bluuebunny/crossref_metadata_2025_split huggingface dataset:
Influence of ABO blood group on the natural history of advanced pancreatic adenocarcinoma (PC).
Authors: Teo MinYuen , Mohd Sharial Mohd Syahizul Nuhairy , Naidoo Jarushka , Jayaram Anuradha , Jayaraman Thevaraajan , Bajwa Raazi , O'Brien Michelle , McDonnell Felicity , Conlon Kevin C. , Geoghegan Justin , Power Derek Gerard , Grogan William , McDermott Raymond S. 
Published: February 2017

307 Background: An association between blood group (ABO) and PC has been demonstrated at epidemiologic and genomic levels. Variations in ABO type may lead to higher pro-inflammatory cytokines levels with modifications in cellular adhesionand signalling promoting carcinogenesis. This study investigated the influence of ABO on the clinical behaviour of advanced PC in patients (pts) , treated with chemotherapy (ctx). Methods: Pts with confirmed PC were identified from 4 institutional databases. Inclusion criteria were unresectable (UPC) or metastatic disease (MPC), receipt of ctx and availability of ABO data. Clinicopathologic details were collected. 200 random anonymied non-cancer ABO samples were collected as control. Descriptive statistics and survival analyses were performed. Results: Between 2001 and 2012, 222 pts met inclusion criteria. Median age was 63 years (range: 33 – 83) 56% were males. 60% of pts had MPC and 27% received doublet ctx. ABO distribution was: A (40%), AB (5%), B (11%) and O (44%). The incidence of blood type A was higher in PC cohort than control (40 vs 30%, p=.03) but identical between UPC and MPC (41 vs 40%, p=.84). Overall survival between type A and non A were identical for the entire cohort (5.8 vs 6.6 mos, HR 1.04 95% CI 0.76 – 1.40, p=.82), UPC (7.6 vs 9.5 mos, HR 1.08 95% CI 0.65 – 1.76, p=.77) or MPC (5.4 vs 4.7 mos, HR 0.94 95% CI 0.66 – 1.34, p=.78). For UPC, 56 pts (64%) had radiographic documentation of the pattern of progression. Type A pts had lower propensity for developing distant metastasis (7/21) than non A (23/35), at 33 vs 66%, p=0.03. Amongst pts with MPC, the incidence of hepatic and pulmonary metastases for type A and non A were identical (77 vs 74%, p=.83; 21 vs 18%, p=.81). However, peritoneal dissemination was less common in type A pts (6 vs 23%, p=.01). Conclusions: Consistent with existing epidemiologic data, the incidence of blood type A is significantly higher in pts with PC, although this does not appear to be stage dependent. ABO did not appear to influence OS in this cohort. However, our data suggests that the pattern of disease spreadmay be related to the ABO blood type. ABO-related glycosylated products could be a target for disease modulation in further studies.
Association of high-throughput RNAi and drug screening with candidate novel therapeutic targets in esophageal carcinoma.
Authors: Chong Irene Yu-Shing , Hooper Sean D. , Cunningham David , Elliott Richard , Chen Lina , Campbell James , Bajrami Ilirjana , Kozarewa Iwanka , Wetterskog Daniel , Wilkerson Paul M. , Lambros Maryou B. , Rao Sheela , Starling Naureen , Chau Ian , Lord Christopher J. , Ashworth Alan 
Published: February 2017

31 Background: Oesophageal cancer is the sixth most commonly diagnosed cancer worldwide and carries a poor prognosis. Targeted therapeutic strategies have relied on the identification of genes which are amplified and overexpressed but the discrimination between genes which drive cancer and those that are coincidental has not yet been fully achieved. Methods: We carried out a functional genetic screen of 714 kinases in 18 tumour cell line models of oesophageal adenocarcinoma (EAC) and squamous cell carcinoma (SCC) to identify genes critical to the survival of specific oesophageal subtypes. High throughput drug screening of 80 compounds, largely comprising those used in clinical trials or in routine clinical practice, was undertaken in parallel to reveal druggable targets and to validate functional screening results. Results: We show proof of principle that the integration of functional and drug profiling results with molecular profiling data is a valid approach for identifying druggable targets by correlating the effects of ERBB2, EGFR and CDK6 gene knockdown with sensitivity to drugs targeting their respective proteins. We have characterised new genetic dependencies for EAC involving TGF beta signalling and the JAK/STAT pathway. Decreased cell viability associated with silencing of ACVR2 and ACVR1C (activin receptors involved in TGF beta signalling) was consistent with sensitivity to nilotinib, a cABL inhibitor that modulates TGF beta signalling. Furthermore, decreased cell viability in EAC models was observed with silencing of JAK2. This strongly correlated with sensitivity to PF-04691502 and BEZ 235, both potent inhibitors of PI3K/mTOR which signal downstream of JAK2. We have validated novel sensitivity to small molecule tankyrase inhibitors in a subgroup of oesophageal models, suggesting that a subset of Wnt dependent oesophageal cancers could be targeted with these agents. Conclusions: The molecular and functional genetics of oesophageal cancer is poorly understood. By generating functional viability and drug sensitivity data for a panel of oesophageal tumour cell lines, we have identified new genetic dependencies and candidate drug targets for this aggressive disease.
Is survival in advanced pancreas cancer (APC) correlated to treatment-related lymphopenia (TRL)?
Authors: Jayaram Anuradha , Teo MinYuen , Mohd Sharial Mohd Syahizul Nuhairy , McDonnell Felicity , Geoghegan Justin , Conlon Kevin C. , Fennelly David , McDermott Raymond S. 
Published: February 2017

313 Background: Relationship between TRL and survival has been described in patients (pts) who receive adjuvant chemoradiotherapy. Evidence on TLR in APC treated with chemotherapy (ctx) is limited. We investigate the effect of ctx on TRL and its association with survival. Methods: Pts with APC were identified from two institutional databases. Inclusion criteria were: locally advanced (LA) or metastatic disease (MPC) and receipt of ctx. Baseline clinicopathologic and biochemical details including lymphocyte count at baseline and between day 21 and 28 were collected. Degree of TRL was collected prior to initiation of ctx and graded according to CTCAE v4. Descriptive statistics and survival analyses were performed. Results: Between 2001 and 2012, 97 pts were included. Median age was 64 years (range: 42 – 79), 58% were males. MPC seen in 57% of pts and 46% received doublet ctx. Ca19-9 ≥10,000 was detected in 77% pts. Uni- and multivariate analyses for six variables are described in the table. Major reduction, as defined by a 33% change in TLC, was described as a major reduction, present in 14 pts (15%). A major reduction of TLC was associated with a median overall survival (OS) of 2.5 mths (95%CI=1.2-5.3) versus 7.1 mths in those with no TLC change (95%CI=5.6-9.3) (p=0.0149). When assessed by CTCAE, difference in OS was also noted for G0 (n=47), G1 (n=39), G>=2(n=10) lymphopenia: 95 pts had grade 0-2 TLC 4 weeks post chemotherapy. OS was 9.7, 5.3 and 1.9 mths for grade 0, 1, and 2 lymphopenia. (p=<0.0001) respectively. Conclusions: TRL is an independent prognostic factor for APC. In comparison to existing data where chemo-radiation increases the grade and rates of TRL, APC pts treated with ctx had lower rates of TRL. This raises the question whether TRL is determined by the underlying biology of APC versus radiotherapy related effect. [Table: see text]
Duodenal and ampullary carcinoid tumors: Using size to predict necessity for lymphadenectomy.
Authors: Dogeas Epameinondas , Hatzaras Ioannis , Cameron John L. , Wolfgang Christopher Lee , Hirose Kenzo , Hruban Ralph H. , Makary Martin , Pawlik Timothy M. , Choti Michael A. 
Published: February 2017

316 Background: The metastatic potential and choice of therapy of duodenal and ampullary carcinoid tumors are poorly understood. We evaluated the local management and outcomes in patients with these uncommon tumors and determined factors predicting risk of nodal involvement. Methods: 117 patients were identified with duodenal or ampullary carcinoid tumors between 1996 and 2012, who were treated in a single high-volume center. Clinicopathologic data and overall survival by local treatment modality were analyzed. Results: Among all patients, 64 (55%) were treated surgically, including 34 (29%) who underwent pancreaticoduodenectomy (PD), 14 (12%) who underwent local resection (partial duodenectomy), and 16 (13.6%) where a carcinoid tumor was found incidentally after PD for another indication. The remaining 53 patients (45%) underwent endoscopic excision. The average tumor size was 1.8 cm (0.1-8.5) and the majority were of duodenal origin (n=93, 80%). Surgical management was more commonly performed for ampullary tumors compared to tumors of duodenal origin (83% vs. 47%, p=0.002), and endoscopic excision was more common with smaller tumors (p=0.001). Most carcinoids were well-differentiated (94%) and 55% were T1/T2. Yet, among the 55 patients in whom lymph nodes were histologically assessed (PD or lymph node sampling), 51% had positive nodes (N+). In addition, on multivariate analysis nodal involvement was strongly associated with tumor size (OR: 9.9, p=0.001). Specifically, tumors larger than 1-cm had positive nodes in more than 70% of cases whereas those ≤1cm had a 5% risk of nodal involvement (1 of 21 patients) (Table). Similar rates of N+ were observed for both duodenal and ampullary carcinoids. With long-term follow-up, only one recurrence was observed (1%). The overall survival was similar among all treatment groups (median=139 months). Conclusions: Lymph node involvement is common in patients with duodenal and ampullary carcinoid tumor, particularly among tumors >1 cm in size. When possible, surgical resection with lymphadenectomy is recommended for such tumors. [Table: see text]
Efficacy and feasibility of chemotherapy and radiation therapy for borderline resectable pancreatic cancer in elderly patients.
Authors: Figura Nicholas , Cruz Alex , Mellon Eric Albert , Chuong Michael , Hoffe Sarah , Springett Gregory M. , Saeed Nadia , Hodul Pamela Joy , Malafa Mokenge Peter , Balducci Lodovico , Shridhar Ravi 
Published: February 2017

320 Background: To date there have been few studies evaluating the efficacy and tolerability of aggressive neoadjuvant chemotherapy and radiation therapy (RT) for patients ≥70 years of age with borderline resectable pancreatic cancer (BRPC). Methods: We performed a retrospective review of our institutional experience treating BRPC from 2006 to June 2012. All patients were staged with a pancreas protocol CT scan, endoscopic ultrasound, and PET/CT scan. The diagnosis of BRPC was confirmed by our GI Tumor Board prior to treatment. Our institutional preference for preoperative chemotherapy included gemcitabine, paclitaxel and capecitabine (GTX). RT techniques included intensity modulated radiation therapy (IMRT) or stereotactic body radiation therapy (SBRT). Restaging scans were performed after RT completion and patients were then considered for surgical resection. The data was analyzed using Kaplan-Meier and Cox regression analysis. Results: This study included 72 BRPC patients with a median age of 65 years (range 36-87). 24 patients (33%) were ≥70 years old. Median follow up for all patients was 12.7 months. 56 patients (77%) received preoperative GTX. Of the patients ≥70 years, 7 were treated with IMRT and 17 with SBRT, compared to 8 who were treated with IMRT and 40 with SBRT in the younger cohort. In the older group, 11 patients (46%) underwent surgery with all attaining microscopically negative margins (R0), compared with 32 patients that underwent surgery in the younger cohort (61.7%), 29 of which received R0 margins (90.6%). Median survival for patients ≥70 years old was 12.6 months compared to 12.8 months for the younger patients. There was no difference in overall survival (p =.606) or progression free survival (p = .312) between the two groups. Multivariate analysis showed that surgery in the entire group was significantly associated with an improvement in overall survival (p = .011). Conclusions: Our data indicates that aggressive neoadjuvant chemotherapy and RT is equally effective for older patients. Neoadjuvant therapy for BRPC should not be withheld basely solely on patient age.
Octreotide LAR use among elderly patients with carcinoid syndrome and survival outcomes: A population-based analysis.
Authors: Shen Chan , Xu Ying , Yao James C. , Shih Ya-Chen T. 
Published: February 2017

322 Background: Octreotide LAR is indicated for the treatment of carcinoid syndrome, diarrhea related to VIPoma, and may delay tumor growth in neuroendocrine tumors (NETs). The pattern of octreotide LAR use in clinical practice and its impact on survival outcomes has not been well-documented. Methods: Using the SEER-Medicare database, we identified NET patients diagnosed between 7/1999 and 12/2007. We excluded those under age 65, enrolled in HMOs, and without continuous Part A and B enrollment within 12 months of diagnosis. Potential indication for octreotide use was defined as ≥ 2 claims for carcinoid syndrome, flushing, diarrhea, or malignant islet cell neoplasm within first year of diagnosis, with the first claim occurring within 6 months of diagnosis. HCPCS codes, J2352 and J2353, were used to identify octreotide LAR treatment. Multivariate logistic regression and Cox proportional hazard survival analyses were performed to ascertain factors associated with octreotide use and evaluate impact of octreotide use on survival; covariates included age, race, region, comorbidity score, urban/rural status, tumor characteristics, neighborhood socioeconomic status and year of diagnosis. Results: Among those with potential indication for octreotide use (carcinoid syndrome and islet cell), 264 (49%) out of 539 distant stage patients, and 83 (10%) out of 850 patients with local regional disease were started on octreotide LAR within 6 months of diagnosis. Multivariate logistic regression showed that patients living in the southern region were less likely to use octreotide. Multivariate proportional hazard model showed that octreotide LAR provided a significant 5-year survival benefit for distant stage patients (HR=.80, p-value=.047); while this survival benefit was not shown for the local/regional stage patients (HR=.97, p-value=.89). Conclusions: This retrospective study suggests a possible survival benefit for use of octreotide LAR in distant stage elderly patients with carcinoid syndrome. Data also suggest that many elderly patients with claims for carcinoid syndrome did not receive octreotide LAR therapy within 6 months of diagnosis. Further studies and improved education are warranted.
Feasibility and efficiency of automatic treatment planning for stereotactic body radiation therapy (SBRT) in pancreatic cancer patients.
Authors: Dholakia Avani Satish , Moore Joseph A. , Wild Aaron Tyler , Yang Wuyang , Evans Kim , McNutt Todd , Herman Joseph M. 
Published: February 2017

323 Background: Overlap volume histogrmas (OVHs) allow for new plans to be generated based upon prior similar treatment plans. The purpose of this project was to clinically deploy a generic and user-friendly interface for using a database populated with OVHs for planning SBRT pancreas patients. An interface for evaluating adherence to protocol tolerances is also developed to aid in the planning process. Methods: A database of previously treated SBRT pancreas patients is used to query the organ at risk (OAR) dose from patients with similar or harder to plan OVHs. For each OAR in a new plan, the database is queried to find the lowest achievable structure dose from all previous patients with a greater than or equal overlap between the selected structure and the target structure. Queried values are then automatically loaded into the inverse planning optimizer objectives and used to generate an optimized plan. Plans are then evaluated using a protocol interface which queries relevant protocol values and displays the values in a color-coded interface. Upon plan completion the system submits the new patient data to the OVH database and stores relevant DVH metrics in the MOSAIQ database for tracking. Results: The interface has been used to successfully plan 5 SBRT patients. All planned patients met protocol requirements. Automatic plans required fewer iterations to produce an acceptable plan. The physician indicated preference to the automatically generated plans due to better adherence to protocol requirements and lower critical structure doses. Conclusions: Automatic planning can be used to generate clinical plans which reduce dose to normal tissues while achieving the dose distribution required by clinical protocols. The protocol interface allows for more rapid evaluation of plan acceptability during planning and for physician review. The system can be deployed clinically, but requires adherence by all participants to standard naming conventions for targets and OARs.
Survival trends among patients with advanced hepatocellular carcinoma in the United States.
Authors: Ghimire Krishna Bilas , Shah Binay Kumar , Nepal Barsha 
Published: February 2017

329 Background: Sorafenib was approved by FDA for treatment of HCC in 2007. This study was conducted to evaluate survival outcome in advanced HCC during 2005-2006 and 2008-2009 using U.S. Surveillance, Epidemiology, and End Results (SEER) cancer registry database.Methods: We analyzed the Surveillance, Epidemiology, and End Results (SEER*Stat) database: Incidence - SEER 18 Regs Research Data + Hurricane Katrina Impacted Louisiana Cases, Nov 2011 Sub (1973-2009 varying) using MP-SIR session. We analysed 1 year relative survival rates among stage IV HCC patients between pre- sorafenib (2005- 2006) and post- sorafenib (2008- 2009) eras. We used seer Z test to compare relative survival rates among cohorts of patients categorized by gender and age groups (<50 and >50 years). Results: There were 2,497 (1,180 in pre-sorafenib era and 1,317 in post-sorafenib era) stage IV HCC patients reported in seer database. Overall 1 year relative survival rates ± standard error (SE) were: 12.5±0.7% (12.5±1% in pre sorafenib era vs 13.1±1.1% in post sorafenib era, Z score= 0.481, p value=0.63). Overall Relative survival rates among men and women were 12.9±0.8% (12.7±1.1% in pre vs 13.4±1.2 in post sorafenib era, Z score=0.254, p value=0.79) and 11.8±1.6% (11.7±2.2% in pre vs 11.5±2.5 post sorafenib era, Z score=0.469, p value=0.63) respectively. There was no significant differences between 1 year relative survival rates by age groups (<50 and >50 years). Conclusions: This study showed no significant difference in 1-year relative survival rates during 2008-2009 as compared to 2005-2006. More studies are required to find out why the findings of SHARP trial have not translated to population-based settings.[Table: see text]
A phase II study of complete neoadjuvant therapy in rectal cancer (CONTRE): The Brown University Oncology Group.
Authors: Perez Kimberly , Pricolo Victor , Vrees Matthew , DiPetrillo Thomas A. , Oldenberg Nicholas , Klipfel Adam , Schechter Steven , Kinsella Timothy J. , Roth Leslie , Cataldo Thomas , Shah Nishit , Olszewski Adam J. , Isdale Debora , Safran Howard , Sikov William M. 
Published: February 2017

335 Background: While preoperative chemoradiation followed by surgery is the standard approach for patients (pts) with newly diagnosed clinical stage II-III rectal cancer, many are unable to tolerate postoperative adjuvant chemotherapy which may compromise disease-free and overall survival. CONTRE is a multicenter phase II study designed to determine the feasibility of administering all chemotherapy prior to surgery and to assess its impact on pathologic complete response (pCR) and complete (R0) resection Methods: Pts with T3-4 and/or N1-2 rectal cancer, staged by endorectal ultrasound (ERUS) and pelvic MRI, receive modified (m) FOLFOX6 every 2 weeks x 8 cycles, followed by repeat MRI and proctoscopy to assess response. Pts then receive 50.4 Gy IMRT with 5-FU 225 mg/m2/day or capecitabine 825mg/m2 BID, 5 days per week during radiation, followed by surgery 4-8 weeks later. Results: Thus far, we have enrolled 36 of a planned 39 pts (median age 58, range 30-79; T2-1, T3-30, T4-2; N1-20, N2-7). 28 of the first 30 (93%) completed 8 cycles of mFOLFOX6. 26 pts have completed chemoradiation while 2 chose to proceed directly to surgery. All patients opted to receive capecitabine during radiation. Grade 3/4 toxicities during chemotherapy and chemoradiation have included diarrhea (16%) and neutropenia (12%), with grade 3 renal and cardiac toxicities reported in one patient each. A clinical complete response after chemotherapy alone was achieved in 3 of 29 (10%). Of the first 21 pts undergoing surgery, pCR has been achieved in 6 (29%) and R0 resections in 100%. Thus far, all pts have been able to undergo sphincter-sparing resections. Study accrual will be completed by the meeting. Conclusions: A larger proportion of stage II-III rectal cancer pts are able to complete mFOLFOX6 (>90% in our cohort) when administered prior to chemoradiation and surgery. Complete neoadjuvant treatment may represent a well-tolerated alternative to the current standard treatment sequence and a platform for the evaluation of novel therapeutics such as targeted agents during preoperative therapy. Funded in part by LIFEcycle, Inc. Clinical trial information: NCT01363843.
Screen detection of serrated polyps by stool DNA multi-target testing (sDNA-MT): Comparison against fecal immunochemical occult blood testing (FIT).
Authors: Heigh Russell I. , Mahoney Douglas W. , Yab Tracy C. , Simonson Julie A. , Boardman Lisa A. , Domanico Michael J. , Berger Barry M. , Lidgard Graham P. , Ahlquist David A. 
Published: February 2017

341 Background: Precursors to 1/3 of colorectal cancer (CRC), serrated polyps have historically been underdetected by screening due to their inconspicuous, nonhemorrhagic, and proximal nature. New generation sDNA-MT show high sensitivity for both CRC and advanced adenomas (Gastroenterology 2012;142:248), but screen detection of serrated polyps by this approach requires further validation. Aim: To assess and compare noninvasive detection of sessile serrated polyps >1cm (SSP) by sDNA-MT and a commercial quantitative FIT. Methods: In a blinded prospective study, a single stool sample used for both tests was collected from 456 asymptomatic adults prior to screening or surveillance colonoscopy (criterion standard). All 29 patients with SSP were included as cases and all 232 with no neoplastic findings as controls. Buffered stool samples were processed and frozen on receipt; Exact Sciences performed sDNA-MT in batches using optimized analytical methods (Gastroenterology 2012;142:S770). The sDNA-MT panel targets methylated BMP3 (mBMP3) and NDRG4, mutant KRAS, β-actin, and hemoglobin. FIT (Polymedco OC-FIT Check) was performed in separate lab <2 days post defecation and evaluated at cutoffs of 50 (FIT-50) and 100 ng/ml (FIT-100). Results: Age/sex distributions were similar in cases and controls: 40% vs 45% > 65 years and 51% vs 59% women, p=NS respectively. SSP median size was 1.2cm (range 1-3cm), 93% were proximal, and 64% had synchronous diminutive polyps. Among sDNA-MT markers, mBMP3 proved highly discriminant for SSP detection (AUC=0.87, p<0.00001); other DNA markers were less informative and provided no incremental sensitivity. Hemoglobin alone showed no discrimination (AUC=0.50, p=NS). At matched specificities, SSP detection by stool mBMP3 was significantly greater than by either FIT-50 or FIT-100 (Table). Conclusions: From a screening and surveillance setting, SSP can be detected noninvasively by stool assay of exfoliated DNA markers, especially mBMP3. FIT appears to have no value in SSP detection. [Table: see text]