bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association of baseline health-related quality of life and survival in esophagogastric cancers.
Authors: Onate-Ocana L. F. , Mireles-de-Villafranca P. , Carrillo J. F. , Vilar-Compte D. , García-Hubard G. , Aiello-Crocifoglio V. 
Published: February 2017

118 Background: Baseline health-related quality of life (HRQL) is a prognostic factor for survival in patients with cancer; however contradictory results have been reported. We studied whether HRQL scores are associated with survival in patients with esophagogastric cancers. Methods: Patients with biopsy proven esophagogastric cancer were recruited prospectively. All were invited to respond the EORTC QLQ-C30 questionnaire. The prognostic role of usual clinical variables and HRQL data was analyzed dividing patients in two groups: 1) palliative intention or 2) curative intention treatments. The Kaplan-Meier and Cox's methods were used for bivariate or multivariate analysis, respectively. Results: A total of 259 cases were included, 99 were woman and 160 male (mean age 54.3). One-hundred thirty-three patients of group one, presented significant association with survival in nine of 15 HRQL scales (p < 0.05). A multivariate model was constructed including basal serum albumin (hazard ratio [HR] 0.48; 95% confidence intervals [CI]: 0.34–0.68), Role functioning scale (HR 0.989; 95% CI: 0.98–0.99), Social functioning scale (HR 1.01; 95% CI: 1.005–1.019) and Nausea/Vomiting scale (HR 1.01; 95% CI: 1.01; 95% CI 1.006–1.02) (model p < 0.0001). One-hundred twenty-six patients of group two, presented significant association with survival in eight of 15 HRQL scales (p < 0.05). A multivariate model was constructed including definitive TNM stages (HR 8.7, 14.2, 10.1 for stages II, III and IV, respectively; reference category stage I), age (HR 1.04; 95% CI: 1.009–1.065), Social functioning scale (HR 0.98; 95% CI: 0.98–0.99), Pain scale (HR 1.024; 95% CI: 1.01–1.04) (model p < 0.0001). Conclusions: These results suggest that HRQL provide significant prognostic information in addition to traditional clinical measures in patients with esophagogastric cancer. Prospective confirmatory studies are warranted. No significant financial relationships to disclose.
Impact of adjuvant chemoradiotherapy on overall survival of gastric cancer patients with D2 lymphadenectomy.
Authors: Jácome A. A. , Wohnrath D. R. , Scapulatempo Neto C. , Fregnani J. T. , Viana L. S. , Santos L. V. , Maia D. C. , Santos J. 
Published: February 2017

120 Background: Adjuvant chemoradiotherapy is the standard treatment in Western countries in gastric cancer patients submitted to curative resection. However, INT 0116 pivotal trial was hampered by suboptimal surgery. There is no efficacy data of this adjuvant therapy in patients who have undergone D2 lymphadenectomy predominantly. Methods: Retrospective study with gastric adenocarcinoma patients stage II to IV M0 who underwent curative resection at Hospital de Câncer de Barretos between January 2002 and December 2007. Standard treatment at institution is D2 lymphadenectomy. Chemoradiotherapy according to INT 0116 was considered as an option for adjuvant therapy. A group of patients did not receive adjuvant therapy based on discretion of physician. We compared 3-year overall survival of the two treatments (chemoradiotherapy versus surgery alone). Survival curves were calculated according to Kaplan-Meier method and compared with log-rank test. Multivariate analysis of prognostic factors related to survival was performed by Cox proportional hazards model adjusted for age, stage and adjuvant chemoradiotherapy. Results: 185 patients were included (61% male). Median age was 61 years old. 34% were stage II, 39% stage IIIA, 16% stage IIIB e 11% stage IV M0. D2 lymphadenectomy was performed in all patients. Eighty-one patients (44%) did not receive adjuvant therapy and one hundred and four received chemoradiotherapy. 3-year overall survival by Kaplan-Meier method was 64.4% for patients who received adjuvant therapy and 61.7% for those who underwent surgery alone (p = 0.415). However, according to Cox proportional hazards model, adjuvant chemoradiotherapy was a prognostic factor for overall survival (HR: 0.52, IC 95% 0.31 – 0.87, p: 0.014), as well as stage (p < 0.001). Age did not present influence on overall survival (p = 0.328). Conclusions: Adjuvant chemoradiotherapy decreased risk of death in three years in patients who underwent curative resection with D2 lymphadenectomy, with a meaningful hazard ratio in our study, and should remain as standard treatment. Ongoing trials will elucidate the role of radiotherapy in this subgroup of patients. No significant financial relationships to disclose.
Outcomes associated with T4 esophageal cancer.
Authors: Meredith K. , Weber J. , Shridhar R. , Hoffe S. E. , Almhanna K. , Melis M. , Biagioli M. , Mcloughlin J. , Barthel J. S. , Karl R. C. 
Published: February 2017

130 Background: Esophageal cancer often presents as locally advanced disease with 15% of patients having T4 tumors upon diagnosis. Esophagectomy was often reserved for palliation given the dismal survival rates and high rates of R1/R2 resections. However, neoadjuvant therapy (NT) has the potential to significantly downstage esophageal cancers and thus increase complete resection rates. We report our experience with surgically resected T4 cancers of the esophagus. Methods: Using a comprehensive esophageal cancer database, we identified patients who underwent an esophagectomy for T4 tumors between 1994 and 2008. Neoadjuvant therapy and pathologic response were recorded and denoted as complete (pCR), partial (pPR), and non-response (NR). Clinical and pathologic data were compared using Fisher's exact and chi-square when appropriate while Kaplan Meier estimates were used for survival analysis. Results: We identified 39 patients with T4 tumors who underwent esophagectomy of which 38 (97%) underwent NT. The median age was 61 (31-79) years with a median follow-up of 32 (5-97) months. There were 3 (7.9%) pCR, 17 (44.7%) pPR, and 18 (47.4%) NR. R0 resections were accomplished in 37 (94.9%). Two patients had incomplete resections. One patient had a R2 resection after NT and was deemed as NR. An additional patient had a R1 resection after NT and was a pPR with a residual 0.2 cm tumor on permanent pathology. There were 14 (35.9%) recurrences with a median time to recurrence of 19.5 (4-71) months. Complete pathologic response represented 1 (7.1%), whereas pPR and NR represented 6 (42.9%), and 7 (50%) respectively of all recurrences. The overall and disease free survival for all patients with T4 tumors was 28% and 34% respectively. Patients achieving a pCR had a 5-year overall and disease free survival of (43% and 47%), compared to pPR (30% and 21%) while there were no 5-year survivors in the NR cohort. Conclusions: T4 esophageal cancer often portends a dismal prognosis even after surgical resection. Historical incomplete resections and dismal survival rates often make surgery palliative rather then curative. However, we have demonstrated that neoadjuvant therapy and down staging of T4 tumors leads to increased R0 resections and improvements in overall and disease free survival. No significant financial relationships to disclose.
The efficacy and tolerability of modified docetaxel, cisplatin, and 5FU in patients with advanced or recurrent gastric cancer: A retrospective analysis.
Authors: Kim J. , Park K. , Yi S. , Lee H. 
Published: February 2017

146 Background: Docetaxel, cisplatin, and 5FU (DCF) significantly improved TTP, OS, and response rate in gastric cancer patients, but resulted in some increase in toxicity compared with cisplatin and 5FU (CF) in multinational study such as V325 report. The main goal of this study is to report the experience of a single center about efficacy and tolerability of modified DCF in advanced or recurrent gastric cancer patients. Methods: A total of 23 patients with advanced or recurrent gastric cancer who had been treated with modified docetaxel, cisplatin and 5FU (mDCF) at Seoul Paik Hospital between Feb 2009 and June 2010 were included. Treatment protocol was 60 mg/m2 of docetaxel, 50 mg/m2 of cisplatin on D1, and 950 mg/m2/day of 5FU continuous infusion on D1-3 until disease progression or intolerance to chemotherapy. Clinical data were collected retrospectively. Results: Twenty-one patients were assessable for response. The ORR was 34.8% (8/23), and DCR 69.6% (16/23). Median PFS and OS were 6.8 months (95% CI, 3.8-9.8) and 11.9 months (95% CI, 6.6-17.2). The main toxicities were anorexia, diarrhea, and neuropathy. Grade 3 or 4 hematologic toxicities were neutropenia in 4 patients (17.4%), leukopenia in 5 patients (21.7%), anemia in 2 patients (8.7%) and thrombocytopenia 1 patient (4.3%). The treatment related death occurred in 1 patient (4.3%) due to febrile neutropenia. The median cycle was 5. Ten patients (43.5%) received chemotherapy more than 8 cycles with tolerable toxicities. Conclusions: Compared with previous studies, the presented mDCF showed a lower ORR, but more acceptable toxicities profiles, and similar PFS and OS in patients with advanced gastric cancer. No significant financial relationships to disclose.
MicroRNA expression profiles associated with pancreatic cancer.
Authors: Schultz N. A. , Werner J. , Willenbrock H. , Roslind A. , Horn T. , Wøjdemann M. , Johansen J. S. 
Published: February 2017

153 Background: The aim was: 1) to define the global microRNA (miRNA) expression pattern in pancreatic cancer (PC) and compare it with normal pancreas (NP) and chronic pancreatitis (CP); 2) to validate reported diagnostic miR profiles in PC; 3) to discover new diagnostic miRs in pancreas samples without micro-dissection of cancer cells. Methods: MiR expression patterns in FFPE tissue blocks from patients operated for pancreatic ductal adenocarcinoma (PDAC, n=170) and ampullary adenocarcinomas (A-AC, n=107) were determined using TaqMan Human miR microarrray (Applied Biosystem; 754 miRs were determined) and compared to profiles of CP (n=23) and NP (n=28). Raw Ct-values were normalized using quantile-normalisation. Results: 83miRs were differentially expressed in PDAC and NP (42 higher expression; 41 reduced expression in PDAC). 32 miRs were differentially expressed in PDAC and CP. The most differentially expressed miRs were miR-614, miR-492, miR-622, miR-135b* and miR-196. The miR signatures of PDAC and A-AC were highly correlated (0.99; only 5 miRs were significantly differentially expressed). An earlier reported diagnostic miR profile for PDAC was validated (mirR196b - miR217), and 3 other significant profiles were identified (Table). A more complex Lasso classifier using 19 miRs could separate PDAC from NP and CP (accuracy = 98%). Conclusions: We identified systematic differences in patterns of miR expressions between tumor tissue including both cancer cells and surrounding desmoplasia obtained from patients with PDAC and A-AC compared to tissue from patients with CP and NP. We validated the diagnostic miR expression profile (miR-196b, miR-217) described by Szafranska et al. (Clin Chem 2008;54:1716-24). Furthermore, we identified 5 miRs which were better to discriminate PDAC and A-AC from CP and NP. Prospective studies are needed to evaluate if this panel of miRs is useful for early diagnosis of patients with PDAC. [Table: see text] No significant financial relationships to disclose.
A molecular prognostic nomogram for resectable pancreatic cancer.
Authors: Chang D. K. , Colvin E. K. , Scarlett C. J. , Pajic M. , Pinese M. , Gill A. J. , Musgrove E. A. , Sutherland R. , Kench J. , Biankin A. V. ,   New South Wales Pancreatic Cancer Network
Published: February 2017

154 Background: Defining clinically and biologically relevant phenotypes in other cancers has led to substantial improvements in the overall outcomes, but as yet none have been defined for pancreatic cancer (PC). About 80% of patients with pancreatic cancer succumb to the disease despite curative resection, many of whom within 6 months of surgery. There is a clear need to better define the biology and clinical behaviour of PC. This study aimed to evaluate the potential clinical utility of biologically relevant molecules as prognostic factors in resected PC. Methods: We assessed the relationship of aberrant S100A4 calcium-binding protein expression with survival in a cohort of 372 patients who underwent surgical resection for PC and derived a nomogram using clinicopathologic variables and aberrant expression of S100A4 and S100A2. Results: High S100A4 expression was an independent poor prognostic factor in both the training (n = 76; HR = 5.00, 95% CI = 2.29 – 10.9; p < 0.0001) and validation sets (n = 296; HR = 1.78, 95% CI = 1.29 – 2.46; p = 0.0004). Incorporating previously published data on S100A2, demonstrated that high expression of S100A4 was still an independent prognostic factor. Aberrant expression of these proteins stratified the cohort into three distinct prognostic groups. A preoperative nomogram using only variables that could be measured preoperatively (tumor size and molecular biomarkers), predicted survival better than nomograms derived from using clinicopathologic variables, which are only determined after examination of the resected specimen. Conclusions: Aberrant expression of S100A4 and S100A2 stratifies PC into distinct prognostic groups and improves the accuracy of prognostic nomograms using variables that can be determined preoperatively. The development and application of such nomograms in routine clinical practice has the potential to improve patient selection and as a consequence overall outcomes for PC. No significant financial relationships to disclose.
Everolimus plus octreotide LAR (E+O) versus placebo plus octreotide LAR (P+O) in patients with advanced neuroendocrine tumors (NET): Updated results of a randomized, double-blind, placebo-controlled, multicenter phase III trial (RADIANT-2).
Authors: Yao J. C. , Hainsworth J. D. , Baudin E. , Peeters M. , Hoersch D. , Anthony L. B. , Klimovsky J. , Grouss K. , Jehl V. , Pavel M. 
Published: February 2017

159 Background: Octreotide LAR has been the foundation of NET therapy; however, additional treatment options are needed. Everolimus, an oral inhibitor of mTOR, demonstrated promising antitumor activity in patients with NET as a single agent and in combination with octreotide LAR in two phase II studies. Methods: Patients (n = 429) with well or moderately differentiated advanced NET and history of carcinoid symptoms received oral everolimus 10 mg/d + octreotide LAR 30 mg IM q 28 days (n = 216) or placebo + octreotide LAR (n = 213). Common primary sites included the small intestine, lung, and colon. The primary endpoint was progression-free survival (PFS) per central review by RECIST. Crossover from P+O to open-label E+O was allowed at disease progression. Results: Median PFS (95% CI) with E+O was 16.4 months (13.67-21.19) vs. 11.3 months (8.44-14.59) for P+O. E+O was associated with a 23% reduction in risk of progression: HR = 0.77; 95% CI: 0.59-1.00; one-sided p-value = .026 (pre-specified significance boundary is p ≤ .0246). A high rate of informative censoring resulted in loss of power in central review results. Correcting for the informative censoring bias, the pre-specified marginal Cox model using inverse probability of censoring weights (IPCW) analysis showed a significant 5.5-month improvement in median PFS with E+O; HR = 0.60; 95% CI: 0.44-0.84, with one-sided p-value = .0014. The benefit of E+O was seen across all patient subgroups. Updated analyses of the impact of pre-study and post-progression octreotide LAR therapy will be reported. Most frequent drug-related adverse events (AEs) with E+O were stomatitis, rash, fatigue, and diarrhea; mostly grade 1-2. Grade 3-4 AEs reported in >5% were stomatitis, fatigue, diarrhea, infections, and hyperglycemia. Conclusions: In this large phase III trial, E+O provided a 5.1-month clinically meaningful increase in median PFS compared with P+O in the central adjudicated review. Correcting for the informative censoring bias, a significant PFS improvement of 5.5 months was seen, with a p value = .0014. The safety profile of E+O was acceptable. [Table: see text]
Surgical density and its effect on esophageal cancer (EC) and gastric (GC) mortality.
Authors: Ho M. Y. , Albarrak J. S. , Cheung W. Y. 
Published: February 2017

16 Background: Surgical resection plays an integral role in the multimodality treatment of patients with EC or GC. The distribution of thoracic and general surgeons at the county level varies widely across the US. The impact of the allocation of these surgeons on cancer outcomes is unclear. Our aims were to 1) examine the effect of surgeon density on EC or GC mortality, 2) compare the relative roles of thoracic and general surgeons on EC and GC outcomes and 3) determine other county characteristics associated with cancer mortality. Methods: Using county-level data from the Area Resources File, U.S. Census and National Cancer Institute, we constructed regression models to explore the effect of thoracic and general surgeon density on EC and GC mortality, respectively. Multivariate analyses controlled for incidence rate, county demographics (population aged 65+, proportion eligible for Medicare, education attainment, metropolitan vs. rural), socioeconomic factors (median household income) and healthcare resources (number of general practitioners, number of hospital beds). Results: In total, 332 and 402 counties were identified for EC and GC, respectively: mean EC/GC incidence = 5.29/6.83; mean EC/GC mortality=4.70/3.92; 91% were metropolitan and 9% were rural; mean thoracic and general surgeon densities were 10 and 63 per 100,000 people, respectively. When compared to counties with no thoracic surgeons, those with at least 1 thoracic surgeon had reduced EC mortality (beta coefficient -0.031). For GC, counties with 1 or more general surgeons also had decreased number of deaths (beta coefficient -0.095) when compared with those without any surgeons. While increasing the density of surgeons beyond 10 only yielded minimal improvements in EC mortality, it resulted in significant further reductions in GC mortality. Other county characteristics, such as increased number of hospital beds and higher median household income, were correlated with improved outcomes. Conclusions: Mortality from GC appears to be more susceptible to the benefits of increased surgeon density. For EC, a strategic policy of allocating health resources and distributing the workforce across counties will be best able to optimize outcomes at the population-level. No significant financial relationships to disclose.
Intrahepatic cholangiocarcinoma: An international, multi-institutional analysis of prognostic factors and lymph node assessment.
Authors: Pawlik T. M. , Pulitano C. , Alexandrescu S. , Gamblin T. C. , Ferrone C. , Sotiropoulos G. , Marques H. , Bauer T. W. , Gigot J. , Mentha G. ,   International Intrahepatic Cholangiocarcinoma Collaborative Group
Published: February 2017

162 Background: Intrahepatic cholangiocarcinoma (ICC) is a rare and poorly understood primary liver cancer. The role of routine lymphadenectomy at the time of surgical resection remains poorly defined. We sought to identify factors associated with outcome following surgical management of ICC and examine the impact of lymph node (LN) assessment on survival. Methods: 411 patients who underwent curative intent surgery for ICC between 1973-2010 were identified from an international multi-institutional database. Clinical and pathologic data were evaluated using uni- and multivariate analyses. Results: Median tumor size was 6.5 cm. Most patients had a solitary tumor (55%) and no evidence of vascular invasion (64%). Resection involved ≥hemi-hepatectomy (74%) and margin status was R0 (82%). Overall median survival was 28 months and 5-year survival was 32%. Factors associated with adverse prognosis included positive margin status (HR=3.11; p<0.001), multiple lesions (HR=2.16; p=0.007) and vascular invasion (HR=2.13; p=0.01). Tumor size was not a prognostic factor (HR=1.05; p=0.08). Lymphadenectomy was performed in 233 (57%) patients; 87 (37%) had LN metastasis. LN metastasis was associated with worse outcome (median survival: N0 39 months vs. N1 21 months; p=0.02). Preoperative factors such as tumor size, number, and morphologic subtype did not predict presence of LN metastasis (all p>0.05); however, vascular invasion did (OR=2.24; p=0.003). Conclusions: While tumor size provides no prognostic information, tumor number, vascular invasion, and LN metastasis were associated with survival. Presence of LN metastasis cannot be predicted using preoperative tumor features. Lymphadenectomy should be routinely performed for ICC as up to one-quarter of patients will have LN metastasis. No significant financial relationships to disclose.
A comparison of competing lymph node staging schemes in resectable biliary cancer.
Authors: Smith D. D. , Nelson R. A. , Schwarz R. 
Published: February 2017

166 Background: New schemes for lymph node (LN) staging have been proposed to improve upon the AJCC TNM cancer staging convention. We compared AJCC N0/N1 staging with the LN ratio and logarithmic odds systems in predicting overall survival (OS) in resectable biliary cancer patients, including cancer of the gallbladder, extrahepatic bile duct (EHBD), and ampulla of Vater (AOV). Methods: In a large, multiinstitutional U.S.-based biliary cancer data set, we identified 4,288 nonmetastatic resectable biliary cancer patients diagnosed between 1988 and 2006. We compared each subject's AJCC N stage with the two novel staging schemes. We split patients into two groups above or below the median for the two novel staging schemes and analyzed OS. Our comparison metric was the log-rank chi-squared statistic. As a baseline comparator, we included the median number of LNs resected. Results: Median (range) of follow- up was 2.5 years (1 month–19 years), with an overall median survival of 2.0 years (95% CI: 2.0–2.1 years). For all biliary patients combined, we found that the AJCC N0/N1 system and LN ratio schemes performed similarly. For gallbladder cancers (N= 1,340), LN ratio showed higher OS prediction utility, whereas in EHBD (N= 1,083) and AOV cancers (N= 1,865), AJCC staging was superior among competing methods. Conclusions: The LN ratio method is comparable with AJCC N staging for OS prediction, although the AJCC scheme is superior in two of three biliary cancers. We conclude that AJCC staging remains adequate for staging biliary cancers given the newer staging proposals. [Table: see text] No significant financial relationships to disclose.