bluuebunny/crossref_metadata_2025_split huggingface dataset:
Survival impact among occidental patients with metastatic gastric cancer (mGC) treated with ramucirumab as second line treatment (2L): Local experience of a teaching hospital in Chile.
Authors: Salinas Carlos , Barajas Olga , Villanueva Luis , Vasquez Rodrigo , Ahumada Monica 
Published: June 2021

e16007 Background: GC is frequent in Chile, with an incidence of 7.8% and a mortality rate of 11.6% in 2020. Late diagnosis continues to be one of the most important problems, although treatments in advanced stages have experienced important advances in the last 6 years. REGARD and RAINBOW trials showed an increase in median OS when using Ramucirumab alone or in combination with Paclitaxel of 5,2 and 9,4 mths respectively. Although this therapy is not covered by our Public Health Insurance, there are some patients that they can access. Also, there are not too many reports in LATAM pts so we present our local real world data. Methods: We conducted a retrospective study of local data from patients diagnosed with mGC who progressed with standard first-line treatment and were treated with ramucirumab-based regimens from January 2015 to January 2021. Clinical factors were recorded baseline, characteristics of therapy and AE related to toxicity. Toxicity was assessed by CTCAE v5.0 and response to treatment by RECIST 1.1. Results were analyzed by measuring time to progression and survival. Results: The search resulted in 9 pts, 6 men and 3 women between 38 and 72 years (median 59 years). 66% were in ECOG 1 performance status and 33% in ECOG 2, with a median BMI of 23 kg / m2. 33% were smokers and all had some other comorbidity as a medical history. All tumors were adenocarcinomas and 33% had a signet ring cell component on histology. Only one tumor was HER2 +++ and all were MSS (by IHC). The most common first-line treatment received before progression was FOLFOX; 4 to 12 cycles; 8 cycle average. All patients were treated with paclitaxel-ramucirumab as 2L (4 to 19 cycles, mean of 5 cycles). 67% of patients achieved stable disease with the best response. During the follow-up period, 8 patients experienced disease progression in an average of 6.7 months, who switched to 3L with Nivolumab. Relapses during 2L were in the peritoneum and 55% in other sites as well. Only two patients discontinued paclitaxel treatment after 4 cycles due to intolerance and continued to receive Ramucirumab. 44% developed grade 3 toxicities: 50% of them due to taxane-related peripheral neuropathy. Grade 4 or 5 toxicity was not reported. 50% of patients were alive at 6 months of treatment. Conclusions: In our country and LATAM, GC still has a significant medical and socioeconomic burden. Its incidence is still one of the highest in the world, most patients are diagnosed in the metastatic stage and face treatment in deficient PS. In this context, our local real-world data showed consistency with what the literature says, although more data remains to accumulate and describe.
Polymorphism of genes of hemostasis system and methionin exchange in patients with gastrointestinal tumors.
Authors: Kit Oleg I. , Vladimirova Liubov Yu , Zykova Tatiana A. , Katelnitskaya Oksana V. , Maslov Andrey A. , Shevyakova Elena A. , Abramova Natalia A. , Storozhakova Anna E. , Popova Irina L. , Novoselova Kristina A. , Tikhanovskaya Natalia M. , Agieva Aza A. , Ryadinskaya Ludmila A. , Tishina Anna V. , Tishchenko Irina S. , Kabanov Sergey N. , Kalabanova Elena A. , Karnaukhova Valeria S. , Teplyakova Maria A. 
Published: June 2021

e16011 Background: The purpose of the study was to analyze the rates of polymorphic allelic variants of genes of the hemostasis system and methionin exchange in patients with gastrointestinal cancers (GICs). Methods: The study included 69 patients with histologically verified GICs (main group): gastric cancer (GC) – 17, colon cancer (CC) – 42, other tumors – 10 (pancreatic cancer – 6, liver cancer – 3, gallbladder cancer – 1) and 50 patients without cancer (control group). 12 polymorphic loci were determined in genomic DNA samples by Real-time PCR: F2 (G20210А, rs1799963), F5 (G1691A, rs6025), F7 (G10976A, rs6046), F13 (G226A, rs5985), FGB G(-455)A (rs1800790), ITGA2-α2 (C807T, rs1126643), ITGB3-b (Т1565С, rs5918), PAI-1 4G(-675)5G, rs1799889), MTHFR (С677Т, rs1801133 and A1298C, rs1801131), MTR (А2756G, rs1805087), MTRR (A66G, rs1801394). Results: The ratio of genotype frequencies maintained in the Hardy-Weinberg equilibrium in all gene loci except FGB G(-455)A in GC patients (p = 0.02). The rate of an alternative allele in the F2 gene among patients with GICs was 1.4%, in the control group – 1.0%; F5 – 1.0% and 4.0%; F7 – 13.0% and 11.0%; F13 – 31.9% and 32.0%; FGB – 29.7% and 22.0%; ITGA2 – 37.7% and 38.0%; ITGB3 – 17.4% and 21.0%; PAI-1 – 55.1% and 56.0%, MTHFR (Т) – 26.6% and 31.3%; MTHFR (С) – 33.0% and 27.5%; MTR – 29.8% and 26.3%; MTRR – 51.1% and 57.5%, respectively (p > 0.05). AA homozygotes at the FGB G(-455)A locus were more frequent in the main group, compared to controls: 4.3% vs 4.0%; p = 0.02. No differences in the frequency of alternative alleles of the studied genes were found between patients with GC and CC. GG genotype at the FGB G(-455)A locus was found in GC patients in 29.4%, in controls – in 60.0% (OR = 0.28, 95% CI 0.08-0.91); GA genotype – in 70.6% and 36.0% (OR = 4.27, 95% CI 1.29-14.06), AA genotype – in 0% and 4.0% (p = 0.04, χ2 = 6.34), respectively. Conclusions: The univariate analysis demonstrated that carriage of the GA genotype at the FGB G(-455)A (rs1800790) locus could be found more often in patients with GC.
Efficacy and safety of intermittent versus continuous dosing schedule of apatinib combined with docetaxel as second-line treatment for advanced gastric cancer.
Authors: He Yifu , Yan Ying , Wang Gang , Sun Yubei , Xu Tengyun , Wu Shusheng , Luo Huiqin , Ke Lihong , Hu Xiaoxiu , Niu Jiayu , Li Huimin , Chen Wenju , Xu Huijun , Cao Lulu , Sun Yancai , Liu Chenxuan , Ji Chushu , Hu Bing 
Published: June 2021

e16018 Background: Apatinib, a VEGFR-2 tyrosine kinase inhibitor, is wildly used for the treatment of advanced or metastatic gastric cancer. However, dose modification and interruption are happened frequently due to poor patient conditions and treatment-related toxicity. This study was designed to explore the efficacy and safety of intermittent or continuous apatinib therapy in combination with docetaxel. Methods: This was an open-label, randomized clinical trial. Patients with advanced gastric cancer who progressed from first-line treatment were randomly assigned in a ratio of 1:1 to receive intermittent or continuous dosing schedule. In the intermittent dose group (IG), patients received oral apatinib 500 mg/d for 5 days followed by 2 days off. In the continuous dose group (CG), patients received 500 mg daily without interruption. Docetaxel 60 mg/m2 was administered intravenously to patients on Day 1 in a 21-day cycle in both groups. The primary endpoint was progression-free survival (PFS). The secondary endpoints included overall response rate (ORR), disease control rate (DCR), overall survival (OS), and the safety. Results: Between September 15, 2017 and November 30, 2020, 80 patients were screened for eligibility, of which 76 patients were randomly assigned into two groups (38 in the IG and 38 in the CG). In the IG and CG, 38 and 37 patients had ECOG PS 0-1, 16 and 19 patients had history of surgery, both 11 patients with more than 2 metastases, respectively. The baseline characteristics of the two groups were balanced. ORR in the IG was 21.05% vs 18.42% in the CG, and DCR was 60.53% vs 60.53%, respectively. Median PFS were 3.88 months (95% CI, 1.723-6.031) vs 3.98 months (95% CI, 1.055-6.896, p= 0.546), and median OS was 9 months (95% CI, 5.306-12.698) vs 9.40 months (95% CI, 5.204-13.588, p= 0.310) in two groups. The incidence of all grade adverse events (AEs) in the IG and CG were 94.7% and 92.1%, of which the most common AEs were hypertension (55.3% vs 65.8%), anemia (55.3% vs 63.2%), proteinuria (26.3% vs 31.6%), hand-foot syndrome (21.1% vs 26.3%). The incidence of grade ≥3 AEs were 36.8% and 39.5% in the IG and CG, respectively. In addition, the doses of 7 patients were reduced to the 250 mg in the IG, while that of 13 patients in the CG. Conclusions: Apatinib administered intermittently (5 days on/ 2 days off) exhibited similar efficacy to continuous schedule, while with less toxicity. Intermittent dosing schedule of apatinib may be an option for second-line treatment of patients with advanced gastric cancer. Clinical trial information: NCT03334591.
Molecular characteristic of proximal and distal esophagogastric junction adenocarcinomas.
Authors: Xu Lin , Shang Bin , Bi Mingming , Zhong Wei , Zhao Yu , Wang Zhou , Xu Mian , Shi Xiaoliang , Zhang Lin , Chen Gang 
Published: June 2021

e16077 Background: Esophagogastric junction adenocarcinomas (EGJA) are devastating diseases with increasing incidence. The 8th Edition TNM staging of American Joint Committeeon Cancer and Union for International Cancer Control defined that the epicenter of EGJA within 2 cm of the cardia (hereinafter referred to proximal EGJA) is staged according to the staging standard of esophageal cancer, while that more than 2 cm distal from the EGJA (hereinafter referred to distal EGJA) is staged according to the staging standard of stomach cancer. However, the rationality of the new definition in clinical practice is still controversial. Methods: A randomized retrospective study was conducted. Targeted next-generation sequencing of 450 cancer-related genes was performed, by OrigiMed, a College of American Pathologists (CAP) accredited and Clinical Laboratory Improvement Amendments (CLIA) certified laboratory, Shanghai, China, for genomic alteration identification. Results: A total of 198 EGJ patients were included in this study with a median age of 63 years (ranged from 39 to 88 years). Among them, 140 were distal EGJA and 58 were proximal EGJA. Genomic alterations with a high mutation frequency in EGJ include There is no significant difference in the frequencies of these genes between proximal EGJA and distal EGJA. Mutation frequencies of FGFR2 and ZEN217 in distal EGJ were significantly higher than those in proximal EGJA (15.8% vs 5.0%, P = 0.02 and 7.0% vs 0.7%, P = 0.03, respectively). Multivariate regression analysis showed that tumor stage and lymph nodes number were the main factors positively associated with the poor prognosis. However, we found that there was no significant difference in OS between proximal and distal (P = 0.139). Furthermore, our results showed that LRP2 and SPTA1 mutations were significantly associated with better OS of the EGJA patients. Conclusions: In conclusion, with the identification of the mutation landscape of EGJA, the FRFR2 and ZNF127 genes mutations were potential biomarkers to distinguish distal EGJA from proximal EGJA, whereas the LRP2 and SPTA1 gene mutations were potential biomarkers for prognosis prediction in EGJA.
A nationwide analysis of inpatient outcomes and healthcare utilization in HIV versus non-HIV patients with esophageal cancer.
Authors: Sherazi Syed Ali Amir , Achebe Ikechukwu , Asotibe Jennifer C , Pannu Bibek Singh , Attar Bashar , Gupta Shweta , Mullane Michael Russell 
Published: June 2021

e16106 Background: Esophageal cancer (EC) is an aggressive malignancy with poor 5-year survival rates (19.9%). Due to effective Antiretroviral Therapy, mortality from HIV/AIDS has precipitously decreased leading to longer lifespan and increased risk of developing non-AIDS defining cancers. There is paucity of data regarding outcomes of Esophageal Cancers in patients with HIV (HIV-EC). We undertook this analysis to study the outcomes of HIV-EC with healthcare utilization compared to non-HIV-EC patients. Methods: The Healthcare Cost Utilization Project (HCUP) Nationwide Inpatient Sample was queried to identify patients with HIV and non-HIV-EC using ICD-10 codes. Groups were compared for demographic differences, inpatient mortality, length of stay (LOS) and hospital charges. Secondary outcomes studied included rates of septic shock (SS), Esophageal Obstruction (EO), Anemia, Pneumonia, Tracheoesophageal Fistula (TEF), Upper GI Bleed (UGIB), Acute Kidney Injury (AKI), protein energy malnutrition (PEM). Statistics were performed using the t-test, chi-square test and logistic regression. Results: A total of 330 inpatient admissions with HIV-EC and 117505 with non-HIV-EC were identified. Patients with HIV-EC were significantly younger (mean age 58.5 vs 66.9 years, p < 0.001) with 83% under 65 years of age compared to 41% in non-HIV-EC group (p < 0.001). Higher number of HIV-EC patients were African American (AA) (51.5% vs 10%, p < 0.001) with similar gender ratio (19.7% vs 21.3% women), belonged to lowest income quartile zip codes (42% vs 27%, p = 0.01), more likely to be on Medicaid (36% vs 11%, p < 0.001) and hailed from North East (NE) or Southern regions of the US (79% vs 56%, p = 0.003). The overall mortality rate was significantly higher in the HIV-EC group than non-HIV-EC (13.6% vs 8.8%, p = 0.001). The mean inpatient LOS (7.4 vs 6.98 days) and total hospital charges ($65,358 vs $80,620) were not significantly different between the two groups. Rates of PEM were higher in HIV-EC (61% vs 44%, p < 0.01) but rates of sepsis, SS, UGIB, EO, TEF, Anemia, TLS, AKI were not significantly different than non-HIV-EC. There was no difference in rates of specific medical co-morbidities between groups, although HIV-EC had a significantly higher Charlson Comorbidity Index (p < 0.001). Conclusions: Despite being significantly younger, HIV-EC patients have significantly higher mortality compared to non-HIV-EC. However, the inpatient LOS and total charges were not significantly different. HIV-EC were more likely to be AA on Medicaid and from low-income zip codes from the NE or South of the United States. Further studies are needed to study the role of early diagnosis, perhaps screening in younger patients with HIV to prevent mortality.
A multicenter observational study of lenvatinib for unresectable hepatocellular carcinoma in Japan.
Authors: Izumi Namiki , Kudo Masatoshi , Motomura Kenta , Inaba Yoshitaka , Katamura Yoshio , Kondo Yasuteru , Yabushita Kazuhisa , Motoyoshi Katsuaki , Furuse Junji 
Published: June 2021

e16118 Background: Lenvatinib is an oral tyrosine kinase inhibitor that has been available for treatment of unresectable hepatocellular carcinoma (uHCC) in Japan since March 2018. We conducted a multicenter prospective observational study to evaluate the safety and efficacy of lenvatinib in clinical practice. Methods: This study conducted as a prospective study, and enrolled patients with uHCC initially receiving lenvatinib as systemic therapy who gave informed consent from July 2018 through January 2019. The observation period per patient was 12 months and e-CRF was used. Results: 713 patients were registered at 133 clinical sites. The safety analysis set and efficacy analysis set were 703 patients. Patient baseline characteristics included median age:73.0 years (25 to 94), male/ female: 564/139, bodyweight: < 60kg/≥60kg: 323/380, HBV/HCV/alcohol/NAFLD or NASH: 137/287/167/88, Child-Pugh classification A/B or higher: 624/75, BCLC stage A/B/C/D: 57/291/332/11, Vp 0/1/2/3/4: 520/31/52/60/22, with/without extrahepatic metastasis: 236/461. Previous treatment (local and systemic therapy) for hepatocellular carcinoma is with/without TACE: 513/190, median number of TACE treatment: 3.0 times (1 to 26), with/without HAIC: 74/629, with/without TKI pretreatment: 131/572. The initial dose was 8 mg (80.5%) and 12 mg (68.2%) in patients with < 60 kg and ≥60 kg, respectively. Median relative dose intensity was 64.2% and the treatment continuation rate at 3 and 12 months after administration of lenvatinib were 67.3% and 24.8%. Regarding safety, the incidence of treatment-related adverse events (TRAEs) was 84.9% (grade 3 or higher: 42.5%). Common TRAEs (incidence rate ≥10%) were decreased appetite (23.9%), malaise (21.8%), hypertension (21.3%), proteinuria (18.3%), palmar-plantar erythrodysesthesia syndrome (16.5%), hypothyroidism (15.8%), and diarrhea (13.9%). TRAEs of grade 3 or higher （incidence rate ≥2.5%） were proteinuria (6.7%), hypertension (6.4%), malaise (3.8%), decreased appetite (3.6%), platelet count decreased (3.3%), palmar-plantar erythrodysesthesia syndrome (2.7%), diarrhea (2.7%) and hepatic encephalopathy (2.6%). The incidence of TRAEs leading to discontinuation of lenvatinib was 32.9％, and main TRAEs leading to discontinuation of lenvatinib were (incidence rate ≥2%) decreased appetite (6.3%), malaise (4.7%), proteinuria (3.3%) and hepatic encephalopathy (2.4%). Regarding efficacy, the ORR and DCR was 39.5% (95% CI: 35.1, 43.9) and 78.9% (75.1, 82.5) in 494 patients who were evaluated for the best response by mRECIST. The median OS was 498.0 days (95% CI: 439.0, -) in 703 patients. Conclusions: The incidence of TRAEs leading to discontinuation of lenvatinib tended to be higher than in phase 3 REFLECT trials (19.7%), but the safety profile and effectiveness findings for lenvatinib in this study were consistent with previous reports.
A retrospective study on the efficacy and safety of sorafenib or lenvatinib combined with sintilimab in patients with advanced hepatocellular carcinoma.
Authors: Zeng Zhen , Zhang Linzhi , Wu Tong , Cheng Jiamin , Chen Yan , Lu Yinying 
Published: June 2021

e16127 Background: To evaluate the efficacy and safety of sorafenib or lenvatinib combined with sintilimab in patients with advanced hepatocellular carcinoma. Methods: This retrospective study included patients with advanced/metastatic hepatocellular carcinoma who received sintilimab (iv. 200 mg, Q3W) combined with sorafenib (oral, 400 mg twice-daily) (cohort A) or lenvatinib (oral, 12 mg/day for bodyweight≥60 kg or 8 mg/day for bodyweight < 60 kg) (cohort B) as first line therapy between March 2019 to December 2020 in the 5th medical center of the PLA general hospital of China. The primary endpoint was Progression-Free Survival (PFS), and the secondary endpoints included the Objective Response Rate (ORR), Disease Control Rate (DCR), Overall Survival (OS), Time to Progression (TTP) and safety. Results: 45 patients were enrolled, of which 29 were in the cohort A and 16 were in the cohort B. Except for the extrahepatic metastasis (62.1% vs 25.0%, P= 0.029), there were no significant differences in age, gender, weight, ECOG performance status, Child-Pugh, BCLC staging, and the proportion of previous treatment regimens between the two cohorts. The mean (±SD) exposure cycles in the two cohorts were 7.2±6.7 vs 7.1±4.7 ( P= 0.584). The median PFS of cohort A (8.2 months, 95%CI 3.1-19.5) was longer than that of cohort B (5.2 months, 95%CI 2.0-10.8), but there was no significant difference (HR 0.55, 95%CI 0.24-1.29, P = 0.161). However, there was no significant difference between the two cohorts in ORR (24.1% vs 6.3%, P= 0.226), DCR (82.8% vs 75.0%, P= 0.700) and median TTF (8.2 vs 4.6months, HR 0.49, 95%CI 0.21- 1.10, P= 0.074). OS data were not yet mature. There was no significant difference in the incidence of all grades and grade 3-4 adverse events between the two cohorts. The most common grade 3-4 adverse events in the two cohorts were hand-foot syndrome (17.2%, 5/29) and lung infection (12.5%, 2/16). There was 1 patient (immune hepatitis) in cohort A and 2 patients (pulmonary infection) in cohort B leading to treatment interruption due to adverse events, and no deaths due to treatment. Conclusions: Sorafenib or lenvatinib combined with sintilimab showed a good efficacy and safety in patients with advanced hepatocellular carcinoma, the safety and tolerability profiles were consistent with those previously observed. Sorafenib plus sintilimab provided an improved PFS versus lenvatinib, which requires a large sample of randomized controlled trial to confirm.[Table: see text]
Upfront or add-on combination therapeutic strategy exploration in unresectable hepatocellular carcinoma using sorafenib plus sintilimab: A retrospective analysis of real-world evidence.
Authors: Cheng Jiamin , Li Yinyin , Wu Tong , Zhang Zhen , Chen Yan , Su Guodong , Peng Caiyun , Zhang Linzhi , Lu Yinying , Zeng Zhen 
Published: June 2021

e16135 Background: Recently, tyrosine kinase inhibitor plus PD-1 inhibitor regimen has shown promising effects on hepatocellular carcinoma (HCC). So far, no study explored the effectiveness of upfront versus add-on combination therapy in patients with systemic treatment-naïve and treatment-experienced HCCThis study aimed to explore the effectiveness and safety of sintilimab combined sorafenib in patients with untreated or sorafenib monotherapy-refractory unresectable HCC. Methods: In this retrospective study, unresectable HCC patients received sintilimab plus sorafenib from January 2018 to December 2020 were enrolled. According to the prior treatment, patients were grouped as first-line and second-line (received sorafenib combined sintilimab after progression on sorafenib alone). Objective response rate (ORR), disease control rate (DCR), progression free survival (PFS), safety, and the change of Child-Pugh score from baseline to progression were recorded. The PFS was defined as the time from first dosing of sintilimab until disease progressive or death. Results: A total of 31 patients were reviewed, including 19 patients in first-line group and 12 patients in second-line group. There were two patients with Barcelona Clinic Liver Cancer (BCLC) stage B and 17 patients with BCLC stage C in first-line group, and one patient with BCLC stage A and 11 patients with BCLC stage C in second-line group, respectively. The ORR and DCR were 27.8% and 77.8% in first-line group, and 16.7% and 75.0% in second-line group, respectively. Fourteen cases in first-line group and 10 cases in second-line group showed PD during the follow-up. The 6-month PFS rate of first-line group and second-line group were 47.1% and 64.8%, respectively. Thirteen and 9 patients experienced AE in two groups. Four and 2 grade 3 AEs occurred in two groups, respectively. The most frequency AE were hand-foot-skin reaction in both group (58.0% and 50.0%, respectively). One patient discontinued sintilimab due to AE in second-line group. Among PD patients, the Child-Pugh score improved in 2 cases, maintained in 5 cases, and deteriorated in 7 cases in the first-line group; and improved in 3 cases, miantained in 3 cases, and deteriorated in 4 cases in the second-line group. Conclusions: Sorafenib plus sintilimab showed potential anti-tumor effect and tolerance on unresectable HCC, either as first-line therapy or after progression with sorafenib monotherapy. Outcomes.[Table: see text]