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Background: The long-term impact of tyrosine kinase inhibitor (TKI) discontinuation on resistance and survival in patients with advanced gastrointestinal stromal tumours (GIST) is unclear. We report the exploratory long-term outcomes of patients with advanced GIST stopping imatinib in the BFR14 trial., Methods: BFR14, an open-label, randomised, phase 3 trial, was done in 17 comprehensive cancer centres or hospitals across France. Patients with advanced GIST aged 18 years or older with an Eastern Cooperative Oncology Group performance status of 0-3, no previous treatment with imatinib, and no previous malignancy were eligible. Patients were treated with oral imatinib 400 mg daily. Patients with a complete or partial response, or stable disease, according to Response Evaluation Criteria in Solid Tumours (1.0) at 1 year, 3 years, and 5 years from the start of treatment were randomly assigned (1:1) to treatment discontinuation until progression (interruption group) or treatment continuation until progression (continuation group). Randomisation was done centrally with computer-generated permuted blocks of two and six patients stratified by participating centre and presence or absence of residual disease on CT scan. The primary endpoint was progression-free survival. Secondary endpoints included time to imatinib resistance and overall survival. Analyses were conducted on an intention-to-treat basis in all randomly assigned patients who were not lost to follow-up. This trial is registered with ClinicalTrial.gov, NCT00367861., Findings: Between May 12, 2003, and March 16, 2004, after 1 year of imatinib, 32 patients were randomly assigned to the interruption group and 26 to the continuation group. Between June 13, 2005, and May 30, 2007, after 3 years of imatinib, 25 patients were randomly assigned to the interruption group and 25 to the continuation group. Between Nov 9, 2007, and July 12, 2010, after 5 years of imatinib, 14 patients were randomly assigned to the interruption group and 13 to the continuation group. Median follow-up was 235·2 months (IQR 128·8-236·6) after the 1-year randomisation, 200·9 months (190·2-208·4) after the 3-year randomisation, and 164·5 months (134·4-176·4) after the 5-year randomisation. Median progression-free survival in the interruption group versus the continuation group after 1 year of imatinib was 6·1 months (95% CI 2·5-10·1) versus 27·8 months (19·5-37·9; hazard ratio [HR] 0·36 [95% CI 0·20-0·64], log-rank p=0·0003), after 3 years of imatinib was 7·0 months (3·5-11·7) versus 67·0 months (48·8-85·6; 0·15 [0·07-0·32], log-rank p<0·0001), and after 5 years of imatinib was 12·0 months (9·0-16·6) versus not reached (NR; NR-NR; 0·13 [0·03-0·58], log-rank p=0·0016). The median time to imatinib resistance after 1 year of imatinib was 28·7 months (95% CI 18·1-39·1) versus 90·6 months (25·3-156·1; HR 0·93 [95% CI 0·51-1·71], log-rank p=0·82), after 3 years was 66·2 months (43·0-89·6) versus 127·3 months (15·0-239·7; 0·35 [0·17-0·72, log-rank p=0·0028), and after 5 years was 58·6 months (0·0-167·4) versus NR (NR-NR; 0·24 [0·05-1·12], log-rank p=0·049). Median overall survival after 1 year of imatinib was 56·0 months (95% CI 30·3-82·9) versus 105·0 months (20·6-189·6; HR 0·84 [95% CI 0·46-1·54], log-rank p=0·57), after 3 years was 104·0 months (90·7-118·7) versus 134·0 months (89·7-178·3; 0·40 [0·20-0·82], log-rank p=0·0096), and after 5 years was NR (NR-NR) versus 110·4 months (82·7-154·1; 1·28 [0·41-3·99]; log-rank p=0·67), INTERPRETATION: Imatinib interruption in patients with GIST without progressive disease is not recommended. Imatinib interruption in non-progressing patients with GIST was associated with rapid progression, faster resistance to imatinib, and shorter overall survival in the long-term follow-up when compared with imatinib continuation in patients after 3 years and 5 years of imatinib., Funding: Centre Léon Bérard, INCa, CONTICANET, Ligue Contre le Cancer, and Novartis., Competing Interests: Declaration of interests J-YB reports grants from NETSARC+, INTERSARC+, and LYRICAN+ from INCA (to the institution), DEpGyn RHU and LYRICAN+ from the Agence Nationale de la Recherche (to the institution), and ERN EURACAN from the EU commission (to the institution); research support from Novartis, Deciphera, and Bayer (to the institution); membership of steering committees for the Intrigue and Motion studies for Deciphera; and membership of the supervisory boards of Transgène and Innate Pharma. IR-C reports research grants from Bristol Myers Squibb (BMS); consulting fees from and participation on data safety boards of Adaptimmune, Agenus, Amgen, AstraZeneca, BMS, Clovis, Daiichi Sankyo, Deciphera, Eisai, EQRX, GSK, MacroGenics, Merck Serono, Mersana, MSD, Novartis, Onxeo, Roche, and Sutro Biopharma. NP reports research grants from Bayer. DP reports travel grants from Roche and Novartis. ALC reports honoraria from Deciphera and Pharmamar. All other authors declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

Background: The controlled nutritional status score (CONUT) and handgrip strength (HGS) were both predictive indexes for the prognosis of cancers. However, the combination of CONUT and HGS for predicting the prognosis of gastrointestinal cancer had not been developed. This study aimed to explore the combination of CONUT and HGS as the potential predictive prognosis in patients with gastric and colorectal cancer., Methods: A cohort study was conducted with gastric and colorectal cancer patients in multicenter in China. Based on the optimal HGS cutoff value for different sex, the HGS cutoff value was determined. The patients were divided into high and low HGS groups based on their HGS scores. A CONUT score of 4 or less was defined as a low CONUT, whereas scores higher than 4 were defined as high CONUT. The Kaplan-Meier method was used to create survival curves, and the log-rank test was used to compare time-event relationships between groups. A Cox proportional hazard regression model was used to determine independent risk factors for overall survival (OS)., Results: A total 2177 gastric and colorectal patients were enrolled in this study, in which 1391 (63.9%) were men (mean [SD] age, 66.11 [11.60] years). Multivariate analysis revealed that patients with high HGS had a lower risk of death than those with low HGS (hazard ratio [HR],0.87; 95% confidence interval [CI], 0.753-1.006, P = 0.06), while high CONUT had a higher risk of death than those with low CONUT (HR, 1.476; 95% CI, 1.227-1.777, P < 0.001). Patients with both low HGS and high CONUT had 1.712 fold increased risk of death (HR, 1.712; 95% CI, 1.364-2.15, P < 0.001). Moreover, cancer type and sex were stratified and found that patients with high CONUT and low HGS had lower survival rate than those with low CONUT and high HGS in both gastric or colorectal cancer, and both male and female., Conclusion: A combination of low HGS and high CONUT was associated with poor prognosis in patients with gastrointestinal cancer, which could probably predict the prognosis of gastrointestinal cancer more accurate than HGS or CONUT alone., Competing Interests: Conflict of interest All authors declare no conflicts of interest., (Copyright © 2024 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Objectives: The aim of this study was to investigate the relationship among phase angle (PA), malnutrition, and prognosis in patients with gastrointestinal cancer., Methods: In total, 870 patients with gastrointestinal cancer were enrolled. Kaplan-Meier curves and Cox proportional hazards models were used to evaluate the association between PA and survival risk. Restricted cubic spline regression was used for flexibility analysis to explore sex-specific associations between PA and survival. Logistic regression was used to assess the relationships among PA, malnutrition, and cachexia., Results: Low PA was closely associated with poor physical conditions, diminished quality of life, and malnutrition. Patients with low PA had a significantly worse prognosis than those with high PA (60.6% versus 72.8%; log-rank P < 0.001). PA was suitable for the prognostic assessment of patients with advanced-stage tumors. Regardless of sex, patients with lower PA showed significantly poorer survival rates. Cox proportional hazards models identified PA as an independent predictor of prognosis in patients with gastrointestinal cancer (hazard ratio (HR)=0.534; 95% confidence interval (CI)=0.409-0.696, P < 0.001). Subgroup analysis indicated that a high PA was an independent risk factor affecting the prognoses of patients with esophageal, liver, and intrahepatic bile duct cancers. Interestingly, variations in PA had a more significant prognostic effect on survival in men than in women. The logistic regression model confirmed that PA is a valuable indicator for assessing malnutrition and cachexia in patients with gastrointestinal cancer. Among all body composition indicators, PA demonstrated the highest accuracy for prognostic prediction., Conclusions: PA was identified as a robust predictor of malnutrition and poor prognosis in patients with gastrointestinal cancer., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background & Aims: We investigated the benefit-risk profile of aspirin on mortality reduction from chemoprevention of gastrointestinal (GI) cancer vs excess mortality from bleeding among Helicobacter pylori-eradicated patients, and its interaction with proton pump inhibitors (PPIs)., Methods: H pylori-eradicated patients (between 2003 and 2016), identified from a territory-wide database, were observed from the date of H pylori therapy until death or the end of the study (July 2020). Primary exposure was aspirin use as time-varying variable. The primary outcome was GI cancer-related (gastrointestinal, hepatobiliary, or pancreatic cancer) death and the secondary outcome was bleeding-related (gastrointestinal bleeding or intracranial bleeding) death. The adjusted hazard ratio (aHR) of outcomes was calculated by multivariable Cox model after adjusting for age, sex, comorbidities, and concomitant medications. The benefit-risk profile was expressed as the adjusted absolute risk difference of cancer-related deaths and bleeding-related deaths between aspirin users and nonusers., Results: A total of 87,967 subjects were followed up for a median of 10.1 years, with 1294 (1.5%) GI cancer-related deaths and 304 (0.3%) bleeding-related deaths. Aspirin was associated with lower GI cancer-related mortality (aHR, 0.51; 95% CI, 0.42-0.61), but higher bleeding-related mortality (aHR, 1.52; 95% CI, 1.11-2.08). Among PPI users, the aHR of bleeding-related mortality with aspirin was 1.06 (95% CI, 0.70-1.63). For the whole cohort, the adjusted absolute risk difference between aspirin users and nonusers was 7 (95% CI, 5-8) fewer cancer-related and 1 (95% CI, 0.3-3) more bleeding-related death per 10,000 person-years. Among concomitant PPI-aspirin use, there were 9 (95% CI, 8-10) fewer cancer-related deaths per 10,000 person-years without an increase in bleeding-related deaths., Conclusions: GI cancer mortality benefit from aspirin outweighs bleeding-related mortality in H pylori-eradicated subjects, which is enhanced further by PPI use., (Copyright © 2024 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Purpose: The cachexia index is a novel biomarker of cancer cachexia. This systematic review and meta-analysis aimed to evaluate the prognostic impact of cachexia index on prognosis after surgery for gastrointestinal cancer., Methods: In August 2023, we systematically searched PubMed, the Cochrane Library, and Ovid for relevant studies on the oncological outcome after gastrointestinal cancer surgery and analyzed the findings from these studies for meta-analysis., Results: Our systematic and meta-analysis review identified eight studies involving 1876 patients. The number of patients with low cachexia index accounted for 813 patients (43.3%). We found that low cachexia index was associated with worse overall survival (pooled HR, 2.30; 95% CI, 1.85-2.87; z = 7.49; P < 0.001) and disease/relapse/progression-free survival (pooled HR, 1.77; 95% CI, 1.45-2.18; z = 5.50; P < 0.001)., Conclusion: Our meta-analysis showed that cachexia index was associated with oncological outcome after gastrointestinal cancer surgery. However, the limitations of this meta-analysis should be taken into consideration when interpreting the results., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Currently, due to limited long-term evidence, there remains some controversy surrounding the recommended postoperative monitoring strategy for primary low-risk gastrointestinal stromal tumors (GISTs). This study recruited a total of 532 patients diagnosed with very low-risk and low-risk GISTs who underwent endoscopic resection from 2015 to 2021, including 460 very low-risk patients and 72 low-risk patients. Descriptive statistical analysis was used to evaluate the clinical and pathological characteristics of GIST patients, and Kaplan-Meier methods were employed for survival analysis. The results showed that the 5-year recurrence-free survival rates for very low-risk and low-risk patients were 98.5% and 95.9%, respectively. The 5-year disease-specific survival rates for both groups were 100%. Additionally, the 5-year overall survival rates were 99.7% for very low-risk patients and 100% for low-risk patients (P = 0.69). Therefore, it is suggested that routine follow-up monitoring, including endoscopic surveillance and imaging, may not be necessary for very low-risk and low-risk GISTs after endoscopic resection., (© 2024. The Author(s).)

Importance: The incidence of gastrointestinal stromal tumors (GISTs) increased after the implementation of GIST-specific histology coding in 2001, but updated data on trends and survival are lacking., Objective: To examine the evolving epidemiology of GISTs in major organ sites., Design, Setting, and Participants: This descriptive, population-based cohort study used nationally representative data from the National Cancer Institute Surveillance, Epidemiology, and End Results (SEER) Program, including the SEER-22 and SEER-17 registries. Data were from evaluated patients aged 20 years or older with GISTs diagnosed between January 1, 2000, and December 31, 2019. Analyses were last updated on October 29, 2023., Main Outcomes and Measures: Organ site-specific trends in age-standardized incidence rates and annual percent changes (APCs) in rates were estimated by race and ethnicity and, when possible, by sex, age, and primary indicator. Multivariable Cox proportional hazards regression models were used to examine racial and ethnic differences in overall and GIST-specific survival by site., Results: The SEER-22 and SEER-17 datasets contained 23 001 and 12 109 case patients with GISTs, respectively. Patients in the SEER-22 registry had a mean (SD) age of 64 (13) years and 51.3% were men. With regard to race and ethnicity, 9.7% of patients were Asian or Pacific Islander, 12.3% were Hispanic, 19.6% were non-Hispanic Black, and 57.7% were non-Hispanic White. Overall incidence rates of GISTs in the SEER-22 cohort increased substantially over time for all organ sites but the colon (APCs: esophagus, 7.3% [95% CI, 4.4% to 10.2%]; gastric, 5.1% [95% CI, 4.2% to 6.1%]; small intestine, 2.7% [95% CI, 1.8% to 3.7%]; colon, -0.2% [95% CI, -1.3% to 0.9%]; and rectum, 1.9% [95% CI, 0.1% to 3.8%]). There were similar increasing trends by age groups (<50 vs ≥50 years), sex, race and ethnicity, and primary indicator for gastric and small intestine GISTs. Increases were mainly restricted to localized stage disease. Patients in the SEER-17 cohort had a mean (SD) age of 64 (14) years and 51.9% were men. With regard to race and ethnicity, 13.3% of patients were Asian or Pacific Islander, 11.6% were Hispanic, 17.8% were non-Hispanic Black, and 56.6% were non-Hispanic White. Non-Hispanic Black individuals had higher overall mortality for esophageal (adjusted hazard ratio [HR], 6.4 [95% CI, 2.0 to 20.3]) and gastric (adjusted HR, 1.4 [95% CI, 1.2 to 1.5]) GISTs compared with non-Hispanic White individuals. Asian or Pacific Islander individuals also had higher overall mortality for esophageal GISTs (adjusted HR, 5.6 [95% CI, 1.5 to 20.2]). Results were similar for GIST-specific survival., Conclusions and Relevance: In this cohort study using SEER data, the incidence of GISTs in major organ sites increased in the last 2 decades among several population groups. These findings suggest that additional studies are warranted to identify risk factors, because histologic reclassification and higher availability of endoscopy and imaging do not fully explain these unfavorable incidence trends. Prevention efforts are needed to reduce the substantial survival disparities among racial and ethnic minoritized populations.

Introduction: Current strategies for upper gastrointestinal (UGI) cancer screening primarily target cancer-specific risk, with the strongest focus on esophageal adenocarcinoma (EAC). However, all UGI cancers are amendable to screening and early detection with an upper endoscopic examination. This study assesses and explores incidence-based mortality (IBM) for cumulative UGI cancers, aiming to identify race-based or sex-based disparities., Methods: We used Surveillance, Epidemiology, and End Results Research data to analyze patients diagnosed with EAC, esophageal squamous cell carcinoma, cardia gastric cancer, noncardia gastric cancer, or colorectal adenocarcinoma from 2000 to 2019. Age-adjusted IBM was calculated as a rate per 100,000 population and stratified by sex and race/ethnicity. We also compared UGI cancer IBM with that of colorectal cancer, a cancer with established population-wide endoscopic screening guidelines., Results: Cumulative IBM for UGI cancers was 8.40 (95% confidence interval [CI] 8.34-8.46). The highest cancer-specific IBM rates were for EAC (2.26, 95% CI 2.23-2.29), followed by noncardia gastric cancer (2.07, 95% CI 2.04-2.10), cardia gastric cancer (1.60, 95% CI 1.57-1.62), esophageal squamous cell carcinoma (1.21, 95% CI 1.19-1.23), and miscellaneous UGI cancer (1.27, 95% CI 1.13-1.40). UGI cancer IBM was highest among Black men (16.43, 95% CI 15.97-16.89), American Indian/Alaska Native men (15.23, 95% CI 13.75-16.82), and Hispanic men (13.76, 95% CI 13.42-14.11). These rates are significantly greater than among White men (12.81, 95% CI 12.68-12.95)., Discussion: UGI cancers impose a significantly higher mortality burden on non-White population subgroups that are not currently targeted by any systematic screening approach., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The American College of Gastroenterology.)

Background: This study aimed to evaluate if combining low muscle mass with additional body composition abnormalities, such as myosteatosis or adiposity, could improve survival prediction accuracy in a large cohort of gastrointestinal and genitourinary malignancies., Methods: In total, 2015 patients with surgically-treated gastrointestinal or genitourinary cancer were retrospectively analyzed. Skeletal muscle index, skeletal muscle radiodensity, and visceral/subcutaneous adipose tissue index were determined. The primary outcome was overall survival determined by hospital records. Multivariate Cox hazard models were used to identify independent predictors for poor survival. C-statistics were assessed to quantify the prognostic capability of the models with or without incorporating body composition parameters., Results: Survival curves were significantly demarcated by all 4 measures. Skeletal muscle radiodensity was associated with non-cancer-related deaths but not with cancer-specific survival. The survival outcome of patients with low skeletal muscle index was poor (5-year OS; 65.2%), especially when present in combination with low skeletal muscle radiodensity (5-year overall survival; 50.2%). All examined body composition parameters were independent predictors of lower overall survival. The model for predicting overall survival without incorporating body composition parameters had a c-index of 0.68 but increased to 0.71 with the inclusion of low skeletal muscle index and 0.72 when incorporating both low skeletal muscle index and low skeletal muscle radiodensity/visceral adipose tissue index/subcutaneous adipose tissue index., Conclusion: Patients exhibiting both low skeletal muscle index and other body composition abnormalities, particularly low skeletal muscle radiodensity, had poorer overall survival. Models incorporating multiple body composition prove valuable for mortality prediction in oncology settings., (© 2024 The Author(s). Journal of Parenteral and Enteral Nutrition published by Wiley Periodicals LLC on behalf of American Society for Parenteral and Enteral Nutrition.)

Purpose: This study aimed to assess the efficacy of surgery as a treatment option for patients with signet-ring cell carcinoma (SRCC) in the gastrointestinal tract (GI-SRCC)., Methods: Using the Surveillance, Epidemiology, and End Results database, patients with GI-SRCC who underwent surgery or received nonsurgical treatment were included. Propensity score matching (PSM) analysis was used to balance baseline characteristics and reduce bias. Overall survival (OS) was calculated in matching cohorts to estimate prognosis for patients with GI-SRCC. Nomogram was established to predict metastasis for patients with GI-SRCC., Results: The study enrolled a total of 9428 patients with GI-SRCC, with 1689 patients in the nonsurgery group and 7739 patients in the surgery group. After 1:1 PSM, we analyzed 743 patients from each group. Our survival analyses revealed that surgery independently correlated with improved OS for patients with GI-SRCC (hazard ratio, 0.37; 95% CI, 0.33-0.42; P < .001). Subgroup analysis further confirmed the positive impact of surgery on the prognosis of patients with nonmetastatic GI-SRCC. Notably, distinct subsets of patients with metastasis, particularly those originating from the upper GI (esophagus, proximal stomach, and distal stomach) and left colon, demonstrated a significant improvement in OS after surgery. However, no significant survival difference was observed for patients with metastatic right colon and rectum SRCC. Using nomogram, we quantitatively assessed the risk of metastasis in patients with right colon and rectum SRCC, which exhibited robust predictive accuracy, with area under the curve values of 0.829., Conclusion: Our study highlighted surgery's positive impact on prognosis for both patients with nonmetastatic and metastatic upper GI-SRCC and left colon SRCC. Hence, we recommend surgery as a treatment option for these groups. In addition, for patients with metastatic right colon and rectum SRCC ineligible for surgery, our predictive nomogram can offer a convenient tool to aid early intervention and improve prognosis., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2024 Society for Surgery of the Alimentary Tract. Published by Elsevier Inc. All rights reserved.)

Background: Controversy surrounds the indications for endoscopic treatment (ET) versus surgery in addressing gastrointestinal neuroendocrine neoplasms (GI-NENs). This paper aims to compare the long-term survival prognosis between ET and surgery for patients with GI-NENs., Methods: A retrospective analysis of GI-NEN patients diagnosed between 2000 and 2020 was conducted using the SEER database. Overall survival (OS) and cancer-specific survival (CSS) were estimated using the Kaplan-Meier method. Prognostic factors were assessed through univariate and multivariate Cox regression analyses. Propensity score matching (PSM) was employed to adjust for clinical variables., Results: This study encompassed 12,016 patients with GI-NENs, with 3732 patients (31.1%) undergoing ET and 8284 patients (68.9%) opting for surgery. The rectum was the most frequent location for ET, while the small bowel was the predominant site for surgery. Both the ET and surgical groups exhibited similar overall survival risk and cancer-specific survival risk before and after matching. No significant differences in the 1-year, 3-year, 5-year, and 10-year OS and CSS rates were observed between the ET and surgery groups after PSM. Nevertheless, subgroup analysis revealed a significantly better CSS in the ET group than the surgery group, particularly in stage I and tumors sized <10mm ( P <0.01). In the colon subgroup, the OS and CSS of the ET group were superior to those of the surgery group ( P <0.05)., Conclusion: Endoscopic treatment and surgery demonstrate comparable long-term survival prognoses for treating GI-NENs. ET emerges as a viable option for patients averse to surgical interventions., Competing Interests: The authors declare no conflicts of interest, (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Objectives: Gastrointestinal large cell neuroendocrine carcinoma (GILCNEC) has a low incidence but high malignancy and poor prognosis. The main purpose of this study was to thoroughly investigate its clinicopathological features, survival and prognostic factors., Methods: Information on patients with GILCNEC was extracted from the Surveillance, Epidemiology, and End Result program, and prognostic factors were analyzed by analyzing clinicopathological data and survival functions. Finally, multivariate analysis was applied to identify independent risk factors associated with survival., Results: A total of 531 individuals were screened in our study from the Surveillance, Epidemiology, and End Result database. The primary sites are mainly from the following: esophagus in 39 (7.3%) patients, stomach in 72 (13.6%) patients, hepatobiliary in 51 (9.6%) patients, pancreas in 97 (18.3%) patients, small intestines in 27 (5.1%), and colorectum in 245 (46.1%) patients. Esophagus, stomach, pancreas, and colorectum large cell neuroendocrine carcinoma (LCNEC) were more common in males ( P = 0.001). Esophagus LCNEC had inferior overall survival (OS), whereas small intestine LCNEC was associated with better OS. The results of multivariate analysis showed that the American Joint Committee on Cancer Sixth Edition stage, surgery, and radiotherapy were independent prognostic indicators of OS in patients with GILCNEC ( P < 0.05)., Conclusions: The prognosis of patients with GILCNEC varies depending on the primary tumor site. American Joint Committee on Cancer Sixth Edition stage, surgery, and radiotherapy are independent prognostic factors of patients with GILCNEC. Although surgery and radiotherapy can prolong the survival of patients with GILCNEC, their prognosis remains poor, and further prospectively designed multicenter clinical studies are needed to indicate the decision for clinicians., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Most gastrointestinal stromal tumors (GISTs) harbor c-KIT or PDGFRA mutations. Administration of tyrosine kinase inhibitors (TKIs) has significantly improved the survival of patients with GISTs. We aimed to evaluate the clinical outcome of advanced or recurrent GIST patients in Taiwan., Methods: Patients diagnosed between 2010 and 2020 were enrolled. The collected data included baseline characteristics, treatment pattern, treatment outcome, genetic aberrations and survival status. Progression-free survival (PFS) and overall survival (OS) were analyzed and plotted with the Kaplan-Meier method. Cox regression analysis was used to analyze the prognostic factors of survival., Results: A total of 224 patients with advanced or recurrent GISTs treated with TKIs were enrolled. All patients received imatinib treatment. Ninety-three and 42 patients received sunitinib and regorafenib treatment, respectively. The 48-month PFS and OS rates for patients treated with imatinib were 50.5% and 79.5%, respectively. c-KIT exon 9 and PDGFRA mutations were prognostic factors for a poor PFS and PDGFRA mutation was a prognostic factor for a poor OS in patients treated with imatinib in multivariate Cox regression analysis. The median PFS of patients who received sunitinib treatment was 12.76 months (95% confidence interval (CI), 11.01-14.52). Patients with c-KIT exon 9 mutations had a longer PFS than those with other genetic aberrations. The median PFS of patients treated with regorafenib was 7.14 months (95% CI, 3.39-10.89)., Conclusions: We present real-world clinical outcomes for advanced GIST patients treated with TKIs and identify mutational status as an independent prognostic factor for patient survival., (© 2024. The Author(s).)

Background: Sarcopenic obesity (SO) in patients with gastrointestinal cancer is associated with a poor prognosis. We aimed to investigate the prognostic impact of SO in patients with gastrointestinal cancer, as well as the diagnostic cut-off value of SO in patients with gastrointestinal cancer among Chinese population., Methods: We conducted a consecutive cohort study. Between January 2017 and January 2019, 289 patients diagnosed with gastrointestinal cancer were included in our study. Skeletal muscle area, total fat area, and subcutaneous fat area were measured by CT scan. All patients were followed up for 5 years. Receiver operating characteristic curves (ROC) were adopted to determine the cut-off values of visceral fat obesity for the prediction of sarcopenia. Based on the cut-off values, patients with sarcopenia combined with visceral fat obesity were divided into the SO group, and the others were divided into the non-sarcopenic obesity (NSO) group. Kaplan-Meier curves and univariate and multivariate Cox proportional hazard models were employed to explore the associations of body composition profiles with 5-year overall survival and disease-specific survival., Results: Obtained from Youden's Index for ROC for the prediction of 5-year survival, skeletal muscle mass index (SMI) ≤40.02 cm 2 /m 2 with VFA ≥ 126.30 cm 2 in men and SMI ≤32.05 cm 2 /m 2 with VFA ≥72.42 cm 2 in women indicate a risk of poor prognosis in patients diagnosed with gastrointestinal cancer. Patients with SO had poorer 5-year overall survival (OS) than patients with NSO (6.74% vs. 82.84%, p < 0.001), and poorer 5-year DFS (6.74% vs. 81.82%, p < 0.001). In multivariate analysis, we found that the long-term mortality risk was approximately 13-fold higher among patients in the SO group compared to those with no conditions., Conclusions: Preoperative assessment of SO is useful not only for monitoring nutritional status but also for predicting 5-year OS in gastrointestinal cancer patients., (© 2024 The Author(s). Cancer Medicine published by John Wiley & Sons Ltd.)

Introduction: Patients with high-risk resected gastrointestinal stromal tumors (GIST) receiving adjuvant imatinib have improved recurrence-free survival (RFS), however whether a complete cytocidal effect exists is unknown. We investigated this using a normalized recurrence timeline measured from end of oncologic treatment (EOOT), defined as the later of resection or end of adjuvant therapy., Methods: We reviewed patients with resected high-risk GIST at our cancer center from 2003 to 2018. RFS (measured from resection and EOOT), overall survival (OS), and time to imatinib resistance (TTIR) were analyzed using Kaplan-Meier analysis and multivariable Cox proportional hazards modeling. The performance of the Memorial Sloan Kettering (MSK) GIST nomogram was assessed., Results: We identified 86 patients with high-risk GIST with a median 106 months of postsurgical follow-up. One-third (n = 29; 34%) did not receive adjuvant imatinib, while 57 (66%) did for a median of 3 years. The MSK nomogram-predicted 5-year RFS for patients receiving adjuvant imatinib was similar to those who did not (29% vs. 31%, p = 0.64). When RFS was measured from EOOT, the MSK-predicted RFS was independently associated with EOOT RFS (hazard ratio 0.22, p = 0.02), while adjuvant imatinib receipt and duration were not. Neither receipt nor duration of adjuvant imatinib were associated with TTIR or OS (all p > 0.05)., Conclusions: Treatment with adjuvant imatinib delays, but does not clearly impact ultimate recurrence, TTIR, or OS, suggesting many patients with high-risk GIST may receive adjuvant imatinib unnecessarily. Additional studies are needed to establish the benefit of adjuvant therapy versus initiating therapy at first radiographic recurrence., (© 2024 Wiley Periodicals LLC.)

Background: Patients with ruptured gastrointestinal stromal tumour (GIST) have poor prognosis. Little information is available about how adjuvant imatinib influences survival., Methods: We explored recurrence-free survival (RFS) and overall survival (OS) of patients with ruptured GIST who participated in a randomised trial (SSG XVIII/AIO), where 400 patients with high-risk GIST were allocated to adjuvant imatinib for either 1 year or 3 years after surgery. Of the 358 patients with confirmed localised GIST, 73 (20%) had rupture reported. The ruptures were classified retrospectively using the Oslo criteria., Results: Most ruptures were major, four reported ruptures were reclassified unruptured. The 69 patients with rupture had inferior RFS and OS compared with 289 patients with unruptured GIST (10-year RFS 21% vs. 55%, OS 59% vs. 78%, respectively). Three-year adjuvant imatinib did not significantly improve RFS or OS of the patients with rupture compared with 1-year treatment, but in the largest mutational subset with KIT exon 11 deletion/indel mutation OS was higher in the 3-year group than in the 1-year group (10-year OS 94% vs. 54%)., Conclusions: About one-fifth of ruptured GISTs treated with adjuvant imatinib did not recur during the first decade of follow-up. Relatively high OS rates were achieved despite rupture., Clinical Trial Registration: NCT00116935., (© 2024. The Author(s).)

Background: Several doubts remain regarding the optimal use of neoadjuvant imatinib in gastrointestinal stromal tumors (GISTs), such as ideal treatment duration, patient selection, and long-term survival outcomes. This manuscript provides a comprehensive review on neoadjuvant imatinib treatment outcomes and facilitate evidence-based decision-making for the use of imatinib therapy in GISTs., Methods: Four databases (PubMed, EMBASE, Scopus, and Cochrane Library) were searched from inception to September 9, 2023. Meta-analyses of proportions were performed for the outcomes of R0 resection, disease responses, and 1-year, 3-year, and 5-year overall survival (OS) as well as 1-year, 3-year, and 5-year disease free survival (DFS). Sensitivity analyses in the form of leave-one-out analyses, meta-regression, and subgroup analyses were performed for outcomes with substantial statistical heterogeneity., Results: The search yielded 1254 articles, and 36 studies were included in our analysis. Meta-analysis of proportions revealed that 1-year, 3-year, and 5-year OS was 100%, 94%, and 88%, while 1-year, 3-year and 5-year DFS was 99%, 89%, and 79%, respectively. An R0 resection rate of 89% and a disease response rate of 67% was achieved after a mean duration of treatment of 8.41 ± 0.367 months. KIT exon 9 mutation was significantly associated with poorer 5-year DFS., Conclusion: This study quantified key outcomes for neoadjuvant imatinib in locally advanced and metastatic or recurrent GIST. Patients with gastric and rectal tumous stand to benefit from neoadjuvant imatinib with an optimal treatment duration of 8 months. Furthermore, the potential utility of mutational analysis in guiding treatment with neoadjuvant imatinib was demonstrated., (© 2024 International Society of Surgery/Société Internationale de Chirurgie (ISS/SIC).)

Background: Pulmonary embolism (PE) is described as a prognostic factor in patients with cancer however, the prognostic impact of PE remains unknown. This study investigated, the 1-year prognosis following PE in patients with breast-, gastrointestinal-, or lung cancer stratified by cancer status., Methods: All Danish patients with first-time PE from 2008 to 2018 were included. Cancer status was categorized as no cancer, history of cancer, non-active cancer and active cancer. Unadjusted and age-stratified 1-year risk of death was estimated using the Kaplan-Meier estimator. Cause of death was reported using the Aalen-Johansen method., Results: Of 35,679 patients with PE, 18% had a breast-, gastrointestinal-, or lung cancer. Patients with cancer were older compared with no cancer (69.8 years [IQR: 56.2-79.8]). One-year risk of death (95% confidence interval) for active breast-, gastrointestinal-, and lung cancer was 49.5% (44.0%-54.9%), 75.0% (72.5%-77.4%) and 80.1% (78.0%-82.3%) respectively, compared with 18.9% (18.4%-19.3%) for no cancer. Age-stratified analysis revealed no association with increasing age in non-active lung cancer and all active cancers. Further, non-cardiovascular death accounted for an increasing proportion by cancer status (no cancer < history of cancer < non-active cancer < active cancer)., Conclusions: One-year risk of death was dependent on both cancer type and status; no association with age was found for patients with active cancers. Non-cardiovascular death was leading in non-active and active cancers. Thus, the occurrence of first-time PE could be regarded as a marker of cancer severity for patients with breast-, gastrointestinal-, and lung cancer., Competing Interests: Declaration of competing interest The authors report the following relationships unrelated to this study. NN reports speaker fees from Bayer and AstraZeneca. CFA reports research grants from The Danish Heart Foundation, Toyota Foundation, Aase & Ejnar Danielsen's Foundation, Arvid Nilsson's Foundation, The Research and Innovation Foundation of the Department of Cardiology, Herlev and Gentofte University Hospital, Fru Asta Florida Bolding's Memorial Grant and the KV Foundation; support for attending meetings from AstraZeneca and European Heart Foundation Association. ML reports research grants from Karen Elise Jensen Fonden, Danish Heart Foundation, Bayer, and BMS; speaker fees from BMS, Pfizer, Bayer and Astra Zeneca; and advisory board positions with Pfizer and Astra Zeneca. MS reports speaker fees from Novartis, Boehringer Ingelheim, Bayer, Novo, and Astra Zeneca. ELG research grants from Boehringer Ingelheim; speaker fees from Pfizer, Bayer, AstraZeneca and Bristol Myers-Squibb; consulting fees from Bayer, Bristol Myers-Squibb, MSD and Boehringer Ingelheim. AH, JES, SKN, CS, DN and JT report no conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Introduction: Malignant bowel obstruction (MBO) is a common complication of patients with advanced malignancies and has poor prognosis. Currently, there are limited guidelines for MBO management or predicting outcomes for these patients., Objective: To identify patient factors associated with readmission and mortality after hospital admission for MBO., Participants: A 5-year retrospective review was performed from 2017 to 2022 at a single tertiary institution to evaluate patients admitted for MBO. All patients had advanced cancer of gastrointestinal or gynecologic primary. Patient demographics, socioeconomic factors, tumor characteristics, and inpatient outcomes were collected. Multivariable analyses were performed to determine variables predicting hospital readmission for recurrent MBO and 90-day mortality., Results: 210 patients were included. Mean age was 61 years, 28% were male, and 19% did not primarily speak English. 35% of patients lived over 50 miles from the hospital. On multivariable analysis, non-English speaking patients exhibited increased risk of readmission for MBO (OR = 2.82, P = .039). Older age was associated with decreased risk for MBO readmission (OR = .96, P = .007). Ascites was associated with increased mortality (OR = 2.17, P = .043). Earlier palliative care (PC) consultation predicted decreased readmission (OR = .24, P < .001) yet increased mortality at 90 days (OR = 3.20, P = .003)., Conclusion: Patient age, primary language, and PC consult were predictors for MBO readmission, which may impact 90-day mortality. Given the palliative nature of MBO, modifiable factors such as PC consultation and multidisciplinary goals of care discussions should be prioritized in order to reduce readmissions and focus on quality of life (QOL) for this patient population., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Ultra-Processed Foods (UPFs) are increasingly consumed worldwide, even in regions with strong dietary traditions like the Mediterranean and can play a crucial role in the development of chronic diseases, including cancer. This population-based prospective cohort study investigates the association between UPF consumption and gastrointestinal cancers and other causes of mortality in Southern Italy., Methods: Data were collected from 4870 participants in the MICOL and NUTRIHEP cohorts. The EPIC questionnaire was used to elicit information on food and drink consumption and UPFs were categorized by degree of processing according to the NOVA classification. Cox proportional hazards regression and competing risk models were employed for statistical analysis., Results: UPF consumption was positively associated with all-cause mortality: participants in the 3rd UFP quartile, as compared to the lowest, had a 27% higher risk of death (SHR 1.27 95% CI, 1.03; 1.57), while in the highest quartile as compared to the lowest, the risk was 34% higher (SHR 1.34 95% CI, 1.00; 1.79). Higher UPFs intake was also correlated with an increased gastrointestinal cancers mortality risk, especially the 2nd (SHR 1.65, 95% CI: 1.01; 2.71) and 4th quartile (SHR 3.14 95% CI: 1.56; 6.32), with a dose-dependent effect. For the other cancers, a SHR 1.61 (95% CI 1.03; 2.54) was observed for the 3rd quartile., Conclusions: Our results reinforce the link between UPF consumption and cancer risk, emphasizing the urgent need for interventions targeting dietary patterns.

Background: Social conditions and dietary behaviors have been implicated in the rising burden of gastrointestinal cancers (GIC). The "food environment" reflects influences on a community level relative to food availability, nutritional assistance, and social determinants of health. Using the US Department of Agriculture-Food Environment Atlas (FEA), we sought to characterize the association of food environment on GIC presenting stage and long-term survival., Methods: Patients diagnosed with GIC between 2013 and 2017 were identified using the SEER database. FEA-scores were based on 282 county-level food security variables, store-restaurant availability, SNAP/WIC enrollment, pricing/taxes, and producer vicinity adjusted-for factors of socioeconomic status, race-ethnicity, transportation access, and comorbidities. Relative FEA rankings across US counties were averaged into a composite score and assigned to patients by county-of-residence. The association of FEA, cancer stage, and survival were analyzed using multiple logistic regression and cox-proportional hazard models relative to White/non-White race/ethnicity., Results: Among 287,148 patients, the most common GIC-sites were colon (n = 97,942, 34%), pancreas (n = 49,785, 17.3%), liver (n = 31,098, 11.0%) and esophagus (n = 16,271, 5.7%). A worse food environment was independently associated with increased odds of late-stage diagnosis (esophageal odds ratio [OR]: 1.03, 95% confidence interval [CI]: 1.01-1.05; hepatic OR: 1.06, 95% CI: 1.03-1.08; pancreatic OR: 1.04, 95% CI: 1.01-1.06) among all patients; in contrast, food environment was associated with colorectal cancer stage among non-White patients only (OR: 1.04, 95% CI: 1.03-1.06). Worse food environment was associated with worse 3-year survival (colon OR: 1.03, 95% CI: 1.01-1.04; hepatic OR: 1.12, 95% CI: 1.08-1.17; gastric OR: 1.07, 95% CI: 1.01-1.13). Similar associations were noted relative to overall survival among the entire cohort (biliary tract hazard ratio [HR]: 1.03, 95% CI: 1.01-1.05; esophageal HR: 1.02, 95% CI: 1.01-1.04; hepatic HR: 1.07, 95% CI: 1.06-1.09; pancreatic HR: 1.04, 95% CI: 1.02-1.05; rectum HR: 1.03, 95% CI: 1.01-1.04; gastric HR: 1.05, 95% CI: 1.03-1.07), as well as among non-White patients (biliary HR: 1.04, 95% CI: 1.01-1.07; colon HR: 1.03, 95% CI: 1.01-1.05; esophageal HR: 1.05, 95% CI: 1.02-1.08; hepatic HR: 1.08, 95% CI: 1.06-1.10) (all p < 0.003)., Conclusions: Food environment was independently associated with late-stage tumor presentation and worse 3-year and overall survival among GIC patients. Interventions to address inequities across communities relative to food environments are needed to alleviate disparities in cancer care., (© 2024 The Authors. Journal of Surgical Oncology published by Wiley Periodicals LLC.)

Specific data regarding outcome of cats with high-grade and large granular lymphocyte alimentary lymphoma (HGAL and LGL, respectively) treated with multi-agent chemotherapy are scarce. The aims of this multi-centric, retrospective study were to describe the outcome of cats with HGAL and LGL treated with COP- or CHOP-based chemotherapy and to identify potential prognostic factors. Cats with a cytological or histological diagnosis of HGAL or LGL lymphoma treated with COP- or CHOP-based protocol as first-line chemotherapy were included. Data regarding diagnosis, staging, treatment and follow-up were collected. Fifty-seven cats treated with CHOP (n = 37) or COP (n = 20) protocols were included. Complete response (CR), partial response (PR), stable disease (SD) and progressive disease (PD) were observed in 20%, 22%, 36% and 22% of cats, respectively, for an overall response rate of 42%. Median progression-free interval (PFI) was 148 days and overall median survival time (OST) was 131 days. Cats achieving CR, PR or SD showed significantly longer PFI (p < .01) and OST (p < .015) compared with cats with PD. Other positive prognostic factors in multi-variate analysis were rescue treatment (p < .001) and absence of lymph node involvement (p < .03). Negative prognostic factors were diffuse infiltration of the gastrointestinal tract (p = .035) and infiltration of a non-haematopoietic organ (p < .01)., (© 2024 The Authors. Veterinary and Comparative Oncology published by John Wiley & Sons Ltd.)

Purpose: A consensus has not been reached on the value of quality of life (QoL) as a prognostic factor for survival in gastrointestinal cancer. This meta-analysis aimed to investigate the association between functioning scales of the EORTC QoL Questionnaire Core 30 (QLQ-C30) and the overall survival (OS) in patients with gastrointestinal cancer., Methods: A systematic literature search was conducted in PubMed, Web of Science, and Embase databases, until February 7, 2023. The studies included were those that investigated the association between baseline QoL measured by the functioning scales of EORTC QLQ-C30 and OS in patients with gastrointestinal cancer. The prognostic capacity of QoL was calculated by pooling the adjusted hazard ratios (HR) with 95% confidence intervals (CI)., Results: Twenty-four studies' analyses reported by 22 eligible articles involving 11,609 patients were included. When compared with good parameters of QoL, poor global QoL (HR 1.81; 95% CI 1.53-2.13), physical functioning (HR 1.51; 95% CI 1.31-1.74), social functioning (HR 1.67; 95% CI 1.30-2.15), and role functioning scale (HR 1.42; 95% CI 1.20-1.29) were significantly associated with decreased OS. For each 10-point increase in QLQ-C30 parameters, the pooled HR of OS was 0.87 (95% CI 0.83-0.92) for global QoL, 0.87 (95% CI 0.83-0.92) for physical functioning, and 0.93 (95% CI 0.88-0.97) for role functioning. However, each 10-point increase in social, emotional, or cognitive functioning scale did not significantly predict OS., Conclusions: Baseline health-related QoL defined by the physical functioning or global QoL scale of EORTC QLQ-C30 significantly predicts OS in patients with gastrointestinal cancer., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Purpose: This study aimed to determine if Ki-67, a commonly used marker to measure tumor proliferation, is a reliable prognostic factor in various types of gastrointestinal (GI) cancers based on current high-quality multivariable evidence., Methods: A comprehensive search was conducted in PubMed, Embase, Scopus, and ISI Web of Science databases to investigate the association between Ki-67 positivity and overall survival (OS) and disease/recurrence-free survival (DFS/RFS) in GI cancers. Heterogeneity was assessed using Chi-square-based Q and I 2 analyses and publication bias using funnel plots and Egger's analysis. In addition, Ki-67 levels in different GI cancers were examined by different platforms. The prognostic capability of Ki-67, gene ontology (GO), and pathway enrichment analysis were obtained from GEPIA2 and STRING., Results: Totally, 61 studies, involving 13,034 patients, were deemed eligible for our evaluation. The combined hazard ratios (HRs) demonstrated the prediction ability of overexpressed Ki-67 for a worse OS (HR: 1.67, P < 0.001; HR: 1.37, P = 0.021) and DFS/RFS (HR: 2.06, P < 0.001) in hepatocellular and pancreatic malignancies, respectively, as confirmed by multi-omics databases. However, similar correlation was not found in esophageal, gastric, and colorectal cancers. Furthermore, most of the associations were identified to be robust based on different subcategories and publication bias assessment. Finally, enriched Ki-67-related genes were found to be involved in various important signaling pathways, such as cell cycle, P53 signaling network, and DNA damage responses., Conclusion: This study supports that Ki-67 can serve as an independent prognostic biomarker for pancreatic and hepatocellular malignancies in clinical settings., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Gastrointestinal Stromal Tumors (GISTs) are the most common mesenchymal tumors of the GI tract. SEER is an extensive cancer database which proves useful in analyzing population trends. This analysis investigated GIST outcomes between geriatric & non-geriatric patients., Methods: SEER*STAT 8.4.0.1 was used to extract relevant GIST data from 2000 to 2019. Geriatric age was defined as ≥70 years. Variables included age, sex, surgery, cancer-specific death, and overall survival. Statistical tests included univariate analysis using KM survival estimate (95% confidence interval) to calculate 5-year survival (5YS). Log-Rank tests determined statistical significance. Multivariable Cox's PH regression estimated the geriatric hazard death ratio adjusted for sex, stage, and surgery., Results: The number of patients included was 13,579, yielding overall 5YS of 68.6% (95% CI 67.7-69.5). Cancer-specific death was 39.11% in 2000 & 3.33% in 2019. Non-geriatric & geriatric patient data yielded 5YS of 77.4% (76.4%-78.3%) and 53.3% (51.7%-54.8%) respectively (p < 0.0001). For no surgery/surgery, younger patient data yielded 5YS of 48.7% (45.8%-51.4%) and 83.7% (82.7%-84.7%) respectively (p < 0.0001); geriatric data yielded 5YS of 29.3% (26.5%-32.1%) and 62.8% (60.8%-64.6%) respectively (p < 0.0001). Multivariable analysis yielded a geriatric hazard death of 2.56 (2.42-2.70) (p < 0.0001)., Conclusions: Cancer-specific death decreased since 2000, indicating an improvement in survival & treatment methods. Observed lower survival rates overall in the geriatric group. Surgery appeared to enhance survival rates in both groups, suggesting that surgery is an important factor in GIST survival regardless of age. Large prospective studies will help define clinical management for geriatric patients., (© 2024 International Society of Surgery/Société Internationale de Chirurgie (ISS/SIC).)

Background: Sunitinib is an oral anticancer drug approved for the treatment of among others gastrointestinal stromal tumor (GIST). Previous analyses demonstrated an exposure-response relationship at the standard dose, and minimum target levels of drug exposure have been defined above which better treatment outcomes are observed. Therapeutic drug monitoring (TDM) could be used as a tool to optimize the individual dose, aiming at sunitinib trough concentrations ≥37.5 ng/ml for continuous dosing. Nonetheless, data on the added value of TDM-guided dosing on clinical endpoints are currently lacking. Therefore, we evaluate the effect of TDM in patients with advanced and metastatic GIST treated with sunitinib in terms of efficacy and toxicity., Patients and Methods: A TDM-guided cohort was compared to a non-TDM-guided cohort in terms of median progression-free survival (mPFS) and overall survival (mOS). Also, mPFS between patients with and without dose-limiting toxicities (DLTs) was compared. Patients in the prospective cohort were included in two studies on TDM-guided dosing (the DPOG-TDM study and TUNE study). The retrospective cohort consisted of patients from the Dutch GIST Registry who did not receive TDM-guided dosing., Results: In total, 51 and 106 patients were included in the TDM-guided cohort and non-TDM-guided cohort, respectively. No statistical difference in mPFS was observed between these two cohorts (39.4 versus 46.9 weeks, respectively; P = 0.52). Patients who experienced sunitinib-induced DLTs had longer mPFS compared to those who did not (51.9 versus 28.9 weeks, respectively; P = 0.002)., Conclusions: Our results do not support the routine use of TDM-guided dose optimization of sunitinib in patients with advanced/metastatic GIST to improve survival., Competing Interests: Disclosure RHJM reports research funding paid to the institute from Astellas, Bayer, Boehringer-Ingelheim, Cristal Therapeutics, Novartis, Pamgene, Pfizer, Roche, Sanofi and Servier, all outside the submitted work. WTAvdG reports institutional research fees paid to the institute from Lilly and advisory compensation from Springworks, PTC Therapeutics and Agenus, all outside the submitted work. NS reports research grants paid to the institute from Abbvie, Actuate Therapeutics, Amgen, Array, Ascendis Pharma, AstraZeneca, Bayer, Blueprint Medicines, Boehringer Ingelheim, BridgeBio, Bristol-Myers Squibb, Cantargia, CellCentric, Cogent Biosciences, Cresecendo Biologics, Cytovation, Deciphera, Dragonfly, Eli Lilly, Exelixis, Genentech, GlaxoSmithKline, IDRx, Immunocore, Incyte, InteRNA, Janssen, Kinnate Biopharma, Kling Biotherapeutics, Luszana, Merck, Merck Sharp & Dohme, Merus, Molecular Partners, Navire Pharma, Novartis, Numab Therapeutics, Pfizer, Relay Pharmaceuticals, Revolution Medicin, Roche, Sanofi, Seattle Genetics, Taiho and Takeda, all outside the submitted work. NS provided consultation or attended advisory boards for Boehringer Ingelheim, Cogent Biosciences, Ellipses Pharma, Incyte and Luszana. NPvE reports research funding paid to the institute from Astellas and Ipsen, all outside the submitted work. All other authors have declared no conflicts of interest., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Tumour budding shows promise as a prognostic factor in various cancers, but its widespread application is hindered by the lack of large, validated studies and standardized criteria. This meta-analysis aims to review and examine the prognostic role of tumour budding specifically in noncolorectal gastrointestinal and pancreatobiliary tract cancers, broadening our perspective on its clinical relevance. The literature review was conducted through PubMed, Embase, and Web of Science from inception till 20 February 2023. Pooled odds ratio (OR) and hazard ratio (HR) with 95% confidence interval (CI) were calculated to assess the relation between tumour budding and clinicopathologic features, as well as overall survival. Each study was evaluated using the Newcastle-Ottawa Scale and both heterogeneity and publication bias were analysed. In this meta-analysis of 57 studies across various cancer types, multivariate HR revealed worse overall survival in oesophageal squamous cell carcinoma (HR 3.34 [95% CI 2.21-5.04]), gastric adenocarcinoma (2.03 [1.38-2.99]), pancreatic ductal adenocarcinoma (2.56 [2.02-3.25]), and biliary tract adenocarcinoma (3.11 [2.46-3.93]) with high-grade tumour budding. Additionally, high-grade tumour budding consistently correlated with adverse clinicopathological features, including lymph node metastasis, lymphovascular invasion, and distant metastasis without any observed inverse association. High heterogeneity was noted. Our study suggests that tumour budding is a valuable prognostic marker in various cancers. Nonetheless, standardized criteria tailored to specific organ types are necessary to enhance its clinical utility., (© 2024 John Wiley & Sons Ltd.)

Background: Patients with advanced cancer undergoing chemotherapy experience significant symptoms and declines in functional status, which are associated with poor outcomes. Remote monitoring of patient-reported outcomes (PROs; symptoms) and step counts (functional status) may proactively identify patients at risk of hospitalization or death., Objective: The aim of this study is to evaluate the association of (1) longitudinal PROs with step counts and (2) PROs and step counts with hospitalization or death., Methods: The PROStep randomized trial enrolled 108 patients with advanced gastrointestinal or lung cancers undergoing cytotoxic chemotherapy at a large academic cancer center. Patients were randomized to weekly text-based monitoring of 8 PROs plus continuous step count monitoring via Fitbit (Google) versus usual care. This preplanned secondary analysis included 57 of 75 patients randomized to the intervention who had PRO and step count data. We analyzed the associations between PROs and mean daily step counts and the associations of PROs and step counts with the composite outcome of hospitalization or death using bootstrapped generalized linear models to account for longitudinal data., Results: Among 57 patients, the mean age was 57 (SD 10.9) years, 24 (42%) were female, 43 (75%) had advanced gastrointestinal cancer, 14 (25%) had advanced lung cancer, and 25 (44%) were hospitalized or died during follow-up. A 1-point weekly increase (on a 32-point scale) in aggregate PRO score was associated with 247 fewer mean daily steps (95% CI -277 to -213; P<.001). PROs most strongly associated with step count decline were patient-reported activity (daily step change -892), nausea score (-677), and constipation score (524). A 1-point weekly increase in aggregate PRO score was associated with 20% greater odds of hospitalization or death (adjusted odds ratio [aOR] 1.2, 95% CI 1.1-1.4; P=.01). PROs most strongly associated with hospitalization or death were pain (aOR 3.2, 95% CI 1.6-6.5; P<.001), decreased activity (aOR 3.2, 95% CI 1.4-7.1; P=.01), dyspnea (aOR 2.6, 95% CI 1.2-5.5; P=.02), and sadness (aOR 2.1, 95% CI 1.1-4.3; P=.03). A decrease in 1000 steps was associated with 16% greater odds of hospitalization or death (aOR 1.2, 95% CI 1.0-1.3; P=.03). Compared with baseline, mean daily step count decreased 7% (n=274 steps), 9% (n=351 steps), and 16% (n=667 steps) in the 3, 2, and 1 weeks before hospitalization or death, respectively., Conclusions: In this secondary analysis of a randomized trial among patients with advanced cancer, higher symptom burden and decreased step count were independently associated with and predictably worsened close to hospitalization or death. Future interventions should leverage longitudinal PRO and step count data to target interventions toward patients at risk for poor outcomes., Trial Registration: ClinicalTrials.gov NCT04616768; https://clinicaltrials.gov/study/NCT04616768., International Registered Report Identifier (irrid): RR2-10.1136/bmjopen-2021-054675., (©Christopher R Manz, Emily Schriver, William J Ferrell, Joelle Williamson, Jonathan Wakim, Neda Khan, Michael Kopinsky, Mohan Balachandran, Jinbo Chen, Mitesh S Patel, Samuel U Takvorian, Lawrence N Shulman, Justin E Bekelman, Ian J Barnett, Ravi B Parikh. Originally published in the Journal of Medical Internet Research (https://www.jmir.org), 17.05.2024.)

Introduction: Metastatic gastrointestinal stromal tumour (GIST) is considered incurable, and life-long treatment with tyrosine kinase inhibitors is recommended. We investigated whether selected patients with metastatic GIST may remain in durable remission despite imatinib discontinuation., Patients: In this 1-group, prospective, multicentre phase II trial selected patients with oligometastatic (≤3 metastases) GIST discontinued imatinib treatment. Eligible patients had been treated with imatinib >5 years without progression and had no radiologically detectable metastases after metastasectomy, radiofrequency ablation (RFA) or complete response to imatinib. The primary endpoint was progression-free survival (PFS) 3-years after stopping imatinib. Overall survival (OS) and quality of life (QoL) were secondary endpoints., Results: The trial closed prematurely due to slow accrual. Between January 5, 2017, and June 5, 2019, 13 patients were enrolled, of whom 12 discontinued imatinib. The median follow-up time was 55 months (range, 36 to 69) after study entry. Five (42%) of the 12 eligible patients remained progression free, and seven (58%) progressed with a median time to progression 10 months. Median PFS was 23 months and the estimated 3-year PFS 41%. Six of the seven patients who progressed restarted imatinib, and all six responded. Three-year OS was 100%, and all patients were alive at the time of the study analysis. QoL measured 5 and 11 months after discontinuation of imatinib demonstrated improvement compared to the baseline., Interpretation: A substantial proportion of selected patients with oligometastatic GIST treated with imatinib and metastasis surgery/RFA may remain disease-free for ≥3 years with improved QoL after stopping of imatinib.

Background and Aims: Intraductal papillary mucinous neoplasm (IPMN) of the pancreas is a precursor of pancreatic cancer. While earlier research has shown a high prevalence of synchronous/metachronous extrapancreatic tumors in IPMN patients, these studies have often been small with retrospective data collection. The aim of the study was to examine absolute and relative risks of non-pancreatic gastrointestinal (GI) cancer precursors and mortality in histologically confirmed IPMN., Methods: Through the nationwide ESPRESSO histopathology cohort, we retrieved data on IPMN between 1965 and 2016. Each index case was matched to ≤5 general population controls. Through Cox regression, we estimated hazard ratios (HRs) for future GI cancer precursors and death., Results: A total of 117 patients with IPMN and 539 age- and sex-matched controls were included. Over a median of 2.1 years of follow up, we confirmed two (1.7%) incident GI cancer precursors in IPMN vs. four (0.7%) in controls, corresponding to an HR of 1.89 (95%CI = 0.34-10.55). By contrast, IPMN patients were at increased risk of death (HR 3.61 (95%CI = 1.79-7.27)). The most common cause of death in IPMN was pancreatic cancer ( n  = 14; 45.2% of all deaths)., Conclusions: We found no association between IPMN and other GI cancer precursors. This argues against comprehensive routine surveillance for other GI cancer precursors in IPMN patients. Mortality was increased in IPMN with pancreatic cancer being the most common cause of death, indicating the need for lifelong follow up in all resected and non-resected patients with IPMN. However, results should be confirmed in larger cohorts.

Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interest in association with the present study.

Primary gastrointestinal follicular lymphoma (PGI-FL) is a rare extra-nodal lymphoma. Its epidemiology and prognosis remain unclear. We performed a retrospective analysis of eligible patients with 1648 PGI-FL and 34 892 nodal FL (N-FL) in the Surveillance, Epidemiology and End Results (SEER) database. The age-adjusted average annual incidence of PGI-FL was 0.111/100000. The median overall survival (OS) for PGI-FL and N-FL patients was 207 and 165 months respectively. The 5-year diffuse large B-cell lymphoma (DLBCL) transformation rates were 2.1% and 2.6% respectively. Age, sex, grade, Ann Arbor stage, primary site and radiation were independent prognostic factors (p < 0.05). Nomograms were constructed to predict 1-, 5- and 10-year OS and disease-specific survival (DSS). The receiver operating characteristic curves and calibration plots showed the established nomograms had robust and accurate performance. Patients were classified into three risk groups according to nomogram score. In conclusion, the incidence of PGI-FL has increased over the past 40 years, and PGI-FL has a better prognosis and a lower DLBCL transformation rate than N-FL. The nomograms were developed and validated as an individualized tool to predict survival. Patients were divided into three risk groups to assist clinicians in identifying high-risk patients and choosing the optimal individualized treatments., (© 2024 British Society for Haematology and John Wiley & Sons Ltd.)

Introduction: Muscle and adipose tissue measures can be quantified from routinely obtained computed tomography (CT) images and are predictors of chemotherapy-related toxicities and survival among patients with gastrointestinal (GI) malignancies. Most studies to date have consisted of predominantly White patients, and the role of body composition among minoritized racial groups is unknown. We examined racial differences in body composition and survival among patients with GI malignancies., Materials and Methods: This was a prospective cohort study of patients with GI malignancies. Single slices of axial CT images from L3 segments were analyzed using Slice-O-Matic software. The skeletal muscle area (cm 2 ) was divided by height to obtain the skeletal muscle index (SMI, cm 2 /m 2 ). Skeletal muscle radiodensity (SMD) in Hounsfield units (HU) was used for muscle composition. We compared body composition parameters between non-Hispanic (NH)-White and NH-Black participants. Cox models were used to examine the impact of body composition on survival. We proposed new race-specific cutoffs for body composition using optimal stratification., Results: Five hundred forty patients were included, of which 24% were NH-Black. In Cox models stratified by race, each 5 cm 2 /m 2 decrease in SMI was associated with increase in risk of all-cause mortality in NH-Black patients (hazard ratio [HR] 1.25; 95% confidence interval [CI] 1.04-1.49 p = 0.02). With the existing cut points, neither sarcopenia nor myosteatosis was associated with worse survival. Using a new cutoff for sarcopenia in NH-Black patients, NH-Black patients with sarcopenia (HR 2.31 95%CI 1.10-4.88 p = 0.03) and myosteatosis (HR 2.63 95% CI 1.25-5.53 p = 0.01) had worse survival., Discussion: NH-Black older patients with GI cancers and sarcopenia or myosteatosis have worse overall survival., Competing Interests: Declaration of Competing Interest All authors report no conflict of interest., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Many older adults with cancer have ≥2 impairments on geriatric assessment, which affects present and future frailty status, treatment tolerability, and outcomes. Our objective was to identify and describe distinct geriatric assessment impairment classes using latent class analysis (LCA) in older patients with gastrointestinal malignancies and assess 1-year mortality., Methods: We used the Cancer & Aging Resilience Evaluation (CARE) Study, a registry of older adults (≥60 years) at University of Alabama at Birmingham. The analytic cohort included patients with gastrointestinal malignancies who completed a self-administered geriatric assessment (CARE tool) before chemotherapy and had ≥1 geriatric assessment impairment. Thirteen geriatric assessment impairments were used as indicators in LCA. Resultant classes were described, mortality was estimated, and risk contrasts (differences and hazard ratios) were calculated with 95% confidence intervals. For comparison, estimates were provided for frailty categories (robust, prefrail, and frail) determined from 44 items in the CARE tool. Stratified analyses included high-risk (pancreatic, hepatobiliary, and esophageal) versus low-risk gastrointestinal cancers, and stage (IV vs I-III)., Results: Six geriatric assessment impairment classes were identified: Mild impairment (LC1); Social support impairment (LC2); Weight loss alone (LC3); Impaired, low anxiety/depression (LC4); Impaired with anxiety/depression (LC5); and Global impairment (LC6). One-year mortality was 14%, 22%, 29%, 34%, 50%, and 50% for LC1-LC6, respectively. For frailty categories, estimates ranged from 18% (robust) to 40% (frail). In stratified analyses, LC4-LC6 consistently had higher mortality estimates compared to LC1., Conclusions: The 6 geriatric assessment impairment classes showed a wider spread of mortality estimates compared to frailty categories and could be used to identify vulnerable patients and to plan interventions., (© The Author(s) 2023. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Objective: This study aimed to conduct a comprehensive analysis, evaluating the prognostic significance of the baseline Advanced Lung Cancer Inflammation Index (ALI) and Gustave Roussy Immune (GRIm) Score in patients undergoing immune checkpoint inhibitor (ICI) therapy., Methods: A comprehensive search was performed across various databases, including PubMed, the Cochrane Library, EMBASE, and Google Scholar, until October 21, 2023, to compile relevant articles for analysis. The investigation encompassed diverse clinical outcomes, including overall survival (OS) and progression-free survival (PFS)., Results: This analysis included a total of 15 articles, comprising 19 studies involving 3335 patients. Among the 19 studies, nine studies focused on NSCLC, and six studies were conducted on HCC. Pooled results revealed that patients with elevated ALI levels experienced prolonged OS (HR: 0.51, 95% CI: 0.37-0.70, p < 0.001) and extended PFS (HR: 0.61, 95% CI: 0.52-0.72, p < 0.001). Furthermore, a GRIm score > 1 was associated with reduced OS (HR: 2.07, 95% CI: 1.47-2.92, p < 0.001) and diminished PFS (HR: 1.78, 95% CI: 1.35-2.34, p < 0.001) in cancer patients receiving ICIs. Subgroup analysis indicated that ALI cutoff values of 18 exhibited enhanced predictive potential. Additionally, for HCC patients, those with HCC-GRIm score > 2 showed a substantially decreased risk of mortality compared to individuals with HCC-GRIm score ≤ 2 (HR: 2.63, 95% CI: 1.89-3.65, p < 0.001)., Conclusion: The ALI and GRIm score served as dependable prognostic indicators for patients undergoing ICI therapy in the context of cancer treatment., (© 2024. The Author(s).)

Background: Tumor mutational load (TML) has emerged as a potential biomarker for multiple solid tumors. However, data on its prognostic impact on upper gastrointestinal (UGI) cancer are limited. Therefore, the aim of this systematic review and meta-analysis was to assess the prognostic value of TML for the survival of patients with UGI cancer., Method: A comprehensive search of the PubMed, Embase, Cochrane Library, and Web of Science databases was conducted up to February 13, 2023. Eleven studies met our inclusion criteria. Hazard ratios (HRs) for progression-free survival and overall survival and their 95% confidence intervals (CIs) were calculated. Subsequently, the combined HR and its 95% CI were calculated for UGI tract cancers in the high and low TML groups. I 2 statistics and p-values were used to evaluate heterogeneity. Publication bias, sensitivity, and subgroup analyses were performed to determine sources of heterogeneity., Results: In total, 932 patients with UGI tract cancer from 11 publications were included. The high TML group treated with immunotherapy showed significantly improved overall survival (HR = 0.68; 95% CI: 0.53, 0.86; p = .001) and progression-free survival (HR = 0.74; 95% CI: 0.58, 0.95; p = .020) compared with the low TML group., Conclusion: Our study demonstrated that patients with UGI tumors and higher TML have a better prognosis with immunotherapy, suggesting that TML is a promising predictive biomarker for immunotherapy., Registration: The study protocol was registered with the International Prospective Register of Systematic Reviews (PROSPERO Registration No: CRD42023405596)., (© 2024 The Authors. Cancer Reports published by Wiley Periodicals LLC.)

The cachexia index is a novel indicator of cachexia, but its prognostic implications for survival outcomes have not been systematically assessed in patients with gastrointestinal cancer. This systematic review and meta-analysis aimed to examine the association between the cachexia index and survival outcomes in gastrointestinal cancer patients. Two independent reviewers searched PubMed, Embase, and Web of Science to identify studies that evaluated the prognostic significance of the cachexia index in patients with gastrointestinal cancer. The prognostic value of the cachexia index was determined by combining the adjusted hazard ratios (HR) and 95% confidence intervals (CI). Thirteen studies were identified, including a total of 4207 patients. Meta-analysis indicated that a lower cachexia index was associated with shorter overall survival (HR 2.18; 95% CI 1.78-2.66) and disease-free survival (HR 1.72; 95% CI 1.50-1.97) in gastrointestinal cancer patients. Further stratified analysis confirmed the significant association between a lower cachexia index and shorter overall survival in different study designs, regions, patients' age, sample sizes, gastrointestinal cancer subtypes, tumor stages, and follow-up duration subgroups. The cachexia index could be utilized as a predictor of overall survival and disease-free survival in patients with gastrointestinal cancer. However, future prospective studies are required to confirm these findings.

Introduction: Well-calibrated models for personalized prognostication of patients with gastrointestinal neuroendocrine neoplasms (GINENs) are limited. This study aimed to develop and validate a machine-learning model to predict the survival of patients with GINENs., Methods: Oblique random survival forest (ORSF) model, Cox proportional hazard risk model, Cox model with least absolute shrinkage and selection operator penalization, CoxBoost, Survival Gradient Boosting Machine, Extreme Gradient Boosting survival regression, DeepHit, DeepSurv, DNNSurv, logistic-hazard model, and PC-hazard model were compared. We further tuned hyperparameters and selected variables for the best-performing ORSF. Then, the final ORSF model was validated., Results: A total of 43,444 patients with GINENs were included. The median (interquartile range) survival time was 53 (19-102) months. The ORSF model performed best, in which age, histology, M stage, tumor size, primary tumor site, sex, tumor number, surgery, lymph nodes removed, N stage, race, and grade were ranked as important variables. However, chemotherapy and radiotherapy were not necessary for the ORSF model. The ORSF model had an overall C index of 0.86 (95% confidence interval, 0.85-0.87). The area under the receiver operation curves at 1, 3, 5, and 10 years were 0.91, 0.89, 0.87, and 0.80, respectively. The decision curve analysis showed superior clinical usefulness of the ORSF model than the American Joint Committee on Cancer Stage. A nomogram and an online tool were given., Conclusion: The machine learning ORSF model could precisely predict the survival of patients with GINENs, with the ability to identify patients at high risk for death and probably guide clinical practice., (© 2024 S. Karger AG, Basel.)

Purpose: Due to the rarity of primary gastrointestinal lymphoma (PGIL), the prognostic factors and optimal management of PGIL have not been clearly defined. We aimed to establish prognostic models using a deep learning algorithm for survival prediction., Methods: We collected 11,168 PGIL patients from the Surveillance, Epidemiology, and End Results (SEER) database to form the training and test cohorts. At the same time, we collected 82 PGIL patients from three medical centres to form the external validation cohort. We constructed a Cox proportional hazards (CoxPH) model, random survival forest (RSF) model, and neural multitask logistic regression (DeepSurv) model to predict PGIL patients' overall survival (OS)., Results: The 1-, 3-, 5-, and 10-year OS rates of PGIL patients in the SEER database were 77.1%, 69.4%, 63.7%, and 50.3%, respectively. The RSF model based on all variables showed that the top three most important variables for predicting OS were age, histological type, and chemotherapy. The independent risk factors for PGIL patient prognosis included sex, age, race, primary site, Ann Arbor stage, histological type, symptom, radiotherapy, and chemotherapy, according to the Lasso regression analysis. Using these factors, we built the CoxPH and DeepSurv models. The DeepSurv model's C-index values were 0.760 in the training cohort, 0.742 in the test cohort, and 0.707 in the external validation cohort, which demonstrated that the DeepSurv model performed better compared to the RSF model (0.728) and the CoxPH model (0.724). The DeepSurv model accurately predicted 1-, 3-, 5- and 10-year OS. Both calibration curves and decision curve analysis curves demonstrated the superior performance of the DeepSurv model. We developed the DeepSurv model as an online web calculator for survival prediction, which can be accessed at http://124.222.228.112:8501/ ., Conclusions: This DeepSurv model with external validation is superior to previous studies in predicting short-term and long-term survival and can help us make better-individualized decisions for PGIL patients., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: Dysregulated expression of heat shock proteins (HSP) plays a fundamental role in tumor development and progression. Consequently, HSP90 may be an effective tumor target in oncology, including the treatment of gastrointestinal cancers., Methods: We carried out a systematic review of data extracted from clinicaltrials.gov and pubmed.gov, which included all studies available until January 1st, 2022. The published data was evaluated using primary and secondary endpoints, particularly with focus on overall survival, progression-free survival, and rate of stable disease., Results: Twenty trials used HSP90 inhibitors in GI cancers, ranging from phase I to III clinical trials. Most studies assessed HSP90 inhibitors as a second line treatment. Seventeen of the 20 studies were performed prior to 2015 and only few studies have results pending. Several studies were terminated prematurely, due to insufficient efficacy or toxicity. Thus far, the data suggests that HSP90 inhibitor NVP-AUY922 might improve outcome for colorectal cancer and gastrointestinal stromal tumors., Conclusion: It currently remains unclear which subgroup of patients might benefit from HSP90 inhibitors and at what time point these inhibitors may be beneficial. There are only few new or ongoing studies initiated during the last decade., (© 2023. The Author(s).)

Background: Sarcopenia predicts poor prognosis of a variety of gastrointestinal malignancies. However, there is a lack of study on the association between skeletal muscle index (SMI) and the prognosis of gastrointestinal stromal tumor (GIST). The aim of this study is to develop a novel nomogram based on sarcopenia for GIST patients to predict overall survival (OS)., Methods: SMI was measured by computed tomography scan of 107 patients who underwent resection for primary localized gastrointestinal stromal tumor (GIST). Sarcopenia was defined by cutoff values for SMI as 40.1 cm 2 /m 2 and 39.8 cm 2 /m 2 using optimum stratification for males and females respectively. Factors were included in the nomogram were specified by univariate and multiple Cox proportional hazard analysis. Concordance index (C-index) and calibration curves were conducted to measure the discrimination and accuracy of the nomogram. The utility of the nomogram was assessed by the decision curve analysis (DCA)., Results: Twenty-eight (26.2%) of 107 patients were sarcopenic. Sarcopenia was correlated significantly with body mass index, albumin, female sex, resection style, mitotic index, rupture status, survival. Sarcopenia was significantly related to decreased overall survival (p = 0.003).The nomogram including sarcopenia status, resection style and mitotic index had an excellent discrimination with C-index 0.794. The calibration curves represented a good accordance between the actual observation and nomogram prediction for overall survival. Decision curve analysis illustrated that the nomogram was helpful in clinic., Conclusions: We developed a nomogram based on sarcopenia to predict overall survival after resection of GISTs which is an effective and favorable prognostication tool., (© 2022. The Author(s).)

Introduction: There are no formal guidelines for the management of patients with primary gastrointestinal (GI) cancers who have lung-exclusive or lung-predominant metastases. We performed a retrospective analysis to evaluate host and tumor characteristics of this patient population, model patterns and rates of growth, and describe treatment approaches., Materials and Methods: Eligible patients had a GI cancer with either synchronous or metachronous lung metastases but no other visceral or peritoneal sites of involvement. In addition to collecting detailed patient-specific and tumor-specific information, all imaging studies (computed tomography±positron emission tomography scans) were reviewed by an independent radiologist. Up to 5 lung metastases were tracked through each patient's clinical course. Growth rate was estimated using a linear mixed model analysis., Results: Forty patients met eligibility criteria (18 pancreatic, 15 colorectal, 6 hepatobiliary, 1 gastroesophageal; synchronous vs. metachronous, 13 and 27, respectively). Median time from original cancer diagnosis to onset of metachronous lung lesions was 16 months. Interval from first appearance of lung metastases to treatment initiation was 6.2 months. Average growth rate of the largest lesion was 0.21 mm/mo (95% confidence interval, 0.12-0.30), with substantial intrapatient and interpatient variability. Sixty percent of patients underwent locoregional interventions in addition to or in lieu of systemic therapy for their lung metastases. Median survival of the entire study cohort from first appearance of lung metastases was 54 months., Conclusions: Lung metastases from primary GI cancers have a variable but overall indolent natural history and are generally associated with prolonged survival outcomes. Further efforts to define patterns of growth of lung metastases, informed by size, number, and clinical/molecular features, are needed to guide appropriate timing and selection of therapy as well as surveillance strategies., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Many studies reporting that down-regulation of SOCS6 plays vital roles in promoting progression of malignant tumors have been published. The present study was performed to evaluate whether SOCS6 was significantly associated with prognosis of GIST patients., Methods: Immunohistochemical staining was accomplished to evaluate the expression levels of SOCS6 among GIST patients. The impacts of SOCS6 expression on overall survival (OS) and recurrence-free survival (RFS) of GIST patients were assessed by Cox proportional hazard regression model analysis and Kaplan-Meier curve analysis., Results: It was demonstrated that the expression level of SOCS6 was significantly associated with tumor size (P=0.001). Then according to Kaplan-Meier curve analysis, low expression of SOCS6 was significantly correlated with worse OS and RFS of GIST patients. Ultimately, it was revealed by Cox proportional regression model analysis that low expression of SOCS6 was an independent predictive factor for OS and RFS., Conclusions: Low expression of SOCS6 was an independent prognostic factor for GIST, suggesting its potential as a novel biomarker predicting survival of GIST patients., (© 2021. The Author(s).)

Background: Primary gastrointestinal lymphoma (PGIL), an uncommon subtype of lymphoma, accounts for 1%-4% of gastrointestinal cancers. This study, therefore, aimed to investigate the current 10-year epidemiology and outcomes of PGIL., Methods: This retrospective study involved a hospital-based chart review to analyze the epidemiology, clinical features, predisposing factors, and clinical outcomes of patients diagnosed with, and treated for, PGIL. Data covering 10 years was collected of Thai patients aged ≥ 15 years who had been diagnosed as PGIL with pathological confirmation and treated at Siriraj Hospital, Thailand., Results: A total of 175 PGIL patients were enrolled. Their median age was 60 years (range, 20-98), with a male predominance. The stomach was the most common site of gastrointestinal (GI) organ involvement by lymphoma (38.9%), followed by the small intestine (23.4%) and multiple sites of GI involvement (23.4%). Diffuse large B-cell lymphoma (DLBCL) had the highest proportion of PGIL, accounting for 61.1%. The median patient follow-up time was 13.9 months (range: 0-104.9 months). The median overall survival (OS) of PGIL patients was not reached during the 10 years, with a 5-year OS of 64.4%. The probability of having a better OS was demonstrated in patients with a good performance status who received a rituximab-containing regimen., Conclusions: The stomach was the most common site of lymphoma involvement in the GI tract, with DLBCL accounting for the highest proportion of those patients. The long-term survival outcome was significantly improved in patients with good performance status and rituximab exposure. Trial registration Not applicable.

Exercise training is emerging as a supportive treatment strategy in surgical oncology, but its effects remain uncertain in patients with gastrointestinal cancer. The primary objective of this systematic review and meta-analysis was to evaluate the effects of perioperative exercise training on gastrointestinal cancer-specific mortality, recurrence, and surgical outcomes (postoperative complications, hospitalization, surgical stress) in patients with gastrointestinal cancer. Randomized or quasi-randomized controlled trials evaluating the effects of perioperative exercise training versus control in patients with GI cancer were eligible. MEDLINE, EMBASE, CENTRAL, CINAHL, PEDro, and SPORTDiscus were systematically searched on June 20, 2020. Data were synthesized using random-effects meta-analyses. Risk of bias was assessed using the Cochrane risk of bias tool 2, and the certainty of evidence was assessed using GRADE. Study selection, data extraction, risk of bias, and GRADE assessments were performed independently by two authors. Ten randomized controlled trials comprising 448 participants with gastrointestinal cancer were eligible. Meta-analyses indicated no statistical effects of exercise on postoperative complications (risk ratio: 1.11, 95% CI: 0.84; 1.47), readmissions (risk ratio: 2.76; 95% CI: 0.00, 9394.76), or postoperative length of stay (difference in means: -0.47, 95% CI: -17.2; 16.2 days). None of the eligible studies assessed gastrointestinal cancer-specific mortality or recurrence. Overall risk of bias was high or of some concerns in all studies, and the certainty of evidence was very low. The effects of perioperative exercise on cancer-specific and surgical outcomes are unknown in patients with gastrointestinal cancer due to lack of studies and very low certainty of evidence., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2021. Published by Elsevier Ltd.)

Patients undergoing complex gastrointestinal surgery are at high risk of major postoperative complications (e.g., anastomotic leakage, sepsis), classified as Clavien-Dindo (CD) ≥ IIIa. Identification of preoperative risk factors can lead to the identification of high-risk patients. These risk factors can also be used to design personalized perioperative care. This systematic review focuses on the identification of these factors. The Medline and Embase databases were searched for prospective, retrospective cohort studies and randomized controlled trials investigating the effect of risk factors on the occurrence of major postoperative complications and/or mortality after complex gastrointestinal cancer surgery. Risk of bias was assessed using the Quality in Prognostic Studies tool. The level of evidence was graded based on the number of studies reporting a significant association between risk factors and major complications. A total of 207 eligible studies were retrieved, identifying 33 risk factors for major postoperative complications and 13 preoperative laboratory results associated with postoperative complications. The present systematic review provides a comprehensive overview of preoperative risk factors associated with major postoperative complications. A wide range of risk factors are amenable to actions in perioperative care and prehabilitation programs, which may lead to improved outcomes for high-risk patients. Additionally, the knowledge of this study is important for benchmarking surgical outcomes., Competing Interests: Declaration of interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Atypical tumor response patterns during immune checkpoint inhibitor therapy pose a challenge to clinicians and investigators in immuno-oncology practice. This study evaluated tumor burden dynamics to identify imaging biomarkers for treatment response and overall survival (OS) in advanced gastrointestinal malignancies treated with PD-1/PD-L1 inhibitors., Methods: This retrospective study enrolled a total of 198 target lesions in 75 patients with advanced gastrointestinal malignancies treated with PD-1/PD-L1 inhibitors between January 2017 and March 2021. Tumor diameter changes as defined by immunotherapy Response Evaluation Criteria in Solid Tumors (iRECIST) were studied to determine treatment response and association with OS., Results: Based on the best overall response, the tumor diameter ranged from - 100 to + 135.3% (median: - 9.6%). The overall response rate was 32.0% (24/75), and the rate of durable disease control for at least 6 months was 30.7% (23/75, one (iCR, immune complete response) or 20 iPR (immune partial response), or 2iSD (immune stable disease). Using univariate analysis, patients with a tumor diameter maintaining a < 20% increase (48/75, 64.0%) from baseline had longer OS than those with ≥20% increase (27/75, 36.0%) and, a reduced risk of death (median OS: 80 months vs. 48 months, HR = 0.22, P = 0.034). The differences in age (HR = 1.09, P = 0.01), combined surgery (HR = 0.15, P = 0.01) and cancer type (HR = 0.23, P = 0.001) were significant. In multivariable analysis, patients with a tumor diameter with a < 20% increase had notably reduced hazards of death (HR = 0.15, P = 0.01) after adjusting for age, combined surgery, KRAS status, cancer type, mismatch repair (MMR) status, treatment course and cancer differentiation. Two patients (2.7%) showed pseudoprogression., Conclusions: Tumor diameter with a < 20% increase from baseline during therapy in gastrointestinal malignancies was associated with therapeutic benefit and longer OS and may serve as a practical imaging marker for treatment response, clinical outcome and treatment decision making., (© 2021. The Author(s).)

FRG1 has a role in tumorigenesis and angiogenesis. Our preliminary analysis showed that FRG1 mRNA expression is associated with overall survival (OS) in certain cancers, but the effect varies. In cervix and gastric cancers, we found a clear difference in the OS between the low and high FRG1 mRNA expression groups, but the difference was not prominent in breast, lung, and liver cancers. We hypothesized that FRG1 expression level could affect the functionality of the correlated genes or vice versa, which might mask the effect of a single gene on the OS analysis in cancer patients. We used the multivariate Cox regression, risk score, and Kaplan Meier analyses to determine OS in a multigene model. STRING, Cytoscape, HIPPIE, Gene Ontology, and DAVID (KEGG) were used to deduce FRG1 associated pathways. In breast, lung, and liver cancers, we found a distinct difference in the OS between the low and high FRG1 mRNA expression groups in the multigene model, suggesting an independent role of FRG1 in survival. Risk scores were calculated based upon regression coefficients in the multigene model. Low and high-risk score groups showed a significant difference in the FRG1 mRNA expression level and OS. HPF1, RPL34, and EXOSC9 were the most common genes present in FRG1 associated pathways across the cancer types. Validation of the effect of FRG1 mRNA expression level on these genes by qRT-PCR supports that FRG1 might be an upstream regulator of their expression. These genes may have multiple regulators, which also affect their expression, leading to the masking effect in the survival analysis. In conclusion, our study highlights the role of FRG1 in the survivability of cancer patients in tissue-specific manner and the use of multigene models in prognosis., (© 2021. The Author(s).)

Background: Fatty acid-binding proteins (FABPs) have been found to be involved in tumorigenesis and development. However, the role of FABP4, a member of the FABPs, in GISTs (Gastrointestinal stromal tumors) remains unclear. This study aimed to investigate the expression of FABP4 and its prognostic value in GISTs., Methods: FABP4 expression in 125 patients with GISTs was evaluated by immunohistochemical analysis of tissue microarrays. The relationship between FABP4 expression and clinicopathological features and prognosis of GISTs was analyzed., Results: Multiple logistic regression analysis showed that expression of FABP4 correlated with tumor size and mitotic index. Furthermore, FABP4 level, tumor size, mitotic index, and high AFIP-Miettinen risk were independent prognostic factors in GISTs. The Kaplan-Meier survival curve showed that the 5-year survival rate of patients with high-FABP4 expression GISTs was lower., Conclusions: These results suggested that high-FABP4 expression might be a marker of malignant phenotype of GISTs and poor prognosis., (© 2021 The Authors. Journal of Clinical Laboratory Analysis published by Wiley Periodicals LLC.)

Background: Mixed adeno-neuroendocrine carcinomas (MANEC) are a subgroup of mixed neuroendocrine non-neuroendocrine neoplasms (MiNEN) described as mixed neoplasms containing dual neuroendocrine and non-neuroendocrine components. The aim of this study was to appraise the prevalence of MANEC in the lower gastrointestinal (GI) tract and provide reliable estimates of survival., Method: A systematic review was undertaken in accordance with PRISMA guidelines using PubMed, Embase, Cochrane Library of Systematic Review, Web of Science, and Scopus databases, and a Bayesian hierarchical survival pooled analysis was performed., Results: Of 182 unique records identified, 71 studies reporting on 752 patients met the inclusion criteria. Mean age was 64.2 ± 13.6, with a male-to-female ratio of 1.25. Overall, 60.3% of MANEC were located in the appendix, 29.3% in the colon, and 10.4% in the anorectum. More than a quarter (29%) of patients had stage IV disease at diagnosis, with higher prevalence in appendiceal than colonic and anorectal primaries. More than 80% had a high-grade (G3) endocrine component. Of the 152 patients followed up for a median of 20 months (interquartile range limits, 16.5-32), median overall survival was 12.3 months (95% credible interval [95%CrI], 11.3-13.7), with a 1.12 [95%CrI, 0.67-1.83] age-adjusted hazard ratio between metastatic and non-metastatic MANEC. Stage IV disease at diagnosis was more prognostically unfavorable in cases of colonic compared to anorectal origin., Conclusion: MANEC is a clinically aggressive pathological entity. The results of this study provide new insights for the understanding of tumor location within the lower GI tract and its prognosis in terms of overall survival., (Crown Copyright © 2021. Published by Elsevier Ltd. All rights reserved.)