bluuebunny/crossref_metadata_2025_split huggingface dataset:
Rural-urban disparities in colorectal cancer screening: An insight from a statewide database.
Authors: Swaminathan Renugadevi , Morris James D. , Davis Terry C. 
Published: February 2020

69 Background: The Healthy People 2020 initiative aims to increase colorectal cancer (CRC) screening. The common CRC screening options are FIT, FOBT, sigmoidoscopy, and colonoscopy. Colonoscopy allows visualization of the entire colon and offers therapeutic benefit whereas stool tests are less invasive, cost-effective and are easily available. Inequities exist in CRC screening among rural residents which may be contributed to a lower level of education, income, health insurance and access to health care. The purpose of the study is to identify the impact of geographic region on the preference of CRC screening modality among Louisiana adults. Methods: We performed a retrospective cohort study among age-eligible Louisiana adults who had CRC screening either with colonoscopy or stool-based tests using the 2016 Behavioral Risk Factor Surveillance System database (n = 1372). We examined demographic characteristics among participants who had CRC screening with colonoscopy versus who had a stool-based test. Multivariable logistic regression analysis evaluated the association of geographic region and the preference of CRC screening. Results: Participants age 65-75 years old were 36% less likely to have a colonoscopy as compared to age 50-64 years (p = 0.0008). African Americans and Hispanic Americans were 34% (p < 0.006) and 55% (p = 0.057) less likely to have a colonoscopy as compared to Caucasian Americans, respectively. Medicaid and Medicare participants were 82% (p < 0.0001) and 52% (p < 0.0001) less likely to have a colonoscopy compared to participants with private insurance, respectively. After adjusting for age, race/ethnicity, education, income, and insurance the odds of screening colonoscopy was 29% lower for rural residents compared to urban residents of Louisiana (OR 0.71 95% CI 0.53 - 0.94). Conclusions: Individuals residing in rural parishes of Louisiana were more likely to have a stool-based test for CRC screening. Health care providers while considering the reliability and feasibility of CRC screening modality should also incorporate patient’s preferences while offering the screening tests to increase the rate of CRC screening.
Effects of early discontinuation of adjuvant chemotherapy (EDAC) and the timing of treatment on outcomes in patients with early-stage pancreatic cancer (ESPC): Result from a population-based retrospective cohort study.
Authors: Muhammadzai Javeria , Moser Michael , Haider Kamal , Shaw John , Chalchal Haji I. , Gardiner Donald , Zaidi Adnan , Ahmed Osama , Luo Yigang , Brunet Bryan , Dorie-Anna Dueck , iqbal mussawar , Beck Gavin , Ahmed Shahid 
Published: February 2020

694 Background: Although evidence suggests that a delay in initiation of adjuvant chemotherapy (AC) results in inferior outcomes in some cancers, little is known about its detrimental effects in patients with ESPC. Moreover, it is not known if EDAC has been associated with high risk of recurrence and poor survival. The current study aims to determine association between timing and completion of AC and outcomes in ESPC. Methods: Patients with ESPC who were diagnosed from Jan 2007 to Dec 2017 and underwent complete resection in the province of Saskatchewan were examined. Kaplan Meier methods and log rank tests were performed for survival analyses. Cox proportional multivariate analyses were performed for correlation with recurrence and survival. Results: A total 168 patients with ESPC were identified. 97 (57%) patients were excluded as they did not receive AC, were found to have metastatic disease, did not have curative surgery or had received preoperative chemotherapy. Of 71 eligible patients with median age of 69 years (IQR: 57-73), 52% were male, 31% had WHO performance status of 0 and 92% had a comorbid illness. 78% had pancreatic head tumor, 66% had T3 tumor and 63% had node-positive disease. Median time to start of AC from surgery was 73 days (IQR: 59-89). 32% were started AC within 60 days of surgery. 89% received single-agent chemotherapy and 25% received adjuvant radiation. 69% completed planned treatment. Median time to recurrence in group which completed treatment was 22 months (95%CI:15.8-28.2) vs. 9 months (3.3-14.7) if treatment was discontinued early (P < 0.001). Median overall survival of the group that completed treatment was 33 months (17.5-48.5) vs. 16 months (17.5-48.5) if it was stopped early (P < 0.001). On multivariate analysis, EDAC was significantly correlated with recurrent disease (HR = 3.0; 1.6-5.5), P = 0.0001 and inferior survival (HR = 3.2; 1.68-6.12), P < 0.001. No correlation between AC timing and survival was noted. Conclusions: Although timing of AC does not correlate with inferior outcomes, EDAC has been associated with high risk of recurrence and inferior survival in ESPC.
Multicenter retrospective observational study of pancreatic cancer with positive peritoneal lavage cytology intended for surgical resection.
Authors: Todaka Akiko , Nara Satoshi , Motoi Fuyuhiko , Morinaga Soichiro , Hama Naoki , Higuchi Ryota , Konishi Masaru , Shirakawa Hirofumi , Tsumura Hidetaka , Okuyama Hiroyuki , Matsui Hiroto , Shioji Kazuhiko , Sugimachi Keishi , Asagi Akinori , Mizuno Nobumasa , Fukutomi Akira , Furuse Junji 
Published: February 2020

695 Background: Although macroscopically curative resection has been performed for pancreatic cancer with positive peritoneal lavage cytology (CY1), the prognosis is poor in most reports. In 2013, the JASPAC01 trial showed that S-1 was superior to Gemcitabine (GEM) as adjuvant chemotherapy for resected pancreatic cancer, and S-1 was also administered to the patients with CY1 who had undergone macroscopically curative resection. Methods: This is a multicenter retrospective observational study that collected data of the patients with pancreatic adenocarcinoma who were diagnosed with CY1 between 2007 and 2015 and had no other noncurable factors. Results: One hundred twenty-seven patients were enrolled from 14 institutions, and 3 were excluded due to liver metastasis or non-adenocarcinoma. The median age was 67 years old and almost patients had PS 0 or 1. Of the 124 patients, 114 underwent macroscopically curative resection and the median overall survival (OS) and recurrence free survival (RFS) were 16.7 and 7.2 months. Of the resected patients, 80 (70%) had no early recurrence and started postoperative adjuvant chemotherapy. Adjuvant chemotherapy regimens were S-1 in 43 patients (54%), GEM in 31 (39%) and others in 6 (7%). The median OS was 21.0 months with S-1 and 19.2 months with GEM (HR: 0.73, 95%CI: 0.44-1.22, P = 0.23), whereas the median RFS was 10.2 and 7.1 months (HR: 0.58, 95%CI: 0.36-0.95, P = 0.03), respectively. Conclusions: After the report of JASPAC01, most patients with pancreatic cancer with CY1 received macroscopically curative resection and treated with S-1 as adjuvant therapy, however the efficacy was insufficient. We should consider appropriate treatment strategies for patients with pancreatic cancer with CY1 intended for surgical resection.
Multicenter phase I/II study of intravenous gemcitabine + nab-paclitaxel combined with intraperitoneal paclitaxel for pancreatic ductal adenocarcinoma patients with peritoneal metastasis.
Authors: Yamada Suguru , Fujii Tsutomu , Yamamoto Tomohisa , Takami Hideki , Yoshioka Isaku , Yamaki So , Sonohara Fuminori , Shibuya Kazuto , Motoi Fuyuhiko , Hirano Satoshi , Murakami Yoshiaki , Inoue Hitoshi , Hayashi Masamichi , Kodera Yasuhiro , Sekimoto Mitsugu , Satoi Sohei 
Published: February 2020

702 Background: Pancreatic ductal adenocarcinoma (PDAC) patients with peritoneal metastasis (peritoneal deposits and/or positive peritoneal cytology) have an extremely poor prognosis, and an effective treatment strategy remains elusive. Methods: The aim of this study were to determine the recommended dose (RD) for a combination of intravenous (IV) gemcitabine, intravenous nab-paclitaxel, and intraperitoneal (IP) paclitaxel in chemotherapy-naive PDAC patients with peritoneal metastasis and to evaluate the clinical efficacy and safety. Gemcitabine and nab-paclitaxel was administered IV combined with paclitaxel IP on days 1, 8 and 15, followed by 1 week of rest. The frequency of dose-limiting toxicity was evaluated and the RD was determined. The primary endpoint of the phase II part was 1-year overall survival (OS) rate. The secondary endpoints were antitumor effect, symptom relief effect, safety and OS. Results: In the phase I part, RD for IV gemcitabine, IV nab-paclitaxel and IP paclitaxel were determined as 800 mg/m2, 75 mg/m2, and 20 mg/m2, respectively. A total of 46 patients were enrolled in the phase II part and drugs were delivered at the RD. All patients had positive intraperitoneal cytology and 29 patients (63.0%) had the peritoneal dissemination. The median treatment period was 6.0 (0-22.6) months. The response rate and disease control rate were 45.7% and 95.7%, respectively. Ascites disappeared in 40.0% and cytology turned negative in 67.4%. Median CA19-9 decrease ratio was 84.4 (16.9-99.1) %. The median survival time was 12.8 (3.1-32.7) months, and the 1-year survival rate was 52.2%. Finally, conversion surgery was performed in 8 (17.4%) patients and those who received conversion surgery survived significantly longer than those who did not (not reached vs. 11.7 months, P = 0.0070). Grade 3/4 hematologic toxicities occurred in 76.0% and nonhematologic adverse events in 15.0%, of which 6.5% were bowel obstructions. Conclusions: This regimen has shown promising clinical efficacy with acceptable tolerability in chemotherapy-naive PDAC patients with peritoneal metastasis. Clinical trial information: 000018878.
Randomized phase II trial of chemoradiotherapy with S-1 versus combination chemotherapy with gemcitabine and S-1 as neoadjuvant treatment for resectable pancreatic cancer (JASPAC 04).
Authors: Toyama Hirochika , Sugiura Teiichi , Fukutomi Akira , Asakura Hirofumi , Takeda Yuriko , Yamamoto Kouji , Hirano Satoshi , Satoi Sohei , Matsumoto Ippei , Takahashi Shinichiro , Morinaga Soichiro , Yoshida Makoto , Sakuma Yasunaru , Iwamoto Hidetaka , Shimizu Yasuhiro , Uesaka Katsuhiko 
Published: February 2020

724 Background: Although neoadjuvant treatment (NAT) has been widely employed for resectable pancreatic ductal adenocarcinoma (PDAC), it is still unclear what kind of regimen is recommended. The aim of the study is to investigate which chemoradiotherapy (CRT) with S-1 or combination chemotherapy with gemcitabine (GEM) and S-1 is more promising as NAT for resectable PDAC in terms of effectiveness and safety. Methods: Patients with resectable PDAC were enrolled and randomly assigned into either CRT group or chemotherapy group. In the CRT group, a total radiation dose of 50.4 Gy in 28 fractions was administered and S-1, at a dose of 30, 40 or 50 mg according to the body surface area, was orally provided twice a day on the same day of irradiation. In the chemotherapy group, GEM was intravenously administered at a dose of 1000 mg/m2 on day 1 and 8 and S-1 was orally provided at a dose of 30, 40 or 50 mg according to the body surface area twice daily on day 1 to 14 followed by one week reset. Patients in the chemotherapy group received two cycles of this regimen. Surgery was performed between 15 and 56 days after the last day of NAT. The primary endpoint was 2-year progression-free survival (PFS) rate. With 50 patients in each group, the study had 80% power assuming a threshold 2-year PFS rate of 25% and an expected 2-year PFS rate of 40% at 0.05 one-sided alpha. The trial was registered with the UMIN Clinical Trial Registry as UMIN000014894. Results: From April 2014 and April 2017, 103 patients were enrolled from 11 institutions in Japan. One was excluded because of ineligibility, therefore 51 patients in CRT group and 51 patients in chemotherapy group constituted the intention-to-treat analysis. The 2-year PFS rate was 45% (90% CI, 33-60%) in the CRT group and 55% (43-65%) in the chemotherapy group (p = 0.52). The hazard ratio for chemotherapy to CRT was 0.78 (0.46-1.31). The median survival time was 37.7 (95% CI, 30.3-NE) in the CRT group and NE (29.9-NE) in the chemotherapy group (p = 0.30). There was no treatment-related death in both groups. Conclusions: Combination chemotherapy with GEM and S-1 may be more promising compared with CRT with S-1 as NAT for resectable PDAC. Clinical trial information: UMIN000014894.
Outcomes and efficacy of neoadjuvant chemoradiation versus chemotherapy in localized pancreatic cancer.
Authors: Chopra Asmita , Hodges Jacob C. , Olson Adam , Burton Steven A. , Lee Kenneth K. , Bahary Nathan , Singhi Aatur D. , Boone Brian A. , Lotze Michael T. , Hogg Melissa E. , Zeh Herbert , Zureikat Amer H. 
Published: February 2020

727 Background: Neoadjuvant therapy is increasingly used for pancreatic cancer (PDA). The comparative efficacy of neoadjuvant chemotherapy (NC) versus chemoradiation (NCRT) remains uncertain. We aimed to compare NC and NCRT on survival outcomes and pathologic endpoints of PDA. Methods: Single-center analysis of PDAs treated with NC or NCRT between 2008-2018. Average treatment effects (ATE) were estimated after matching cases to controls using Mahalanobis distance nearest-neighbor matching. Competing risk survival analysis and inverse probability weighted estimates (IPWE) were used for disease free survival (DFS) and overall survival (OS) respectively. Results: Of 418 patients (median age 67yrs, 51% females), 327 received NC and 91 received NCRT. NCRT patients had more locally advanced disease, cross-over NC regimens (gemcitabine & 5-FU based), longer neoadjuvant therapy duration, open surgery and vascular resection (all p < 0.05). NCRT was associated with lower LN positivity, LNR, LVI and PNI, higher R0 rates, and higher near complete and complete pathologic responses (all p < 0.05, table). After adjustment, NCRT was associated with a significant reduction in LN positivity [95%CI = (-)0.41-(-)0.07; p = 0.007] and LVI [95%CI = (-)0.36-(-)0.03; p = 0.02]. While NCRT was associated with improved OS on UVA (25.5 vs. 21.6 months; p = 0.04), it was not significantly associated with OS by IPWE after adjusting for adjuvant therapy [95%CI = (-)5.02-16.3; p = 0.3] or DFS on competing risk analysis (95%CI = 0.78-1.31; p = 0.96). Conclusions: Although NCRT is associated with improved pathologic surrogates, it is not associated with improved survival in PDA. [Table: see text]
Clinical significance of monitoring KRAS in tissue and plasma of pancreatic cancer patients.
Authors: Watanabe Fumiaki , Suzuki Koichi , Rikiyama Toshiki 
Published: February 2020

745 Background: KRAS monitoringprovides valuable information for early diagnosis and prediction of treatment outcome in colorectal cancer. KRASmutation is observed in only half of colon cancer patients, whereas it is detected in 90% of pancreatic cancer patients. Therefore, investigating tumor DNA in plasma by KRAS monitoringmay be even more valuablein pancreatic cancerpatients. In this study, we elucidated the clinicalsignificance of KRASmonitoring in pancreatic cancer patients during treatment. Methods: KRASin tumor tissues was analyzed for mutations by Scorpion ARMS or RASKET in 83 patients with pancreatic tumors. KRASin plasma was analyzed for mutations(G12D, G12V, G12C, G12A, G12S, G12R, G13D, Q61L, and Q61H) using droplet digital polymerase chain reaction in 88 patients who underwent the curative surgery (N = 45) or the chemotherapy (N = 33) and who had KRAS mutation in their tissues. Results: KRASmutation in tumor tissues was detected in 74 of 83 patients (89.2%). These 74 patients showed significantly poorer prognosis (MST; 32) than the seven patients without mutation (p = 0.03), whose MST were 193. Monitoring of KRASin plasma revealed KRASmutation in 35 of 88 patients (39.8%). In patients who underwent the chemotherapy (N = 33), 2years OS of patients who detected KRASmutation in plasma (N = 23) was 16.4% and them which not detected it (N = 10) was 53.3% (p = 0.18). But in the curative resection group (N = 45), 3years OS of patients who detected KRASmutation in plasma (N = 12) was 16.7% and them which not detected it (N = 33) was 68.2% (p = 0.00). Conclusions: KRASmutation in tissue and plasma could be a valuable predictive and prognostic biomarker in pancreatic cancer patients.
Analysis of pancreatobiliary adenocarcinoma (PBC) treatment response and resistance utilizing circulating tumor DNA (ctDNA).
Authors: Banerjee Madhulika , Boiles Alejandro Recio , Veeravelli Sumana , Leiva Jorge Andres , Saboda Kathylynn , Roe Denise , McBride Ali , Babiker Hani M. 
Published: February 2020

758 Background: Accurate disease monitoring in PBC is instrumental for optimal therapeutic decision-making. CA 19-9 is the most utilized biomarker, though it has limited sensitivity/specificity and cannot be used in CA 19-9 non-secretors (n-S). ctDNA is a potentially helpful monitoring aid and surrogate for PBC n-S. Serial ctDNA could identify emerging resistant driver mutations. Our study prospectively examined ctDNA in PBC patients receiving treatment and retrospectively correlated it with clinical response. Methods: We performed genomic testing of ctDNA from metastatic PBC patients’ plasma from 11/2016 to 08/2019. This included 77 patients, of those, 18 had >1 ctDNA measurement with 49 correlative data points in total. Demographics, serial CA 19-9 levels and imaging results were collected. ctDNA analysis by parallel sequencing of amplified target genes (74) using Guardant360 was obtained. We correlated imaging and CA 19-9 responses with molecular alterations in patients receiving systemic chemotherapy. Descriptive statistics and logistic regression of the data was performed. Results: Of those included, median age was 66 yo, 50% male, and 92% pancreatic ductal adenocarcinoma. Baseline ctDNA showed 103 mutations including TP53 12.6%, KRAS 9.7%, MET 6.8%, APC, ARID1A and NF1 4.8% each, and others < 3%. 44% of patients were n-S with 75% having both TP53 and KRAS mutations. APC, ARID1A, and NF1 were only present in n-S. 91% vs 90% KRAS and 84% vs 78% TP53 of n-S and secretors (S), respectively, had correlation between ctDNA levels and imaging response. S TP53 and KRAS mutations correlated to CA19-9 levels and scans in 78% and 70% responses. New TP53 subclonal variant mutations were the most common resistance mutations for all progressions (75%). A logistic regression model of imaging progression on change in CA19-9 secretion and TP53 or KRAS expression was not statistically significant. Conclusions: Baseline ctDNA level changes ( TP53 and KRAS) can potentially act as a biomarker of response in PBC, specifically in n-S. TP53 subclonal mutations were the most common resistant alterations at progression and can be explored as future targets. This is being explored in larger prospective trials.
The effect of TGF-β on PD-L1 expression on PDAC TAMs.
Authors: Trebska-McGowan Katarzyna , Makowski Liza , Alvarez Marcus A. , Kansal Rita , Husain S. Mazher , Pingili Ajeeth K. , Glazer Evan Scott 
Published: February 2020

764 Background: Pancreatic Ductal Adenocarcinoma (PDAC) has less than a 10% five year survival and will become the second leading cause of US cancer mortality in the next decade. Immunotherapy, such as checkpoint inhibition against anti-Programmed death-ligand 1 (PD-L1) has not been successful in the treatment of PDAC patients. Both tumor associated macrophages (TAMs) and the TGF-β protein are ubiquitous in PDAC tumors. We hypothesize that TGF-β increases the overall number of TAMs and degree of PD-L1 expression of TAMs in PDAC. Methods: Our lab has a mouse pancreatic cancer cell line derived from a genetically engineered mouse model (KPC mice that spontaneously form PDAC tumors that are similar to human PDAC). We orthotopically implanted this cell line into the pancreas of immunocompetent C57BL/6 (B6) mice. In groups of 5 each, mice were treated with saline (control) or TGF-β. We investigated tumor burden, the number of TAMs (CD45+, CD11b+F4/80hi, Ly6C−, Ly6G−/lo) in the tumors with flow cytometry and the percentage of TAMs expressing PD-L1 in the pancreas and metastatic lesions in the liver. Results: As a percent of leukocytes in the tumor, PDAC liver metastases had more TAMs compared to tumors in the pancreas (33 ± 5% vs 10 ± 4%, P = 0.001). Compared to controls, TGF-β treatment significantly increased the percent of PD-L1 expressing TAMs (32 ± 6 % vs 12 ± 5%, P = 0.013, see Figure) in the pancreas but no effect was evident on TAM density. In liver metastases, treatment with TGF-β decreased the overall TAM density (P = 0.039) but did not affect the number of PD-L1 positive TAMs. Conclusions: TGF-β plays pivotal role in the progression of PDAC and demonstrates context dependent activity. Our results suggest that an immunosuppressive effect mediated by PD-L1 expression on TAMs may be initiated by TGF-β. Future investigations will focus on understanding the role of the PDAC – TAM interaction to develop effective immune therapies for PDAC patients.
Genomic associations in metastatic pancreatic cancer (mPC).
Authors: Rengan Anil Kumar , Dotan Efrat , Devarajan Karthik , Vijayvergia Namrata 
Published: February 2020

765 Background: mPC is an aggressive cancer, and molecular profiling provides further insight into pathogenesis and treatment. We sought to illustrate the molecular landscape of mPC in relation to post-metastatic survival and VTE incidence. Methods: With IRB approval, we retrospectively analyzed charts of mPC patients who underwent molecular profiling. Fisher’s exact test (categorical) and Mann-Whitney test (continuous) were used to compare groups. Log-rank test, Cox proportional hazards model and weighted Cox regression were used for survival analysis. Results: Between 2009 and 2018, 98 out of 502 mPC patients (19.5%) underwent molecular testing. Of these, 70% were tested after 2015. The most common mutations were in KRAS (79.2%), TP53 (59.0%), CDKN2A (35.9%), BRCA (16.4%), PIK3CA (9.4%) and SMAD4 (7.4%). Concurrent KRAS and TP53 mutations were found in 62.3% of patients. KRAS mutation was positively associated with Jewish ancestry (OR 2.3; p < 0.05), and TP53 mutation was positively associated with younger age at diagnosis (63.5 vs. 67 years; p < 0.05). KRAS and TP53 mutations were negatively associated with tobacco use (OR 0.43 and 0.3, respectively; p < 0.05). There was no association between any mutation and metastatic site. Both KRAS and TP53 mutations were positively associated with VTE (OR 2.55 and 2.71, respectively; p < 0.05). Interestingly, TP53 mutation portends worse survival (HR 3.85; p < 0.05) whereas CDKN2A mutation confers improved survival (HR 0.55; p < 0.05). No patient received targeted therapy for their specific mutations. Conclusions: Molecular testing is becoming more prevalent in the mPC treatment paradigm. Among our cohort, concurrent KRAS and TP53 mutations were frequently identified. Incidence rates of the most common mutations were similar to those observed in prior literature. KRAS and TP53 mutations were associated with higher incidence of VTE. TP53 mutation was associated with poorer prognosis.