bluuebunny/crossref_metadata_2025_split huggingface dataset:
Type of fiducial marker and clinical outcomes in stereotactic body radiation therapy for pancreatic cancer.
Authors: Baclay J Richelcyn , Minneci Madeline , Abid Dania , Toesca Diego Augusto Santos , von Eyben Rie , Pollom Erqi L. , Chang Daniel Tandel 
Published: January 2021

414 Background: Stereotactic body radiation therapy (SBRT) for pancreatic cancers has been shown to improve local control, and is an important option for treatment, especially for unresectable disease. Verifying the tumor location prior to delivery of SBRT is challenging, so fiducial markers are used to track tumor location. There is currently no standard of which fiducials to use in treatment. This study would like to compare outcomes of patients treated with SBRT using different fiducial markers. Methods: Records of patients diagnosed with primary pancreas cancer who were treated with chemotherapy and SBRT were reviewed from 2006-2019. Patients were excluded if they were treated with Cyberknife, were metastatic at presentation, recurrence /persistent disease after Whipple/radiation therapy, were secondary metastatic disease (from another primary), and if they were resected after SBRT. Patients were categorized according to the fiducial used for tumor tracking during SBRT treatment: gold seeds, intrabiliary stent, or both. Cumulative incidence of local recurrence (CIR) was analyzed with death as competing event, and time to over-all survival was estimated using Kaplan-Meier curves. Results: A total of 129 patients with available fiducial information were included in this study, of which 64 (49.6%) were treated with SBRT using gold seeds, 23 (17.8%) using intrabiliary stent, and 42 (32.6%) using both the seeds and stent. There were no difference between groups in terms of baseline characteristics such as age (p = 0.169), sex (p = 0.293), and stage grouping (p = 0.293). Median follow-up time was 15 months (range: 0.3-37.3 months). The 6- and 12-month CIR were 1.5% (95%CI, 0.1%-7.4%) and 11% (95%CI, 4.8%-20.2%) for patients treated with seeds, 4.3% (95%CI, 0.2%-18.6%) and 30.4% (95%CI, 13.1%-49.8%) for patients treated with stent, and 4.8% (95%CI, 0.8%-14.6%) and 19.5% (95%CI, 9.0%-32.9%) for patients treated with both (p = 0.007). Median time to overall survival was 15.3 months (95%CI, 13-17.8 months) for patients treated with seeds, 21.3 months (95%CI, 14.7-29.6 months) for patients treated with stent, and 15.7 months (95%CI, 11.5-19.7 months) for patients treated with both (p = 0.307). Univariate analysis for predictors of local failure did not show significance for age (p = 0.812), or advanced stage (p = 0.483), but was significant for the presence of seeds (p = 0.006). Conclusions: The type of fiducial marker used for tracking during pancreas SBRT treatment was associated with local failure but no difference in overall survival. Further analysis is warranted to see which clinical factors contribute to this difference.
Evaluating the intratumor microbiome of pancreatic ductal adenocarcinoma (PDAC) by analyzing the fresh frozen tissues obtained by endoscopic ultrasound-guided fine needle aspiration (EUS-FNA).
Authors: Nakano Shintaro , Kawamoto Yasuyuki , Harada Kazuaki , Yuki Satoshi , Ito Ken , Saitoh Rika , Yamamura Takahiro , Hirata Hajime , Takishin Yunosuke , Furukawa Ryutaro , Nagai Kousuke , Kuwatani Masaki , Komatsu Yoshito , Sakamoto Naoya 
Published: January 2021

418 Background: Recent studies implied that intratumor microbiome was associated with carciniogenesis, development, prognosis and chemoresistance of pancreatic cancer (PC). There was more abundant bacteria in tumor tissue of pancreatic cancer than that of healthy controls. In clinical setting, diversity of intratumor bacteria was associated with good outcome of patients with resected pancreatic cancer. Specific intratumor bacteria could inactivate gemcitabine, which is crucial drug for PDAC, and may contribute to the resistance of gemcitabine.While most previous studies analyzed intratumor bacteria in PC by using resected tumor tissues, it was often impossible to obtain tumor sample from unresectable advanced PC. In addition, it is unclear whether tiny tissue obtained by endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) is useful for analyzing intratumor microbiome.Therefore, we planned to evaluate the intratumor microbiome by analyzing the sample from EUS-FNA. Methods: This study was carried out as a single center, prospective observational study. The patients with PC were eligible for this study. PC tissues were collected from patients who undergo EUS-FNA. Biopsy tissues from the duodenal and gastric mucosa were also collected from the same patients. All samples were immediately stored at -80°C until use. Bacterial DNA was extracted from these specimens and 16S rRNA sequencing was performed. The endpoints of this study were success rate of detecting intratumor bacteria and association between intratumor bacteria and bacteria on the duodenal or gastric mucosa. Results: A total of 90 tissue samples from 30 patients were collected. The median age was 70 years (range 54-86 years), 19/5/6 patients had pancreatic head/body/tail tumor, 16s rRNA sequencing analyses showed that 24 samples (80%) of FNA from pancreatic tumor, 30 samples (100%) of gastric mucosa and 29 samples (97%) of duodenum mucosa could be analyzed. In diversity analyses, PC showed a lower alpha diversity compared to gastric or duodenum tissue. There was a significant difference in microbial structure between PC and duodenum tissue. In PC, dominant phylum was Proteobacteria and dominant genus was Acinetobacter. Conclusions: PC tissues obtained by EUS-FNA were useful for analyzing intratumor microbiome.
Mutational profile analysis and related outcomes in primary and metastatic pancreatic cancer (PC).
Authors: Rohatgi Abhinav , Desai Aveena , Hindenburg Alexander A. 
Published: January 2021

427 Background: PC has not been well molecularly characterized and there is an unmet need in our understanding of the biological properties of PC. One previous study has found that the presence of CDKN2A mutations is an independent negative prognostic OS indicator. We evaluated molecular analysis on tumor specimens to determine whether increased mutational burden affects survival. Methods: PDAC samples from patients seen at the NYU Perlmutter Cancer Center at Winthrop Oncology Hematology Associates between 2015-2020 were profiled using next generation sequencing through Foundation Cdx. Genomic data was correlated with mined clinical data. Pt outcomes were correlated with the presence of mutations defined in 3 categories: 3 or less mutations, 4 mutations, 5 or more mutations. Results: Our cohort (N = 81) included 42% men and 58% women. 55% percent had primary (localized and locally advanced) disease and 44% had stage IV disease. Genetic mutations were most commonly found in KRAS, CDKN2A, TP53, NOTCH, SMAD4. Mutations seen less frequently were BRAF, HER2, RB1, ARID1A, MTAP, MLL, BRCA2. 43% of pts had 3 or less mutations, 15% 4 mutations, 42% had 5 or more mutations. There was no difference in number of mutations present between primary vs metastatic cancers. Median PFS was 13.5 months and overall survival (OS) for all pts was 20.0 months. The OS in primary group was 26.1 mos while it was 12.4 mos in the metastatic group. Patients with 5+ mutations had a 1.5 mos decreased OS and a 10% decreased 24-mos OS%. When stratified by primary (localized) disease, there was an 8.3 mos decrease in the 5+ mutation group vs 3 mutation group. When stratified by metastatic disease at diagnosis, there was no appreciable difference in OS between mutational groups. Conclusions: In the primary PC cohort, increasing burden of gene alteration patterns from 3 to 5+ mutations is correlated with decreased overall survival. The effect did not extend to the metastatic group likely due to disease burden driving survival whereas in primary PC group, survival reflected the tumor biology. This suggests that as additional carcinogenic pathways (DNA repair, growth, apoptosis) are mutated, tumor biology becomes more aggressive. This study provides an impetus for mutational profiling in early stage pancreatic cancer. These findings can contribute to the use of molecular profiles for prognostication and further development of targeted therapies. [Table: see text]
Evaluating the clinical impact of primary tumor location in pancreatic adenocarcinoma.
Authors: Carhart Randi Zukas , Micaily Ida , Fratamico Roberto Stefan , Daskalakis Constantine , Lam Sophia , Cohen Steven J. , Basu Mallick Atrayee 
Published: January 2021

428 Background: Pancreatic adenocarcinoma is the fourth most common cause of cancer-related death in the US. The location of the primary lesion has long been thought to influence survival due to differences in time to presentation and ability to undergo cancer directed surgery. We hypothesized that patients with tumors arising in the body or tail (distal) would have poorer survival than patients who presented with lesions in the head of the pancreas (proximal) and that this difference would be true regardless of stage at diagnosis due in part to other factors such as intrinsic differences in the biology of these tumor types. A retrospective chart review at a single center with a high volume of pancreatic cancer directed surgery was carried out to address this question. Methods: Institution database was queried to identify patients with the ICD9 diagnosis of pancreatic adenocarcinoma of the head, body, and tail between 2014-2017; the inclusion criteria were 18 years or older, biopsy proven adenocarcinoma and a single mass in the pancreas at presentation. A total of 907 entries were screened with 324 patients being analyzed (236 proximal and 88 distal). CDC National Death Index registry and obituary reports were utilized to determine official dates of death. Results: Overall median survival was statistically higher in the proximal group than the distal group 16.0 vs 11.2 months (p=0.015). However, there was no significant difference in survival by stage of the proximal group over the distal group with stage I/II in the proximal group surviving 21 months versus distal 25.7 months, p=0.436; stage III, proximal surviving 11.7 months versus distal 18.0 months, p=0.393; stage IV, proximal surviving 6.5 months versus distal 4.9 months, p=0.675. The distal group was more likely to be metastatic on diagnosis (59% versus 18%) and was less likely to undergo surgery (34% vs 50%). In the surgical group, there was similar survival of 24.6 months in the proximal group versus 19.4 distal (p=0.795). Conclusions: Patients in the proximal group had a higher overall survival than the distal group as expected. Overall, however, when broken down by stage or surgery, the difference in survival between the proximal and distal groups was minimal with Hazard Ratio 0.96 (95%, CI=0.7, 1.30). Therefore, early stage diagnosis or surgery strongly account for the survival benefit in the proximal population rather than other factors like an intrinsic difference in the nature of the tumors themselves.
Significant lipid and neutrophil accumulation and active inflammasome in high BMI tumor regions of human pancreatic ductal adenocarcinoma.
Authors: Khattab Ahmed , Patruni Sunita , Garciafigueroa Yesica , Phillips Brett , Engman Carl , Khatoon Nazia , Shankar Karthik , Rizvi Ali , Miller Stacey , Giannoukakis Nick , Monga Dulabh K. 
Published: January 2021

438 Background: Obesity is an established risk factor for cancer and cancer-related mortality. Adipocytes may act as a “damage” signal resulting in the accumulation of innate immune cells, fueling an inflammatory micro-environment. Among the innate immune cells, tumor-associated neutrophils (TANs) are confirmed to accumulate inside the tumor. As obesity is a significant risk factor for a poorer prognosis in pancreatic ductal adenocarcinoma (PDAC), we hypothesize that obesity-driven adipose fuels the progression of PDAC in a TAN and inflammasome-facilitated manner. This may happen through several mechanisms, including genomic instability of aggressive PDAC clonal populations. Methods: Tissue from resected tumors of PDAC patients (n = 44) with a body-mass index (BMI) > 27 (obese [n = 21]) and BMI < 22 (normal [n = 23]) were incubated with anti-human CD66b antibodies and detected using standard immunofluorescent microscopy techniques. Images were acquired in a Zeiss Axioplan microscope workstation and analyzed by ZEN and Metamorph software. Results: We identified the presence of adipocytes in all tissue sections and CD66b+ neutrophils in all tissue sections of normal BMI patients and in 81% of high BMI patients. There is a significantly greater density of adipocytes in the tumor environment when compared to adjacent normal areas, suggesting that these cells are acting as a damage signal. Our novel data also shows that high BMI results in a significantly higher neutrophil count in tumor specific tissue when compared to patients with a low BMI. These data suggest an association between BMI and inflammasome accumulation in the tumor environment. Conclusions: Our data uniquely shows that CD66b+ neutrophils tend to accumulate inside PDAC in high BMI patients and this is associated with intra-tumoral active inflammasomes. The higher concentrations of these inflammasomes in higher BMI patients may be of mechanistic relevance in understanding how inflammation induces progression of PDAC. A larger cohort of tissues from PDAC obtained from low and high BMI individuals will be needed to test our hypothesis and to begin to decipher the role of obesity on inflammation and PDAC progression.
Prognostic impact of chemoradiation-related lymphopenia in patients with locally advanced pancreatic cancer.
Authors: Kim Daniel W , Lee Grace , Weekes Colin D. , Ryan David P. , Parikh Aparna Raj , Allen Jill N. , Qadan Motaz , Ferrone Cristina R. , Fernandez-del Castillo Carlos , Hwang William L. , Hong Theodore S. , Wo Jennifer Y 
Published: January 2021

439 Background: Chemoradiation (CRT) induced lymphopenia is common and associated with poorer survival in multiple solid malignancies. The objective of this study was to evaluate the prognostic impact of lymphopenia in patients with nonmetastatic, unresectable pancreatic ductal adenocarcinoma (PDAC) treated by neoadjuvant FOLFIRINOX (5-fluorouracil [5FU]/leucovorin/irinotecan/oxaliplatin) followed by CRT. We hypothesized that severe lymphopenia would correlate with worse survival. Methods: The inclusion criteria for this single-institution retrospective study were: 1) biopsy-proven diagnosis of unresectable PDAC, 2) absence of distant metastasis, 3) receipt of neoadjuvant FOLFIRINOX followed by CRT, and 4) absolute lymphocyte count (ALC) available prior to and two months after initiating CRT. In general, CRT consisted of 5FU or capecitabine and RT with 58.8 Gy over 28 fractions. Lymphopenia was graded according to CTCAE v5.0. The primary variable of interest was lymphopenia at two months, dichotomized by ALC of < 0.5/μl (Grade 3 lymphopenia). The primary endpoint was overall survival (OS). Cox modeling and Kaplan-Meier methods were used to perform survival analyses. Results: A total of 138 patients were identified. Median follow-up for the entire cohort was 16 months. Median age was 65. Fifty-six percent were female, 86% were Caucasian, and 97% had ECOG ≤1. Median tumor size was 3.8 cm. Tumor location was pancreatic head in 63%, body in 22%, tail in 8%, and neck in 7%. Median baseline ALC for the entire cohort was 1.5 k/ul. Two months after initiating CRT, 106 (77%) had severe (Grade 3 or worse) lymphopenia. While there were no significant differences in baseline patient or disease characteristics, patients with severe lymphopenia received higher doses of RT with longer duration of treatment compared to those without severe lymphopenia. On multivariable Cox model, severe lymphopenia at two months was significantly associated with increased hazards of death (HR = 4.00 [95% CI 2.03-7.89], p < 0.001). Greater number of neoadjuvant FOLFIRINOX cycles received prior to CRT was associated with lower hazards of death (HR = 0.84 [95% CI 0.77-0.92], p < 0.001). The 12-month OS was 73% vs. 90% in the cohort with vs. without severe lymphopenia, respectively (log-rank p < 0.001). Conclusions: Treatment-related lymphopenia is common and severe lymphopenia may be a prognostic marker of poorer survival in locally advanced pancreatic cancer. Closer observation in high-risk patients and minimization of RT dose and duration are potential approaches to mitigating CRT-related lymphopenia. Our findings also suggest an important role of the host immunity in pancreatic cancer outcomes, supporting the ongoing efforts of immunotherapy trials in pancreatic cancer.
Gastrointestinal cancer mortality rate global trends over the last century.
Authors: Sidhu Ravina , Powar Perneet , Calla Ritu Priya , Vyas Dinesh 
Published: January 2021

457 Gastrointestinal Cancer Mortality Rate Global Trends Over the Last Century Background: Global gastroenterology cancer mortality trends have drastically changed over past decades due to alterations in risk factors such as diet, populations, exposures, and medical advancements. This study investigates specifically how meat consumption, the biggest evolving risk factor for GI cancer mortality, has influenced various gastrointestinal incidence rates globally. Although the correlation between meat consumption and cancer risk has been investigated, a global temporal study investigating the national mortality rates of gastrointestinal cancers relating to meat production remains unexplored. We researched causes for the trends between meat production and GI cancer mortality in the USA, Canada, Japan, France, and Singapore. Methods: Cancer mortality data was collected from the WHO Cancer Mortality Database, specifically the IARC database. Meat consumption data was unavailable between the 1960s-2010, so meat production data was used and obtained from the FAOSTAT. Results: The pancreatic cancer mortality rate increased in each country except Canada. This spike is due to increased meat consumption, obesity, lack of screening modalities, poor prognosis, and late diagnosis of the disease. Canada’s 1% drop in mortality rate can be attributed to a decreased smoking rate amongst men (62% to 16% from 1965-2017) as well as a decline in meat consumption. The mortality rates of gastric and colorectal cancer (CRC) have decreased despite a meat production increase. Decreased H. pylori prevalence (Europe: 48.8% to 39.8%, North America: 42.4% to 26.6%, and Western Asia: 53.6% to 54.3%) , better food preservation, and improvement in environmental conditions have lowered gastric cancer incidence. The CRC mortality rate in the USA, Canada, Japan, and France decreased mostly due to colonoscopy screening measures, better treatment, and decreased red meat consumption. In Singapore, increased obesity and high caloric diets account for an increased CRC mortality rate despite decreased meat production. This rate is exacerbated by lower screening rates due to decreased CRC risk awareness. Conclusions: Gastric and CRC mortality rates decreased despite increased meat production, while pancreatic cancer incidence rates have increased. These trends are further investigated and necessary to understand to lower the mortality rates of GI cancers on a global scale.
Socioeconomic status (SES) and survival outcomes in patients with gastrointestinal (GI) cancers: An analysis of 1.4 million patients in the National Cancer Database (NCDB).
Authors: Salem Mohamed E. , Trufan Sally Jeanne , Symanowski James Thomas , Kadakia Kunal C. , Hartley Marion L. , Graves Kristi D , Musselwhite Laura W. , Kim Edward S. , Raghavan Derek , Hwang Jimmy J. 
Published: January 2021

458 Background: SES and access to care are factors that may impact patient outcomes. We examined the impact of SES on survival in patients (pts) with GI cancers. Methods: Data obtained from the NCDB were used to examine the association between SES and outcomes of GI cancer pts. Pts were categorized by income and education levels. Logistic regression, Cox proportional hazards models, and chi-square tests were used to examine the differences between the groups. Results: A total of 1,409,177 pts diagnosed with GI cancers between 2004 and 2016 were retrospectively studied (table). The majority of pts were male (54.3%), and 83.7% were white, 11.5% black, and 4.7% of other races. Of the entire cohort, 31% of pts lived in the highest income areas, whereas 18.3% were in the lowest and 50.6% in middle-income areas; 23% lived in the highest high school graduation rate (>93%) areas, whereas 17.4% lived in the lowest graduation rate (< 79%) areas; and 82.4% resided in metropolitan areas. Pts in the lowest compared to highest income areas were more likely to be black (OR: 6.5, 6.4-6.6), uninsured (2.9, 2.8-3.0), or have Medicaid (4.13, 4.04-4.22), and have a Charlson-Deyo score ≥ 1 (1.35, 1.33-1.36). In the multivariate analysis, cancer type, stage, tumor differentiation, income, education, insurance status, gender, race, Charlson-Deyo score, and type of treatment center were independent predictors for survival. After controlling for other factors, black pts had a 3% increased risk of death (HRadj = 1.03; 1.02-1.03; p < 0.001). Pts from lowest vs highest education areas had a 2% increased risk of death (HRadj = 1.02; 1.01-1.03; p < 0.001). Pts from the lowest income vs highest income areas had a 13% increased risk of death (HRadj = 1.13; 1.12-1.14; p < 0.001). Pts with Medicaid insurance had a 33% (HRadj: 1.33, CI 1.32-1.34, p < 0.001) and uninsured pts had 22% (HRadj: 1.22 (1.20-1.23, p < 0.001) increased risk of death compared to pts with private insurance. Pts from urban or rural areas vs metropolitan areas had a 1% increased risk of death (HRadj = 1.01; 1.00-1.02; p < 0.001). Conclusions: Low SES is associated with worse survival in pts with any GI cancer. Pts with low-income status and Medicaid or no health insurance had the highest risk of mortality. These stark inequities must be addressed with renewed efforts to identify, treat, and better support pts at highest risk for poor outcomes. [Table: see text]