bluuebunny/crossref_metadata_2025_split huggingface dataset:
National Comprehensive Cancer Network (NCCN) category I/FDA-approved metastatic pancreatic adenocarcinoma (mPDAC) treatments in commercially insured patients: An analysis of inpatient (IP) and emergency room (ER) admissions.
Authors: Cockrum Paul , Surinach Andy , Arndorfer Stella , Koeller Jim M. , Kim George P. 
Published: May 2020

e16739 Background: There are currently four NCCN category 1 systemic regimens approved in the United States for the treatment of mPDAC: FOLFIRINOX (FFX), gemcitabine+nab-paclitaxel (gem+nab-P), gemcitabine monotherapy (gem), and liposomal irinotecan + 5-fluorouracil/leucovorin (5-FU/LV) following progression with gem-based therapy. There is limited real-world research on the IP admissions and ER visit healthcare resource utilization (HRU) of patients receiving these treatments. Methods: Using the IQVIA PharMetrics Plus administrative claims database, data were analyzed for adult patients with mPDAC treated with NCCN category 1 regimens in first through fourth line of therapy between January 1, 2014 and May 31, 2019. For each line of therapy, continuous treatment was defined as the time from first administration of a therapy until the last administration. Mean all-cause and mPDAC-related IP admissions, ER visits, inpatient length of stay (LOS) during treatment were assessed. Results: Of the 2,731 patients with mPDAC included in the study, 101 (3.7%) were treated with a liposomal irinotecan based regimen, 1,316 (48.2%) were treated with gem+nab-P, 612 (22.4%) with FFX, and 624 (22.8%) with gem in any treatment line. The mean number of IP admissions was 1.2 for liposomal irinotecan treated patients, 1.5 for gem+nab-P, 1.5 for FFX, and 1.2 for gem. Among patients with at least one IP admission the mean LOS was 4.5 days for liposomal irinotecan, 5.4 days for gem+nab-P, 3.8 for FFX, and 5.1 for gem treated patients. Patients treated with liposomal irinotecan had a mean of 1.3 ER visits during treatment. Gem+nab-P, FFX, and gem-treated patients experienced 1.7, 1.4, and 1.8 mean ER visits, respectively. Mean mPDAC-related IP admissions ranged from 1.1 – 1.5, ER visits ranged from 1.1 – 1.7, and mean LOS ranged from 3.8 – 5.5 days. Conclusions: In this descriptive retrospective study patients receiving liposomal irinotecan, across all treatment episodes, generally experienced numerically lower mean IP admissions and ER visits. LOS was similar across all regimens. Further studies are necessary to characterize the IP and ER HRU burden among mPDAC patients treated with approved regimens.
Performance of neoadjuvant therapy in locally advanced adenocarcinoma of the pancreas: A single large volume center experience.
Authors: Lee Teresa , Zhan Tingting , Chanda Subikram , Barsouk Adam , Nauheim David , Renslo Bryan , Shergill Mandeep , Jiang Wei , Chao Timothy , Lavu Harish , Yeo Charles , Posey James 
Published: May 2020

e16745 Background: Pancreatic adenocarcinoma (PC) is a disease with low 5-year survival rates even in patients who undergo surgical resection: ~10% overall and 20-35% in those with negative lymph nodes and R0 operation. Adjuvant chemotherapy (CT) has demonstrated benefit; however, not all patient are candidates for multi-agent CT post-op. Early use of systemic therapy might improve outcomes. As a leading referral center for pancreatic resection in a tri-state area, we present a single institution real-world experience of neoadjuvant CT (neo-CT) in PC patients principally with degrees of vascular abutment at presentation. Methods: We identified 90 patients scheduled for pancreatectomy from 2015 to 2019 who received neo-CT. Three had an aborted procedure due to occult metastatic disease. Of those who underwent resection (n = 87), most were borderline or locally advanced (n = 79) with a few deemed resectable (n = 5) or metastatic (n = 3) prior to CT. 80 patients (92%) had R0 resection, though final pathology showed R1 resection in 5 and distant metastases in 2 patients. 72% of patients (n = 63) received 5-FU-based neo-CT, while 28% (n = 24) received gemcitabine-based CT. 36% (n = 31) received neoadjuvant radiation (RT) (with or without concurrent CT) in addition to CT, and 43% (n = 37) had adjuvant therapy, either CT, RT, or a combination. 4 patients received additional therapies on clinical trial. 41 patients (47%) completed >6 months of peri-operative CT, with 23 of those (26%) completing 6 months prior to surgery. We evaluated pathologic regression scores and compared those with very good response (score 0-1) post-CT vs. partial (score 2) or no response (score 3). Results: Median progression-free survival (PFS) from start of treatment in our cohort was 1.9 years (95% CI 1.4-NR) while median overall survival (OS) was 3.0 years (95% CI 2.4-NR). Duration of neo-CT did not affect PFS or OS. Logrank tests of OS curves of the 3 pathologic response groups indicated a statistically-significant difference (p = 0.004), with longer OS in patients with score 0-1 and shorter OS in patients with score 3. Conclusions: This analysis involves patients treated in both community and academic settings. We observed improved survival among those with best pathologic responses. The majority of cases with lower residual tumor burden received FOLFIRINOX. We are analyzing molecular data in this cohort and will conduct adjusted analyses for clinical characteristics. The prospective selection of multiagent CT in PC may be influenced by molecular profile and early response assessment.
A phase II trial of cabozantinib and erlotinib for patients with EGFR and c-Met co-expressing metastatic pancreatic adenocarcinoma (PDAC).
Authors: Turk Anita Ahmed , Sehdev Amikar , Shahda Safi , O'Neil Bert , Helft Paul R. , Spittler Aaron John , Flynn Janet , Loehrer Patrick J. 
Published: May 2020

e16764 Background: Both EGFR and the c-MET receptors are overexpressed in a majority of PDACs. Inhibition of both receptors simultaneously may be required for anti-tumor activity. Erlotinib, an EGFR inhibitor, has modest activity in metastatic PDAC and is approved by the FDA in combination with gemcitabine. Cabozantinib is a tyrosine kinase inhibitor targeting AXL, FLT-3, KIT, MER, MET, RET, ROS1, TIE-2, TRKB, TYRO3, and VEGFR-1, -2, and -3. Preclinical data suggests that the addition of cabozantinib to erlotinib leads to tumor shrinkage and improvement in survival in a KPC PDAC mouse model compared to gemcitabine alone. This phase II study tests this hypothesis in patients with metastatic PDAC that co-express c-MET and EGFR. Methods: Key eligibility includes patients (pts) with metastatic PDAC with EGFR and c-MET overexpression (as determined by centrally tested IHC of 2+ or greater) that have progression on one prior chemotherapy regimen. Patients were treated with cabozantinib (40mg daily) and erlotinib (100mg daily) continuously. This dosing is based on previous combination data in NSCLC. This is a single arm two-stage phase II study with a primary endpoint of overall response rate. Secondary endpoints include of PFS, DCR and OS. Results: From October 2017 to October 2019, 43 pts were screened with 7 pts (median age 62 [range 51-76)] enrolled and treated on study. Pts had a median of 1 line of prior systemic chemotherapy. Most common reason for screen failure was due to lack of co-expression of c-MET and EGFR. EGFR IHC expression was +2 in 4 pts, +3 in 3 pts; c-MET IHC expression was +2 in 5 pts and +3 in 2 pts. Most common any-grade adverse events attributable to cabozantinib and erlotinib include: diarrhea (71%), AST increase (43%), fatigue (43%), nausea (43%), and rash (43%). Only one grade 3 event of fatigue occurred. All pts had clinical and/or radiographic progression within 1-2 months after initiating study therapy. Conclusions: The combination of cabozantinib and erlotinib was well tolerated with manageable toxicity. Due to lack of clinical responses, this study has been terminated due to futility. Clinical trial information: NCT03213626 .
Sarcopenia and sarcopenic obesity in pancreatic ductal adenocarcinoma (PDAC) patients undergoing surgery after neoadjuvant therapy (NAT): Clinical implications.
Authors: Trestini Ilaria , Paiella Salvatore , Sandini Marta , Hank Thomas , Pollini Tommaso , Sperduti Isabella , Melisi Davide , Auriemma Alessandra , Soldà Caterina , Tregnago Daniela , Avancini Alice , Malleo Giuseppe , D'Onofrio Mirko , Gianotti Luca , Pilotto Sara , Bria Emilio , Salvia Roberto , del Castillo Carlos Fernandez , Bassi Claudio , Milella Michele 
Published: May 2020

e16769 Background: Nutritional status may be markedly affected by NAT for PDAC. Sarcopenia and sarcopenic obesity have been studied in several types of cancers and have been reported to be associated with higher morbidity and mortality. The present study assessed the impact of sarcopenia/sarcopenic obesity and changes in body composition (BC) following NAT on surgical and survival outcomes in patients (pts) undergoing surgery for PDAC. Methods: PDAC pts with available CT-scans (both at diagnosis and preoperatively) undergoing surgical resection after NAT at two academic medical institutions from 2013 to 2015 were retrospectively evaluated. BC was assessed by analyzing axial L3 CT images before and after NAT. Data were correlated with overall survival (OS) using a Cox regression model. Kaplan-Meier curves were compared with Log-Rank test. Results: The final cohort consisted of 108 pts, with a median age of 63 years and a median follow-up of 16 months. Ninety-one pts (89.8%) received FOLFIRINOX. Sarcopenia and sarcopenic obesity were found at diagnosis in 41.7% and 16.7% of pts, respectively. After NAT, all body compartments significantly changed (p < 0.001); the prevalence of sarcopenia and sarcopenic obesity decreased to 30.5% and 10.2%, respectively, after NAT. These BC phenotypes were related to a higher overall complications rate after surgery (69.7% vs. 30.3%, p = 0.027 and 81.8% vs. 18.2% %, p = 0.048, respectively). Particularly, cardiac complications were associated with sarcopenia (9% vs. 0%, p = 0.028) and pts that developed postoperative complications had higher preoperative total adipose tissue (300 vs. 229 cm2, p > 0.05). With regards to OS, sarcopenic obesity at baseline (HR 3.45, p = 0.023) was found to be a significant independent predictor for OS at multivariate analysis. Conclusions: Our data provide evidence that BC impacts on both surgical and survival outcomes in PDAC pts undergoing NAT before resection. The associations with worse clinical outcomes emphasize the role of nutritional evaluation, as well as the need to develop appropriate evidence-based nutritional interventions during NAT.
New-onset diabetes mellitus and risk of pancreatic cancer: A systematic review and meta analysis.
Authors: Albawaliz Anas , Bataineh Adam , El Kurdi Bara , Babar Sumbal , Abonofal Abdulrahman , Alhabhbeh Ammar , Alomari Mohammad , Qasem Abdulraheem M.S. , Sanaka Madhusudhan 
Published: May 2020

e16778 Background: Several epidemiologic studies have illustrated a general association between diabetes mellitus and pancreatic cancer (PC). Very few, however, described a temporal association between the new onset of diabetes mellitus, particularly within the first 2 years of diagnosis, and the development of PC. We sought to systematically review the literature and perform the first meta-analysis to study the risk of PC among patients with new-onset diabetes mellitus (NOD). Methods: A systematic literature search was conducted in PubMed, MEDLINE, EMBASE, and Cochrane databases from inception through November 2019 to identify studies evaluating the relationship between NOD and PC. NOD was defined as diabetes mellitus diagnosed within 3 years or less prior to diagnosis of PC. Studies were examined and relevant data was extracted and analyzed using Comprehensive Meta-Analysis software. A random effect meta-analysis approach was used to pool the data and odds ratio was used to calculate the overall effect estimate. Results: A total of 283 articles were identified by the search but only 4 relevant studies met our inclusion criteria and they examined a total of 42055 cases and 2402213 controls. The odds ratio of pancreatic cancer development among patients with NOD was 3.021 (CI 2.192- 4.165) compared to controls with significant heterogeneity (I2= 90%). Meta regression evaluating relevant variables such as mean age, race and smoking were not able to explain the heterogeneity. A meta-regression model accounting for sample size as an independent factor showed that sample size was inversely correlated to the OR of PC in patients with NOD and was able to explain 93% of the noted heterogeneity between studies. Conclusions: Our meta-analysis has shown a significant temporal association between NOD and pancreatic cancer. Diabetes mellitus, being mostly diagnosed in an outpatient setting by primary care physicians (PCPs), can be the first clue to detect pancreatic cancer at an early stage, and thus contribute to more favorable outcomes. These findings might guide PCPs to consider pancreatic cancer in the differential diagnosis in high risk patients. Further studies are needed to discern the role of NOD in pancreatic cancer screening. Attention is required to the possible inflationary effect of low sample sizes on the odds of developing PC after NOD.
Value-based estimate of market size and opportunity for economic benefit through innovative pancreatic cancer (PC) therapies.
Authors: Picozzi Vincent J. , Manax Victoria G. , Kim Semmie , Wintrob Zachary , Mandelson Margaret T. , Korfin Michele , Del Priore Giuseppe , Goldberg Robert 
Published: May 2020

e16790 Background: Over the past 20 years, cancer drugs have contributed to increased life expectancy, reduced mortality, decreased hospitalization and decreased use of medical services. The economic value of these improvements is about as large as the value of the increase in the US gross domestic product during that time period. Recently, a health economic study presented at ASCO GI 2020 cited that every $1 (adjusted for inflation) spent on innovative PC treatments reduced non-drug expenditures by $9, thereby lowering the total cost of care for PC patients. Accordingly, the commercial opportunity of a new therapy should be measured by some combination of the clinical, economic and social value generated. We demonstrate the value of a novel PC drug from this perspective. Methods: Analysis of SEER survival and incidence data between 2008 and 2016 shows the introduction of new medicines for PC of all stages was associated with a cumulative increase of 26,456 life years, or 2.52 life years per patient. It was also associated with quality of life improvements, measured by a decline in hospitalizations rates and emergency room visits that can also lead to more days at work, at school and with family. Several studies have suggested the average value of an additional year of life, for the age of a typical patient diagnosed with PC, is at least $250,000. Using this figure, the value of 26,456 life years gained from 2008-2016 is $6.61 billion (26,456*$250,000) to patients, the healthcare system and society, as a result of advancing medical innovation for patients with PC. Results: The median annual list price of a life-enhancing cancer therapy is $150,000 per patient. Using the NCI treatment prevalence estimator (holding incidence constant), we estimate that between 2020-2025, there will be an additional 10,728 advanced PC patients requiring treatment who could benefit from innovative drugs. The total cost of these drugs for these patients would be $1.61 billion. However, the economic value of the life years saved would be $6.76 billion (10,728*2.52 life years*$250,000 = $6.76 billion). A review of cancer medicine payor coverage suggests a new PC therapy that produces such value would be able to obtain coverage from US payors given this value-based price. Conclusions: A value-based approach to estimating the opportunity for clinical and economic benefit reveals significant potential for new PC medicines.
Circulating tumor DNA analysis to detect minimal residual disease and predict recurrence in patients with resectable pancreatic cancer.
Authors: Yang Liu , Jiang Jiahong , Ye Song , Xu Yaping , Huang Dongsheng 
Published: May 2020

e16799 Background: Pancreatic ductal adenocarcinoma (PDAC) is one of the leading causes of cancer death, partly due to the high recurrence rates for patients with resectable PDAC. Current postoperative surveillance methods including monitoring of clinical symptoms, tumor markers and CT imaging, lack sensitivity and specificity to identify minimal residual disease (MRD). Methods: We investigated whether the detection of circulating tumor DNA (ctDNA) could identify MRD and predict relapse in postoperative patients with PDAC. In this study, we performed panel-captured sequencing to detect somatic mutations. Matched tissue samples were obtained to verify mutation. Results: A total of 27 patients and 65 plasma samples were included. Among the somatic mutations, KRAS and TP53 were the most recurrent genes in both tissue and plasma samples. The detectable rate of ctDNA increased with the stage of PDAC. The maximal variant allele fraction (VAF) of ctDNA had a positive correlation with tumor largest diameter (p = 0.0101). Patients with ctDNA-positive status postoperatively had a markedly reduced disease-free survival (DFS) compared to those with ctDNA-negative status (HR, 5.20; p = 0.019). Positive vascular invasion significantly influenced disease-free survival (DFS) (p = 0.036), and positive postoperative ctDNA status was an independent prognostic factor for DFS (HR = 3.60; 95% CI, 1.15-11.28; p = 0.028). Conclusions: Postoperative ctDNA detection provides strong evidence of MRD and identifies patients with a high risk of relapse. ctDNA detection is a promising approach for personalized patient management during postoperative follow-up.
A novel prediction model to identify patients with early-stage pancreatic cancer.
Authors: Cherry Daniel R , Chen Qinyu , Murphy James Don 
Published: May 2020

e16801 Background: Pancreatic cancer has an insidious presentation with four-in-five patients presenting with disease not amenable to potentially curative surgery. Efforts to screen patients for pancreatic cancer using population-wide strategies have proven ineffective. We applied a machine learning approach to create an early prediction model drawing on the content of patients’ electronic health records (EHRs). Methods: We used patient data from OptumLabs which included de-identified data extracted from patient EHRs collected between 2009 and 2017. We identified patients diagnosed with pancreatic cancer at age 40 or later, which we categorized into early-stage pancreatic cancer (ESPC; n = 3,322) and late-stage pancreatic cancer (LSPC; n = 25,908) groups. ESPC cases were matched to non-pancreatic cancer controls in a ratio of 1:16 based on diagnosis year and geographic division, and the cohort was divided into training (70%) and test (30%) sets. The prediction model was built using an eXtreme Gradient Boosting machine learning algorithm of ESPC patients’ EHRs in the year preceding diagnosis, with features including patient demographics, procedure and clinical diagnosis codes, clinical notes and medications. Model discrimination was assessed with sensitivity, specificity, positive predictive value (PPV) and area under the curve (AUC) with a score of 1.0 indicating perfect prediction. Results: The final AUC in the test set was 0.841, and the model included 583 features, of which 248 (42.5%) were physician note elements, 146 (25.0%) were procedure codes, 91 (15.6%) were diagnosis codes, 89 (15.3%) were medications and 9 (1.54%) were demographic features. The most important features were history of pancreatic disorders (not diabetes or cancer), age, income, biliary tract disease, education level, obstructive jaundice and abdominal pain. We evaluated model performance at varying classification thresholds. When applied to patients over 40 choosing a threshold with a sensitivity of 20% produced a specificity of 99.9% and a PPV of 2.5%. The model PPV increased with age; for patients over 80, PPV was 8.0%. LSPC patients identified by the model would have been detected a median of 4 months before their actual diagnosis, with a quarter of these patients identified at least 14 months earlier. Conclusions: Using EHR data to identify early-stage pancreatic cancer patients shows promise. While widespread use of this approach on an unselected population would produce high rates of false positives, this technique could be employed among high risk patients, or paired with other screening tools.
Similar response rates and survival with PARPi treatments for patients harboring somatic versus germline BRCA mutations: A meta-analysis and systematic review.
Authors: Mohyuddin Ghulam Rehman , Aziz Muhammad , Britt Alec , Wade Lee , Sun Weijing , Baranda Joaquina Celebre , Al-Rajabi Raed Moh'd Taiseer , Saeed Anwaar , Kasi Anup 
Published: May 2020

e16802 Background: PARP inhibitor (PARPi) has recently been approved for various cancers. However, trials have mostly recruited pts with germline BRCA (gBRCA) mutations, and it is unclear whether PARPi have similar efficacy in pts with somatic BRCA (sBRCA) mutations. We aimed to determine the efficacy of PARPi in pts with sBRCA mutations. Methods: Per PRISMA guidelines, systematic review of PubMed, Embase, Cochrane RCT, and Web of Science Collection was performed from inception thru Jan 2020 to identify studies. Our inclusion criteria were clinical trials and retrospective studies that reported use of PARPi in pts with both s and g BRCA mutations. We performed a meta-analysis comparing overall response rate and PFS with PARPi in pts with s versus g BRCA mutations. Results: After screening, 18 studies met our criteria for including both s and g BRCA mutations. Only 8 studies reported response rates for both s and g BRCA mutations (Table). In those studies, 24 out of 43 pts with sBRCA mutations (55.8%), and 69 out of 157 (43.9%) pts with gBRCA had a response to PARPi (pooled OR 1.13, p value = 0.399, I2 = 0). In all five studies that reported PFS, there was no obvious difference in outcomes between sBRCA (HR in these studies ranged 0.23 to 0.27) versus gBRCA (HR ranged 0.17 to 0.27), however a precise statistical analysis could not be done. Conclusions: Our meta-analysis and systematic review of the literature indicates similar outcomes of PARPi therapy in pts with s and g BRCA mutations. Investigation of use of PARPi therapy in a broader patient population, and the inclusion of sBRCA mutations in future clinical trials is essential. [Table: see text]