bluuebunny/crossref_metadata_2025_split huggingface dataset:
HALO 109-301: A randomized, double-blind, placebo-controlled, phase 3 study of pegvorhyaluronidase alfa (PEGPH20) + nab-paclitaxel/gemcitabine (AG) in patients (pts) with previously untreated hyaluronan (HA)-high metastatic pancreatic ductal adenocarcinoma (mPDA).
Authors: Tempero Margaret A. , Van Cutsem Eric , Sigal Darren , Oh Do-Youn , Fazio Nicola , Macarulla Teresa , Hitre Erika , Hammel Pascal , Hendifar Andrew Eugene , Bates Susan Elaine , Li Chung-Pin , De La Fouchardiere Christelle , Heinemann Volker , Maraveyas Anthony , Bahary Nathan , Layos Laura , Sahai Vaibhav , Zheng Lei , Lacy Jill , Bullock Andrea J. ,   HALO 109-301 Investigators
Published: February 2020

638 Background: HA is a major component of the tumor microenvironment (TME) in PDA. PEGPH20 degrades tumor HA, remodeling the TME. In PDA models, PEGPH20 has shown antitumor activity and increased TME delivery of anticancer agents to improve efficacy. A randomized phase 2 study showed promising results for PEGPH20+AG (PAG) in mPDA and identified HA accumulation as a biomarker. We present results from a phase 3 study (NCT02715804) of PAG for pts with HA-high mPDA. Methods: Pts ≥18 years with untreated HA-high mPDA were randomized (stratified by geographic region) 2:1 to PAG or placebo+AG (AG). HA status was prospectively determined with VENTANA HA RxDx Assay, with HA-high defined as ≥50% staining of a tumor sample. Treatment was administered IV in 4-wk cycles (3 wks on, 1 wk off) until progression or intolerable adverse events (AEs): PEGPH20 3.0 µg/kg twice wkly for Cycle 1 and once wkly (QW) thereafter, A 125 mg/m2 QW and G 1000 mg/m2 QW. Prophylactic enoxaparin 1 mg/kg was given daily for thromboembolism (TE) risk. The primary endpoint was overall survival (OS); secondary endpoints included progression-free survival (PFS), objective response rate (ORR) and safety. Response was independently assessed per RECIST v1.1. The estimated sample size was ~500 pts to detect a hazard ratio (HR) for OS of 0.67 (93% power, 2-sided α = 0.05) after 330 deaths. Results: As of 20 May 2019, 494 pts were randomized with 492 (327 for PAG and 165 for AG) included in ITT analyses (2 pts excluded due to site violations). Baseline characteristics were balanced for PAG vs AG. After 330 deaths, median OS for PAG vs AG was 11.2 vs 11.5 mo (HR 1.00, 95% CI 0.80–1.27; P = 0.97); median PFS was 7.1 vs 7.1 mo (HR 0.97, 95% CI 0.75–1.26); confirmed ORR was 34% vs 27%. Grade (G) 3+ AEs (PAG vs AG) included neutropenia (44% vs 47%), thrombocytopenia (21% vs 16%) and fatigue (16% vs 10%); G3+ rates were 6% vs 7% for TE events, 5% vs 2% for bleeding events and 13% vs 5% for musculoskeletal events. Conclusions: PAG did not improve clinical outcomes vs AG. The PAG safety profile was consistent with that of previous studies. Clinical trial information: NCT02715804.
Impact of biliary metal and plastic stents on preoperative staging for pancreatic cancer.
Authors: Hachem Hachem , Reddy Sanjay S. , Tokar Jeffrey , O'Halloran Eileen , Higa Jennifer , Sapp Abby , Civitarese Albert , Bartel Michael 
Published: February 2020

646 Background: Multiple studies have shown the superiority of biliary metal compared with plastic stents for pre-operative (preop) biliary drainage in pancreatic cancer (PDAC). Despite the importance of preop cross-sectional imaging, particularly in the era of neoadjuvant treatment, there is no data on the impact of such stents on the quality of preop cross-sectional imaging. We hypothesis, that biliary metal stents negatively impact the accuracy of preop cross-sectional imaging in pancreatic cancer, with unknown impact for the adequacy of surgical candidacy. Methods: Data of all patients undergoing pancreatic resection for PDAC between 1/1/2012 and 1/1/2018 was retrospectively abstracted. Clinical staging based on preop cross-sectional imaging following biliary stent placement (within 2 months prior surgical resection) was compared with the surgical pathology (staging gold standard). Accuracy of clinical and surgical pathology staging was compared. Logistic regression was performed to control for biliary stent type, neoadjuvant treatment and patient baseline characteristics including BMI and type of imaging. Results: 312 patients underwent pancreatic resections. 118 patients required preop biliary drainage in setting of PDAC, including 92 ERCPs of which 83 were successful (46 plastic and 37 metal stents). 76 patients underwent neoadjuvant chemoradiation therapy. Surgical pathology revealed following stages: 0 n = 4, 1A n = 5, 1B n = 8, 2A n = 20, 2B n = 24, 3 n = 1, 4 n = 14. 96% underwent preop CT and 4% MRI pancreas protocol imaging. Exact correlation between clinical and surgical pathology was present in only 48% of cases (57% plastic, 46% metal stent), with 28% of clinical T overstaging, 4% clinical T understaging, 16% clinical N understaging and 4% unable to stage due to artefacts. More importantly, 8% patients were incorrectly staged to be surgical candidates (14% plastic, 6% metal). Controlling for stent type, neoadjuvant treatment and BMI did not impact preop cross-sectional imaging accuracy. Conclusions: Despite their impact on preop cross-imaging biliary metal stents did not negatively impact the accuracy and patient selection for surgical candidacy compared with biliary plastic stents in PDAC.
A colorectal cancer screening initiative to assist the healthcare for the homeless program within the Harris Health Safety-net Health Care System.
Authors: Rosen Allison , Escobar Betsy , Datar Gandhar , Chenier Roshanda , Montealegre Jane , Jibaja-Weiss Maria 
Published: February 2020

65 Background: The homeless population presents unique challenges for Colorectal Cancer (CRC) screening and follow-up, due to difficulty completing at home procedures such as stool-based screening and prepping for a colonoscopy. Harris Health System’s Healthcare for the Homeless Program (HHS-HHP) screens patients for CRC using strategies such as on-site stool collection to promote completion of fecal immunochemical tests (FIT). According to the HHS screening algorithm, there are currently no targeted interventions at HHS-HHP to address diagnostic follow-up of FIT-positive patients who require colonoscopy Homeless patients face barriers to colonoscopy, notably the structure of shelters, which makes it difficult to prep for a colonoscopy; and the lack of a companion to accompany patients to and from their procedures. Methods: We reviewed data regarding FIT screening and colonoscopy completion from Harris Health for the 2016-2017 fiscal year. We convened meetings with administrators of the Star of Hope Cornerstone Community and HHS-HHP to examine barriers faced by this population and identify potential interventions to address them. Results: For the 2016-17, fiscal year the average FIT completion rate for the entire population was 72% versus the homeless population was 38%. In the colonoscopy database, 173 homeless patients had positive FITs, but only 43 got their colonoscopy (25%). Reasons for not getting the colonoscopy were poor prep, not being able to reach the patient, and no-shows. There is an obvious need for an intervention to assist homeless patients in completing a colonoscopy after a positive FIT. Conclusions: Our project will assist with the care coordination for the homeless patients requiring a colonoscopy. We plan to coordinate care with the homeless shelters to schedule the use of a private, subacute care room (respite unit), if available, to ensure the patients appropriately prep the night before their procedure. In addition, medical student volunteers will be serving as companions for this project; thus, we plan to work with the patient and shelters to provide volunteers accompany patients to and from their procedures.
Safety and efficacy of chemotherapy in older adults with locally advanced and metastatic pancreatic ductal adenocarcinoma (PDAC).
Authors: Ostios-Garcia Lorena , Saade Patricia , Grossman Joseph Elan , Lanniello Leanne , Bullock Andrea J. 
Published: February 2020

654 Background: PDAC is often diagnosed in patients (pts) ≥75yrs. However, older adults comprise a small proportion of subjects in prospective trials, and there is little reported on the safety and efficacy of chemotherapy in this population. Methods: Records were reviewed on all pts ≥75yrs treated with chemotherapy for locally advanced and metastatic PDAC at a single institution from April 2010 - March 2018. Response rate (RR), progression free survival (PFS), overall survival (OS) and toxicities were compared among the different regimens, and among pts < or ≥80yrs. Survival was estimated with the Kaplan-Meier method and compared by log-rank test. Univariate analyses were performed by Fisher’s exact test and multivariate analyses by a Cox-regression model to identify factors associated with PFS and OS in this population. Results: 67 pts were treated, median age 81yrs (range: 75-90), stage III (34, 51%) and IV (33, 49%). Chemotherapy regimens included: gemcitabine alone (39), gemcitabine/nab-paclitaxel (17), gemcitabine/vinorebine (1), FOLFOX (8) and FOLFIRINOX (2). 59 (88%) pts required dose adjustments due to toxicity; no differences by age or regimen. RR, PFS, and OS did not differ by age or regimen (Table), although sample size was small. Age >80yrs was associated with reduced PFS (p 0.03). On univariate analyses liver metastases and performance status (PS)>1 were associated with reduced OS; PS>1 was associated with reduced OS on multivariate analysis. Conclusions: Among pts with locally advanced and metastatic PDAC ≥75yrs, there were no differences in RR, PFS or OS by chemotherapy regimen. PS was the only variable associated with reduced OS. Older adults with PS 0-1 are likely to benefit from chemotherapy for non-resectable PDAC.[Table: see text]
Comparison of clinicopathological characteristics and prognosis of borderline resectable pancreatic cancer according to the location of the primary tumor.
Authors: Takeda Tsuyoshi , Sasaki Takashi , Mie Takafumi , Furukawa Takaaki , Kanata Ryo , Kasuga Akiyoshi , Matsuyama Masato , Ozaka Masato , Sasahira Naoki 
Published: February 2020

662 Background: Little is known about the clinicopathological and prognostic differences between borderline resectable (BR) pancreatic head (Ph) and pancreatic body/tail (Pbt) cancer. Therefore, we conducted this study to compare the clinicopathological features and prognosis of BR pancreatic cancer (PC) according to the location of the primary tumor. Methods: We retrospectively investigated consecutive patients with BR PC who initiated neoadjuvant chemotherapy (NAC) between March 2015 and April 2019. We compared clinicopathological characteristics and prognosis between Ph and Pbt cancer. Furthermore, multivariate survival analysis was performed using cox proportional hazard model. Results: A total of 104 patients with BR PC (median age 68, male 49%) were included in this study. The location of the tumor was Ph 72 and Pbt 32, respectively. The initial regimen of NAC was nab-paclitaxel/gemcitabine in 102 and gemcitabine in 2, respectively. The median cycle of NAC was 4. Median age, sex, primary tumor size, performance status, neutrophil to lymphocyte ratio, and serum level of carbohydrate antigen 19-9 at the time of the initiation of NAC were not significantly different between Ph and Pbt cancer, while the modified glasgow prognostic score (mGPS) was lower in Pbt cancer (mGPS = 0; 78% vs. 94%, p = 0.05). R0/R1 resection rate (81% vs. 69%, p = 0.21) and median survival time (928 days vs. NA, p = 0.13) were also not different between Ph and Pbt cancer. Multivariate survival analysis revealed that R0/R1 resection (HR, 0.11; p < 0.01) and Ph (HR, 2.29; p = 0.03) were independent prognostic factors for survival in patients with BR PC. Conclusions: Although R0/R1 resection rate was similar between BR Ph and Pbt cancer, Pbt cancer had a higher rate of mGPS score of 0 compared to Ph cancer. Furthermore, R0/R1 resection (HR, 0.11) and Ph (HR, 2.29) were independent prognostic factors for survival in patients with BR PC.
Impact of dose reductions on clinical outcomes among patients (pts) with metastatic pancreatic cancer (mPC) treated with liposomal irinotecan (nal-IRI) in oncology clinics in the United States.
Authors: Cockrum Paul , Surinach Andy , Kim George P. , Mercer Daniel , Koeller Jim M. , Miksad Rebecca A. 
Published: February 2020

665 Background: The recommended starting dose for nal-IRI is 70mg/m2 (free base, equivalent to 80 mg/m2 salt-based dosing). This study evaluates the impact of nal-IRI dose reductions on clinical outcomes. Methods: Using the nationwide Flatiron Health electronic health record-derived database, de-identified data were extracted and analyzed for adult mPC pts treated with nal-IRI Jan 2014-Jan 2019 and who initiated treatment at approximately the recommended dose (RD), 70mg/m2 +/- 5mg. Initial dose was derived from structured medication records, prioritizing administrations. The cumulative dose (CD) of nal-IRI over the first six weeks of treatment, the presence of dose reductions (DR) – (a decrease ≥ 7mg/m2), overall survival (OS) from treatment initiation, and duration of treatment (DoT) were assessed. Results: 257 mPC pts treated with nal-IRI (median age: 68y, IQR: 61 - 73) were identified initiating therapy at approximately the RD. 26.5% (N = 68) of pts experienced a DR during treatment. Mean 6-week CD was 175.8 mg/m2 (SD: 77.9) among pts with no DR. For pts with DR, mean CD was 191.8 mg/m2 (53.2). Median DoT was 6.1 wks (IQR: 2.1 – 15.3). Pts that experienced a DR had a longer median DoT: 15.1 wks (7.1 – 23.0) vs 4.3. wks (2.1 – 12.1) for pts with no DR. Overall Median OS (mOS) was 4.2 months (95% CI: 3.7 – 5.4). mOS for DR pts was 7.2 mos (95% CI: 5.5 – 9.7) and 3.7 mos (3.0 – 4.1) for pts who did not experience a DR. Conclusions: This real-world analysis suggests that reducing the dose of subsequent administrations of nal-IRI during treatment is associated with pts remaining on therapy longer, experiencing a larger CD, and a with longer OS. Additional real-world prospective studies are necessary to characterize the impact of nal-IRI dosing on clinical outcomes.
Real-world patterns of care among patients with metastatic pancreatic cancer (mPC).
Authors: O'Reilly Eileen Mary , Surinach Andy , Wu Zheng , Cockrum Paul 
Published: February 2020

666 Background: Pancreatic cancer is the third deadliest cancer in the US and mPC has a 2.9% 5-year survival. The analyses herein describe treatment patterns, trends in usage, and overall survival (OS) in mPC. Methods: Using the Flatiron Health EHR-derived database, data were extracted and analyzed for patients with mPC (pts) between Jan 1, 2014 and Jun 30, 2019. The database includes de-identified data from over 280 cancer clinics (~800 sites of care) representing more than 2.2 million U.S. cancer patients available for analysis, with 80% of pts from community centers and 20% from academic centers. Lines of therapy in the metastatic setting are derived from structured medication records. OS from metastatic diagnosis was reported using the Kaplan-Meier method. Results: 7,666 pts with mPC were identified. 5,687 (74.2%) received therapy in the metastatic setting. Pts who didn’t receive therapy in the metastatic setting were more likely to be older (p < 0.0001) and less likely to have been diagnosed initially with stage IV disease (p < 0.0001) than pts who were treated. The frequency of (1L) regimens were gemcitabine plus nab-paclitaxel (GnP) 46.8%, FOLFIRINOX (FFX) 24.1%, gemcitabine monotherapy 9.3%, and FOLFOX 3.8%. Gemcitabine monotherapy use was 12.9% in 2014 and 7.3% in 2018. GnP (31.4%), FFX (12.3%), FOLFOX (11.4%), and liposomal irinotecan (nal-IRI) + 5-FU/LV (10.2%) were the most frequent second line (2L) regimens. Between 2015 and 2018 nal-IRI based regimens increased from 6% to 17.6% in 2L. In the third line (3L) setting nal-IRI + 5FU/LV (19.3%), GnP (12.1%), FOLFOX (11.4%), and FFX (9.1%) were the most common treatments. Aggregate median OS (mOS) for treated pts was 8.1 mos (95% CI 7.8 – 8.4), and mOS for untreated pts was 2.8 mos (2.6 – 3.0), p < 0.0001. Conclusions: Survival for mPC is improving and practice patterns are changing. GnP is the most commonly used 1L regimen, followed increasingly by nal-IRI + 5-FU/LV in 2L and 3L. Further studies are necessary to understand the treatment gaps for pts with mPC. [Table: see text]
Impact of prior irinotecan exposure on outcomes of metastatic pancreatic cancer (mPC) patients.
Authors: O'Reilly Eileen Mary , Surinach Andy , Dillon Allison , Cockrum Paul , Yu Kenneth H. 
Published: February 2020

667 Background: Published data suggests prior exposure to irinotecan infers a lower likelihood of benefit to liposomal irinotecan. This analysis seeks to expand this hypothesis by evaluating U.S. patterns of care to understand how prior irinotecan therapy impacts outcomes in mPC. Methods: Using the Flatiron Health database, data were extracted and analyzed for treated mPC patients (pts) in the 2L+ setting between Jan 1, 2014 and Jun 30,2019. Therapies of interest included: gemcitabine/ nab-paclitaxel (GnP), FOLFOX, FOLFIRI, FOLFIRINOX (FFX), and liposomal irinotecan/5-FU/LV (nal-IRI). The reference date for each treatment group was the date of treatment initiation. Prior irinotecan was defined as any irinotecan given in a prior regimen in mPC diagnosis. Cox proportional hazard (PH) methods were used to calculate mortality hazard ratios (HRs). HRs were adjusted to account for demographics and relevant covariates. Pts with prior exposure to irinotecan were used as the reference population for the Cox PH model (an HR < 1 represents worse survival for exposed pts relative to the unexposed). Results: N = 1,978 were included in this analysis. The median age at treatment initiation, and the proportion of pts previously treated with irinotecan are reported in table. Crude mortality was: GnP pts, HR 0.93 [95% CI: 0.77 – 1.11, adjusted HR, 0.94, 0.76 – 1.15]; nal-IRI pts, HR 0.81 [0.64 – 1.02, adjusted HR: 0.89, 0.67 – 1.19]; HR for FOLFOX was 0.55 [0.38 – 0.78, adjusted HR: 0.51, 0.33 – 0.79]. HRs are not reported for FFX and FOLFIRI due to the small numbers with prior irinotecan exposure. Conclusions: In mPC, prior irinotecan treatment may not preclude benefit from later treatment with nal-IRI or GnP as can be seen from the adjusted and unadjusted HRs. These findings are hypothesis-generating and need to be considered in the context of wide CI’s, retrospective nature and the limitations of such data. Further study is required to understand the less-favorable signal observed with FOLFOX and prior irinotecan.[Table: see text]
Distinct clinical characteristics of young-onset pancreatic cancer patients.
Authors: Goksu Suleyman Yasin , Kazmi Syed Mohammad Ali , Sanford Nina Niu , Aguilera Todd Anthony , Hsieh David , Sanjeevaiah Aravind , Verma Udit , Kainthla Radhika , Khosama Leticia , Maxwell Mary Claire , Fangman Benjamin David , Bleeker Jonathan Scott , Beg Muhammad Shaalan , Atiq Muslim 
Published: February 2020

674 Background: Young-onset pancreatic adenocarcinoma (YOPC) is uncommon but there are limited studies for these patients. We used a population based registry to compare the characteristics and outcomes of young-onset vs. older patients with pancreatic adenocarcinoma. Methods: We selected the patients with pancreatic adenocarcinoma from the SEER registry diagnosed between 2004 and 2015. Cases with age of diagnosis less than 50 were termed young-onset pancreatic cancer. Stage 4 patients were excluded. We compared baseline characteristics of YOPC vs. older using Chi-square. Kaplan Meier and Cox regression were used for survival analysis of these patients. Results: Of 28,904 patients, 1,415 (4.9%) had YOPC while 27,489 (95.1%) were older. YOPC were more likely to have stage 3 compared to older patients with PC (31.6% vs. 25.3%). YOPC had a higher rate of surgery than older patients (40% vs. 29.1%, p < 0.001), were more likely to be male, black and of Hispanic ethnicity. The primary tumor location was not different between the two groups. Overall survival (OS) was higher in YOPC versus older patients (12 vs. 9 months, p < 0.001). The analysis of multivariable Cox regression confirmed that there is a significant association between survival and YOPC group after adjusting for stage, grade, gender, ethnicity, surgery and race (HR 1.23, 95% CI: 1.13-1.33, p < 0.001). Conclusions: Patients with non-metastatic YOPC represent a group of patients with distinct clinical characteristics. YOPC have a higher rate of surgery and better overall survival compared to older patients. [Table: see text]
Clinicopathological features of pancreatic cancer-related diabetes.
Authors: Lee Michael , Wong Hui-Li , Tsang Erica S. , Addison Sean McKay Fenlon , Topham James T. , Karasinska Joanna , Kalloger Steve , Loree Jonathan M. , Schaeffer David F. , Renouf Daniel John 
Published: February 2020

675 Background: Epidemiological studies suggest pancreatic ductal adenocarcinoma (PDAC) may be strongly interrelated with diabetes. However, little is known about the clinicopathological features of pancreatic cancer related diabetes. Methods: A retrospective chart review was undertaken of all patients with advanced PDAC treated with at least one cycle of palliative chemotherapy at BC Cancer, Vancouver between Jan 2012- Dec 2015. Diagnosis of diabetes was determined by consultation documentation and/or fasting glucose > 7mmol/L or HbA1c > 48mmol/L. Peripancreatic diabetes is defined as diabetes diagnosis < 3 years prior to PDAC diagnosis. Results: 578 patients were identified with median age 66 (49-81), 54.6% male, 39.5% non-smoker and 63.5% ECOG 0/1. 27.3% confirmed diabetics, of which 75.8% (119/157) have peripancreatic diabetes. At initial diagnosis, 11.2% were deemed upfront resectable, 44.0% borderline/locally advanced, and 55.1% metastatic. Median overall survival (OS) for the cohort based on stage of disease at initial diagnosis for borderline, locally advanced and metastatic was 22 months (16.1-27.9), 12 months (10.1-13.9) and 6 months (5.0-7.0) respectively. There was no association with diabetes status and OS noted (p = 0.58). Statistical differences were noted in BMI (24.1 v 26.1, p = 0.003), and proportion of Charlson comorbidity index (CCI) of 2 (2.2 v 88.3%, p < 0.01) between non-diabetic and diabetic patients respectively. Statistical difference between peripancreatic diabetes compared to long-term diabetes were noted in resectable status (18.6 v 7.6%, p = 0.048), weight loss > 2kg (78.6 v 60.5%, p = 0.035), hypertension (25.9 v 59.8%, p = 0.002) and dyslipidemia (18.5 v 42.7%, p = 0.024). Conclusions: The majority of patients diagnosed with advanced PDAC with diabetes appeared to develop diabetes within 3 years prior to diagnosis. Further studies to assess the potential role of pancreatic cancer screening investigations in newly diagnosed diabetics are warranted.