bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evolution of clinical outcomes of metastatic pancreatic adenocarcinoma: A 10-year single-institution retrospective study.
Authors: Ellithi Moataz , Abdallah Mohamed A. , Shahid Mahum , Ailts Isaak , Waligoske Kate , Fanta John , Bell Matthew , Fischer McKenna , Nelson Morgan , Bleeker Jonathan 
Published: May 2020

e16760 Background: Pancreatic adenocarcinoma represents the fourth leading cause of cancer-related death in the United States. A majority of patients have locally advanced or metastatic disease at the time of diagnosis. For many years, gemcitabine monotherapy was the standard of care for advanced disease, until recent studies demonstrated survival benefits for FOLFIRINOX (5-FU, leucovorin, irinotecan, and oxaliplatin) and Gem/nab-P (gemcitabine/nab-paclitaxel). In this study, we evaluated the clinical outcomes in patients with metastatic pancreatic adenocarcinoma in a single health system before and after the incorporation of these newer treatments into practice. Methods: A retrospective study of metastatic pancreatic adenocarcinoma patients diagnosed between January 2009 to December 2018 with follow up until December 2019. Overall survival (OS) and progression-free survival (PFS) were calculated using Kaplan-Meier survival analysis. Univariate and multivariable Cox regression analyses were used to explore predictors of survival. Results: 394 patients were diagnosed with metastatic pancreatic adenocarcinoma at Sanford Health hospitals during the study period. There was no statistically significant difference in OS between the cohort diagnosed between 2009-2013 compared to 2014-2018, with median OS of 4.7 and 3.6 months respectively; in those receiving at least one line of chemotherapy, the median OS was 6.7 and 7.3 months. While subgroup analysis of all study population based on the type of first-line chemotherapy showed improved survival with FOLFIRINOX and Gem/nabP as compared to gemcitabine monotherapy [10.7, 6.9, 4 months respectively] (Wilcoxon Test of Homogeneity of Survival Curves p = 0.0002). Univariate and multivariate Cox regression analysis of all study data revealed that at the time of the diagnosis, age (HR: 1.021, p = 0.0013), ECOG performance status > 1 (HR: 3.47, p = 0.0001), serum albumin (HR: 0.708, p = 0.0002), Neutrophil-to-Lymphocytes ratio (HR: 1.076, p≤0.0001) and platelets-to-lymphocyte ratio (HR: 0.998, p = 0.0031) were predictors of survival. Conclusions: Although newer treatments appear to offer improved survival for eligible patients, overall outcomes for metastatic pancreatic adenocarcinoma in this cohort were similar before and after the incorporation of newer treatment regimens. Further advances in the treatment and early detection of pancreatic cancer are needed to improve clinical outcomes.
Molecular validation of the 8th edition AJCC cancer staging system in patients with resected pancreatic cancer: Proposal of integrative translational staging system.
Authors: Lee Sung Hwan , Lee Sunyoung S. , Lee Ju-Seog 
Published: May 2020

e16765 Background: Even though the 8th edition AJCC cancer staging system for pancreatic cancer has validated with major clinicopathologic factors in multiple clinical cohorts, there is still an unmet need for integrative consideration using multi-omics data to stratify the patients with pancreatic cancer elaborately. Methods: We performed a comprehensive analysis and profiling using genomic, transcriptomic, and proteomic data from TCGA-PAAD and other translational cohorts (4 cohorts, n = 340). Molecular features and major subtypes were analyzed mutually with clinical and pathologic factors, especially the 8th AJCC staging system. Results: Aggressive molecular subtypes, basal-like and squamous subtype, were significantly associated with a higher nodal stage, but tumor size didn't show a clear association with molecular features. The activated stroma of pancreatic cancer microenvironment was significantly correlated with poor differentiation and large tumor size. The mutational pattern of KRAS and several transcriptomic pathways such as eptihelial-mesenchymal transition and DNA repair were differently presented in each clinical stage from the 8th AJCC TNM staging system. The optimal algorithm was identified to show significantly higher performance for the prediction for cancer relapse and cancer-specific survival in discovery and validation cohorts. The in silico prediction for molecular target agents and immunotherapy were performed for final clusters from optimal stratification system revealed from the integrative analysis. Conclusions: Our comprehensive multi-omics analysis reveals clear needs for the combination of clinical staging and molecular profiling and provides crucial evidence for precision strategy in patients with resectable pancreatic cancer.
Racial disparities in pancreatic resection and survival among elderly patients: A SEER database analysis.
Authors: Park Seojin , Waters Dexter , Walsh Karen , Handley Nathan , Lavu Harish 
Published: May 2020

e16784 Background: For localized pancreatic cancer treatment, surgical resection is the only potentially curative option. Currently, little is known about whether racial disparities exist in elderly patients’ access to resection and outcomes after resection. This study aims to understand the relationship between race/ethnicity and both resection rate and survival after surgery in elderly patients. Methods: The analysis included patients aged ≥65 years diagnosed with locoregional resectable (stage I and II according to the 6th AJCC TNM staging system) pancreatic cancer between 2007 and 2016 in the Surveillance, Epidemiology, and End Results database. Patients without complete surgical or survival data were excluded from the analysis. Multiple logistic regression was used to assess the association between race/ethnicity and receipt of resection. The effect of resection on 6-month and 5-year overall survival (OS) was evaluated using multivariate Cox proportional hazards regression, controlling for other clinical and demographic factors, such as sex, age, martial status, residence region, tumor location, tumor size, and year of diagnosis. Results: Of 12,829 patients, 4,310 (46.0%) received resection and 5,062 (54.0%) did not. Median follow-up among resected patients was 16 months (1-60 months), and 6-month and 5-year OS was 62.83% and 4.54%, respectively. The majority of the patients were white (73.1%), followed by Hispanic (9.3%), black (9.1%), and other (American Indian, Asian/Pacific Islander) (8.6%). Black (OR 0.69; 95%CI 0.60-0.80) and Hispanic patients (OR 0.78; 95%CI 0.68-0.90) were less likely to receive resection compared to white patients. While Hispanic patients had worse 6-month OS compared to white patients (HR 1.43; 95%CI 1.19-1.72), 5-year OS was not significantly different across the racial/ethnic groups. Other factors significantly worsened 5-year OS were being age 75 years or older, living in South region, and having tumor size greater than 50mm. Conclusions: Our findings support that racial disparities exist in resection rate in elderly populations. However, no racial difference was seen in the long-term survival after pancreatic resection. This may suggest that improving the access to resection for minorities with pancreatic cancer may improve their health outcomes. [Table: see text]
Combined recombinant humanized anti-PD-1 monoclonal antibody (JS001) and nab-paclitaxel/gemcitabine (AG) as the first-line therapy for patients with advanced pancreatic adenocarcinoma: Preliminary results of an open-label, phase Ib/II clinical study.
Authors: Cheng Ke , Li Zhiping , Cao Dan 
Published: May 2020

e16792 Background: To determine evaluate the safety and efficacy of nab-paclitaxe, gemcitabine (AG) and Recombinant Humanized Anti-PD-1 Monoclonal Antibody (JS001) for patients with advanced pancreatic ductal adenocarcinoma (PDAC). Methods: This was a single-arm, open-label, phase 1b/2 clinical trial of nab-paclitaxel plus gemcitabine plus Anti-PD-1 Monoclonal Antibody in which 11 patients with previously untreated advanced PDAC were enrolled from December 2018. Patients were treated with nab-paclitaxel 125 mg/m2 on days 1 and 8 plus gemcitabine 1000 mg/m2 on days 1 and 8 plus fixed dose of JS001 240mg on day 1 of a 21-day cycle until progression or toxicity or receiving maintance therapy. Safety monitoring, RECIST 1.1, and irRECIST assessments were conducted. Results: 11 chemotherapy naïve PDAC patients with a median age of 52 years old were treated. 5 were men and all patients had an ECOG of 0 or 1. Grade 3/4 events were observed in 27.3% of patients (2 patients presented hematological toxicity ), and JS001 was discontinued because of asymptomatic elevated cardiac biomarkers and hypothyroidism as immunotherapy-related toxicities in a female patient, no patient was discontinued AG therapy because of chemotherapy-related adverse events. Of the 11 evaluable patients, the disease control rate (partial response [PR] + stable disease[SD]) was 81.8%. There were 2 patients with PR and 1 patient with complete response respectively, and overall response rate (ORR) was 27.3%. The median progression-free survival (PFS) was 7 months and all patients survive at the last following-up in Jan-2020. All patients were proficient mismatch repair (pMMR) status. Whole-exome sequencing was performed on 7 patients, no immunotherapy-associated gene was detected, and next comprehensive analysis of somatic alterations was ongoing. Conclusions: Combined JS001 and AG can be safely given to chemotherapy naïve PDAC patients. Efficacy appears to be promising over previously reported results for standard AG chemotherapy every 28 days gemcitabine and nab-paclitaxel dosing. Comprehensive data available was ongoing to analysis the potential effect to efficacy of the combination.
Impact of surveillance among patients with resected pancreatic cancer following adjuvant chemotherapy.
Authors: Wong Selina , Gondara Lovedeep , Renouf Daniel John , Lim Howard John , Gill Sharlene 
Published: May 2020

e16795 Background: Pancreatic adenocarcinoma carries a poor prognosis and high risk of recurrence even after surgery and adjuvant chemotherapy (AC). Guidelines recommend against routine surveillance imaging due to lack of evidence supporting a survival benefit. With current first-line chemotherapy options, it is unclear whether surveillance scans allow for early detection of asymptomatic disease and therefore an opportunity to offer fit patients chemotherapy. We describe the patterns of surveillance in patients followed at a Canadian provincial cancer agency and determine whether routine imaging after AC is associated with receipt of palliative chemotherapy (PC). Methods: A retrospective review was completed to identify patients treated at British Columbia (BC) Cancer centres between January 1, 2010 and December 31, 2016 who had undergone curative intent resection and received at least one cycle of AC. Baseline characteristics, number of scans done after completing AC to recurrence, and PC were collected. Logistic regression analysis was performed. Results: A total of 151 patients followed at BC Cancer were identified. Patients who recurred within 28 days after AC were excluded, leaving 142 patients, of which 115 patients had recurrence (81%). We defined 2 cohorts based on number of scans done between completion of AC and recurrence: those with 0-1 scans were “symptomatic” recurrences (22 patients, median age 68y, 64% female, and 91% node-positive) and those with > 1 scan were “surveillance” recurrences (93 patients, median age 64y, 43% female, and 81% node-positive). Patients who underwent surveillance scans were more likely to receive PC at time of recurrence, though statistical significance was not reached (OR 2.11, 95% CI 0.75-6.58, p = 0.17). Conclusions: Despite guidelines, the majority of patients treated in BC underwent surveillance imaging. Within the limits of our sample size, we demonstrated a trend towards increased likelihood of receiving PC in patients who receive surveillance scans following AC. With efficacious PC options available, studies to determine whether receipt of PC in asymptomatic recurrences detected on imaging translates into improved survival and/or quality of life are warranted.
Skeletal muscle index and adverse events during a bladder cancer treatment episode.
Authors: Ngo Steven , Diamantopoulos Leonidas Nikolaos , Maldonado Reno , O'Malley Ryan Blair , Laidlaw Grace , Fintelmann Florian J. , Holt Sarah K , Gore John L. , Schade George R. , Lin Daniel W. , Grivas Petros , Montgomery Robert B. , Hsieh Andrew Caleb , Cheng Heather H. , Yezefski Todd , Schweizer Michael Thomas , Yu Evan Y. , Wright Jonathan L. , Psutka Sarah P. 
Published: May 2020

e17016 Background: While sarcopenia is associated with increased mortality in bladder cancer, there is limited data in patients treated with neoadjuvant chemotherapy (NAC) that associates skeletal muscle index (SMI) and adverse treatment-associated outcomes. Herein, we evaluate associations between baseline SMI and severe adverse events (SAEs) during NAC and post-radical cystectomy (RC) 90-day Clavien ≥3 complications. Methods: SMI (cross sectional area of skeletal muscle, cm2 / height2, m2) was measured on an axial computed tomography (CT) image at the level of the third lumbar vertebral body, within 60 days prior to NAC and RC. Patients were classified as being sarcopenic, according to sex-specific consensus definitions: Male: SMI < 55, Female: SMI < 39. Associations with SAEs during NAC and 90-day Clavien grade 3-5 complications were assessed with multivariable logistic regression. Results: CT scans of sufficient quality (2005-18) were available for 143 patients. There were no significant differences in clinicopathologic characteristics between the study cohort and patients without available imaging (N = 261). Median SMI for men and women was 52.1 and 40.9 cm2/m2; 86 (60%) were sarcopenic. SAEs were observed in 92 patients (64%), resulting in hospitalization during NAC in 27 (19%), while 20 (14%) patients did not complete planned NAC due to SAEs. After adjusting for age, performance status, and clinical stage, SMI was not independently associated with NAC-associated SAEs. Postoperative complications occurred in 82 (57%) patients, including infectious complications (39; 27%), wound dehiscence (8; 6%), 90-day readmission (27; 19%). Wound healing complications including dehiscence, clinically significant hernia, urine leaks, or fistulae occurred in 33 (23%). While SMI was not independently associated with risk of complications overall (OR: 1.00, 95% CI: 0.96 - 1.03), it was associated with infectious complications (OR: 0.96, 95% CI: 0.92 - 0.99, p = 0.02), and wound dehiscence (OR: 0.93, 95% CI: 0.86 - 0.99, p = 0.02) with a trend towards significance for associations with any wound-healing complications (OR: 0.96, 95% CI: 0.91 - 1.00, p = 0.08). Conclusions: In the largest reported series of post-NAC patients with RC and detailed follow-up, pretreatment SMI was not associated with SAEs during NAC but was associated with serious infectious complications and wound dehiscence after RC. This data highlights the potential value in measuring SMI to identify patients at risk for select SAEs. Future studies should assess the benefit of prehabilitation before and during NAC.
Predicting residual tumor for T1 high-grade bladder urothelial carcinoma before second transurethral resection specimens.
Authors: Takeuchi Ario , Shiota Masaki , Inokuchi Junichi , Eto Masatoshi 
Published: May 2020

e17018 Background: Second transurethral resection (TUR), which is now recommended for all T1 high-grade bladder urothelial carcinoma, may not be necessary for patients with minimal tumor burden at the first TUR. T1 microstaging by the recognition of the muscularis mucosae or vascular plexus may be one promising method for evaluating tumor burden, but is sometimes technically difficult to assess. The number of TUR chips with tumor invading into lamina propria (T1chips) is easy to assess and can be available for all patients with T1 bladder urothelial carcinoma. Our aim was to determine clinicopathological factors which can predict the existence of residual tumor on the second TUR specimens for T1 high-grade bladder urothelial carcinoma. Methods: A total of 50 patients were diagnosed with T1 high-grade bladder urothelial carcinoma after the first TUR. We performed second TUR for the 50 patients. The median interval from the first and the second TUR was 6 week (range, 2-10). Voided urine cytology was taken in all patients between the first and the second TUR, at least 1 week after the first TUR. The existence of proper muscle tissue was confirmed in all specimens for the first and the second TUR. Tumor size, the number of tumor, the presence of carcinoma in situ (CIS), the number of TUR chips containing lamina propria invasion (T1chips) were recorded for the first TUR specimens. Results: A total of 20 (40%) patients had residual tumor on the second TUR. The second TUR stage was: T0 30 (60%); Ta/is 7 (14%); T1 9 (18%); and T2 4 (8%), respectively. In univariate analysis, positive urine cytology before the first TUR (48% vs 0% in negative), positive urine cytology between the first and second TUR (76% vs 21% in negative), and multiple T1 chips on the first TUR specimens (58% vs 6% in one T1 chip) were associated with residual tumor on the second TUR. In addition, in multivariate analysis, the number of T1 chips on the first TUR and urine cytology between the first and the second TUR were the significant predictors for residual tumor on the second TUR. Of 15 patients with multiple T1 chips and positive urine cytology between the first and the second TUR, 13 (87%) had residual tumor on the second TUR, compared to 0% (0/15) in those with one T1 chip and negative urine cytology between the first and the second TUR. Conclusions: Second TUR may not be necessary for all patients with T1 high-grade bladder urothelial carcinoma. The number of T1 chips on the first TUR and urine cytology between the first and the second TUR are useful factors for predicting second TUR stage.
MSK-ACCESS for the detection of fibroblast growth factor receptor-3 (FGFR3) mutations in plasma cell-free (cf)DNA of metastatic urothelial carcinoma (mUC) patients (pts) pre- and on erdafitinib (erda) therapy.
Authors: Sarfaty Michal , Teo Min Yuen , Funt Samuel Aaron , Lee Chung-Han , Aggen David Henry , Ratna Neha , Regazzi Ashley Marie , Al-Ahmadie Hikmat , Brannon Angela Rose , Berger Michael F. , Solit David B. , Rosenberg Jonathan E. , Bajorin Dean F. , Iyer Gopa 
Published: May 2020

e17034 Background: The pan-FGFR inhibitor erda was recently FDA-approved for pretreated mUC pts harboring FGFR2/3 alterations. We explored concordance of FGFR3 mutation profiles between the primary tumor and cfDNA using the MSK-ACCESS platform. We also correlated changes in FGFR3 cfDNA mutant allele fraction (MAF) with response to drug. Methods: Plasma samples were collected from mUC pts started on erda at baseline, on treatment (tx), and at progression. Demographic and clinical characteristics were obtained. Baseline tumors were sequenced with MSK-IMPACT (ref) and plasma samples were sequenced using MSK-ACCESS, a cfDNA platform that sequences 129 genes using unique molecular indexes to generate > 15,000x coverage and detection of somatic mutations down to 0.1% MAF. Results: Between 08/2019-1/2020, 11 pts received erda 8mg daily. Of these, 3 pts increased dose to 9mg daily based on phosphorus level, 4 required dose reductions and 6 dose interruptions. In 5 pts, erda was discontinued for disease progression. FGFR3 S249C was the most frequent alteration detected (64%) followed by Y373C (18%), R248C and S371C (both 9%). Pre-treatment plasma FGFR3 profiles were concordant with tissue in 91% (10/11) of pts and additional FGFR3 mutations were detected in 3 cases (27%, Table), including 1 pt with an FGFR3-TACC3 fusion and hotspot mutations only in cfDNA. In 2 responding pts, the mutant allele was undetectable on erda. Conclusions: A high degree of concordance between primary tumor and cfDNA FGFR3 mutation detection was observed. FGFR3 mutations exclusive to cfDNA were found in a subset of pts. Further pt accrual and follow-up are ongoing to assess for correlations between erda response and tx-related changes in cfDNA MAF, and to assess whether cfDNA can identify resistance mechanisms. [Table: see text]
Phase Ib study: APL-1202 (APL) in combination with Bacillus Calmette-Guerin (BCG) in recurrent non-muscle invasive bladder cancer (NMIBC).
Authors: Sfakianos John , Shore Neal D. , Zhuang John 
Published: May 2020

e17039 Background: APL is a selective human methionine aminopeptidases II (MetAP2) inhibitor. In preclinical studies, APL has demonstrated both anti-angiogenic and anti-tumor activities as well as a potential synergistic effect with BCG or PD-1. A. This phase 1b study assesses the tolerability and pharmacokinetics (PK) characteristics of oral APL and intravesical BCG combination in HR NMIBC pts. Methods: Pts who had received a prior induction course of BCG within 12 weeks (wks) of enrollment and were scheduled to receive either maintenance or another induction course of BCG were given 750 mg/day APL (2x125 mg tablet, TID) for 12 wks. The tolerability and PK of APL was evaluated one wk prior to first BCG instillation and during combination use with BCG. AEs were evaluated to assess safety and tolerability. Wilcoxon matched-pair signed-rank test was used for PK analysis. Results: Six pts (4M, 2F) with a median age of 72.5 yrs (range 58-81 yrs) were enrolled; 4 pts had grade 3 Ta and 2 pts had Tis. Four and 2 pts received induction and maintenance course of BCG, respectively. Six AEs of grade 1 or 2 were reported by 3 pts, and they were respiratory and head congestion, acid reflux, rash, bronchitis, nausea, and cystitis. None of these AEs were judged to be related to APL. Five pts completed the study and 1 pt dropped out due to a grade 1 cystitis after receiving 4 wks of APL and 2 doses of BCG. The PK results suggested similar PK characteristics (plasma AUCtau, Cmax and t1/2, and urinary excreted faction Ae%). Conclusions: APL was well tolerated when given for 12 wks to NMIBC pts who also received induction or maintenance BCG. Further study of APL in combination with BCG is warranted. Clinical trial information: NCT03672240.