bluuebunny/crossref_metadata_2025_split huggingface dataset:
Global multi-center phase I trial of the intraperitoneal infusion of anti-EpCAM x anti-CD3 bispecific antibody catumaxomab for advanced gastric carcinoma with peritoneal metastasis.
Authors: QI Changsong , Wu Shikai , Kim In-Ho , Cai Shirong , Wang Jufeng , Kim Seung Tae , Wang Jaw-Yuan , Bai Li-Yuan , Lin Cheng-Yao , Liang Zhezhao , Wei Jian Xin , Shen Lin 
Published: June 2022

e16102 Background: Advanced gastric cancer (GC) patients (pts) have high incidence of peritoneal metastasis (PM), resulting in ascites, cachexia and poor life quality. EpCAM is highly expressed on GC but no on peritoneum. Catumaxomab intraperitoneal infusion (i.p.) was previously demonstrated to eradicate EpCAM+ cancers and control the malignant ascites in Europe (Heiss. Int. J. Cancer.2010). We present initial safety, pharmacokinetics (PK), and efficacy from the multi-center phase I trial of Catumaxomab on GC pts with PM in Asian population (NCT04222114). Methods: GC pts who had progressed on at least two prior standard systemic therapies with peritoneal metastasis were enrolled. Pts received Catumaxomab i.p. of 10 μg, 20 μg, 50 μg and 150 μg on days 1, 4, 8 and 11, respectively in the 1st cycle. From the 2nd cycle, Pts received Catumaxomab i.p. of 20 μg, 50 μg, 150 μg on days 1, 4 and 8, respectively. The cycle was 42 days in Cohort A, and 28 days in Cohort B. Catumaxomab PK were evaluated, tumor measurements and quantification of ascites by five-point method (Oriuchi, JJCO,2005) were performed Q6W. The primary endpoint was overall survival (OS); secondary endpoints were response rate of ascites, progression-free interval of peritoneal metastatic lesions and puncture-free survival (PuFS); Data cut-off date was Jan 29,2022. Results: 17 pts from 14 sites (median age: 52.5 yr, ECOG PS: 0 [n=2], 1 [n=14], 2[n=1], Cohort A:9, Cohort B:8) were treated. There were no dose-limiting toxicities (DLTs). The most common treatment-emergent adverse event (TEAE) was pyrexia (76.5%) and abdominal pain (58.8%). Grade ≥3 treatment related adverse events (TRAE) of abdominal pain (23.5%), bilirubin conjugated increased (23.5%), lymphocyte count decreased (17.6%), ALT increased (11.8%), and AST increased (11.8%) were reported. No treatment related death or neurotoxicity occurred in the study. Median overall survival was 102 days (95%CI: 38-166), with 10 (58.8%) deaths observed. For ascites, CR+PR was observed in 4 cases (33%), no PD case was reported. No therapeutic ascites drainage was recorded after cycle 1. Median PuFS was 116 days (95%CI: 28-157). Median progression-free interval of peritoneal metastatic lesions was 102 days (95%CI: 38-166). PK: Catumaxomab concentrations in plasma increased in a dose-dependent manner and were similar to Caucasian population in Europe. Conclusions: This clinical study indicated that multiple cycles of Catumaxomab i.p. were safe and well tolerated in Asian population. PK profile was similar. Early efficacy signals were promising, especially in pts with ascites, which will be further investigated in phase 3 study. Clinical trial information: NCT04222114.
Comprehensive molecular characterization of Chinese patients with biliary tract cancers.
Authors: Liu Daren , Ye Dan , Wu Jinhong , Yu Yangyang , Zhao Lele , Xiao Mingzhe , Qi Chuang 
Published: June 2022

e16153 Background: Biliary tract cancers are clinically heterogenous with poor prognosis. The traditional location-based classification of biliary tract cancers is helpful while the boundary between subtypes is still ambiguous. We hereby analyzed the comprehensive molecular characterizations across different types among biliary tract cancers and further to identify the similarities and differences and help with the individualized treatment. Methods: Tumor tissue samples from 219 Chinese biliary tract cancer patients were profiled by next generation sequencing with a 539 gene panel by the Illumina NovaSeq 6000 (Illumina, San Diego, CA, USA) sequencing platform. Tumor mutation burden (TMB) was calculated by counting all nonsynonymous mutations per megabase of coding sequences. Results: A total of 219 biliary tract cancer (BTC) patients with a median age of 61 years(range 29–83 years) were enrolled, including 147 gallbladder cancer (GBC), 51 intrahepatic cholangiocarcinoma (iCCA) and 21 hilar cholangiocarcinoma (hCCA). These samples consisted of 93 males and 126 females. The most frequent mutated genes were TP53 (73%), ARID1A (18%), MUC16 (16%) in GBC, TP53 (57%), KRAS (35%), ARID1A (16%), PIK3CA (16%) in iCCA, TP53 (48%), KRAS (29%), ARID1A (14%) in hCCA. The mutation of BCORL1 (P = 0.002) and IRF4 (P = 0.006) had a significant association with age. The median TMB was 4.26 mutations/Mb in GBC, 2.94 mutations/Mb in iCCA and 2.84 mutations/Mb in hCCA. Patients with ATM mutation and FAT1 mutation had a significant higher TMB level (P＜0.001). The mutations of common target genes in different types of BTC were analyzed. The mutations of IDH1, target gene of Ivosidenib, were detected in 4 (1.83%) patients (1 in GBC, 2 in iCCA, 1in hCCA). The mutations of FGFR1/2/3/4, target gene of Erdafitinib, were detected in 10 (4.57%) patients (8 in GBC, 2 in iCCA, 0 in hCCA). The most frequently affected pathways in GBC, iCCA and hCCA were TP53 (78.2%, 60.8%, 47.6%), RTK-RAS (52.4%, 64.7%, 47.6%), PIK3 (34%, 39.2%, 33.3%). Conclusions: The genomic profiling and molecular characterization among different anatomic locations could support the exploration of tumor development mechanism and provide theoretic basis for developing diagnosis and treatment methods for biliary tract cancers patients.
GATA6 amplification is associated with improved survival of TP53-mutated pancreatic cancer.
Authors: Yang Jung-In , Ha Taehoon , Zhou Edward , Tzanavaris Chris , Deschênes Astrid , Boyd Jeff , Hollweg Christopher , Zhu Xinhua , King Daniel 
Published: June 2022

e16285 Background: Recent investigation in pancreatic adenocarcinoma (PDAC) demonstrates an association of molecular subtype with chemosensitivity and prognosis. TP53 and GATA6 are two genes independently associated with worse survival in PDAC. Here, we evaluated treatment outcome by genetic alterations of TP53 and GATA6 among patients with pancreatic cancer across New York’s largest health care system. Methods: This is a retrospective analysis of patients at Northwell Health diagnosed with PDAC between 2014 to 2021. Surgical status was used to segregate patients into two groups: resected and unresected. TP53 and GATA6 mutation status was compared for disease-free survival (DFS) (resected) or progression-free survival (PFS) (unresected), and for overall survival (OS). Additionally, patient survival by type of chemotherapy administered was evaluated. The Kaplan–Meier method was used to determine overall survival (OS), and the Wilcoxon test was used to compare survival curves. Results: Tumor mutational profiling data were available for 129 patients. TP53 mutations were found in 105 patients (81.4%), GATA6 amplifications were found in 18 patients (14.0%), and 16 patients had both mutations. TP53 mutations were associated with a worse OS compared to the wild-type TP53 population (n = 24) (median OS 22.7 months, 95% CI 12.5 to 41.1, vs. 44.3 months, 95% CI 24.5 to 80.3, HR 1.97, p = 0.048). Among patients with a TP53 mutation, a survival advantage was observed in those who had a GATA6 amplification compared to those who did not (median OS 25.5 months, 95% CI 10.9 to 44.6, vs. 22.1 months, 95% CI 12.6 to 51.5, HR 1.68, p = 0.038). In patients with unresected PDAC, the survival advantage of GATA6 amplification within TP53 mutated group was more prominent than the absence of the amplification (median OS 23.8 months, 95% CI 10.0 to 56.5, n = 12 vs. 10.5 months, 95% CI 4.4 to 24.8, n = 55, HR 0.52, p = 0.008). In the TP53 mutation group, among 33 patients who received Gem/NabP as the first-line chemotherapy, patients with GATA6 amplification (n = 8) had significantly improved survival compared to those without GATA6 amplification (n = 25) (mean OS 23.1 months, 95% CI 8.5 to 63.0, vs. 9.4 months, 95% CI 3.44 to 26.6, HR 0.51, p = 0.027). Conclusions: Genetic mutations in TP53 were associated with shorter OS than wild-type TP53. Contrary to our initial expectation that co-mutation would be associated with even worse survival, we found that GATA6 amplification appeared to attenuate poor prognosis observed in TP53-mutant patients. Additionally, GATA6 amplification may be a predictive marker for better responses to Gem/NabP chemotherapy.
Prognostic value of CA 19-9 and carcinoembrionic antigen (CEA) in duodenal adenocarcinoma (DA): An institutional retrospective cohort study.
Authors: Altshuler Ellery , King William , Richhart Raymond , Hones Keegan , Mathavan Akash , Mathavan Akshay , Leach Daniel F. , Murtaza Yasmeen , Lee Jimmy , Manfrini Denise , Mathavan Mohit , Chowdhury Zahara , Rogers Sherise C. , Nassour Ibrahim , Ramnaraign Brian Hemendra , Sahin Ilyas , Franke Aaron J , George Thomas J. , Hughes Steven J. , Fabregas Jesus C. 
Published: June 2022

e16306 Background: Duodenal adenocarcinoma (DA) is a rare malignancy with poor outcomes. Tumor markers are used to assess disease response and to monitor for recurrence. Specifically, CA-19-9 and CEA have been validated for use in pancreatic cancer and colorectal cancer, respectively. However, these tumor markers have never been validated in patients with DA. We aim to assess the association of these biomarkers with clinical outcomes in patients with DA. Methods: This is a retrospective cohort study. After obtaining IRB approval (IRB202102705), we accessed the University of Florida medical records of patient treated for DA from January 1, 2006, until December 31, 2021. CA 19-9 and CEA were collected as continuous variables and were analyzed as binary variables: normal vs. high, using the maximum normal value as a cut-off (normal CA 19-9 < = 35 U/ml; CEA < = 3 ng/ml). Analysis was conducted using Kaplan Meyer curves, log-rank test and Cox proportional hazards model. Results: A total of 68 patients were included in the final analysis. Median age was 67 years and median follow-up was 22.2 months. CA 19-9 and CEA were elevated in 36.8% and 48.5% of patients, respectively. Patients with an elevated CA 19-9 had a median overall survival (OS) of 8.5 months vs. 27.4 months in patients with normal levels (HR 1.67; 95%CI 0.94–2.99; p = 0.081). Patients with an elevated CEA had a median OS of 13.4 months vs. 16.8 months in patients with normal level normal levels (HR 1.43; 95%CI 0.81–2.52; p value = 0.221). In a sensitivity analysis, a concomitant elevation of both tumoral markers was significantly associated with worsened OS (HR 1.9; 95%CI 1.05–3.06; p = 0.035). Conclusions: In patients with duodenal adenocarcinoma, elevation of both CA 19-9 and CEA was associated with a statistically significant worse overall survival. CA 19-9 level had a higher prognostic impact on OS than CEA levels. To our knowledge, this is the first study to evaluate the role of CA 19-9 and CEA in patients with DA. Further research is required for validation.[Table: see text]
In vitro and in vivo investigations of anlotinib in bladder cancer treatment.
Authors: Meng Zeji , Pei Xinqi , Gu Yanan , Li Lei , He Dalin , Wu Kaijie 
Published: June 2022

e16505 Background: Bladder cancer is one of the most common malignancy in urinary system. Fibroblast growth factor receptor 3 (FGFR3) is the most common alteration gene in bladder cancer, occurring in approximately 70% of non-metastatic bladder cancer and 20% of metastatic bladder cancer. Anlotinib is a potent oral, multi-target tyrosine kinase inhibitor with a favorable safety which mainly targets vascular endothelial growth factor receptor (VEGFR), FGFR, platelet-derived growth factor receptors, and c-kit. This study aims to investigate the role of anlotinib in bladder cancer compared with FGFR3 inhibitor erdafitinib i n vitro and in vivo. Methods: MTT, colony formation, and Transwell assays were performed on bladder cancer cells (SW780 and UMUC14) to confirm the effects of anlotinib and erdafitinib on proliferation, migration and invasion. Apoptotic effect was evaluated by Annexin V/propidium iodide double staining, and the levels of the protein and mRNA were examined by RNA-seq, Western blotting and RT-qPCR. Finally, mice with palpable xenografts were treated either with anlotinib and erdafitinib for 8 days before they were sacrificed for measuring the sizes and weights of the tumors. Results: To assess the roles of anlotinib in bladder cancer, we treated SW780 cell line which had FGFR3-BALAP2L1 fusion mutation and UMUC-14 cell line which had a FGFR3 (MuS247C) mutation with DMSO, anlotinib and erdafitinib. As seen in MTT, colony formation and Transwell assays, anlotinib repressed cell proliferation, migration and invasion as erdafitinib. Compared with vehicle, Anlotinib promoted cell apoptosis of bladder cancer cells. To further explore the mechanism, anlotinib and erdafitinib suppressed p-Erk1/2 and p-AKT, while only anlotinib inhibited the expression of VEGF-a. Compared with erdafitinib, the inhibitory ability of anlotinib was weaker than that of erdafitinib in cell line with FGFR3 (MuS247C) mutation, on the contrary, it was much stronger in cell line with FGFR3-BALAP2L1 fusion mutation. In addition, the in vivo data from xenagrafts also supported that anlotinib could significantly repress tumor growth with FGFR3 fusion mutation, and the efficacy was better than erdafitinib. Conclusions: Anlotinib could repress the proliferation, migration and invasion of bladder cancer cells by inhibiting the phosphorylation of Erk1/2 and AKT, and the suppression VEGF-a expression, whose effects was better than erdafitinib in bladder cancer with FGFR3 fusion mutation. Therefore, anlotinib might be a potential novel targeted agent to treat the bladder cancer patients with FGFR3 fusion mutations, and clinical trials are needed for further investigation.
VISIOCYT1 clinical trial: Artificial intelligence for the diagnosis of bladder urothelial lesions.
Authors: Lebret Thierry , Radulescu Camélia , Guy Laurent , Roumiguié Mathieu , Courtade-Saïdi Monique , Piaton Eric , Verhoest Gregory , Rioux Nathalie , Savareux Laurent , De Vergie Stéphane , Renaudin Karine , Kandel Christine , Gonzalez Samia , Borgès Ruth , Cochand-Priollet Béatrix , Nivet Sebastien , Pignot Geraldine 
Published: June 2022

e16558 Background: Voided urinary cytology is a non-invasive test, but it suffers from a lack of sensitivity (Se), particularly in low-grade urothelial lesions, and it remains pathologist-dependent. In order to improve the performance of urinary cytopathology, the VitaDX company (France) developed a medical device which uses whole-slide digitalization and artificial intelligence algorithms to identify tumor cells. The device allows complete analysis of morphological characters of voided urothelial cells, such as the shape, size and color of the nuclei. Methods: VISIOCYT1 is a prospective, multicenter clinical trial involving 319 patients divided into two groups: 1) patients with non-muscle invasive bladder tumors (NMIBC) confirmed by histology, and 2) control patients with negative urinary cytology and cystoscopy. The primary objective of the study was to evaluate the Se of the VisioCyt test. Specificity (Sp) and comparison of Se and Sp of conventional urinary cytology vs. the VisioCyt test were also calculated. Results: A total of 319 patients were included (170 in the NIMBC group vs. 149 controls). Overall Se was 80.9% and 45.9% for VisioCyt test and conventional urinary cytology, respectively (p = .002). Negative cytology being an inclusion criterion, a 100% Sp was attributed to the control group. It was calculated at 61.8% for the VisioCyt test. Concerning grade, the VisioCyt test allowed higher Se to be obtained in the low grade tumor category (66.7% vs. 26.1% for conventional urinary cytology, Mc Nemar test, p < .0001). A higher Se was also observed in high grade tumors: 93.7% vs. 62.8% (p < .0001). Conclusions: The VisioCyt test greatly improves the performance of urinary cytopathology in the diagnosis of urothelial bladder tumors, particularly in low grade, pTa lesions. Its implementation could dramatically reduce the need for cystoscopy in patients followed after conservative treatment of bladder cancer. Clinical trial information: NCT02966691. [Table: see text]
Combining IL-12 immunocytokine (M9241) with docetaxel in metastatic prostate cancer: A phase I study.
Authors: Atiq Mohammad O. , Chandran Elias Bin Aris , Meininger Luke , Karzai Fatima , Bilusic Marijo , Marte Jennifer L. , Arlen Philip M. , Cordes Lisa M. , Strauss Julius , Redman Jason , Floudas Charalampos S. , Pastor Danielle M. , Owens Helen , Hankin Amy , Williams Monique , Figg William Douglas , Dahut William L. , Schlom Jeffrey , Gulley James L. , Madan Ravi Amrit 
Published: June 2022

e17033 Background: M9241 is an immunocytokine that targets single- and double-stranded DNA which allows the treatment to localize IL-12 to necrotic tumor (Xu, CCR 2017). M9241 was well-tolerated as a monotherapy in a Phase I study with solid tumors (Strauss J, CCR 2019). Additional preclinical data has demonstrated synergy of M9241 with cytotoxic therapy. This is the first study to examine the safety of a novel combination of chemotherapy and immunocytokines in metastatic prostate cancer. Methods: This safety analysis included patients with mCSPC or mCRPC. Patients were enrolled in a 2-dose level (DL) escalation cohort of M9241 (DL 1: 12mcg/kg, DL 2: 16.8mcg/kg) combined with docetaxel (75mg/m2) with 6 patients planned per DL. A third DL of 8mcg/kg will enroll 6 more patients after the 16.8mcg/kg DL has fully enrolled. All patients were treated with ADT. Patients were initiated on treatment with docetaxel with a plan for mCSPC patients to receive six 3-week cycles of combined treatment and mCRPC patients to continue until progression or unacceptable toxicity. M9241 was given starting with the second cycle of treatment for each patient. Dose-limiting toxicity (DLT) was evaluated in the first 6 weeks after start of docetaxel (from cycle 1 day 1 through the end of the first cycle with M9241). Results: The study has enrolled 10 patients out of a planned 18 for the safety portion. Age range is 58-82 with a median of 69 years. Race distribution is 80% White and 20% Black. Gleason scores for patients were 8 (40%), 9 (40%), and 10 (20%). No DLTs were seen with either dose-level. Only 1 patient had a Grade 4 AE, neutropenia. Grade 3 toxicities included anemia, diarrhea, leukopenia, and hypotension (each occurring in 10% of the patients). The most frequent adverse events (AEs) of any grade were anemia (40%) and lymphopenia (40%), followed by fatigue (30%), diarrhea (20%), and fever (20%). Conclusions: We established a safe dose-level of M9241 at ≥ 12mcg/kg. Updated clinical data from the safety cohort (n = 18) will be presented. This demonstrates that an immunocytokine and chemotherapy can be safely combined for treatment in metastatic prostate cancer. Two planned expansion cohorts will evaluate docetaxel and M9241 in mCSPC and mCRPC, respectively. Clinical trial information: NCT04633252.
Systematic review of real-world evidence studies in women’s cancer at key congresses and factors related to high tier acceptance.
Authors: Szamreta Elizabeth A. , Modi Mansi , Periyasamy Ramu , Yamsani Bhavani , Kulkarni Sumedha , Monberg Matthew J. 
Published: June 2022

e17533 Background: Real-world evidence (RWE) studies complement clinical trials (CT) and address a variety of issues, such as adherence, cost, comparative effectiveness, and treatment patterns. This systematic review assessed prevalence and characteristics of RWE presented at oncology congresses. Methods: Data on women’s cancers (cervical, ovarian, endometrial, and multiple [gyn/other]) work were extracted from the databases of American Society of Clinical Oncology (ASCO) and The Society of Gynecological Oncology (SGO) congresses (2018-2020). The primary objective was to identify the proportion of CT vs RWE. Secondary objectives were to: a) describe the tier of acceptance for RWE vs CTs; b) describe prevalence of types of RWE; c) analyze the characteristics (data source, design, authorship, outcome(s) assessed, and presence of statistically significant results) associated with RWE acceptance. Results: Of 3163 abstracts screened, 2271 were included (1756 RWE vs 515 CTs). RWE represented a higher proportion of work at SGO vs ASCO (90% vs 59%). Overall, more RWE vs CTs was accepted as a poster (75% vs 60%) or publication only (19% vs 11%), while less was accepted for oral presentation (4% vs 20%). Among RWE, 90% had academic author(s), 44% used clinical data, around one quarter used another data repository/registry, and about 14% used medical record or chart review data. Nearly two thirds of RWE studies reported significant results, while 6% contained no significant results. There was no clear association between authorship or significance of results and tier of acceptance. About 60% of RWE studies were retrospective, 9% were prospective, 4% focused primarily on PROs, and 2% were economic models. The most common outcomes assessed in RWE studies were molecular analyses (18%) and survival based on treatment efficacy (13%). Among molecular analyses, most (68%) were accepted as a poster, with 26% accepted as publication only and 4% as oral. An even greater fraction (77%) of survival/efficacy analyses were accepted as a poster, 18% as publication only and even fewer (2%) as oral. Conclusions: RWE was more frequently presented than CTs at both ASCO and SGO. However, across congresses and cancer types, a smaller proportion of RWE vs CT work was accepted as an oral presentation. Results indicated high interest in CTs; RWE studies utilizing clinical data or data repository/registry data, and those with molecular and/or survival outcomes, were most common. The results demonstrate that while RWE studies are prevalent and provide valuable data for healthcare decision-making, they do not always achieve the visibility of CTs.[Table: see text]