bluuebunny/crossref_metadata_2025_split huggingface dataset:
Disproportionate morbidity and mortality in African American and Asian patients from colorectal cancer: A nationwide analysis.
Authors: Franco Jorge , Franco Diana , Farooq Umer , Ma Irene 
Published: June 2022

3628 Background: Published literature points towards the disproportionate prevalence of colorectal cancer (CRC) in ethnic groups. Racial minorities are also prone to higher mortality due to inequalities in access to healthcare. Therefore, we examined the disparities in hospital-related outcomes among racial groups from CRC. Methods: We investigated the National Inpatient Sample 2019 employing International Classification of Diseases-10 (ICD-10) codes to include adult patients with CRC. We compared various outcomes stratified by racial groups with White as the reference group. Analyses were performed using STATA (v 14.2), considering 2 sided P< 0.05 as statistically significant. Proportions were compared using Fisher exact test and continuous variables using Student’s t-test. Confounding variables were adjusted using multivariate logistic and linear regression analyses and included: gender, Charlson Comorbidity Index, median household income for patients’ zip codes, hospital location/region/bedside, and insurance status. Results: Out of 732,492 included patients, 72.77% White, 13.66% African American (AA), 9.91% Hispanics, and 3.65% Asians were in the cohort. AA and Asians had higher mortality odds than White, while Hispanics had mortality similar to White. AA had a lower mean length of stay by 0.74 days than White. All racial groups incurred higher mean total charges compared to White. AA and Hispanics had lower odds of undergoing colectomy. Overall, all racial groups had high morbidity compared to White. Among subgroups, the odds of morbidity markers (sepsis, lower GI bleed, and acute renal failure) were higher in AA and Asians than Hispanics. Post-op adhesions and DVT/PE were not significantly different among racial groups. Conclusions: AA and Asians disproportionately suffer from higher mortality from colorectal cancer than Hispanics and White. Lower colectomy rates (a definitive CRC treatment) in AA and higher in-hospital complication burden in Asians are possible explanations; however, further research needs to establish if race-specific genomics are also responsible for disparities. [Table: see text]
Impact of immune-related adverse events (irAEs) on PD-1/L1 inhibitors efficacy in advanced esophageal cancer.
Authors: Qin Wenru , Wang Linlin 
Published: June 2022

4061 Background: The recent development of Immune checkpoint inhibitors (ICIs) has improved treatment outcomes for patients with esophageal cancer, although it may initiate autoimmune-related disorders in some patients. Across disease sites, patients who experience irAEs while on therapy with anti-PD-1 and anti-PD-L1 antibodies have been documented to experience improved outcomes as measured by overall response rate (ORR), progression-free survival (PFS) and overall survival (OS). Methods: We reviewed the medical records and the following characteristics of patients were collected: age, gender, Eastern Cooperative Oncology Group performance status (ECOG PS), stage, histology, history of surgery, metastatic sites, therapy line, presence of target lesion according to the response evaluation criteria in solid tumors (RECIST) version 1.1, LDH level before initiating ICIs treatment. We divided the patients treated with ICIs into two groups based on occurrence of irAEs. We compared the efficacy between the irAE - and irAE + groups. Results: There were total 295 patients. Of all the patients, 143 patients (50.2%) suffered from irAEs. The median patient age was 60 years (range, 36–84). Baseline characteristics including gender, ECOG PS, tumor location, history of surgery, histology, number of organs with metastases, site of metastases, therapy line, history of drinking, history of smoking between patients with or without irAE were not significantly different. The most frequent irAEs were Anemia(71/295, 24.07%), Pneumonitis (55/295, 18.64%), Cardiovascular toxicities (35/295, 11.86%). There were no grade 5 adverse events related to immunotherapy. Objective response was observed in 92 patients (31.19%), 54 of the 143 patients with irAEs had objective response (37.76%) in contrast with 38 of the 152 cases without irAEs (25.00%). Median PFS in patients with irAEs was 10.27 months and 6.2 months in those without irAEs (p<0.001). Median OS in patients with irAEs was 15.4 months and 9.2 months in those without irAEs(p<0.001).Multivariate analyses identified an ECOG PS ≥2, cycles ≤8, and without irAEs as independent poor prognostic factors (p=0.003, p <0.001 and p=0.011). Multivariate analysis demonstrated that ECOG PS ≥2, Therapy line≥22nd,without radiation and absence of irAEs were associated with a poor overall survival(p=0.022, p=0.006, p. <0.001 and p=0.002). Multivariable analysis also revealed that Cycles>8, Radiation and Antiangiogenic therapy were positively associated with occurrence of irAEs(p<0.001, p=0.002, p=0.025). Conclusions: In advanced esophageal cancer treated with PD-1/L1 inhibitors., patients with irAEs showed a markedly improved efficacy over patients without irAEs.
Toripalimab combined with gemcitabine and S-1 in the first-line treatment of advanced biliary tract cancer.
Authors: Li Wei , Wang Yueqi , Yu Yiyi , Li Qian , Wang Yan , Zhang Chenlu , Xu Xiaojing , Guo Xi , Cui Yuehong , Hao Qing , Huang Lujia , Liu Houbao , Liu Tianshu 
Published: June 2022

4081 Background: Gemcitabine combined with platinum/fluorouracil drugs is the standard first-line treatment for advanced biliary tract cancers (BTCs), but the overall effect needs to be further improved. This study intended to explore the safety and efficacy of toripalimab combined with chemotherapy in the first-line treatment of advanced BTCs. Methods: This single-arm, phase II clinical trial enrolled patients with advanced BTCs who had not received systemic treatment. Toripalimab combined with chemotherapy were applied as first-line treatment: toripalimab (240 mg, iv, d1), gemcitabine (1000 mg/m2, iv, d1&d8), and S-1 (40-60mg bid po, d1-14, Q21d). The primary endpoint was progression-free survival (PFS), and the secondary endpoints included overall survival (OS), objective response rate (ORR), duration of response (DOR) and safety. The study explored the association between response with PD-L1 expression, tumor mutational burden (TMB) and genetic variations identified by next-generation sequencing (NGS) of peripheral blood. Results: 50 patients were enrolled from January 2019 to August 2021 with a median follow-up time of 24.0 months (4.3-31.0). The median PFS was 7.0 months (95%CI: 5.0-8.9 months); median OS was 15.0 months (95%CI: 11.6-18.4 months). Of the 49 patients who completed the evaluation for tumor response, the ORR was 30.6% (95%CI: 17.2%-44.0%), and the disease control rate was 87.8% (95%CI: 78.2%-97.3%). The most common treatment-related adverse events (TRAEs) were leukopenia (98.0%), neutropenia (92%), and anemia (86.0%). Grade III/IV TRAEs included leukopenia (38.0%), neutropenia (32%), skin rash (6%), anemia (2.0%), mucositis (2%) and immune-related colitis (2%).Among them, the Grade III/IV immune-related adverse events irAEs) worthy of attention included were skin rash and immune-related colitis. There was no significant difference in PFS and OS among intrahepatic cholangiocarcinoma, extrahepatic cholangiocarcinoma and gallbladder cancer. Exploratory study showed that patients with CPS≥1 had longer PFS. However, there was no significant correlation between TMB and PFS. Conclusions: Toripalimab combined with gemcitabine and S-1 (GS) has shown good safety in the first-line treatment of advanced BTCs. Although the primary endpoint did not reach the preset goal, toripalimab plus GS as first-line treatment has shown encouraging data of PFS and OS in patients with advanced BTC, which is worthy for further verification. Biomarker analysis showed that the expression level of PD-L1 could predict the curative effect. Clinical trial information: NCT03796429.
Bortezomib in PTEN-deficient patients with advanced intrahepatic cholangiocarcinoma: An open-label, prospective, phase II trial.
Authors: Yuan Zhen-gang 
Published: June 2022

4092 Background: Intrahepatic cholangiocarcinoma (ICC) is the second-most common primary liver malignancy after hepatocellular carcinoma. Prognosis of cholangiocarcinoma is poor and therapy options are limited. Bortezomib in unselected patients with BTC has been failed in previous clinical trial. Our previous research dedicates that PTEN-deficient facilitates sensitivity to proteasome inhibition in intrahepatic cholangiocarcinoma. In this open-label，prospective，phase II trial, we explore the efficacy and safety of bortezomib in PTEN-deficient advanced intrahepatic cholangiocarcinoma patients who have progressed during Gemcitabine based treatment. Methods: Between August 1, 2017, and July 31, 2021, A total of 130 patients were under went PTEN immunohistochemical staining for screening and 15 patients enrolled. Patients with PTEN-deficient advanced intrahepatic cholangiocarcinoma who had progressed after GC/Gemox therapies received bortezomib 1.3 mg/m2 days 1, 4, 8, and 11 of a 21-day cycle. The primary endpoint was objective response rate according to Response Evaluation Criteria in Solid Tumors v1.1. Results: The overall response rate was 23.1% (3/13) and disease control rate was 53.8% (7/13). The Median time of follow up was 4.2 months (95% CI: 0.7̃17.2 months). median progression-free survival was 2.3 months and the median overall survival was 9.6 months. Adverse events of any grade were reported in 14 patients. Thrombopenia was the most common toxicity. Conclusions: Bortezomib provided an encouraging objective response and disease control as second-line therapy for PTEN-deficient Patients with advanced intrahepatic cholangiocarcinoma, and improving the overall survival to 9.6 months. Bortezomib would be a promising treatment option in PTEN-deficient selected patients.
A prospective, multicenter, phase II trial of albumin-paclitaxel plus cisplatin versus gemcitabine plus cisplatin in first-line treatment of advanced biliary tract tumors.
Authors: Yang Xiao , Zhuang Liang , Dai Yuhong , Qiu Hong , Yuan Xianglin 
Published: June 2022

4099 Background: The prognosis of biliary system tumors is poor, Gemcitabine combined with cisplatin has been the standard first-line treatment for advanced biliary system tumors, but its efficacy and adverse effects are unsatisfactory. Albumin-paclitaxel is a novel paclitaxel with a broad-spectrum anti-tumor effect, which has been widely used in the treatment of digestive system malignant tumors. Therefore, we designed this study to investigate the efficacy and safety of the combination of albumin-paclitaxel and cisplatin compared with gemcitabine combined with cisplatin in patients with previously untreated advanced biliary tract tumors. Methods: This is a multicenter, randomized, controlled, investigator-initiated Phase II trial designed to enroll patients with unresectable, recurrent, or metastatic cholangiocarcinoma (including intrahepatic cholangiocarcinoma, extrahepatic cholangiocarcinoma, and gallbladder carcinoma). After enrollment, patients were randomly assigned to the experimental TP group (albumin paclitaxel 125mg/m2 iv, D1, 8 cisplatin 75mg/m2 IV, D1 Q21 ) or the control GP group (gemcitabine 1000mg/m2 IV, D1, 8 cisplatin 75mg/m2 iv, D1 Q21) and received six cycles of chemotherapy. The primary endpoint was PFS, and the secondary endpoint was OS, ORR, and safety. Results: Up to January 2022, 67 patients were enrolled, the 41male and 26 female patients had a median age of 55(range 32-74) years. Of the 67 enrolled patients, 33 were randomly assigned to the TP group and 34 to the GP group. Among the these patients, 47 were diagnosed with intrahepatic cholangiocarcinoma, 7 with extrahepatic cholangiocarcinoma, and 13 with gallbladder cancer. 48 patients had completed at least 2 cycles of chemotherapy and were available for evaluation, mPFS in the TP and the GP groups was 7.7 and 7.5 months, respectively (HR 1.33, CI 0.61 - 2.91,P = 0.469), mOS in TP and GP groups was 12.1 months and 12.9 months, respectively (HR 1.62, 95% CI 0.67-4.17,P = 0.271). After the first assessment, the ORR was 39.4% and 35.3% in the TP group and the GP group, respectively. In terms of side effects, bone marrow suppression (61% vs 76%) was the most predominant adverse events in both groups, abnormal liver and kidney function (56% vs 67%), gastrointestinal reactions (including nausea, vomiting, diarrhea, constipation, etc.) (46% vs 43%), rash or allergy (44% vs 37%), and other side effects such as fever and influenza symptoms (21% vs 24%) were also observed in the TP group and the GP group. Conclusions: The result of this study showed that the regimen of albumin paclitaxel combined with cisplatin was non-inferior to gemcitabine combined with cisplatin in terms of PFS, OS and ORR, and the safety advantages of the combination of albumin paclitaxel and cisplatin make it a potential regiment for first-line treatment of advanced biliary tract tumors. Clinical trial information: ChiECRCT-20180167.
Quantitative analysis of spatial distribution of lymphocytes in hepatocellular carcinoma: A biomarker correlated with survival and gene expression in cancer immune system.
Authors: Lee Hong-Seok , Kim Kyungdoc , Kang Guhyun , Jung Kyu-Hwan , Kaseb Ahmed Omar , Lee Sunyoung S. 
Published: June 2022

4119 Background: Tumor microenvironment (TME) is known to impact prognosis in hepatocellular carcinoma (HCC). Although digital pathology and artificial intelligence have been adopted in modern medicine and oncology, few quantitative biomarkers have been identified to predict the prognosis and guide treatment for HCC via an automated analysis of TME at the cellular level. Methods: Histopathological images and clinical data of 365 cases with HCC were obtained from TCGA (The Cancer Genome Atlas), and 60 of HCC pathology images and cancer lesion annotations were collected from PAIP2019 [1]. DenseNet-based HCC segmentation model (F1-score, 0.904) and Hover-Net-based cell detection model (F1-score, 0.914) were developed using PAIP2019 and MoNuSac datasets, respectively [2,3,4]. Each histopathology image of TME was segmented via the segmentation model into two areas: 1) non-tumoral regions that include the stroma; 2) tumoral regions where HCC cells are concentrated. The cell detection model recognized individual cells on images, specified lymphocytes, and calculated ratios of lymphocyte to total cell count (RLTCC) in segmented regions. RLTCC was then correlated with clinical survival outcomes, HCC primary risk factors, and RNA expression profiles. Results: RLTCC in tumoral regions was not significantly associated with prognosis. Patient groups with higher RLTCC in non-tumoral regions (RLTCC in NT) showed better overall survival (OS) than those with lower RLTCC in NT regardless of HCC risk factors (median OS 45.7 vs 18.6 months; log hazard ratio of -1.6 ± 1.1, p=0.006). These patients had significantly enriched expression of genes (p<0.05) related to cancer antigen presentation (higher gene expression by +33.7%), recognition of cancer cells by T-cell (+32.0%), T-cell priming and activation (+32.2%), immune cell localization to tumors (+31.9%), and killing of cancer cells (+24.7%). Those with HCC etiology of hepatitis B and C had more patients in the higher RLTCC in NT (17/21 patients, 81.0%; 23/29, 79.3%, respectively). In comparison, those with alcohol consumption showed equal distribution (26/53, 49.1%). The RLTCC in NT in hepatitis B/C groups was statistically higher than alcohol consumption group (p<0.05). Conclusions: A digital prognostic biomarker, RLTCC in NT of TME was identified as a significant prognostic indicator, and it was shown to correlate with RNA gene expression related to T-cell mediated cancer immunity. A retrospective analysis of clinical response from systemic therapy in relation to digital biomarkers is underway and will be reported. References: [1] Kim et al. Med. Image Anal. 67 (2021). [2] Riasatian, Abtin, et al. Med. Image Anal. 70 (2021). [3] Graham, Simon, et al. Med. Image Anal. 58 (2019). [4] Verma, Ruchika, et al. IEEE Trans Med Imaging 39.1380-1391 (2020).
Comparative genomic analysis and its prognostic impact on survival between viral hepatitis-related and non-viral hepatitis intrahepatic cholangiocarcinoma.
Authors: Chiang Nai-Jung , Tan Kien Thiam , Huang Chung-Yu , Chen Ming-Huang , Chiu Tai-Jan , Shan Yan-Shen , Li Chien-Feng , Chen Li-Tzong 
Published: June 2022

4120 Background: Intrahepatic cholangiocarcinoma (IHCC) is hard-to-treat cancer with a high mortality rate worldwide. Hepatitis B virus (HBV) or hepatitis C virus (HCV) is involved in the development of IHCC, especially in Asian countries. Despite rapidly growing genomic profiling studies of IHCC in Western and Eastern populations in recent years, less on genomic heterogeneity of viral hepatitis-related and non-viral hepatitis IHCC been reported. This study aims to provide a comprehensive genomic analysis of IHCC and its prognostic value in IHCC populations with or without viral hepatitis infection. Methods: FFPE tissues from 157 patients with IHCC were subject to next-generation sequencing using the FoundationOne CDx (n = 52) or ACTOnco + comprehensive genomic profiling panels (n = 105). Genomic alterations and features, including single nucleotide variations (SNVs), short insertions and deletions (InDels), copy-number variations (CNVs), fusion genes (only FoundationOne CDx), tumor mutations burden (TMB), and microsatellite instability (MSI) status, were analyzed. The prevalence of genetic mutations and their prognostic values were compared between patients with a history of hepatitis B/C infection (BC; n = 71, 45.2%) and those without hepatitis B/C infection (NBNC; n = 79, 50.3%). Seven patients had no medical record of HBV or HCV infection. Results: The most frequently mutated genes in BC- and NBNC-related IHCC populations were TP53, KRAS, and IDH1. The genetic alternations related to PI3K/AKT/mTOR signaling pathway and copy number gain of receptor tyrosine kinase were relatively dominant in BC-related IHCC. In contrast, the Ras/Raf/MAPK pathway alterations were frequently common in NBNC-related IHCC. In addition, we investigated the correlation between commonly altered genes or pathways and overall survival (OS). Interestingly, the prognostic biomarkers in BC- and NBNC-related IHCC were significantly different. The results showed that TP53 DNA-binding domain (DBD) and TET2 mutations were associated with poor prognosis in BC-related IHCC. On the contrary, CDKN2A deletion and Ras/Raf/MAPK pathway alteration were associated with inferior prognosis in NBNC-related IHCC. However, neither the PI3K/AKT/mTOR signaling alteration nor IDH1/2 mutation affected the OS in BC- or NBNC-related IHCC. Notably, we found that SWI/ SNF complex involved in ARID1A, ARID1B, ARID2, PBRM1, and SMARCA4 alterations exhibited a beneficial prognosis in BC-related IHCC patients, which has not been discussed in previous studies. Conclusions: This study provides comparative genomic profiling between BC- and NBNC-related IHCC and shows genomic heterogeneity and different dominant prognostic biomarkers and activated signaling pathways. Different treatment strategies should be considered in these two subpopulations based on these results.
Association of LAG-3 expression in circulating T cells and response to combination temozolomide (TMZ) and nivolumab (NIVO) in advanced neuroendocrine neoplasms (NENs): Results from an investigator-initiated phase 2 trial.
Authors: Sukrithan Vineeth , Benner Brooke , Wei Lai , Goyal Ashima , Zhou Ye , Suffren Sheryl-Ann , Pilcher Carly , Christenson Gwen , Curtis Nancy , Schwarz Emily , Savardekar Himanshu , Norman Ruthann , Kleiber Barbara , Wesolowski Robert , Otterson Gregory Alan , Verschraegen Claire F. , Carson William Edgar , Shah Manisha H. , Konda Bhavana , Owen Dwight Hall 
Published: June 2022

4123 Background: LAG-3 is an immune checkpoint present on NK cells, activated T cells and myeloid cells that inhibit T cell responses. Recent evidence demonstrating the safety and efficacy of LAG-3 inhibition has increased interest in this pathway for the treatment of multiple malignancies but the role in NEN is unclear. We present results from correlative peripheral blood mass cytometry (CyTOF) performed in a phase 2 trial (NCT03728361) of the combination of NIVO and TMZ in pts with advanced NEN. Methods: Patients (pts) with progressive NEN of any grade or primary location and any line of therapy were eligible. Small cell lung cancer was excluded. Clinical results from NCT03728361 will be presented in a separate abstract. Study treatment consisted of NIVO 480 mg IV every 4 weeks and TMZ 150 mg/m2 for 5 consecutive days out of a 28-day cycle. Peripheral blood mononuclear cells (PBMCs) were available from 16 out of 28 patients at screening (baseline) and cycle 1, day 15 (C1D15) and analyzed via CyTOF. Antibody labelling was performed using a 37 marker Maxpar Direct Immune Profiling Assay (Fluidigm). Immune cell populations were compared using two sample t-tests between pts with partial response (PR) and non-partial response (non-PR). Results: At screening, no differences were observed in PD-1, TIM3, or KLRG1 positive T-cell populations between pts with PR or non-PR. Patients with a PR had a significantly lower % of LAG-3 expressing T cells (p=0.029). There was a trend towards a lower % CD8+LAG-3+ T cells in pts with PR (p=0.086). At C1D15: The % of CD8+ LAG-3+ T cells were significantly higher in PRs vs. non-PR (p = 0.015). In matched samples comparing T cell populations at screening to C1D15, LAG-3+ CD8+ T cells increased significantly in PRs when compared to non-PRs (p=0.021). Conclusions: The % of LAG-3+ T cell population at baseline associates with non-response to TMZ/NIVO in NENs. Among responders, there was a significant increase in CD8+ LAG-3+ T cells by Day 15 compared to baseline indicating a potential mechanism of immune escape and eventual resistance. Clinical trial information: NCT03728361. [Table: see text]