bluuebunny/crossref_metadata_2025_split huggingface dataset:
Unexpected gallbladder cancer as the source of some unknown primary cancers.
Authors: Zhang Xiaowei , Liu Xin , Luo Zhiguo , Hu Xichun , WANG Qifeng , Hu Silong , Zhou Liangping , Jiang Shiyu 
Published: June 2021

e16177 Background: CUP (Cancer of Unknown Primary) represents a frequent cancer type causing incomparable difficulties in pathological diagnosis as compared to other tumor types. To explore and analyze the causes of CUP (Cancer of Unkown Primary) patients with misdiagnosis in patients after laparoscopic cholecystectomy with cholecystitis or cholecystolithiasis. Methods: 13 patients with CUP (Cancer of Unkown Primary) were recruited in this research, who accepted the multidisciplinary discussion of the CMUP (Cancer of Multiple or Unknown Primary) multidisciplinary team. Our team analyzed the clinical data and pathological characteristics of these patients, and tried to find the common characteristics of the CUP patients whose primary site is the gallbladder that has been already removed. Results: 13 patients were received laparoscopic cholecystectomy because of previously considered cholecystitis or cholecystolithiasis. The gallbladder is considered as the primary organ supported by the pathological features of the metastatic sites. Importantly, all these patients have local abdominal wall and/or local perigallbladder lymph node metastases. Among them, 3 cases were diagnosed as gallbladder cancer, and 1 case was considered as high-grade intraepithelial neoplasia after pathological consultation, which were recognized as benign disease. Among the 13 cases, 9 cases showed local thickening of the gallbladder wall by preoperative CT or B-ultrasound. The median recurrence time was 16.4 months (9-48 months). Of the 13 patients, 5 received radical resection again, and received GP (gemcitabine plus platinum) chemotherapy after surgery. Of the 8 patients who were unable to undergo radical surgery, 5 received first-line GP based chemotherapy, 2 received first-line PD-1 immunotherapy combined with anti-vascular targeted drugs, and 1 received tegafur monotherapy due to poor physical condition. Till now, these patients are still under follow-up. Conclusions: Unexpected gallbladder cancer is the source of some unknown primary cancers. For these patients with cholecystitis or cholecystolithiasis, B-ultrasound examination should not be performed alone, and CT or MRI examination should be performed when necessary. We should pay high attention to the patients with cholecystitis or gallstone thickening of the gallbladder wall or other high-risk gallbladder cancer. Before surgery, clinical data should be analyzed comprehensively, and rapid frozen examination should be performed on patients suspected of having cancer. In order to avoid misdiagnosis, we should pay attention to the principle of none tumor and avoid the risk of incision implantation. If unexpected gallbladder cancer is found, radical operation should be performed as soon as possible.
Neoadjuvant radiotherapy to improve overall survival in resectable hepatocellular carcinoma.
Authors: Luo Zhiwen , Che Xu , Cai Jianqiang , Zhao Hong , Jin Jing , Tang Yuan , Chen Bo , Bi Xinyu 
Published: June 2021

e16178 Background: There is little evidence for the association between neoadjuvant radiotherapy (NRT) and improved overall survival (OS) in patients with resectable hepatocellular carcinomas (HCCs). This study aimed to determine whether NRT provides a survival benefit in these patients. Methods: We enrolled patients with resected HCC identified in the Surveillance, Epidemiology, and End Results database (2004–2015). Multiple imputation plus inverse probability of treatment weighting (IPTW) reduced selection bias. IPTW-adjusted Kaplan-Meier curves and IPTW-adjusted Cox proportional hazards models compared OS between different treatment groups. Sensitivity analyses tested the robustness of the estimates. Subgroup analysis identified the patients who could benefit most from NRT. Results: We enrolled a total of 11920 patients diagnosed between 2004 and 2015 in the study. Of these, 134 patients underwent NRT, the others underwent surgery alone (SA). The median OS in NRT was not approached, whereas in SA it was 52.0 (interquartile range, 34.25, 100.75) months. The 5-year IPTW-adjusted rates of OS in NRT versus SA were 65.3% and 46.6%, respectively. In IPTW-adjusted Cox proportional hazards regression analysis, NRT was associated with a significant OS benefit (hazard ratio [HR], 0.549; 95% confidence interval [CI], 0.327-0.921; p = 0.023). The results were robust in sensitivity analysis (E-value 2.39). Subgroup analysis demonstrated improved OS in the NRT cohort among younger patients (HR, 0.46; 95% CI, 0.26-0.83), N0 status (HR, 0.51; 95% CI, 0.28-0.94), and alpha-fetoprotein (AFP)-positive patients (HR, 0.28; 95% CI, 0.12-0.65). Conclusions: Patients with resectable HCCs may derive a survival benefit from NRT. Younger age ( < 65 years) with a positive AFP level at N0 status could be indicators for NRT. These findings enlighten current guidelines to consider NRT in patients with resectable HCCs. The present study establishes a reasonable basis for further prospective studies.
Anchored matching-adjusted indirect comparison (MAIC) of regorafenib (REG) versus cabozantinib (CAB) in advanced hepatocellular carcinoma (HCC).
Authors: Proskorovsky Irina , Krotneva Mira , Ozgurdal Kirhan , Jaeger Savina , Su Yun 
Published: June 2021

e16188 Background: REG and CAB, two therapies for second-line (2L) advanced HCC, have been evaluated vs. placebo (PBO) in randomized phase III trials, RESORCE (NCT01774344) and CELESTIAL (NCT01908426), respectively. In the absence of head-to-head studies, indirect treatment comparison (ITC) is needed to compare the efficacy and safety of REG vs. CAB. Anchored MAIC is an ITC method adjusting for cross-trial heterogeneity using PBO as the common comparator or anchor. Methods: Patient-level data from RESORCE were available to match the inclusion criteria and published baseline characteristics of CELESTIAL. 2L patients with prior sorafenib exposure of >3 months were included in the analyses. Overall survival (OS), progression-free survival (PFS), and Grade 3/4 treatment-emerging adverse events (TEAEs) occurring in > 10% of patients were compared. Matching was conducted for the following covariates, which were either imbalanced across trials or likely treatment effect modifiers (EMs): gender, region, Eastern Cooperative Oncology Group (ECOG), prior sorafenib duration, extrahepatic spread, macrovascular invasion, hepatitis B (HBV), hepatitis C (HCV), alcohol use, and alpha-fetoprotein (AFP) ≥400 ng/mL. Anchored MAIC were used to compare the relative effect of each treatment. To account for violation of the proportional hazards assumption, in addition to hazard ratios (HRs), restricted mean survival time (RMST) was estimated to quantify differences in OS and PFS. For safety, the relative effects were expressed as risk differences (RDs) (REG – CAB). Results: After matching, the effective sample sizes of REG and its PBO arm were 214 and 82, respectively. For OS, REG showed favorable although not statistically significant HR, and 30% longer mean survival with an RMST ratio approaching statistical significance. For PFS, there was no numerical difference in HR and no clinically meaningful difference based on RMST analyses (Table). REG showed lower incidence of diarrhea [RD of -7.1% (NE, NE)] and fatigue [RD of -6.3% (-14.6, 2.0)]. Conclusions: In this anchored MAIC, REG showed favorable OS and safety profile, especially for diarrhea and fatigue. No clinically meaningful difference was observed for PFS. The analysis could be limited by reduced sample size after matching and unobserved or missing EMs that could not be adjusted.[Table: see text]
Efficacy of immunotherapy in hepatocholangiocarcinoma (HCC-CC): Proof of concept.
Authors: Diab Osama , Khan Maloree , Abbasi Saqib , Saeed Anwaar , Kasi Anup , Baranda Joaquina Celebre , Sun Weijing , Al-Rajabi Raed Moh'd Taiseer 
Published: June 2021

e16194 Background: Hepatocholangiocarcinoma (HCC-CC) is a rare form of cancer with a poor prognosis. Of all primary liver cancers, the incidence of HCC-CC ranges from 0.4 to 14.2%. HCC-CC is a mixed carcinoma with findings of both hepatocellular carcinoma and cholangiocarcinoma. Immune checkpoint inhibitors are a potent first line treatment in hepatocellular carcinoma with multiple clinical trial showing effectiveness in cholangiocarcinoma. HCC-CC has limited proven treatment options as patients are generally excluded from clinical trials. In this study we reviewed outcomes of patients with HCC-CC who received immune checkpoint inhibitor in a single center. Methods: Records of patients who had a pathological confirmed HCC-CC by a subspecialized hepatic pathologist at the University of Kansas medical center were reviewed. We identified 6 patients with locally advanced unresectable or metastatic HCC-CC that received immune checkpoint inhibitor between February 2017 and January 2021. Baseline characteristics were obtained, as well as best response, line of therapy, and duration of response. Results: Of the six patients 4 (66%) received PD-1 inhibitor alone and 2 (34%) received combination therapy with CTLA-4 inhibitor for the treatment of HCC-CC. There were 3 (50%) females and 6 (100%) with prior hepatitis C infection. four (66%) patients had metastatic disease and 2 had locally unresectable advanced disease. Objective response rate was 83.3%. One patient achieved complete response and had a treatment holiday after receiving treatment for 2 years, and restarted immunotherapy upon relapse. Four patients had a partial response, of which two passed away after disease progression. One patient had stable disease on 2 different lines of immunotherapy then progressed. Of those who responded, one patient received immunotherapy, 3 (50%) received liver directed therapy and two received chemotherapy or Lenvatinib as first line treatment (Table). Conclusions: Immune checkpoint inhibitors demonstrate potential activity in patients with HCC-CC without unexpected side effect in this unmet need high-risk population. Larger studies are needed to confirm activity and efficacy in this setting.[Table: see text]
Clinical outcomes and efficacy of endoscopic ultrasound guided ablation of pancreatic cancer a systematic review and a meta-analysis.
Authors: Ehsan Hamid , Yousaf Muhammad Nadeem , Wahab Ahsan , Neupane Karun , Sana Muhammad Khawar , Rafae Abdul , Masood Adeel , Ahmed Zahoor , Muneeb Ahmed , Tayyeb Muhammad 
Published: June 2021

e16261 Background: Endoscopic ultrasound-guided ablation therapy (EUS-A) is a minimally invasive technique increasingly used for the management of surgically unresectable pancreatic cancer. The data on the efficacy and clinical outcome of EUS-A for unresectable pancreatic cancer is lacking. We conducted this systematic review and meta-analysis to evaluate the safety, technical and clinical success of EUS-A therapies specifically for unresectable pancreatic cancer. Methods: Studies were identified with a comprehensive search for EUS-A and pancreatic cancer on PubMed, Google Scholar, Web of Science and Embase data search as of October 2020. The technical and clinical success rates of EUS-A were primary outcomes while adverse events (AEs) rate was secondary outcome. We defined technical success as successful placement of probe within tumor and able to perform ablation regardless of tumor outcome. Clinical success was defined as symptomatic improvement and/or any reduction in tumor size or evidence of necrosis on radiological imaging after EUS-A. A compute pooled analysis was performed using the ‘meta’ package by Schwarzer et al. in the R programming language (version 4.0.2) using random effect model. Results: Nineteen studies including 192 patients (54% females) were included. Common pancreatic tumors were nonfunctional neuroendocrine tumor (NNET) 43.5% (97), followed by locally advanced pancreatic ductal adenocarcinoma (LAPDAC) 27.3% (61), insulinoma 17.9% (40), cystic neoplastic lesions 8.5% (19). The pancreatic head was the most common site of tumor 49.8% (111), followed by body, neck and tail 44.8% (100). EUS-RFA was the most commonly used ablative therapy 63% (12/19 studies), followed by EUS-EA (ethanol ablation) 26% (5/19 studies) while EUS-A using laser and lauromacrogol injection was used in one study each. The mean number of ablation sessions per patient was 1.4 based on the total 243 sessions in 176 patients. The pooled technical success rate of EUS-A was 99.5% [95% CI = 0.90-0.97, I2 = 0%]. The pooled clinical success rate calculated out of total number of pancreatic lesions was 91.1% [95% CI = 0.79-0.92, I2 = 16%]. Clinical improvement in symptoms was reported in 11 studies and a complete resolution or decrease in tumor size was reported in 16 studies. The pooled AEs rate was 22.9% [95% CI = 0.17-0.37, I2 = 43%]. Common AEs were abdominal pain 7.8% (15), pancreatitis 5.2% (10) and pancreatic pseudocyst 2.1% (4). The median follow-up was 9.5 months. Conclusions: EUS-A is a safe and promising modality in the management of unresectable pancreatic cancer with a high technical and clinical success rate. Large prospective studies and clinical trials are required for comparison of clinical outcome of different EUS-A therapies and its widespread application for unresectable pancreatic cancer.
The role of selective internal radiation therapy for liver metastases from pancreatic adenocarcinoma after progression on prior chemotherapy.
Authors: Hackett Jonathan O , Crothers Rebecca S , Shaughnessy Emma , Cardaci Giuseppe , Kaard Alaar , Dean Andrew Peter 
Published: June 2021

e16272 Background: Selective internal radiation therapy (SIRT) has established benefit for liver metastases in colorectal cancer. Very little data exists on the use of SIRT for liver dominant metastatic pancreatic cancer. A 2015 phase II trial by Gibbs et al suggested that SIRT at diagnosis may be beneficial in liver metastases in pancreatic cancer, particularly in those who have had a previous primary resection. Methods: In this single-institute retrospective audit we identified eleven patients who had liver predominant metastatic adenocarcinoma of the pancreas who received SIRT at any stage of their treatment. Data was analysed from our electronic patient databases. Results: 11 patients with adenocarcinoma of the pancreas, who had SIRT following progression on chemotherapy were identified. 3 had a primary surgical resection. All patients had received a minimum of one line of chemotherapy and had ECOG performance status of 2 or less. The median time from diagnosis to SIRT was 13 months (range 5-24 months). Patients received Yttrium-90 microspheres with a median activity of 2.1GBq with all eleven receiving concurrent infusional 5-FU 225mg/m2/day for 7 days prior and 14 days after. The median survival after SIRT therapy was 6 months (range 2-19 months). The median overall survival from diagnosis was 20 months (range 12-31 months). SIRT appeared safe and well-tolerated with no associated 30 day all-cause mortality. One patient developed radiation induced asymptomatic portal hypertension and liver cirrhosis. Conclusions: This is the first report of the use of SIRT with radiosensitising concurrent infusional 5FU for metastatic pancreatic cancer after failure of prior chemotherapy. We conclude that SIRT with concurrent infusional 5FU offers an additional treatment option for patients with liver dominant metastatic pancreatic cancer, who maintain a good PS who have progressed on prior lines of chemotherapy. This can provide a durable treatment response and requires further exploration.
A multicenter, prospective evaluation of a urine-based assay for bladder cancer diagnosis.
Authors: Wang Liang , Liang Yiming , Shi Min , Ma Tonghui , Deng Jianhua , Ding Degang 
Published: June 2021

e16509 Background: At present, bladder cancer is diagnosed mainly through cystoscopy as the "gold standard" method, which is invasive, costly, and painful for patients. Meanwhile, the current non-invasive liquid biopsy approaches, such as FISH or cytology, still do not show adequate performance in the diagnosis of bladder cancer because of the unsatisfactory sensitivity. Therefore, developing a novel method that performs higher sensitivity and specificity, especially negative predictive value(NPV) is an urgent issue to be addressed and will be very helpful for the clinical application. Methods: From October 2019 to October 2020, we designed a multicenter, prospective study, in which 321 hematuria patients were enrolled, including 218 males and 103 females, and their average age was 56. Based on the final pathological diagnosis, 121 patients were confirmed as bladder cancer and 200 samples were benign urinary diseases. 100ml urine samples were collected from each patient before the endoscopy examination. The Genetron Uro-18 assay, which included a 17 gene mutation panel and the methylation test on ONECUT2, was used in this study. The regions in the panel were selected based on the TCGA database, as well as previous publications. 321 urine DNA libraries were generated using multiplex PCR methods and then sequenced on the Ion S5 System. The CpG-sites on the ONECUT2 gene were detected by bisulfite-specific real-time PCR. Results: In these samples, a total of 205 oncogenic mutations were found in 13 genes in the panel. Mutations on TERT, PIK3CA, FGFR3, and TP53 genes showed significantly higher occurrence. 103 samples were found to be mutation-positive, 92 of which were pathologically confirmed as bladder cancers. When only gene mutations were considered, the sensitivity and specificity of this assay were 76.0% and 94.5%, respectively. The methylation of ONECUT2 had a performance in the test with a sensitivity of 74.4% and specificity of 93.0%. Combining the mutation panel with the ONECUT2 methylation test will improve the sensitivity (86.0%) of this assay, but slightly hampered the specificity (91.0%). The positive predictive value(PPV) and negative predictive value(NPV) of the combination were 85.2% and 91.5%. The sensitivity was as high as 91.5% when low-grade bladder cancer samples were excluded. In contrast, the sensitivity of cytology and FISH tests were only 48.4% and 62.0%. Conclusions: The novel urine-based liquid biopsy assay has excellent performances in the diagnosis of bladder cancer, with sensitivity and NPV reaching 86.0% and 91.5%, which improved significantly than cytology and FISH tests. Thus this assay will be more beneficial for patients with urinary diseases which significantly reduces the current burden of repeat cystoscopies and cytology tests.
Three versus four cycles of neoadjuvant gemcitabine cisplatin for muscle invasive bladder cancer (MIBC).
Authors: Major Catherine Kendall , Williams Michael Brandon , Fleming Mark T. 
Published: June 2021

e16524 Background: The standard of care for MIBC is neoadjuvant (NAC) cisplatin-based chemotherapy with either 3-4 cycles of dose dense MVAC or 4 cycles of gemcitabine/cisplatin (GC) followed by radical cystectomy. However, due to toxicity some patients are unable to complete intention to treat full course chemotherapy. We aim to identify any variation in overall survival (OS) and progression-free survival (PFS) with 3 vs 4 cycles of neoadjuvant GC in the setting of miUCB. We hypothesize that there will be a statistically significant difference in OS and PFS with three vs four cycles of neoadjuvant GC. Methods: A consecutive retrospective chart review of patients with MIBC treated with three or four cycles of neoadjuvant cisplatin-based chemotherapy from 2009-2020 was performed. R Studio was used to generate Kaplan-Meier curves representing OS and PFS with p-values. Results: One hundred and twenty-one patients were identified. Patient characteristics are described in the table below. Eighty-six patients received 4 cycles of GC and thirty-five patients received 3 cycles. Ninety-five patients proceeded to cystectomy: 93 received a radical cystectomy, 1 received a partial cystectomy, and 1 was aborted due to positive lymph nodes. There was a statistically significant difference in OS between those who got 3 or 4 cycles (p=0.03) and PFS (p=0.014). Median OS for those who got 3 cycles and 4 cycles was 52 months and 92 months respectively. Conclusions: Toxicity can preclude patients from receiving four cycles of GC and this study demonstrates a significant difference in overall OS and PFS between those who receive 3 vs 4 cycles of GC.[Table: see text]
RNF43 mutations to predict survival from treatment with immune checkpoint inhibitors and are associated with a high tumor mutation burden in bladder cancer.
Authors: Li Liping , Yang Mengmei , Huang Mengli 
Published: June 2021

e16528 Background: Immune checkpoint inhibitors (ICIs) targeting PD-1/L1 have been approved as first-line treatment for cisplatin-ineligible patients and as second-line therapy for patients with metastatic urothelial carcinoma of the bladder. Biomarkers can help select patients who are more likely to response to ICIs. RNF43 is an E3 ubiquitin ligase that acts as a negative regulator of Wnt/β-catenin signaling pathway. In colorectal cancer (CRC) patients treated with immune checkpoint inhibitors (ICIs), RNF43 mutations predicted longer overall survival (OS). The impact of RNF43 mutations on the efficiency of ICIs in bladder cancer(BLC) remains to be explored. Methods: We downloaded the mutation and clinical data of 211 BLC patients treated with ICIs from the immunotherapeutic cohort published by Samstein et al. (2019). OS analyses were conducted using Kaplan-Meier curves and log-rank tests. Wilcoxon test was used for the comparison of TMB. We also downloaded a TCGA cohort for prognostic analysis. The correlations between RNF43 and immune infiltrates were analyzed in the TIMER2.0 database. Statistical significance was set at p = 0.05. Results: RNF43 mutations were identified in 4.3%(9/211) and 3%(13/438) BLC patients in the immunotherapeutic and TCGA cohort, respectively. In the immunotherapeutic cohort, patients with RNF43 mutations had significantly longer OS (25 months vs 8 months; p = 0.015) and higher tumor mutation burden(TMB, 42.3 vs 7.9; p = 3.15E-06) than RNF43-wild-type patients. Different from this, no significant difference was found in OS between RNF43-mutant and RNF43-wild-type BLC patients with standard treatment in the TCGA cohort (p = 0.696). These results indicated that RNF43 was not a prognostic factor but a predictive biomarker of survival in BLC treated with ICIs. No difference was observed in subsets of immune cells between RNF43-mutant and the RNF43-wide-type BLC patients, including neutrophils, macrophages, CD8+ T cells, Tregs, B cells and NK cells. Conclusions: RNF43 mutations may be a predictor of survival benefit from ICIs in bladder cancer and correlated with higher TMB. Further studies in other ICI-treated cohorts are needed to confirm these results.