bluuebunny/crossref_metadata_2025_split huggingface dataset:
The role of PRRX1 in esophageal cancer.
Authors: Guo Jinbao 
Published: June 2022

e16046 Background: Recently, paired related homeobox 1 (PRRX1) was identified as a new EMT inducer that induces EMT in solid tumor. Interestingly, the functions of PRRX1 are significantly different, high expression of PRRX1 predicts less metastasis of breast cancer and a better prognosis. However, we observed the opposite relationship in gastric cancer, which was also reported in colorectal cancer and pancreatic cancer. While the function of PRRX1 in oesophageal cancer and whether PRRX1 induces EMT in oesophageal cancer metastasis have not been determined. Methods: One hundred primary oesophageal cancer tissue specimens were collected, immunohistochemical staining was performed to detect the expression of PRRX1. Cell proliferation, the migration and invasion were detected with different PRRX1 expression in oesophageal cancer cells. And the relationship between PRRX1 and Wnt/β-catenin pathway was also explained. Results: Regulation of PRRX1 expression might exert obvious effects on cell proliferation, especially the migration and invasion of oesophageal cancer cells. Moreover, silencing PRRX1 expression using a short hairpin RNA (shRNA) produced the opposite effects. In addition, when PRRX1 was overexpressed, inhibition of the Wnt/β-catenin pathway with XAV939 negated the effect of PRRX1 on EMT, whereas when PRRX1 was downregulated, activation of the Wnt/β-catenin pathway with LiCl impaired the effect on EMT. Conclusions: PRRX1 is expressed at high levels in oesophageal cancer specimens and is closely related to tumour metastasis in patients with oesophageal cancer. Additionally, PRRX1 induces EMT in oesophageal cancer metastasis through activation of Wnt/β-catenin signalling.
Adjuvant immunotherapy in patients with resected esophageal and gastroesophageal junction cancer: Real-world evidence from Nova Scotia.
Authors: Sheridan Margaret , Snow Stephanie Leann 
Published: June 2022

e16047 Background: Post-operative immunotherapy (POI) with nivolumab has become the standard of care for eligible patients with esophageal and gastroesophageal junction cancers (EGEJC) who had pre-operative chemoradiation (POCRT) and definitive surgery. However, not all patients who receive POCRT are eligible for POI. Objective: The primary objective was to determine the proportion of patients who receive POCRT that are eligible for POI in a real-world population. Further, we aimed to identify the specific barriers to POI to determine factors which could be strategically addressed to maximize access to curative intent treatment. Methods: All patients residing in mainland Nova Scotia who received POCRT between July 2016 and April 2019 were analyzed. Disease, patient, and treatment characteristics were collected via chart review. The relative proportion of patients who (1) had definitive surgery, (2) were eligible to receive POI and (3) would have accepted POI were collected. The specific reasons for non-eligibility or refusal of POI were captured. Results: A total of 65 patients received POCRT during the study period. 44 of those went on to have definitive surgery. All 44 of these patients were then screened for eligibility to be enrolled in a trial of POI. 23 were eligible, but 12 declined trial enrolment. 21 were ineligible, with the most common reason being a pathological complete response (n=11). Of the 21 patients who did not undergo surgery, 12 were found to have new metastatic disease on pre-operative restaging and 9 were felt to be too frail. Conclusions: Only 35% of patient receiving POCRT were eligible for POI. This is important real-world data when planning allocation of resources and adapting health care budgets for novel treatments and indications.
Real-world effectiveness of anlotinib plus PD-1 inhibitors as chemo-free therapy in advanced or metastatic esophageal cancer.
Authors: Wang Junsheng , Hong Yonggui , Wu Tao , Lu Ping , Chang Zhiwei , Liang Wei , Zhang Guifang 
Published: June 2022

e16052 Background: Immunotherapy, particularly with anti-PD-1/PD-L1 antibodies, has shown therapeutic efficacy in various malignancies. Compared with chemotherapy, anti-PD-1 antibody monotherapy improved the median overall survival in advanced or metastatic esophageal cancer. The combination of an anti-PD-1/PD-L1 antibody with an angiogenesis inhibitor has shown efficacy in many cancers which including esophageal cancer. The purpose of this study is to investigate the efficacy and safety of anlotinib plus PD-1 inhibitors as chemo-free therapy during the treatment of esophageal cancer in the real world setting. Methods: This prospective, multicenter real-world study (NCT04966611) evaluated the efficacy and safety of anlotinib plus PD-1 inhibitors in the chemo-free therapy setting for advanced or metastatic esophageal cancer patients (pts). Primary endpoint was evaluation of PFS (progression-free survival), and secondary endpoints included ORR (objective response rate), DCR (disease control rate) and OS (overall survival). The response to treatment was evaluated according to RECIST version 1.1. In addition, adverse events were evaluated by CTCAE v5.0. Results: Between May 2020 and Dec 2021, 50 pts were enrolled. 45 comprised the evaluable population. In the full analysis set, 44 had squamous cell and 1 patient had adenocarcinoma histology. 29 (64.4%) of 45 pts were male. 10 (22.2%) had an ECOG performance status of 0, 32 (71.1%) status of 1 and 3 (6.7%) status of 2. Twenty (44.4%) pts had distant metastases and 29(64.4%) pts had comorbidities. 15 pts had previously used anti-PD-1/PD-L1 antibody or vascular targeting drugs, of which 5 cases had combined the two drugs. Among all evaluable pts, 5(11.1%) pts received first-line, 27(60.0%) second-line and 13(28.9%) third & above line therapy. Among all pts, 1 patient achieved complete response (CR), 16 pts partial response (PR), 25 pts stable disease (SD), illustrating an ORR of 37.8% and a DCR of 93.3%. In the first line therapy, ORR was 60.0%, DCR was 100%.In the second line therapy, ORR was 37.0%, DCR was 96.3%. In the third & above line, ORR with 30.8%, DCR with 84.6% was observed. Median PFS was not reached. Treatment related adverse events (trAEs) were reported in 24 pts(53.3%). No patient had grade 3 or more trAEs. Conclusions: Anlotinib plus PD-1 inhibitors in chemo-free therapy for advanced or metastatic esophageal cancer was active and showed excellent tumor response and was generally well tolerated. Further investigation is required in a larger real-world cohort to validate the benefit of anlotinib plus PD-1 inhibitor in esophageal cancer. Clinical trial information: NCT04966611.
Detection of targetable fusion alterations in gastric cancer in the Chinese population.
Authors: Liu Zhenhua , Zhu Bowen 
Published: June 2022

e16061 Background: Despite a decreasing incidence and mortality globally, gastric cancer (GC) remains a main threat to public health, especially in China. Consistently, drug therapy is a big challenge for gastric cancer. Although HER2-directed therapy and immune checkpoint inhibitors have achieved great success, other valid targeted drugs are required to develop. Targeted drugs of NTRK gene fusion have been approved in solid tumors including GC by FDA. Moreover, FDA has granted Zenocutuzumab fast-track approval for patients with NRG1 gene fusion in solid tumors. However, in China, gene fusion and functional characterization have not been reported to date in detail. Methods: In order to estimate the fraction of patients who may benefit from targeted drugs, we retrospectively analyzed the fusion alterations in gastric cancer tissue samples from 955 Chinese patients. Remarkably, as fusion partners, all genes included fusion analysis possess experimental or approved drugs. The clinicopathological characteristics were retrieved from the medical records in hospital. Chi-square analysis was used to investigate the relationship of gene fusions with drivers mutations, MSI, TMB and MMR. Results: We found 2.82% (27/955) of patients harboring fusion genes, including MET, ROS1, ALK, FGFR1/2, NTRK, BRAF, EGFR and so on. Among them, EML4-ALK, EWSR1-FLI1 and EGFR-SEPTIN14 have been described in other studies, but 88.9% (24/27) fusion genes are previously unreported. Sequencing results indicate that fusion genes are significantly enriched in patients with ERBB2 gene amplification. In addition, there is no obvious correlation between the positive rate of gene fusion and clinical features including age and gender. Similarly, MSI status, TMB and MMR are included for correlation analysis with gene fusion. Unfortunately, the results are not statistically significant. Conclusions: Our work characterizes the landscape of targetable fusion alterations in gastric cancer in the Chinese population and investigates that targetable fusion testing should be advised to patients with disease progression after receiving standard therapy.
Camrelizumab combined with SOX in the first-line treatment of unresectable advanced or metastatic gastric/gastroesophageal junction (G/GEJ) adenocarcinoma: A single-arm, prospective, and open-label clinical study.
Authors: Liu Wenlou , Qin Xiaobing , Zhao Yang , Ge Yan , Tang Juanjuan , Wang Hongmei , Han Zhengxiang 
Published: June 2022

e16090 Background: First-line chemotherapy for advanced human epidermal growth factor receptor 2 (HER2)-negative gastric/gastroesophageal junction (G/GEJ) adenocarcinoma results in median overall survival (mOS) < 1 year. The programmed death (PD)-1 inhibitor provided superior OS in advanced G/GEJ adenocarcinoma combind with chemotherapy. However, the continuous explore about PD-1 inhibitors of first-line treatment with G/GEJ adenocarcinoma patients is promising. Camrelizumab, an anti-PD-1 monoclonal antibody, has been shown to have synergistic antitumor effects in the treatment of G/GEJ adenocarcinoma patients. We aimed to evaluate the safety and efficacy of camrelizumab combined with SOX in the first-line treatment of advanced G/GEJ adenocarcinoma. Methods: In this study (ChiCTR2000029691), eligible patients were diagnosed as unresectable advanced, postoperative recurrent ormetastatic, HER2-negative G/GEJ adenocarcinoma, and treatment-naive with chemotherapy, VEGFR2 inhibitors or PD-1/PD-L1 inhibitors. Patients received camrelizumab (200 mg, I.V., d1) and SOX regimen (oxaliplatin, 130 mg/m2, d1; S-1, 20mg/m2, bid, d1-14) every 3 weeks, until disease progression, intolerable toxicities, or physician/patient withdrawal. The safety and efficacy were assessed by investigators per CTCAE v5.0 and RECIST v1.1, respectively. The primary endpoint was progress free survival (PFS), and the secondary endpoints were overall survival (OS), objective response rate (ORR), and disease control rate (DCR). Results: From March 30, 2020 to March 18, 2021, 27 patients had been enrolled to receive therpy with camrelizumab and SOX regimen. The patients were characterized with a median age of 60 years (range 26-79), 88.9% males and 11.1% females, 40.7% GEJ adenocarcinoma, 88.9% lymph node metastasis, 25.9% liver metastases, and 18.5% of patients had a history of tumor-related surgery. As of Nov 2, 2021, with a median follow-up of 8.8 months (range, 0.9-16.8), safety and efficacy were assessed in 20 evaluable patients, with overall response of 8 partial response (PR) and 9 stable disease (SD). Confirmed ORR and DCR were 40.0% (95% CI, 20.0%-63.6%) and 85.0% (95% CI, 61.1%-96.0%), respectively. The median PFS and OS were 12.7 months (95% CI, 4.9-20.5) and 16.8 months (95% CI, 3.5-30.0), respectively. Grade 3-4 treatment-related adverse events occurred in 18.5% of patients, with anemia and neutropenia ranking the most frequent. No new safety signals was identified. Conclusions: Camrelizumab combined with SOX was well tolerated and demonstrated encouraging efficacy for previously untreated with chemotherapy, VEGFR2 inhibitors or PD-1/PD-L1 inhibitors, unresectable advanced or metastatic, HER2-negative G/GEJ adenocarcinoma. Clinical trial information: ChiCTR2000029691.
Clinical and molecular characteristics of advanced esophageal/GEJ cancer with brain metastasis.
Authors: Liang Kai-li , Feliciano Josephine Louella , Marrone Kristen , Murray Joseph Christopher , Tackett Sean , Hales Russell K. , Voong K. Ranh , Battafarano Richard James , Yang Stephen , Broderick Stephen , Ha Jinny Suk , Forde Patrick M. , Brahmer Julie R. , Lam Vincent K. 
Published: June 2022

e16092 Background: Brain metastasis (BRM) in gastroesophageal (GE) cancer is uncommon, but contributes to poor prognosis and significant symptom burden. While HER2 overexpression has been suggested as a potential driver of BRM, clinicopathologic and molecular determinants of BRM in GE cancer and their impact on clinical outcome remain incompletely understood. Methods: We retrospectively analyzed clinicopathologic data from 323 advanced esophageal/GEJ patients (pts) at Johns Hopkins from 2003 to 2021. Univariate and multivariate logistic regression were performed to investigate the association between several clinical and molecular features and the occurrence of BRM, with particular focus on HER2 overexpression (by IHC and FISH) and PD-L1 expression (by IHC) as measured by the combined positive score (CPS). Overall survival was estimated using the Kaplan-Meier method. Results: Median age was 64 and most pts were white (90.4%). Tumors were 73.7% esophageal primary, 82.7% adenocarcinoma, 43.8% HER2+, and 11.1% CPS ≥ 1. Cumulative incidence of BRM in overall cohort and within HER2+ subgroup was 14.6% (47 pts) and 25.4% (16 pts), respectively. Pts with BRM (not already present at time of stage IV diagnosis) had median onset of 10.8 months. Seventeen (36.2%) pts had a solitary brain lesion and 10 (21.7%) were asymptomatic. On univariate analysis, adenocarcinoma and HER2 overexpression were associated with increased risk of BRM (OR 3.45; 95% CI 0.09-0.96; p = 0.043 and OR 2.72; 95% CI 1.11-6.67; p = 0.028, respectively). Notably, the HER2 association was strengthened when HER2 equivocal tumors were re-classified as positive in an exploratory analysis (OR 3.55; 95% CI 1.38-9.14; p = 0.009). Adenocarcinoma and HER2 overexpression were collinear in the multivariate model. In pts with BRM, OS was improved in HER2+ pts (16.72 months; 95% CI 12.3-21.1 months; log-rank p = 0.039 and OR 0.33; 95% CI 0.11-0.99; Cox regression p = 0.049). CPS and primary tumor location were not associated with increased BRM. Conclusions: HER2 overexpression identifies an esophageal/GEJ molecular subtype that is significantly associated with increased risk of BRM; though with improved OS (compared to non-HER2+ BRM) and later onset CNS progression, likely reflecting durable extra-CNS control on targeted systemic therapy and a potential HER2+ subgroup with relatively indolent biology. Prevalence of asymptomatic and solitary brain lesions supports increased brain surveillance for this population.
Comparative effectiveness of trimodal therapy versus definitive chemoradiation in older adults with locally advanced esophageal cancer.
Authors: Gaber Charles , Shaheen Nicholas J. , Edwards Jessie K. , Sandler Robert S , Nichols Hazel , Sanoff Hanna Kelly , Lund Jennifer Leigh 
Published: June 2022

e16093 Background: The comparative effectiveness of trimodal therapy versus definitive chemoradiation for older adults with locally advanced esophageal cancer is uncertain. Only two randomized trials have considered this comparison, and older adults and patients with adenocarcinomas were underrepresented. Older adults have greater frailty and may not benefit from adding surgery to chemoradiation. Methods: A cohort of adults 66-79 years of age diagnosed with incident locally advanced esophageal cancer between 2004 and 2017 was identified using the Surveillance Epidemiology and End Results-Medicare database. We used observational data to emulate a hypothetical trial comparing trimodal therapy and definitive chemoradiation. Outcomes included overall mortality, esophageal cancer-specific mortality, functional adverse events, and healthy days at home. Results: The study population included 1,240 individuals with adenocarcinomas and 661 with squamous cell carcinomas. Amongst older adults diagnosed with adenocarcinomas, the five-year risk of mortality was 73.4% (95% CI: 69.1–77.4) in the trimodal therapy group and 83.8% (95% CI: 78.6–87.2) in the definitive chemoradiation group (RR= 0.88, 95% CI: 0.82–0.95). Amongst older adults diagnosed with squamous cell carcinomas, the five-year risk of mortality was 62.6% (95% CI: 50.9–73.5) in the trimodal therapy group and 72.3% (95% CI: 67.6–76.3) in the definitive chemoradiation group (RR= 0.87, 95% CI: 0.70–1.01). Results for all outcomes are presented in the Table. Conclusions: Trimodal therapy was associated with lower mortality than definitive chemoradiation. The benefits were smaller than suggested by prior observational studies. These findings can be used with clinical expertise and patient preferences to enhance shared decision-making. [Table: see text]
Clinical performance of a liquid biopsy test based on the detection of multiple DNA methylation biomarkers for early detection of gastrointestinal cancers.
Authors: Ma Yong , Zhao Guodong , Wang Kai , Song Lishuang , Xiong Shangmin , Li Hui , Chen Guangxia , Pei Bing , Shen Xizhong , Fei Sujuan , Zheng Minxue 
Published: June 2022

e16096 Background: Gastrointestinal cancers (colorectal cancer, gastric cancer and esophageal cancer) are the most prevalent malignant tumors in China, resulting in 975,537 new cases and 958,675 deaths in 2020. Currently, the gold standard for the early detection of these cancers remains to be gastrointestinal endoscopy. However, the invasiveness, low throughput and high cost of these procedures have prevented its wide acceptance by Chinese population. The objective of this study was to develop a liquid biopsy test based on the detection of multiple DNA methylation biomarkers (SpecGastro test) and evaluate its clinical performance for early detection of gastrointestinal cancers. Methods: Two hundred and eighty-two gastrointestinal cancer patients (98 colorectal cancers, 136 gastric cancers and 48 esophageal cancers) and 195 control subjects were included. Ten milliliters of peripheral blood was drawn and 3.5 mL plasma was separated for cell-free DNA extraction and bisulfite conversion. The converted DNA was subsequently examined by SpecGastro test, a multiplex qPCR assay that detected six methylation biomarkers and one internal control. Results: Overall sensitivity for SpecGastro test was 76.6% (95% CI: 71.1-81.3%) with a specificity of 89.2% (95% CI: 83.8-93.1%). Sensitivities for colorectal cancer, gastric cancer and esophageal cancer were 87.8% (95% CI: 79.2-93.2%), 69.9% (95% CI: 61.3-77.3%) and 72.9% (95% CI: 57.9-84.3%), respectively. A high AUC of 0.903 (95% CI: 0.873-0.928) indicated that SpecGastro test distinguished gastrointestinal cancer patients from control subjects with high accuracy. Conclusions: Our analysis demonstrated the utility of SpecGastro test to detect three types of gastrointestinal cancers with high sensitivity and specificity. These results supported the feasibility of this blood-based SpecGastro test as a complementary tool to the existing single-cancer early detection tests.
PRO-based symptom management versus usual care for patients with gastric and esophageal cancer who undergone previous surgery: A randomized controlled trial.
Authors: He Yifu , Wu Shusheng , Ding Conglan , Fan Liyuan , Ke Lihong , Yan Ying , Li Mengge , Luo Huiqin , Hu Xiaoxiu , Niu Jiayu , Li Huimin , Xu Huijun , Chen Wenju , Cao Lulu 
Published: June 2022

e16104 Background: In China, the incidence of gastric cancer and esophageal cancer ranks second and third, respectively. These patients often suffer from malnutrition, anorexia and gastroesophageal reflux, which have a serious implication on their subsequent treatment. However, due to the specificity of the current medical situation in China and the heavy treatment workload of clinicians, there is no efficient and easy way to manage the symptoms of these patients. Methods: Subjects were randomized in a 1:1 ratio after enrollment into the Patient-Reported Outcome (PRO) -based symptom management group and the usual care group. The PRO group were assessed for anorexia, gastroesophageal reflux, nutritional status, BMI in the hospital before each cycle of chemotherapy via an electronic data platform. The doctors responded the assessment results and provided interventions, including advice for home care, drug prescription, and telephone follow-up, before patients are discharged from the hospital. Patients were assessed and managed every 3-4 weeks at the time of return for chemotherapy during 16 weeks. Patients in the usual care group underwent symptom assessment only the first and the 16th weeks, during which the surgeons only managed the symptoms with usual care modalities. The primary endpoint is number of symptoms at the 16th weeks and the secondary endpoint are the incidence of each symptom at the 16th weeks. Results: The interim results of the trial is reported. From Apr 2021 to Dec 2021, 55 pts completed the clinical observation, including 25 pts in the PRO group and 30 pts in the usual care group. The number of overall symptoms in the PRO group was significantly lower than in the usual care group (1 (0-1.5) vs 2 (1-3)). The incidence of nutrition risk (28.0% vs 56.7%), anorexia (24.0% vs 60.0%) and gastroesophageal reflux(8.0% vs 50.0%) in the PRO group was significantly lower than that in the usual care group, and there was no statistically significant difference about underweight (defined: BMI<18.5, 24.0% vs 36.7%) and depression (0.0% vs 6.7%). Conclusions: Compared to usual care, nutritional risk, anorexia, and GERD rates were effectively controlled in patients with previously surgically resected gastric and esophageal cancers through 16 weeks of patient-reported outcome based symptom management, with assessment scores confirming the same results, providing clinicians with an easy-to-operate and effective means of symptom management. Clinical trial information: ChiCTR2100041701. [Table: see text]