bluuebunny/crossref_metadata_2025_split huggingface dataset:
Description of initial treatment for newly diagnosed metastatic carcinoid (cNET) and pancreatic neuroendocrine (pNET) patients.
Authors: Bobiak Sarah , Choti Michael A. , Benson Al B. , Strosberg Jonathan R. , Bloomston Mark , Bergsland Emily K. , Zornosa Carrie C. , Kulke Matthew , Nakakura Eric K. , Shah Manisha H. , Yao James C. 
Published: March 2020

e14542 Background: There is limited descriptive information regarding treatment (tx) patterns for NET from clinic practice data. The primary aim of this analysis was to describe initial tx among NET pts as a first step in understanding tx patterns for NET. Methods: The National Comprehensive Cancer Network (NCCN) Oncology Outcomes Database was queried to identify newly diagnosed pts presenting to 7 NCCN institutions with a confirmed metastatic cNET or pNET diagnosis in 2004 or 2005. Pts with a minimum of 5 years of follow up or confirmed death were included in the analysis. Pt demographics, clinical characteristics, initial tx, and 5-year survival were described. Results: Among 187 cNET pts, 52% were male, median age at diagnosis was 58, and 51% alive. Approximately 58% had a known primary tumor; 65% of which were in the small bowel. Most cNET pts (85%) presented with symptoms, 33% had carcinoid syndrome. Initial tx included surgical therapy in 43%, drug therapy in 41%, and other therapies in 16%. The majority (82%) had imaging prior to treatment, among which 79% had a CT scan and 35% had somatostatin receptor scintigraphy (SRS). The most frequent biomarker test was for CGA (performed in 64 pts, elevated in 53). Of 76 cNET pts receiving initial drug therapy, 82% were treated with a somatostatin analog (SA); others received chemotherapy or targeted therapy. Kaplan-Meier (K-M) curves indicated a 5-year survival of 62% and 56% among pts receiving surgery or drug therapy as initial tx, respectively. Among 104 pNET pts, 61% were male, median age at diagnosis was 54, and 41% alive. Approximately 82% presented with symptoms among which 25% were hormone related. Among the 84% of pts imaged prior to treatment, CT scan was most common (79%) and 38% had SRS. The most common initial tx among pNET pts was drug therapy (56%); 60% received a SA; 31% received chemotherapy. Only 25% underwent surgery as initial tx. K-M curves indicated a 5-year survival of 63% among surgical pts in contrast to 31% for pts whose initial tx was drug therapy. Conclusions: Initial tx among the majority of pts was either surgery or drug therapy. Among cNET and pNET pts receiving drug therapy, 82% (n=62) and 60% (n=35) respectively, received an SA.
Phase I dose-escalation study of talimogene laherparepvec (T-VEC) for advanced pancreatic cancer (ca).
Authors: Chang Kenneth J. , Senzer Neil N. , Binmoeller Kenneth , Goldsweig Howard , Coffin Robert 
Published: March 2020

e14546 Background: T-VEC is an investigational, immune-enhanced oncolytic herpes simplex virus type I that selectively replicates in solid tumors. This was an open-label, dose-escalation study of T-VEC administered by endoscopic ultrasound (EUS)-guided fine needle injection (FNI) for advanced pancreatic ca. Methods: Eligibility criteria included ≥ 18 yrs old, ECOG 0-2, pathologically confirmed pancreatic ca with measurable disease (tumors ≥ 1 cm dia), and failure or unable to receive standard tx. T-VEC was administered at wks 6, 12, 18 to a single pancreatic tumor in 4 cohorts (C), 3 pts each enrolled sequentially (extended dosing allowed in pts thought to have benefit): C 1: 1 dose of 104 PFU/mL then 2 of 105 PFU/mL; C 2: 1 dose of 105 PFU/mL then 2 of 106 PFU/mL; C 3: 1 dose of 106 PFU/mL then 2 of 107 PFU/mL; C 4: 1 dose of 106 PFU/mL then 2 of 108 PFU/mL. 2 doses/pt were required for enrollment to the next C. A C could be expanded to 6 if 1 related DLT occurred. If 2 DLTs occurred, dose escalation was stopped. Endpoints were safety and activity as assessed by CT tumor dia changes from screening. Results: 17 pts were enrolled in C 1-3 given at least 1 dose of T-VEC; 65% were men; median age 54; 76% white, ECOG 0-1 82%. C 4 was not opened because of early study termination (not related to safety). 7/17 (41%) received all 3 planned doses and 8 (47%) had at least 1 post-dose CT scan. Only C 3 showed a median decrease in injected tumor dia with 2/4 pts achieving substantial tumor reductions (-36% and -33%). 3 pts (in C 1and C 3) showed decreases in the dia of ≥ 1 uninjected tumors (in liver, pancreas, kidney, and chest); 1 pt had disappearance of a nonmeasurable tumor in the liver. A dose trend was not observed for reductions of uninjected tumors. Most common AEs were ascites (47%), dehydration (41%), anemia, abdominal pain, constipation, and nausea (each 35%), and vomiting (29%). 2 pts (12%) had a grade 5 AE, both considered unrelated to T-VEC. Conclusions: EUS-guided FNI of T-VEC in advanced pancreatic ca, at initial doses of 104 to 106 PFU/mL followed by up to 107 PFU/mL, was feasible and tolerable. Evidence of biologic activity was observed. Future studies should be conducted in pts with less advanced disease, to allow sufficient time to receive multiple doses before PD.
Bevacizumab plus temsirolimus as second-line treatment for advanced hepatocellular carcinoma (HCC).
Authors: Chelis Leonidas , Deftereos Savas , Xenidis Nikolaos , Amarantidis Kiriakos , Hamalidou Eleni Kyrillos , Dimopoulos Prokopios , Michailidis Prodromos , Christakidis Evagelos , Mimidis Kostantinos , Pitsiava Dimitra , Karayiannakis Anastasios , Kakolyris Stylianos 
Published: March 2020

e14567 Background: The mTOR pathway has a central role in HCC not only in the tumor growth but also in the insulin driven hepatocarcinogenesis and is reported activated in 40-50% of HCC patients. Temsirolimus is an mTOR inhibitor with proven efficacy in renal cell carcinoma. The angiogenesis inhibitor bevacizumab has shown promising activity in HCC. Sorafenib represents the only drug with proven efficacy in HCC but currently there is no standard 2nd line treatment for patients who progress on sorafenib. Therefore, we performed a phase II study to determine the activity of a bevacizumab plus temsirolimus combination in second-line HCC. Methods: Patients who had progressed on sorafenib were eligible. Other eligibility criteria included ECOG PS 0-2 and Child- Pugh score A. The combination consisted of bevacizumab 10 mg/Kg plus temsirolimus 25 mg (total dose) given i.v. biweekly. After the enrolment of the 1/3 of the preplanned 40 patients (n=13) an interim analysis had to be performed to evaluate biologic activity. Biologic activity was defined either as a partial response by RECIST criteria or a > 50% decline in AFP in at least 2 of 13 patients. An expanded panel of possible biomarkers of response including VEGF, HGF, FGFb, TSP-1 and others, were measured at baseline. Results: The median age of the first 13 patients was 67 years (53-79 years) . The patients performace status was 0 (n=3), 1 (n=4) and 2 (n=6) and 11 of 13 patients had extrahepatic disease. Four patients had radiographic partial responses and five patients had > 50% reduction in AFP. Seven patients (53,8%) showed bioactivity. It is of note that two of them experiencing durable and long lasting partial remissions of 20 and 16 months respectively are still on treatment. One patient developed reversible posterior leycoencephalopathy syndrome (Grade 4 ) and one grade 4 hypertension. Grade 3 non-hematologic toxicities included hyperglycemia (n=3), hyperlipidemia (n=2), diarrhea (n=2) and infection (n=2). Conclusions: The combination of bevacizumab plus temsirolimus is well tolerated with encouraging activity. The study's preplanned criteria for activity have been met and the study continues accrual.
A multicenter random assignment phase II study of irinotecan and flavopiridol versus irinotecan alone for patients with p53 wild-type gastric adenocarcinoma (NCI 8060).
Authors: Janjigian Yelena Yuriy , Tang Laura H. , Shibata Stephen , Kelsen David Paul , Segal Michal , Cheng Catherine , Schwartz Gary K. , Doyle L. Austin , Shah Manish A. 
Published: March 2020

e14586 Background: Preclinical studies demonstrate that tumors wild-type for p53 (p53wt) are refractory to irinotecan relative to non-functional or mutant p53, and that sequential therapy with flavopiridol, a cyclin dependent kinase inhibitor that inhibits homologous recombination and DNA repair, and irinotecan overcomes p53 mediated drug resistance in vivo. This phase II study is designed to assess cell cycle mediated drug resistance in p53wt gastric cancer, and test the hypothesis that administration of flavopiridol following irinotecan can overcome resistance to irinotecan. Methods: Pts with advanced p53wt (≤ 20% nuclear IHC staining using D07 antibody) gastric adenocarcinoma and disease progression on non-irinotecan chemotherapy regimen were randomized in 2:1 fashion to irinotecan 100 mg/m2 followed 7 h later by flavopiridol 60 mg/m2 administered over 1h or irinotecan 100 mg/m2 administered weekly on a 2 week on/1 week off schedule. Response assessment is performed every 2 cycles and the primary endpoint is 3-month progression free survival (PFS). Pre- and post-treatment biopsies were obtained for molecular assessments of p53 mediated drug resistance. Results: To date 30 of 55 patients screened were p53wt (54%), 19 pts were randomized to receive irinotecan + flavopiridol (n=13) and irinotecan (n=6). Median characteristics of 19 evaluable patients: age 61 (44 to 76), KPS 80% (70 to100), 13 male, 1 prior regimen (1 to 2). The common treatment emergent toxicities were anemia (Grade 2/3 21%), neutropenia (grade 2/3 31%, grade 4 .05%), nausea (grade 2/3 21%) and fatigue (grade 2/3 37%). With irinotecan + flavopiridol 1/13 (8%) confirmed partial response was seen and 5 month disease stabilization in 3/13 (23%) patients. No responses were seen with single agent irinotecan. The median PFS was similar, 1.6 mos irinotecan + flavopiridol vs 1.3 mos in irinotecan group (p=0.21). Conclusions: 54% of gastric cancers are p53wt. Correlative tissue analysis including p53 sequencing, p21, Rad51 is ongoing. Due to lack of activity with irinotecan alone, an amendment to a single arm irinotecan + flavopiridol study is planned.
Somatostatin receptor (SSTR) expression and proliferative index (Ki 67) in 100 patients (pts) with gastroenteropancreatic neuroendocrine tumors (GEP-NETs): Clinical-pathological correlation.
Authors: O'Connor Juan Manuel , Pesce Veronica , Mendez Guillermo Ariel , Bestani Claudia , Marmissolle Fabiana , Giacomi Nora , Belli Susana , Domenichini Enzo , Chacon Matias , Zamora Victor , Cabanne Ana , Roca Enrique Luis 
Published: March 2020

e14598 Background: Somatostatin receptor expression (SSTR), mainly subtypes 2 and 5, is a feature of well differentiated GEP-NETs. Such expression has a prognostic and predictive value for the use of somatostatin analogs.Ki 67, present during the cycle phases (G1, S, G2 y M) is a nuclear antigen associated with cell proliferation. The correlation between both clinical and pathological factors is under active investigation in patients with GEP-NETs. Methods: An analysis including 100 patients in the database of the Argentum Group was performed. Consecutive patients were included during the 2006-2007 period. In all cases, a centralized revision of the sample was conducted for diagnosis confirmation.The study of SSTR receptors in tissue and Ki67 was conducted using IHQ.The Kaplan-Meier method was used to analyse survival. Log-rank test was used for the comparative analysis of the variables of interest. Results: The expression of at least one of the SSTRs 2 (a) or 5 was found in 86% and 62% of cases respectivevly in this population. The univariate analysis showed significant differences in the expression of SSTR2 (a) but not in the expression of SSTR 5.The expression of the proliferative index (Ki 67) was associated with significant differences in relation to OS at 5 years, 84% (Ki 67 under or equal to 2%), 66% (Ki 67 between 3 and 15%) and 13% (Ki 67 over 15%). The OS at 5 years in patients with SSTR 2/5 positive and Ki 67 under 2% was 86%, 64% in pts. with SSTR 2/5 positive and Ki 67 over 2% and 20 % in pts. with SSTR 2/5 negative, independent Ki 67 (p .0023). Conclusions: The expression of at least one of the SSTRs 2 (a) or 5 was found in 86% and 62% of cases respectivevly in this population. In the population with GEP-NETs under study, a subgroup of patients with a better prognosis was identified in association with the expression of SSTR 2/5 and Ki67 below 2%. The assessment of SSTR 2(a) and 5 in tissues, together with the study of the proliferative index are a useful tool for prognosis assessment in these patients.
Prognostic value of epidermal growth factor receptors (EGFR) on overall survival of gastric cancer patients.
Authors: Jácome Alexandre A. A. , Wohnrath Durval R. , Scapulatempo Neto Cristovam , Carneseca Estela C. , Nunes Joao Soares , Viana Luciano S. , Serrano Sergio Vicente , Santos José Sebastião 
Published: March 2020

e14599 Background: The human EGFR family is involved in the pathogenesis and progression of several solid tumors. However, there is no consensus about the prognostic role of HER2 expression and of other members of EGFR family in gastric cancer patients. The aim of this study was to evaluate the prognostic value of members of the EGFR family in gastric cancer. Methods: Retrospective study with 201 patients with gastric and esophagogastric junction (EGJ) adenocarcinoma stages 0 to IV (AJCC 6th edition) who underwent primary tumor resection between January 2006 and December 2008 at Barretos Cancer Hospital, Barretos, São Paulo, Brazil. Tissue from primary tumors were analyzed by tissue microarray technology. IHC scores 0 and 1+ were classified as negative and scores 2+ and 3+ as positive, both for membrane and cytoplasmic expression of HER1, HER2, HER3 and HER4. The HER2 scoring system for gastric cancer was used for classification. Correlations between receptor expression and clinicopathological characteristics were performed according to the chi-square test. Survival analysis was calculated according to a parametric Weibull model with a mixture model incorporating long-term survivors. Multivariate analysis of prognostic factors was performed by a regression model incorporating long-term survivors with the Weibull distribution. Results: Membrane expression of HER1, HER2 and HER4 were 9%, 17% and 15%, respectively. No membrane expression of HER3 was observed. Cytoplasmic expression of HER1, HER3 and HER4 were 45%, 62% and 24%, respectively. Expression of HER2 and HER3 correlated with intestinal-type histology (p: 0.001 and p < 0.001, respectively) and advanced age (p: 0.011 and p: 0.008, respectively). According to a regression model adjusted for age, surgical radicality, surgical modality, Laurén histology, adjuvant therapy, TNM stage and receptors expressions, only TNM stage showed prognostic influence. Conclusions: Expression of HER2 and other members of EGFR family did not have influence on the overall survival in the gastric cancer population studied. The elaboration of a systematic review with meta-analysis or a prospective study could help elucidate this controversial issue.
Surgical resection and its relationship to survival for recurrent hepatocellular carcinoma after living donor liver transplantation.
Authors: Ikegami Toru , Shirabe Ken , Yoshizumi Tomoharu , Morita Kazutoyo , Toshima Takeo , Muto Jun , Yoshiya Shohei , Uchiyama Hideaki , Soejima Yuji , Maehara Yoshihiko 
Published: March 2020

e14602 Background: Although liver transplantation offers excellent recurrence-free survivals for treating hepatocellular carcinoma (HCC), cases with recurrent diseases usually result in miserable outcomes. In this study, the indication and efficacy of surgical resection for the recurrent diseases after living donor liver transplantation (LDLT) for HCC. Methods: A total of 153 recipients, who underwent LDLT for HCC between 1997 and 2011, were included. The endpoints analyzed were survivals from time of LDLT and from the time of recurrence. Results: Twenty-three patients had recurrence of HCC after LDLT. The mean period until the initial recurrence after LDLT and the mean duration until death after the initial recurrence were 17.1 months (n=23) and 17.4 months (n=16), respectively. A univariate analysis showed that gender (p<0.01) des-gamma-carboxy prothrombin <300 mAU/ml (p=0.02), interferon therapy (p=0.02), early posttransplant tumor recurrence (p<0.01), and eligibility for a surgical resection (p<0.01) all had a beneficial impact on survival from tumor recurrence. Other factors at LDLT including Milan criteria, tumor number, tumor size or alpha-fetoprotein had no impact on the survival after recurrence. Multivariate analysis showed eligibility for a surgical resection (odds ratio 12.3, p<0.0199 and des-gamma-carboxy prothrombin <300 mAU/ml (odds ratio 5.3, p=0.04) were the independent beneficial factors on survival from tumor recurrence. Surgical resection was performed in 12 patients for the initial recurrences at lung (n=5), peritoneum (n=2) lymph nodes (n=2), liver (n=1), bone (n=1) and adrenal gland. The 2-year survival rate after recurrence in the patients surgery was indicated or not indicated was 72.2% and 18.2%, respectively (p<0.01). Conclusions: Surgical therapy could be useful for patients who experience a recurrence of HCC after LDLT to improve their outcome, when such treatment is available.
Interventional oncology for older patients with liver and kidney malignancies.
Authors: Monfardini Lorenzo , Orsi Franco , Bonomo Guido , Vigna Paolo Della , Monfardini Silvio 
Published: March 2020

e14607 Background: Less invasive procedures, such as those provided by interventional oncology are often offered to older patients(pts) believing that the benefits outweigh the drawbacks for non-fit vulnerable older pts, but reports in the English literature are very few. The purpose of this study was then to provide information on results and complications of interventional oncology procedures in pts with liver and kidney cancer older than 70 years ,analysing the incidence of complications, loco regional responses and duration of hospital staying and to compare these findings with those of pts younger than 70. Methods: Prospectively collected data on all pts that underwent liver bland arterial embolisation (BAE) with or without radiofrequency ablation and kidney radiofrequency ablation (RFA) at the Interventional Radiology Unit of the European Institute of Oncology, were analyzed comparing incidence of complications, loco regional responses and duration of hospital staying for pts older and younger than 70 years. Results: From April 2007 to March 2011 163 pts (109 males and 54 females) , 66 (40.5 %) older and 97 ( 59.9 %) younger than 70 years were treated with interventional oncology procedures. Of these 56 had an hepatocarcinoma,76 liver metastases and 31 a kidney cancer. The ASA score was homogeneously distributed in older and younger patients. The overall complication rate in patients older than 70 was 4.5 % (3/66) and in younger 3,1 % (3/97), without a significant difference (p=0.69). In pts older than 70 years mean hospitalization was 2.3 nights (36 were inpts for 2 nights, 8 for 3 and 3 for 4) while in the 81 younger pts the mean hospitalization was 2.2 nights (67 were inpts for 2 nights, 12 for 3 and 2 for 4). Objective response rates were 52.8% in older versus 46.3% in younger pts (p=0.55). Conclusions: Our study has confirmed thatliver BAE even followed by RFA and renal RFA in older liver and renal cancer pts are as safe and effective as in younger ones. Age alone should then not be considered as a risk factor in selected older pts.
Effect of a novel CDX2 splice variant on tumorigenicity in gastroesophageal junction adenocarcinoma xenografts.
Authors: Witek Matthew , Waldman Scott A , Snook Adam , Schulz Stephanie 
Published: March 2020

e14619 Background: Patients with locally advanced adenocarcinoma of the gastroesophageal junction (GEJ) that undergo aggressive neoadjuvant chemoradiation therapy followed by an extensive oncologic resection have a 25-50% risk of developing locoregional recurrences and/or distant metastases. There is an unmet need for biomarkers that predict tumor behavior following neoadjuvant therapy that can be used to direct future therapy. CDX2, an intestine-specific transcription factor that regulates proliferation and differentiation, is ectopically expressed by epithelial cells lining the GEJ during intestinal metasplasia and retained by adenocarcinomas. To date, CDX2 has not been shown to contribute to the tumorigenic potential of GEJ adenocarciomas limiting its use as a predictive or prognostic marker. Methods: CDX2 mRNA from GEJ tissues were sequenced. Wild type and splice variant transcripts and proteins were analyzed by Western blot, RT-PCR, luciferase assays, and fluorescent IHC. In vitro and in vivo proliferation assays were performed with OE19 cells retrovirally transduced to over-express either GFP or CDX2/AS. Results: We identified a novel splice variant of CDX2, CDX2/AS (alternative splicing) encompassing a protein in which the 85 carboxyl-terminal residues in CDX2 are replaced with a 45 residue domain enriched in arginine and serine. CDX2 and CDX2/AS were concomitantly expressed in adenocarcinomas arising from the GEJ. CDX2/AS localizes to nuclear matrix associated foci with splicing factors in contrast to CDX2 that exhibits a diffuse nuclear expression pattern. CDX2/AS did not activate promoters of putative CDX2-dependent genes but inhibited CDX2 transcriptional activity. Over-expression of CDX2/AS in the GEJ adenocarcinoma cell line OE19 did not impact its growth in vitro but did significantly increase its tumorigenicity in nude mice. Conclusions: We discovered a CDX2 splice variant with dominant-negative properties that increases the tumorigenic potential of GEJ adenocarcinoma xenografts. Further investigation examining the relationship between CDX2/AS expression and human tumor characteristics will determine its value as a prognostic and/or predictive biomarker.