bluuebunny/crossref_metadata_2025_split huggingface dataset:
Gene expression profiles in Hispanic patients with early-onset gastric cancer.
Authors: Ju Michelle R , Hong Changjin , Karalis John D , Hammer Suntrea , Porembka Matthew R. , Hwang Tae Hyun , Wang Sam C. 
Published: January 2023

464 Background: A larger proportion of Hispanic gastric cancer patients are diagnosed at a young age than patients of other ethnicities. Despite diagnosis at an early age, young Hispanic patients also present more frequently with advanced disease. Whether there are molecular differences between tumors from young and old Hispanic gastric cancer patients is unknown. Methods: We performed RNA-sequencing on pre-treatment tumor samples of gastric cancer patients of self-identified Hispanic ethnicity. We stratified patients into two groups: <50 years and ≥50 years. Differentially expressed genes between groups were detected using the DESeq2 package (RStudio). We performed Gene Set Enrichment Analysis (GSEA) to identify pathways that were uniquely overexpressed in each age group. Results: 57 patients were included in our study. 23 patients were <50 years and 33 patients were ≥50 years. Comparison of the top 10% most differentially expressed genes showed no clustering based on age. However, visual inspection of the top 40 most differentially expressed genes revealed 2 distinct patterns of gene expression between age groups. GSEA revealed upregulation of DNA replication, cell cycle, and DNA repair pathways in the younger patients The tumors in younger patients also had upregulation of multiple immune activation pathways. Cancers from older patients had upregulation of programmed cell death pathways. Conclusions: Early-onset gastric cancer in Hispanic patients may represent a distinct biologic process.
Nomogram to predict peritoneal dissemination in gastric cancer.
Authors: Penumadu Prasanth , Kohli Pavneet , Dubashi Biswajit , Ganapathy Sachit 
Published: January 2023

465 Background: Peritoneal metastasis is a poor prognostic factor in patients with gastric cancer and cannot be predicted, that can tailor oncological treatment. We retrospectively analyzed the clinicopathological data among 110 gastric cancer patients. Methods: Univariate logistic regression was performed with peritoneal disease as the outcome to assess potential risk factors associated with it. We found that age, gastric outlet obstruction, VEGF, Ki67, p53 and NLR ratio were significant factors associated with peritoneal disease. Using multiple logistic regression, the adjusted odds ratio and 95% confidence interval were estimated. The predictive accuracy of this regression model was estimated using ROC curve analysis and Area under the curve, sensitivity and specificity were estimated. A nomogram was plotted based on the regression coefficient for the prediction of peritoneal disease. Results: It was estimated that age less than 40 years had 0.19 (0.05, 0.79), GOO positive had 2.04 (0.69, 6.03), VEGF positive had 4.69 (1.79, 12.33), elevated Ki67 had 3.94 (1.55, 9.97), positive p53 had 0.43 (0.17, 1.11) and NLR ratio had 1.15 (0.88, 1.51) odds of having peritoneal disease from multiple logistic regression. The regression model had significant goodness of fit for the data (Hosmer-Lemeshow test P value < 0.001). On estimating the AUC from the ROC curve for the model, we found that it had a good discriminatory ability with AUC = 0.81. Sensitivity was estimated to be 71.15%, whereas specificity was estimated to be 72.41% for the model. Subsequently, a nomogram was plotted based on the regression estimated from this model. Conclusions: The nomogram could risk-stratify those at risk of developing peritoneal disease and modify therapeutic strategies like selecting patients for prophylactic intraperitoneal chemotherapy or other novel therapeutic strategies. However, the nomogram needs to be validated prospectively.
Risk of gastric cancer among patients with newly diagnosed ulcerative colitis: A nationwide population-based study.
Authors: Kim Hee Man , Kang Dae Ryong , Kim Hyun-Soo 
Published: January 2023

471 Background: We aimed to assess gastric cancer risk in patients with newly diagnosed ulcerative colitis (UC). Methods: Based on claims data of the Korean National Health Insurance from January 2006 to December 2015, we identified 30,546 patients with UC and randomly selected 88,829 age- and sex-matched non-UC individuals (controls). Hazard ratios (HRs) adjusted for covariates were calculated using multivariate Cox proportional-hazards regression. Results: Overall, 77 (0.25%) patients with UC and 383 (0.43%) non-UC individuals developed gastric cancer during the period. HR of UC was 0.60 (95% CI: 0.47–0.77) for gastric cancer, compared to non-UC individuals. When stratified according to age and sex, HRs in 20-39, 40-59, and ≥ 60 years of age at diagnosis of UC were 0.19 (95% CI: 0.04–0.98), 0.65 (95% CI: 0.45–0.94), and 0.60 (95% CI: 0.49–0.80), and HR of male UC patients was 0.54 (95% CI: 0.41–0.73) for gastric cancer. However, among UC patients, multivariable analysis revealed that HR in ≥ 60 years of age at diagnosis of UC were 12.34 (95% CI: 2.23-68.16), consistent with old age as a risk factor of gastric cancer in general population. Conclusions: Patients with UC had a decreased gastric cancer risk compared with non-UC individuals. Further research is needed to elucidate the reason.
The impact of race and ethnicity on survival in primary liver cancer: A propensity-adjusted analysis.
Authors: Ozer Muhammet , Goksu Suleyman Yasin , Kazmi Syed Mohammad Ali 
Published: January 2023

500 Background: Primary liver cancer is the fifth most common malignancy and the second most frequent cause of cancer-related death worldwide. Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer, followed by Intrahepatic cholangiocarcinoma (ICC), and the incidence of liver cancer is rapidly rising in the United States. Race and ethnicity affect the outcomes in many solid cancers; therefore, we aimed to study the effect of race and ethnicity on overall survival (OS) in primary liver cancer. Methods: We selected adult patients who had primary liver cancer (HCC and ICC) diagnosed between 2004 and 2016 using the NCDB database. We stratified the patients into two groups as white and black. We performed the Kaplan-Meier method for median overall survival (OS), and the Cox regression method for multivariate analyses after adjusting for clinically significant confounding variables. Also, we used 1:1 nearest neighbor propensity score matching to reduce selection bias. Results: A total of 122,049 patients, 83.1% was white, 16.9% was black. Black patients were more likely to be young ( p<.001), to live in the metropolitan area ( p<.001) and South Atlantic states ( p<.001), to be treated academic/research facility ( p<.001), to be uninsured ( p<.001). In contrast, white patients were most frequently to be highly educated ( p<.001), to have higher income ( p<.001), to travel longer distances (≥50 miles) for treatment ( p<.001). Also, black patients had a higher rate of HCC ( p<.001), advanced stage ( p<.001), high metastasis rate ( p<.001), whereas white patients had a higher rate of ICC ( p<.001), higher comorbidity ( p<.001), high treatment rate (surgery, chemotherapy, and radiotherapy) ( p<.001). The gender percentage was similar in both groups. In unmatched groups, white patients had significantly better median OS compared to black (9.9 vs. 8.4 months, p<.001), but this difference did not continue after adjusted for age, sex, facility type, insurance status, income, education, rurality, travel distance, comorbidity, metastatic rate, treatment receipt (surgery, chemotherapy, radiotherapy), primary site (HR=1.01 95% CI: 0.99-1.03, p=.18). In ethnic groups, Hispanics had significantly improved OS compared to non-Hispanic white (NHW) and non-Hispanic black patients (NHB) (median OS 12 vs. 9.7 vs. 8.5 months, respectively, p<.001), and this significance was persisted with multivariate analysis (HR=0.80 95% CI: 0.78-0.82, p<.001). After propensity score matching, white and black patients were similar OS (p=NS) but Hispanics were still significantly improved OS versus NHW and NHB patients (HR=0.76 95% CI: 0.71-0.80, p<.001). Conclusions: Black patients had a higher stage, percentage of metastasis and lower treatment rate, but they had a similar OS compared to white patients. Hispanics had significantly improved OS than others, even after adjusted for clinically important confounding variables.
Health-related quality of life (HRQoL) impact of lenvatinib (len) plus pembrolizumab (pembro) versus len plus placebo (pbo) as first-line (1L) therapy for advanced hepatocellular carcinoma (aHCC): Phase 3 LEAP-002 study.
Authors: Llovet Josep M , Kudo Masatoshi , Merle Philippe , Meyer Tim , Qin Shukui , Ikeda Masafumi , Xu Ruocai , Edeline Julien , Ryoo Baek-Yeol , Ren Zhenggang , Cheng Ann-Lii , Galle Peter R , Kaneko Shuichi , Kumada Hiromitsu , Kamble Shital , Norquist Josephine M , Mody Kalgi , Dubrovsky Leonid , Siegel Abby B. , Finn Richard S. 
Published: January 2023

506 Background: In LEAP-002 (NCT03713593), len + pembro achieved a median OS of 21.2 mo vs 19.0 mo with len + pbo with manageable safety in both arms in 1L aHCC, although the significance thresholds for OS and PFS were not met. We present here the results of prespecified exploratory patient (pt)-reported outcomes (PROs). Methods: 794 pts were randomized. PROs were assessed by EORTC QLQ-C30, EuroQol-5D5L (EQ5D-5L), and EORTC QLQ-HCC18 questionnaires. Analysis population for HRQoL endpoints included pts who received ≥1 dose of study Tx and completed ≥1 HRQoL assessment. Least squares mean (LSM) score changes from baseline (BL) to wk 27 were compared using a constrained longitudinal data analysis model (covariates: Tx, time, Tx by time interaction, and stratification factors). Kaplan-Meier method was used to estimate time to deterioration (TTD, time to 1st onset of ≥10 [out of 100] deterioration from BL in a given scale or subscale/confirmed by a 2nd adjacent ≥10 deterioration from BL) for EORTC QLQ-C30 global health status (GHS)/QoL, physical functioning (PF), and EORTC QLQ-HCC18 abdominal swelling, pain and fatigue, as reported by pts. Stratified Cox proportional hazards model was used to assess the magnitude of the Tx difference (HR) between arms in TTD. Results: Compliance with PRO assessments was >91% from BL until wk 27 in both arms. From BL to wk 27, LSM changes in GHS/QoL, PF, role functioning (RF), QLQ-HCC18 functional/domain scores and EQ5D-5L VAS were generally similar between the two arms (Table). Treatment with len + pembro delayed deterioration of patient-reported quality of life vs len + pbo (median TTD, 11.5 vs 4.3 mo; HR, 0.80; 95% CI, 0.65-0.98). LSM score difference (95% CI) was 0.5 (-2.5, 3.4) for GHS/QoL, -1.7 (-4.5, 1.1) for PF, -1.0 (-4.9, 2.9) for RF, 1.0 (-2.2, 4.3) for abdominal swelling, 2.0 (-1.2, 5.2) for fatigue, 2.0 (-1.0, 5.0) for pain, and 0.6 (-2.0, 3.2) for EQ5D-5L VAS. Median TTD in QLQ-C30 PF (5.7 vs 9.1 mo; HR, 1.14; 95% CI, 0.93-1.41) and QLQ-HCC18 abdominal swelling (NR vs NR; HR, 1.19; 95% CI, 0.89-1.60) /fatigue (2.9 vs 2.8 mo; HR, 0.98; 95% CI, 0.81-1.19)/pain (9.6 vs 7.9 mo; HR, 0.93; 95% CI, 0.75-1.16) was similar between the arms. Conclusions: Len + pembro generally preserved HRQoL vs len + pbo in 1L for aHCC. Combined with efficacy and safety results from LEAP-002, these findings support continued development of len + pembro in HCC. Clinical trial information: NCT03713593 . [Table: see text]
Outcome of receiving lenvatinib following immunotherapy in patients with advanced hepatocellular carcinoma.
Authors: Gile Jennifer , Palmer Mathias Earl , Storandt Michael H. , Bekaii-Saab Tanios S. , Tran Nguyen H. , Mahipal Amit 
Published: January 2023

507 Background: Lenvatinib, a multikinase inhibitor, is an FDA approved treatment for advanced hepatocellular carcinoma (HCC) in the first line setting. Atezolizumab and bevacizumab are considered new standard of care as first line therapy after results of the IMBrave 150 trial. Currently, we do not have data to suggest any second-line treatment after administration of immunotherapy. We describe the clinical outcomes in patients with advanced HCC who received lenvatinib following treatment with immunotherapy. Methods: We conducted a multicentric, retrospective analysis of patients with advanced HCC diagnosed between 2010 and 2021 at Mayo Clinic in Minnesota, Arizona, and Florida. The study was reviewed and approved by the intuitional review board. The primary outcomes were overall survival (OS) and progression free survival (PFS). Results: We identified 53 patients with advanced HCC who received lenvatinib following immunotherapy. Most patients (83%) were male. Median age at start of lenvatinib was 67 years old. Forty-two (79%) patients had a Child-Pugh score of A at diagnosis while 30 (58%) patients were still Child-Pugh A at time of lenvatinib initiation. Risk factors for HCC included Hep C (43%), alcohol use (34%), NASH (15%) and hepatitis B (7%). Forty-five (85%) patients received lenvatinib in the 2nd line and 8 (15%) patients received it as third line or later. At time of data extraction, 38 (72%) patients had died. Median PFS was 4 months (95% CI: 3 – 6) and median OS from time of lenvatinib initiation was 13 months (95% CI: 6 – 24). The most common adverse events of any grade included fatigue (53%), hypertension (37%), AST elevation (30%), anorexia (28%), bilirubin elevation (25%) and diarrhea (25%). Twenty-one (40%) patients experienced grade 3 or higher adverse events including hypertension (25%), confusion (6%), acute kidney injury (2%), hyperkalemia (2%), ALT elevation (2%), proteinuria (2%), arthralgia (2%), heart failure (2%), AST elevation (2%), bilirubin elevation (2%), palmar-plantar erythrodysesthesia (2%), oral mucositis (2%), weight loss (2%), hypothyroidism (2%), anorexia (2%), fatigue (2%) and diarrhea (2%). Seven patients stopped treatment due to adverse events: 1 for hypertension, 2 for confusion, 1 for heart failure, 2 for fatigue, and 1 for elevated bilirubin. Conclusions: The optimal sequencing of therapy for patients with advanced HCC following progression on immunotherapy remains unknown. We found that median OS was 13 months in patients who received lenvatinib after immunotherapy which is comparable to survival in other studies when used as first line therapy. Our experience demonstrates that patients may benefit from treatment with lenvatinib following initial progression on immunotherapy.
Immunohistochemical and genetic profiles do not predict behavior of mixed hepatocellular intrahepatic cholangiocarcinoma.
Authors: Sucre Santiago , Paredes Rodrigo , Peters Mary Linton Bounetheau 
Published: January 2023

516 Background: Combined hepatocellular intrahepatic cholangiocarcinoma (HCC CC) is a rare tumor defined by pathologic characteristics of both hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC). Immunohistochemical (IHC) and genetic profiles (GP) are used for diagnosis and therapeutic decisions, however often mixed tumors are treated as ICC given the presumption this subtype dominates response. Recent studies challenged this practice by demonstrating improved response with immune oncology (IO) therapy. Methods: We identified nine patients with biopsy-proven mixed HCC CC between September 2013 and March 2022. We classified IHC as related to either HCC (HepPar1, Glypican3, CD10, Glutamine Synthetase, CEA, AFP, Arginase1) or ICC (CK19, CK7, CK20, CDX2, Mucicarmine, CA9, MOC31). GP results were classified as HCC-related (TERT, CTNNB1, MYC) or ICC-related (ARID1A, FGFR2, IDH1). Treatment selection, duration of response, and survival were recorded. Results: All subjects had a mix of IHC markers, although six had a preponderance of HCC-related IHC. GP information was available for seven patients, of whom six demonstrated mutations relating only to HCC, and one demonstrated mutations relating only to ICC. All sequenced tumors were MSS, and six of the seven were TMB low. Four subjects used only liver directed therapy for small intrahepatic tumors. Four subjects underwent systemic therapy, a mix of HCC and ICC regimens, three of whom used IO agents. Median survival was 12 months. Conclusions: HCC CC tumor profiling by IHC and GP was more closely aligned with HCC than ICC. However, the median survival for these patients was lower than expected for liver-restricted HCC, more congruent with an ICC phenotype. Although liver-directed therapy was used, the duration of response was shorter than expected for HCC, even in HCC-like tumors. For those receiving systemic therapy, most subjects did not achieve median response with any regimen. Although a previous case series showed good response to IO agents, in our cohort we did not see this effect. In this series, mixed HCC CC was more aggressive than HCC, with largely poor response to both liver directed and systemic therapy. We have insufficient information to correlate systemic treatment response relative to IHC or GP.[Table: see text]
An active trend of immunotherapy combination regimen as second-line therapy for advanced biliary tract cancer: A multicenter retrospective study.
Authors: Ying Jieer , Weng Haimin , Xu Qi , Li Jingjing , Wei Qing , Zeng Pengfei , Chen Yuemiao 
Published: January 2023

520 Background: FOLFOX as second-line therapy remains the standard of care in patients with biliary tract cancer (BTC), but its efficacy is suboptimal. Currently, cytotoxic chemotherapy, targeted therapy, and immunotherapy alone or in combination are being tested in patients with pretreated advanced BTC for in clinical trials. This study aimed to evaluate and compare the anticancer of distinct treatment regimen in patients with advanced BTCs who progress after first-line chemotherapy. Methods: Patients diagnosed BTC who received second-line therapy were retrospectively identified at 3 sites across the Zhejiang province between January 1, 2018, and June 31, 2022. Clinicopathological information and therapeutic outcome, including subtype of BTC, response per RECIST v1.1, treatment duration, adverse events (AE), progression-free survival (PFS), and overall survival (OS), were recorded and estimated. Results: A total of 98 patients with BTCs were reviewed and recruited eventually: the chemotherapy group (cohort A, n=30), the chemotherapy plus ICIs group (cohort B, n=25), the TKIs group (cohort C, n=17), and the TKIs plus ICIs group (cohort D, n=26). The median PFS and OS were 2.4 months (95%CI: 1.6–3.2) and 7.0 months (95% CI: 6.4–7.5) for cohort A, 3.9 months (95%CI: 2.8–5.0) and 10.7 months (95% CI: 6.9–14.5) for cohort B, 1.6 months (95%CI: 0.8–2.4) and 7.1 months (95% CI: 0.7–13.5) for cohort C, and 4.7 months (95%CI: 3.1–6.2) and 10.1 months (95% CI: 4.1–16.1) for cohort D, respectively. In the cohort A, B, C, and D, confirmed ORRs were 10%, 20%, 11.8% and 19.2%, separately, and DCRs were 46.7%, 68%, 43.8% and 76.9%, respectively. The efficacy of ICIs plus TKIs was optimal in terms of tumor response and associated with prolong PFS. Six patients (20%), nine patients (36%), five patients (29.4%), and elven patients (42.3%) were experienced ≥ grade 3 treatment-related AEs in cohort A, B, C, and D, respectively. Conclusions: Immunotherapy combination strategy beyond first-line systemic chemotherapy plays a positive role in advanced BTCs. Both TKIs plus ICIs and chemotherapy plus ICIs could be considered as candidates to second-line trails and turn into a competitive second-line treatment regimen for advanced BTCs in clinical practice.
Short- and long-term real-world survival for metastatic bile duct cancer, 2000 to 2018.
Authors: Wood Sarah Jeanne , Nghiem Van , Williams Grant Richard , Paluri Ravi Kumar , Outlaw Darryl Alan , Gbolahan Olumide B. 
Published: January 2023

523 Background: Real-world survival outcomes in metastatic biliary tract cancer (BTC) are largely unknown. Quoted numbers are often based on reports of clinical trials and hospital registry data and may not be representative of patients treated in the real world. Furthermore, the impact of more widespread adoption of standard combination chemotherapy since 2010 on survival is unclear. We performed a population-based survival analysis of patients who presented with metastatic BTC, including intrahepatic cholangiocarcinoma, extrahepatic cholangiocarcinoma and gallbladder cancer. Methods: Utilizing the Surveillance, Epidemiology, and End Results (SEER) database, we collected data for patients diagnosed with metastatic BTC from 2000 to 2018 and stratified by overall survival (OS) of ≤ 3 months (short-term survivors) or ≥ 12 months (long-term survivors), before and after 2010. Additional patient and tumor characteristics, including anatomic location, prior surgical intervention, age, sex, race, and marital status were retrieved. Survival was analyzed using the Kaplan-Meier method. Multivariate cox regression models assessing effects of patient and tumor characteristics between short-term and long-term survivors were employed. Results: Of the 13,287 cases retrieved, 57% were female. Median age was 68 years (range 10-100). Prognosis correlated with anatomic location, marital status, and period of diagnosis. 41% of patients were short term survivors and only 20% were long term survivors. Median OS was 4.5 months for the entire cohort. Median OS only improved marginally from 3.5 months pre-2010 to 4.5 months post-2010 ( p<0.001). Long-term survivors tended to be younger, with a median age at diagnosis of 64 years vs 72 years ( p<0.001). Within the long-term survivor cohort, intrahepatic disease was significantly associated with improved outcomes (HR 0.81, 95% CI 0.73 – 0.90, p= 0.001). Conclusions: The real-world prognosis of metastatic BTC is remarkably poorer than described in clinical trials as a large proportion of patients survive less than three months. Over the last decade, the improvement in survival has been minimal.