic CCA (iCCA), perihilar CCA (pCCA) and extrahepatic CCA (eCCA).

Unraveling Emerging Anal Cancer Clinical Biomarkers from Current Immuno-Oncogenomics Advances.

Anal squamous cell carcinoma (ASCC) is a rare gastrointestinal malignancy associated with high-risk human papillomavirus (HPV) and is currently one of the fastest-growing causes of cancer incidence and mortality in developed countries. Although next-generation sequencing technologies (NGS) have revolutionized cancer and immuno-genomic research in various tumor types, a limited amount of clinical research has been developed to investigate the expression and the functional characterization of genomic data in ASCC. Herein, we comprehensively assess recent advancements in "omics" research, including a systematic analysis of genome-based studies, aiming to identify the most relevant ASCC cancer driver gene expressions and their associated signaling pathways. We also highlight the most significant biomarkers associated with anal cancer progression, gene expression of potential diagnostic biomarkers, expression of therapeutic drug targets, and emerging treatment opportunities. This review stresses the urgent need for developing target-specific therapies in ASCC. By illuminating the molecular characteristics and drug-target expression in ASCC, this study aims to provide insights for the development of precision medicine in anal cancer.

Tumor cell dissociation‐enhanced intravesical chemotherapy of orthotopic bladder cancer

AbstractFrequent intravesical chemotherapy is still the adopted clinical option after bladder cancer surgery with low adhesion, poor selectivity, low permeability, and drug resistance. Herein, we develop an ingenious bladder cancer dissociation method to enhance intravesical chemotherapy and tumor self‐exclusion with urine. Ethylene diamine tetraacetic acid (EDTA), a common Ca2+ chelator, is loaded with the typical clinical bladder instillation drug doxorubicin (Dox) in chitosan‐modified hollow gold nanorods and subsequently coated with cancer cell membranes. After bladder perfusion, the nanoplatform exhibits high affinity toward bladder tumors under homologous targeting, assisting in long‐term retention. Under NIR‐II laser irradiation, the photothermal effect accelerates the unloading of cargo, and the released EDTA then disrupts intratumoral junctions by depriving and chelating Ca2+ from the intercellular calcium‐dependent connexin. The consequential intertumoral dissociation gives access to the deeper penetration of Dox and allows the exclusion of the shed small tumor masses from the body with the urine. This distinctive tumor dissociation concept holds great promise for modern clinical intravesical chemotherapy and perhaps for other gastrointestinal malignancies.

Oncolytic virus CF33-hNIS monotherapy for the treatment of gastrointestinal (GI) malignancies.

749 Background: CF33-hNIS is a novel chimeric DNA vaccinia virus engineered with the human sodium-iodide symporter (hNIS) gene. CF33-hNIS selectively replicates in tumor cells leading to cell lysis and the release of tumor- and virus-associated antigens stimulating antitumor immunity. Here, we report results of patients with GI malignancies enrolled on a first-in-human phase 1 ascending, multiple dose, safety and tolerability study of CF33-hNIS, administered intratumorally (IT) or intravenously (IV) in adult patients with metastatic or advanced solid tumors (MAST). Methods: The MAST study is evaluating the safety of CF33-hNIS administered IT or IV, alone or in combination with pembrolizumab in patients with advanced or metastatic solid tumors with ≥ 2 prior lines of therapy (NCT05346484). CF33-hNIS is administered in 21-day cycles on C1D1 and C1D8, then D1 of each cycle thereafter. Pembrolizumab begins C2D1 for the combination groups and is administered Q3W. The co-primary endpoints are safety and to identify the recommended phase 2 dose. Secondary endpoints include objective response rate according to RECIST v1.1 and iRECIST, and to assess levels of viral replication via Single-Photon Emission Computerized Tomography (SPECT) with technetium-99. Results: As of Aug 2023, we report early results from seven patients with GI malignancies who received CF33-hNIS alone, including: colorectal cancer (3), bile duct (2), pancreatic (1) and hepatocellular carcinoma (1). The disease control rate is 86%. Notably one patient with cholangiocarcinoma, treated IT with 3.0x107 PFU, presented with pseudoprogression with a 49% increase in tumor burden after two cycles of therapy. By the 4th cycle they achieved a complete response (CR) with no known recurrence. A second patient with bile duct cancer, who previously progressed on checkpoint blockade therapy, achieved stable disease for &gt;5 months upon receiving IV-administered CF33-hNIS (3.0x107 PFU). Treatment-related adverse events for the CR patient included grade 1 fever and injection site reaction. All other patients experienced no treatment-related adverse events. SPECT analysis of the CR patient reveals intense levels of viral replication within the injected lesion and a concomitant increase in Th1 cytokines in cycle three that coordinated with tumor reduction. In-depth immunological changes in peripheral blood and on-treatment tumor biopsies will be presented. Conclusions: CF33-hNIS can replicate within cholangiocarcinoma lesions, as shown by SPECT imaging, and drive immunological changes known to promote antitumor immunity. CF33-hNIS monotherapy may be an effective and safe treatment option for GI malignancies, including cholangiocarcinoma, a rare disease with an unmet medical need. Treatment with CF33-hNIS monotherapy was well tolerated and the study has advanced to examine combination therapy with pembrolizumab. Clinical trial information: NCT05346484 .

Prognostic impact of ectopic fat deposition within psoas muscle in patients undergoing systemic chemotherapy for stage IV gastric cancer.

285 Background: Sarcopenia is a progressive condition characterized by loss of skeletal muscle mass, muscle strength, and physical function, and is identified as an important prognostic factor in malignant tumors. The patients of gastrointestinal (GI) malignancies are often poor nutrition, weight loss, and loss of skeletal muscle mass due to pathophysiology such as the dysfunction of nutritional absorption and GI obstruction. The prevalence of sarcopenia is high in GI malignancies, especially in advanced gastric cancer (GC), which is reported to be 30%. Recently, in assessing sarcopenia, muscle quality as well as skeletal muscle mass has been considered important and some studies suggest that intramuscular adipose tissue is useful in assessing muscle quality. In this study, we focused on the fat ratio within psoas muscle (FRPM) and sought to clarify the impact of FRPM on overall survival (OS) in GC patients undergoing systemic chemotherapy. Methods: We retrospectively analyzed the patients with histologically confirmed stage IV GC receiving at least one systemic chemotherapy between February 2017 and March 2021 in our hospital. We measured PMI (Psoas Muscle Index: bilateral muscle mass (cm2)/height squared(m2)) and FRPM both at the lumber three level on the CT images before chemotherapy. PMI and FRPM values were classified into two groups, High and Low, according to whether they were higher or lower than the median, and differences in OS were analyzed for each group. Results: The analysis included 79patients (median age: 69 years, 59 males). The median FRPM was 1.67%. The FRPM-high group and the FRPM-low group were 40/39patients, respectively. The median PMI in male and female patients was 4.35 cm2/m2 and 2.88 cm2/m2. Thirty male patients and ten female patients were defined as the PMI-high group, and the remaining 39 patients were in the PMI-low group. The 1, 2 and 3year cumulative OS rate in patients with FRPM-high and FRPM-low was 67.3%, 14.3% and 7.6% in the FRPM-high group and 74.8%, 40.5% and 32.4% in the FRPM-low group ( P = 0.0341). The 1, 2 and 3year cumulative OS rate in patients with PMI-high and PMI-low was 86.7%, 40.4% and 30.0% in the PMI-high group and 55.8%, 12.8% and 6.4% in the PMI-low group ( P &lt; 0.0001). In the multivariate analysis of factors associated with OS, PMI ( P = 0.0047) and FRPM ( P = 0.0019) were independent predictors for the OS. Conclusions: High-FRPM may be associated with declined physical activity, suggesting that skeletal muscle function may be an important prognostic factor in patients with GC receiving systemic chemotherapy.

Oxaliplatin desensitization in patients with GI malignancies: Experience from a tertiary cancer center.

89 Background: Oxaliplatin hypersensitivity is not uncommon in patients with gastrointestinal (GI) cancers receiving chemotherapy. The use of oral premeditations (dexamethasone, cetirizine and famotidine) starting 24 hours before treatment and continuing for a total of three days, further intravenous premedication (dexamethasone, chlorphenamine and famotidine) 30 minutes before treatment and the gradual administration of oxaliplatin over 6.5 hours in four separate escalating doses (desensitisation protocol) is commonly used in such cases. While desensitisation is an option, especially in severe cases, responses and survival outcomes upon rechallenge are not well described. Methods: A retrospective chart review of patients with various GI malignancies who received oxaliplatin-based desensitisation chemotherapy after a severe drug reaction between October 2019 and October 2022 at a single cancer centre was performed. Clinicopathological characteristics and oncological outcomes were assessed. Results: Forty-four patients with a median age of 61 years (range 38-81) were studied. The majority had a diagnosis of CRC (n=22; 50%), followed by oesophago-gastric (n=19; 4%), appendiceal (n=1), cholangiocarcinoma (n=1), and cancer of unknown primary (n=1). More than two thirds of patients (n=32, 73%) were treated with palliative intent. The most common regimens associated with oxaliplatin hypersensitivity reactions after a median of 3 cycles (range 1-10) were FOLFOX (n=24, 55%), CAPOX (n=18, 41%), FLOT (n=1) and FOLFOXIRI (n=1). Seven patients (16%) had another reaction after desensitisation, leading to discontinuation of treatment. Thirty-seven patients (84%) completed treatment as planned. Treatment outcomes after desensitisation included 5 (11%) patients with no evidence of disease (NED) after adjuvant treatment, 16 (37%) patients with disease control, including 3 (7%) partial responders (PR) and 13 (30%) patients with stable disease (SD), and 23 (52%) patients with progressive disease (PD). Conclusions: Oxaliplatin desensitisation is feasible with low discontinuation rates and leads to acceptable oncological outcomes. All patients should be offered desensitisation to allow continuation of active systemic therapy.

Evaluation of a real-world clinico-genomics database of patients with upper gastrointestinal (GI) malignancies in Japan.

400 Background: The genomic profile of gastrointestinal (GI) cancers provides essential information for precision medicine, however, there is limited availability of real-world data in Asian populations as they are not well-represented in most publicly accessible clinico-genomic databases. In this retrospective study, we evaluated the clinical and genomic characteristics of upper GI cancer patients in the database from an academia-industry collaborative nationwide cancer genome screening project in Japan. Methods: The Screening Projectfor Individualized Medicine in Japan (J-SCRUM) GI-SCREEN enrolled advanced GI cancer patients from 26 sites before planned or during systemic therapy from 2015 to 2019. Archived formalin-fixed paraffin-embedded tumor tissue was analyzed by next-generation sequencing (NGS) using Oncomine Cancer Research Panel and Oncomine Comprehensive Assay. Patients with gastric (GC), esophageal (EC) and pancreatic (PC) cancers were identified in the database. The frequency of key actionable genomic alterations in each cancer cohort was explored and compared to similar upper GI cohorts in The Cancer Genome Atlas (TCGA), a publicly available genomics database initiated in 2005 and concluded sample collection in 2013 with most samples from White cancer patients. Results: A total of 872 GC (mean age at registration [SD]: 64y [12]; percent males: 65%), 265 EC (64y [9]; 78%) and 495 PC (64y [10]; 60%) patients were identified. The majority (&gt;70%) of samples were obtained from primary sites. Adenocarcinoma was the most common histological type for GC (85%) ad PC (76%), while squamous cell (76%) was the most common among EC patients. In the GC cohort, the prevalence of key actionable genomic alterations in J-SCRUM GI-SCREEN vs TCGA (N = 380) was, TP53 mutation (49% vs 49%), ERBB2 amplification (14% vs 13%), PIK3CA mutation (11% vs 14%), MYC amplification (9% vs 12%) and MET amplification (2% vs 3%). In the EC cohort, the prevalence in J-SCRUM vs TCGA (N = 182) was TP53 mutation (77% vs 87%), NFE2L2 mutation (21% vs 10%), PIK3CA mutation (9% vs 9%) and CDKN2A mutation (8% vs 8%). In the PC cohort, the prevalence in J-SCRUM vs TCGA (N = 150) was KRAS hotspot mutation (90% vs 93%), KRAS G12D (43% vs 41%), KRAS G12V (32% vs27%), TP53 mutation (58% vs 64%), BRCA1/2 deleterious mutation (5% vs 5%), ATM deleterious mutation (6% vs 5%) and MYC amplification (5% vs 5%). Conclusions: As part of a nationwide cancer genome screening project, J-SCRUM GI SCREEN database provides comprehensive genomic information for Asian population (Japan). The prevalence of key actionable gene alterations in each tumor type was highly comparable between J-SCRUM GI-SCREEN and TCGA data.