bluuebunny/crossref_metadata_2025_split huggingface dataset:
Relationship between cholangitis, initial chemotherapy regimen, and overall survival in patients with unresectable pancreatic adenocarcinoma.
Authors: Lumish Melissa , Wang Thomas , Darnell Elijah , Hernandez-Barco Yasmin , Krishnan Kumar 
Published: May 2019

e15788 Background: Chemotherapy remains the primary therapy for patients with unresectable pancreatic adenocarcinoma, though response to therapy is variable. Patients with pancreatic adenocarcinoma frequently develop jaundice and cholangitis and require endoscopic biliary stenting. Here, we investigate the association between cholangitis, initial chemotherapy regimen, and one-year survival in patients with unresectable pancreatic adenocarcinoma. Methods: We conducted a retrospective chart review of all patients who received metal stents for biliary obstruction with pancreatic adenocarcinoma over a five-year period at the Massachusetts General Hospital. Only patients with unresectable cancer were included. We compared the association between survival and cholangitis within four subgroups: no chemotherapy, gemcitabine alone or in combination, FOLFOX combination and FOLFIRINOX. The statistical methods used were the chi-squared test for categorical variables, regular ANOVA for continuous variables, and log-rank (Mantel-Cox) test for survival analysis. Results: In total, we identified 74 patients who did not develop cholangitis and 52 patients who developed at least one episode of cholangitis. Among patients undergoing chemotherapy, cholangitis was associated with decreased survival within each subgroup (p-value = < 0.001). At one year from diagnosis, there was an association between cholangitis and decreased survival among patients receiving chemotherapy, independent of the number of episodes of cholangitis. Among those who were not receiving chemotherapy, cholangitis was not associated with survival outcome (p-value = 0.60). Conclusions: In conclusion, the development of cholangitis in patients receiving chemotherapy for metastatic pancreatic cancer is associated with decreased survival. This association is not affected by the number of episodes of cholangitis or by chemotherapy regimen. These data suggest that the development of cholangitis among patients receiving chemotherapy for pancreatic cancer may be a predictor of poor clinical outcomes. Further studies are needed to understand the impact of the local tumor microbial environment and to determine whether cholangitis is a surrogate for a more aggressive disease phenotype.
Efficacy and tolerability of adjuvant gemcitabine and capecitabine in patients with resected pancreatic cancer in US population: A single network experience.
Authors: Kaur Gurveen , Jahangiri Vida , Park Seon Jo , Wegner Rodney E , Monga Dulabh K. 
Published: May 2019

e15789 Background: Adjuvant chemotherapy with combination of gemcitabine and capecitabine improved overall survival (OS) with an acceptable toxicity profile in the European patient population. However, limited data is available for tolerability and efficacy of the combination regimen in the adjuvant setting in the US population. Herein, we report a single network experience with the combination regimen. Methods: We retrospectively evaluated 45 patients with pancreatic cancer who were treated at our institution from 1/1/2017 – 12/31/2018. Eligible patients were aged 18 years or older and had undergone complete macroscopic resection for ductal adenocarcinoma of the pancreas. These patients received adjuvant combination chemotherapy with gemcitabine (1000 mg/m2) and capecitabine (1660 mg/m2). Electronic medical record was reviewed to collect patient data. Medcalc software was used for statistical analysis including Kaplan Meier analyses. Results: Median age of patients was 64.6 years (range 47-87). Majority of patients had stage II disease (73.5%). Seventy-one percent of patients were able to receive 6 cycles of chemotherapy. Median OS for all patients was 20.2 months (95% CI 11.7-22.7). Median OS for patients who received < 6 vs 6 cycles was 14.9 months (95% CI 6.6-14.9) vs 21.5 months (95% CI 11.9-22.9) (p = 0.21). Median progression free survival (PFS) for all patients was 19.3months (95% CI 13.1-25.7). Median PFS for patients with < 6 vs 6 cycles was 7.3 months versus 22.2 months (p = 0.0002). Overall, 31.1% of patients developed disease progression. Of note, 33.3% and 71.1% of patients required dose reductions for gemcitabine and capecitabine respectively. Fifteen grade 3-4 adverse events were reported of which 11 were hematologic and 4 non-hematologic. Conclusions: This single institution analysis shows a trend in improvement for PFS for patients able to complete adjuvant therapy with gemcitabine and capecitabine following pancreatic resection. It is worth noting, however, that dose reductions were required in the majority of patients. Therefore, we propose investigating a modified regimen of gemcitabine and capecitabine in the US population.
Influence of post-resection time to chemotherapy in pancreatic adenocarcinoma on overall survival.
Authors: Abel Stephen , White Richard , Schiffman Suzanne , Williams Kenneth , Thakkar Shyam , Monga Dulabh K. , Finley Gene Grant , Islam Mohammed , Kirichenko Alexander V. , Wegner Rodney E 
Published: May 2019

e15791 Background: Pancreatic adenocarcinoma is an aggressive malignancy with a high propensity for distant spread. To date, surgery remains the only potentially curative treatment option; which has traditionally been followed by adjuvant chemotherapy. Past research from the pancreatic literature as well as other disease sites has shown conflicting outcomes as it relates to timely delivery of adjuvant chemotherapy. We thus used the National Cancer Database (NCDB) to evaluate time to initiation of chemotherapy following pancreatic resection and if there was any correlate with outcome. Methods: We identified patients diagnosed with stage 1-3 pancreatic adenocarcinoma in the NCDB, excluding those with stage IV disease, those treated nonoperatively, with adjuvant or neoadjuvant chemotherapy or radiotherapy and those with unknown or inadequate ( < 3 months) follow-up. Receiver operator curve analysis identified an interval of 66 days as associated with outcome. Multivariable logistic regression analysis identified variables associated with increased time to chemotherapy postoperatively ( > 66 days). Propensity matching was done to account for indication bias. Overall survival (OS) was compared between both propensity-matched groups receiving earlier and postponed chemotherapy post-resection, with an additional breakdown by stage. Results: In total, 6,873 and 3,348 patients received chemotherapy before and after the 66 day cutoff, respectively. Predictors of expedited chemotherapy included lower comorbidity, treatment outside a community program in an urban location, having insurance, Caucasian race and treatment after 2009. Median overall survival was 21.8 months for all patients and of these, 6462 were stage 1. 5-year OS was 20% in patients receiving chemotherapy within 66 days and 18% in those not (p = 0.0266). In stage 1 patients, 5-year OS was 23% versus 21% (p = 0.0116) in favor of expedited chemotherapy. In stage 2 patients, 5-year OS was 16% in both arms (p = 0.7231). Higher stage and comorbidity score, treatment at a community cancer program, lower salary, increased time from surgical resection to chemotherapy, higher grade, positive margins, and more distant year of treatment were associated with worse prognosis. Conclusions: The present propensity-matched analysis showed a significant benefit to earlier delivery of chemotherapy in the adjuvant setting, with the largest benefit seen in stage 1 patients.
Hospitalization cost and length of stay in pancreatic cancer population: A national inpatient database study.
Authors: Enofe Ikponmwosa , Rai Manoj P. , Nemakayala Divyesh Reddy , Tatineni Shilpa , Aluko Atinuke , Bedi Prabhjot Singh , Yam Julie , Khan Nazia Naz S , Laird-Fick Heather 
Published: May 2019

e15793 Background: Pancreatic cancer accounts for 7% of all cancer deaths in the U.S. It contributes to burgeoning health care cost and is associated with poor prognosis. The aim of this study was to describe the disease burden, pattern of resource utilization, hospital cost and outcomes among hospitalized pancreatic cancer patients based on the location of disease. Methods: We conducted a retrospective study utilizing the 2014 national inpatient sample database. Adult records with a primary discharge diagnosis of pancreatic cancer were included. Records with no specification on cancer location were excluded. Regression models (logistic and linear) were used to estimate adjusted odds ratios (OR), mean length of stay (LOS) and hospital charges (HC). Covariates included sociodemographic factors, co-morbidities and therapeutic surgical procedures received during hospitalization. Results: A total of 4,799 discharge records met the inclusion criteria. Overall, 74.3% had cancer in the pancreatic head and 25.6% had cancer in the body and tail. Pancreatic head cancers were more common in whites (73%). Patients with cancer in the body and tail more commonly experienced metastasis than patients with pancreatic head cancer (23.8% versus 20.4% p = 0.02). Compared to pancreatic head cancers, patients with body and tail cancers were more likely to have a pancreatectomy during index hospitalization (OR 45, 95% CI 27.8 - 65.2). Alternatively, cancers of the pancreatic head were more likely to have an endoscopic pancreatic procedure during index hospitalization compared to body and tail (OR 7.39, 95% CI 3.9 -13.9). Pancreatic head cancers were associated with a significantly longer mean hospital LOS (8.1 versus 6.4 days, mean difference 1.66, p < 0.001) and higher mean cost of hospitalization (Mean HC $85,263.40 versus $56,156.60 p < 0.001) compared to cancer in the body and tail. Conclusions: Despite lower rate of metastasis and pancreatectomy, patients hospitalized for pancreatic head cancers have longer hospital LOS and higher healthcare cost burden. Our findings may inform physicians, patients, and policymakers and may help channel resources toward specific patient population to reduce healthcare cost and improve outcomes for individuals and healthcare organizations.
Impact of no treatment vs other nonsurgical treatments in Pancreatic Adenocarcinoma National Cancer Database: 2004-2014.
Authors: Saha Sukamal , Elgamal Mohamed , Cherry Meghan , Buttar Robin , Devisetty Kiran , Gayar Hesham , Wiese David , Grewal Sandeep Singh , Eilender David S. , Arora Madan L. 
Published: May 2019

e15795 Background: Surgery remains the only curative treatment option in pancreatic adenocarcinoma, yet in more than 50% of the patients (pts) the disease is too advanced or at very high risk and considered inoperable. They are either managed with no treatment or other nonsurgical methods. Hence, we analyzed a large cohort of pancreatic adenocarcinoma pts undergoing No Treatment vs Chemotherapy, Radiation or Chemoradiation to determine their impact on survival. Methods: Only pancreatic adenocarcinoma pts who had no surgery in the National Cancer Database (NCDB) from 2004–2014 were included. Of that group, patients with unknown or missing data about chemotherapy or radiation treatment or less than 3 years of survival data were excluded. Pts were stratified into 4 groups: Chemotherapy, Radiation Therapy, Chemoradiation and No Treatment. Overall 1-, 2- and 3-year survival was calculated and the groups were compared using Pearson’s chi-squared. Results: Of the total 309,709 pancreatic cancer pts in the NCDB 2004–2014, 111,421 (36.0%) remained after application of the study criteria. Of these, 43,203 (38.8%) received chemotherapy only, 2,453 (2.2%) received radiation only, 15,764 (14.1%) received chemoradiation and 50,001 (40.0%) had no treatment. Overall survival for 1, 2, and 3 years was best in the chemoradiation group with a 1 year survival of (40.0%) compared to chemotherapy only (22.4%), radiation only (14.9%) and no treatment (9.6%). Overall, only (19.0%) of pts survived for 1 year, (5.4%) survived for 2 years and (2.3%) survived for 3 years. (Table) Conclusions: Survival in pancreatic adenocarcinoma pts remains dismal without surgery. Best survival in nonsurgical pts was seen after combination Chemoradiation therapy and worst survival in No Treatment group. Hence, whenever possible, a combination Chemoradiation should be offered even as palliation in non-surgical pancreatic adenocarcinoma pts.[Table: see text]
Role of OncoTherad immunotherapy in the regulation of toll-like receptors-mediated immune system and RANK/RANKL signaling: New therapeutic perspective for non-muscle invasive bladder cancer.
Authors: Fávaro Wagner José , Iantas Sonia Regina , Gonçalves Juliana Mattoso , Dias Queila Cristina , Reis Ianny Brum , Billis Athanase , Duran Nelson , Alonso João Carlos Cardoso 
Published: May 2019

e16004 Background: The new modalities for treating patients with non-muscle invasive bladder cancer (NMIBC) for whom Bacillus Calmette-Guerin (BCG) has failed or is contraindicated are recently increasing due to the development of new drugs. In this scenario, a new perspective is represented by OncoTherad immunomodulator. OncoTherad is a nanostructured inorganic phosphate complex associated to glycosidic protein, developed by University of Campinas/ Brazil, which exhibits antitumor properties. This study detailed and characterized the therapeutic effects of OncoTherad based on activation of Toll-Like Receptors (TLRs) signaling pathways and regulation of receptor activator of nuclear factor kβ (RANK)/RANK ligand (RANKL) cytokine system in an animal model of NMIBC, as well as, compared these effects with BCG treatment. Methods: Fisher 344 female rats were submitted to NMIBC induction with N-methyl-N-nitrosourea (MNU). MNU treated animals were further divided into 3 groups (10 animals per group): the NMIBC group received 0.30 mL of saline solution; the NMIBC-BCG group received of 2 mg/mL of BCG; the NMIBC-OncoTherad group received 20 mg/Kg dose of OncoTherad. All animals were treated intravesically every other week for 6 weeks. Results: Our results demonstrated that OncoTherad intravesical immunotherapy led to distinct activation of TLRs 2 and 4-mediated innate immune system, resulting in increased interferons signaling pathway, which was more effective (80.0%) in the NMIBC treatment, when compared to BCG treatment (20.0%). Interferon signaling pathway activation induced by OncoTherad led to increase of iNOS expression, resulting in apoptosis and histopathological recovery. Also, OncoTherad immunotherapy decreased RANK/RANKL expression, resulting in reduced regulatory T (Treg) cells. Conclusions: The decreased of RANK/RANKL expression by OncoTherad was fundamental to up-regulation interferon signaling pathway and in suppresion of abnormal cell proliferation. Thus, OncoTherad immunotherapy could be considered an important therapeutic strategy for NMIBC, as well as, opens a new perspective for treatment of BCG-refractory or relapsed patients.
Single cell analysis of urothelial carcinoma (UC) liver metastases identifies epithelial-mesenchymal transition (EMT) as a potential mechanism of resistance to immunotherapy.
Authors: Lattanzi Michael , Tredwin Lily M. , Deng Fang-Ming , Chiriboga Luis , Zeck Briana , Forcato Claudio , Serrano Jonathan , Mohamed Hussein , Snuderl Matija , Balar Arjun Vasant 
Published: May 2019

e16018 Background: UC liver metastases are associated with a low response rate to immune checkpoint blockade (ICB) and short survival. We sought to identify tumor specific factors promoting resistance to ICB. Methods: DEPArray is a dielectrophoresis based cell sorting platform for isolating immunohistochemically-defined cell populations from formalin-fixed paraffin-embedded (FFPE) tissue. Available FFPE tissue blocks of mUC liver metastases from patients (pts) treated with ICB were selected for analysis. Following histologic evaluation, tissue blocks were digested to yield cellular suspensions for immunophenotypic DEPArray sorting by keratin (K) and vimentin (V) to identify carcinoma cells and stromal cells, respectively. Cell pools were further analyzed for recurrent mutations and copy number alterations by a targeted OncoSeek panel and by MiSeq. Results: 12 unique patient samples were profiled. Median age was 73 (range 65-89), 11/12 male, 7 (58%) were platinum-refractory, and 4 (33%) received only ICB. 7 (58%) biopsies were obtained prior to initiation of ICB (1PR, 1SD, 5PD). Routine H&E sections generally revealed tumors completely devoid of immune cells, but admixed with atypical mesenchymal cells ranging from 5% to 60% of cellular composition. DEPArray sorting by K and V identified three discrete cell populations: K+/V- carcinoma cells, K-/V+ stromal cells, and K+/V+ cells that exhibited mesenchymal morphology. Of 8 samples with adequate cell counts (range 75-154 cells), next-generation sequencing (NGS) identified that K+/V- carcinoma cells and K+/V+ double positive cells shared unique somatic alterations in 7 (88%) pts, including point mutations in FGFR3, ERBB2, FBXW7, PIK3CA, FLT3 and STK11, and amplification of CDK4. In one liver responder to ICB, V+ stromal cells carried a putative germline TP53 R248W mutation. Conclusions: Archival FFPE tissue from mUC liver metastases can be digitally sorted by DEPArray to yield pools of ~100 cells suitable for NGS. UC liver metastases exhibit a population of K+/V+ cells with clonal somatic alterations suggestive of an EMT cancer cell phenotype that may be playing a role in ICB resistance.
Programmed death-ligand 1 (PD-L1) expression in small cell carcinoma of bladder.
Authors: Sanguino Angela , Samiei Arash , Pasricha Gurleen , Harinath Lakshmi , Miller Ralph , Lyne John , Silverman Jan F , Mao Shifeng 
Published: May 2019

e16019 Background: Small cell carcinoma of bladder (SCCB) is a rare but aggressive variant of bladder neoplasm. There is limited insight for risk prognostication and treatment guidance in this entity. Immune checkpoint inhibitors (ICI), anti-PD-1 or anti-PD-L1 antibodies, have been approved for treating urothelial carcinoma, while the evidence of their efficacy in SCCB is lacking. PD-L1 expression in tumor tissue of urothelial cancer has been postulated to correlate with response to ICI but with controversy. We have studied the expression of PD-L1 in SCCB and its association with patient survival. Methods: Nineteen cases of SCCB diagnosed between 2011 and 2017 in a single center were identified. Formalin-fixed paraffin-embedded tumor samples were stained for PD-L1 (Ventana PD-L1 SP142). Cases showing positive stain in 5% or more of tumor cells and tumor stromal mononuclear cells (TSMC) were considered positive. Results: Among 19 cases of SCCB, 4 (21%) stained positive for PD-L1. All 4 cases had strong PD-L1 staining ( > 30%) seen in the TSMC but barely in tumor cells (focal < 5% cells in 2/4 cases). Except for one patient who died from surgery, all remaining 3 patients with positive PD-L1 staining are still alive. Twelve out of 19 SCCB patients developed metastatic disease; 4 of them were treated with ICI. The only responder of the 4 patients had strong PD-L1 expression in TSMC cells. The overall survival for patients with positive PD-L1 staining was 41 months versus 14 months for those with negative staining (p = 0.09). Age, pathologic stage and treatments were similar between the two groups. Conclusions: In our study, PD-L1 expression was seen in 21% of tumor samples from patients with SCCB, mostly in TSMC, but minimal in tumor cells. The strong expression of PD-L1 in TSMC correlates with a trend of improved survival and potential response to ICI in SCCB. PD-L1 expression in TSMC, rather than tumor cells, could be used as a marker for prognosis in SCCB.
Comparing costs of radical cystectomy versus trimodal therapy for patients diagnosed with localized muscle-invasive bladder cancer.
Authors: Phillips Daniel , Dafashy Tamer , Shan Yong , Ray-Zack Mohamed Danny , Hudgins Hogan K , Jazzar Usama , Tyler Douglas S. , Freedland Stephen J. , Swanson Todd A. , Baillargeon Jacques G. , Hu Jim C. , Kaul Sapna , Kamat Ashish M. , Gore John L. , Mehta Hemalkumar B , Williams Stephen Bentley 
Published: May 2019

e16021 Background: Earlier studies on the cost of muscle-invasive bladder cancer treatments lack granularity and are limited to 180 days. The objective of this study is to compare the one-year costs associated with trimodal therapy versus radical cystectomy, accounting for survival and intensity effects on total costs. Methods: This cohort study used the Surveillance, Epidemiology, and End Results (SEER)-Medicare database. Data analysis was performed from March 5, 2018 through December 4, 2018. A total of 2,963 patients aged 66-85 years diagnosed with clinical stage T2-4a muscle-invasive bladder cancer from January 1, 2002 through December 31, 2011. Total Medicare costs within one year of diagnosis following radical cystectomy versus trimodal therapy were compared using inverse probability of treatment-weighted (IPTW) propensity score models, which included a two-part estimator to account for intrinsic selection bias. Results: Median costs were significantly higher for trimodal therapy than radical cystectomy in 90 days ($83,754 vs. $68,692; median difference $11,805, 95% CI $7,745 to $15,864), 180 days ($187,162 vs. $109,078; median difference $62,370, 95% CI $55,581 to $69,160), and 365 days ($289,142 vs. $148,757; median difference $109,027, 95% CI $98,692 to $119,363), respectively. Outpatient care, radiology, medication expenses and pathology/laboratory costs contributed largely to the higher costs associated with trimodal therapy. On IPTW-adjusted analyses, patients undergoing trimodal therapy had $129,854 (95% CI $115,793-$145,299) higher costs compared with radical cystectomy one year after diagnosis. Conclusions: Compared to radical cystectomy, trimodal therapy was associated with higher costs among patients with muscle-invasive bladder cancer. Extrapolating cost figures resulted in nationwide excess spending of $444 million for trimodal therapy compared with radical cystectomy for patients diagnosed in 2017.