bluuebunny/crossref_metadata_2025_split huggingface dataset:
Liver-directed therapy (LDT) and systemic chemotherapy for pancreatic adenocarcinoma with liver metastases (PCLM): Experience of 12 years.
Authors: Goyal Shreya Prasad , Jose Jyothi , Greben Craig R. , Lobko Igor , Grimaldi Gregory Michael , Ghaly Maged , Daly Kevin P , Saif Wasif M. 
Published: May 2020

e16768 Background: PCLM has a poor prognosis with a median survival of ≤6 months. Treatment options are limited as only few patients can undergo curative surgery, therefore locoregional therapies such as LDT offer an adjunct to systemic therapies. Combination of LDT and systemic therapies is a strategy to enhance the effect of radioembolization or chemotherapy alone, akin to the use of radiotherapy with chemotherapy. The purpose of this retrospective study was to evaluate the efficacy of incorporating trans-arterial radioembolization (TARE) with 90Y, trans-arterial chemoembolization (TACE), and radiofrequency ablation (RFA) with systemic chemotherapy in the treatment of PCLM. Methods: We retrospectively evaluated 42 patients, with data available on 39 patients, with PCLM who underwent LDT between February 2007 and March 2019. Patient outcomes were assessed using Response Evaluation Criteria in Solid Tumors (RECIST), Version 1.1 including disease response, median overall survival (mOS) from the time of diagnosis of metastatic disease, and mOS following receipt of LDT. Treatment-related adverse events were assessed using Common Terminology Criteria for Adverse Events (CTACE), Version 5.0. Results: Of 39 patients, 56% underwent TARE, 36% RFA, and 7.8% TACE. The selection of modality was based on institutional standards and at the discretion of the referring physician. The mOS was 5 months (range 4-5.5 months) from the application of LDT and the one-year mOS was 7.8 months (6.5-9.5 months). Overall and liver specific disease response assessed with follow-up imaging (range 4-12 weeks post therapy) was complete response in 2.5%, partial response in 59%, stable disease in 21%, and progression of disease in 18% of patients. The mean interval between the diagnosis and initial LDT was 6 months. All patients received single course of TARE for each diseased liver lobe. In 26% of patients who had bilobar liver disease, the combination treatments for both diseased lobes was defined a single course. The mean Y90 radiation dose delivered to the right lobe was 1.00 GBq and to the left lobe was 0.64 Gbq. Grade 3 toxicities included abdominal pain in 13%, hyperbilirubinemia in 7.7%, fever in 7.7%, abscess in 2.6%, and thrombocytopenia in 5.1% of patients. No treatment-related grade 4 or 5 toxicities were seen. Conclusions: LDT can be safely combined with systemic chemotherapy for the treatment of PCLM. Patient outcomes following this treatment strategy are promising but prospective evaluations are needed to validate these preliminary findings.
PhaseI/IIa Study evaluating the safety, efficacy of K-001 in advanced pancreatic ductal adenocarcinoma.
Authors: Cui Jiujie , Yang Haiyan , Chen Donghui , Hu Jiong , Zhang Haiyan , Jiao Feng , Liu Min , Liu Jue , Wang Li-Wei 
Published: May 2020

e16770 Background: K-001 is a potent, oral anticancer drug made from active ingredients of marine microorganisms. Its former phase I study did not observe the dose limited toxicity (DLT). Thus, further phase I/IIa trial was conducted to determine maximum tolerated dose (MTD), safety profile and antitumor effects of K-001 in advanced pancreatic ductal adenocarcinoma (PDAC). Methods: This open-label phase I/IIa study involved a dose-escalation to determine maximum tolerated dose (MTD), recommended dose (RD) of K001 in patients with pancreatic ductal adenocarcinoma, followed to obtain preliminary evidence of efficacy in patients who could potentially benefit from treatment. Results: Doses from 1350mg to 2160mg twice daily were evaluated. No dose-limiting toxic effects were observed. Totally, 47 adverse events (AE) were observed which included 27 (57.4%) grade 1 AEs, 17 (36.2%) grade 2 AEs and 3 (6.4%) grade 3 AEs. Only 2 AEs which were indigestion and gastrointestinal flatulence were affirmed to research drug and both grade 2. These two AEs were both symptoms of digestive system. For grade 3 AEs, The AEs were not dose dependent. Twelve patients were assessable for response. Clinical activity was observed at all doses tested with durable Response Evaluation Criteria in Solid Tumor (RECIST) . The objective RECIST response rate (ORR) was 0% (complete response + partial response) and the disease control rate (DCR) was 83.3% (10 of 12). Conclusions: K001 has promising efficacy and light side-effect profile. The activity observed demonstrates clinical benefit in pancreatic ductal adenocarcinoma, justifying the conduct of further studies. Clinical trial information: NCT02720666 .
Survival outcomes of neoadjuvant versus adjuvant chemotherapy in early-stage pancreatic adenocarcinoma: A subgroup analysis of the National Cancer Database.
Authors: Kumar Rohit , Bhandari Shruti , Singh Sunny R K , Malapati Sindhu Janarthanam , Rojan Adam 
Published: May 2020

e16777 Background: Early-stage disease is diagnosed in 10-20% of patients with pancreatic adenocarcinoma (PAC). The current standard of care is upfront surgery followed by adjuvant chemotherapy (AC). The administration of the latter may be limited due to postoperative complications. The aim of this study is to determine the subgroups of patients with early-stage PAC who derive maximum benefit of neoadjuvant chemotherapy (NAC). Methods: Using the National Cancer Database 2004-15, we identified 20,003 patients with clinical stage I or II PAC who had surgery and received chemotherapy in any sequence. The baseline characteristics were compared using Pearson's chi‐square test between patients who received NAC versus AC. A separate multivariate Cox-proportional Hazard regression analysis was done for each subgroup to identify patients with the maximum survival benefit from NAC. Hazard ratio (HR) < 1 connotes survival benefit in favor of NAC. Results: Of the study population, 24% of the patients received NAC. The patients in the NAC group had more PAC of head (80% vs 73%), stage II disease (72% vs 53%), CA19-9 levels 50 U/ml (66% vs 59%), multiagent chemotherapy (68% vs 27%) and were treated at an academic facility (66% vs 52%) compared to the AC group. The p-value was < 0.001 for all comparisons. The age and sex distribution were similar in both groups. On multivariate survival analysis in the overall population, NAC had improved survival compared to AC (HR 0.88 95%CI 0.82-0.93, p < 0.001). Subgroup multivariate survival analysis is shown in the table. Conclusions: In early stage PAC, there is a trend towards survival benefit of NAC compared to AC in most subgroups. The maximum benefit is seen in younger patients with Stage II disease, high CA19-9 levels and fewer comorbidities who receive multiagent chemotherapy. This finding may partly be explained by better tolerability of preoperative compared to postoperative chemotherapy. A randomized clinical trial is needed to establish the optimal chemotherapy timing in patients with early-stage PAC who are treated with curative intent. [Table: see text]
Real-world dosing, management, and clinical outcomes of patients (pts) with metastatic pancreatic adenocarcinoma (mPDAC) treated with liposomal irinotecan.
Authors: Abushahin Laith I. , Cockrum Paul , Surinach Andy , Belanger Bruce 
Published: May 2020

e16780 Background: Pancreatic cancer remains one of the most lethal cancers in the United States (US) with a 5-year relative survival of 10%. Liposomal irinotecan is a topoisomerase inhibitor indicated, in combination with 5-fluorouracil and leucovorin, for pts with mPDAC following disease progression on gemcitabine-based therapy. This study examines the real-world use and therapeutic management of pts with mPDAC treated with liposomal irinotecan. Methods: This retrospective observational study utilized the Flatiron Health EHR-derived de-identified database from over 280 cancer clinics in the US. Data were analyzed for adult pts with mPDAC treated with liposomal irinotecan based regimens between Nov 2015 and Oct 2019. Pts were categorized into two starting dose groups: 70mg/m2 and < 65mg/m2. Pt characteristics, overall survival (OS), duration of treatment (DOT), and impact of dose reductions (DR, reduction ≥ 7mg/m2) were assessed among pts who received ≥3 cycles of treatment (tx). Results: Of the 532 pts (median age: 69y, IQR: 62-75) included in the study, 95 (18%) had an ECOG score of 2+ at tx initiation. Of the 184 pts (69y, 42 – 84) that did not receive 3 cycles of tx, 47 (25%) had an ECOG score of 2+ and 83 (45%) had two or more prior lines of tx. 348 pts (69y, 43 – 85) received ≥3 cycles of tx. 116 (33%) pts had two or more prior lines of tx, 209 (60%) had an ECOG score of 0-1, 48 (14%) had an ECOG score of 2+, and 91 (26%) had missing scores. 220 (63%) initiated tx at 70mg/m2 and 128 (37%) initiated at < 65mg/m2. 83 (38%) 70mg/m2 and 26 (20%) < 65mg/m2 pts experienced a DR during tx. 43 (52%) and 14 (54%) of the DRs occurred within the first 6 wks of tx in the 70mg/m2 and < 65mg/m2 cohorts, respectively. Median DOT was 12.6 weeks for 70mg/mg2 and 9.1 wks for < 65mg/m2 pts; DOT was longer among pts with a DR: 19.0 wks and 16.1 wks, respectively. Median OS (mOS) was 7.2 months (95% CI: 6.2 – 8.1) and 6.2 mos (5.0 – 7.4) for pts receiving 70mg/m2 and < 65mg/m2, respectively. mOS for pts with a DR was 8.9 mos (7.3 – 10.8) and 7.7 mos (5.0 – 14.9) for pts receiving 70mg/m2 and < 65mg/m2, respectively. mOS for pts with no DR was 6.0 mos (4.8 – 7.2) and 6.0 mos (4.7 - 7.2) for those receiving 70mg/m2 and < 65mg/m2, respectively. Conclusions: In this descriptive study among pts who were able to receive ≥3 cycles of liposomal irinotecan and remain on tx for ≥4 wks, DRs were effective in extending DOT and OS, independent of starting dose. The longest DOT and OS were observed in the pts who received 70mg/m2 with DRs. Pts who received 70mg/m2 and < 65mg/m2 had similar OS in the absence of DRs.
Effect of access to germline genetic testing on pancreatic cancer precision treatment across disease stage and ethnicity.
Authors: Esplin Edward D. , Truty Rebecca , Yang Shan , Nielsen Sarah M. , Klint Margaret , Lincoln Stephen E , Ngo Nhu , Das Kingshuk , Samadder Jewel , Nussbaum Robert Luke 
Published: May 2020

e16783 Background: PARP inhibitor (PARPi) treatment was recently approved for pancreatic cancer (PaCa) patients with germline mutations in 2 DNA damage repair (DDR) genes. Despite criteria recommending germline multigene panel testing for all PaCa patients, barriers to testing remain, including among underserved populations, which limit access to precision therapies. We initiated a sponsored testing program that increases access to germline genetic testing for PaCa in two ways: 1) offering a comprehensive multigene panel, and 2) removing the barrier of cost. Here we present initial results from this program, including the diagnostic yield in patients across stages of PaCa and clinical utility of the findings. Methods: We retrospectively analyzed de-identified data from 966 PaCa patients tested on an 84 gene panel as part of the program to date. The only inclusion criterion was a willingness to participate in the sponsored program by the patient and the provider who ordered the testing. Data included likely pathogenic (LP) and pathogenic (P) mutations, disease stage and ethnicity. Results: In total, 166 (17%) patients were positive for P/LP germline mutations in 30 genes. Mutation rate by ethnicity was: Caucasian 17%, African American 12%, Hispanic 16%, Ashkenazi Jewish 20%, Asian 3%. Only 25% of patients with P/LP variants reported a family history of cancer. There was no statistical difference in mutation rates by stage (p = 0.11) [Table]. In positive patients, 83 (78%) had mutations conferring potential eligibility for DDR gene-specific precision therapies or clinical treatment trials. 28 (26%) were potentially eligible for olaparib due to BRCA1/2 mutations, 8 (7%) were potentially eligible for pembrolizumab, and 47 (44%) for PARPi clinical trials. Conclusions: This study found 8.5% of all PaCa patients tested are potentially eligible for germline-based precision therapies and/or clinical treatment trials. Of mutation positive patients, 75% did not report a family history of cancer. The positive rate was not statistically different between patients with stage I and stage IV PaCa, underscoring the recommendation to test all patients with PaCa. This program had a 1.5% increased relative uptake among African American patients compared to a standard insurance reimbursement delivery model. These data suggest reducing barriers improves PaCa patient access to genetic information that enables precision therapy. [Table: see text]
Novel nanobiosensor based protease biomarkers for early detection and prognosis of pancreatic cancers.
Authors: Kasi Anup , Houghton James Kaiser , Saeed Anwaar , Williamson Stephen K. , Zambrano Obdulia Covarrubias , Bossmann Stefan H 
Published: May 2020

e16787 Background: Identifying novel biomarkers for early detection and prognosis would allow for improved survival outcomes in pancreatic cancer (PC). Arginase has been implicated in tumorigenesis through its production of L-ornithine. Its aberrant expression provides metabolites for tumor proliferation. Methods: In our study, 47 patients with metastatic PC, 29 with localized PC, and 50 healthy controls were enrolled at KU Cancer Center from 2000 to 2019. Overall survival (OS) was retrospectively assessed and correlated to serum protease levels at diagnosis. Protease expression was analyzed using nanobiosensors, which utilized fluorescent nanoparticles read by Spectra Scan to measure arginase, matrix metalloproteinases (MMPs), urokinase plasminogen activator (uPA), neutrophil elastase (NE), cathepsin B (CTSB), and cathepsin E (CTSE). Survival analysis was completed by Kaplan-Meier method. Results: Protease expression in localized vs. healthy cases was significant for (CTSB [p = 1.33E-10], MMP1 [p = 6.66E-21], MMP3 [p = 1.39E-13], MMP9 [p = 2.77E-08], NE [p = 0.00015], uPA [p = 2.55E-11]) and borderline significant for arginase [p = 0.05082]. Protease expression in metastatic vs. healthy cases was significant for (CTSB [p = 7.06E-06], MMP1 [p = 3.08E-12], MMP3 [p = 2.51E-14], MMP9 [p = 1.73E-08], NE [p = 0.01430], uPA [p = 0.00024]). Further, metastatic vs. localized cancer was significant for (arginase [p = 0.00034], CTSB [p = 0.00584], MMP1 [p = 2.03E-13], NE [p = 2.29E-10], and uPA [p = 6.58E-07]. Characteristics of 21 localized PC patients are illustrated in Table. Median OS was 25m in localized PC with low Arginase expression (mean < 215) vs 17.5m in high Arginase expression (p = 0.0477). Conclusions: Expression pattern of CTSB, MMP, NE, arginase, uPA proteases showed statistical significant difference for detection of localized PC vs metastatic PC vs healthy cases. In localized PC, lower arginase expression showed a statistically significant improvement in survival vs high arginase expression. Arginase expression was borderline significant for detection of localized PC vs healthy controls, likely due to small sample. Arginase as a potential biomarker for early detection and prognosis of PC warrants validation in a larger cohort. [Table: see text]
FOLFIRINOX versus sequential 5-FU, oxaliplatin, and irinotecan-based regimens in patients with recurrent pancreatic cancer (rPDAC).
Authors: Rehman Hasan , Chi Jeffrey , Hakim Nausheen , Jose Jyothi , Moriarty Linda , Lamont Carol , Saif Wasif M. 
Published: May 2020

e16791 Background: There is a paucity of data to guide treatment for rPDAC after curative resection and gemcitabine-based adjuvant chemotherapy. Our aim was to investigate whether combination treatment upfront with all active agents is better than sequential administration of these drugs in patients with rPDAC following curative therapy. Methods: We retrospectively analyzed overall survival (OS), progression-free survival (PFS), response rate (RR), and adverse events (AEs) in patients treated for rPDAC. Patients received FOLFIRNOX upfront versus sequential therapy in the following order based on patient’s presence of toxicities (FOLFOX —> FOLFIRI, FOLFOX—> liposomal irinotecan/5FU, liposomal irinotecan/5FU —> FOLFOX). Each treatment was administered per NCCN guidelines with regulated staging scans, blood work, and office visits. Data was collected about chemotherapy dose, ECOG performance status (PS), RR, PFS, OS, and AEs. Results: 55 patients were identified with ECOG PS ≤ 2 and male:female ratio 35:20. Results for FOLFIRINOX, FOLFOX followed by FOLFIRI, FOLFOX followed by liposomal irinotecan/5FU, and vice versa are as follows respectively: PFS 4.0, 3.5, 3.5, and 3.0 months; OS 8.0, 7.5, 7.0, and 8.3 months; RR 10%, (8%, 3%), (9%, 4%), and (3%, 5%). One of the patients in the mFOLFIRINOX was able to undergo metastasectomy. The table summarizes the toxicities and dose modifications seen. Conclusions: Upfront FOLFIRINOX versus sequential regimens of oxaliplatin and irinotecan-containing regimens resulted in similar PFS and OS but higher AEs as expected. However, surgery was only possible in patients receiving FOLFIRINOX. Our findings support the use of sequential treatment in rPDAC who are not potential surgical candidates. Further investigative work is warranted to optimize sequencing of active agents in this setting where prognosis has historically been poor. [Table: see text]
Early detection for pancreatic cancer in individuals at elevated-risk, using endoscopic ultrasound (EUS) and magnetic resonance imaging (MRI) of the abdomen: Feasibility and preliminary outcomes.
Authors: Raff Joshua P. , Noyer Charles , Boxer Nicole , Sadan Sara , Costin Dan , Roayaie Sasan , Gordon Mark , Kaumaya Meghan , Hopkins Una , Cortese Marisa , Rice Melissa Rowan , Goel Sanjay 
Published: May 2020

e16798 Background: There are no accepted guidelines for testing individuals at elevated risk for developing pancreatic duct adenocarcinoma (PC). We initiated a prospective screening and surveillance program for individuals at elevated risk for PC. Methods: Eligibility for the Pancreatic Cancer Early Detection Protocol (PCEDP) was based on germ line status and/or family history of PC, provided that the imparted risk was either five times that of the general population or 7.5% lifetime risk for developing PC. Testing was continued alternating between Endoscopic Ultrasound (EUS) and Magnetic Resonance Imaging (MRI) of the abdomen. Objectives were was to analyze the number, type, and location of pancreatic conditions found and their associations with genetic or family history; and to evaluate the outcomes and/or complications that may have resulted from our testing. Results: From April 2014 through October 2019 we received 238 queries, out of which 75 individuals (31%) enrolled in the PCEDP. Eligibility was based upon individual’s germ line only (45%), family history only (32%), and both (23%). Germ line mutations were observed in 34 (BRCA2), 9 (BRCA1), 4 (ATM), 3 (PALB2), and 3 (CDKN2A) individuals. Median age at consent was 57, 60% were female,and88%, 4%, 3%, and 1% self-identified as Caucasian, African American, Hispanic, and Asian, respectively. 133 EUS procedures and 83 MRIs have been performed. No serious adverse events occurred. Standard Insurance approved and paid for the vast majority of tests. Four individuals withdrew (5%) and three (4%) were lost to follow up. Ten individuals (13%) were found to have abnormal findings in the pancreas and therefore met an endpoint of the study, including seven anechoic cysts and three suspected intraductal papillary mucinous neoplasms (IPMN). All individuals with endpoints were recommended to continue surveillance with EUS. Eight of the ten endpoints were found on baseline EUS, one one from baseline MRI, and one was found on the 3rd EUS. One of the individuals with a 2.5cm IPMN seen on baseline EUS underwent a subsequent distal pancreatectomy, with pathology revealing high grade dysplasia. Conclusions: Screening and surveillance for PC using EUS alternating with MRI was feasible and well tolerated in our population of individuals with an elevated risk. Baseline EUS was successful in detecting 10/75 = 13% of enrollees with some abnormal pancreatic finding, including one requiring intervention with a high grade pre-malignant IPMN.
Deaths among pancreatic cancer in-hospital, and the utilization of palliative care.
Authors: Kasi Anup , Al-Rajabi Raed Moh'd Taiseer , Saeed Anwaar , Sun Weijing , Abbasi Saqib 
Published: May 2020

e16803 Background: Pancreatic cancer has a dismal 5 year survival of 5-10%. Deaths commonly occur in-hospital as they present with acute complications. The purpose of this study is characterize this population compared to all pancreatic deaths, identify causes for admission, trends in palliative care utilization and its effect on costs and patient stay. Methods: From the years of 2002 to 2014, admissions for patients with a diagnosis of pancreatic cancer were identified using the National Inpatient Sample. Annual trends in death were compared to overalls deaths using SEER data. Trends in hospital length of stay (LOS) and total charges (TC) were assessed, as well as utilization of palliative care. The effect of palliative care utilization on hospital LOS and TC were also identified. Results: 97,389 (weighted) patient deaths occurred from 2002 to 2014, with 7,634 in 2002, compared to 7,200 in 2014. Compared to total overall deaths of 38,026 and 42,047 respectively. Signifying 25% (2002) to 21% (2014) total patients expiring in an in-patient setting. The most common billed primary diagnosis was sepsis at 15.5%, followed by acute renal failure and fluid disorder (12.5%) and liver failure (5.3%). Overall length of stay trended down from 9.0 days to 7.5 days (p < 0.001). And total charges for admission increased from $36,704 to $88,063 (p < 0.001). Palliative care consults increased from 12% in 2002 to 45% in 2014. In 2014, the TC for deaths among those who received palliative care consults was $52,612 (p < 0.001 when compared to all deaths). LOS among these patients also decreased from 7.5 days to 6.2 days. When looking at patients with sepsis who did not die, a palliative care consult decreased costs from $86,738 to $74,544 (p < 0.001). LOS was not significantly different at 8.8 days compared to 8.5 days (p = 0.15). Conclusions: A quarter of patients with pancreatic cancer die in an in-hospital setting. Palliative involvement decreased health care resource utilization. In reviewing patients who developed sepsis without in-hospital mortality, a palliative care consult decreased total charges of admission.