bluuebunny/crossref_metadata_2025_split huggingface dataset:
HPG80 (Progastrin), a novel blood-based biomarker for detection of neuroendocrine neoplasms.
Authors: Chauhan Aman , Prieur Alexandre , Kolesar Jill , Arnold Susanne , Cousin Thierry , Payen Lea Francoise , Sands Madison , Napier Dana , Evers Mark , Anthony Lowell Brian 
Published: February 2020

628 Background: Neuroendocrine neoplasms (NENs) are heterogeneous tumors which originate from various organs and are of variable aggressiveness based on grade and morphology. Current biomarkers for NENs lack sensitivity and specificity, especially for high-grade NENs (small and large cell neuroendocrine carcinomas). hPG80, progastrin, is a novel bio-marker which is easily measured in plasma using an ELISA test. Physiologically, hPG80, an 80 amino acid protein, is the precursor of the gastrointestinal hormone gastrin. It is synthetized by gastric antrum G cells, and then processed into gastrin by multiple enzymatic processes. In pathological conditions, the GAST gene, which encodes hPG80, was shown to be over-expressed in human solid tumors from various primary sites. hPG80 is unprocessed and released from the tumor cells and becomes detectable in the blood. This study is the first to explore hPG80 in NENs. Methods: hPG80 was quantified in the plasma from 31 NEN patients using DxPG80 technology (ECS-Progastrin, Switzerland). Progastrin concentrations in 18-70 YO (n = 557) and 18-25 YO (n = 137) healthy blood donors were compared to 31 stage IV NENs patients. The study was IRB approved. Results: Mean age of study cohort at the time of blood collection was 60.9 years. 21 patients had grade 1 and 2 well differentiated NET. 10 patients had high grade NEN (Small cell, large cell and poorly differentiated NEC). High grade sub cohort also included two well differentiated grade 3 NET patients. Mean hPG80 in NENs was 14.17 pM as compared to 2.04 pM and 0.99 pM in 18-70 and 18-25 YO control groups (p < 0.0001), respectively. Subgroup analysis of NENs revealed mean hPG80 of 24.61 pM in high-grade NENs (n = 10) vs 10.88 pM in G1/2 NETs (n = 21). Conclusions: This first-ever study of plasma hPG80 in NENs suggests hPG80 may be a diagnostic and/prognostic blood-based biomarker in both low and high-grade NENs and further study is warranted. A prospective trial is ongoing in high-grade NEN to evaluate its role in monitoring of disease (NCT03958045) and further studies in low-grade NETs are underway. This research was supported by Cancer Center Support Grant (CCSG) from the National Cancer Institute (P30 CA177558) and ECS Progastrin.
Blood neuroendocrine gene transcripts (NETest) as a diagnostic of pancreatic neuroendocrine tumors and to identify the efficacy of surgical resection.
Authors: Partelli Stefano , Muffatti Francesca , Andreasi Valentina , Falconi Massimo , Modlin Irvin Mark 
Published: February 2020

631 Background: Surgery is the only treatment for cure of pancreatic neuroendocrine tumours (PNET). There are no effective biomarkers to assess completeness of resection and predict recurrence. The aims of this study were 1) evaluate if blood measurement of neuroendocrine gene transcripts (NETest) were diagnostic of PNET and 2) assess if blood levels correlated with the resection type (R0/ R1/R2). We compared transcript analysis with Chromogranin A (CgA), the current standard of care. Methods: A prospective, longitudinal, single center study (ClinicalTrials.gov ID: NCT03012789) of 30 PNETs. Blood for NETest and CgA were collected preop and on postop day 30 (POD30). Transcript measurement: real-time quantitative reverse transcription PCR and multianalyte algorithmic analysis (NETest) (normal 0-20, > 20 stable and > 40 progressive disease; CgA: (ELISA) (normal < 109mg/ml). Analysis: Student’s t test, Mann-Whitney U test and Fisher’s exact test. Data: mean±SEM. Results: Surgical resections ( n= 30) were: 26 R0, 2 R1, 2 R2. In vitro diagnostic: Preop NETest positive in all 30 (NETest: 38±4) (1005) whereas CgA levels positive (220±66ng/ml) in 9 (30%, p< 0.0001). Surgery R0: ( n= 26): NETest significantly decreased from pre-op of 45±3 to 21±4 ( p< 0.001) at POD30. Post operatively 13 (50%) exhibited an elevated score. One patient (Ki67 18%; extensive nodal involvement) had a score of 80, consistent with residual progressive disease. The remaining 12 had NETest levels of 27 at POD 30. CgA was elevated in 8 (31%) with no decrease at POD30 (154±44ng/ml vs. 109±22ng/ml). R1/R2 ( n= 4): NETest scores unchanged (42±17 vs 46±16) at POD30. CgA levels unchanged (378±332 vs. 753±634ng/ml). Conclusions: The NETest is an accurate in vitro diagnostic biomarker for PNET (100%). After R0 resection NETest decrease indicates the blood test is concordant with tumor removal. Elevated post-resection scores are consistent with residual disease and with reported recurrence rates after pancreatic surgery. CgA exhibited no clinical utility. At 1 month post-surgery, the NETest provides an early indication of high risk recurrence patients who can be stratified for further therapy. Clinical trial information: NCT03012789.
A randomized, multicenter, phase II trial of gemcitabine (G), cisplatin (C) +/- veliparib (V) in patients with pancreas adenocarcinoma (PDAC) and a known germline (g)BRCA/ PALB2 mutation.
Authors: O'Reilly Eileen Mary , Lee Jonathan W. , Zalupski Mark , Capanu Marinela , Park Jennifer , Golan Talia , Tahover Esther , Lowery Maeve Aine , Chou Joanne F. , Sahai Vaibhav , Brenner Robin , Kindler Hedy L. , Yu Kenneth H. , Zervoudakis Alice , Vemuri Shreya , Stadler Zsofia Kinga , Do Richard K. G. , Dhani Neesha C. , Chen Alice P. , Kelsen David Paul 
Published: February 2020

639 Background: gBRCA 1,2 mutations occur in 5-8% PDAC. Platinum and poly-ADP ribose polymerase inhibitors (PARPi) effective in BRCA-mut cancers. Phase I GC + V high RR 78%; combination may delay resistance in PDAC (O’Reilly, Cancer, 2018). Herein, we evaluate GC +/- V in a multi-national, randomized phase II trial. Methods: Eligibility: Untreated germline (g)BRCA, PALB2 mut PDAC; measurable stage III/IV; ECOG 0-1. Randomized 1:1 Arm A or B. Treatment: Arm A: G 600 mg/m2 IV, C 25 mg/m2 IV, d3 and 10, V 80 mg PO BID day 1-12, all q 3 weeks or Arm B: GC only. Primary endpoint: RECIST 1.1 response rate (RR). Simon 2-stage per arm: null hypothesis 10% vs promising 28%; type I, II error 10%. Secondary endpoints: progression-free survival (PFS), OS (m), disease control rate (CR+PR+SD), safety and correlative analyses. PFS, OS compared between arms using log-rank test and RR, DCR using Fisher’s exact test between arms. Results: N = 52 enrolled 01/14- 11/18. N = 2 withdrew Arm B. N = 50 for ITT. Male = 22 (44%), Female = 28. Median age = 64 years (range 37-82). BRCA1 N = 12, BRCA2 N = 35, PALB2 N = 3. Stage III N = 8; Stage IV N = 42. Hematologic Toxicity: Arm A vs Arm B: Gd 3-4 neutropenia 13 (48%) vs 7 (30%); Gd 3-4 platelets 15 (55%) vs 2 (9%); Gd 3-4 anemia 14 (52%) vs 8 (35%). Non-hematologic toxicity similar Arm A vs B. Exploratory analyses (combined Arms): Med OS if > 4 m platinum → PARPi: 23 m (95%CI 6.5- 53.9). Med OS by BRCA: BRCA1: 14 m (8.1- 18.5); BRCA2: 20.2 m (12.3- 24.4). Med OS by ECOG: ECOG 0: 23 m (13.8- 24.5); ECOG 1: 14.3 (8.1 vs 16.4). Two-year OS rate for entire cohort: 30.6% and 3-year OS: 17.8%. Conclusions: GC +/- V very active in gBRCA/PALB2 mut PDAC with high RR, PFS, OS with both A, B significantly exceeding threshold RR. Improved DCR arm A vs B, but with greater heme toxicity A vs B. Study confirms GC as reference treatment in gBRCA/PALB2 with durable survival in subset. Funding: National Cancer Institute, CTEP, Lustgarten Foundation, AbbVie. Clinical trial information: NCT01585805 . [Table: see text]
The clinical utility of the 2017 Fukuoka Guidelines and 2015 American Gastroenterological Association Guidelines for the management of intraductal papillary mucinous neoplasms.
Authors: Lanke Gandhi , Campbell Donald , Coronel Emmanuel , Bhutani Manoop S. , Weston Brian , Ross William A. , Kim Michael Paul , Nogueras-Gonzalez Graciela M. , Katz Matthew H. G. , Lee Jeffrey H. 
Published: February 2020

640 Background: Mucinous cystadenocarcinoma are malignant and mucinous pancreatic cysts (PC) have malignant potential. The management of PC remains controversial despite consensus guidelines. This study aims to evaluate the clinical utility of the 2017 Fukuoka Guidelines (FG) and 2015 American Gastroenterological Association Guidelines (AGA-G) for the management of PC. Methods: 212 patients who underwent EUS for PC between 2010 and 2017 were identified. The FG and AGA-G were used to define worrisome and high-risk cyst features. Receiver Operating Characteristic (ROC) curve was used to define sensitivity (SN), specificity (SP), positive predictive value (PPV) and negative predictive value (NPV). Results: 141 of 212 patients had IPMNs.EUS-FNA was performed in 76.5% with no reported complications. Median follow-up was 4.2 years. The majority of the IPMNs were in the pancreatic head (44.7%) or body (39.7%) while only 15.6 % were in the tail. Using the FG, 46.1% had at least one worrisome feature (FG-W) and 7.1% had at least one high risk feature (FG-HR). Using the AGA-G, 28.4% had at least one HR feature (AGA-HR1) and 1.4% patients had two or more risk factors (AGA-HR2). A change in cyst character (increase of > 5 mm in 2 years, development of a solid component, or new pancreatic duct dilation) was noted in 43.2% patients. The median time to cyst change was 21 months. For prediction of cyst changes, the FG-W had a SN of 45.8%, SP of 55.4%, PPV 45%, and NPV 56%. FG-HR had a SN of 14.3%, SP of 53.2%, PPV 1.7%, and NPV 91.8%. AGA-HR1 had a SN of 35.3%, SP of 51.5%, PPV 20%, and NPV 69.9%. AGA-HR2 had a SN of 0%, SP of 54.2%, PPV 0%, and NPV 97.3%. No difference was seen in cyst change or development of high risk or worrisome features with CEA > 192 vs. < 192 (p = 0.99). During follow up, 14 patients died, but only one patient died of pancreatic cancer. Conclusions: FG and AGA-G are difficult to validate because malignant cyst transformation is rare. There was no correlation between any cyst characteristics on EUS and cyst changes. FG-W had the best performance in predicting changes. Surgical candidates should be carefully selected, as these guidelines have a limited clinical utility.
Determining when endoscopic ultrasound (EUS) changes management for patients with pancreatic cystic neoplasms.
Authors: Sidhu Hasrit , Maher Khaola , Farnell Dave , Chen Leo , Gan Ian , Segedi Maja 
Published: February 2020

641 Background: Pancreatic cystic neoplasms (PCNs) are being incidentally detected at an increased rate due to the widespread use of CT and MRI. CT and MRI cannot always differentiate between malignant and benign PCNs. EUS is an emerging tool that provides higher quality descriptions of pancreatic cysts and can be used to differentiate between benign and malignant features. Considering that EUS is a resource dependent tool, we hope to identify the PCN cases in which EUS changes management. Methods: We conducted a retrospective case-control chart review evaluating patients, who were diagnosed with pancreatic cysts and underwent EUS for analysis between January 1, 2010 and December 31, 2017. We determined whether EUS correctly identified high-risk features (HRFs) relative to CT/MRI and whether EUS upstaged or downstaged the CT/MRI diagnosis to change overall patient management. Results: EUS was found to have a high specificity (> 95%) for all high-risk features identified in the AGA and FG guidelines and a low sensitivity ( < 70%) for all high risk features except cyst size > 3cm (82.35%) and mural nodule < 5mm (100%). EUS was found to change management in 29.4% of cases (18.2% upstaged, 11.2% downstaged). EUS screening led to a total of three adenocarcinoma diagnoses, in which two were reported to be invasive. Conclusions: The high specificity of EUS supports its use in the differentiation of high risk PCNs identified on cross-sectional imaging. Its low sensitivity indicates that the reliance on operator experience may be a substantial limitation resulting in inconclusive diagnoses. In conclusion, considering that EUS is successful in changing patient management of PCNs, it should be readily referred when any HRF is identified on cross-sectional imaging.
Pancreatic cancer (PaC)-specific health-related quality of life (HRQoL) with maintenance olaparib (O) in patients (pts) with metastatic (m) PaC and a germline BRCA mutation (gBRCAm): Phase III POLO trial.
Authors: Hall Michael J. , Golan Talia , Hammel Pascal , Reni Michele , Van Cutsem Eric , Macarulla Teresa , Park Joon Oh , Hochhauser Daniel , Arnold Dirk , Oh Do-Youn , Reinacher-Schick Anke C. , Tortora Giampaolo , Algül Hana , O'Reilly Eileen Mary , McGuinness David , Cui Karen , Joo Seongjung , Yoo Hyun Kyoo , Patel Nikunj , Kindler Hedy L. 
Published: February 2020

648 Background: In POLO (NCT02184195), maintenance O significantly improved progression-free survival vs placebo (P) in pts with a gBRCAm and mPaC without compromising HRQoL (Hammel Ann Oncol 2019). We report additional predefined exploratory HRQoL data from the PaC-specific EORTC QLQ-PAN26 questionnaire. Methods: Pts were randomized to O (300 mg bid; tablets) or P. QLQ-PAN26 was completed at baseline (BL), after 1, 2, 3 + 4 weeks (wk) of treatment, every 4 wks until progression, at discontinuation, and 30 days after last dose. Scale range = 1–100 (higher score = greater symptoms); a 10-point change was predefined as clinically meaningful. Adjusted mean change from BL (CFBL) was analyzed by mixed model for repeated measures; time to sustained clinically meaningful deterioration (TSCMD) by log-rank test. Results: Analyses included the 89/92 O- and 58/62 P-arm pts with BL data (overall compliance: 97.8% vs 98.3%). Symptom scores were well balanced in both groups at BL and remained low and stable over time (Table). There were no clinically meaningful between-group differences in adjusted mean CFBL symptom scores. TSCMD in symptoms were not significantly different with O vs P. Conclusions: HRQoL was preserved with maintenance O, as shown by a low and stable PaC symptom burden over time, with no difference vs P. These data support the clinical benefit of O in pts with a gBRCAm and mPaC. Clinical trial information: NCT02184195 . [Table: see text]
The impact of primary tumor location (PTL) and age on the risk of developing noncolonic second primary malignancy (SPM) in colon cancer (CC) patients (PTS).
Authors: Chu Charles , Lin Albert Y. 
Published: February 2020

67 Background: Colon cancer remains one of the leading causes of cancer death worldwide. There has been a renewing interest in the role of PTL (right- or RS vs. left-sided or LS) in CC for their differences in biology, prognostic and predictive features. Given the increasing incidence of early-onset (age 20-49) CC, coupled with their longer life expectancy, we seek to examine the effects of PTL and age in the development of SPM in a population-based cohort. Methods: Surveillance, Epidemiology, and End Results (SEER) Program data were queried to identify CC PTS diagnosed between 1973-2015 with complete follow-up information and available data on SPM. Using SEER*Stat, we calculated standardized incidence ratios (SIRs) -- the ratio of observed to expected cases of SPM based on incidence data in the general US population and compared by PTL (RS vs. LS) and age of diagnosis (20-49 vs. >49). Results: A total of 269,442 (RS/LS=46.4%/53.6%) CC PTS were obtained. Overall RS, compared with LS, CC PTS have a higher likelihood of developing SPM in all sites (OR: 1.09, 95% CI: 1.08- 1.11 vs. 1.03, 1.02-1.04). RS CC PTS and age 20-49 group, compared with other subgroups, has a much greater likelihood of being diagnosed with the following SPM:small intestine, urinary tract, bile duct, gynecologic (GYN), and stomach cancers, as shown in the Table below. Conclusions: Our results show that the increased risk in non-colonic SPMs in CC PTS is associated with RS CC and age less than 49, suggesting the implications on survivorship care and surveillance of SPMs. Furthermore, there may be a possible overlap with Lynch syndrome in these PTS with SPM given the overlap in the presentation of cancer patterns and early-onset of CC, suggesting the indication for MMR testing. [Table: see text]
Neoadjuvant therapy (NAT) and its role for pancreatic adenocarcinoma (PC) in the current era: Institutional experience.
Authors: Walzer Emily , Deng Mengying , Handorf Elizabeth A. , Blumenreich Aryeh , Pease Lauren , Dorta Marianna , Sorice Kristen , Lynch Shannon M. , Vijayvergia Namrata , Dotan Efrat 
Published: February 2020

672 Background: PC affects 57,000 people in the U.S. annually with poor long-term outcomes. NAT for localized disease has increasingly been used but lacks robust prospective data. We investigated the disease course and outcomes for patients (pts) undergoing NAT versus upfront surgery for PC at a high-volume academic center. Methods: Utilizing our IRB-approved retrospective database of metastatic PC pts (year 2000-2017), we identified pts who presented with localized disease and were considered for surgery and present the baseline tumor and treatment characteristics here. Fisher’s exact and Wilcoxon Rank-Sum tests were used for categorical data and Kaplan Meier (KM) curves for survival data when comparing those who had upfront surgery versus surgery following NAT. Results: 352 pts with localized disease at diagnosis were included in our analysis with median age of 65 y (range 38-89) and 45% females. NAT was used in 225 (64%) pts while 109 pts (31%) had upfront surgery and 18 pts (5%) received no treatment. Adjuvant therapy was given to 77% of pts after upfront surgery and 48% of pts after surgery following NAT. NAT regimen consisted of chemotherapy (CTx) and radiation for 48%, CTx alone for 8% and radiotherapy alone for 44% of pts. Of those receiving CTx, 24% received triple agent while 51% and 25% received dual and single agent therapy. Pt factors (age, CCI, gender, BMI, smoking status, race) did not differ between those receiving upfront surgery and surgery following NAT but upfront surgery was associated with a lower stage at diagnosis (p < 0.0001). Surgical resection after NAT occurred in 79 pts (35%) with median overall survival of 26.3m vs 19.7m (p = 0.06) in those who had upfront surgery. Survival rates at year 1, 3, and 5 years were 94%, 34%, and 8% for those with NAT followed by surgery vs 76%, 17%, and 11% for those with upfront surgery (p = 0.06). Conclusions: Use of NAT is prevalent, yet only 35% of pts make it to surgical resection. Survival was improved for pts who underwent resection following NAT versus upfront, although the difference was not statistically significant. Additional research is warranted to define the optimal NAT approach for pts with borderline resectable PC.
First-line drug selection versus sequential treatment in advanced pancreatic cancer: Does it really matter? Multi-institutional Canadian perspective.
Authors: Barrera Ivan , Papneja Neha , Ranger Jill , Papneja Abhishek , Novotny Petr , Ahmed Shahid , Batist Gerald , Kavan Petr 
Published: February 2020

673 Background: Folfirinox (FFX) and Gemcitabine with nab-Paclitaxel (GN) are both proven to be superior to Gemcitabine (G) in the first line treatment (1LTx) for advanced pancreatic cancer (APC). Yet, the optimal 1LTx selection nor sequential Tx (ST) has not been fully established. Therefore, the best choice for 1LTx is a matter of debate often influenced by access to drugs. This analysis was conducted to compare outcomes based on 1Ltx selection and ST in APC. Methods: We assessed patients (pts) with APC who received either FFX or GN as 1LTx during 2010-2019 at three Canadian institutions. As well as the ST used. The main objective was to assess survival. Kaplan method and log-rank test were used for survival curves. Results: This retrospective study included 231 pts; 1LTx included 143 pts on FFX and 88 pts on GN. FFX pts were predominantly male; 89(62.2%) vs 46(52.3%) and slightly younger (median age 62 vs 66) than GN. WHO performance status (PS) of 0 were 38 (28.4%) vs 14 (16.5%) and 1 were 90 (67.2%) vs 65 (76.5%) respectively. There were more grade 3-4 toxicity in FFX vs GN group: GI 55 (38.5%) vs 15 (17%) and hematologic 51 (35.4%) vs 20 (22.7%) respectively. Grade 3-4 neutropenia rates were similar in both regimens. The median PFS of FFX was 5.5 months (95% CI: 5.0-6.7) vs 5.1 (95% CI: 3.8-7.1) with GN (p=0.37). The median OS with FFX was 9.3 months (95% CI: 7.5-11.1) vs 10.2 (95% CI: 6.8-11.3) with GN (p=0.81). There were not statically significant. Table shows Tx frequency across 4LTx. 2LTx and beyond regimens included G, GN, FFX, Capecitabine, Irinotecan liposome plus 5-FU, Irinotecan and clinical trials. Conclusions: Our results revealed that pts who received 1LTx FFX or GN had similar PFS and OS even though 1LTx FFX group was younger with better PS, allowing to continue 2-4LTx more frequently when compare with 1LTx GN group. Therefore, 1LTx selection appear to have more impact in our pts rather than ST, whereas GN is less toxic and seems a preferable 1LTx choice for most pts. FFX could be reserved for young high-performance pts. [Table: see text]
Perioperative complication rates following neoadjuvant therapy in pancreatic adenocarcinoma.
Authors: Deig Christopher R. , Beneville Blake , Liu Amy , Kanwar Aasheesh , Grossblatt-Wait Alison , Sheppard Brett C. , Gilbert Erin W. , Lopez Charles D. , Billingsley Kevin G. , Nabavizadeh Nima , Thomas Charles R. , Grossberg Aaron 
Published: February 2020

688 Background: Whether upfront resection or total neoadjuvant therapy is superior for the treatment of potentially resectable pancreatic adenocarcinoma (PDAC) remains controversial. The impact of neoadjuvant treatment on major perioperative complication rates for patients (pts) undergoing resection for PDAC is commonly debated. We hypothesized that rates would be comparable among patients receiving neoadjuvant chemoradiation (neo-CRT), neoadjuvant chemotherapy alone (neo-CHT), or upfront surgery. Methods: This is a retrospective study of 208 pts with PDAC who underwent resection within a multidisciplinary pancreatico-biliary program at an academic tertiary referral center between 2011-2018. Data were abstracted from the medical record, an institutional cancer registry and NSQIP databases. Outcomes were assessed using χ2, Fisher’s exact test and two-tailed Student’s t-tests. Results: 208 pts were identified: 33 locally advanced, borderline or upfront resectable pts underwent neo-CRT, 35 borderline or resectable pts underwent neoadjuvant-CHT, and 140 resectable pts did not undergo neoadjuvant therapy. There were no statistically significant differences in major perioperative complication rates between groups. Overall rates were 36.4%, 34.3%, and 26.4% for pts who underwent neo-CRT, neo-CHT alone, or upfront resection, respectively (p = 0.38). No significant difference were observed in complication rates (35.3% v. 26.4%; p = 0.19) or median hospital length of stay (10 days v. 10 days; p = 0.87) in pts who received any neoadjuvant therapy versus upfront resection. There were two perioperative deaths in the neo-CRT group (6.1%), zero in the neo-CHT group, and four in the upfront resection group (2.9%); p = 0.22. Conclusions: There were no significant differences in major perioperative complication rates, hospital length of stay, or post-operative mortality in pts who underwent neoadjuvant therapy (neo-CRT or neo-CHT alone) versus upfront surgery. Notably, neo-CRT had comparable perioperative complication rates to neo-CHT alone, which suggests neoadjuvant radiation therapy may not pose additional surgical risk.