bluuebunny/crossref_metadata_2025_split huggingface dataset:
Incidence trends of gastroenteropancreatic neuroendocrine tumors in the United States from 1975 to 2012.
Authors: Lee Mi Ri , Harris Cynthia , Baeg Kiwoon Joshua , Wisnivesky Juan P. , Kim Michelle Kang 
Published: January 2019

231 Background: Although multiple studies document a rise in gastroenteropancreatic neuroendocrine tumor (GEP-NET) incidence over the past several decades, there are limited national data regarding recent trends. Using a population-based registry, we evaluated GEP-NET incidence trends in the US population from 1975-2012 by age and calendar year at diagnosis and year of birth. Methods: GEP-NET cases between 1975-2012 were identified from the most recent version of the Surveillance, Epidemiology, and End Results (SEER) registry based on histologic and site codes. We calculated overall annual incidence, age-adjusted incidence (number of cases per 100,000), annual percent change (APC), and average APC by 5 year age intervals. We also evaluated the incidence rates by age, period, and birth year cohorts. Results: We identified 22,744 patients with GEP-NETs. In adults age 25-39 years, GEP-NET incidence rates declined from the mid 1970s to early 1980s, then increased until 2012 (Table 1). In adults age 40 and older and between ages 15-24 years, incidence rates generally increased continuously from 1975 to 2012. Adults age 40-69 years demonstrated the most rapid increases in average APC, approximately 4-6% per year. Overall incidence rates were highest in adults age 70-84 years. Since the late 1880s, GEP-NET incidence has increased in consecutive birth cohorts. Conclusions: Our study demonstrates that more recent generations have had higher incidence rates than more distant generations. In addition, GEP-NETs are more common among older adults and the number of GEP NETs has increased in past decades. [Table: see text]
Correlative analysis of circulating tumor (ct) DNA and tumor mutational analysis (TMA) in patients with advanced pancreatobilliary malignancies (PBM).
Authors: Babiker Hani M. , Liu Alex John , Recio Boiles Alejandro , Saboda Kathylynn , Liau Joy , Scott Aaron James , Elquza Emad , Mahadevan Daruka 
Published: January 2019

235 Background: Tumor archival tissue (TT) MA of PBM is challenging due to insufficient specimen acquired from fine needle aspirations. This is a barrier to analyzing specimens for targeted therapy (clinical trial enrollment). The correlation of cell free ctDNA and TMA has not been studied extensively. We hypothesize that somatic TMA correlates with ctDNA and will be a surrogate for enrollment to targeted trials. Methods: We retrospectively identified PBM patients evaluated in the Phase I Program and analyzed ctDNA and TT. ctDNA was extracted from plasma, genomic alterations were analyzed by parallel sequencing of amplified target genes (73 genes) using Illumina Hi Seq (Guardant360). Direct sequence analysis was performed on genomic DNA isolated from FFPE TT using the Illumina MiSeq platform, 592-whole gene targets (Caris MI/X). The primary objective was to correlate the mutation concordance rate (mCR, common mutations/all mutations) between ctDNA and TT. We utilized Stata 15 for descriptive analysis, Spearman correlation coefficient, and Wilcoxon Sign Rank test for statistical analysis. Results: Between 03/2016-08/2017, 28 patients (M:F 1:1) were identified, 89.2% had pancreatic adenocarcinoma, 54% were treatment naïve and age ranged from 52-83 years old. The mCR for ctDNA was 31% (21/67) and the mCR for TT was 38% (21/55). These mCRs were highly correlative with a Spearman’s Rho = 0.89, (p < 0.0001). The mCR in ctDNA was compared to mCR in TT using Wilcoxon Sign Rank Test and was found to not be statistically different (p = 0.69). Adequate TT for MA occurred in 64 % (18/28) of patients. Percentage of DNA alterations found was 89.3% (25/28) in ctDNA and 94.4% (17/18) in TT. Moreover, 61% (11/18) of patients had at least 1 shared mutation. Percentages of driver mutations identified were 92% (23/25) in ctDNA and 100% (17/17) in TT. The most common driver mutations in ctDNA were TP53, KRAS, SMAD4, and NF1. The most common driver mutations in TT were KRAS, TP53, CDKN2A, and SMAD4. Conclusions: There was a statistically significant correlation between mCR of ctDNA and TMs in PBM (p < 0.0001).
Effectiveness of colon cancer awareness month compared to pancreatic cancer awareness month at increasing internet search activity.
Authors: Nagpal Sajan Jiv Singh , Mukhija Dhruvika , Sharma Ayush , Khanna Sahil 
Published: January 2019

240 Background: Colorectal and Pancreatic cancers have high mortality with about 50,000 patients dying from each annually. Cancer awareness months (CAMs) have been earmarked by cancer societies to change public attitudes towards prevention, screening and treatment of various cancers. Awareness campaigns lead by these societies have benefited significantly from readily available Internet access and growing social media. Internet search activity has been used as a surrogate tool to gauge public interest and awareness. We aimed to assess if cancer awareness months impact internet search activity for these cancers. Methods: Using Google Trends, a public web facility of Google Inc. based on Google Search, we compared the relative frequency of search of terms ‘Colon Cancer’ and ‘Pancreatic Cancer’ between 1st January 2004 and 31st December 2016 (n=156 months). The program assigns a reference value of 100 for the point of maximum popularity from among the search terms, and provides relative monthly scores for all terms, which we termed relative interest scores (RIS). Within each cancer, the median RIS was then compared for their respective awareness months (n=13; March for CRC and November for PC) to the to the remaining months (n=143). Results: The median (IQR) RIS for CRC was significantly higher for CRC during its CAM:54 (51-63) as compared to other months:47 (44-50); p=0.0001. However, there was no significant difference in the median RIS for PC during its CAM: 33 (27.5-35.5) as compared to other months: 31 (27-33); p=0.43. The point of maximum popularity during the study period (i.e. RIS 100), and other peaks in search volume for PC corresponded to significant news events associated with PC, and PC search volumes surpassed CRC in those months. Conclusions: Ongoing campaigns for CRC awareness appear to be effective in increasing internet search activity during its respective CAM. While differences could be due to established CRC screening guidelines, other reasons behind the success of CRC awareness campaigns should be adopted by PC as awareness campaigns for the two cancers are otherwise similar.
Racial disparities in the presentation of hepatocellular carcinoma in the population 65+ years in the United States.
Authors: Kaufman Michael Ross , Delgado David J. , Costa Stephanie , George Brandon , Mitchell Edith P. 
Published: January 2019

249 Background: Insufficient evidence exists regarding the presentation and management of elderly patients with hepatocellular carcinoma (HCC). The purpose of this study was to describe racial differences in cancer staging of elderly (65+) patients with HCC diagnosed in the United States. Methods: A retrospective cohort study was conducted using the 1973-2014 Surveillance, Epidemiology and End Results Program (SEER) database of the National Cancer Institute. Patients with primary hepatocellular carcinoma, diagnosed between 2004 and 2014, and with complete information on race, gender, year of diagnosis, age, marital status, region and stage at diagnosis (Derived SEER Summary Stage 2000, and Derived American Joint Committee on Cancer (AJCC) Stage Group, 6th Edition) were included. Descriptive statistics were used to compare sociodemographic and clinical variables with race. Univariate and multivariate logistic regressions were preformed to describe the association of race with the diagnosis of late stage HCC (Regional/Distant vs Localized Stage for SEER Summary Stage, and Stage III/IV vs Stage I/II for AJCC Stage Group). Results: The sample consisted of 19,902 HCC patients: 69.7% White, 9.2% Black, 20.2% API, 1.0% AI; 69.1% male; 45.1% diagnosed in 2004-2009; 56.2% age 65-74, 35.6% 75-84, and 8.2% 85 and older; 58.3% married; 7.4% Midwest, 12.4% Northeast, 17.0% Southeast, 63.2% Pacific West; 44.9% Regional/Distant Stage (SEER Summary Stage) and 41.2% Stage III/IV (AJCC Stage Group). After controlling for confounding variables, Asian/Pacific Islanders had a decreased odds of presenting with late stage disease relative to whites in both the SEER Summary Stage (OR: 0.867, CI:0.805-0.934) and AJCC Stage Group (OR: 0.904, CI:0.838-0.975). Conclusions: Racial disparities exist at the presentation of HCC in the 65+ population. Asian/Pacific Islanders are less likely to be diagnosed with late stage HCC compared to whites. There is a need to study further these relationships in subpopulations.
Impact of hospital teaching status on stage I pancreatic cancer survival.
Authors: Chan Andy , Masuda Zachary K. , Walters Ryan W , Silberstein Peter T. , Aurit Sarah J 
Published: January 2019

257 Background: Burke et al. (2017) revealed that academic hospitals had lower patient mortality rates for common conditions compared to community-based hospitals. We conducted a retrospective study to compare survival of Stage I pancreatic cancer patients in academic versus community-based hospitals throughout the US. Methods: We identified 6,276 patients with single primary Stage IA or IB adenocarcinoma of the pancreas from the NCDB diagnosed from 2004-2012. We only included those who had a partial pancreatectomy, Whipple procedure, or no surgical intervention. In this subset, treatment was classified as none, chemotherapy, radiation, or chemoradiation; we examined the number of days from diagnosis to treatment. Unadjusted survival stratified by facility type was estimated with the Kaplan-Meier method; multivariable Cox regression was used to adjust for patient and facility level characteristics. Results: The log-rank test indicated that survival for patients who received treatment from an academic facility was significantly longer than those treated at a community-based facility (p < 0.001). After adjusting for patient and facility characteristics, however, survival was no longer significantly associated with facility type (p = 0.52). Holding all else constant, patients who underwent a surgical intervention had a lower risk of death (HR = 0.44, 95% CI: 0.40 to 0.48). Chemoradiation had a lower risk than both radiation (HR = 0.75, 95% CI: 0.65 to 0.86) and chemotherapy (HR = 0.88, 95% CI: 0.82 to 0.95). Risk of death was increased for older males, those without private insurance, and patients with Stage IB adenocarcinoma. Conclusions: In the largest study examining the association between hospital teaching status and Stage I pancreatic cancer mortality, our data suggests that there is not a significantly lower mortality rate for patients at academic hospitals compared to patients at community-based hospitals. [Table: see text]
A phase 2 and biomarker study of sorafenib combined with FOLFOX in patients with advanced hepatocellular carcinoma (HCC).
Authors: Goyal Lipika , Zheng Hui , Abrams Thomas Adam , Miksad Rebecca A. , Bullock Andrea J. , Allen Jill N. , Yurgelun Matthew B. , Sheehan Susan , Lynch Patricia , Afflitto Anthony James , Dinicola Caroline , Maurer Jordan Robert , Reyes Stephanie , Knowles Michelle , Galway Aralee , Clark Jeffrey W. , Birnbaum Emilie , Khachatryan Anna , Duda Gabriel Dan , Zhu Andrew X. 
Published: January 2019

270 Background: Sorafenib is the standard first line treatment for advanced HCC and showed a median time to progression (TTP) of 5.5 months and an overall response rate (ORR) of 2% in the phase III SHARP trial. FOLFOX has shown modest activity in HCC with a progression free survival (PFS) of 2.9 months and ORR of 8% in a phase III trial. In this single-arm, multicenter phase 2 and biomarker study, sorafenib plus FOLFOX was evaluated in the first line treatment of advanced HCC. Methods: Patients with histologically proven advanced HCC, Child Pugh A liver function, and no prior systemic therapies received sorafenib 400mg orally twice daily during a 2-week lead-in, followed by concurrent modified FOLFOX (5-FUCI 1200mg/m2/day for 46 hours and LV 400mg/m2 bolus, Oxaliplatin 85mg/m2) on day 1 and 15 of each 28-day cycle. The primary endpoint was TTP, calculated from date of study entry to date of radiological or clinical disease progression. Serial plasma anti-angiogenic and anti-inflammatory biomarkers were evaluated. Results: The study enrolled 40 patients with advanced HCC: median age, 65 years; male 85%; Child Pugh A5, 70%; BCLC stage C, 95%; HCC etiology, HCV 40%, HBV 13%, alcohol 13%. Grade 3/4 adverse events were notable for AST (23%), ALT (15%), bilirubin (10%), diarrhea (10%), anemia (10%), hypertension (5%), hand-foot syndrome (5%), and thrombocytopenia (5%). Dose reductions for sorafenib and FOLFOX were done in 73% and 65% of patients, respectively. The median TTP was 8.8 months (95%CI, 6.5-11.2). The ORR was 18%, and the stable disease rate was 55%. Among 36 patients with a baseline AFP ≥ 5 ng/mL, 10 (28%) had a ≥ 50% drop in AFP. Low baseline plasma levels of sVEGFR1, VEGF-C, and bFGF and high levels of s-cMET and IL-12 tended to associate with longer TTP (p < 0.10). Decreased s-cMET at day 15 and decreased s-cMET and IL-2 at day 43 were associated with longer TTP (p < 0.05). Conclusions: Sorafenib+FOLFOX demonstrated encouraging clinical efficacy with moderate toxicity in the first line treatment of advanced HCC. Initial biomarker evaluation suggested a correlation between TTP and baseline angiogenic markers as well as changes in IL-2 and s-cMET. Complete biomarker analysis will be presented at the meeting. Clinical trial information: NCT01775501.
Widespread somatic loss of heterozygosity as a possible marker of disease aggressiveness in metastatic well differentiated pancreatic neuroendocrine tumors.
Authors: Akala Omobolaji Oyekunle , Shah Ronak , Untch Brian R. , Kelly Virginia , Chou Joanne F. , Ladanyi Marc , Berger Michael F. , Klimstra David S. , Reidy Diane Lauren , Raj Nitya Prabhakar 
Published: January 2019

275 Background: To assess the utility of molecular profiling to predict tumor biology, we performed next-generation sequencing (NGS) of metastatic well differentiated (WD) pancreatic neuroendocrine tumors (panNETs) in the routine practice setting. Our institutional NGS platform allows for evaluation of genetic alterations that contribute to tumorigenesis (sequence variants, copy number alterations, insertions/deletions, select rearrangements) as well as somatic loss of heterozygosity (LOH). Methods: NGS was performed using MSK-IMPACT, a matched tumor-normal sequencing platform that interrogates 468 cancer-related genes. LOH for all cases was determined by analysis of total, allele-specific, and integer DNA copy number genome-wide using the FACETS algorithm. Results: Since 2014, NGS has been performed in 96 tumor samples from 80 patients. The most commonly altered genes were MEN1 (56%), DAXX (40%), ATRX (25%), and TSC2 (25%). LOH was highly prevalent, identified in 51/96 samples (53%). A significant association (q-value < 0.05) was noted between LOH and the presence of altered MEN1, DAXX, PTEN, or TSC2. LOH was recurrently observed in chromosomes 1, 2, 3, 6, 8, 10, 11, 15, 16, 21, and 22. Since MEN1 alterations predict improved outcome, comparison was made between patients with LOH present/MEN1 wild type (WT) tumors (n = 16) and LOH absent/MEN1 altered tumors (n = 21); inferior overall survival (OS) was noted with LOH present/MEN1 WT status (p < 0.01). High grade pathology was observed in 6/16 (38%) LOH present/MEN1 WT tumors and in 1/21 (5%) LOH absent/MEN1 altered tumors (p < 0.0001). The mean Ki-67 index of LOH present/MEN1 WT tumors was 22% and that of LOH absent/MEN1 altered tumors was 9%. Conclusions: This is the first study to report widespread somatic LOH in metastatic WD panNETs. PanNETs appear to exhibit more LOH overall than virtually any tumor type studied. In this cohort, LOH was a prognostic marker of inferior OS and was associated with more aggressive pathologic features. LOH warrants further investigation as it may help better characterize these clinically heterogeneous tumors.
Mucosal injury of small intestine in patients with advanced gastric cancer who developed chemotherapy induced diarrhea (CID).
Authors: Sakumura Miho , Ando Takayuki , Hosokawa Ayumu , Mihara Hiroshi , Takagi Hiroaki , Yoshita Hiroki , Nanjo Sohachi , Ueda Akira , Fujinami Haruka , Kajiura Shinya , Ogawa Kohei , Sugiyama Toshiro 
Published: January 2019

28 Background: Fluoropyrimidine is a key drug for patients with advanced or recurrent gastric cancer. It causes diarrhea, a common non-hematological toxicity. The consensus guideline suggests aggressive treatment including intravenous fluids and antibiotics, is necessary for patients with severe diarrhea accompanied by fever and sepsis. However, the frequency of complicating signs and the actual degree of damage of small intestinal mucosa have not been reported. We evaluated complicating signs and mucosal injury in patients with complicated CID. Methods: Between April 2007 and December 2016, 170 patients with advanced or recurrent gastric cancer who underwent S-1 or capecitabine based chemotherapy were retrospectively analyzed. Diarrhea was evaluated with CTCAE v4.0, and complicated CID was defined as CTC grade 3 or 4 diarrhea or grade 1 or 2 diarrhea with following signs: cramping, vomiting, decreased performance status, fever, sepsis, neutropenia, frank bleeding, and dehydration. To evaluate mucosal injury of small intestine, capsule endoscopy was performed in patients with complicated CID. Results: Among 170 patients, 15 patients (8.8%) showed complicated CID during chemotherapy (S-1 based chemotherapy, n = 13/148; capecitabine based chemotherapy, n = 2/22). Among the profile of complicated signs, cramping, fever, and vomiting were frequent, and observed in 11 (73%), 7 (47%), and 5 (33%) patients, respectively. Ten patients received capsule endoscopy after improvement of CID, and 6 (60%) patients had multiple erosions or ulcerations in small intestine. Conclusions: The incidence of complicated CID caused by fluoropyrimidine based chemotherapy was less frequent in patients with advanced or recurrent gastric cancer. However, most patients showed mucosal injury of small intestine in capsule endoscopy. Therefore, these findings strongly support the guideline that recommends aggressive therapeutic approach for patients with complicated CID.
Cell free circulating tumor DNA ERBB2 amplifications are targetable in patients with pancreatic ductal adenocarcinoma.
Authors: Barzi Afsaneh , Raymond Victoria , Wang-Gillam Andrea , Lanman Richard B. 
Published: January 2019

282 Background: Molecularly targeted therapies have led to improved clinical benefit, however few targeted therapies exist in pancreatic ductal adenocarcinoma (PDAC). ERBB2 (HER2) amplifications (AMP) in PDAC have been described as potentially targetable, especially in KRAS wild type tumors. We describe the incidence of ERBB2 AMP in patients (pts) with PDAC who underwent cell-free circulating tumor DNA (cfDNA) testing with a CLIA/CAP/NYSDOH approved 73 gene assay. Methods: The Guardant Health Clinical Database was queried (March 2014-July 2017) for pts with a diagnosis of PDAC and an ERBB2 AMP identified on cfDNA (Guardant360). Copy number AMP ≥ 2.12 is reported. Pts with multiple cfDNA timepoints were included if an ERBB2 AMP was identified at any timepoint. Results: 30 pts met inclusion criteria (1.7% of pts with PDAC (1722)). Median age at test order was 63 years (range 24 to 92). 26 pts had one cfDNA timepoint, three pts had two, and one patient had three. In the pts with multiple timepoints, ERBB2 AMP was identified at one timepoint each for a total of 30 timepoints from 30 unique pts. In two pts, ERBB2 AMP was initially not detected (ND) and detected subsequently. In two pts, ERBB2 AMP was initially detected and subsequently ND. Median number of alterations per test was 6 (range 1 to 13). Median ERBB2 AMP was 2.47 copies (range 2.14 to 7.51). Concurrent KRAS single nucleotide variant was identified in 20 tests (66.7%); G12D(6), G12V(5), Q61H(1); G12D/ KRAS AMP(6), G12R/ KRAS AMP(2). Clinical follow-up was available for three pts, two of whom were treated with anti-HER2 therapy. One patient with a low ERBB2 AMP (2.20 copies) / KRAS wild type progressed on multiple lines of therapy. Following identification of cfDNA ERBB2 AMP, Traztuzumab was added to the FOLFOX regimen with clinical improvement and significant decline in CA19-9 (1,847 to 22 U/mL) over a four-month period. ERBB2 AMP decreased to undetected over the same period. For the past 8 months, patient has been on Trastuzumab alone with further decrease in CA19-9 (16 U/mL). Conclusions: cfDNA detects potentially targetable ERBB2 AMP in pts with PDAC, and targeted anti-HER2 therapy should be explored, even when these amplifications are detected at the lower range.
Is there association between characteristics of gastric tumor growth and activation of different growth factor systems?
Authors: Frantsiyants Elena , Goroshinskaya Irina A. , Surikova Ekaterina Igorevna , Bandovkina Valeria A. , Pogorelova Yulia A. , Nemashkalova Ludmila A. , Maslov Andrey A. , Medvedeva Dar'ja E. , Kaminskiy Gennadiy V. , Malinin Sergey A. , Tishchenko Irina , Chilhahyan Lusegen , Kit Oleg Ivanovich 
Published: January 2019

29 Background: Signet-ring cell carcinoma of the stomach (SRCC) is significantly associated with poor prognosis and low treatment effectiveness, compared to adenocarcinoma of the stomach (AC). One of the causes of SRCC aggressive course can be its diffuse invasive growth pattern. The ability of tumor cells to synthesize and/or capture growth factors ensures the independent tumor development. VEGF, EGF, IGFI and EGFII facilitate neoangiogenesis and regulation of malignant processes in paracrine/autocrine mechanisms. The purpose of the study was to find the difference between local levels of VEGF, EGF, IGFI and IGFII in tumor and intact tissues in AC and SRCC. Methods: Levels of VEGF, EGF, EGFR, IGF-I and IGFII were determined by ELISA in tumor and intact gastric tissues of 15 AC patients and 10 SRCC patients (T2-3N0-2M0, G2-3), mean age 62.8±2.38 years. Results: Levels of IGF-I, IGF-II and VEGF in intact gastric tissues were similar in AC and SRCC. EGF and EGFR levels in AC were 2.9 and 1.5 higher than in SRCC. Levels of VEGF in AC tumor tissues, compared to intact gastric tissues, increased by 2.3 times, EGF and EGFR did not change, and IGFI and IGFII decreased by 2.1 and 1.8 times, respectively. Tumor tissues of SRCC patients showed the increased levels of EGF (by 2.9 times) and EGFR (by 1.8 times); VEGF and IGF were similar to the levels in intact tissues. SRCC was characterized by the activation of systems of EGF and IGF, but not VEGF. AC demonstrated the stimulation of VEGFA neoangiogenesis. Conclusions: The activation of systems of EGF and IGF in SRCC could be associated with some characteristics of the diffuse growth pattern and the tumor origin from neuroendocrine cells which facilitates the autocrine/paracrine regulation of the invasive growth. AC requires neoangiogenesis which is realized primarily by the VEGF system.