bluuebunny/crossref_metadata_2025_split huggingface dataset:
Capecitabine and temozolomide (CAPTEM) in neuroendocrine tumor of unknown primary.
Authors: Chauhan Aman , Raajasekar Arun Kumar Arumugam , Myint Zin , Murray Leaundra , Anthony Lowell Brian 
Published: September 2018

e15691 Background: Better diagnostics, recognition and knowledge of neuroendocrine tumors (NETs) have led to consistent growth in incidence and prevalence of the disease. Being an orphan disease, therapeutic options are limited. Scarce data exists regarding use of Capecitabine and Temozolomide (CAPTEM) in neuroendocrine tumors. There are no published data on use of CAPTEM in neuroendocrine tumors of unknown primary. NETs of unknown primary accounts for 10-15 % of NETs. Historically NETs with unknown primary are thought to be relatively aggressive, conferring a poorer prognosis. Methods: Patients with neuroendocrine tumor with unknown primary were identified from Markey Cancer Center database over a five-year period (2012-2016). Patients treated with CAPTEM regimen were analyzed for radiological response in first scan, time to progression on treatment and toxicity. IRB approval was obtained. Results: 56 patients with neuroendocrine tumors of unknown primary were identified. 12 patients were treated with CAPTEM. Median age of study cohort was 62 years. 6/12 were females. Seven patients were grade II, 4 were grade III and only one was grade I NET. CAPTEM was used as front line systemic therapy in 9 patients. Mean duration of treatment before progression was 10.8 months. 6 patients showed reduction in metastatic tumor volume at first q 3 monthly CT scan. 3 patients had stable disease and 3 patients showed disease progression at first surveillance scan. Following were the rates of common side-effects. Grade 2 thrombocytopenia (n = 4), Grade 1 lymphocytopenia (n = 3), hand/foot syndrome Grade 1 (n = 1), Grade 3(n = 1), Fatigue, Grade 1 (n = 6) Conclusions: CAPTEM shows activity in neuroendocrine tumor of unknown primary. Currently FDA approved treatment options for grade I and grade II GI NETs includes somatostatin analogs and everolimus. Both of which are cytostatic and of limited use in case of visceral crisis or bulky disease where disease shrinkage is required. CAPTEM should be considered for grade II NETS of unknown primary.
Role of 92 gene cancer classifier assay in neuroendocrine tumor of unknown primary.
Authors: Chauhan Aman , Murray Leaundra , Raajasekar Arun Kumar Arumugam , Myint Zin , Anthony Lowell Brian 
Published: September 2018

e15696 Background: Neuroendocrine tumor of unknown primary constitutes about 10-15 % of all neuroendocrine tumors. Identification of primary site can helps alter the management. Sunitinib is FDA approved for management of pancreatic neuroendocrine tumors, everolimus is approved for gastroenteropancreatic and bronchial NETs, immune checkpoint inhibitors are active in Merkel cell carcinoma and MIBG treatment is standard of care for pheochromocytoma. Methods: Patients with neuroendocrine tumor with unknown primary were identified from Markey Cancer Center database over a five-year period (2012-2016). Patient who underwent 92-gene reverse transcriptase polymerase chain reaction cancer classification assay (BioTheranostics Tissue Type ID) were analyzed. IRB approval was obtained. Results: 56 patients with neuroendocrine tumors with unknown primary were identified. Median age of cohort was 61 years. 28/56 patients were males. 92 gene cancer ID assay was used in 38 out of 56 patients. Primary site of tumor was identified with > 95% certainty in 36 out of 38 patients. The test reported pancreatic NET as the primary site for 10 patients, gastrointestinal NETs for 14 patients, bronchial carcinoid for 5, large call NEC for 3, Merkel cell carcinoma for two and pheochromocytoma in one patient. Conclusions: Tissue type ID was able to identify a primary site in NETs of unknown primary in majority (94.7%) of cases. The result had direct implication in management of patients with regards to FDA approved treatment options in 13/38 patients (pNETs, merkel cell and pheochromocytoma).
Molecular classification of neuroendocrine tumors: Clinical experience with the 92-gene assay in >24,000 cases.
Authors: Hendifar Andrew Eugene , Soifer Harris S , Israel Mason , Schnabel Catherine A. 
Published: September 2018

e15700 Background: Histological diagnosis of metastatic neuroendocrine tumors (NET) can be straightforward, but identification of the specific NET tumor type/subtype is often challenging based on morphology alone. Accurate identification of tumor type/subtype in NETs of unknown primary has implications for grading, staging, and treatment decision-making as availability of targeted therapies increases. The 92-gene assay (CancerTYPE ID) is a validated gene expression classifier of 50 tumor type/subtypes (including 7 NET subtypes) for patients with unknown/uncertain diagnoses. In this study, 92-gene assay results from cases submitted for clinical testing with molecular diagnoses of NET were evaluated. Methods: A de-identified database was created under an IRB approved protocol that contains clinical and molecular information from consecutive cases submitted for clinical testing with the 92-gene assay with sufficient tissue for testing. In this analysis, patient demographics and distribution of molecular diagnoses were analyzed based on biopsy site, age, and gender. Chi-squared tests were used to compare between subgroups. Results: Analysis included 24,484 patients. Median age was 65y (51% female). The 92-gene assay rendered a molecular diagnosis of NET in 6.3% of cases (n = 1551). Small/large cell lung carcinoma (50%) was the most common NET molecular diagnosis, followed by GI carcinoid (14%), islet cell (14%), Merkel cell (10%), and lung carcinoid (9%). In liver biopsies (39% of cases), all 7 NET subtypes were identified by the 92-gene assay. The proportion of molecular diagnoses classified as small/large cell lung NET increased with age, from 25% in < 40y to 45% in 40-65y and 55% in > 65y, and the proportion of islet cell NET decreased with age (p < 0.0001). Men had a higher proportion of molecular diagnoses that were small/large cell lung NET (53%) vs women (46%; p < 0.0001). Conclusions: These findings highlight the utility of molecular classification to identify distinct NET tumor types/subtypes to improve diagnostic precision and treatment decision-making. In addition, significant differences in the distribution of molecular diagnoses of NET subtype by age and gender were identified.
Y-90 radioembolization comparative outcomes between solid tumor malignancies: A single institution experience.
Authors: Harris Joshua , Atluri Prashanti , Desouza Neha , Hoffman Jason , Eweka Abie 
Published: September 2018

e15704 Background: Transcatheter arterial radioembolization with Y90 is a locoregional therapy for unresectable hepatic malignancy with a more favorable side effect profile compared to trans-arterial chemoembolization. Increasingly, TARE is being utilized in multiple tumor types, for patients with primary hepatic malignancy or metastatic disease that is either liver-dominant or liver-only in distribution. Methods: This single-institution, retrospective study included all patients with hepatic malignancy treated with TARE from May 2012 to June 2016. Primary diagnoses included colon, breast, HCC, carcinoid, pancreatic or gastric cancer. Response was determined according to RECIST 1.1 criteria, based on each patient's followup cross-sectional imaging. 67 doses were administered to 44 patients. The mean dose administered was 25.27 mCi. The primary endpoint was response to therapy. The secondary endpoint was time to progression, in the liver. Results: Initial post-treatment cross-sectional imaging was obtained at an average of 13.9 (± 3.55 weeks, 95% CI) weeks on all patients, with 68% of patients demonstrating partial response, 29% stable disease and 3% of patients with progression. Median imaging follow-up was 6.86 months (± 1.5 months, 95% CI). Over that time period, 16% of patients developed recurrent or disease progression in previously treated lesions. In these patients, the median time to liver progression was 66 weeks. Conclusions: TARE is an effective and durable means of attaining control of disease in the liver. Patients with HCC demonstrated the highest response rate overall. This data adds to the building body of evidence supporting the use of TARE, and is unique as it comparatively assesses TARE response rates in various hepatic malignancies. [Table: see text]
Germline BRCA1 mutations and pancreatic adenocarcinoma: A literature review.
Authors: Al-Taee Ahmad , Gill Ammara , Mahon Suzanne M. , Jallad Bassel 
Published: September 2018

e15716 Abstract Background: Pancreatic adenocarcinoma (PAC) is the fourth leading cause of cancer-related deaths in the United States. Although the vast majority of cases are sporadic, up to 10% of cases are related to a hereditary cancer predisposition syndrome, the most common of which is germline BRCA mutation. Although BRCA2 mutation has been well described in the literature, data on BRCA1 mutation-associated PAC is limited. This work aims at reviewing the literature on BRCA1 mutation-associated PAC and discussing the relevant findings. Methods: We have searched the Pubmed database for articles using the search terms “pancreatic”, “BRCA”, BRCA1”, “adenocarcinoma” or any combination of these keywords. Data about epidemiology, staging, prior history of other tumors, and management were collected. Systematic data extraction and assessments of quality were carried out by two reviewers, and good agreement was found. Results: A total of 13 studies were selected for review and included a total of 149 patients. The prevalence rate of PAC among patients with germline BRCA1 mutations ranged between 0.002% and 0.03%. Moreover, the prevalence of BRCA1 mutations in patients with BRCA-related PAC was found to be between 27% and 30%. Of note, PAC was diagnosed as the first tumor in 74% of patients with BRCA1-related PAC. The most common stage at diagnosis was stage 4 (56%) followed by stage 2 (22%). Conclusions: Germline BRCA1 mutation-associated PAC is an under-recognized entity when compared to BRCA2 mutations. Given the incredibly poor prognosis and the growing interest in targeted therapies, physicians need to be familiar with BRCA1 mutations as a possible etiology of PAC. A significant number of patients with BRCA1 mutation-associated PAC were diagnosed with PAC as the first tumor. Therefore, upper gastrointestinal screening should be considered in patients with germline BRCA1 mutations.
Second-line (SL) chemotherapy containing oxaliplatin (OXA) in metastatic pancreatic cancer (PC): Whom should we trust?
Authors: Caparello Chiara , Vivaldi Caterina , Montagnani Francesco , Musettini Gianna , Pasquini Giulia , Pecora Irene , Catanese Silvia , Lencioni Monica , Falcone Alfredo , Fornaro Lorenzo , Vasile Enrico 
Published: September 2018

e15719 Background: After the intensification of first-line treatment in metastatic PC the number of patients fit and able to receive a SL treatment is increasing; despite these results, the choice of SL chemotherapy remains a challenging issue. The role of OXA in SL setting has given conflicting results in CONKO-003 and PANCREOX trials; the reasons of this inconsistency are difficult to understand. Methods: In order to detect a possible advantage from the use of oxaliplatin in SL, we pooled together the results of randomized phase II/III studies adding OXA to fluoropyrimidines after a gemcitabine-based first-line. Hazard ratios (HRs) for progression-free (PFS) and overall survival (OS) with 95% confidence intervals (CIs) were extracted, while the number of events was used for RR to determine odds ratio (OR) with corresponding 95%CIs. Fixed-effect and random-effect models were used as appropriate, on the basis of the evidence of a non-significant or significant heterogeneity among trials, respectively. The Review Manager software was used (version 5.3). Results: Three studies were identified; main characteristics and results are summarized in the table. No benefit in overall survival derived from the use of OXA (HR 1.03, 95% CI, 0.64-1.67; p=0.90) but significant heterogeneity was reported (p=0.003); the addition of OXA produced a significant benefit in terms of PFS (HR 0.81, 95% CI 0.68-0.97; p=0.02) with a higher chance of response (OR 1.81, 95% CI 1.01-3.24; P=0.05). Interestingly heterogeneity between trials was less evident in PFS and RR than in OS suggesting that this could be a confounding element in the interpretation of data. Conclusions: The reasons of conflicting results concerning the use of oxaliplatin doublets in SL setting are not clear. Given the recent advances in first-line setting, it would be interesting to identify an optimal sequential strategy, hopefully in a personalized approach. [Table: see text]
The neutrophil to lymphocyte ratio as a prognostic factor among a diverse population with advanced pancreatic cancer.
Authors: Shusterman Michael , Jou Erin , Kaubisch Andreas , Chuy Jennifer W. , Rajdev Lakshmi , Tang Justin , Ohri Nitin , Aparo Santiago , Goel Sanjay 
Published: September 2018

e15729 Background: The neutrophil to lymphocyte ratio (NLR), a marker of systemic inflammatory response, has been suggested as a prognostic marker in patients with pancreatic adenocarcinoma (PAC). Black and Hispanic patients have been underrepresented in studies evaluating the significance of NLR in PAC. We investigated the prognostic significance of NLR in patients with advanced PAC treated at the Montefiore-Einstein Center for Cancer Care (MECCC) in the Bronx, NY. Methods: We included patients who were chemotherapy naive and treated for unresectable or metastatic PAC at MECCC between 2006 and 2015. Demographics, clinical characteristics and treatment data were collected. Overall survival was determined by the Kaplan-Meier method and Cox proportional-hazards models were built to assess survival differences adjusting for clinically relevant and statistically significant variables. Results: 201 patients were included in the study. Median age was 65 (range 32, 90). 52% were male. 41 were White (19%), 71 Black (33%), 71 Hispanic (33%), and 33 Other (15.3%). 66 (30.6%) had unresectable disease and 135 (62.5%) metastatic disease. An NLR ≥ 4 was associated with a worse OS compared to an NLR ≤ 4 (median 10 vs. 16.4 months; HR 1.895; 95% CI 1.390, 2.585; P < 0.0001). Predictors of worse OS on univariate analysis were ever smoker status (HR 1.365; P = 0.05), metastatic disease (HR 1.736; P = 0.001), and albumin ≤ 3.5 g/dL (HR 2.558; P< 0.0001). An NLR ≥ 4 on multivariate analysis remained significantly associated with worse OS (HR 1.665; 95% CI 1.188, 2.334; P = 0.003) after adjusting for age, gender, ever smoker status, metastatic disease, and albumin. Conclusions: In a cohort with significant minority patient representation, an NLR ≥ 4 was associated with significantly worse overall survival in patients with advanced pancreatic cancer. An elevated NLR in advanced PAC may be an important independent predictor to risk stratify patients and predict poor OS in future analyses.
Calcium channel blockers use and overall survival in pancreatic cancer patients receiving gemcitabine.
Authors: Kraj Leszek , Śliwczyński Andrzej , Krawczyk-Lipiec Joanna , Woźniak Krzysztof , Waszczuk-Gajda Anna , Rybski Sebastian , Wyrwicz Lucjan 
Published: September 2018

e15756 Background: Preclinical studies have shown that calcium channel blockers (CCB) may potentiate anticancer effect of chemotherapy via intra-cellular drug accumulation. Gemcitabine-based chemotherapy is commonly used in pancreatic cancer (PC) patients. The aim of this study was to determine whether CCB may affect overall survival (OS) in PC patients receiving gemcitabine-based chemotherapy. Methods: The retrospective cohort of PC patients treated with gemcitabine between 2007 and 2016 was identified in the Polish National Health Fund databases. Electronic records of prescriptions were searched to identify in this cohort patients receiving CCB (amlodipine, nitrendipine, felodipine, lacidipine). The primary endpoint was OS and it was determined by Kaplan-Meier methods and compared by the log-rank test. Results: In total 4628 PC patients treated with gemcitabine (median OS 7.7 months; 95% CI: 7.4-7.9) were identified. Among these 380 patients were prescribed any CCB. There was a significant difference (p < 0.001) in median OS between patients prescribed CCB (n = 380; OS 9.3 months; 95% CI: 7.8-11.0) and those who did not (n = 4214; OS 7.6 months; 95% CI: 7.3-7.8) with hazard ratio for death 0.70 (95% CI: 0.62-0.79). Notably, the survival curves tended to flatten in CCB group, with 24% of patients alive at 2 years (95% CI: 20-29%) and 15% alive at 5 years (95% CI: 11-19%), compared with 11% (95% CI: 10-12%) and 4% (95% CI: 4-5%) in controls respectively. Conclusions: The use of CCB in PC patients receiving gemcitabine-based chemotherapy was associated with improved OS. Further validation is needed to evaluate effectiveness of CCB-gemcitabine combinations in the management of PC.
Clinical and pathological features of solid pseudopapillary neoplasm (SPN) of the pancreas: A retrospective review of cases at Mayo Clinic.
Authors: Sanhueza Cristobal T. , Jin Zhaohui , Smyrk Thomas C. , Hartgers Mindy L. , Alberts Steven R. , Mahipal Amit 
Published: September 2018

e15757 Background: SPN is a rare neoplasia of the pancreas, defined by the World Health Organization (WHO) as an epithelial low-grade malignant neoplasm, with a high-grade malignant transformation potential. Literature in this subject is scarce and limited only to small retrospective series. Methods: This is a retrospective study aiming to characterize patients with the diagnosis of SPN at Mayo Clinic between 1992 and 2016. Demographics, clinical and pathological features, recurrence rate and overall survival were recorded. Malignant SPN was defined as per the WHO 2010 classification (Perineural invasion, angioinvasion or deep tissue invasion) and compared to Benign SPN. Results: 44 patients with SPN were identified. 39 patients (88.6%) were female. Median age at diagnosis was 27.5 (Range: 13-64). The most frequent presentation was abdominal pain (52.6%), whereas 36.8% were diagnosed based on incidental imaging findings. Majority (60.4%) of the tumors were located at the pancreatic tail, and 48.5% were solid-cystic lesions. Vascular and lymph node involvement were infrequent. 15 cases (30.23%) were classified as malignant. Tumor size was associated with malignant behavior (Table). Three patients had a metastatic presentation. All but 1 patient were treated with surgery. R1 resection was more frequent in malignant SPN, and 2 patients experienced disease recurrence. Two Stage IV patients were treated with surgery and experienced long term survival, one of them without evidence of disease. There was only 1 death recorded. Conclusions: SNP presents predominantly on young women. The prognosis is excellent even in presence of malignant features, and a complete surgery remains as the main treatment. [Table: see text]
Correlation of early tumor shrinkage (ETS) and depth of response (DoR) with resectability in patients (pts) with unresectable locally advanced pancreatic cancer (LAPC) undergoing primary treatment with FOLFOXIRI.
Authors: Vivaldi Caterina , Catanese Silvia , Fornaro Lorenzo , Cappelli Carla , Caparello Chiara , Musettini Gianna , Pasquini Giulia , Pecora Irene , Lencioni Monica , Vasile Enrico , Falcone Alfredo 
Published: September 2018

e15777 Background: FOLFIRINOX is a reasonable option in LAPC. GONO FOLFOXIRI has been shown to provide similar efficacy in advanced disease. ETS and DoR, emerging as relevant endpoints in colorectal cancer, have been rarely investigated in LAPC. Methods: Unresectable LAPC pts treated with FOLFOXIRI were identified. Computed tomography (CT) scan was performed every 8 weeks; after that, multidisciplinary team assessed resectability. ETS was defined as the reduction of ≥20% of target lesions’ diameters at first evaluation. DoR was the % of maximal tumor shrinkage at the nadir compared to baseline. Primary endpoint was the correlation of ETS and DoR with radical (R0) resection. Secondary endpoints were correlation of ETS and DoR with overall survival (OS) and progression-free survival (PFS). Radiologist was blinded to survival data. Survival curves were estimated using the Kaplan-Meier method. Log-rank and chi-square tests were applied. Results: Sixty pts were included. Median age was 62 years (range: 34-74), tumor location was head in 68% and body-tail in 32%. At a median follow-up of 26.9 months, response rate was 37%, median OS and PFS were 15.7 and 10.3 months, respectively. Thirty patients (50%) underwent R0 surgery after chemotherapy. Two pts died due to early surgical complication and were censored at the date of surgery for survival analyses. Among 55 evaluable pts, ETS was reached in 19 pts and median DoR was -17% (range: -65 to +100). A strong association between ETS (p = 0.0002) and DoR (p < 0.0001) with R0 resection was observed. In the overall population, ETS was significantly associated with better PFS (14.5 vs 9.4 months, p = 0.037), while no difference in OS was shown (p = 0.63). DoR was significantly associated both with PFS (13.6 vs 7.8 months, p = 0.014) and OS (19.8 vs 14.5 months, p = 0.047). Conclusions: FOLFOXIRI may allow achieving resectability in selected pts. ETS and DoR are significantly associated with R0 resection. Maximizing response with active regimens could be an effective strategy in LAPC. Further validation of ETS and DoR as surrogate endpoints in larger prospective series is required.
Second-line treatment in patients with pancreatic ductal adenocarcinoma: A meta-analysis.
Authors: Sonbol Mohamad Bassam , Firwana Belal , Wang Zhen , Ahn Daniel H. , Borad Mitesh J. , Makhoul Issam , Ramanathan Ramesh K. , Bekaii-Saab Tanios S. 
Published: September 2018

e15779 Background: There is paucity of data regarding the best available second-line treatment following progression on gemcitabine-based regimens in metastatic pancreatic ductal adenocarcinoma (PDAC). While a Nanoliposomal formulation of irinotecan (MM398) is considered a standard of care, there is conflicting data relating to the use of oxaliplatin in this setting. We performed a meta-analysis to determine the effectiveness of adding oxaliplatin (OX) or various irinotecan (IRI) formulations to a fluoropyrimidine (FP) as a second-line in PDAC patients. Methods: We searched different databases, including PubMed, Embase and Cochrane, to identify randomized controlled trials comparing FP monotherapy to FP combination therapy that includes either oxaliplatin (FPOX) or various irinotecan formulations (FPIRI) in PDAC patients who progressed after first-line treatment. Secondary analyses were planned to assess the effectiveness of FPOX and FPIRI compared to FP. Outcomes of interest included overall survival (OS) and progression-free survival (PFS). The overall effect was pooled using the DerSimonian and Laird random effects models. Results: Five studies (2 with FPIRI and 3 with FPOX) with 895 patients were identified. Patients randomized to FPIRI/FPOX had a significantly improved PFS (HR = 0.74, CI 0.62 to 0.89) and a trend towards an improved OS compared to FP monotherapy (HR = 0.88, CI 0.65 to 1.19). When comparing FPIRI to FP, there was an improvement in both PFS (HR = 0.64, CI 0.47 to 0.87) and OS (HR = 0.70, CI 0.55 to 0.89) in patients treated with the combination. Conversely, FPOX showed only a modest improvement in PFS (HR = 0.81, CI 0.67, 0.97) with no improvement in OS (HR = 1.03, CI 0.64 to 1.67). Conclusions: Combination chemotherapy with oxaliplatin or various irinotecan formulations seem to improve PFS vs. single agent FP. FPIRI, but not FPOX seem to confer an OS advantage. Oxaliplatin with FP following gemcitabine failure may need further confirmatory studies to establish its role in refractory pancreas cancer.