bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identifying factors impacting subsequent gemcitabine dose intensity in patients undergoing chemoradiation for locally advanced pancreatic cancer.
Authors: Shaikh Talha , Burki Meher , Wang Lora S , Egleston Brian , Hoffman John Parker , Cohen Steven J. , Meyer Joshua E. 
Published: February 2017

455 Background: Systemic therapy is a critical part of the management of locally advanced pancreatic cancer (LAPC) due to the risk of distant failure. In the clinic, anecdotal evidence suggests that maintaining dose intensity of chemotherapy is more challenging after prior chemoradiotherapy (CRT). We thus evaluated whether treatment or patient factors limit the amount of systemic therapy received in LAPC patients receiving CRT. Methods: Following IRB approval, we retrospectively reviewed all patients diagnosed with LAPC undergoing CRT between 2006 and 2012. Exclusion criteria included receipt of non-gemcitabine chemotherapy or chemotherapy prior to CRT. Patient and treatment factors were evaluated for their relationship to total gemcitabine dose received during CRT and within the first three months post-CRT. Statistical analysis was performed using regression models. Results: A total of 76 patients met the inclusion criteria with a median age of 69 (range 44-89) and a median follow-up of 13.2 months (range 3-68). The median gemcitabine dose received during CRT was 3,000 mg/m2 of a planned 3,600 mg/m2 and post-CRT was 5000 mg/m2 of a planned 9,000 mg/m2. Patients receiving a higher percentage of the desired chemotherapy dose during CRT received a lower percentage of desired chemotherapy dose post-CRT (p<0.01). Patients who underwent subsequent surgical resection (p<0.01) or received a higher radiation dose (p=0.03) were more likely to have received a higher total post-CRT chemotherapy dose. There were no variables correlated to chemotherapy dose received during CRT. Conclusions: Our analysis suggests that chemotherapy dosing during CRT rather than radiation dose impacts subsequent gemcitabine dose intensity. As a number of different CRT regimens are utilized in practice, this finding warrants further confirmation in a larger database.
The value of tissue protein expression as a predictor of efficacy for first- or second-line therapy (tx) in metastatic ductal pancreas cancer (PDAC) in patients (pts) receiving either gemcitabine (G)-based tx or 5FU (F)-based tx.
Authors: Carcas Lauren , Macintyre Jessica , Merchan Jaime R. , Hosein Peter Joel , Akunyili Ikechukwu Immanuel , Restrepo Maria , Garcia Monica T. , Portelance Lorraine , Sleeman Danny , Levi Joe U , Rocha Lima Caio Max S. 
Published: February 2017

460 Background: No validated biomarkers exist to direct treatment decisions in PDAC. Decisions regarding tx choices are based on age, organ function, and performance status. Defining predictors of efficacy to F (alone or in combination) or G (alone or in combination) in PDAC are urgently needed. Histologic subtype by immunohistochemistry (IHC); pancreatobiliary type (PB), intestinal type (I), gastric type (Ga) and intestinal/gastric type (I/G); may predict benefit to G or F. Methods: Charts of PDAC pts from 2 institutions from 2007 to 2013 having both pathology specimen and a qualifying tx (FOLFIRINOX, FOLFOX, FOLFIRI, Capecitabine or G or G and nab-paclitaxel) were reviewed. IHC phenotypes were defined by staining >25% CDX2 = I, >25% MUC5 = Ga, >25% CDX2 and MUC5 = I/G, >25% MUC1 = PB. Results: 51 pts were identified. 4 cases had Stage II disease without recurrence after adjuvant tx and were excluded. 5 tumors were PB, 1 I, 3 I/G, 38 Ga. 41 (87%) had Ga or I/G type. Due to lack of statistical power for the other histologic subtypes, response to F or G was only analyzed in the 35 metastatic pts with the Ga subtype. 14 were metastatic at diagnosis. 24 males. Median age 57. 21 Hispanic, 14 Non-Hisp. The PFS for Ga treated with F based tx (>12 m) versus G (~9 m) based tx in the 1st line approached statistical significance (p=0.050). In multivariable analysis with adjustments for clinical stage, ECOG, age at dx, there was a significant lower risk of progression in pts treated with F based tx versus G based tx (HR=0.278, p=0.0315). Conclusions: There was near statistical significance favoring F based tx over G based tx in PDAC Ga subtype (p=0.05). Historically, G has proven superior to F as a single agent but our findings suggest F in combination may be superior to G in combination, at least for the treatment of Ga subtype.
Treatment of hepatocellular carcinoma using hypofractionated stereotactic radiosurgery.
Authors: Lederman Ariel Joseph , Loksen Mordecha , Lowinger Thomas , Izon Daniel , Lederman Gilbert S. 
Published: February 2017

461 Background: Hypofractionated stereotactic Radiosugery (HFSR) is a non-invasive focused radiation treatment that delivers high dose therapy to cancer. HFSR for treatment of HepatocellularCarcinoma is analyzed in this prospective study. Methods: Twenty-three Hepatocellular Carcinomas (HCCs) were treated in 19 patients. All patients were prospectively evaluated before and after treatment. Age at treatment ranged from 11 to 84 years (mean 57) with 12 males and 6 females. Twenty-two percent of patients had prior chemotherapy, 17% had prior surgery and one patient had embolization. Tumor volumes ranged from 3 to 1,684cc (mean 312). The HCCs were treated with 500-800 cGy per fraction (median 600), in 5 or 6 fractions (median 5). For a total of 2,500-4,000 cGy (median 3,000). Cancers were followed with contrast CT and/or MRI scans and reviewed independently by radiologists. Control of the treated cancer is defined as cessation of growth, shrinkage or disappearance of the cancer after treatment. Results: Follow up ranged from 2 to 52 months. There was a 95.6% control rate at 14 months. By dose, volume, age, sex and prior treatment, there was no statistically significant difference in outcome. Conclusions: HFSR for HCCs is a generally well tolerated, non-invasive treatment modality with a high rate of local tumor control. Patients continue to be evaluated for longer follow up, progression free survival and overall survival. HFSR remains an attractive option for those in whom standard approaches have not produced desired results and for patients seeking an alternative to surgical or chemotherapeutic treatment.
Effect of metformin use on the survival outcomes in diabetic patients with resectable pancreatic cancer: A single-institutional experience and meta-analysis.
Authors: Ambe Chenwi , Mahipal Amit , Fulp William J. , Chen Dung-Tsa , Malafa Mokenge Peter 
Published: February 2017

465 Background: Observational studies have shown that metformin use in diabetic patients decreases both cancer incidence and mortality. The aim of this study was to determine whether metformin use had a survival benefit in patients with resected pancreatic cancer. Methods: All patients with diabetes who underwent pancreatic resections for adenocarcinoma between 12/1/1986 and 4/30/2013 at our institution were identified. Patients were categorized by metformin use. Survival analysis was done using the Kaplan Meier method, with log rank test, and Cox proportional hazards multivariable regression models. The comprehensive Meta-Analysis version 2.2 was used to perform a meta-analysis using data from our study and the only other published study. Results: The study from our institution was comprised of 19 patients receiving treatment with metformin, and 25 patients not receiving metformin. There were no significant differences in major clinical and demographic characteristics between metformin and non-metformin users. The estimated median survival for metformin users was 35.3 months (95% CI 10.7 - not estimable) vs. 20.2 months (95% CI 14.4-58.6) for nonusers. The estimated 2, 3 and 5 year survival rates for non-metformin users were 42% (95% CI 22-62%), 28% (95% CI 7-55%) and 14% (95% CI 1-43%) respectively. Metformin users fared better with corresponding rates of 68% (95% CI 41-84%), 34% (95% CI 12-59%) and 34% (95% CI 12-59%) respectively. Metformin users had a 46% lower risk of death; hazard ratio 0.54 (95% CI 0.16-1.86) in a multivariate analysis, p = 0.3275. For the meta-analysis, there were a total of 111 patients from both studies. There were 46 metformin users and 65 nonusers. Metformin users had a 33% lower risk of death; the HR 0.668 (95 % CI 0.397-1.125), in a multivariate analysis p= 0.129. Conclusions: Although the findings of the current study suggests that metformin use does not significantly impact survival outcomes in diabetic patients with resected pancreatic cancer, there appears to be a clinically meaningful improvement in survival. The potential benefit of metformin should be investigated in adequately powered prospective studies.
Long-term survivors after sorafenib therapy in unresectable hepatocellular carcinoma.
Authors: Imura Satoru , Shimada Mitsuo , Morine Yuji , Ikemoto Tetsuya , Arakawa Yusuke , Iwahashi Shuichi , Saito Yu , Yamada Shinichiro , Shibata Hiroshi , Miyake Hidenori 
Published: February 2017

470 Background: Sorafenib is one of the standard therapies for unresectable HCC. Recently, so-called “conversion” cases, who had received curative resection after sorafenib therapy, have been reported sporadically. Here, we investigated outcome of sorafenib treatment and characteristics of long-term survivors. Methods: 1) Thirty-five patients with advanced HCC underwent sorafenib therapy were enrolled. 2) The data of 59 patients from main three hospitals in Tokushima were reviewed to study the characteristics of long-term survivors. Results: 1.) The median treatment period was 3.7mo. The 1-year survival rate was 58%. The rate of partial response was 9% and the rate of stable disease was 34%. These two patients were converted to the surgical resection after sorafenib therapy. Conversion case: 50-year old male with huge unresectable HCC underwent sorafenib therapy as initial treatment. Three months after sorafenib induction, main tumor was shrunken and some intrahepatic metastase were disappeared. Right lobectomy as curative resection could be performed. He has no recurrence for 2 years after surgery. 2.) Of 59 patients, over three-years survivors were four patients (L-group) and twenty-three patients were dead within 1 year after sorafenib induction (S-group). Between the two groups, there was no significant difference in age, gender, liver function, and tumor markers. Only the response to sorafenib was significant factors for long-term survival. Sorafenib administration was continued for more than 3 years in two patients of L-group, but withdrawn in two patients. However, other treatments such as TACE or radiation were done soon after withdrawal. Conclusions: Sorafenib combined with surgical treatment may contribute to improve prognosis of patients with initially unresectable HCC.
Risk factors for 6-month continuation of S-1 adjuvant chemotherapy for resected pancreatic cancer.
Authors: Katayama Yusuke , Aoyama Toru , Asari Masahiro , Murakawa Masaaki , Yamaoku Koichiro , Kanazawa Amane , Higuchi Akio , Shiozawa Manabu , Akaike Makoto , Ueno Makoto , Morimoto Manabu , Yamamoto Naoto , Yoshikawa Takaki , Rino Yasushi , Masuda Munetaka , Morinaga Soichiro 
Published: February 2017

471 Background: The factors which affect the six-month continuation of adjuvant chemotherapy with S-1 have not been fully evaluated in pancreatic cancer. The objective of this retrospective study was to clarify the risk factors for the discontinuation of S-1 adjuvant chemotherapy after six months of treatment. Methods: The study included patients who underwent curative surgery for pancreatic cancer, were diagnosed with stage II or III disease, had a serum creatinine level < 1.2 mg/dl and received adjuvant S-1 between June 2007 and March 2014. Results: Forty patients were eligible for the present study. A comparison of the six-month continuation stratified by each clinical factor using the log-rank test revealed a significant difference in the creatinine clearance (CCr) between the patients who continued and discontinued the treatment. A CCr of 60 ml/min was regarded as a critical point. The uni- and multivariate Cox’s proportional hazard analyses demonstrated that the CCr was the only significant independent predictive factor. The six-month continuation rate was 70.8% in the patients with a CCr > 60 ml/min, and was 25.0% in patients with a CCr < 60 ml/min (P=0.008). The patients with a CCr < 60 ml/min developed adverse events more frequently and earlier than those with a CCr > 60 ml/min. Conclusions: A CCr < 60 ml/min was a significant risk factor for the six-month discontinuation of S-1 adjuvant chemotherapy in pancreatic cancer patients, even though the renal function was judged to be normal based on the serum creatinine level. Careful attention is therefore required to improve the S-1 continuation in patients with a CCr < 60 ml/min.
Micro- and macroarteriolar blockade of hepatocellular carcinoma (HCC): Ramping up the dose of sorafenib over two weeks before hepatic arterial chemoembolization (HACE) for liver cancer.
Authors: de la Torre Andrew N , Castaneda Ismael , Contractor Sohail 
Published: February 2017

472 Background: Multiple sessions of hepatic artery chemo-embolization (HACE) are usually necessary to achieve partial or complete ablation of a hepatoma (HCC). Blocking the pro-angiogeneic environment and re-establishment of tumor microvasculature with the tyrosine kinase inhibitor sorafenib administered prior to HACE may enhance tumor necrosis and possibly patient survival. Methods: Twenty patients with inoperable HCC were subject to 2 weeks of sorafenib, followed by HACE using Adriamycin and mitomycin C. The first 10 patients were treated with a sorafenib 400 mg twice a day. The second 10 patients had their dose of sorafenib ramped up from 200 mg twice a day to 400 mg twice a day over 1-2 weeks according to tolerability. Patients were continued on sorafenib during as many HACE procedures needed to achieve no evidence of enhancement on multi-phase imaging. Results: The mean length of treatment for the ramped up group was significantly longer that the non-ramped up group as shown in table 2. (3.90 vs 3.05, N < 0.05). There was no significant difference in survival, nor adverse events between groups. Three patients (5, 12, 13) ultimately went on to receive a liver transplant. Conclusions: Use of sorafenib prior to HACE is feasible and safe. Ramping up the dose over 2 weeks allows more patient to stay on treatment longer. Further studies are needed to determine how best to combine sorafenib with HACE in order to increase survival and eligibility of patients to be listed for liver transplant. Clinical trial information: NCT00949182.
Effect of preoperative hepatic and regional arterial chemotherapy on metachronous liver metastasis after curative colorectal cancer resection: A prospective, multicenter, randomized controlled trial.
Authors: Xu Jianmin , Xia Jianguo , Gu Yan , Lin Jianjiang , Ding Kefeng , Wei Ye , Qin Chunzhi , Zhu Dexiang , Ren Li , Qin Xinyu 
Published: February 2017

511 Background: To evaluate the addition of preoperative hepatic and regional arterial chemotherapy (PHRAC) on prognosis for stage II and III colorectal cancer in a multicenter setting. Methods: Patients with clinical stage II or stage III colorectal cancer (CRC) were randomly assigned to receive PHRAC plus adjuvant therapy (PHRAC arm) or adjuvant therapy alone (control arm). The primary end point was disease free survival (DFS). Second end points were incidence of metachronous liver metastasis, overall survival (OS) and safety. Results: A total of 688 patients from 5 centers of China were randomly assigned to each arm. Five-year DFS were 75% for PHRAC arm and 61% for control arm (HR 0.60; 95% CI, 0.45 to 0.80; p<0.001). Five-year liver-metastasis rate was 8% and 18% in PHRAC arm and control arm, respectively (HR 0.39; 95% CI, 0.24 to 0.64; p<0.001). Five-year OS was 81% in PHRAC arm and 72% in control arm (HR 0.59; 95% CI, 0.42 to 0.84; p=0.003). There were no significant differences in morbidity or mortality between two arms. The results of eligible patients were barely changed. Subgroup analysis shows differences of DFS, liver-metastasis rate and OS were significant in stage III patients, but not in stage II patients. Conclusions: Additional PHRAC could reduce the incidence of metachronous liver metastasis and improve DFS and OS in patients with stage III CRC, without compromising patient safety. Clinical trial information: NCT00643877.
Racial disparities in survival after young-onset colorectal cancer.
Authors: Stoffel Elena Martinez , Ruterbusch Julie , Rozek Laura S. , Cote Michele L. 
Published: February 2017

524 Background: Despite overall reductions in morbidity and mortality from colorectal cancer (CRC), racial disparities persist. In addition, incidence among individuals age <50 is rising. Our aim was to compare survival of young onset CRC cases diagnosed in black and white individuals. Methods: Using data from the National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) program we identified individuals with CRC between the ages of 20 to 49, diagnosed in 2000-2008. Kaplan-Meier and Cox proportional hazards models were used to compare stage-specific 5 year survival between black and white individuals with young onset CRC. Results: A total of 26,236 incident young onset CRC cases (22,121 white, 4,115 black) were identified during the 9 year study period. Overall survival at 5 years following CRC diagnosis was 54.8% among blacks and 67.4% among whites (p<0.001), with blacks having a significantly higher hazard of death after adjusting for age, sex, stage, tumor site, and treatment history (HR 1.34, 95% CI 1.26-1.43). Stratifying by stage at CRC diagnosis, blacks had worse survival at every disease stage compared with whites, with the greatest racial disparities observed among stage II cancers of colon (HR 1.68 95% CI 1.38-2.04) and stage II and III cancers of the rectum (HR 1.78, 95% CI 1.51-2.09, and HR 1.86, 95% CI 1.54-2.24, respectively). Conclusions: Survival after diagnosis of CRC at young age is significantly worse among blacks compared to whites, even among individuals with early stage disease. These findings suggest that differences in tumor biology may play a role in racial disparities in CRC outcomes, which may have implications for adjuvant treatment.
Routine screening for mismatch repair proteins: The impact on genetic testing.
Authors: O'Kane Grainne , Flannery Delia , O'Connor Katrina , Nolan Carmel , Farrell Michael P. , Green Andrew J. , Meighan Brian , McCormick Paul , Kennedy M. John , Muldoon C. , Gallagher David James 
Published: February 2017

525 Background: Lynch Syndrome (LS) accounts for approximately 3% of all colorectal cancers (CRC) and is caused by germline mutations in DNA mismatch repair (MMR) genes. Increasing literature supports routine screening for LS using immunohistochemistry (IHC) to detect loss of MMR protein expression on tumour samples. We evaluated genetic clinic referrals and consequent LS diagnoses at our institution pre and post the adoption of universal screening. Methods: Reflex immunohistochemistry (rIHC) on all colorectal adenocarcinomas was implemented in November 2008. Prior to this IHC was performed at the pathologist’s discretion or upon request. Tumour specimens reviewed from November 2004 to October 2008 (pre rIHC) and from November 2008 to October 2012 (post rIHC) were evaluated and patients with evidence of MMR deficiency (MMR-D) were identified. The number of genetic referrals and number of patients with confirmed LS were determined. Results: During an 8-year period, 1,131 pathology specimens were reviewed in 1,103 patients (Table). Completion of IHC increased from 19% to 75% post implementation of rIHC. Ninety-two percent of incomplete samples in the post rIHC period (133/145) had insufficient tumour material for analysis. In patients with available IHC, 18/96 (20%) in the pre rIHC era were MMR-D of which 44% were referred to genetics, resulting in the diagnosis of LS in 4 patients. In the post rIHC era 30/429 (7%) of patients had evidence of MMR-D of which 20% were referred for genetic testing resulting in the detection of 3 LS patients. Conclusions: Universal testing for MMR protein expression is difficult to achieve, and does not necessarily result in increased genetic testing or Lynch Syndrome diagnosis. Systematic work-up of test results is essential once mismatch repair evaluation is initiated. [Table: see text]
Clinicopathologic characteristics of early onset colon-rectal cancer: A single center experience.
Authors: Perez-Florez Narjust , Gandhi Arpita , Gromko Larysa Jessica , Fernandez Enoc , Jennis Andrew , Bamboat Zubin M. , McCain Donald A. , Gutierrez Martin 
Published: February 2017

538 Background: Colorectal cancer (CRC) is the second leading cause of cancer deaths in the U.S. Early recognition of CRC in young patients (pts) is a challenge, and clinicopathologic features at the time of presentation are not well described. The aim of this study was to compare clinico-pathological characteristics and survival between early onset CRC (Age <50) and late onset CRC (Age ≥50). Methods: We reviewed the records of all patients diagnosed with CRC at our institution from 1999 to 2013. Total of 3,066 pts were studied. Demographics, tumor characteristics, and survival rate were analyzed. Patients with polyposis syndromes or genetic predisposition for CRC were excluded. Kaplan-Meier and Cox regression were used for the statistical analysis. Results: Of 3,066 pts, 425 pts (14%) under the age of 50 were identified (28-49). Hispanics (13% vs 8%, p<0.01) and African Americans (7% vs. 4%, p<0.009) were more prevalent in the early onset subgroup (EO) when compared to the late onset subgroup (LO). Pts were more likely to have sigmoidal and rectal tumors in the EO 187 (44%) than in the LO 799 (30%), (p<0.0001). Mucinous and signet cell tumors were more frequent histological subtypes in EO pts (12% vs. 7%, p<0.0003; 5% vs. 3%, p<0.04, respectively). At diagnosis, EO pts were more likely to have well-differentiated tumors and advanced disease than LO pts (59% vs. 34%, p<0.0001; 61% vs. 44%, p<0.0001, respectively). Median survival was 133 months in EO (95% CI: 113-160) and 87 months in LO (95% CI: 77-89) (p<0.01). African American descent (OR: 1.6 p<0.009), Hispanic ethnicity (OR: 1.9 p<0.001) right-colon tumors (OR: 1.65 p<0.003) and positive margins (OR: 1.98 p<0.001) were independent and significant predictors of survival by multivariate analysis in the EO subgroup. Colon cancer was the primary cause of death in 24% of EO vs. 11% LO (p<0.0001). Conclusions: In our cohort, EO subgroup was more likely to have advanced disease with predominance of well-differentiated and left-colon tumors. EO subgroup has better overall survival and that could be explained by the lack of comorbidities in this group. Further research should aim to elucidate the basis of these differences, as this could potentially impact screening and management.