bluuebunny/crossref_metadata_2025_split huggingface dataset:
Oxaliplatin based chemotherapy for advanced well-differentiated neuroendocrine tumors: A systematic review and meta-analysis.
Authors: Wang Jian , Wang Xiangling , Chu Yunxia , Li Shuguang , Hao Jing 
Published: June 2023

e16240 Background: Currently, chemotherapy is predominantly considered in advanced well-differentiated neuroendocrine tumors (NENs) with high ki67 proliferation index and tumor burden. So far, no standard regimen is available and alkylating agents alone, such as temozolomide or in combination with 5-fluorouracil or capecitabine are widely used. Besides, oxaliplatin based chemotherapy has shown promising antitumor activity without being influenced by the MGMT status. In the current SRMA, we aim to address the efficacy of oxaliplatin based chemotherapy in advanced well differentiated NENs. Methods: We conducted a systematic database search using PubMed/MEDLINE and EMBASE. Eligible studies included randomized and single-arm trials, prospective observational and retrospective studies documenting the clinical efficacy of oxaliplatin based chemotherapy for advanced well-differentiated NENs. The pooled overall response rate (ORR), median progression-free survival (PFS), and median overall survival (OS) were calculated and weighted using generic inverse variance in a random-effects model, as well as subgroup analysis for pts with pancreatic NETs (pNETs) and extra-pancreatic NETs (epNETs), G1-2 and G3 NETs. Results: 14 of 24 identified publications were included with a combined total of 865 patients in 3 phase II trial and 11 retrospective studies. 495 pts received FOLFOX, 155 pts XELOX, 130 pts GEMOX and 138 pts plus bevacizumab. 48.4% (419/865) patients were pNETs, and G3 NETs accounted for 21.7% (188/865). The pooled ORR was 27.9% (237/865, 95% CI: 23.2-32.5). pNETs showed much higher ORRs (37.7%,114/303, 95% CI: 31.1-44.3) than epNETs (14.9%, 40/251, 95% CI: 10.5-19.2), χ2 = 32.17, p < 0.001. ORRs in G1-2 NETs was 23.1% (66/273, 95% CI: 18.2-28.1), while in G3 NETs was 45.7% (42/85, 95% CI: 29.7-61.6), χ2 = 19.60, p < 0.001. FOLFOX plus bevacizumab showed a higher ORR (38.3%, 38/98, 95% CI: 28.8-47.9) than the oxaliplatin based regimens without bevacizumab (26.9%, 166/594, 95% CI: 23.4-30.4), χ2 = 4.745, p = 0.029. The median PFS in pNETs was 8.1 months (n = 247, 95% CI: 6.3-9.9), similar to 8.4 months in epNETs (n = 211, 95% CI 5.7-11.2). The median PFS in G1-G2 and G3 NET was 13.4 months (95% CI 9.1-17.6) and 7.1 months (95% CI 4.1-9.6) respectively. Besides, FOLFOX plus bevacizumab also showed a trend of a longer PFS (12.4months, 95% CI 9.5-15.2) than those without bevacizumab (7.6months, 95% CI 6.8-8.3). The pooled median overall survival was 28.8months (95% CI 26.7-30.9). Conclusions: Among the advanced well-differentiated neuroendocrine tumors, oxaliplatin based chemotherapy alone or plus bevacizumab could be a good alternative regimen, especially in pts with pNETs and G3 NETs.
Association of guideline adherence in diagnosis and treatment of pancreatic neuroendocrine tumors with survival.
Authors: Overheu Oliver , Gisder Doreen M. , Noepel-Duennebacke Stefanie , Kraeft Anna-Lena , Janot-Matuschek Monika , Uhl Waldemar , Tannapfel Andrea , Reinacher-Schick Anke C. 
Published: June 2023

e16241 Background: Clinical guidelines and their adherence are important instruments to ensure quality in diagnosis and treatment, especially when treating rare diseases like pancreatic neuroendocrine tumors (PanNET). However, data on guideline adherence and its impact on outcome in PanNET is limited. Methods: Cases of PanNET according to 2017 WHO definition at our university hospital between 2010 and 2019 were retrospectively identified. Adherence to ENETS guideline 2007/2012 and the German S2k guideline was evaluated among four categories (diagnostics: chromogranin A (CgA) testing, somatostatin receptor imaging, discussion in an interdisciplinary tumor board; pathology: reporting of grading, Ki67 and synaptophysin expression; surgical treatment; systemic treatment including aftercare). Guideline adherence within these categories was valued with one point per fulfilled criterion and a final score between 0-8 points was calculated. Data was analyzed using Student’s t-test, Chi-square test and Spearman’s correlation coefficient test. Results were considered significant at α = 0.05. Results: Overall, 115 patients (47% female) with a diagnosis of PanNET were identified. Mean age was 61 (±13.5) years. Mean overall survival (OS) was 45 months, mean recurrence free survival (RFS) was 47 months. During the study period 21 patients (18%) had died, 6 patients (5%) were lost-to-follow-up and 11 patients (10%) had a recurrent disease after initially curative resection. 24 patients (21%) presented with metastatic disease upon diagnosis. Guideline adherence concerning pathology reports (97%) as well as systemic (91%) and surgical treatment (75%) was high, while complete adherence in diagnostic modalities was low (5%). However, the latter was mainly driven by lack of CgA testing (31%), and somatostatin receptor imaging (11%) not being performed on initial diagnosis, but in most cases during follow-up. Subsequently, complete guideline adherence (8/8) across all categories was rare (3%). However, a higher overall score was associated with survival (p = 0.032, V = 0.321). Long term survivors had a higher mean overall adherence score (5.6 vs. 6.1; p = 0.05). In addition, the composite score of surgical and systemic therapy was significantly correlated with RFS (ρ = 0.254, p = 0.016). Conclusions: The quality in diagnosis and treatment of PanNET in our cohort was high. These are the first data to demonstrate a positive impact of guideline adherence on survival and RFS in PanNET.
Correlating peptidylglycine alpha-amidating monooxygenase (PAM) expression with clinicopathologic variables in gastrointestinal (GI) neuroendocrine tumors (NETs).
Authors: Sim Jordan , Marginean Horia , Jirovec Anna , Vickers Michael M. , Marginean E. Celia , Asmis Tim , Marginean Bianca , Goodwin Rachel Anne 
Published: June 2023

e16243 Background: Peptidylglycine alpha-amidating monooxygenase (PAM) is a hypoxia-responsive protein which is responsible for peptide alpha-amidation, important in neuroendocrine hormone maturation. A prior study of well-differentiated neuroendocrine tumors of multiple sites, both GI and non-GI, has shown that PAM expression by immunohistochemistry correlates with important clinical and pathologic parameters. We assessed PAM expression by immunohistochemistry using two separate scoring systems in patients with well-differentiated neuroendocrine tumors (NETs) exclusively of the GI tract and assessed its correlation with clinical and pathologic variables. Methods: A tissue microarray was constructed from 58 patients with NETs of the GI tract. Two separate scoring systems were used, the immunoreactive score (IRS) and one as described by Horton et al (2020). The IRS score was derived by scoring for intensity (range 0-3) and percent of cells staining (range 0-4), multiplying these to give an overall IRS between 0 and 12. These results were dichotomized into 0-1 (negative) and 2-12 (positive). The score as described by Horton et al is a 4-tiered system: 0, no staining; 1, very faint and scarce staining; 2, staining easily visible in > 50% of tissue; 3, moderately dark and intense staining across 50% of tissue; 4, very intense dark staining across > 50% of tissue. These were then divided into negative (0), low (1) and high (2-4) scores. Clinical and pathologic variables were collected from the clinical records and correlated with PAM staining. Results: Patients had NETs involving the stomach (n = 1), duodenum (n = 3), ileum (n = 18), small bowel (n = 12), cecum (n = 2), and pancreas (n = 13). Twenty-one patients (36.2%) had 1 metastatic site, 12 patients (20.7%) had > = 2 metastatic sites and 25 patients (43.1%) lacked metastases. IRS and Horton scores were compared and were correlated (p = 0.007). By IRS, 9 patients (31%) had negative staining, and 20 patients (69%) had positive PAM staining. PAM staining did not correlate with functional status of the tumor (p = 1), synchronicity of disease (p = 1), number of metastatic sites (p = 0.69), Octreotide receptor positivity (p = 0.72) or blood chromogranin A (p = 0.58) and urine 5 HIAA levels (p = 0.52). PAM scoring also did not correlate with Ki-67 of primary tumors (p = 0.57). Conclusions: In our GI NET cohort, PAM staining did not correlate with any of the assessed clinical variables or with Ki-67 of primary tumors. A previous study of NETs involving more body sites found that PAM staining did inversely correlate with Ki-67 scoring. This difference may be due to our assessment of solely gastrointestinal NETs.
Effects of pancreatic enzyme replacement therapy (PERT) on overall survival (OS) in patients (pts) with advanced pancreatic ductal adenocarcinoma (APDAC) and evidence of pancreatic enzyme insufficiency (PEI): A single institution, retrospective, cohort study.
Authors: Picozzi Vincent J. , Najjar Anas , Harb Diala E , Kort Jens J , Mandelson Meg T. 
Published: June 2023

e16254 Background: Weight loss (WL)/cachexia is common in APDAC and associated with multiple adverse pt outcomes. Current NCCN guidelines recommend PERT in PDAC patients with PEI. However, little evidence exists regarding PERT use and clinical outcomes in PDAC, especially APDAC. We present here data on impact of PERT use from our institution. Methods: Study pts were identified from the Virginia Mason PDAC database (01-2010-12/2019). Eligibility criteria included: 1) No upfront resection, 2) no prior PDAC therapy, 3) FE 1 < 200 µg/g or documented evidence of PEI at diagnosis, 4) treatment at least to initial restaging event (8 wks), and 5) data regarding PERT use/dosage available. Pts were stratified by PERT/non-PERT usage. PERT use was defined by prescription for >50% of time from initial Rx to 1st restage using recommended dosing per package insert. Pts on PERT for < 50% of time during this time frame and/or prescribed less than recommended dose were excluded from analysis. Results: 505 total pts were study eligible, PERT 197(39%), non-PERT 308(61%). WL (80 vs 65%, p< 0.001) and cachexia (74 v 54%, p<0.001) were more common in PERT pts. ECOG PS 2 (4 vs 9%, p=0.02) and non-metastatic disease (51 vs 40%, p=0.02) more common in non-PERT pts. Other pt characteristics (age, sex, diabetes at dx, serum albumin, NLR, BMI distribution, % obese) were similar in both groups. OS after adjustment for PS and stage was 15.7 mo (95% CI 13.6-18.3 mo) among PERT users vs. !2.6 mo non-PERT users (95% CI 11.0 -13.7 mo, p=0.02, adjusted hazard ratio 0.81 (95% CI 0.67-0.99). Pts receiving PERT also tended to have a higher therapeutic response rate by both Ca 19.9 and CT: but without statistical significance (p=0.10, 0.09, respectively). Regarding nutrition, PERT vs. non-PERT pts at 8 weeks experienced less WL (-0.4 vs. -1.5 kg, p=0.03) and less change in BMI (-0.3 vs -1.6, p=0.02). This was true even in cachectic pts at dx (change in BMI + 0.1 vs -1.7, p=0.01). Additional analyses of impact of PERT on QOL are ongoing, including in a subset of patients who underwent serial PG-SGA scoring. Conclusions: In this pt cohort, APDAC pts prescribed PERT per recommended dosing had a statistically significant improvement in median OS vs. those not prescribed PERT. This remained true in multivariate analysis after adjustment for population imbalances. PERT use was also associated with a statistically significant reduction in weight loss and change in BMI at 8 weeks, even in those patients defined as cachectic at diagnosis. Further investigation into a) impact of PERT on quality of life, b) mechanisms producing the above observations, c) confirmatory observations in independent datasets, and d) additional therapeutic interventions designed to mitigate weight loss/cachexia in PDAC are needed.
Dosing patterns and treatment patterns in real-world patients with metastatic pancreatic ductal adenocarcinoma (mPDAC) who received FOLFIRINOX in the first line.
Authors: MacEwan Joanna P. , Silver Michelle , Cockrum Paul , Sanders Chad , Kim George P. 
Published: June 2023

e16255 Background: While FOLFIRINOX (FFX) demonstrated a significant overall and progression-free survival benefit vs. gemcitabine in the PRODIGE 4/ACCORD 11 trial among previously untreated patients (pts) with metastatic pancreatic ductal adenocarcinoma (mPDAC), treatment with FFX was associated with a higher rate of grade 3/4 adverse events (AEs). In an effort to reduce toxicity, modified FFX (mFFX) regimens that employ lower doses of components of the regimen have been developed. To better understand the frequency and degree of dose modifications in practice, we examined real-world (RW) dosing patterns among mPDAC pts receiving FFX in first line (1L). Methods: This retrospective observational study utilized the Ontada Clinical Data View: Pancreatic Cancer database. Adult pts diagnosed with mPDAC between January 2015 and November 2022 who initiated treatment with FFX or mFFX within 90 days of their diagnosis for metastatic disease (1L) were included in the study. Pts were required to have an available body surface area measurement within 7 days of the index date. Doses of each FFX component were measured during cycles in which pts received all four components of the FFX regimen on the same date. mFFX was defined as administration of < 150mg/m2 of irinotecan or < 2,720mg/m2 5-FU total during cycle 1. Results: Of the 1,326 pts eligible meeting inclusion criteria and receiving 1L treatment with FFX or mFFX, 1,325 received mFFX and 1 received FFX. The median age at 1L initiation was 65yr (IQR: 58–70), 57% (754 pts) were male, 69% (916 pts) were white, 15% (197 pts) had an ECOG score of 0, 42% (550 pts) had an ECOG score of 1, and 78% (1028 pts) were stage IV at diagnosis. The bolus of 5-FU was frequently omitted—only 20% (262 pts) received it in the first cycle. If pts received the bolus, they did not receive the 5-FU infusion, with the exception of 1 pt. For pts receiving at least two cycles, the percentage of pts with dose reductions of ≥10% (≥20%) between the first and last cycle were 20% (11%) for the 5-FU infusion, 18% (13%) for the 5-FU bolus, 34% (21%) for irinotecan, 12% (9%) for leucovorin, and 40% (28%) for oxaliplatin. Median starting doses were 2400, 401, 152, 399, and 85 mg/m2 for the 5-FU infusion, bolus 5-FU, irinotecan, leucovorin, and oxaliplatin components, respectively. The median number of cycles was 5 (IQR: 3–10) and the median dose intensity per week was 940 mg/m2 for 5-FU, 179 mg/m2 for leucovorin, 38 mg/m2 for oxaliplatin, and 73 mg/m2 for irinotecan. Conclusions: In a RW cohort of pts with mPDAC treated with 1L FFX, almost all received a modified version of the regimen. The 5-FU bolus was omitted for most pts. Doses of other components fell over time for a notable percentage of patients, which may reflect clinician efforts to manage FFX toxicity.
A pilot study of liposomal irinotecan plus 5-FU/LV combined with paricalcitol in patients with advanced pancreatic cancer whose disease progressed on gemcitabine-based therapy.
Authors: Grierson Patrick , Suresh Rama , Tan Benjamin R. , Pedersen Katrina Sophia , Amin Manik A. , Park Haeseong , Trikalinos Nikolaos , Liu Jingxia , Lim Kian-Huat , wang-gillam Andrea , Bansod Sapana Prakashrao 
Published: June 2023

e16263 Background: 5-FU-based chemotherapy is the standard of care for patients with advanced pancreatic cancer progressed on gemcitabine-based therapy. Based on the NAPOLI-1 study, 5-FU/LV/liposomal irinotecan is currently an FDA-approved regimen in the second-line setting with median progression free survival (mPFS) 3.1 months, median overall survival (mOS) 6.1 months and objective response rate (ORR) 16%. In pancreatic cancer mouse models, vitamin D was shown to remodel the desmoplastic stroma and when combined with chemotherapy significantly improved animal survival. Methods: We conducted a pilot study in patients with advanced pancreatic cancer progressed on gemcitabine-based therapy treated with 5-FU (2,400mg/m2)/LV (400mg/m2)/liposomal irinotecan (70mg/m2) with paricalcitol in two dose level cohorts: paricalcitol 75mcg IV on day 1 weekly (N=10, dose level 1) or 7mcg/kg IV on day 1 weekly (N=10, dose level 2). The primary endpoint was safety and toxicity. Dose-limiting toxicities (DLT) were assessed during cycle 1. Secondary endpoints include ORR, PFS and OS. Results: Between 8/29/2019 to 5/6/2021, a total of 20 patients were enrolled in the study. No DLTs or grade 4 adverse events were observed in either paricalcitol cohort. The most common toxicities were gastrointestinal (nausea, diarrhea), fatigue and anemia and were similar in both cohorts. Only one grade 3 adverse event was possibly due to paricalcitol (spinal fracture, dose level 1). 2/17 (12%) evaluable patients experienced an objective response (both in dose level 2), one of which was confirmed. Disease control rate (DCR) was 65%. Median follow up was 6.15 months. At the time of analysis, mPFS of all patients is 3.57 months (95% CI 1.28 – 8.12) and mOS is 6.14 months (95% CI 2.43 – 11.77). The mPFS is 3.55 months (0.79-6.21) for dose level 1 and 4.83 months (0.62-9.96) for dose level 2. The mOS is 6.15 months (0.79-8.12) for dose level 1 and 6.66 months (1.78-14.53) for dose level 2. Correlative analysis shows increased tumor vascularity (via CD31) and a trend toward decreased stromal fibrosis (via Sirius Red) in dose level 2. Conclusions: Administration of paricalcitol in combination with liposomal irinotecan and 5-FU/LV is well tolerated in patients with advanced pancreatic cancer and survival outcomes were comparable to liposomal irinotecan plus 5-FU/ LV. Clinical trial information: NCT03883919 .
Impact of homelessness on outcomes among pancreatic cancer hospitalization: Insight from the 2016-2020 National Inpatient Sample.
Authors: Pagidipally Alekhya , Sharma Shivani , Dandwani Mehndi , Chennapragada Suma Sri , Ramphul Kamleshun , Verma Renuka , Sanikommu Sailaja , Sombans Shaheen , Mejias Stephanie G , Dhillon Balkiranjit Kaur , Lohana Petras , Arti Fnu , Kumar Vijay 
Published: June 2023

e16264 Background: Homelessness is a major socio-economic issue in the United States, affecting an estimated 171 per 100,000 persons in certain states. While pancreatic cancer (PC) tends to have a poor prognosis, the disease requires an early diagnosis, proper care, and follow-ups. As there is a paucity of data highlighting differences in patient characteristics and outcomes of homeless patients with PC, a retrospective study was conducted via a national database. Methods: We used data from the 2016-2020 National Inpatient Sample (NIS), the most extensive hospital database, to identify patients with a diagnosis of pancreatic cancer. Patients with a status of “homeless” were located via the ICD-10 code “Z590”, per suggestions from HCUP and past studies. Several differences in patient characteristics were explored between homeless cases of PC and non-homeless cases via Pearson’s Chi-Square tests. Finally, the adjusted odds ratio (aOR) and 95% Confidence intervals (CI) of various outcomes such as mortality, pulmonary embolism, septicemia, and hepatic failure were calculated via multivariable logistic regression models. Results: Our study identified 544855 pancreatic cancer cases, including 1380 patients classified as homeless (0.3%). 81.5% of homeless patients were males (vs. 52.1%), and 24.6% were admitted on weekends (vs. 20.6%). Moreover, Medicaid was the prime insurer among homeless patients (47.6% vs. 8.6%) with a higher mean hospital charge ($86796 vs. $70610). Racial differences were also observed as 51.9% of homeless cases were Whites (vs. 71.2%), while 31.6% (vs. 13.8%) were Blacks, and 11.3% (vs. 8.2%) were Hispanics. A higher proportion of homeless cases had palliative care utilization (27.9% vs. 19.1%), a Do-Not-Resuscitate (DNR) order (25.7% vs. 23.1%), and required pancreatic and proximal biliary dilation/stenting (4.0% vs. 2.2%). Homeless patients admitted with pancreatic cancer also expressed higher odds of in-hospital mortality (8.7% vs. 7.4%, aOR 1.625, 95% CI 1.280-2.064, p<0.01). No statistical significance was found for events of pulmonary embolism (aOR 1.231, p=0.160), septicemia (aOR 1.044, p=0.674), and hepatic failure (aOR 0.892, p=0.549). Conclusions: Homeless patients with PC were linked with higher in-patient mortality. Various racial and socio-economic differences were also observed. Several efforts to ameliorate access to care among homeless patients and an early diagnosis may help improve the outcomes.
Outcomes among patients with pancreatic malignancy on long-term anticoagulation hospitalized for acute pulmonary embolism: A nationwide analysis.
Authors: Syal Arshi , Arya Yajur , Casipit Bruce Adrian , Dourado Claudia 
Published: June 2023

e16266 Background: Pancreatic cancer is known to have an increased risk of thromboembolic events. Acute pulmonary embolism further complicates the clinical picture and confers a poor prognosis in this population. Data regarding prophylactic anticoagulation in patients with pancreatic malignancy is lacking, although there is evidence that prophylaxis does reduce incidence of venous thromboembolism in pancreatic malignancy. Whether this benefit equates to improved clinical outcomes needs further clarification. Methods: We utilized the 2018-2020 National Inpatient Sample (NIS) Database in conducting a retrospective cohort study. We identified patients who have pancreatic malignancy and acute pulmonary embolism using appropriate ICD-10 CM codes. We stratified patients based on the presence or absence of long-term anticoagulation. A survey multivariable logistic and linear regression analysis was used to calculate adjusted odds ratios (ORs) for the primary and secondary outcomes. A p value of <0.05 was considered statistically significant. The aim of this study is to investigate the outcomes among patients with pancreatic malignancy hospitalized for acute pulmonary embolism looking primarily at the in-hospital mortality, hospital length of stay (LOS) as well as total hospital charges. Results: We identified a total of 160,000 hospitalized patients with acute pulmonary embolism, of which 0.6% (1,120/160,000) had malignant neoplasm of the pancreas and 20.09% (225/1120) are on long-term anticoagulation. The overall in-hospital mortality among those with pancreatic malignancy hospitalized for acute PE was 5.91% (66/1,120). Among those who are on long-term anticoagulation, the overall in-hospital mortality rate was lower at 4.44% (10/225), however, it was not significantly different from those who are not on anticoagulation 6.29% (14/225) (p value=0.64). Utilizing a stepwise survey multivariable logistic regression model that adjusted for patient and hospital level confounders, the use of long-term anticoagulation among hospitalized acute PE patients with history of pancreatic malignancy did not significantly decrease risk for in-hospital mortality (adjusted OR 0.37; 95% confidence interval [CI], 0.09-1.57; p=0.18), hospital LOS (adjusted OR 0.80; 95% confidence interval [CI], 0.63-10.26; p=0.86) or total hospital charges (p=0.32). Conclusions: Our analysis showed that among patients with pancreatic malignancy hospitalized for acute pulmonary embolism, the use of prior long-term anticoagulation did not significantly decrease the risk for in-hospital mortality, hospital LOS as well as total hospital charges. Prospective studies with control of possible confounders are warranted to further clarify the use of prophylactic anticoagulation in pancreatic malignancy and its impact on outcomes.