bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phase II trial of terelizumab combined with radiotherapy of locally advanced unresectable esophageal squamous cell carcinoma: TREC trial.
Authors: Liu Changmin , Yu Zeshun , Hao Yanzhang , Wang Feng , Wang Zhenbo , Tian Lijun , Wang Yue , Ning Fangling 
Published: June 2023

e16086 Background: Concurrent chemoradiotherapy (CCRT) is the standard therapy for locally advanced unresectable esophageal squamous cell cancer (ESCC)，However, some patients cannot tolerate or are unwilling to CCRT. The aim of this phase II trial was to assess the efficacy and safety of the tirelizumab combined with radiotherapy in patients of locally advanced unresectable ESCC. Methods: Key eligibility criteria were as follows: ESCC of clinical stage Ⅱ-Ⅳa; aged 18 to 90 years; cannot tolerate or are unwilling to CCRT; ECOG performance status 0 or 1; and performed radiotherapy: Involvement field irradiation, nodal GTV (GTVn) (regional lymphatic metastasis) radiotherapy dose 60Gy, the esophageal gross tumor volume (GTVt) radiotherapy dose 50Gy, if the gastroscope pathology is completely relieved, otherwise it is 60Gy. All patients registered before radiotherapy. The patient received concurrent therapy with tirelizumab (200mg every time, 3-week cycle), until the disease progresses or clinical benefits are lost (the longest time is 12 months). The primary endpoint was the esophageal gross tumor pathological complete remission rate (pCR). Results: Between 01 August 2021 and 31 December 2022, 31 patients were enrolled, and 27 completed radiotherapy and at least two times of tirelizumab treatment. Data cutoff date was 31 January 2023, median follow-up time among survivors after radiotherapy was 9 months (range 4-20). The esophageal gross tumor pCR rate was 66.7% (95% CI, 14.3%-52.3%) and treatment-related adverse events (TRAEs) of low severity (grade 1-2, 48.1%; grade 3, 7.4%; grade 4-5, no). No treatment-related mortality occurred. Two (7.4%) patients had tumor recurrence and two (7.4%) patients died (Infection and heart disease). The 1-year PFS rate, median PFS and median OS had not been reached yet. For locally advanced unresectable ESCC that can't receive CCRT, the combination of tirelizumab and radiotherapy shows promising efficacy and acceptable toxicity, providing a feasible and effective choice. The research of long-term survival analysis is under way. Conclusions: Concurrent radiotherapy with tirelizumab shows promising efficacy and controllable safety for patients with locally advanced ESCC who are unable or unwilling to undergo CCRT, and warrants further evaluation in larger studies. Clinical trial information: ChiCTR2100053182 .
Neoadjuvant tislelizumab plus chemotherapy for resectable locally advanced esophageal squamous cell carcinoma (ESCC): Interim analysis of a phase 2 study.
Authors: Zhuo Na , Qiu Wei , He Jia , Li Li , Wang Qiang , Yu Shuangni , Liu Wei , Zhao Lin , Bai Chunmei 
Published: June 2023

e16087 Background: Esophageal cancer (EC), as the sixth most frequently diagnosed cancer and the fourth leading cause of cancer death, poses a major health threat in China. Neoadjuvant treatment is recommended for resectable diseases with high recurrent risks; however, benefits with platinum-doublet chemotherapy are modest. Although the addition of tislelizumab, a anti-PD-1 antibody to chemotherapy has shown survival benefit in unresectable or metastatic EC, data are lacking to support such combination as a neoadjuvant modality. Here, we report the interim analysis of efficacy and safety of a prospective, phase 2 clinical trial evaluating tislelizumab plus chemotherapy as neoadjuvant treatment for locally advanced ESCC. Methods: Adults with clinical stage II-IVA (T3-T4 and/or node positive), potentially resectable ESCC, ECOG PS 0-1, and no known PD-1 expression were enrolled to receive tislelizumab (200mg) plus chemotherapy (docetaxel 75mg/m2 plus cisplatin 75mg/m2 or carboplatin AUC = 5 if CCr < 60ml/min) every 3 weeks for 4 cycles. Adjuvant tislelizumab up to 9 months were optional according to patients’ will. The primary endpoint was pathological complete response (pCR). Secondary endpoints include R0 resection, disease free survival (DFS), adverse events (AE), and biomarkers for predicting efficacy. Results: Between November 11, 2020 and Feburary 10, 2023, 28 patients with clinical stage III (n = 13) or IVA (n = 15) diseases were enrolled. 27 completed neoadjuvant treatment and 5 withdrew early because of disease progression (n = 2), serious AEs (n = 2) and bronchoesophageal fistula (n = 1). 21 patients underwent McKeown MIE and 20 (95.2%) acheived R0 resection. One patient was awaiting surgery. pCR (ypT0N0) was achieved in 33.3% (7/21) patients. According to the CAP tumor regression grading system, 3 (14.3%) cases were categorized as grade 1, 7(33.3%) were categorized as grade 2 and 4 (19%) were categorized as grade 3 in primary tumor. Most treatment related AEs (TRAEs) during neoadjuvant setting were mainly of grade 1 or 2. Grade 3 or 4 TRAEs occurred in 37.0% patients (10/27) and 14.8% (4/27) was considered immune-related. Surgical complications of any grade occurred in 4 patients (19.0%), 3 of which were grade 3. No grade 5 events were noted. 14 (66.7%) patients were able to continue adjuvant tislelizumab after surgery. Conclusions: Neoadjuvant tislelizumab plus chemotherapy has achieved encouraging pCR rate and tolerable safety activity in this study. Clinical trial information: ChiCTR2100043772 .
Comparison of efficacy and safety of neoadjuvant regimens for resectable esophageal squamous cell carcinoma: A meta-analysis.
Authors: Wang Ting , Cai Liyu , Guo Zefeng , You Peimeng , Liu Shengbo , Qiu Hongrui , Li Hao , Wu Shaowei , Zhou HaiYu 
Published: June 2023

e16098 Background: Recent studies have demonstrated that preoperative neoadjuvant therapy in esophageal carcinoma can bring extra survival benefits compared to surgical resection alone or postoperative adjuvant therapy. There is still a lack of high-level evidence from large randomized controlled clinical trials to define the interval between neoadjuvant therapy and surgery, radiotherapy dose and target area plans after neoadjuvant treatment, therefore we adopted a meta-analysis to compare the efficacy and safety of different neoadjuvant treatment options in esophageal squamous cell carcinoma (ESCC) in these clinical studies. Methods: Articles were retrieved from PubMed, Cochrane, Embase, Web of Science databases and abstracts of ASCO and ESMO meetings in 2021-2022 by the terms esophageal cancer, neoadjuvant therapy, Inclusion criteria: a: Patients with excisable stage esophageal cancer. Histopathological confirmed squamous carcinoma of the esophagus; b: At least one reported primary outcome as follows: pathological complete response (pCR) rate; major pathological response (MPR) rate. Statistical analysis was performed on Stata 16.0 and R 4.0 with a significance level of 0.05. Results: A total of 39 clinical studies with a total of 2,434 patients, mostly male, were included, with a predominance of phase 2 trials. 16 neoadjuvant chemotherapy combined with immunotherapy (nICT), 2 neoadjuvant immunotherapy alone, 5 neoadjuvant chemoradiotherapy combined with immunotherapy (nICRT), 15 neoadjuvant chemoradiotherapy (nCRT), 1 neoadjuvant chemotherapy, 32 single-arm studies, and 7 randomized controlled trials. The overall neoadjuvant therapy pCR rate was 36% (95% CI: 32%-40%) and the overall MPR rate was 55% (95% CI: 47%-63%). The nICT pathological complete response rate was 31% (95% CI: 26%-36%), nCRT pathological complete response rate was 38% (95% CI: 32%-44%) and nICRT complete pathological response rate was 49% (95% CI: 39% -59%). Complete pathological response rates were 36% (95% CI: 31%-41%) for neoadjuvant immunotherapy (with immunotherapy) and 33% (95% CI: 13%-54%) for neoadjuvant immunotherapy alone. 26 studies had a mean R0 resection rate of 93%, with the majority of patients achieving R0 resection. Conclusions: From this Meta-analysis it can be concluded that nICRT has the best complete pathological response rate of all neoadjuvant treatments and nCRT has a better complete pathological reponse rate than nICT, but most of them are not phase 3 clinical trials, therefore more studies are needed to further clarify the benefit of neoadjuvant radiotherapy combined with immunotherapy in esophageal squamous cell carcinoma.
The impact of anti-EGFR therapy when added to first-line standard platinum-gemcitabine chemotherapy in advanced biliary tract cancers: A meta-analysis of randomized studies.
Authors: Findakly Dawood , Haddad Philip A. 
Published: June 2023

e16109 Background: Biliary tract cancers (BTCs) represent the second-most common primary liver cancers. They are a heterogeneous group of tumors that include Intrahepatic cholangiocarcinoma, extrahepatic cholangiocarcinoma, gallbladder adenocarcinoma, and ampullary carcinoma. BTCs are usually diagnosed in an advanced stage and carry a poor prognosis. A better understanding of cancer biology has led to advances in targeted treatments in other cancers but remains an unmet need in BTCs. We conducted this meta-analysis to evaluate the efficacy of anti-EGFR therapy when added to the standard platinum-gemcitabine chemotherapy as first-line in patients with advanced BTCs. Methods: A review of the medical literature was conducted using online databases. Inclusion criteria consisted of English language, diagnosis of biliary tract tumors, randomized studies of first-line platinum-gemcitabine with and without anti-EGFR therapies, and studies that reported overall (OS) and progression free survival (PFS). A meta-analysis using the fixed effects and random effects models was conducted. Results: Four randomized studies with a total of 569 patients were included. Three studies were randomized phase 2 and one was randomized phase 3. Three studies used oxaliplatin and one used cisplatin in addition to gemcitabine as the standard combination. Panitumumab was used in two studies while cetuximab and erlotinib were used in one study each. The addition of anti-EGFR agent to first-line platinum-gemcitabine in advanced BTC resulted in a superior OS (HR = 0.72, 95%CI 0.61-0.85) and PFS (HR = 0.76, 95%CI 0.63-0.92). When the analysis was restricted to anti-EGFR monoclonal antibodies, their PFS benefit persisted (HR = 0.72, 95%CI 0.55-0.95), but their OS benefit failed to reach statistical significance (HR = 0.83, 95%CI 0.65-1.07). Conclusions: This is the first meta-analysis to show the addition of anti-EGFR agents to the standard first-line platinum-gemcitabine chemotherapy improves OS and PFS in advanced BTC.
PVR expression in tumor microenvironment of advanced hepatocellular carcinoma.
Authors: Lu Li-Chun , Lee Yi-Hsuan , Shao Yu Yun , Liu Tsung-hao , Cheng Ann-Lii , Hsu Chih-Hung 
Published: June 2023

e16113 Abstract Background: PVR (CD155)/TIGIT signaling has been investigated as a new immune checkpoint target in many cancers, including hepatocellular carcinoma (HCC). However, the expression and clinical significance of PVR, the ligand of TIGIT, have not been explored in the tumor microenvironment (TME) of advanced HCC. Methods: Patients with HCC who had adequate tumor tissues obtained at advanced stage were enrolled in the study. The membranous staining of PVR of tumor tissues, detected by immunohistochemistry (IHC), was semiquantitatively scored as IHC 0, 1, 2, or 3 if < 1%, ≥1% but < 5%, ≥5% but < 10%, or ≥10% of tumor cells (TCs) and tumor-infiltrating immune cells (ICs) were PVR positive. The correlation of PVR expressions and other clinic-pathologic factors was analyzed. Results: Sixty-seven patients were included in the study. Among them, 57 (85.1%) were male, 32 (47.8%) were aged over 60 years, 48 (71.6%) were HBV-reactive, and 23 (34.3%) had been treated with sorafenib before obtaining tumor tissues. Thirteen (19.4%) and 18 (26.9%) tumor samples showed positive PVR expressions in TCs and ICs, respectively (TCs, IHC 1/2/3: 3/3/7; ICs, IHC 1/2/3: 7/3/8). The expressions of PVR in TCs or ICs were not associated with sex, age, HBV/HCV infection, previous sorafenib treatment, or overall survival of the patients. Notably, in both TCs and ICs, the intensities of PVR expression were inversely correlated with PD-L1 expression for patients with at least IHC ≥1 in either PVR or PD-L1 (TCs, n = 26, r = -0.6966, p < 0.0001; ICs, n = 46, r = -0.4548, p = 0.0015). Conclusions: PVR expression can be identified in both TCs and ICs of TME of advanced HCC. The expressions of PVR and PD-L1 were inversely correlated. These findings may provide clinical implications for development of combination immunotherapy in advanced HCC. (This work is supported by grants from the Ministry of Science and Technology, Taiwan, MOST 110-2314-B-002-204-MY3). [Table: see text]
Efficacy of low dose sorafenib and capecitabine in the management of hepatocellular cancer.
Authors: Mateen Abdul , Abdullah Famya , Akhtar Muhammad Saeed , Quraishi Arif Moin , Sattar Amir , Hashmi Quratul Ain , Sanwal Isharat Shehrood , Jamil Faryal , Safdar Rida , Adil Allah Rakha 
Published: June 2023

e16117 Background: Hepatocellular cancer (HCC) is one of the commonest cancers in Pakistan due to endemic hepatitis B and C diseases. Its incidence is continuously rising due to lack of public awareness and lack of routine screening of the affected population. Most of the patients present in advanced stage of the disease excluding option for curative surgical options. These patients are mostly not fit enough to tolerate systemic therapies in full doses. So, we have to adapt ourselves to lower dosage so that it can be tolerated without many untoward side effects. Methods: This study was aimed to assess the efficacy of low dose sorafenib (400 mg daily in two divided doses) and capecitabine (1000 mg daily in two divided doses) in advanced hepatocellular carcinoma. Patients were prescribed this treatment for six months and then response was assessed using computed tomography or ultrasound and alpha fetoprotein (AFP) levels. Progression-free survival (PFS) and overall survival (OS) were also assessed. Results: Total of one-hundred fifty-five patients were enrolled. One hundred thirteen patients completed the treatment for six months and were evaluated for response. A total of 28 (25%) of patients progressed during treatment and were shifted to other treatment options. Nine patients (8%) had complete response, thirty-four (30%) had partial response, forty-two (37%) had stable disease and twenty-eight (25%) had progressive disease. Seventy-four patients (65%) showed significant reduction in AFP levels. A total of 85/113 (75%) patients were available for assessment of PFS and OS. Two-year PFS and OS were 32% and 43% respectively. Mean and median PFS (year) were 1.82 ±0.19 (95% confidence interval 1.48 to 2.17) and 1.27±0.16 (95% confidence interval 0.94 to 1.57) respectively. Mean and median OS (year) were 2.73 ±0.24 (95% confidence interval 2.39 to 3.16) and 2.27±0.13 (confidence interval 2.02 to 2.54) respectively. Twenty-six patients had one or more episode of grade 2 diarrhea, eleven patients developed encephalopathy, thirteen patients developed hand foot syndrome and nineteen patients showed grade 2 thrombocytopenia. Conclusions: Low dose sorafenib and capecitabine is effective in the treatment of advanced HCC with excellent tolerability and minimal toxicity.
Anti–PD-1 combination regimen as first-line therapy in advanced biliary tract cancer and biomarker exploration: A retrospective study.
Authors: Guo Jingyi , Zhou Qun , Zhou Mingzhen , Dai Hengheng , Li Lin , Liu Baorui , Shen Jie 
Published: June 2023

e16130 Background: Combination strategy of immune checkpoint inhibitors has potential to replace chemotherapy as a new first-line therapy for advanced biliary tract cancer (BTC). The aims of this study were to assess the efficacy of anti-PD-1 combination therapy in the first-line treatment of advanced BTC and to find reliable biomarkers associated with overall survival (OS). Methods: Clinical data from patients with advanced BTC who received chemotherapy or anti-PD-1 combination therapy as first-line were collected. The primary outcome of this study was OS. Blood test results were collected from patients who received anti-PD-1 in the week prior to treatment to calculate inflammation scores and analyze their relationship with OS. A total of eight scores were selected for analysis, including platelet-to-lymphocyte ratio (PLR), neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-C-reactive protein (CRP) ratio (LCR), lymphocyte-to-monocyte ratio (LMR), CRP to-albumin ratio (CAR), systemic immune-inflammation index (SII), prognostic nutritional index (PNI), and pan-immune-inflammation value (PIV). Moreover, archival tissues were collected for genetic testing and immunohistochemical staining to analyze genetic changes and the infiltration of immune cells in tumor tissues in relation to survival. Results: From January, 2018, to July, 2022, 64 patients were recruited: 11 were in the chemotherapy group, 21 were in the anti-PD-1 plus chemotherapy group, 21 were in the anti-PD-1 plus targeted therapy group and 11 were in the triple group (anti-PD-1 plus chemotherapy and targeted therapy). The median overall survival (mOS) was 7.9 months, 11.3 months, 12.8 months and 28.7 months, respectively. Compared to first-line chemotherapy, mOS was significantly prolonged in the triple group ( p= 0.031). The results of inflammation scores showed that patients with high LCR (≥0.4), high LMR (≥2.5), low CAR ( < 0.18), high PNI (≥44.3) or low PIV ( < 480.9) had significantly prolonged mOS compared to those with different scores ( p< 0.05). Genetic testing results suggested that patients with poor survival all had TP53 mutations and had higher levels of KRAS and ERBB2 mutations. Immunohistochemical results showed that a low FOXP3/CD8 ratio (≤0.27) was associated with prolonged OS ( p= 0.029). With CD4-low, CD8-high, CD56-positive, CD163-high, FOXP3-high and MPO-high in TME as one factor, we calculated immunoscore according to the number of factors. The high immunoscore group ( > 2) showed significantly superior OS ( p= 0.003). Conclusions: First-line anti-PD-1 antibody combination therapy was superior to chemotherapy, and triple therapy significantly improved survival. Peripheral blood immune-inflammation score, FOXP3/CD8 ratio and immunoscore have potential as biomarkers for predicting the efficacy of first-line anti-PD-1 antibody therapy in advanced BTC.
Donafenib combined with anti-PD-1 antibodies plus transarterial therapy for initially unresectable hepatocellular carcinoma.
Authors: Wen Yaohong , Fu Shunjun , He Guolin , Cai Lei , Liu Yahong , Li Xinmin , Xu Yuyan , Wang Chunming , Zhong Kaihang , Zhang Cheng , Xie Qingyu , Pan Mingxin 
Published: June 2023

e16135 Background: Given its clear efficacy and high safety demonstrated in the phase 3 ZGDH3 study, donafenib has been recommended by the Chinese guidelines for the first-line treatment of unresectable hepatocellular carcinoma (uHCC). Recently, combination therapies have shown favorable results. However, triple therapy with donafenib, anti-PD-1 antibodies, and transarterial therapy has not yet been investigated. Thus, we aimed to investigate the efficacy and safety of triple therapy with donafenib, anti-PD-1 antibodies, and transarterial therapy in patients with uHCC. Methods: A single-center, retrospective study was performed based on the medical records of consecutive patients diagnosed with HCC who were not suitable for curative surgery or local ablation at Zhujiang Hospital of Southern Medical University from June 2021 to October 2022. Patients with ≥18 years, Child-Pugh score ≤7, ECOG PS ≤1, no prior systemic therapy, having at least one measurable lesion (per mRECIST) were enrolled. Patients were treated with donafenib 200 mg orally twice daily, anti-PD-1 antibodies intravenously every three weeks, and transarterial therapy until disease progression or unacceptable toxicity. Endpoints include objective response rate (ORR, the proportion of patients with partial or complete response according to mRECIST and RECIST v1.1), surgical conversion rate (the proportion of patients who successfully underwent resection), progression-free survival (PFS), overall survival (OS), disease control rate (DCR), and safety. Results: A total of 27 patients were enrolled (median age 52 years [range, 29–74], 81% males, 85% with HBV infection, 41% with cirrhosis, 48% with AFP level ≥400 ng/mL, and 67% in BCLC C). All patients received donafenib and anti-PD-1 antibodies with hepatic arterial infusion chemotherapy (HAIC, n = 10), transarterial chemoembolization (TACE, n = 8), or both (n = 9). By the cutoff date of January 6, 2023, the median follow-up duration was 6.8 months (95% confidence interval [CI], 5.9–7.7), and 17 (63.0%) patients were still undergoing treatment. The ORR and DCR were 59.3% and 92.6% by mRECIST, and 18.5% and 88.9% by RECIST v1.1, respectively. The surgical conversion rate was 22.2%, and the median surgical conversion time was 3.4 months (range, 2.2–4.6). The median PFS was 8.3 months (95% CI, 6.8–9.8), and median OS was not reached. The 6-month PFS rate and 12-month OS rate were 74.7% and 72.9%, respectively. Grade 3 treatment-related adverse events (TRAEs) were observed in 5 patients (18.5%), the most common of which was increased total bilirubin (11.1%). No grade 4/5 TRAEs occurred. Conclusions: Donafenib combined with anti-PD-1 antibodies plus transarterial therapy shows promising efficacy and manageable toxicity in patients with initially uHCC. Clinical trial information: NCT05638438 .