bluuebunny/crossref_metadata_2025_split huggingface dataset:
Assessment of the incidence of medical events reported following Y90 treatment.
Authors: Prins Petra , Wahnschafft Simone , Guevara Kiara Rivera , Khan Ahsum , Fishbein Anna , Unger Keith Robert 
Published: March 2017

491 Background: Radioembolization (Y90) is a minimally invasive procedure combining embolization and radiation therapy to treat primary and metastatic liver tumors. During radioembolization, resin beads loaded with the radioactive isotope, yttrium Y-90, are administered through the hepatic arterial vasculature. Although the safety profile of Y90 is well described, the number of dosage errors associated with treatment delivery is unknown. The purpose of this study is to assess incidence of medical events reported following Y90 treatment. Methods: A search was conducted of the US Nuclear Regulatory Commission events notification database for reported medical events between January 2000 and July 2016 using the following search terms: Y90, SIRS spheres, and TheraSpheres. Results: We recorded 96 reported medical events related to Y90 treatment: 26% were related to human error, 20% to equipment malfunction, 14% to catheter blockage, 2% were caused by catheter movement, 5% were the result of improper microsphere migration, and 33% had undetermined cause. The human error-related events consisted of application of an incorrect dose (82%), administration to the incorrect liver lobe (7%), or targeting of the wrong organ (11%). For the events involving incorrect dose administration, the total dosage exceeded the prescribed dose by greater than 20% in 5 events, while the total dosage was less than the prescribed dose by > 20% in 86 events. In 12 cases, dose inaccuracies were indicated but final dose administered was not reported. Conclusions: Although the incidence of medical events was relatively small, equipment failure and human errors were frequent. Under dosages occurred more often than over dosages. Stopcock malfunction and catheter blockage were common causes and equipment redesign should be considered. Human errors involving administration of the incorrect dose are potentially avoidable with procedural modifications.
Stereotactic body radiotherapy for hepatocellular carcinoma in the setting of poor liver function: A case series.
Authors: Valakh Vladimir , Williams Graeme 
Published: March 2017

493 Background: Role of stereotactic body radiotherapy (SBRT) to the liver for patients with poor hepatic function after transcatheter arterial chemoembolization (TACE) has not been established. We reviewed results of SBRT for men with hepatocellular carcinoma (HCC) and Child-Pugh (CP) score ≥ 8 cirrhosis after TACE. Methods: Following a median of 3 TACE treatments, five males with severe cirrhosis received SBRT for persistent or progressive HCC in 2011-14. Clinico-pathologic characteristics and treatment details were retrospectively retrieved. Results: Median age at diagnosis was 55 years (range, 48 – 55). Median interval between cancer diagnosis and SBRT was 38 months (range, 3 – 60). All 5 patients experienced decline in CP score after TACE, for a median of drop of 1 point (range, 1 – 3) between the initiation of TACE and referral for radiotherapy. At time of SBRT, 4 had CP class B and 1 class C cirrhosis with median CP score of 9 (range, 8 – 11). There were no distant metastases and one patient had extrahepatic tumor extension. Three of 5 exhibited clinical symptoms of decompensated cirrhosis within 30 days before radiotherapy and one had portal vein thrombosis. Median MELD score at SBRT was 15 (range, 12 – 18). SBRT to a median total dose of 27.5 Gray (range, 27.5 – 30) was delivered in 5 once daily fractions. Median radiotherapy course duration was 9 days (range, 5 – 18). All patients had single radiation therapy targets with median largest tumor dimension of 3.6 cm (range, 2.4 – 6.2). Median planned target volume was 24 cm3(range, 17 – 197). Sorafenib was given prior to SBRT to one patient, concurrently to one, and sequentially after radiotherapy to another. There were no acute complications. Two patients died within 20 days from completion of SBRT. Median follow up for surviving > 20 days was 10 months (range, 5 – 13). None experienced radiographic tumor progression after radiotherapy. Estimated overall survival was 40% at 6 months (95% confidence intervals, 0 – 83.8%). Conclusions: For HCC patients with CP score ≥ 8 following TACE, prognosis after liver SBRT was poor.
Clinical outcomes in borderline resectable pancreatic cancer: A cohort study.
Authors: Sohal Davendra , Altujjar Mohammad , Tullio Katherine , Abazeed Mohamed , Pelley Robert James , McNamara Michael J. , Estfan Bassam N. , Shapiro Marc A. , Khorana Alok A. 
Published: March 2017

494 Background: The management of borderline resectable pancreatic cancer (BRPC) remains unsettled and the predictors of outcome are uncertain. We evaluated the role of neoadjuvant therapy (nRx) and outcomes in patients with BRPC. Methods: We conducted a retrospective cohort study of consecutive patients with BRPC who received nRx and were followed at the Cleveland Clinic. A histopathologic diagnosis of pancreatic carcinoma was required. Tumor anatomy was assessed by contrast-enhanced cross-sectional imaging (CT or MRI), and BRPC was defined as a tumor-vessel wall interface involving one or more of: celiac artery, superior mesenteric artery, common hepatic artery, main portal vein, superior mesenteric vein; making margin-negative resection unlikely. Baseline laparoscopy was performed to rule out occult metastatic disease. Chemotherapy (CT), radiation (RT), surgery details, and pathologic and survival outcomes were evaluated. Hazard ratios (HR) with 95% confidence intervals (CI) and 2-sided p-values are presented. Results: The study population comprised 79 patients from 2009 to 2014. Median age was 64 years; 52% were male; 85% were Caucasian. Pancreatic head/neck were the primary site in 81%; body/tail in 19%. Vascular involvement included arterial in 32 (41%), and venous in 65 (82%) patients. nRx included RT in all patients; 77 (97%) received CT; gemcitabine (n = 50, 63%) was the most common agent. After CT/RT, 36 (46%) patients had unresectable/inoperable disease: 29 (37%) for anatomic reasons, 4 (5%) for physiologic reasons, and 3 (4%) for both. Surgical resection was performed in 43 (54%) patients; 38 (88%) had negative margins; 30 (70%) had negative nodes; 32 (74%) received adjuvant CT. There were no statistically significant predictors of resection. After median follow-up of 27 mths, there have been 45 deaths (57%); median overall survival (mOS) is 23.5 mths (95% CI: 16-28 mths). Only cancer resection was associated with survival (mOS, resected: not reached; mOS, not resected: 12.8 mths; HR: 0.30, 95% CI: 0.16-0.56, p = 0.0002). Conclusions: Surgical resection, if feasible, of BRPC is associated with improved OS. Strategies to improve the odds of resection should be evaluated in prospective studies.
Nab-paclitaxel and gemcitabine in advanced pancreatic cancer: The one-year experience of the National Cancer Institute of Naples.
Authors: Ottaiano Alessandro , Capozzi Monica , De Divitiis Chiara , Von Arx Claudia , Di Girolamo Elena , Nasti Guglielmo , Cavalcanti Ernesta , Tatangelo Fabiana , Romano Giovanni , Tafuto Salvatore 
Published: March 2017

497 Background: Pancreas adenocarcinoma is the sixth cause of cancer-related death worldwide and the mortality is increasing in the Western Countries. Recently, the association between nab-paclitaxel (nab-P) and gemcitabine (GEM) has significantly improved progression-free (PFS) and overall survival (OS) compared to GEM monotherapy (PFS: 5.5 vs 3.7 months; OS: 8.5 vs 6.7 months). Methods: Patients affected by metastatic pancreas adenocarcinoma were treated at the Department of Abdominal Oncology of the National Cancer Institute of Naples from July 2015 to July 2016 with nab-P at 125 mg per square meter of body-surface area followed by GEM at 1000 mg per square meter on days 1, 8, and 15 every 4 weeks. Computed tomography (CT) was done every three months of therapy. Toxicity was graded with NCI-CTC criteria v4.0. Objective responses were evaluated with RECIST. Analysis of time-to-progression is only descriptive. Pain was evaluated with a visual analogic scale. Results: Twenty-three patients were treated. Median age was 67 years (range: 45-81); 8 patients were ≥ 70 years old. Performance Status (PS) ECOG was 2 in 8 patients, 1 in 10 and 0 in 5. Twelve patients presented with diffuse hepatic metastases, 4 with carcinosis, 7 with more than one organ involvement. They received a median number of 13 administrations (range: 3-32) of therapy. During therapy Nab-P was reduced at 100 mg per square meter in all patients. The most common G3/G4 adverse events were neutropenia (13.0% G4, 8.6% G3, none was febrile), neuropathy (30.4% G3) and asthenia (G3 17.3%). The disease control rate was 43.4% (PR+SD 10/23); PR was registered in three patients (response rate: 13.0%). Twelve patients progressed and seven dead at September 20. The median time-to-progression was 7.9 months (95% confidence interval 5.8-11.2). After three months of therapy the PS improved in 14 patients as well as pain in 18 patients. Conclusions: We present an experience with nab-P and GEM association in a series with poor PS and highly metastatic disease relatively to the previous randomized study. The schedule is feasible with nab-P at 100 mg per square meter and it achieves a good disease control rate as well as a clinical benefit.
Borderline resectable pancreas adenocarcinoma managed with neoadjuvant chemoradiotherapy: A prospective case series.
Authors: Mandaliya Hiren A. , Martin Jarad , Majid Adeeb , Gani Jon , Sridharan Swetha , Ackland Stephen P. , Kumar Mahesh , Shah Kalpesh , Chen Stanley , Fay Michael , Lynam James F. , Van Der Westhuizen Andre , Mallesara Girish , Philcox Stephen , Bonaventura Tony , Day Fiona 
Published: March 2017

499 Background: Borderline resectable pancreas cancers (BRPC) often require vascular reconstruction, have higher rates of operative margin positivity and confer a poor prognosis. In 2014, our high-volume pancreatectomy, gastrointestinal tumor multidisciplinary treatment (GI MDT) group endorsed a consensus anatomical definition of BRPC consistent with NCCN criteria. Diagnostic and staging tests were standardized and a neoadjuvant chemoradiotherapy protocol adopted with the goals to (1) improve R0 resection rate and (2) prevent futile surgery in rapidly progressive disease. Methods: Neoadjuvant chemoradiotherapy (CRT) consisted of 50.4Gy in 28# and concurrent capecitabine 830mg/m2 bd. Pancreatectomy was planned 4-8 weeks later unless repeat imaging showed progressive disease. Comprehensive, prospectively defined data items were collected on all patients (pts) diagnosed with BRPC. Results: Nine pts have been diagnosed with BRPC by the GI MDT. Seven pts received full dose of CRT, one pt progressed during CRT hence stopped early and one pt didn’t receive CRT due to significant deterioration beforehand. CRT was tolerable in all eight pts who received it; there were no dose modifications for toxicity. Post-CRT, three pts underwent curative-intent resection and all are still alive (494, 319 and 172 days post-CRT). One was found to have a solitary liver metastasis during surgery (resected), R1 resection (SMV margin involvement) of T3N1 tumor and is receiving palliative chemotherapy. Two other pts underwent R0 resections (T3N0, T3N1) with histopathologic response to CRT. Four pts showed progressive disease on post-CRT imaging (all local & distant progression) and subsequently received palliative therapy. Median survival (first dose CRT to death) in the 5 CRT pts who have succumbed was 509 days (range 363-577). Conclusions: In this small prospective, unselected cohort the majority of pts diagnosed with BRPC demonstrated disease progression during/after neoadjuvant CRT and did not proceed to surgical resection, underscoring the poor prognosis of this pancreas cancer subset. Neoadjuvant CRT is well tolerated and did not preclude subsequent surgery in those patients with stable disease.
Molecular staging of gastric cancer with a novel panel of prognostic microRNAs.
Authors: Woo Yanghee , Behrendt Carolyn E. , Fong Yuman 
Published: March 2017

52 Background: Molecular heterogeneity of gastric cancer discerns patient survival in ways that clinically-based prediction models cannot. To date, individual microRNAs(miRs) expressed by gastric tumors have been associated with survival. We offer a unique molecular-based method of prognosticating the survival of gastric cancer patients with an efficient panel of miRs. Methods: From The Cancer Genome Atlas(TCGA), we studied subjects with gastric adenocarcinoma, who had undergone R0-R1 resection and had data on clinical characteristics, overall survival (OS), and miR expression. Of miRs quantified by TCGA, miRs expressed by at least 15% of subjects’ tumors were evaluated as continuous variables. From 10 replicate samples, each containing 80% of current subjects, miRs were selected using proportional hazards regression adjusted for age with stepwise selection. Cross-validated miRs were retained for the panel if they optimized an accelerated failure-time model of OS using the full cohort. Results: Among subjects (n=254, age 64.7+10.9 years), median OS was 2.38 (95% Confidence Interval: 2.09-3.85) years. Of the 913 evaluable miRs, 10 distinct miRs (miR-373, miR-548ay, miR-659, miR-891a, miR-1243, miR- 4685, miR-6718, miR-6733, miR-6808, and miR-8072) were cross-validated as being prognostic and retained for the age-adjusted panel. Panel-predicted survival estimates, grouped into tertiles, distinguished progressively worse survival at 2 years, OS was 81.0%+5.1% for upper tertile, 61.5%+6.3% for middle tertile, and 29.6%+6.3% for lower tertile. As shown in Table 1, each tertile included subjects at all levels of TNM stage, and tertile was not significantly associated with stage (chi-square test, p=0.26). Conclusions: This unique miRs panel represents a molecular staging system for gastric cancer that has the potential to prognosticate patients' survival more accurately than existing clinical systems can. [Table: see text]
Randomized trial of irinotecan and cetuximab with or without vemurafenib in BRAF-mutant metastatic colorectal cancer (SWOG 1406).
Authors: Kopetz Scott , McDonough Shannon L , Morris Van Karlyle , Lenz Heinz-Josef , Magliocco Anthony Martin , Atreya Chloe Evelyn , Diaz Luis A. , Allegra Carmen Joseph , Wang Stephen E. , Lieu Christopher Hanyoung , Eckhardt S. Gail , Semrad Thomas John , Kaberle Kimberly , Guthrie Katherine A , Hochster Howard S. 
Published: March 2017

520 Background: BRAF V600 mutations are associated with rare objective responses to the mutated BRAF inhibitor vemurafenib in patients with mCRC. Blockade of BRAFV600 by vemurafenib causes feedback upregulation of EGFR, whose signaling activities can be impeded by cetuximab. In murine models of BRAFV600 mCRC, the combination of irinotecan, cetuximab, and vemurafenib leads to greater anti-tumor activity, as suggested by a prior Phase 1B study. Methods: Patients (pts) with BRAFV600 mutated and extended RAS wild-type mCRC were randomized to irinotecan (180 mg/m2 IV every 14 days) and cetuximab (500 mg/m2 IV every 14 days) with or without vemurafenib (960 mg PO twice daily). Patients had received 1 or 2 prior regimens, with no prior anti-EGFR agents, although prior irinotecan was allowed. Crossover from the control arm to the experimental arm was allowed after documented progression. The primary endpoint was progression-free survival (PFS, investigator assessed), with 90% power to detect a HR of 0.5, with two-sided type 1 error of 5%. Results: 106 patients were enrolled (54 in the experimental arm) from 12/2014 to 4/2016, with ECOG PS ≤ 1. Median age of 62 years, 59% female, and prior irinotecan therapy in 39%. PFS was improved with the addition of vemurafenib (HR = 0.42, 95% confidence interval [CI] of 0.26 to 0.66, P < 0.001) with median PFS of 4.4 (95% CI: 3.6 – 5.7) months vs 2.0 (95% CI: 1.8 – 2.1). Response rate was 16% vs 4% (P = 0.09), with disease control rate of 67% vs 22% (P < 0.001). Grade 3/4 adverse events higher in the experimental arm included neutropenia (28% vs 7%), anemia (13% vs 0%), and nausea (15% vs 0%). There was no increase in skin toxicity or fatigue. No new safety signal was observed. Approximately 50% of patients in the control aim crossed over at the time of progression. Overall survival and efficacy at cross-over data remain immature. Conclusions: The addition of vemurafenib to the combination of cetuximab and irinotecan resulted in a prolongation of progression-free survival and a higher disease control rate, indicating that simultaneous EGFR and BRAF inhibition is effective in BRAFV600 mutated CRC. Clinical trial information: NCT02164916.
The International Watch & Wait database (IWWD) for rectal cancer: An update.
Authors: Valk Maxime van der ,   International Watch and Wait Database Consortium
Published: March 2017

521 Background: In 2014 the IWWD was established by EURECCA and the Champalimaud Foundation. The main goal of this database is to collect all available data to expand knowledge on the benefits, risks and oncological safety of organ preserving strategies in rectal cancer. In April 2015 the database was opened for data registration. Methods: An international multicentre observational study. Data was collected by participating centres and stored in a highly secured NEN7510 certified and encrypted research data server. Each centre always retains full ownership of their data. Results: In August 2016 the database included 775 patients from 11 countries and 35 participating institutes. 90% of all patients were included because of a clinical complete response (n = 679). All other reasons for a watch-and-wait regimen were excluded for the present analyses. As shown in table 1, imaging modalities used to assess response after induction therapy were variable. Induction treatment consisted of chemo-radiotherapy in 90% of cases. Median follow-up time is 2.6 years (range 0-24 years). Local regrowth occurred in 25% (n = 167) of all patients, of which 84% in the first 2 years of follow-up. A local regrowth was located endoluminal in 96% (n = 161) and in the loco-regional lymph nodes in 4% (n = 7). Distant metastasis occurred in 7% (n = 49). The overall 3 year-survival of all patients was 91% and for patients with a local regrowth this was 87%. Conclusions: This is the largest series of patients with rectal cancer in which surgery was omitted after induction therapy. These data illustrate differences in induction therapy as well as imaging strategies and provide some crude outcome data. Further data collection on the Watch-and-Wait strategy for rectal cancer is needed to increase knowledge on oncological safety of omitting surgery. This may contribute to international consensus on staging, treatment and surveillance guidelines in rectal cancer care. [Table: see text]
Expression of COX-2 and 15-PGDH in adenomas removed during pretreatment colonoscopy to predict chemopreventive efficacy of the selective COX-2 inhibitor, celecoxib.
Authors: Wang Jiping , Cho Nancy L , Zauber Ann G. , Hsu Meier , Dawson Dawn , Srivastava Amitabh , Mitchell-Richards Kisha , Markowitz Sanford D. , Bertagnolli Monica M. 
Published: March 2017

524 Background: The APC trial showed that patients at high risk for colorectal adenoma development experienced a 33-45% reduction in post-polypectomy adenoma detection when treated with the selective cyclooxygenase-2 (cox-2) inhibitor, celecoxib. Unfortunately, this study also found a small increased risk of cardiovascular toxicity among celecoxib users, preventing broad use of this agent for chemoprevention. Celecoxib inhibits expression of prostaglandin E2 (PGE2), an inflammatory mediator produced by fatty acid metabolism via cyclooxygenases, and degraded through the activity of 15-prostaglandin dehydrogenase (15-PGDH). Methods: Adenomas collected from APC trial participants prior to treatment were examined using immunohistochemistry (IHC) to assess expression of cox-2 (high vs. low) and 15-PGDH (present vs. absent). A combined variable to estimate tumor PGE2 levels identified cases as PGE2 low (Cox-2 low/15-PGDH present) or PGE2 high (Cox-2 high/15-PGDH present; Cox-2 high/15-PGDH absent; or Cox-2 low/15-PGDH absent). Mantel–Cox test was used to evaluate whether markers of PGE2 expression in these adenomas predicted benefit from celecoxib treatment for the primary study outcome of adenoma detection. Results: Biomarker determinations were achieved for 1295 cases, or 71% of patients with available outcome data. Patients whose baseline adenomas demonstrated elevated Cox-2 achieved the greatest overall reduction in adenoma risk with celecoxib treatment (RR 0.37; p = 0.0001). This risk reduction was less significant in the low Cox-2 category (RR 0.64). Patients with low estimated tumor PGE2 did not benefit from celecoxib for adenoma prevention (RR 0.95; p = 0.83). This is compared to a 41% reduction in adenoma detection with celecoxib treatment for patients in the high PGE2 category (RR 0.59; p < 0.0001). Conclusions: IHC to determine expression of target enzymes in pre-malignant adenomas provides significant prognostic and predictive information in patients treated with celecoxib for prevention of colorectal adenomas.
Effect of thymidine kinase 1 expression on prognosis and treatment outcomes in refractory metastatic colorectal cancer: Results from two randomized studies of TAS-102 versus a placebo.
Authors: Yoshino Takayuki , Shinozaki Eiji , Yamazaki Kentaro , Komatsu Yoshito , Nishina Tomohiro , Baba Hideo , Tsuji Akihito , Tsuji Yasushi , Yamaguchi Kensei , Sugimoto Naotoshi , Denda Tadamichi , Muro Kei , Takayama Tetsuji , Esaki Taito , Hamamoto Yasuo , Moriwaki Toshikazu , Shimada Yasuhiro , Goto Masahiro , Tanase Takanori , Ohtsu Atsushi 
Published: March 2017

529 Background: TAS-102 is an oral nucleoside antitumor agent, comprising trifluridine (FTD) and tipiracil. FTD is incorporated into DNA after phosphorylation by thymidine kinase 1 (TK1). This study aimed to investigate the association between TK1 expression and TAS-102 efficacy in refractory metastatic colorectal cancer (mCRC) patients (pts). Methods: Data from two randomized phase 2 and phase 3 studies of mCRC pts refractory to standard therapies were analyzed for treatment outcomes in relation to TK1 expression. Expression was measured using immunohistochemistry, and staining was classified according to intensity and scored 0, 1+, 2+, or 3+. Occupancy rates of the areas scored 2+ and 3+ in tumor cells were calculated in 5% intervals, and divided into two groups (high or low TK1) at each cut-off point. Results: TK1 expression was evaluated in 329 pts. Baseline characteristics and treatment outcomes were comparable between the TK1-refined and intention-to-treat populations. Pts with high TK1 expression who received the placebo had a poor prognosis, while those receiving TAS-102 showed a significant improvement in overall survival (OS) at cut-off points of 5% to 15%, and 30%. Conclusions: High TK1 expression could be a poor prognostic factor and a predictive factor of TAS-102 efficacy in mCRC pts. [Table: see text]