bluuebunny/crossref_metadata_2025_split huggingface dataset:
A multicenter phase II study of sorafenib in Japanese patients with hepatocellular carcinoma and Child Pugh A or B cirrhosis.
Authors: Suzuki Eiichiro , Kaneko Shuichi , Okusaka Takuji , Ikeda Masafumi , Yamaguchi Kensei , Moriguchi Michihisa , Sato Tosiya , Furuse Junji 
Published: February 2017

354 Background: Sorafenib has been used as the first-line treatment for advanced hepatocellular carcinoma (HCC), however, its efficacy and safety in Japanese patients (pts), especially those with Child-Pugh (CP) B cirrhosis, have not yet been fully examined. This study was conducted to evaluate the efficacy and safety of sorafenib in Japanese pts with HCC and CP B or CP A cirrhosis. Methods: The eligibility criteria were patients 1) with pathologically or clinically proven HCC, 2) with an ECOG performance status 0 to 2, 3) aged 20 to 79 years, 4) with measurable lesions, 5) with adequate hematological, renal and Child Pugh class A or B liver functions. Sorafenib was administered orally at the dose of 400 mg twice daily. Administration was continued until the detection of disease progression or appearance of unacceptable toxicity. The primary endpoint of the study was progression-free survival (PFS), and the secondary endpoints included objective response, overall survival (OS), and toxicity. Results: Forty CP A pts and 12 CP B pts were enrolled between April 2010 and January 2012. The median PFS in the CP A pts was 3.3 months (M) and that in the CP B pts was 3.2 M. Among the pts with CP A, there was one patient with confirmed complete response (2.5%), 3 pts with partial response (7.5%), and 19 pts (47.5%) with stable disease (SD). Among the pts with CP B, there were no treatment responses, and 8 (66.7%) pts had SD. The median overall survival in the CP A pts was 13.4 M and that in the CP B pts was 7.4 M. With regard to toxicities, fewer CP A pts experienced grade 3/4 toxicities than CP B pts (77.5% vs. 91.6%). The grade 3/4 toxicities in the CP A and B pts, respectively, included thrombocytopenia (10% and 25%), hand foot skin reaction (27.5% and 16.7%), Erythema multiforme (0% and 16.7%), and upper gastrointestinal bleeding (0% and 16.7%). There were no treatment-related deaths in either group of patients. Conclusions: This study shows that sorafenib is effective and well-tolerated in Japanese patients with HCC and Child Pugh class A liver cirrhosis, consistent with previous reports. The outcome was poorer and severe toxicities were more frequent in patients with Child Pugh B cirrhosis than in those with Child Pugh A cirrhosis. Clinical trial information: 000002972.
Utility of [18F] flourodeoxyglucose positron emission tomography (FDG-PET) to predict resectability after neoadjuvant therapy in patients with unresectable pancreatic cancer on CT scans.
Authors: Khawandanah Mohamad Osama , Kurkjian Carla , Penaroza Shyla , Arnold Charles , Herman Terence S. , Talbert Michael , Postier Russell , Pant Shubham 
Published: February 2017

357 Background: The standard imaging approach in patients with pancreatic cancer is contrast enhanced computed tomography (CT), however, Response Evaluation Criteria in Solid Tumors (RECIST) may not be adequate in evaluating response to neoadjuvant therapy. A growing body of evidence exists to suggest that there is additional useful information to be gained from the use of FDG-PET scans in this setting. Methods: We conducted an IRB approved retrospective chart review of patients with locally advanced or borderline resectable pancreatic adenocarcinoma who underwent neoadjuvant therapy at the University of Oklahoma and who had PET/CT imaging before and/or after neoadjuvant therapy between September 2006 and September 2013. Complete remission (CR) was defined as decrease in SUV to ≤ 3.0 or background, and partial response (PR) was defined as decrease in SUV from baseline, but > 3.0. Results: A total of 13 patients underwent Whipple surgery after neoadjuvant therapy at our institution. Four patients (31%) had persistent unresectable disease on CT scans post-neoadjuvant therapy, but demonstrated CR (three patients) or PR (one patient; Pre-treatment SUV: 10.1, Post Treatment: 4.6) on the PET scan. These patients underwent Whipple surgery based on PET response. All four (100%) patients underwent R0 resection. Two patients (50%) received neoadjuvant chemo-radiation in addition to chemotherapy. Conclusions: Response on FDG-PET/CT can be a predictor of R0 resection in cases with evidence of unresectable disease on conventional CT scan. A protocol to study larger number of patients prospectively is being designed.
Long-term outcome of patients with hepatocellular carcinoma treated with hypofractionated stereotactic radiation therapy as a bridge to liver transplantation.
Authors: Katz Alan W. , Rosenzweig Douglas P 
Published: February 2017

368 Background: Stereotactic hypofractionated radiation therapy (SHORT) is a safe, non-invasive, treatment modality for patients with hepatocellular carcinoma (HCC). The purpose of this study was to evaluate the long-term outcome of patients with HCC receiving SHORT as a bridge therapy to LT. Methods: We reviewed 9 consecutive patients who underwent LT between 2008 and 2010 after receiving SHORT as bridge therapy. Radiation therapy was delivered using a 6 MV linear accelerator and an infrared based patient posititiong system. Total dose was 50 Gy in 10 fractions. Doses were prescribed to the 100% isodose line (IDL), with the 80% IDL covering the gross tumor plus a minimum margin of 7 mm. Survival was measured from the date of LT. Results: Median time from completion of SHORT to LT was 5.9 months (range; 0.9-15.7 months). After a median follow up of 48.6 months (range; 17.8-65.3 months) all patients were still alive. No significant surgical complications were seen in any of the patients. 8 patients demonstrated necrosis in the treated tumors, ranging from 8-100%. Only 1 patient did not show any treatment effect on pathological examination. One patient developed recurrent disease in a lymph node and in the transplanted liver, both treated by SHORT with complete response. Conclusions: SHORT is a safe and effective bridging therapy with patients experiencing excellent disease-free and overall survival following LT.
The time trends of gallbladder cancer and cholangiocarcinoma in 1,047 patients.
Authors: Mitsunaga Shuichi , Ikeda Masafumi , Shimizu Satoshi , Ohno Izumi , Takahashi Hideaki , Okuyama Hiroyuki , Kuwahara Akiko , Ochiai Atsushi 
Published: February 2017

376 Background: Gallbladder cancer (Gb ca) and cholangiocarcinoma (CC ca) are major primary sites in biliary tract cancer. Progresses of diagnosis and anti-cancer therapy for Gb and CC ca lead to the changes of patients’ characteristics and overall survival time, but is not fully understood. This study aimed to identify the time trends in patients with Gb and CC ca. Methods: The inclusive criteria in this study was the patients receiving initial treatment including surgery (Op), chemotherapy (Chemo), radiotherapy (RT), or best supportive care (BSC) for Gb or CC ca in our institution, and 1047 patients were reviewed. Patient who received initial treatment at 1992-2005 were in 54.1 % of the study subjects and was defined as Group 1. Patients with initial treatment at 2006-2012 were categorized to Group 2 and were in 45.9% of all patients. The differences between two groups were evaluated, and the features of Group 2 were identified. Results: Age more than 60 years (Odd ratio [OR]: 2.37), the absence of distant metastasis (OR: 2.13), and ECOG performance status score (PS) = 0 (OR: 1.70) were identified as the independent features of Group 2. The rates of Op, Chemo, RT, and BSC were 38.5, 24.7, 14.9, and 21.7% in Group 1, and 40.8, 49.9, 1.5, and 6.0% in Group 2. The rate of Chemo in Group 2 was higher than that in Group 1 (P < 0.01). The median times of overall survival (OS) in Op, Chemo, RT, and BSC were 21.1, 5.2, 6.9, and 2.4 months in Group 1 and 60.6, 9.2, 10.5, 2.8 months in Group 2. The OS in Op or Chemo of Group 2 was longer than that in Group 1 (P < 0.01, P < 0.01). The independent poor prognostic factors were distant metastasis (HR: 3.91), Group 1 (1.81), and PS > 0 (1.72) in all patients, distant metastasis (HR: 3.56), Group 1 (2.12), biliary drainage (1.75) in Op, and PS>0 (HR: 1.97), Group 1 (1.74), and distant metastasis (1.64) in Chemo. Conclusions: The recent trends in patients with Gb and CC ca were aging, low rates of distant metastasis, good PS, increased cases with chemotherapy, and the prolonged survival times in surgery and chemotherapy. The presence of distant metastasis, the worsened PS, and the previous treatment group were the independent poor prognostic factors.
Increasing disparities in age-related incidence of colon and rectal cancer in the United States, 1975-2010.
Authors: Bailey Christina Edwards , Hu Chung-Yuan , You Y. Nancy , Chang George J. 
Published: February 2017

392 Background: The overall incidence of colorectal cancer (CRC) has been decreasing since 1998, but there has been an apparent rise in the incidence of CRC in young adults. The primary aim of this study was to evaluate age-related disparities in secular trends in CRC incidence in the United States. Methods: A retrospective cohort study was performed using the Surveillance, Epidemiology, and End Results (SEER) registry. All patients diagnosed with colon or rectal cancer from 1975 to 2010 was queried. SEER*Stat (version 8.04, National Cancer Institute) was used to obtain the annual cancer incidence rates, annual percent change (APC), and corresponding p values for the secular trends. Results: Overall age-adjusted CRC incidence decreased by 0.92% between 1975 and 2010. There has been a steady decline in the incidence of CRC in patients age 50 years or older, but the opposite trend has been observed in patients 20 to 34 years of age. The APC for patients with localized, regional, and distant colon cancer at diagnosis in the 20 to 34 year age group was 1.10 (95% CI 0.28 to 1.93; p=0.01), 0.91 (95% CI 0.23 to 1.61; p=0.01) and 1.81 (95% CI 0.88 to 2.75; p<0.001). The APC for patients with localized, regional ,and distant rectal cancer in the 20 to 34 year age group was 4.03 (95% CI 3.02 to 5.05; p<0.001), 3.05 (95% CI 1.95 to 4.17; p<0.001) and 2.66 (95% CI 1.33 to 3.99; p<0.001). Based on current trends, in 2030 the incidence rate for colon and rectal cancer will increase by 90% and 124.2% respectively for patients 20 to 34 years of age while decreasing by 37.8% and 34.3% for patients 50 to 75 years of age. Conclusions: There has been a significant increase in the incidence of CRC diagnosed in patients age 20 to 34, with a decline in older patients. Further studies are needed to determine the cause for these trends and identify potential preventive and early detection strategies. [Table: see text]
Efficacy of a population-based colorectal cancer screening program and analysis of outcomes in screen-detected and non-screen-detected tumors.
Authors: Mansouri David , Mcmillan Donald C. , Morrison David S. , Crighton Emilia M. , Horgan Paul G. 
Published: February 2017

394 Background: Population based faecal occult blood test (FOBt) screening for colorectal cancer reduces cancer specific mortality through the detection of early stage disease. However, programmes are limited by uptake and the characteristics of the test itself. The aim of the present study was to compare features of screen detected (SD) and non-screen detected tumours (NSD) and assess the effect on cancer specific mortality. Methods: Prospectively maintained databases of both the prevalence round of a biennial population based FOBt screening programme and a regional cancer audit database were analysed. Mortality data was obtained from the national registry. Results: Of the 395,097 males and females aged 50 to 74yrs invited to screening, 203,886 (52%) responded, 6,085 (3%) tested positive and 4,632 (76%) attended for colonoscopy. A total of 951 patients were diagnosed with cancer within two years of screening invite: 378 (40%) SD and 573 (60%) NSD. Of the NSD patients, 376 (66%) were non-responders, 134 (23%) were FOBt negative and 63 (11%) did not attend or did not have cancer diagnosed at colonoscopy. Therefore, estimated FOBt sensitivity was 77%, and specificity was 99%. Comparing SD and NSD patients, SD patients were more likely to be male, less socioeconomically deprived, have a tumour with a lower Dukes stage, and more likely to have a left-sided tumour (all p<0.05). In addition, SD patients were more likely to undergo an operation with a curative intent, less likely to undergo an emergency procedure, and less likely to die within 30 days of their procedure (all p<0.001). With a median follow-up of 2 years, SD patients had improved cancer specific survival versus NSD patients (p<0.001). This remained significant on multivariate survival analysis (Cox proportional hazards) including age, sex, deprivation, emergency presentation, tumour site and stage, and curative surgery (p<0.001). Conclusions: Independent of established prognostic factors, SD patients have more favourable outcomes than those with NSD tumours. Therefore, further studies to improve the response rate to a screening invitation and the sensitivity of the current screening test are warranted.
Nomogram for predicting overall and colostomy-free survival for patients with anal cancer.
Authors: Tsikitis Vassiliki Liana , Lu Kim , Kim Jong Sung , Billingsley Kevin G. , Thomas Charles R. , Herzig Daniel 
Published: February 2017

400 Background: The incidence of anal cancer, currently about 5,000 persons a year, is increasing in the United States. Its treatment has evolved from a radical surgical treatment including abdominoperineal resection to a combined chemoradiotherapy (CRT) (Nigro protocol) approach which allows for sphincter preservation. The specific aim of this study was to develop an accurate model and nomogram to predict overall (OS) and colostomy free survival (CFS) for patients (pts) presenting with anal cancer. Methods: Pts with de novo anal cancer were selected from the National Cancer Database (NCDB) from years 1998-2010. The database included 53,523 pts. After excluding anal margin cancer pts and pts with missing data points; 1,823 pts were included and their data analyzed. Variables included time to death, censoring indicator, age, race, sex, tumor size, surgery status, nodal status, radiation (RT) and chemotherapy (CT) separately and as a CRT. A stratified Cox proportional hazards model for OS and a logistic regression model for CFS were developed, respectively. For each primary end point, our final model was validated to ascertain whether predicted values from the model are likely to accurately predict responses on future subjects or subjects not used to develop our model. Results: Statistically significant variables in the CFS model were age, nodal status, TNM stage, RT (p ≤ 0.0001), and tumor size (p = 0.010). Similarly, for OS model statistically significant variables (all with p ≤ 0.005) fitted across the strata of TNM clinical stage included age, sex, tumor size, nodal status, and CRT. Nomograms that predict events are based on our final models with the estimated mean absolute bootstrap calibration error being only 0.011 for OS model and 0.02 for CFS model, respectively. Conclusions: A nomogram can predict OS and CFS over lifetime. Such outcome prediction tools may potentially be used as prognostic and decision support tools to guide therapy and predict pts that may need surgery in their lifetime.
The role of metformin for primary prevention in non-elderly diabetic colorectal cancer patients.
Authors: Sehdev Amikar , Shih Ya-Chen T. , Vekhter Benjamin , Lyttle Christopher , Polite Blase N. 
Published: February 2017

406 Background: There is growing evidence for the beneficial effect of metformin in reducing the incidence of colorectal cancer (CRC) in diabetic patients. However, no such studies are done in the US population. We conducted a case control study (N=8,046) in non-elderly diabetic adult US population (age 18-64 years) to investigate the role of metformin for the primary prevention of CRC. Methods: MarketScan claims database was used to identify diabetic patients with CRC using ICD-9 codes. Only incident cases of CRC in diabetic patients were included in the study. Two matched controls (matched for age, sex, and geographical region) were selected per case. The exposure to metformin was assessed from prescriptions in the 12 months prior to the earliest date of CRC diagnosis. The primary objective was to assess the odds of having CRC in metformin users as compared nonusers. Adjusted odds ratios (AOR) were calculated by adjusting for multiple potential confounders using conditional logistic regression. Results: The mean age of CRC patients was 56 years, 60% were males. Metformin was prescribed to 38.13% patients. A total of 37% (995/2,682) patients developed CRC in metformin exposed group compared to 62.9% (1,687/2,682) patients in non-metformin exposed group. In a multivariate model, any metformin use was associated with a statistically significant 12% reduced risk of developing CRC (AOR 0.88, 95% CI, 0.79-0.98, p<0.026). Prescribed NSAIDs were also associated with decreased incidence of CRC (AOR 0.84, 95% CI, 0.73-0.97, p=0.019). Variables associated with increased incidence of CRC in the multivariate model were IBD (AOR 1.94, 95% CI, 1.13-3.33, p<0.015); use of insulin (AOR 1.45, 95% CI, 1.27-1.65, p<0.001); coronary artery disease (AOR 1.66, 95% CI, 1.43-1.93, p<0.001). There was no significant relationship between CRC incidence and obesity (AOR 1.19, 95% CI, 0.93-1.53, p=0.158); polycystic ovary disease (AOR 0.32, 95% CI, 0.03-2.76, p=0.3); sulfonylureas (AOR 1.09, 95% CI, 0.96-1.24, p=0.15); thiazolidinediones (AOR 0.94, 95% CI, 0.82-1.08, p=0.41); statins (AOR 0.914, 95% CI, 0.82-1.01, p=0.108). Conclusions: The use of metformin appears to reduce the incidence of CRC in non-elderly diabetic adult US population.
Characterization of family history profiles in a large series of Lynch syndrome carriers.
Authors: Saraiya Devki , Wiyrick Sara J. , Tong Barry S. , Moyes Kelsey , Garner Elizabeth 
Published: February 2017

414 Background: The identification of Lynch syndrome carriers is an unmet medical need. Large studies characterizing family history profiles of unaffected individuals diagnosed with Lynch syndrome in the absence of a known family mutation have not been reported. Methods: We queried our laboratory database for unaffected patients who underwent Lynch syndrome genetic testing between September 2010 and May 2013 and had a positive test result. All individuals underwent full sequence and large rearrangement analysis of MLH1 and MSH2, and full sequence analysis of MSH6. Some patients also underwent full sequence and large rearrangement analysis of PMS2 and large rearrangement analysis of MSH6 and EPCAM. Those being tested for a known mutation in the family and patients undergoing single gene testing were excluded. We assessed family history profiles in 200 unaffected patients with genetically confirmed Lynch syndrome. Results: Of the 200 patients, 162 female and 38 male Lynch syndrome carriers were identified. Mutations in MLH1 and MSH2 were the most common (30.0% and 32.5%) while mutations in MSH6, PMS2, and EPCAM accounted for 21.0%, 13.5%, and 3.0% of all deleterious mutations, respectively. Eighteen patients did not have a first or second degree relative with colorectal cancer. Only 37.8% (73/193) of individuals had a first- or second-degree relative meeting the Amsterdam II criteria and 76.8 % (149/194) of individuals had a first or second degree relative meeting the Revised Bethesda criteria. The average PREMM1,2,6 score was 10.0% with 43.5% (87/200) falling below 5%. In this large cohort, 15.5% (31/200) had neither a first or second degree relative who met the Amsterdam II or Revised Bethesda criteria nor a PREMM1,2,6 score of 5% or greater. Conclusions: In order to improve detection of Lynch syndrome in the population, it is important to consider genetic testing in unaffected individuals even in the absence of a known family mutation. Development of guidelines that include having a single affected relative and extra-colonic cancers is needed to support healthcare providers in identifying appropriate patients for testing.
Universal screening for Lynch syndrome (LS) in colorectal cancer (CRC) and survival.
Authors: Haraldsdottir Sigurdis , Wu Christina Sing-Ying , Hampel Heather , Frankel Wendy , Pan Xueliang Jeff , Bekaii-Saab Tanios S. , Goldberg Richard M. 
Published: February 2017

415 Background: It has been argued that universal screening for LS should be performed on all patients (pts) diagnosed with CRC because screening LS pts and their relatives can detect early cancers and improve outcomes. This approach is being adopted by many comprehensive cancer centers around the country. The Ohio State University (OSU) began screening for deficient mismatch repair (dMMR) proteins by immunohistochemistry (IHC) on all CRC cases in 2006. This retrospective study aims to assess whether universal screening with IHC followed by conclusive testing (BRAF mutation in setting of MLH1 deficiency, and/or gene sequencing) affects pts survival. Methods: All CRC pts diagnosed at OSU from 3/2006-6/2012 with dMMR testing per IHC were included, and their charts were reviewed. Chi-square test was used to for categorical parameters, t-test was used for continuous variables, and the log-rank test for overall survival (OS) to compare the difference between pts with full conclusive testing vs those without full testing. Patients who expired within 4 weeks of diagnosis were excluded (n=10) from the OS analysis. Results: One hundred and twenty-two tumors (15.7% of 777 tumors tested) had dMMR by IHC during the study period. Fifty-one pts went on to have conclusive testing done; thirteen patients (25.5%) were diagnosed with LS, 29 patients (56.9%) had MLH1-hypermethylated tumors, and 9 patients (17.6%) were not found to have MMR mutations on gene sequencing. In an OS analysis, patients undergoing conclusive testing had significantly longer survival as compared to those with abnormal IHC without further testing (median OS not reached vs. 38 months, p=0.04). The difference was similar and remained marginally significant (p= 0.04-0.09) after correcting for age, stage and testing date using different models. Conclusions: Patients who had conclusive testing after initial abnormal universal screening with IHC had significantly longer OS compared to pts who had abnormal IHC without follow-up testing. It is possible that ascertainment bias and pts compliance influenced survival so larger prospective studies that document stage and treatment are needed to determine if increased surveillance in the setting of a LS diagnosis leads to better OS.