bluuebunny/crossref_metadata_2025_split huggingface dataset:
Matched therapies for advanced gastric cancer based on genotype: A real-world study in China.
Authors: Liu Qin , Yang Ju , Wu Nandie , Liu Song , Zhang Yipeng , Chen Hui , Zhao Xiaochen , Bai Yuezong , Liu Baorui , Wei Jia 
Published: June 2021

e16098 Background: Systemic therapy options for patients with advanced gastric cancer (GC) are limited. We here presented the efficacy results for advanced GC patients matched to targeted therapies or immunotherapies based on the identification of tumor tissue genotypes. Methods: We selected 30 patients diagnosed between 2014 and 2020 with advanced GC at Nanjing Drum Tower Hospital, the affiliated Hospital of Nanjing University Medical School identified with actionable alterations and received ≥1 matched therapies. Tumor biopsy specimens from the patients were analyzed using NGS and/or selected immunohistochemistry and fluorescence in situ hybridization. Results: In these 30 patients, median age at diagnosis was 63 years (range 28-83) and 6 (20%) were female. In total, 11 (37%) harbored c-MET amplification/overexpression (received savolitinib or crizotinib, cohort A), 9 (30%) harbored HER2 mutation/overexpression (received RC48-ADC or trastuzumab, cohort B), 6 (20%) dMMR/MSI-H/TMB-H (received sintilimab, pembrolizumab, tislelizumab or nivolumab, combined with antivascular or not, cohort C), 2 (7%) KIT mutation/amplification (received imatinib or anlotinib, cohort D), 1 (3%) BRAF V600E mutation (received vemurafenib, cohort E) and 1 (3%) EGFR mutation (received afatinib, cohort F). Except for three patients in cohort C, all patients received at least one previous line systemic therapy. In cohort A, three of 11 patients had an objective response (1 complete response and 2 partial responses, objective response rate (ORR) 27%), disease control rate (DCR) was 45%, median progression-free survival (mPFS) was 2.1 months, and median overall survival (mOS) was 3.7 months. In cohort B, ORR was 44% (4/9), DCR was 78% (7/9), mPFS and mOS was 3.1 months and 5.5 months, respectively. In cohort C, ORR was 17% (1/6), DCR was 67% (4/6), mPFS and mOS was 1.9 months and 6.8 months, respectively. In cohort D, no patient had objective response or disease control. In cohort E, the one patient had PR. Stable disease was observed in the patient in cohort F. In all cohorts, ORR was 30% (9/30), DCR was 60% (18/30), mPFS and mOS was 2.7 months and 5.8 months, respectively. Conclusions: Overall, 30 patients with advanced GC were treated with matched therapies according to specific genotype. These real-world outcomes suggested that matched therapies for advanced GC has promising efficacy, supporting the adoption of genotyping in treatment determination.
Phase II study of combining immunotherapy and pulsed low dose rate radiotherapy for abdominal metastasis of gastric cancer.
Authors: Yang Yang , Yan Jing , Liu Juan , Li Shuangshuang , Gao Shanbao , Wei Jia , Liu Baorui 
Published: June 2021

e16099 Background: Immune-mediated responses against tumor antigens by checkpoint inhibitors (CPIs) may be enhanced by radiotherapy and the combination may hold therapeutic promise. Pulsed low dose rate radiotherapy (PLDR) is an effective strategy for abdominal tumor by taking advantage of low dose hyper-radiosensitivity with maximizing tumor response and minimizing adverse events by radiotherapy. In this phase II study, we prospectively analyzed the response and adverse events of the combination strategy of CPIs and PLDR for abdominal metastasis of gastric cancer. Methods: Eligibility criteria included pathologically confirmed advanced gastric adenocarcinoma with abdominal metastasis. Patients received XELOX regimen chemotherapy, anti-PD-1 toripalimab, and PLDR for abdominal metastasis, prescription dose was 50-56Gy/25-28f. The primary endpoint was objective response rate (ORR) and safety. Secondary endpoints were regional response rate (RRR) and regional controlled rate (RCR) for radiotherapy target tumor, progression-free survival (PFS), and overall survival (OS). Results: Between November 2018 and June 2020, 24 patients were enrolled and included in the efficacy analysis. 13 of them were first line therapy, and 11 of them were second line therapy. The ORR was 70.8% and the combination regimen were tolerable. The RRR was 83.3% and the RCR was 95.8%. The median PFS was 11.1 months and the median OS was not yet reached. Conclusions: In this phase II clinical trial, the combination of Immunotherapy and radiotherapy provided good response and toleration for abdominal metastasis of gastric cancer. It suggested clinical efficacy of this regimen in patients with advanced gastric cancer. Clinical trial information: NCT03061162.
Germline HLA-B evolutionary divergence to influence efficacy of immune checkpoint blockade therapy in gastrointestinal cancer.
Authors: Lu Zhihao , Shen Lin , Zhang Henghui , Chen Huan , Jiao Xi , Wang Yujiao , Wu Lijia , Sun Huaibo , Li Shuang , Gong Jifang , Li Jian , Zou Jianling , Yang Keyan , Mao Beibei , Zhang Lei , Zhang Xiaotian , Peng Zhi , Lu Ming , Wang Zhenghang 
Published: June 2021

e16101 Background: To date, although a number of biomarker-related investigations have focused on the intrinsic properties of tumor cells and immune microenvironment, how germline genetics influences efficacy of immune checkpoint inhibitors (ICIs) immunotherapy in gastrointestinal (GI) cancer is scarcely understood. Methods: Our investigation enrolled 94 metastatic GI cancer patients treated with ICIs recruited from Peking University Cancer Hospital (PUCH) between August 1, 2015, and May 24, 2019. A publicly available dataset from the Memorial Sloan Kettering (MSK) Cancer Center (MSK GI cohort) was used for validation. For the PUCH cohort, we performed HLA genotyping by whole exome sequencing (WES) analysis on the peripheral blood mononuclear cell (PBMC) from all 94 patients. Tumor tissues from 86 patients were subjected to WES analysis and immune oncology-related RNA profiling. Results: We assessed the clinic relevance of germline HLA heterozygosity and evolutionary divergence (HED, a quantifiable measure of HLA-I evolution) to immunotherapy in patients with advanced GI cancers from the PUCH cohort. Our data showed that neither HLA heterozygosity nor mean HED correlated with the overall survival (OS) in the PUCH cohort. However, patients with high HLA-B HED showed a better OS and durable clinic benefit (DCB) rate compared with the lower subgroup (p < 0.05 for all comparison). The prognostic value of HLA-B HED was consistently validated in the MSK GI cohort (N = 84). Notably, a combinatorial biomarker based on HLA-B HED and tumor mutation burden (TMB) could better stratify potential responders (86 patients with tumor samples). Survival analysis performed on the PUCH and MSK GI cancer datasets further demonstrated the potential joint utility of HLA-B HED and TMB for prognosis stratification. Moreover, HLA-B HED high subgroup was characterized with a lower prevalence of TP53 mutation and enrichment of multiple immune related pathways, indicating an immune-inflamed phenotype of this subgroup. Conclusions: Taken together, our data create an intriguing argument for the germline HLA-B sequence divergence and TMB as complementary biomarkers in guiding patient selection for GI cancer immunotherapy. Further investigation revealed a potential HLA-B restricted mutational pattern of TP53, and can be indicative of tumor immune microenvironment in GI cancer.
Predictors of 30-day readmission rate after total gastrectomy in patients with gastric malignancy.
Authors: Salazar Miguel , Gauto Estefania , Upadhyay Banskota Shristi Upadhyay , Palacios Pedro , Shrivastava Trilok , Baral Binav , Rodriguez Alarcon Pierre Alexander , Elsebaie Maha , Khanal Nabin 
Published: June 2021

e16109 Background: Total gastrectomy with lymph node dissection is curative for early gastric malignancy which accounts for 1.5% of cancer cases in the U.S. Readmissions are common postoperatively, and are associated with increased morbidity, mortality, hospital costs and decreased quality of life. We hence aim to identify incidence, impact and independent predictors for readmission in patients who underwent total gastrectomy in gastric malignancy. Methods: We conducted a retrospective cohort study of the 2017 National Readmission Database (NRD) of adult patients readmitted within 30 days after an index admission for total gastrectomy with a concomitant diagnosis of gastric malignancy. T-test was used for continuous variables and chi square test was used for categorical variables. Multivariate regression was used to identify predictors for unplanned readmissions. ICD 10 codes were used to identify diagnoses and procedures. Results: A total of 1,779 patients with gastric malignancy underwent total gastrectomy. The 30-day readmission rate was 18.5%. Main causes for readmission were sepsis, ventricular fibrillation, recurrent STEMI. Readmitted patients were more likely to be on chemotherapy. (40.1% vs 27.2%; P<0.01) and more likely to be discharged to a skilled facility (13.5% vs 17.9%; P<0.01). The total health care in-hospital economic burden of readmission was $6.5 million in total charges and $25 million in total costs. Independent predictors of readmission were major bleeding, respiratory failure requiring mechanical ventilation, peripheral parenteral nutrition, history of non-alcoholic hepato-steatosis, and prolonged length of stay. Conclusions: Readmissions after gastrectomy in patients with gastric malignancies are associated with lower in-hospital mortality yet pose a substantial economic burden on healthcare. The lower mortality might be explained by the relatively stable course and lower comorbidities of patients who become eligible for discharge after surgery. Further studies are suggested. Modifiable risk factors like malnutrition and sepsis warrant special attention to decrease readmissions and improve overall outcomes.[Table: see text]
Clinical efficacy and safety of proton beam or photon radiation in combination with immune checkpoint inhibitors in patients with advanced hepatocellular carcinoma.
Authors: Su Chung Wei , Huang Pei-Wei , Chou Yung-Chih , Lin Chen-Chun , Hong Ji-Hong , Hou Ming-Mo 
Published: June 2021

e16113 Background: Management of advanced hepatocellular carcinoma (HCC) remains a challenge. IMbrave150, a pivotal trial reported impressive overall survival benefit using combination strategy of atezolizumab and bevacizumab compared to sorafenib. We wonder the efficacy and safety when combining radiotherapy with immune checkpoint inhibitors (ICIs), which radiation might provide better local treatment and possible trigger abscopal effect. The aim of this study is retrospectively reporting the real-world efficacy and tolerability of proton beam or photon radiation plus ICIs in patients with advance stage HCC. Methods: We retrospectively reviewed all BCLC stage C HCC patients who have received combination therapy with ICIs plus proton or photon therapy with well documented basic characteristics and prompt treatment efficacy evaluation between 1st of January 2016 to 31st of October 2019 at a single medical center in Taiwan. 20 patients had ICIs plus proton and 32 patients had ICIs plus photon were included for analysis. Overall survival (OS) and progression free survival (PFS) were evaluated by Kaplan-Meier estimator. Results: Baseline characteristics were generally similar between ICIs plus proton or ICIs plus photon, while most patients in proton group did not receive prior systemic treatment and had less local therapies prior ICIs combine with radiotherapy. Median follow-up time was 10.7 months. The median Progression free survival (PFS) was not reached in ICIs plus proton group and 3.6 months (95% CI 2.7-4.6) in ICIs plus photon group (P = 0.007). The median OS was not reach in ICIs plus proton group and 12.1months (95% CI 6.4-17.7) in ICIs plus photon group (P = 0.007). Comparing ICIs plus proton group versus photon group, objective tumor response is 50% versus 9%, disease control rate is 80% versus 47% in each group. During follow-up, 7 patients (35%) in proton group achieved complete remission (CR). There was difference in radiation filed, 19 patients (95%) in proton group and 15 patients (47%) in photon group targeted on liver tumors, and more patient received > 50Gy treatment dose in proton group compared to photon group (90% versus 20%). Proton group has lower failure rate in both inner- or out-field compared to photon group. Grade 1 to grade 2 skin-dermatological and gastrointestinal toxicity remained the most frequent reported adverse events in both groups. There are only one therapy related grade 3 dermatitis in ICIs plus proton group and one grade 3 hepatitis, one grade 5 pneumonitis in ICIs plus photon group. Conclusions: This study reported real-world efficacy and safety of ICIs in combination with proton or photon therapy. Most adverse events were manageable. The combination of ICIs and proton therapy has impressive CR rate and OS benefit. Further prospective randomized trial is warranted for confirm our finding.
Triple combination therapy comprising angiogenesis inhibitors, anti-PD-1 antibodies, and hepatic arterial infusion chemotherapy in patients with advanced hepatocellular carcinoma.
Authors: Zhang Ti , Zhang Jinliang , Zhang Xihao , Mu Han , Yu Ge , Xing Wenge 
Published: June 2021

e16124 Background: The effects of single-drug therapy for the systemic treatment of advanced unresectable hepatocellular carcinoma (HCC) remain unsatisfactory, promoting the emergence of multi-drug and combination therapies. Here we assess the safety and efficacy of a triple combination therapy for treating advanced HCC. Methods: This single-center retrospective study included patients with unresectable HCC treated with triple combination therapy comprising angiogenesis inhibitors (oral apatinib 250 mg/day, lenvatinib 8 mg/day, or sorafenib 400 mg BID), anti-programmed cell death 1 antibodies (iv camrelizumab or sintilimab, 200 mg every 3 weeks), and hepatic arterial infusion chemotherapy (FOLFOX every 4–8 weeks). Eligible patients had completed at least one cycle of therapy and had an imaging assessment. Treatment-related adverse events (TRAEs) were assessed according to the Common Terminology Criteria for Adverse Events. Efficacy data were summarized according to modified RECIST (mRECIST) and RECIST v1.1. Results: Of 34 patients who received triple combination therapy, 25 (19 men and 6 women; median age: 59 years [range: 49–78]) had an imaging assessment. TRAEs were manageable; 28.0% of patients experienced grade 3–4 TRAEs. Efficacy outcomes are summarized in the Table. The objective response rate was 96.0% (mRECIST), the median time to response was 50.5 days (95% CI: 31.02–64.00) and the surgical conversion rate was 56%, indicating a robust therapeutic effect. Overall, 12 patients (48.0%) achieved a complete response (CR), 12 (48.0%) achieved a partial response, and one (4.0%) had stable disease (mRECIST). Fourteen patients (56.0%) underwent surgical resection, after which seven (28.0%) achieved a pathologic CR. After a median follow-up of 9.67 months, no cases of post-operative recurrence or metastasis emerged. Conclusions: Triple combination therapy had a robust therapeutic effect with a high surgical conversion rate in patients with advanced HCC. TRAEs were acceptable, and long-term efficacy is reasonably expected. Summary of efficacy outcomes (n = 25).[Table: see text]
Preliminary results of the phase II ALTER-H004: Anlotinib combined with TACE as adjuvant therapy in hepatocellular carcinoma patients at high risk of post surgery recurrence.
Authors: Wu Zheng , Wang Zheng , Zhang Lei , Song Xiaojing , Du Xilin , Tan Kai 
Published: June 2021

e16125 Background: Hepatocellular carcinoma (HCC) is one of the most common malignant tumors with high incidence and mortality worldwide. Presumably, adjuvant therapy is an efficient treatment for reducing recurrence in patients (pts) with hepatectomy, especially in those with high recurrence factors. Transarterial chemoembolization (TACE) can block the blood supply of the tumor, besides, high concentration of chemotherapeutic drugs can be accumulated within the tumor. It is recommended in several guidelines prophylactic TACE for pts with high recurrence risk factors after hepatectomy, which mainly include grade 1-2 microvascular invasion (M1-2) and portal vein tumor thrombus resection. Moreover, angiogenic inhibitors based therapy has constituted the crucial treatment strategy in HCC. As a novel multitarget tyrosine kinase inhibitor, anlotinib was demonstrated to be an effective first and second-line monotherapy for pts with advanced or recurrent HCC in China. The aim of this phase II trial was to evaluate the efficacy and safety of anlotinib as maintenance adjuvant treatment following inductional TACE in pts with HCC. Methods: A total of 48 histologically confirmed HCC pts who undertook hepatectomy within 1-2 months will be enrolled. The recruited pts who did not recieve any previous tumor-related treatment must have any of the following high risk factors: ≥5cm and <10cm of tumor diameter, tumor number ≥3, tumor microvascular invasion M1 or M2, portal vein tumor thrombus resection (Cheng’s classification Ⅰ/Ⅱ). Enrolled pts were received conventional TACE treatment with pirarubicin or epirubicin and platinum within 1-2 months after hepatectomy. On the 4th day after TACE treatment, oral anlotinib (12mg, qd, 2 weeks on 1 week off) was given until disease recurrence or unacceptable toxicity. The primary endpoint was disease free survival (DFS). Secondary endpoints included 1-year DFS rate, time to recurrence and safety. Results: By the cutoff date of January 26, 2021, 10 pts were enrolled and received at least once tumor assessment. According to RECIST version 1.1, 9 of them did not progress and 1 relapsed, in whom the DFS was 2.4 months. Most of treatment-related adverse events (TRAEs) were rash (20.0% Grade≤2), pain (20.0% Grade=1) and hypertension (10.0% Grade=1). Only one patient had grade 3 TRAE which was leukocytopenia (10.0%). No more grade 3 or above TRAEs occurred. Conclusions: The current results indicated that anlotinib combined with TACE as adjuvant therapy in HCC pts at high recurrence risk exhibited preliminary and implicational anti-tumor efficacy and manageable toxicity. The conclusion should be validated in more pts consecutively. Clinical trial information: NCT04213118.
Comprehensive molecular characterization of Chinese patients with intrahepatic and extrahepatic cholangiocarcinoma.
Authors: Yi Bin , Liu Lianke , Gu Dejian , Chen Rongrong , Xia Xuefeng , Jiang Xiaoqing 
Published: June 2021

e16128 Background: Cholangiocarcinoma (CCA) is a heterogeneous disease arising from a complex interaction between host-specific genetic background and multiple risk factors. Globally, CCA incidence rates exhibit geographical variation, with much higher incidence in parts of the Eastern world compared to the West. Therefore, understanding the molecular characteristics of Chinese CCA patients is helpful for individualized treatment of patients. Methods: We reviewed 397 Chinese cholangiocarcinoma patients, including 125 extrahepatic and 272 intrahepatic, with paired tumor-normal samples sequenced by a 1021 gene panel. Tumor mutational burden(TMB) was defined as the number of somatic non-synonymous mutations per megabase of the panel region. Results: The genomic profiling was analyzed and indicated that TP53 and KRAS were the most frequently mutated gene, which were detected in 47% and 27% samples. The common targets gene of FGFR2 and IDH1 were detected in 6% and 4% patients in our cohort. Meanwhile, the prevalence of gene mutated was compared between intrahepatic and extrahepatic cholangiocarcinoma. The TP53 mutation was more frequently prevalence in intrahepatic cholangiocarcinoma (51% vs 36%, p = 0.0048); and the FGFR2 fusion more detected in extrahepatic cholangiocarcinoma (4% vs 10%, p = 0.0214). The TMB was also analyzed in our study and ranged from 1 to 194 (median:5). No difference was found between intrahepatic and extrahepatic cholangiocarcinoma in TMB. Besides, the TP53 mutations showed significant association with higher TMB (p < 0.0001), both intrahepatic and extrahepatic cholangiocarcinoma; and KRAS mutations showed significant association with higher TMB (p = 0.029) in intrahepatic cholangiocarcinoma. Interesting, KRAS mutations was also association with TMB in extrahepatic cholangiocarcinoma; The KRAS-mutated & TP53-wildtype(wt) patients showed higher TMB than double-wt patients (5.5 vs 4, p = 0.048) and the only TP53-mutated patients showed higher TMB than double-mutated patients (8 vs 6, p = 0.047). Conclusions: In conclusion, the genomic profiling and molecular characterization were difference between intrahepatic and extrahepatic cholangiocarcinoma, which may helpful in clinical diagnosis and treatment.
Real-world effectiveness of lenvatinib monotherapy among previously treated unresectable hepatocellular carcinoma patients in United States clinical practices.
Authors: Singal Amit G. , Nagar Saurabh P , Hitchens Abigail , Iyer Shrividya 
Published: June 2021

e16129 Background: In the United States (U.S.), lenvatinib monotherapy was approved in August 2018 for first-line treatment of patients with unresectable hepatocellular carcinoma (uHCC) based on the pivotal trial, REFLECT. Treatment patterns in uHCC are evolving with recent approvals. The main objective of our real-world data (RWD) study was to assess treatment patterns and clinical effectiveness of lenvatinib among previously treated uHCC patients in U.S. clinical practices. Methods: A retrospective patient chart review study was conducted among U.S. adult patients (≥18 years) with uHCC and ECOG status of 0 or 1, who initiated lenvatinib monotherapy as second- or later-line systemic therapy between Aug 2018 and Sept 2019. Data were extracted from individual patients’ electronic health records and captured in electronic case report forms. Clinical outcomes assessed include provider-reported best response, progression-free survival (PFS) and overall survival (OS). PFS and OS were estimated using Kaplan-Meier methods. For PFS, patients were censored at end of treatment or end of follow-up in case of ongoing treatment, while censoring occurred at end of follow-up for OS. Results: Of 164 patients, median age was 62 years, majority were male (72%), and most were Caucasian (56%) followed by African American (23%). The most common liver disease etiologies were alcohol-related (32%), hepatitis C (26%), non-alcoholic steatohepatitis (21%) and hepatitis B (15%). Only one-third (31%) had Child Pugh A cirrhosis, with nearly half (49%) having Child Pugh B cirrhosis. Most patients had Barcelona Clinic Liver Cancer Stage B (24%) or C (38%) disease. Median body weight was 77 kg, and the median starting dose of lenvatinib was 12 mg daily. Median duration of lenvatinib treatment was 6.9 months, with 43% of patients remaining on lenvatinib at end of follow-up. RECIST v1.1 was reported as the criteria used to assess response in 60% of patients. Provider-reported best response was complete response (CR):9%, partial response (PR):45% and stable disease (SD): 26%. Median PFS and median OS were estimated to be 12.5 months and 14.0 months respectively. At 6 and 12 months, landmark PFS was 71% and 52%, respectively and landmark OS was 84% and 58%, respectively. PFS and OS estimates were consistent in subgroup analyses among those who had received lenvatinib in the second-line (81%, n=133) or treated with lenvatinib post immunotherapy (66%, n=109) (Table). Conclusions: Results from this retrospective real-world study affirm the clinical effectiveness of lenvatinib monotherapy among previously treated uHCC patients, including those with prior immunotherapy.[Table: see text]