bluuebunny/crossref_metadata_2025_split huggingface dataset:
A correlative analysis of biochemical and radiologic hepatic disease in metastatic pancreatic adenocarcinoma (PA).
Authors: McHugh Deaglan Joseph , Teo MinYuen , Rozumna-Martynyuk Nataliya , McDermott Raymond S. 
Published: March 2020

e15163 Background: The liver is the most common site of distant metastases (mets) in patients with PA. We aimed to study radiomorphology of PA-related liver mets and its correlation with the degree of biochemical hepatic dysfunction. The impact of liver failure on patient mortality was also assessed. Methods: Using National Cancer Institute-Organ Dysfunction Working Group guidelines, patients were stratified into 4 groups A (Normal), B (Mild), C (Moderate), D (severe) based on serum bilirubin and aspartate transaminase levels. Two sets of results were recorded for each patient - at diagnosis (baseline) and the the last available prior to death. CT scan at diagnosis were used to measure both the number and diameter of two largest lesions for each patients’ liver mets. Results: 58 patients with metastatic PA were identified. 5 of these patients were excluded from this study as their imaging was not available. 34 (59%) had hepatic mets. Of 34 patients, 47.1% (n=16) had diffuse mets. 23.5% (n=8) had 6-10 liver mets. 20.6% (n=7) had 2-5 liver mets. 8.8% (n=3) had a solitary metastasis. Four of these patients were excluded as they were still alive at the time of the biochemical analysis. Of 31 patients at baseline: 25.8% (n=8), 35.5% (n=7), 22.6% (n=7), 16.1% (n=5) of patients had group A, B, C and D hepatic dysfunction respectively. The median time between last liver function testing and death was 10 days (range 0-114 days). Prior to death, 16.1% (n=5), 35.5% (n=11), 6.5% (n=2), 41.9% (n=13) of patients had group A, B, C and D dysfunction respectively. Of the 13 patients with severe hepatic dysfunction prior to death, 7 had no radiographic evidence of extrinsic obstruction. No difference in number of liver mets were seen between groups A and B when compared to C and D. However, groups C+D had higher mean size, 2.8 x 2.3 vs. 2.4 x 1.8 cm (p=0.047). No survival difference was noted (4.6 vs 2.5 months, p=0.425). Conclusions: The majority of patients had diffuse liver mets at diagnosis. There was no significant correlation between the radiological burden of hepatic disease and the degree of hepatic impairment at diagnosis. PA-related liver mets was the likeliest cause of death in up to 22.6% of patients.
Temozolamide plus capecitabine as salvage treatment for patients with advanced neuroendocrine tumors (NETs) in the community setting.
Authors: López-López Carlos , Jiménez Paula , Crespo Guillermo , Grande Enrique , Custodio Ana B. , Mangas-Izquierdo M. , Pérez Arnillas Quionia , Barrio-Alonso M. J. , Soria Rivas Ainara , Barriuso Jorge 
Published: March 2020

e15169 Background: Streptozotocin and doxorubicin-based chemotherapy schemes have been widely used in the treatment of advanced NETs. Unfortunately, balance between efficacy and toxicity is clearly improvable. Novel combinations of cytotoxic agents like temozolamide and capecitabine have shown promising antitumoral activity in retrospective series.We aimed toevaluate the efficacy and safety of this combination in patients with advanced NETs derived from the daily clinical practice. Methods: We analyzed the clinical outcome of 34 patients (pts) treated with temozolamide (150 mg/m2 qo, days 10-14) plus capecitabine (1.000 mg/m2 bid, days 1-14) every 28 days, between June-2008 and December-2012 in five referenced centers in Spain. Results: 21 pts (61%), were pancreatic primary NETs (pNETs). 8 pts (24%) were treated as first-line. 26 pts (76,5%) had ECOG 0 or 1. One (2,9%), 18 (52,9%), and 11 (32,4%) pts had low (G1), intermediate (G2) or high-grade (G3) respectively. Grade was not available in 4 pts (11,8%). Median administered cycles were 8 (range 1-26). At the time of the data cut-off (Dec-2012) 5 pts (14,7%) were still on treatment after a median follow up of 6,4 months. 13 pts (38,2%) had partial response (PR) and 12 (32,4%) stable disease (SD) according to RECIST 1.1 criteria. Estimated median time to progression (TTP) was 9,4 months IC95% (4,2-14,6) in the intention to treat population. Thrombocytopenia was the most frequent toxicity found in grade 3 or more (9%). Other grade 3 toxicities according to CTCAE v4.0 were observed in less than 5% of pts. Conclusions: These encouraging results show a promising activity and a favorable safety profile of the combination of temozolamide and capecitabine in patients with advanced NETs and deserves for further clinical research in the future.
Survival analysis of treatment with S-1, alone or in combination with CDDP (SP), in elderly patients with advanced gastric cancer: A 10-year retrospective cohort study.
Authors: Makiyama Akitaka , Kajitani Tatsuhiro , Oda Hisanobu , Fujimoto Chinatsu , Esaki Taito 
Published: March 2020

e15170 Background: In Japan, the elderly population is increasing, and steadily increase the number of deaths in the elderly gastric cancer patients. However, the standard treatment of elderly gastric cancer has not been established, either treatment of S-1 or SP is carried out in the clinical practice, while SP is considered as standard therapy in the young people. Now, we investigated the impact of S-1 and SP on survival time in clinical practice. Methods: Between 2003 and 2012, advanced gastric cancer patients over 70 years of age received S-1 or SP as first line therapy were retrospectively reviewed to investigate clinical outcomes. Patient characteristics analyzed included age, gender, performance status (PS), tumor histology, renal function and metastatic site. In addition, we have analyzed prognostic factors in multivariate analysis. Results: Among 93 patients (pts), 67 pts (72%) received S-1 and 26 pts (28%) received SP. Patient characteristics between the two groups showed no significant differences in gender, histology, metastatic site, or creatinine clearance level, but did show an imbalance in PS (tended with better at SP group) and age (tended with younger at SP group), significantly. Even though the background factors were favorable results in SP group, there were no significant differences in median progression-free survival (median 139 vs. 102 days; p = 0.96) and overall survival (median 330 vs. 263 days; p = 0.55) between S-1 and SP group, respectively. Grade 3-4 neutropenia (10 vs. 27%, p < 0.05) , fatigue (3 vs. 15%, p < 0.05) and Grade 1-2 creatinine increased (9 vs. 31%, p < 0.01) were more frequent in the SP group than in the S-1 group, respectively. According to the multivariate analysis, exposure to CDDP was not independently associated with a better prognosis. Conclusions: Despite the obvious limitations of this analysis, there does not appear to be a benefit for the addition of CDDP in the elderly gastric cancer patients due to the increase of toxicity. A randomized controlled trial in this age group is warranted. We will also report the results of clinically meaningful prognostic factors associated with the primary treatment at annual meeting.
Expression of immunohistochemical markers in ampullary cancer (AC) and association with behavior.
Authors: De Barros E. Silva Milton Jose , Ribeiro Adriana Regina G. , Begnami Maria D. , Costa Felipe D'Almeida , Costa Wilson Luiz , Maia Joyce Maria L. , Mello Celso Abdon , Freitas Helano C. , Diniz Alessandro Landskron , Ribeiro Heber Salvador de Castro , Coimbra Felipe José Fernandez , Fanelli Marcello Ferretti 
Published: March 2020

e15184 Background: Curiously, the ampulla is formed by the union of two distinct types of mucosa: intestinal (GI) and pancreatobiliary(PB). Based on this fact, ACs could have different biologic behaviors. Methods: Between 1999 and 2012 we performed a retrospective analysis of patients with AC that underwent a pancreaticoduodenectomy (PD) with curative intent in our institution and the expressions of immunohistochemical markers related to GI origin (CK20 and CDX2) and to PB origin: (CK7 and MUC1) and its association with outcomes. Results: Twenty-seven patients underwent (PD), (M:F=15:12), median age was 62 (range33-83), 85.2% had R0 resection, 29.6% had positive lymph-nodes, 44.4% had perineural invasion, 22.2% had vascular invasion, 29.6% had lymphatic invasion, 59.2% had moderately differentiated tumors. AJCC stage pathologic grouping was: I=33.3%, II=37%, III= 29.6%; Median follow-up was 33.8 months. Relapse free survival was 43% in 3 years and overall survival was 53.7% in 5 years. The relapse rate was 59.2% and the majority of these relapses (69%) were distant metastasis without local relapse. Only positive lymph-node status (p=0,004, HR: 5.99) and R1 resection (R1: p=0.015, HR: 8.75) were independent prognostic factors for relapse on multivariate analysis. Among the patients, 21 were evaluated for the expression of immunohistochemical markers. Ten AC were classified into TGI type, 9 into PB type and 2 into unusual. An association between PB type and positive lymph node status (p=0.05) and more advanced stage (p=0.05) was found (Fisher’s exact test). There was no difference in relapse and survival between the histological subtypes, however, more PB patients had received adjuvant therapy. Conclusions: Histological subtypes of AC may have different behavior, but they are frequently neglected during decision of adjuvant therapy.
Prognostic factors of neuroendocrine tumors (NETs) in a Mexican cohort.
Authors: Camargo Vanessa Rosas , Huitzil-Melendez Fidel David , Gamboa-Dominguez Armando , Cano Garia Fernando , Galvan Salazar Gabriel , Leon-Rodriguez Eucario 
Published: March 2020

e15186 Background: NETs comprise a heterogeneous group of neoplasms regarding clinical behavior. Our aim was to identify clinical and pathological variables associated with survival in a mexican cohort. Methods: We retrospectively reviewed the medical records of all gastroenteropancreatic(GEP)-NETs with histopathological confirmation evaluated at our Institution from January 2000 to December 2011. Relevant clinical and histopatholocical features were recorded. Overall survival (OS) was estimated using Kaplan Meier method and survival distributions were compared using the Log rank test. Results: 175 patients with GEP-NETs were identified in the study period. We excluded 35 patients with insulinomas and 40 patients with lesions amenable to endoscopic resection given 100% cancer specific survival. Therefore, 100 patients with GEP-NETs (61% gastrointestinal / 39% pancreatic) with malignant potential were analyzed: median age 53 y/o, 55% were male, 39% were localized, 4% had regional spread and 57% were metastatic at presentation. 35% of patients harbored functional tumors. 32% of patients showed isolated liver metastasis while 24% of patients showed hepatic and extrahepatic metastatic disease. 37% were NETs grade 1/2, 56% were neuroendocrine carcinomas and 6% were mixed neuroendocrine carcinoma / adenocarcinoma. Median OS was 79.6 months. Univariate analysis identified clinical stage (P=0.002), weight loss (P=0.000), jaundice at presentation (P=0.036), ECOG performance status (P=0.000), resection of primary tumor (P=0.000) and resection of metástasis (P=0.001) as significantly associated with survival. Multivariate analysis excluded resection of primary tumor only. Conclusions: In this mexican cohort, clinical factors were the most important determinants of prognosis.
Survival following initiation of everolimus for second-line treatment of metastatic renal cell carcinoma: Prognostic factors in clinical practice and comparison to clinical trials.
Authors: Wong Michael K.K. , Jonasch Eric , Pal Sumanta Kumar , Signorovitch James E. , Lin Peggy L. , Liu Zhimei , Wang Xufang , Culver Kenneth W. , Scott Jeffrey A. , George Daniel J. , Vogelzang Nicholas J. 
Published: March 2020

e15500 Background: Current overall survival (OS) for metastatic renal cell carcinoma (mRCC) patients in clinical practice may differ from clinical trials. We aimed to identify and validate prognostic factors for OS in practice-based patients receiving 2nd-line everolimus (EVE), and to compare their OS vs. the RECORD-1 trial of EVE for mRCC. Methods: Two separate samples of oncologists/hematologists reviewed charts for patients initiating 2nd-line EVE between 2009 and 2011 following a 1st-line tyrosine kinase inhibitor (TKI). OS was defined as time from EVE initiation to death (censored at last follow-up). In the 1st sample of charts (the study sample), prognostic factors were identified via multivariable Cox proportional hazards models with stepwise selection. Prognostic factors considered included age, duration of mRCC and 1st-line treatment, metastatic sites, diabetes, histological subtype, ECOG and KPS score, and progression during 1st-line treatment. Model performance was assessed in the 2nd sample (the validation sample). Kaplan-Meier (KM) estimates for OS were compared between chart data and RECORD-1. Results: The study and validation samples included 220 and 97 patients, respectively. Significant prognostic factors were clear cell histology (hazard ratio (HR) = 2.9), KPS score <80% (HR = 2.9), duration of mRCC <1 year (HR = 2.7), progression on 1st-line TKI (HR = 2.2), and liver metastasis (HR = 1.9) (all P <.05). In the validation sample, KM estimates for 1-year OS were 90% for patients with 0-2 risk factors, 62% for patients with 3 risk factors, and 20% for patients with 4-5 risk factors (log-rank P <.001). OS estimates were consistent between both chart samples with 1-year OS probabilities of 67% and 68% and median OS of 19 and 23 months. In RECORD-1 1-year OS was 60% and median OS was 14.8 months (Motzer et al., 2010, Cancer). Conclusions: Prognostic factors for OS following 2nd-line EVE for mRCC in clinical practice were consistent with those previously identified in trial data. However, OS with 2nd-line EVE in clinical practice was longer than observed in trial data, and was not associated with type of 1st-line TKI.
Effect of sunitinib and pazopanib on necrosis and autophagic cell death in cancer cells: Role of cathepsin B.
Authors: Santoni Matteo , Amantini Consuelo , Morelli Maria Beatrice , Farfariello Valerio , Nabissi Massimo , Liberati Sonia , Bonfili Laura , Eleuteri Anna Maria , Mozzicafreddo Matteo , Burattini Luciano , Berardi Rossana , Cascinu Stefano , Santoni Giorgio 
Published: March 2020

e15513 Background: Tyrosine kinase inhibitors (TKI), such as sunitinib, sorafenib and pazopanib, have replaced immunotherapy as the standard of care for metastatic renal cell carcinoma (mRCC). However, their use in sequential or combined strategies is limited by the lack of evidences on TKI-induced cell death in cancer cells. Aim of our study was to evaluate the different mechanisms responsible of the anti-proliferative and cytotoxic effects induced in vitro by µM doses of sunitinib, sorafenib and pazopanib in 5637 and J82 bladder cancer (BC) cell lines. Methods: The viability of BC cell lines were tested by MTT assay. Autophagy was evaluated by western blot analysis with anti-LC3 and anti-p62 antibodies, acridine orange staining and cytofluorimetric analysis. Necrotic cell death was evaluated by Annexin-V/PI staining and FACS analysis. The cathepsin B activation was evaluated by western blot using an anti-cathepsin B antibody; the cathepsin B proteolytic activity was determined using the fluorogenic Z-Arg-Arg-AMC peptide and the fluorescence of the hydrolyzed 7-amino-4-methyl-coumarin was detected by a SpectraMax Gemini XPS microplate reader. Results: We found that sunitinib and pazopanib markedly reduced at mM dose the viability of BC cells. Treatment for 24h with 20µM of sunitinib, by triggering “Incomplete autophagy”, induced necrosis of BC cells. In addition, sunitinib as a lysosomotropic agent, entered free within the lysosomes, where by increasing lysosomal pH and impairing cathepsin B activity, induced lysosomal-dependent necrosis. By contrast, treatment of BC cells for 72h with 20µM of pazopanib induced autophagic cell death, which was markedly reversed in a dose-dependent manner by the autophagic inhibitor 3-MA. The pazopanib-induced autophagic cell death was associated with increased procathepsin B cleavage and enhanced cathepsin B activity. Conclusions: Overall, our results show different cathepsin B-dependent cancer cell death mechanisms induced by sunitinib or pazopanib, providing the biological basis for novel molecularly targeted approaches.
Retrospective analysis of sorafenib as first or second target therapy in mRCC patients in Italian centers: An update.
Authors: Derosa Lisa , Gernone Angela , Morelli Franco , Sava Teodoro , Zustovich Fable , Rossi Lorena , Ferrari Vittorio D. , Sabbatini Roberto , Gasparro Donatello , Felici Alessandra , Cascinu Stefano , Calvani Nicola , Lo Re Giovanni , Rizzo Mimma , Iacovelli Roberto , Bracarda Sergio , Porta Camillo , Galligioni Enzo , Cogoni Alessio Aligi , Procopio Giuseppe ,   RESET Study Group
Published: March 2020

e15524 Background: With several agents available for the treatment of metastatic renal cell carcinoma (mRCC) a better understanding of their use in daily clinical practice is fundamental in the decision-making process. Methods: The REtrospective analysis of Sorafenib (So) as 1st or 2nd targET therapy (RESET) in mRCC was a retrospective, observational field study that assessed the use and safety of So in clinical practice in Italian centers. Treatments were determined by physicians per local prescribing guidelines. Patients (pts) treated with So single agent as 1st or 2nd target therapy (TT) for mRCC between 1st Jan 2008 and 31st Dec 2010 were eligible for inclusion. Endpoints included safety, overall survival (OS), progression-free survival, response rate and treatment duration. Subgroup analyses included age, ECOG performance status, prior therapy, number of metastases and line of TT with So. Results: From Feb to Jul 2012, 358 pts from 37 Italian centers were enrolled. The most common ≥ grade 3 drug-related adverse events were hand-foot skin reaction (6.7%), rash (2.2%), hypertension, fatigue and diarrhea (1.7% each). In the overall population, median OS was 17.2 months (mos) (95% CI 15.4 – 19.6 mos) and median PFS was 5.9 mos (95% CI 4.9-6.7 mos). Median duration of treatment with So was 5.03 mos. Disease control (complete response + partial response + stable disease) was observed in 198(56%) pts. In pts receiving So as first or as second TT median OS was 19.9 mos (95% CI 15.9-25.3 mos) and 16.3 mos (95% CI 13.0-18.2 mos) respectively. In the subgroup of pts treated with So 1st TT followed by sunitinib (Su) 2nd TT (44 pts) and Su 1st TT followed by So 2nd TT (173 pts), median OS was 30.4 mos (95% CI 22.0-34.8 mos) and 16.6 mos (95% CI 13.1-18.2 mos) respectively. There were 269(76%) pts that received a total of 2 lines of therapy for mRCC, 133(38%) pts 3 lines and 43(12%) pts 4 lines of therapy. Conclusions: The efficacy and safety profile of So in the setting of Italian community-based daily clinical practice was similar to data reported in prospective clinical trials. The efficacy of So was observed in both the subgroups of pts receiving So as either the first or second TT for mRCC, with intriguing OS data in first line.
Epithelial-mesenchymal transition markers in metastatic transitional cell carcinoma (mTCC) patients under vinflunine treatment.
Authors: Sacristan Felipe , Aparicio Guadalupe , Grande Enrique , Haz-Conde Mar , Medina Villaamil Vanessa , Figueroa Angelica , Valladares Ayerbes Manuel , Antón Aparicio Luis M. 
Published: March 2020

e15532 Background: Vinflunine (VFL) demonstrated in vitro antiproliferative effects in human tumour cell lines, and in vitro antitumor activities against subcutaneous tumour xenografts. Recently, we demonstrated that VFL causes these effects through tubulin instability, which is one of the leading intracellular molecular process that drives epithelial-mesenchymal transition (EMT). In addition, VFL may induce up-regulation in expression levels of E-cadherin/N-cadherin cocient. Methods: The study included a retrospective analysis of 18 patients with mTCC treated with carboplatin-based chemotherapy. The patients who demonstrated objective response (38.8%) continued with vinflunine 320 mg/m2 one day every three weeks until progression. EMT protein expression (E-cadherin, beta-catenin, vimentin, CK18) was evaluated by Western blotting and also by immunohistochemistry (IHQ). Results: Overall mean age of patients was 71 years. The median overall survival was 3.5 years for the carboplatin-based chemotherapy (95% CI, 0.377-3.623). In patients treated with VFL, it was demonstrated a correlation of performance status and overall response with the histological type and age. We also found a relationship between different EMT markers in patients that received VFL. Conclusions: The above data provide evidence for an intrincate mechanism by which VFL could stop the transition from epithelial cells to the invasive mesenchymal phenotype. Molecular mechanism of Snail, Slug, Twist and Hakai will be reported.
Association of topoisomerase II expression and cancer-specific death in patients with surgically resected clear cell renal cell carcinoma.
Authors: Gardner Faithlore Patrice , Joseph Richard Wayne , Serie Daniel , Hilton Tracy W. , Parasramka Mansi , Eckel-Passow Jeanette , Cheville John , Leibovich Bradley C. , Parker Alexander S. 
Published: March 2020

e15539 Background: Despite the development of prognostic algorithms based on clinico-pathologic features, the ability to identify aggressive forms of clear cell renal cell carcinoma (ccRCC) remains suboptimal. Topoisomerase IIA (TOP2a) is a biomarker of DNA replication and a target for antineoplastic agents. Herein, we evaluate the association of TOP2a expression in ccRCC tumors with pathologic features of aggressiveness and risk of cancer-specific death. Methods: We identified 1,380 patients who underwent nephrectomy to treat clinically localized ccRCC between 1/16/1990 and 4/14/2009. TOP2a expression was assessed using IHC and scored as number of positive cells per mm2. We evaluated TOP2a expression using a continuous variable and tertile categories. For associations with pathologic features we employed Kruskal-Wallis tests and for associations with cancer-specific survival we generated Cox proportional hazard regression models. Results: HigherTOP2a expression is associated with later stage, higher grade and higher MayoSSIGN score (all p < 0.001). The risk of death from RCC increases with increasing TOP2a expression (p trend < 0.0001), and this association remained strong after after multivariate adjustment for well-known predictors of RCC aggressiveness. Compared to patients in the lowest tertile, those patients with tumors in the highest tertile of TOP2a expression were at increased risk of RCC death (HR=2.62 95% CI 1.95-3.54; p<0.0001). Interestingly, among those patients with low risk disease (SSIGN score 0-3; ~95% 10 year survival), those with high TOP2a were at increased risk of RCC death (HR=3.48 95% CI 1.56-7.76; p =0.002). Conclusions: Higher TOP2a expression is associated with more aggressive pathologic features and increased risk of cancer-specific death among patients undergoing surgery for localized ccRCC. If confirmed, these data support further inquiry for TOP2a as a prognostic and predictive biomarker for ccRCC patients.