bluuebunny/crossref_metadata_2025_split huggingface dataset:
Efficacy and safety of perioperative chemotherapy combined with tislelizumab and trastuzumab for HER2-positive resectable gastric/gastroesophageal junction cancer (GC/EGJC): Preliminary results of a phase 2, single-arm trial.
Authors: Zhao Chunlin , Meng Xiangrui , Shan Zhengzheng , Jiang Jianwu , Liu Xinyu , Li Haohao , Sun Junfeng , Ding Chaohui , Xia Jin , Liu Zhiqiang , Wang Feng 
Published: June 2023

e16084 Background: Recently, immunotherapy combined with trastuzumab and chemotherapy have been recommended by the clinical guidelines of many countries as the first-line treatment for advanced HER2-positive G/GEJ adenocarcinoma. Combining chemotherapy with tislelizumab and trastuzumab in the neoadjuvant/adjuvant setting may benefit patients with locally advanced, resectable HER2-positive GC/GEJC. Methods: This study is a multicenter, single-arm, open-label phase 2 study (NCT04819971). Patients with histologically confirmed cT2-4NxM0 or cTxN+M0, (TNM 8th edition), resectable gastric adenocarcinoma are eligible for this study. Neoadjuvant therapy will be administered for four cycles. The patients will receive tislelizumab and trastuzumab for 1 cycle (Q3W), followed by tislelizumab and trastuzumab combined with DOS (Docetaxel + Oxaliplatin + S-1) for 3 cycles (Q3W). Surgery is planned 4-6 weeks after preoperative treatment. Patients who have complete surgical resection will receive adjuvant therapy starting within 4–6 weeks after surgery for 6 cycles (three cycles of tislelizumab and trastuzumab combined with DOS regimen, followed by 6 weeks of tislelizumab and trastuzumab for 6 cycles. The primary endpoint was pathological complete response rate (pCR). Secondary endpoints included R0 resection rate, 1-year and 2-year event-free survival (EFS), overall survival (OS) and safety. Results: From September 13, 2021 to February 01, 2023, 12 patients were enrolled (58.0% male, median age 61 years old), and the median follow up time was 7.3 months (0.4-16.9). Seven patients completed surgery, and 5 patients were undergoing neoadjuvant therapy. The R0 resection rate was 100%, 3 patients (42.9%) achieved pCR, and 4 patients (57.1%) achieved major pathological remission (MPR). Postoperative pathology showed tumor downstaging in 5 cases after neoadjuvant therapy, with a decrease rate of 71.4%. Median OS and EFS have not been reached. The most common AEs (all grades, grade ≥3) were anemia in 1 (8.3%) and neutropenia in 1 case (8.3%). The immune-related adverse events were all grade 1 included 2 thyroid dysfunction (16.7%), 1 abnormal liver function (8.3%), and 1 of elevated blood sugar (8.3%). No grade 3 or higher immune-related AE was observed. No treatment related deaths were reported. Conclusions: According to the preliminary results, tislelizumab combined with trastuzumab and standard chemotherapy in the perioperative period of HER2-positive GC and EGJ have a good clinical benefit trend and controllable security. Clinical trial information: NCT04819971 .
A single-center, prospective, single-arm, phase II trial to evaluate the adjuvant efficacy of camrelizumab with docetaxel plus S-1 for stage III (PD-L1+/dMMR/EBV+) gastric cancer after D2 resection.
Authors: Ni Bo , Xia Xiang , Guan Yujing , Yang Linxi , Ji Linhua , Zhao Enhao , Cao Hui , Zhao Gang , Zhu Chunchao , Zhang Zizhen 
Published: June 2023

e16089 Background: Immunotherapy has demonstrated promising efficacy and favorable safety profile for unresectable or metastatic gastric cancer (GC) by several high-quality studies. However, few have examined the immunotherapy efficacy for locally advanced GC (LAGC) in the perioperative setting, especially as adjuvant therapy after D2 resection. Here, a phase II trial reports the adjuvant efficacy of camrelizumab with docetaxel plus S-1 in patients (pts) with PD-L1 positive, deficient mismatch repair (dMMR) or Epstein-Barr virus (EBV) positive LAGC (NCT04152889). Methods: This is a single-center, prospective, open-label and single-arm phase II study. Chemotherapy-naive adult pts receiving D2 resection and histologically confirmed as PD-L1 positive (CPS > 5), dMMR or EBV positive LAGC (stage III) were enrolled. Pts received camrelizumab (200mg, D1), docetaxel (40mg/m2, D1, free at first course) and S-1 (80-120mg, D1-14) every 3 weeks for seven courses, sequenced by camrelizumab (200mg, D1) and S-1 (80-120mg, D1-14) every 3 weeks for up to one year, until disease relapse or intolerable toxicity. Primary endpoint was 1-year relapse-free survival (RFS). Herein, the safety and efficacy data after 1-year postoperative therapy courses were reported. Results: From Jan. 2020 to Jan. 2022, 19 pts (median age 59 years, range 34-75, 13 men and 6 women) were enrolled, of whom 15 were CPS > 5, 3 were dMMR, and 1 was EBV positive. pTNM stage IIIA, B and C were 10 (52.6%), 3 (15.8%) and 6 (31.6%), respectively. The cut-off date for the final follow-up data was Feb. 1, 2023 with a median follow-up period for surviving patients of 25.1 months. All 19 pts had experienced treatment related adverse events (TRAEs), of whom, grade 3-4 TRAEs occurred in 9 (47.4%), 2 pts (10.5%) discontinued therapy, and 11 pts (57.9%) delayed the therapy. Furthermore, the OS rate of 19 pts at 1/2 years was 100% and 88.9%, while the RFS rate at 1/2 years was 100% and 92.3%, respectively. The dead and recurrent cases all belonged to PD-L1 positive subgroup. Conclusions: Adjuvant therapy of camrelizumab with docetaxel plus S-1 shows acceptable safety and promising efficacy for PD-L1 positive, dMMR, or EBV positive stage III GC pts after D2 resection. Clinical trial information: NCT04152889 .
Variation of body composition and its impact on survival in a global population of patients receiving multimodal treatment for esophageal cancer.
Authors: Boshier Piers R , Low Donald E. ,   INSPECT Authors' Group
Published: June 2023

e16093 Background: Growing evidence has supported a role for body composition in predicting survival in patients undergoing esophagectomy. This study seeks to define baseline variation and clinical correlates of body composition in an international cohort of patients undergoing esophagectomy for cancer. Methods: Patients who underwent esophagectomy in fourteen high-volume centers between January 2007 to December 2019 were eligible for inclusion. Skeletal muscle, visceral and subcutaneous adipose tissues within CT images, acquired at the time of diagnosis, were analyzed by a single trained assessor in accordance with a standardized protocol. Survival status was censored June 2022. Results: In total 1716 patients were recruited to this study from three global regions: North America (n = 386; 22.5%), Europe (n = 940; 54.8%) and Asia (n = 390; 22.7%). Patients were predominantly male (79.5%) and adenocarcinoma was the most common histological subtype (66.6%). Wide variation in skeletal muscle (17.1 to 83.5cm2), visceral (0.2 to 170.1cm2) and subcutaneous adipose tissue (0.2 to 216.8cm2) was observed. Characteristics that were significantly associated with levels of muscle and adiposity were global region, sex, age and histological subtype. Compared to adenocarcinoma, SCC was associated with significantly (p < .0001) lower levels of muscle and adiposity, a finding that was independent of global region, sex, and age using a multivariable linear regression model (p < .0001). Reduced skeletal muscle and an excess of total adiposity at the time of diagnosis was associated with 90-day mortality and worse long-term survival. A nomogram including skeletal muscle, total adiposity at diagnosis and other tumor and patient specific variables was constructed to allow convenient survival prediction. Conclusions: This is the first study to assess parameters of body composition in a global cohort of patients receiving multimodal therapy for esophageal cancer. Findings highlight important regional and disease specific variation in body composition parameters and demonstrate the clinical utility of these measurements in predicting both early and late survival after esophagectomy. Results are intended to inform future guidelines for the use of body composition assessment in routine clinical practice.
Eligibility of patients with esophageal and gastroesophageal cancer for biology-guided radiotherapy in a retrospective cohort.
Authors: Olaechea Santiago , Song Tidie , Gilmore Linda , Infante Rodney E , Desai Neil B , Dan Tu , Zhang Yuanyuan , Westover Kenneth D. , Timmerman Robert D. , Oz Orhan K. , Iyengar Puneeth , Garant Aurelie 
Published: June 2023

e16100 Background: Biology-guided radiotherapy (BgRT) is a novel radiotherapy modality that uses real-time positron emission tomography (PET) to guide radiotherapy beamlets. The FDA recently cleared BgRT for clinical use for tumors in lung and bone using 18F FDG radiotracer. We sought to identify esophageal cancer (EC) and gastroesophageal junction cancer (GEJC) patients who may be BgRT candidates based on diagnostic FDG PET/CT imaging. Methods: Through IRB-approved extraction of patient medical record data from an institutional repository of prospectively maintained data, we verified a database of EC and GEJC patients diagnosed at a US tertiary care center between 01/01/2006 and 12/31/2013. When insufficient diagnostic clinical information was present, patients were excluded. Patient and tumor qualities were quantified and subjected to parameters of tumor diameter (≥2cm, <5cm) and maximum standardized uptake value (≥6) to observe potential characteristics of a patient population eligible for this novel BgRT mechanism. Results: Thirty patients met tumor size and FDG uptake criteria for BgRT therapy out of an overall patient cohort of 90 patients. A significantly greater proportion of patients within the BgRT-eligible cohort presented with esophageal tumors (83.3%) compared to non-eligible patients (58.3%, P=0.0177). Otherwise, there was no significant variation of patient sex, race, tumor histology, tumor stage, comorbidity score, and pre-treatment weight loss between patients eligible and not eligible for BgRT therapy. Conclusions: After applying current boundaries of tumor size and radiotracer uptake for effective BgRT intervention, we observed broad applicability of the novel treatment modality across EC/ GEJC patients of varying characteristics and tumor qualities. The high eligibility of patients with tumors located within the esophagus supports further investigation of BgRT in their management. [Table: see text]
Clinical efficacy and safety of immune checkpoint inhibitor in combination with regorafenib therapy as second⁃line regimen for patients with unresectable hepatocellular carcinoma.
Authors: Li Jinpeng , Jia Yuntao , Song Jinlong 
Published: June 2023

e16105 Background: Combined systemic and local therapy is a promising treatment strategy for patients with advanced hepatocellular carcinoma (HCC). Transarterial chemoembolization (TACE), tyrosine kinase inhibitors (TKI) and PD-1 antibodies are all recommended for patients with unresectable HCC (uHCC). This study was aimed to evaluate the efficacy and safety of TACE combined with TKIs and camrelizumab in the treatment of uHCC. Methods: In this multicenter, single-arm phase II trial (ChiCTR2000039508), patients with intermediate-stage uHCC who had a Child-Pugh score ≤ 7 and had not received prior systemic anti-cancer treatment would receive treatment with TACE followed by immunotherapy with camrelizumab 200 mg every 3 weeks plus a TKI agent selected from lenvatinib (12 mg/day for bodyweight ≥60 kg or 8 mg/day for bodyweight <60 kg), sorafenib 400 mg bid or donafenib 200 mg bid until intolerable toxicity or disease progression. During the study treatment, patients assessed as eligible for resection would undergo surgery. The primary endpoint was objective response rate (ORR) per modified RECIST. Secondary endpoints included progression-free survival (PFS), disease control rate (DCR), duration of response (DOR) and overall survival (OS). Results: From September 2020 to November 2021, 87 patients (81 men and 6 women; median age, 56 years) were enrolled. Among them, 43 (49.4%) patients had extrahepatic metastases, and 65 (74.7%) patients had HBV infection. As of September 28, 2022, the median duration of follow-up was 13.6 (0.83-24.9) months. A total of 34 patients (39.1%) died, and the median OS was not reached. The median PFS was 10.5 months (95% CI: 7.8-13.1). The ORR rate was 71.3% (62/87), and the DCR rate was 89.7% (78/87) per mRECIST. According to RECIST version 1.1, the ORR rate was 35.6% (31/87), and the DCR rate was 87.4% (76/87). The ORR and PFS showed consistent benefits in subgroups based on ECOG score, HBV infection, baseline alpha-fetoprotein level, combined TKI, and the number of TACE treatments. Ten patients (11.5%) successfully underwent conversion therapy and all achieved R0 resection. Two patients achieved a complete pathological response (pCR) and four achieved a major pathological response (MPR). The most common AEs were hypoproteinemia (92%), elevated lactate dehydrogenase (80.5%), elevated glutamic oxaloacetic transaminase (79.3%), elevated bilirubin (78.2%), abdominal pain (62.1%), nausea (33.3%), and RCCEP (26.4%). The incidence of grade 3-4 adverse reactions was 67.8%, and no treatment-related deaths occurred. Conclusions: TACE combined with TKI and camrelizumab showed promising clinical benefits. It can effectively control tumor progression and provide opportunities for resection with acceptable safety, which will bring great benefits to uHCC.
Diagnostic and prognostic biomarker value of blood circulating inflammatory cytokines in hepatocellular carcinoma.
Authors: Chamseddine Shadi , Kaseb Ahmed Omar 
Published: June 2023

e16115 Background: Circulating inflammatory cytokines play critical roles in tumor-associated inflammation and immune responses. Recent data has suggested that several interleukins (ILs) mediate carcinogenesis in hepatocellular carcinoma (HCC). However, the predictive and prognostic value of circulating ILs has yet to be validated. Our study aimed to evaluate the association of the serum ILs with overall survival (OS) and clinicopathologic features in a large cohort of HCC patients. Methods: We prospectively collected data, and serum samples from 767 HCC patients treated at The University of Texas MD Anderson Cancer Center between 2001 and 2014, with a median follow-up of 67.4 months (95% CI: 52.5, 83.3). Biomarker association with overall survival (OS) was evaluated by the Log-rank method. Results: The median OS in this cohort was 14.2 months (95% confidence interval [CI]: 12, 16.1 months). Clinicopathologic features were more advanced, and OS was significantly inferior in patients with high circulating levels of IL1-R1, IL-6, IL-8, IL-10, IL-15, IL-16, and IL-18. Conclusions: In conclusion, our study shows that several serum IL levels are valid prognostic biomarker candidates and potential targets for therapy in HCC.
Immune checkpoint inhibitor plus tyrosine kinase inhibitor with or without transarterial chemoembolization for unresectable hepatocellular carcinoma.
Authors: Pan Hongyu , Ruan Minghao , Jin Riming , Zhang Jin , Li Yao , Wu Dong , Sun Wen , Wang Ruoyu 
Published: June 2023

e16123 Background: Transcatheter arterial chemoembolization (TACE) has been combined with immune checkpoint inhibitor (ICI)-based systematic therapies for unresectable HCC (uHCC) with promising efficacy. However, whether the addition of TACE to the combination of ICI and tyrosine kinase inhibitor (TKI) (ICI+TKI+TACE) is superior to ICI+TKI combination therapy is still not clear. Thus, this study compares the efficacy of ICI+TKI+TACE triple therapy and ICI+TKI doublet therapy in patients with uHCC. Methods: uHCC patients treated with either ICI+TKI+TACE triple therapy or ICI+TKI doublet therapy were retrospectively recruited between January 2016 and December 2021 at Eastern Hepatobiliary Surgery Hospital. The patients from ICI+TKI+TACE group and ICI+TKI group were further subjected to propensity score matching based on the baseline characteristics. The primary outcome was progression-free survival (PFS) in matched patients. The secondary outcomes were overall survival (OS) and objective response rate (ORR). Post-progression survival (PPS) as well as treatment-related adverse events (TRAEs) were also assessed. Results: A total of 120 patients were matched. The median PFS was 8.4 months in ICI+TKI+TACE triple therapy group versus 6.6 months in ICI+TKI doublet therapy group (HR 0.72, 95%CI 0.48-1.08; p=0.115). Similar results were obtained in term of OS (26.9 versus 24.2 months, HR 0.88, 95% CI 0.51-1.52; p=0.670). The ORR in the triple therapy group was comparable with that in the doublet therapy group (16.6% versus 21.6%, p=0.487). Further subgroup analysis for PFS illustrated that patients without previous locoregional treatment (preLRT) (10.5 versus 3.7 months, HR 0.35 [0.16-0.76]; p=0.009), without previous treatment (10.5 versus 3.5 months, HR 0.34 [0.14-0.81]; p=0.015) or treated with lenvatinib (14.8 versus 6.9 months, HR 0.52 [0.31-0.87]; p=0.013) can significantly benefit from triple therapy compared with doublet therapy. A remarkable interaction between treatment and preLRT ( p=0.049) or TKIs-combined ( p=0.005) was also detected in term of PFS. Kaplan-Meier analysis of PPS revealed that patients with post progression treatment displayed significant improved survival in both ICI+TKI+TACE and ICI+TKI groups. The incidence of TRAEs was comparable between two groups. Conclusions: In selected uHCC patients (without preLRT or treated with lenvatinib as combination), the addition of TACE to ICI+TKI combination therapy can remarkably improve PFS.
Arterial chemotherapy in advanced hepatocellular carcinoma: An evolutionary trajectory exploration and pooled outcome analysis.
Authors: Chen Qi-Feng , Lyu Ning , Zhao Ming 
Published: June 2023

e16125 Background: Hepatic artery infusion chemotherapy (HAIC) is widely used for the treatment of advanced hepatocellular carcinoma (HCC), particularly in East Asia. However, there have been inconsistent conclusions on the effectiveness of HAIC in previous studies, and the analysis landscape regarding relevant articles and clinical trials is lacking on this topic. We conducted a bibliometric analysis to explore the development of HAIC, and a pooled analysis using individual patient data to evaluate the outcomes of HAIC in advanced HCC. Methods: The Web of Science Core Collection was searched from its earliest records until October 2022, to identify studies associated with HAIC for advanced HCC. Relevant documents were collected and analyzed using R bibliometrix. During the same period, two international clinical trial registered platforms, ClinicalTrials.gov and ChiCTR.org, were searched for oxaliplatin-based HAIC utilization in HCC. A total of 845 patients treated with HAIC or its combination therapy from 17 pre-registered studies were analyzed to assess the overall survival (OS), progression-free survival (PFS), objective response rate (ORR per Response Evaluation Criteria in Solid Tumors (RECIST)), disease control rate (DCR per RECIST), and adverse events (AEs). Results: We identified 539 studies and derived the evolutionary trajectory of HAIC from the perspective of scientometry. Contributions of publications were presented at the country, institution, and author levels. Conversion therapy, Folfox, oxaliplatin and immunotherapy became new research foci. A total of 88 registered trials were identified and a comprehensive landscape of these trials was provided. Further interactive exploration of the trials was accessible through a HAICshiny application (https://sysucc.shinyapps.io/clinical-trial-of-HAIC-FO/). The OS was 13.7 months (95% confidence interval (CI) 12.2-15.3), and the corresponding times were 13.2, 13.8, 12.8, and 13.7 months in the cisplatin, oxaliplatin, HAIC monotherapy, and concomitant therapy subgroups, respectively. The corresponding PFS was 7.0 months (95% CI 6.5-7.8) in the whole cohort and 5.2, 7.7, 7.6, and 6.8 months in the subgroup cohorts. According to RECIST criteria, ORR and DCR reached 0.34 and 0.80, respectively. Comparable survival and tumor response were observed between the HAIC and its combination therapy groups. The incidence of AEs was identified, and most of them were manageable. Conclusions: This study illustrates the evolutionary trajectory of HAIC from the perspective of scientometry. The efficacy outcomes of HAIC in the treatment of advanced HCC were verified with manageable safety profiles. Further trials regarding HAIC implementation are emerging, and more effort is required to improve the quality of trials.
Regorafenib as a first-line agent alone or in combination with an immune checkpoint inhibitor for advanced hepatocellular carcinoma efficacy and safety of patients: A real-world study.
Authors: Bai Yi , Yu Jianfa , Cheng Chuanliang , Chen Dapeng , Zhang Yamin 
Published: June 2023

e16126 Background: Results from the RESORCE-III RCT demonstrated that sequential sorafenib-regorafenib treatment significantly improved overall survival compared with the placebo group. However, there are no retrospective studies of regorafenib as a first-line agent for treating patients with advanced hepatocellular carcinoma in a real-world setting. Therefore, we aimed to explore the efficacy and safety of regorafenib as a first-line agent alone or in combination with immune checkpoint inhibitors (ICIs) in treating patients with advanced hepatocellular carcinoma in a real-world setting. Methods: We reviewed medical data from 48 patients with advanced hepatocellular carcinoma treated with regorafenib as a first-line agent alone or combined with ICIs between December 2018 and February 2022. These patients were treated with regorafenib for at least 28 consecutive days (21 days on and 7 days off the drug). The progression-free survival (PFS), overall survival (OS), objective response rate (ORR, RECIST 1.1 criteria) and disease control rate (DCR) were observed. Results: A total of 48 patients were enrolled in this study, 26(54.2%) receiving regorafenib as monotherapy and 22(45.8%) receiving the combination ICIs. The median age in the monotherapy group was 54 years (range 38-74), male/female (69.2%/30.8%), BCLC stage B/C (42.3%/57.7%), Child-Pugh A/B score (57.7%/42.3%); the median age in the combined ICIs group was 53 years (range 42-75), male/female (68.2%/ 31.8%), BCLC stage B/C (36.4%/63.6%), Child-Pugh A/B score (54.5%/45.5%). Median PFS (mPFS) was 7.7 months (95% CI:5.9-10.4) and median OS (mOS) was 16.7 months (95% CI:14.3-23.6) in 48 patients. In the regorafenib monotherapy group, mPFS was 5.9 months (95% CI:5.6-10.3) and mOS was 13.9 months (95% CI:13.5-22.5); in the combined ICIs group, mPFS was 7.8 months (95% CI:7.3-14.5) and mOS was 23.6 months (95% CI:16.6-NA). The ORR and DCR were 20.8% and 72.9% in the overall treatment group, 15.4% and 65.4% in the monotherapy group, and 27.3% and 81.8% in the combined ICIs treatment group, respectively. Among the adverse events, rates were 34.6% (9/26) and 36.4% (8/22) in the monotherapy and combined ICIs groups, respectively, with only one grade III/IV adverse event in the monotherapy group and no grade III/IV adverse event in the combined ICIs group. Conclusions: This retrospective, real-world, preliminary study demonstrates that regorafenib as a first-line agent alone or in combination with ICIs has a high safety profile and more prolonged survival in patients with advanced hepatocellular carcinoma, particularly in combination with ICIs.