bluuebunny/crossref_metadata_2025_split huggingface dataset:
Racial parity in esophageal cancer treatment at an integrated healthcare system.
Authors: Hsu Diana S. , Banks Kian C , Kwak Hyunjee V. , Chang Amber , Truong Thach-Giao , Velotta Jeffrey B. 
Published: June 2022

e16105 Background: This study evaluates survival outcomes of esophageal cancer patients treated at a large, tertiary care integrated healthcare system and whether there are differences based on race. Methods: We conducted a retrospective study from January 2010 to December 2019 among patients at Kaiser Permanente Northern California (KPNC). Self-reported racial ethnic groups included Caucasian, African American, Hispanic, Asian, and Other. Kaplan Meier and Cox regression analyses were used to evaluate differences in race, age, stage, and treatment utilization in relation to overall survival. Results: A total of 1,692 patients were diagnosed with esophageal cancer. Of these, 11% were Asian, 8.1% were Hispanic, and 6% were African American. Caucasians had the oldest mean age at diagnosis, 70.2 years, and the Hispanics had the youngest mean age at diagnosis, 64.6 years (p < 0.001). There were no statistically significant differences in stage at time of diagnosis between race groups (p = 0.41). Adenocarcinoma was more common in Caucasians and Hispanics, while squamous cell was more common in African Americans and Asians (p < 0.001). Treatments received by the patients included, surgery, chemotherapy, radiation, and a combination thereof (multimodal). There was no statistical significance among the races in treatment modalities received, including multimodal therapy (p = 0.12-0.66). The difference in mean overall survival (OS) between the race groups was not statistically significant. Kaplan-Meier survival analyses were performed and demonstrated statistically significant differences in mean OS between the two histologies, with adenocarcinoma having the highest survival of 33.9 months (p < 0.001). Conclusions: We identified racial parity in survival outcomes and treatment utilization for esophageal cancer patients who were treated at a large integrated healthcare system where patients have equal access to care.[Table: see text]
Comparison of tumor registry reporting and gastrointestinal oncologist determination of intrahepatic cholangiocarcinomas: A quality review analysis.
Authors: Raufi Alexander , Safran Emma , Breakstone Rimini , Almhanna Khaldoun 
Published: June 2022

e16113 Background: Diagnosing cholangiocarcinoma (CCA) can be challenging and these tumors are often misclassified as adenocarcinomas of unknown primary (AUP). Accurate identification is critically important to determine the true incidence and to understand the epidemiology of these cancers. Methods: As a quality assessment, gastrointestinal oncologists at our institution reviewed the tumor registry records of all patients diagnosed with intrahepatic CCA, extrahepatic CCA, hepatocellular carcinoma, adenocarcinoma of unknown primary, and adenocarcinoma not otherwise specified. Mixed hepatocellular/cholangiocarcinoma was excluded. Results: Initially the tumor registry reported 37 cases of intrahepatic CCA at the Lifespan Cancer Institute/Rhode Island Hospital between 2017-2020. However, review of the registry records by gastrointestinal oncologists revealed 10 additional cases of intrahepatic cholangiocarcinoma. These cases had been entered into the tumor registry with diagnosis codes of liver adenocarcinoma NOS (n = 8), liver cancer (n = 1) and liver NOS (n = 1). Following review, a total of 47 cases of intrahepatic CCA and 59 cases of extrahepatic CCA were identified at our institution between 2017-2020. The mean age of intrahepatic CCA was 58 and 48% were women. The mean age of extrahepatic CCA was 73 and 42% were women. The updated numbers were reported to the state tumor registry. Conclusions: Difficulties in diagnosis of cholangiocarcinoma may underestimate the true incidence of this disease in the United States. Careful review of tumor registry data across the United States would likely reveal large discrepancies between actual and reported incidence of this disease and further study is warranted.
Immunotherapy with nivolumab after progression on lenvatinib in advanced hepatocellular carcinoma: A real-world Indian experience.
Authors: Rauthan Amit , Patil Poonam , Murthy Nitin Yashas , Somashekhar S.P. , Zaveri Shabber , Aswath Rajashri , V Prathyush , Jomi Chinnu 
Published: June 2022

e16117 Background: Firstline treatment of advanced hepatocellular carcinoma (HCC) till recently has been sorafenib or lenvatinib. Lenvatinib, due to its better tolerability and efficacy (in PFS) over sorafenib, is our preferred first line treatment. Nivolumab, with an objective response rate (ORR) of 14.3% and median duration of response of 16.6 months, was approved by FDA on the basis of the CheckMate-040 trial in patients who progressed or were intolerant to sorafenib. There is very limited data of immunotherapy on progression with lenvatinib. Methods: This is a single center, retrospective analysis of patients with advanced HCC who progressed on first line lenvatinib and received treatment with nivolumab. The endpoints were objective response rate (ORR), progression free survival (PFS), overall survival (OS) and toxicity. Results: 15 patients who progressed on lenvatinib, received nivolumab at 3 mg/kg, 2 weekly as second line therapy between July 2019 to July 2021. There were 2 females and 13 males. Median age was 66 years (37-77 years). All patients were BCLC stage C. AFP was elevated in 11 patients. Child Pugh score was A in 10 patients, and B in 5 patients. 7 patients had background of hepatitis B and 1 had hepatitis C. The number of cycles of nivolumab ranged from 2 to 13 cycles. 3 patients (20%) had partial response, 2 had stable disease and 10 (66.6%) had progressive disease by recist criteria. The ORR was 20% and median PFS was 3 months. Median OS was 8 months. The common side effects were hypothyroidism in 7 (46.6%), fatigue in 4 (26.6%) and skin rashes in 3 (20%) patients. Conclusions: Immunotherapy with nivolumab showed limited efficacy in our patients of HCC who have progressed on lenvatinib. There were few patients who showed durable response, but there are no biomarkers to choose these patients. The immune related side effects were manageable. With the first line approval of combination therapy with atezolizumab and bevacizumab, single agent second line immunotherapy with its limited efficacy, may have a reduced role in HCC management.
Efficacy and safety of regorafenib alone or in combinations for advanced hepatocellular carcinoma: A multicenter real-world study.
Authors: Zhu Haidong , Zhu Xiaoli , Song Yusheng , Wang Qi , Wu Jianbing , Xu Hao , Teng Gaojun 
Published: June 2022

e16122 Background: The earlier randomized phase III RESORCE trial demonstrated that regorafenib improved overall survival in advanced hepatocellular carcinoma (HCC) patients progressing on sorafenib treatment, with a median survival of 10.6 months and a hazard ratio of 0.63 (95% CI 0.50-0.79, p < 0.0001). Meanwhile, more data were published from retrospective studies evaluating the sequence of single drug sorafenib and regorafenib in advanced HCC patients treated in real-world settings [eg, REFINE study (N = 1000; 100 from China)].We aimed to explore the efficacy and safety of regorafenib alone or in combinations in advanced HCC patients in a real-world setting. Methods: This retrospective multicenter study included pathologically or clinically diagnosed advanced HCC patients who received regorafenib alone or in combinations in first to fourth line settings for at least 28 consecutive days. The primary endpoints were objective response rate (ORR, RECIST 1.1 criteria) and progression-free survival (PFS). The secondary endpoints included overall survival (OS) rate at 6-month and 12-month, disease control rate (DCR) and safety. Kaplan-Meier method was used to calculate survival data. Results: A total of 61 advanced HCC patients (55 male vs. 6 female, 2 first-line recipients vs. 47 second-line recipients vs.11 third-line recipients vs. 1 fourth-line recipients, median age of 53.5 years) from 6 Chinese centers were included between January 2018 and June 2021. Most patients had BCLC stage C (96.7%) and a Child-Pugh A or B score in 23% or 57.4% of cases respectively. 23 (37.7%) patients received single drug regorafenib therapy, the remaining patients (62.3%) received different combination therapies, including regorafenib plus immune checkpoint inhibitors (ICIs) (29.5%), regorafenib combined with TACE (14.8%), and triple therapy (TKI, ICI, TACE) (18.0%). The ORR and DCR of 61 recipients were 71.7% and 83.3%, with a median PFS of 12.67 months (range 7.47-13.97). The 6-month, 12-month OS rates were 80.2% and 68.9%. In second-line recipients, the 6-month, and 12-month OS rates were 85.6% and 76.7%, with a PFS of 12.67 months. 36 recipients had treatment-related adverse events (TRAEs); most frequent TEAEs (≥5%) included fatigue (12.4%), abdominal pain (8.5%), anorexia (7%), rash (7%), diarrhea (6.2%), and hand-foot syndrome (6.2%). Conclusions: Regorafenib alone or in combination is effective and safe in advanced HCC patients, with a high response rate as well as long survival, especially in second-line recipients.
GemOX plus immune checkpoint inhibitor in combination with lenvatinib or NGS-guided targeted therapy in patients with biliary tract cancers.
Authors: Zhang Wei , Xiang Dong , Lu Chen , Chen Liu , Song Tianqiang , Lu Wei 
Published: June 2022

e16133 Background: The combination of gemcitabine-based chemotherapy and immune checkpoint inhibitors has made great progress recently in advanced biliary tract cancer (BTC). Multi-target TKI lenvatinib or next-generation sequencing (NGS)-guided molecular targeted therapy are also promising. The aim of this study was to explore the anti-tumor effects of combined GemOX plus anti-PD-1 sintilimab and TKI either by lenvatinib or by NGS-guided targeted therapy if there is available target for local advanced or metastatic BTCs. Methods: This is a prospective single arm clinical study. Patients with local advanced or metastatic BTC were given intravenous infusion of standard GemOX (85mg/m2 oxaliplatin on day 1 and gemcitabine 1000mg/m2 on a 1-8-day schedule of a 3-week treatment cycle) plus 200mg q3w of sintilimab and lenvatinib or targeted therapy based on NGS (olaparib for BRCA1/2 mutation, dasatinib for IDH1/2 mutation, afatinib for EGFR mutation, lenvatinib for PDGFR and KIT mutation, lenvatinib for FGFR/KIT mutation). The primary end point was objective response rate (ORR), and the secondary end points were progression-free survival (PFS) and overall survival (OS). Tumor response was evaluated according to RECIST v1.1 criteria. Results: From November 2020 to December 2021, 22 patients with locally advanced or metastatic BTCs (6 GBC, 14 iCCA, 1 pCCA and 1 dCCA) were enrolled in the regimen, with an average age of 58.4 years. Partial response (PR) was achieved in 10 cases, stable disease (SD) in 9 cases and progression disease (PD) in 3 cases (13.6 %). The objective response rate (ORR) was 45.5%, and the disease control rate (DCR) was 86.4%. By December 31st, 2021, the median follow-up time was 13.1 months. The most common adverse events were anorexia (68.2%), nausea (68.2%), vomiting (36.36%), hair loss (45.5%) and bone marrow suppression (63.6%). During the treatment, the incidence of adverse reactions was 81.8%, and the incidence of grade 3/4 adverse events was 9.09%. For 14 patients with NGS, 5 patients were treated by targeting IDH2, EGFR, FGFR2, PDGFRA/KIT, BRCA2 and resulted in 1 SD and 4 PR with an ORR of 80% and DCR of 100%. The ORR and DCR were both 100% for 4 patients with programmed cell death ligand-1 (PD-L1) expression. While for the 3 patients with supper-progression markers such as RET, MDM2 and FGF14/STK24, there were 2 SD and 1 PD with an ORR of 0% and DCR of only 33%. Conclusions: In patients with advanced BTCs, the combination of GemOX plus sintilimab and lenvatinib or NGS-guided targeted therapy showed promising ORR and DCR, especially for the patients with positive PD-L1 expression and targetable gene alterations.
The best benefit population treated with lenvatinib plus anti-PD-1 for unresectable hepatocellular carcinoma.
Authors: Chang Xiujuan , Yu Shumin , Pang Jianzhi , Zhang Wei , Kong Huifang , Huang Jiagan , Zhang Guojie , Zhang Huixin , Gu Yueyue , Zhang Jihai , Dong Zheng , Chen Yan , Yang Bin , Liu Jingping , Yang Yongping , Zeng Zhen 
Published: June 2022

e16152 Background: To assess the efficacy and safety of lenvatinib plus anti-PD-1 versus lenvatinib alone in patients with unresectable hepatocellular carcinoma (u-HCC) and explore the characteristics of the benefit population for combination therapy. Methods: This retrospective study included 70 u-HCC patients that were treated with lenvatinib plus anti-PD-1 and 140 patients treated with lenvatinib alone in Fifth Medical Center of Chinese PLA General Hospital and Electric Power Hospital of Beijing from November 2017 to February 2021. Clinical features were balanced by stabilized inverse probability of treatment weighting (SIPTW). The primary endpoint was overall survival (OS). The secondary endpoints were progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), and adverse events (AEs). Subpopulation treatment effect pattern plot (STEPP) revealed differential treatment effects. The safety was evaluated by Common Terminology Criteria for AEs version 5.0. Results: During the median follow-up of 21.6 months, 120 (57%) patients died. The combination group showed better OS (21.4 vs. 14 months, p = 0.041), PFS (8.0 vs. 6.3 months, p = 0.015), ORR (38.6% vs. 22.9%, p = 0.026), and DCR (85.7% vs. 69.3%, p = 0.016) than the monotherapy group in unadjusted cohort, which was similar to SIPTW adjusted cohort. The two groups had comparable and manageable AEs. Macrovascular invasion (MVI, HR 2.6, 95%CI 2.18 - 3.92), extrahepatic spread (EHS, HR 2.16, 95%CI 1.49 - 3.13), and Child-Pugh B (CPB, HR 2.08, 95%CI 1.45 - 2.99) were independent factors of OS. Combination therapy improved the 12-month survival rate by 38% for patients with MVI or EHS and CPB, and by up to 18% in the other population. Conclusions: In conclusion, lenvatinib plus anti-PD-1 showed a favorable efficacy and controllable safety for u-HCC patients in real-world practice. The absolute improvement of the 12-month survival rate with combination therapy was more substantial in patients with major vascular invasion or extrahepatic spread and Child-Pugh B.
Lenvatinib combined with hepatic arterial infusion of modified FOLFOX regime as an initial treatment in patients with intermediate-stage hepatocellular carcinoma beyond up-to-seven criteria.
Authors: Shi Feng , Mai Qicong , Chen Meng , Li Chunlin , Chen Xiaoming 
Published: June 2022

e16154 Background: Transcatheter arterial chemoembolization (TACE) is not effective for intermediate-stage hepatocellular carcinoma (HCC) beyond up-to-seven criteria (substage B2) and also impairs the hepatic functional reserve, resulting in poor prognosis. This study aimed to investigate the efficacy and safety of lenvatinib combined transarterial infusion chemotherapy with FOLFOX regimen (FOLFOX-HAIC) for substage B2 HCC. Methods: This study retrospectively enrolled and analyzed 18 patients with substage B2 HCC from Nov. 2019 to Nov. 2021. Patients were orally administered with 8 mg(≤60kg) or 12mg(> 60kg) lenvatinib once daily initially, and FOLFOX-HAIC (oxaliplatin 85 mg/m2, leucovorin 400 mg/m2, fluorouracil bolus 400 mg/m2 on day 1, and fluorouracil infusion 2,400 mg/m2 for 46 hours) was performed every 3 weeks and up to 6 sessions. Then patients were treated with lenvatinib alone. Patients with downsizing HCC was allowed for potential curative therapies (surgical resection or ablation). Best response according to the RECIST 1.1 and mRECIST criteria, progression-free survival (PFS) and treatment-related adverse events (TRAE) were evaluated. Results: 18 patients (median age: 63.0 years) underwent a total of 77 cycles of HAIC therapy (mean: 4.3; range: 2-6). All patients were classified as Child-Pugh A class. The ORR were 83.3% (RECIST 1.1) and 94.4% (mRECIST), the disease control rate (DCR) was 100% (RECIST1.1/mRECIST). With a median follow-up period of 12.9 months, the median PFS was 10 months. During the follow-up period, no patient died, and 8 of 18 (44.4%) patients experienced progression. 6-, 9-, and 12-months PFS rates were 94%, 74%, and 55%, respectively. TRAE occurred in 15 of 18 patients (83.3%). Two grade 3 TRAE (hepatic encephalopathy and hypertension) was observed. Conclusions: Lenvatinib combined with FOLFOX-HAIC was well tolerated and had shown promising ORR, PFS rates in patients with intermediate-stage HCC beyond up-to-seven criteria. A prospective large-scale trial is needed to justify these results. [Table: see text]
Adjuvant lenvatinib after radical resection in patients with hepatocellular carcinoma (HCC): Preliminary analysis of a prospective, multi-center, single-arm study.
Authors: Zhou Jian , Sun Hui-Chuan , Huang Zhi-Yong , Liu Lianxin , Wen Tianfu , Zhu Xiao-Dong , SHI Yinghong , Gao Qiang , Qiu Shuang-Jian , Ding Zhenbin , Wang Zheng , Ye Qing-Hai , Huang Xiao-Wu , Huang Cheng , Peng Yuan-Fei , Shi Guoming , Wang Xiao-Ying , Fan Jia 
Published: June 2022

e16158 Background: Chinese guidelines recommend surgical resection for patients with China Liver Cancer (CNLC) Stage Ia−IIIa HCC (equal to BCLC stage A/B and selected patients with BCLC stage C). Despite treatment, however, patients with CNLC stage IIb (tumor number > 3) and IIIa (vascular invasion) disease have a high recurrence risk and poor overall survival (OS). Here we assessed the efficacy and safety of adjuvant lenvatinib in patients with high risk of disease recurrence. Methods: In this multi-center, single-arm, prospective clinical trial (NCT04227808), patients underwent radical (R0) resection for CNLC Stage IIb/IIIa HCC within 4-6 weeks were eligible and received treatment of lenvatinib (8 or 12 mg/day for body weight < 60 and ≥60 kg, respectively. Dose modifications were permitted due to adverse reactions) until disease recurrence, intolerable toxicity or death. The primary endpoint was 1-year recurrence-free survival (RFS), and secondary endpoints included OS and safety. The total planned enrollment for this study is 50 patients and here we report our preliminary analysis results. Results: A total of 59 patients were screened from Mar 2020 to Dec 2021 and 50 were enrolled in the study. By the cut of date (Dec 31, 2021), 42 patients had at least one set of follow-up data and were included in the present analysis. The 42 patients were predominantly male (83.3%, n = 35), and the median age was 55.5 years (range: 26–73). 78.6% (n = 33) were HBV-positive and 21.4% (n = 9) of disease were non-viral. Five patients (11.9%) had CNLC Stage IIb and 37 (88.1%) had CNLC Stage IIIa HCC. The median duration of treatment was 8.4 months (range: 1.7-18.7) with a median follow-up of 11.3 months (95% CI: 6.6−15.9). 24% (n = 10) had experienced dose reduction or delay. The 1-year RFS rate was 50.5%, while the median RFS was 16.5 months (95% CI: 11.3–21.7). Two deaths occurred: one secondary to disease recurrence and one from hepatic encephalopathy without recurrence. In total, 90.5% (n = 38) of patients experienced ≥1 treatment-related adverse events (AE) of any grade, and five patients (11.9%) had grade 3 treatment-related AEs (thrombocytopenia in two cases, proteinuria in two cases, and elevated aspartate aminotransferase in one case). There was no treatment-related death. Conclusions: Adjuvant lenvatinib was well-tolerated in patients with CNLC Stage IIb/IIIa HCC after R0 resection. The median RFS was longer than our historical data (mRFS = 9.03 months), and these findings warrant further investigation in a controlled study. Funding: Eisai Co., Ltd. Clinical trial information: NCT04227808.
Hepatic arterial infusion chemotherapy with oxaliplatin plus raltitrexed versus oxaliplatin plus fluorouracil in intermediate and advanced hepatocellular carcinoma: A retrospective study.
Authors: Zang Mengya , Li Qi , Hu Xiaoyun , Yuan Guosheng , Li Rong , Guo Yabing , Chen Jinzhang 
Published: June 2022

e16166 Background: Hepatic arterial infusion chemotherapy (HAIC) showed promising outcomes for advanced hepatocellular carcinoma (HCC) and was recommended in patients with advanced HCC in Asia. HAIC with oxaliplatin, 5-fluorouracil, and leucovorin (FOLFOX) was most commonly used in China. However, Continuous infusion (over 46 hours) with fluorouracil was inconvenient for arterial infusion. Raltitrexed, another antimetabolic drug with long plasma concentrations half-life, could be used in short infusions. HAIC with raltitrexed plus oxaliplatin (RALOX) was reported to be effective and safe in HCC. This study aimed to compare efficacy and safety of HAIC with raltitrexed plus oxaliplatin versus oxaliplatin plus fluorouracil in intermediate and advanced HCC. Methods: Sixty-six patients with intermediated and advanced HCC were included in this retrospective study between March 2019 and November 2020. Thirty-three patients were treated with HAIC of FOLFOX (oxaliplatin 85 mg/m2, leucovorin 400 mg/m2, 5-fluorouracilbolus 400 mg/m2 on day 1, and 5-fluorouracil infusion 2400 mg/m2 for 46 h, every 3 weeks). Another thirty-three patients received HAIC of RALOX (oxaliplatin 100 mg/m2, raltitrexed3 mg/m2, every 3 weeks). Objective response rate (ORR), diseases control rate (DCR), progression-free survival (PFS) and treatment-related adverse events were analyzed. Results: The ORR was both 33.3% in the FOLFOX group and RALOX group per RECIST 1.1 criteria ( P = 1.00). The DCR was 90.9% and 87.9% in the FOLFOX group and RALOX group, respectively ( P = 1.00). The median PFS was 10.7 months in the FOLFOX group versus 7.9 months in the RALOX group ( P= 0.251). Grade 3/4 treatment-related adverse events were comparable between the two groups, including neutropenia, thrombocytopenia, elevated aminotransferase level and nausea. Conclusions: The efficacy and safety of HAIC with raltitrexed plus oxaliplatin was comparable to HAIC with oxaliplatin plus fluorouracil in intermediate and advanced HCC.