bluuebunny/crossref_metadata_2025_split huggingface dataset:
INTENSIVE: InterNaTional rEgistry oN Sars-cov-2 posItiVe nEuroendocrine neoplasm patients.
Authors: Spada Francesca , Gervaso Lorenzo , La Salvia Anna , Garcia-Carbonero Rocio , Hernando Jorge , Capdevila Jaume , Hofland Johannes , de Herder Wouter , Koumarianou Anna , Rossi Maura , Boselli Sabrina , Tamayo Darina , Bagnardi Vincenzo , Laffi Alice , Rubino Manila , Sonbol Mohamad Bassam , Fazio Nicola , Halfdanarson Thorvardur Ragnar 
Published: June 2021

e16205 Background: Data about neuroendocrine neoplasms (NENs) patients with SARS-CoV-2 are scanty and specific indications for clinical practice are missing. Our aim is to create an international registry about NENs patients affected by SARS-CoV-2 positivity to give a worldwide representation of the situation. Methods: This is an observational retrospective/prospective multicenter survey based on a direct email invitation. All types of NEN are eligible except SCLC and MiNEN. Patients fulfilling the inclusion criteria from March 1st, 2020 up to the end pf pandemic will be recruited. Electronic CRFs are filled out using the REDCap database. Local Institutional Review Board approval is required before data entry. Results: Eighty-one centers, 24 in and 57 outside Italy, representing 39 countries and 5 continents, were contacted. Fourteen centers did not respond and 15 declined the invitation. Among the remaining 52, 6 centers are currently recruiting and 8 are active but not recruiting yet. As of the current abstract submission deadline, 67 patients have been included, mostly GEP-NET (75%), non-functioning (86%), metastatic (85%) and on active treatment [47% somatostatin analogs (SSAs), 10% everolimus, 12% tirosin-kinase inhibitors (TKIs), 10% peptide receptor radionuclide therapy (PRRT), 15% chemotherapy]. Median age at NEN diagnosis was 57 years whilst the median age at SARS-CoV-2 diagnosis was 62 years. Almost all patients reported COVID-19-related symptoms, more commonly fever (67% of patients), cough (55%) and dyspnea (51%), in 28% of cases exertional and in 22% at rest. More than one third of patients (n, 24) had a pneumonia. The most common therapies for COVID-19 were antibiotics, steroids and hydroxychloroquine. Eleven patients (16%) needed oxygen therapy, three (4%) sub-intensive care and none intensive care. Fifty-six patients (84%) clinically recovered, six (9%) with sequelae, whereas five (7%) died. Among these latter 4 had a NET and 1 a NEC, and no patients have been receiving chemotherapy. With regard to the anti-tumor therapy no change occurred in 66% of patients, temporary interruption in 30%, and definitive discontinuation in 3%, 2% missing. Conclusions: Most of the NEN patients completely recovered from COVID-19, in many cases without any anti-tumor therapy adjustment. No clear correlations were observed with type, primary site and treatment of NEN. The recruitment is ongoing.
Outcomes of pancreatic ductal adenocarcinoma (PDAC) patients treated with neoadjuvant stereotactic body radiation therapy (SBRT) or conventionally fractionated radiation therapy (CFRT).
Authors: Zhu Fan , Wang Haoyu , Ashamalla Hani 
Published: June 2021

e16209 Background: Hypothesis: Neoadjuvant SBRT can improve survival when compared to CFRT in PDAC patients who received chemotherapy. Past retrospective studies have shown improved outcomes of definitive SBRT when compared to CFRT without accounting for chemotherapy.1 We aim to study the outcomes of neoadjuvant SBRT vs CFRT accounting for chemotherapy. Methods: The National Cancer Database (NCDB) was queried for cases of PDAC from 2004-2015. Patients who received surgery and chemotherapy were included. Exclusion criteria were prior hormonal therapy or immunotherapy, lack of pathological confirmation or lack of information about chemotherapy. Log-rank test and Cox proportional hazards model were used to compare survival by radiation modalities. Predictors for overall survival (OS) were identified. Propensity score-matched (PSM) analysis balancing for different variables including type of chemotherapy was conducted. Results: Among 1604 patients, 223 (13.9%) had SBRT, and 1381 (86.1%) had CFRT. The median survivals were 30.0 and 26.0 months ( P = 0.010), while the 2-year survival rates were 63.4% and 53.7% for SBRT and CFRT patients, respectively. SBRT tended to be offered to older patients (age≥65: 56.1% vs 47.3%, P = 0.018), healthier patients (CCI=0: 72.2% vs 63.6%, P = 0.016), patients with worse cT staging (cT3 and cT4: 80.7% vs 69.7%, P = 0.008) and patients who got more multi-agent chemotherapy (89.2% vs 50.5%, P < 0.001). In the cohort with positive clinical lymph nodes (cN+), CFRT tended to decrease the pN staging more when compared to SBRT ( P = 0.032) (Table). In multivariate analysis, multi-agent chemotherapy (HR, 0.72; P < 0.001) was associated with better OS. SBRT did not show significantly better OS when compared to CFRT (HR, 0.81; P = 0.13) after accounting for other covariates including chemotherapy. PSM (1:1 match) analysis matched 223 pairs. SBRT did not show significant OS benefit (HR, 0.80; P = 0.17) when compared to CFRT. Conclusions: SBRT may be superior to CFRT in univariate analysis. However, after accounting for multi-agent chemotherapy, there is no significant survival difference between neoadjuvant SBRT and CFRT. Studies with larger sample size are desired. Neoadjuvant CFRT offers more significant nodal down-staging in patients with clinically positive lymph nodes (cN+) when compared to SBRT. Reference: Zhong J, Patel K, Switchenko J, et al. Outcomes for patients with locally advanced pancreatic adenocarcinoma treated with stereotacticbody radiation therapy versus conventionally fractionated radiation. Cancer2017 Sep 15;123(18):3486-3493. pN staging of cN+ cohort[Table: see text]
Immunoregulation related gene of CSMD2 and RNA activity as potential predicter of 2-year survival in pancreatic cancer: A DNA and RNA sequencing analysis.
Authors: Yan Jiafei , Li Si , Xi Wenjing , Chen Dongsheng , Xiao Mingzhe 
Published: June 2021

e16212 Background: The 5-year survival rate of pancreatic cancer remains as low as 3%-15%. One of the key approaches to enrich current treatment options or improve effectiveness is new biomarker probing. We conducted DNA and RNA sequencing analysis to reveal potential biomarkers related to overall survival. Methods: Whole-exome sequencing, RNA sequencing and clinical data for 209 patients with pancreatic cancer were downloaded from TCGA. Clinical factors and mutational landscape (insertion/ deletion/ single nucleotide variant) were compared between group of OS2+ (OS longer than 2 years) and OS2- (OS longer than 2 years) with T test and Chi-square Test. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were conducted with RNA sequencing data to clarify the functional differences between the two groups. Results: The rates of OS2+ for patients in stage of I/II/III/IV was 43% (9/21), 17.8% (27/152), 0% (0/4), 0% (0/5), respectively. 152 patients in stage II were included for further analysis. No difference of sex and age were found between group of OS2+ and OS2-. Tumor mutation burden was comparable between the two groups. Mutation landscape showed the two groups had the accordance of 50% in top 10 genes. Mutations of CSMD2(18.5% vs. 5.0% , P = 0.026), CMYA5(14.8% vs, 2.5% , P = 0.019) and KCNA6(14.8% vs, 3.3%, P = 0.034) were more frequent in OS2+ group. CSMD2 is thought to be involved in the control of complement cascade of the immune system, and its low expression was significantly associated with differentiation, lymphatic invasion, and tumor size in colorectal cancer. CMYA5 was predicted as novel oncogene in breast cancer with the tool of Moonlight, it may also participate tumor activity in pancreatic cancer. The role of KCNA6 in cancer cell activity is barely known yet. Evaluation of differentially expressed genes between the two groups detected difference in leukocyte differentiation and T cell activation (GO analysis) and MAPK signal pathway (KEGG panalysis), these immunoregulation and MAPK pathways may play critical roles in tumor development and progression and affect the prognosis of pancreatic cancer. Conclusions: Pancreatic cancer with 2-year survival presented significant different DNA and RNA alterations, in which CSMD2 and pathway of leukocyte differentiation and T cell activation are closely associated with immunoregulation. These might provide guidance for prognose management and development of new therapeutic targets. Further mechanistic insights and prospective validation studies are warranted.
Pancreatic cancer outcomes in Nova Scotia: Searching for small windows of opportunity.
Authors: Sun Peiran , Ramjeesingh Ravi 
Published: June 2021

e16219 Background: While pancreatic cancer (PC) globally has poor outcomes, there are still regional variation in PC outcomes in Canada. Nova Scotia (NS) has been documented to have some of the worst outcomes in PC but the details and barriers to the care of PC in NS have never been analyzed. Methods: A retrospective chart review was performed on PC patients (pts) diagnosed in NS from 2013 to 2017 for patient characteristics, referral pattern, treatments and wait times. Cox proportional hazards methods were used to analyze overall survival (OS) with Age, Stage, Eastern Cooperative Oncology Group Performance Status (PS), Charleston Comorbidity Index (CCI), receiving ERCP and receiving chemotherapy as covariates in the multivariate analysis. Results: 667 consecutive pts were identified, which included 357 males and 310 females with a median age of 71 at diagnosis. 42 (6.25%) lived beyond 2 years, while 163 (24.4%) survived for under 30 days and 260 (39%) survived for under 60 days. Patients with a limited survival (under 30 days) when compared to pts who survived > 60 days are older (mean 75 vs 71, P < 0.05), had a higher proportion of ECOG > 2 (81.6% vs 20.3%, P < 0.01), and a higher proportion of stage 4 disease (73.9% vs 41.2%, P < 0.01). There was no significant difference in any measure of wait times. Pts with limited survival were less likely to be seen by Medical Oncology (MO) (20.9% vs 70.9%, P < 0.001), and less likely to receive chemotherapy (1.2% vs 45%, P < 0.001) or ERCP (27% vs 53.8%, P < 0.01). Multivariate analysis showed that receiving ERCP (P = 0.027) and chemotherapy(P < 0.001) are independent predictors of survival, even when accounting for PS, CCI, stage, and age. Conclusions: Analysis of PC outcomes in NS demonstrates a large proportion of pts dying within 30 days of diagnosis. Those pts are older and present with higher stage and worse PS but did not have any significant difference in diagnostic and referral wait times. Those pts receive fewer referrals to Oncology services, fewer potentially life prolonging treatments and we uniquely discovered ERCP as an independent predictor of survival in our population. While further work is needed, this study characterized some of the unique challenges of PC care in NS as a province with a higher proportional of older adults and highlights potential opportunities to improve early healthcare delivery in older adults with limited windows for care.
Primary pancreatic adenocarcinoma (PPDA) and metastatic pancreatic adenocarcinoma (MPDA): Are they genomically distinct?
Authors: Singh Sunny R. K. , Leonard-Murali Shravan , She Ruicong , Lin Chun-Hui , Freaney Jonathan , Poisson Laila , Khan Gazala 
Published: June 2021

e16226 Background: PDA is an aggressive disease with a dismal prognosis. Advances in next-generation sequencing (NGS) have enabled targeted therapies, revolutionizing treatments of several solid tumors. Their role in the management of PDA is limited, in part due to the paucity in our understanding of targetable genomic events. We sought to evaluate genomic differences between PPDA and MPDA in the tumor and tumor immune microenvironment (TIME). The genomic changes after chemotherapy (CTX) administration were also evaluated. Methods: NGS data derived from tumor samples of 150 unique patients was analyzed. Targeted 648 gene DNA sequencing was performed using the Tempus xT and xO assays. Patients were allocated into 2 cohorts: PPDA (n = 75) and MPDA (n = 75), which were overall similar in terms of their demographics. The frequencies of somatic mutations were compared. The immune infiltrate was imputed from RNAseq. Proportions of immune cells (IC), and the tumor mutational burden (TMB) relative to the proportion of IC in the TIME, were also analyzed. Kaplan Meier Survival estimates for most frequent mutations and TMB were calculated. Results: The most frequently mutated genes amongst the 150 study subjects were: KRAS (92.7%), TP53 (76.7%), CDKN2A (45.3%), SMAD4 (31.3%), ATM (12.7%) and ARID1A (10.7%). Patients in the MPDA cohort had a higher rate of mutation in several genes when compared to PPDA, most notably in TP53 (85.3% vs 68.0%, p = 0.010), ARID1A (16.0 vs 5.3%, p = 0.037) CDKN2A (49.3 vs. 41.3%, p = 0.3) and SMAD4 (33.3 vs. 29.3 p = 0.7). We also evaluated if the genetic changes between PPDA and MPDA are associated with alterations in the TMB and differences in the TIME. A higher TMB was seen amongst patients in the MPDA vs PPDA cohort (2.73 vs 1.73 Mut/Mb, p = 0.008). TMB was also significantly increased after CTX (2.22 vs 1.63 Mut/Mb p = 0.049). TMB ≥ 3 was associated with decreased odds of progression free survival ≥ 12 months (OR 0.26 95% CI 0.078-0.822, p = 0.023). Regarding immune infiltrate, the proportion of CD4 and CD8 T cells were higher in the PPDA cohort. Macrophages and NK cells were more prevalent the MPDA cohort. TMB had a positive correlation with the degree of macrophage infiltration in the TIME (Multivariate estimate: 1.70, p value 0.01). Conclusions: PPDA and MPDA are biologically dissimilar entities with genomic disparity. Associated differences were observed in TMB and TIME. There is a differential increase in the spectrum of mutations in MPDA as compared to PPDA, specifically in p53, ARID1A, CDKN2A and SMAD4. The burden of increased mutations in MPDA is associated with an increase in the TMB and tumor associated macrophages. The role of serial NGS in the management of PDA both in early and late disease should be investigated further to identify evolving genomic changes that correlate with outcome.
Positive association between Helicobacter pylori infection and pancreatic cancer: A case-control study.
Authors: Otieno Steve , Jain Amit L , Mohammed Omar , Patel Jay R , Collyer John , Deleeuw Peter , Husain Arshad , Weir Alva Bowen 
Published: June 2021

e16243 Background: Pancreatic adenocarcinoma is a malignancy with a very poor prognosis. The 5-year overall survival is about 9%. Helicobacter pylori ( H. pylori) is a known risk factor for gastric adenocarcinoma and gastric mucosa-associated lymphoid tissue (MALT) lymphoma. Whether H.pylori is a risk factor for pancreatic adenocarcinoma is still unclear. Previous observational retrospective studies trying to see if there is an association between H.pylori and pancreatic adenocarcinoma have used serology as a marker for H.pylori infection, but these have yielded mixed results. We seek to probe the association of H.pylori infection and pancreatic adenocarcinoma in a case-control study using histology for H.pylori bacteria from esophagogastroduodenoscopy (EGD) biopsies. Methods: A database for patients diagnosed with pancreatic adenocarcinoma at the Veterans Affairs Medical Center in Memphis, TN, from 1988 to 2018 was analyzed to obtain suitable cases. Pathology was reviewed to confirm the diagnosis and then the charts were reviewed to determine if the patient had undergone an EGD and if biopsies done obtained were tested for H.pylori. H.pylori positivity was determined using Steiner staining of the biopsy samples. 402 charts were reviewed and 51 cases meeting the above criteria were obtained. Controls were obtained by reviewing charts for all EGDs that were tested for H.pylori. Care was taken to make sure patients did not have any history of pancreatobiliary malignancy. 130 matched controls fit the screening criteria. Univariate and multivariate logistic regression analysis was done to analyze the risk factors. Results: Significantly more subjects in the case group (53%) were found to have H.Pylori infection compared to the control group (18%). Risk factors associated with pancreatic cancer in the literature, including age, race, smoking history, obesity, alcohol consumption, chronic pancreatitis, and diabetes, were analyzed using multivariate logistic regression. The results revealed that pancreatic cancer was significantly associated with a positive family history of pancreatic cancer (OR = 11.2, 95%CI 2.8-44.4, p = 0.001) and H.Pylori infection (OR = 5.5), 95%CI 2.4-12.7,p < 0.001). Conclusions: A positive association was found between H.pylori infection and pancreatic adenocarcinoma.
An internal review of rates of palliative medicine referral for patients with advanced pancreatic cancer.
Authors: Huffman Deanna , Shankar Karthik , Alnimer Lynna , Samhouri Yazan , Vusqa Urwat , Srinivasamaharaj Srividya , Monga Dulabh K. 
Published: June 2021

e16245 Background: Patients diagnosed with advanced pancreatic cancer face many challenges in addition to symptom burden including psychological stressors and often the need for supportive care at home. In recent years, both clinical trials and retrospective reviews have confirmed the benefits of early integration of palliative care services such as improved quality of life and reduced symptom intensity. The American College of Clinical Oncology recommends patients with advanced cancer receive directed palliative care services early after diagnosis and in concurrence with active treatment. While the benefit of palliative care services is clear, the best way to integrate palliative services has not been determined. Our project aims to review the rates of palliative care consultation in patients with advanced pancreatic cancer intending to improve patient outcomes. Methods: We retrospectively reviewed the electronic medical records of all patients diagnosed with pancreatic cancer at Allegheny General Hospital diagnosed between 2009-2020. Summary statistics are presented as percentages for categorical data and median with interquartile range for quantitative data. Results: Of the 171 patients reviewed, 121 competed all treatment and evaluation within our health network. Median age was 63 years (IQR 40-91 years); 55 patients (45%) were male. The majority were white (88%). At the time of diagnosis, 28% of our patients had stage IV disease and 19.8% of patients with stage IV disease had documented palliative care referrals. Eight patients had pain documented at diagnosis, six patients underwent celiac plexus neurolysis, 31 underwent palliative radiation and 43 patients had documented opiate use. Of the 6 patients who underwent celiac plexus neurolysis, only 4 documented pain at 6-month follow-up. Of the 31 patients who underwent palliative radiation, 6 documented pain at 6-month follow-up. Conclusions: Palliative care is an integral part of usual care for pancreatic cancer. Our analysis showed that palliative care is underutilized in our hospital with only 19.8% of patients having documented palliative care visits. While patients may refuse palliative care consult, other contributing factors are likely the lack of access or lack of early involvement of palliative care team members. Integration of palliative care has been proven repeatedly to improve quality of life in patients diagnosed with advanced pancreatic cancer. We aim to improve palliative care integration in out patients’ care by adding a hard stop to electronic medical records to remind physicians to offer palliaitive care to the patients, in addition to arranging medical grand rounds and various lectures to increase awareness of the importance of palliative care in this setting.
Real-world safety and medication use of second-line (2L) 5-fluorouracil (5-FU)–based regimens among patients (pts) with metastatic pancreatic ductal adenocarcinoma (mPDAC).
Authors: Kim George P. , Cockrum Paul , Surinach Andy , Wang Shu , Wainberg Zev A. 
Published: June 2021

e16248 Background: Chemotherapy-related adverse events (AEs) can negatively impact the treatment of pts. Managing and preventing these toxicities often require additional medications. This study examined the proportion of pts with mPDAC treated with 5-FU–based regimens in 2L who experienced AEs during treatment, and the proportion who received medication to manage those AEs. Methods: Data were extracted for pts diagnosed with mPDAC who initiated 2L treatment Jan 2016 to Aug 2020 from the Flatiron Health database. Pts included were treated with FOLFIRINOX (FFX), FOLFOX, FOLFIRI, or liposomal irinotecan (nal-IRI). The occurrence of grade 3 (G3) and grade 4 (G4) neutropenia and G3/G4 thrombocytopenia were determined using lab results and the grading criteria from the CTCAE v4.03. The occurrence of diarrhea and nausea/vomiting (N/V) were identified via ICD-10-CM codes. The use of atropine and granulocyte colony stimulating factor (G-CSF) during treatment was assessed. Duration of therapy (DOT) was assessed for each regimen. Descriptive statistics for AEs, medication use, and DOT were reported. Results: Of the 825 eligible pts, 29.0% (n=239) received FFX, 40.2% (n=332) received regimens containing nal-IRI, 24.0% (n=198) received FOLFOX, and 6.8% (n=56) received FOLFIRI. The median DOT (IQR) was 15.1 weeks (wks) (7.1 – 30.1), 12.9 wks (6.0 – 24.8), 11 wks (6.4 – 24.0), and 12.7 wks (8.3 – 24.6) for pts who received FFX, nal-IRI, FOLFOX, and FOLFIRI, respectively. G3/G4 thrombocytopenia (<50,000/mm3) presented in 9.6%, 2.4%, 8.1%, and 14.3% of pts treated with FFX, nal-IRI, FOLFOX, and FOLFIRI, respectively. G3/G4 neutropenia (<1000/mm3) presented in 22.6%, 12.3%, 14.6%, and 19.6% of pts treated with FFX, nal-IRI, FOLFOX, and FOLFIRI, respectively. The median (Q1-Q3) cumulative dose of the G-CSF pegfilgrastim was 18mg (12 – 45), 18mg (12 – 48), 24mg (12 – 36), and 30mg (13 – 48) for pts treated with FFX, nal-IRI, FOLFOX, and FOLFIRI, respectively. Atropine use was higher in pts treated with FFX and FOLFIRI (90.8% and 94.6%, respectively) than for pts treated with nal-IRI (75.6%). The full study results are reported in the table. Conclusions: In this study of AEs among pts with mPDAC treated in 2L, pts who received liposomal irinotecan had the lowest proportion of thrombocytopenia and neutropenia. Diarrhea was similar across the cohorts despite the high proportion of use in atropine for pts treated with FFX and FOLFIRI.[Table: see text]