bluuebunny/crossref_metadata_2025_split huggingface dataset:
Readmission after robotic Ivor Lewis esophagectomy: Earlier discharge, increased readmissions?
Authors: Salem Ahmed I. , Shridhar Ravi , Hoffe Sarah E. , Almhanna Khaldoun , Meredith Kenneth 
Published: February 2017

149 Background: Readmissions after esophagectomy are costly and incidence can be as high as 25%. The robotic assisted approach has potential benefits of earlier discharge compared to conventional techniques, however it is unclear what impact an earlier discharge will have on readmission rates. We sought to examine the impact of early discharge on readmission rates with robotic approaches. Methods: A retrospective review of all patients undergoing robotic assisted Ivor Lewis esophagectomy (RAIL) from 2009-2015 was conducted. Clinicopathologic factors and surgical outcomes were recorded and compared. We then compared outcomes to a historical cohort from the Surveillance, Epidemiology, and End Results-Medicare data (2002 to 2009). Length of stay, 30-day and 90-day readmissions, and mortality were determined. All statistical tests were two-sided and a p-value < 0.05 was considered statistically significant. Results: We identified 147 patients who underwent RAIL. There were 78.9% (116) male with an average age 66 ±10 years. Adenocarcinoma was the predominant histology in 86% (126) patients, 9.52% (14) patients had squamous cell histology, and 4.76% (7) patients had other histology. Neoadjuvant therapy was administered to 77.6% (114) patients. In the SEER database 1,744 patients with esophageal cancer underwent esophagectomy: 80% of patients (1,390) were male, with a mean age of 73 years; 71.8% of tumors (1,251) were adenocarcinomas, and 38% of patients (667) received neoadjuvant therapy. Median length of stay was 13 days, 30-day mortality was 8.8% (158 patients), and 90 day mortality was 17.9% (302) compared to median LOH of 9 days, 30-day mortality of 0.6% (1) and 90-day mortality of 1.4% (2)% in the robotic cohort, p < 0.0001, p = 0.007, and p < 0.0001. Readmission rates at 30 and 90 days were 18.6% (212) and 31.3% (356) in the SEER patients, and 3.4% (5) and 5.4% (8) in the robotic cohort p = 0.001 and p < 0.001. Conclusions: RAIL is a safe surgical technique that provides an alternative to conventional approaches to esophageal resection. Patients undergoing RAIL had lower mortality rates and LOH. Despite the lower LOH, RAIL was associated with lower 30 and 90-day readmissions.
Final overall survival (OS) analysis with modeling of crossover impact in the phase III GRID trial of regorafenib vs placebo in advanced gastrointestinal stromal tumors (GIST).
Authors: Demetri George D. , Reichardt Peter , Kang Yoon-Koo , Blay Jean-Yves , Joensuu Heikki , Schaefer Klaus , Wagner Andrea , Casali Paolo Giovanni , Kappeler Christian 
Published: February 2017

156 Background: GRID showed that regorafenib (REG) improves progression-free survival (PFS; primary endpoint) vs placebo (PBO) in patients (pts) with advanced GIST after failure of at least imatinib and sunitinib (HR 0.27; 1-sided p < 0.0001). An interim OS analysis at the time of the primary PFS analysis showed a positive trend (HR 0.77; p = 0.199) despite 85% of PBO pts crossing over to REG. An exploratory analysis modeling the impact of crossover on OS suggested a benefit for REG. We present exploratory analyses of OS comparing crossover correction results at different times, including at the planned final OS analysis. Methods: Data cut-off dates for OS analyses were 26 Jan 2012 (final PFS analysis), 31 Jan 2014, and 8 Jun 2015 (final OS analysis). The impact of crossover on OS was modeled using 2 randomization-based methods: rank preserving structural failure time (RPSFT) and iterative parameter estimation (IPE), both considered best choice among correction analytics. Hazard ratios (HRs) and 95% CIs were derived using the Cox model. Results: Pts were randomized (2:1) to REG (n = 133) or PBO (n = 66). Data maturity in terms of deaths of randomized pts was 23%, 70%, and 81%. At data cut-off for the final OS analysis, a total of 162 deaths occurred: REG 109 (82%) and PBO 53 (80%); 7 pts remained on treatment. Compared to the 2012 OS analysis, continued crossover treatment further diluted the treatment effect, evidenced by the increasing HR in the ITT analysis at later times (Table). Conclusions: IPE correction provides more stable estimated median times and HRs than RPSFT. These exploratory analyses modeling the impact of crossover to active drug suggest that REG has a greater OS benefit than noted in the ITT analysis. Such sensitivity analytics are needed to understand fully the benefits of active drugs in crossover trials. Clinical trial information: NCT01271712. [Table: see text]
Survival and prognosticators of gastric cancer patients with only positive peritoneal lavage cytology.
Authors: Kano Kazuki , Sato Tsutomu , Maezawa Yukio , Segami Kenki , Nakajima Tetsushi , Ikeda Kousuke , Aoyama Toru , Hayashi Tsutomu , Yamada Takanobu , Oshima Takashi , Rino Yasushi , Masuda Munetaka , Ogata Takashi , Cho Haruhiko , Yoshikawa Takaki 
Published: February 2017

16 Background: Treatment strategies for only positive peritoneal lavage cytology findings have not yet been established. The objective of this retrospective study was to clarify the survival and prognosticators in these patients. Methods: Overall survival (OS) rates were examined in 39 patients with gastric cancer who underwent a curative resection and had positive peritoneal cytology in the absence of overt peritoneal metastases between January 2000 and June 2015. Univariate and multivariate analyses were performed to identify risk factors using a Cox proportional hazards model. Results: A total of 39 patients were evaluated. The median overall survival was significantly longer in the 34 patients who received chemotherapy after surgery than that in the 5 who did not (19.1 vs 5.9 months, p < 0.01). Among the patients who received chemotherapy after surgery, univariate and multivariate analyses showed that pN3b was an independent significant prognosticator (hazard ratio of 4.169 with 95% CI: 1.108-15.684, p = 0.035). The median OS was 15.8 months when the patients diagnosed with N3b was 33.1 months when the patients diagnosed with N3a or lower. Conclusions: The prognosis of gastric carcinoma with positive peritoneal lavage cytology without peritoneal metastasis is still poor and need more aggressive treatment. The lymph node metastasis was a significant prognosticator in these patients.
Safety, PD-L1 expression, and clinical activity of avelumab (MSB0010718C), an anti-PD-L1 antibody, in Japanese patients with advanced gastric or gastroesophageal junction cancer.
Authors: Nishina Tomohiro , Shitara Kohei , Iwasa Satoru , Hironaka Shuichi , Muro Kei , Esaki Taito , Satoh Taroh , Yamaguchi Kensei , Machida Nozomu , von Heydebreck Anja , Watanabe Morihiro , Doi Toshihiko 
Published: February 2017

168 Background: The programmed death-1 receptor (PD-1) and its ligand (PD-L1) are key therapeutic targets in the reactivation of the immune response against cancer. Avelumab* (MSB0010718C) is a fully human anti-PD-L1 IgG1 antibody being investigated in clinical trials. We report safety and clinical activity from this phase Ib dose expansion JAVELIN study (NCT01943461) of avelumab in Japanese patients (pts) with advanced gastric or gastroesophageal junction adenocarcinoma (GC/GEJ) based on level of PD-L1 expression. Methods: GC/GEJ pts (ECOG performance status 0-1 at trial entry) received avelumab 10 mg/kg Q2W by IV infusion until confirmed progression, unacceptable toxicity, or withdrawal. Tumors were assessed every 6 wks (RECIST 1.1). Best overall response rate (ORR) and progression-free survival (PFS) were evaluated. Adverse events (AEs) were graded by NCI-CTCAE v4.0. PD-L1 expression on fresh tissue samples collected up to 6 mos prior to trial was assessed by immunohistochemistry using various cutoff criteria. Results: As of Mar 11 2015, 20 pts (18 GC, 2 GEJ) were treated with a median follow-up of 6 mos. Treatment-related treatment-emergent AEs (TR-TEAEs) of any grade occurred in 18/20 pts (90%); one patient (5%) reported a grade 3 TR-TEAE (alanine aminotransferase increase). There were no treatment-related deaths. Confirmed ORR was 15.0% based on 3 partial responses (PR) and the disease control rate (PR + stable disease) was 65.0%. PD-L1 expression was evaluable in 19 pts. Pts with PD-L1+ samples (n = 5 [26.3%]; ≥ 1% cutoff) showed a 40.0% ORR compared with 7.1% ORR in pts with PD-L1− samples (n = 14 [73.7%]; p= 0.155). Median PFS was 12.3 wks (95% CI: 3.1, ne) for PD-L1+ and 11.1 wks (6.0, 12.1) for PD-L1− ( ≥ 1% cutoff). PFS rate at 12 wks was 60.0% (95% CI: 12.6, 88.2) and 32.1% (10.2, 56.9) for PD-L1+ and PD-L1− pts, respectively. Conclusions: Single agent avelumab showed an acceptable safety profile and clinical activity in GC/GEJ pts. A trend of higher ORR and higher PFS rate was observed in PD-L1+ pts compared with PD-L1− in this small cohort. Further analysis is ongoing and expansion of this cohort to 40 pts is underway. *Proposed INN. Clinical trial information: NCT01943461.
Circulating biomarkers exploratory study in loco-regional gastroesophageal adenocarcinoma patients.
Authors: Longo Federico , Earl Julie , Martinez-Avila Jose Carlos , Guerrero Carme , Pachon Vanesa , Rodríguez Garrote Mercedes , Ferreiro REYES , Gómez Rueda Ana , Molina Javier , Villamayor Delgado Maria , Martinez Saez Olga , Salgado Alfonso Cortes , Muñoz del Toro Jacobo , Cortez Castedo Silvia Patricia , Olmedo Garcia Maria Eugenia , Lopez Hervas Pedro , Priego Pablo , Galindo Julio , Guillén Ponce Carmen , Carrato Alfredo 
Published: February 2017

17 Background: Patients diagnosed with gastroesophageal adenocarcinoma (GEA) have a poor prognosis despite curative attempts with multimodal treatment including surgery, chemotherapy (CT) and radiotherapy (RT). VEGF, EpCAM, MUC1, CK19 and CK20 and CD133 have shown to provide additional prognostic information in advanced GEA patients. Methods: Circulating mRNA of total VEGF (and 2 VEGF isoforms 121 and 165), EpCAM, MUC1 and CD133 were determined in 36 loco-regional GEA patients (pts). Blood samples were collected before surgery or, when indicated, before the preoperative chemotherapy treatment, within a 7 days window. Additionally, 14 healthy volunteers and 7 advanced GEA pts were included to comparative analyses. The Wilcoxon test was used to assess differences in expression among the groups. Results: Pre-surgery CT was administered in 30 pts (79%). ECF or its modifications were administered in 22 pts, and FOLFOX in 7 pts. Type of resection achieved was R0 (19 pts, 59%), R1(7 pts, 22%) and R2 (6 pts, 10%). Post-surgery CT was administered in 22 pts (73%) including ECF or its modifications (10 pts), FOLFOX (7 pts) and CT-RT (4 pts). PFS occurred in 19 pts (61%) and 34 patients remained alive at the time of this analysis. Patients diagnosed with loco-regional GEA exhibited over expression as compared to healthy volunteers of VEGFi121 in 17 pts (47%) by 33-fold median change (IQR 5-43, %, p = 0.0008); VEGFi165 in 17 pts (47%) by 15-fold (IQR 5-36, p = 0.002); total VEGF in 19 pts (53%) by 15 fold (IQR 8-59, p = 0.01); EpCAM in 8 pts (22%) by 3-fold (IQR 0.5-3, NS); MUC1 in 19 pts (53%) by 23-fold (IQR7-59, p = 0.0008); and CD133 in 2 pts (6%) by 55-fold (IQR 28-83, NS). CK20 expression was not detected in healthy controls but was detected in 3 patients. Conclusions: VEGF and its isoforms VEGF121 and VEGF165 and MUC1 are potential diagnostic biomarkers in GEA. Due to the short follow-up of patients we cannot yet evaluate their role as prognostic biomarkers.
Evofosfamide (TH-302) in combination with gemcitabine in previously untreated patients with metastatic or locally advanced unresectable pancreatic ductal adenocarcinoma: Primary analysis of the randomized, double-blind phase III MAESTRO study.
Authors: Van Cutsem Eric , Lenz Heinz-Josef , Furuse Junji , Tabernero Josep , Heinemann Volker , Ioka Tatsuya , Bazin Igor , Ueno Makoto , Csõszi Tibor , Wasan Harpreet , Melichar Bohuslav , Karasek Petr , Macarulla Teresa , Guillén Ponce Carmen , Kalinka-Warzocha Ewa , Horvath Zsolt , Prenen Hans , Schlichting Michael , Mehdi Fazal , Bendell Johanna C. 
Published: February 2017

193 Background: Pancreatic ductal adenocarcinoma (PDAC) is invariably diagnosed at an advanced stage and has poor clinical outcome. Hypoxia is a significant prognostic factor in PDAC progression and is associated with poor prognosis. Evofosfamide (Evo, previously known as TH-302) is a hypoxia-activated prodrug of bromo-isophosphoramide mustard (Br-IPM) that is preferentially activated under hypoxic conditions. The addition of Evo to gemcitabine (Gem) significantly improved progression-free survival (PFS) in a randomized phase II trial in advanced PDAC (NCT01144455). Methods: MAESTRO is an international, randomized, double-blind, placebo-controlled phase III trial of Evo/Gem vs Placebo/Gem in patients (pts) with measurable, locally advanced unresectable or metastatic PDAC (NCT01746979). Evo and Gem were administered intravenously at a dose of 340 mg/m2 and 1,000 mg/m2, respectively, on days 1, 8, and 15 of a 28-day cycle. Treatment continued until disease progression. Key eligibility criteria included ECOG PS 0/1 and no neoadjuvant or adjuvant chemotherapy <6 months prior to entry. The primary endpoint was overall survival (OS) with the study designed to detect a HR of 0.75 with 90% power. Secondary endpoints included PFS and objective response rate (ORR), employing a hierarchical testing procedure with a 2-sided α=0.05 at each level. Results: A total of 693 pts were randomized to treatment with Evo/Gem (n=xxx) or Placebo/Gem (n=yyy). Baseline pt characteristics were similar between treatment arms. The OS HR was X.XX (95% CI: Y.YY, Z.ZZ; p=A.AAA). Median OS was AA.A months (m) for Evo/Gem vs BB.B m for Placebo/Gem. Median PFS was C.C m and D.D m, respectively (HR E.EE [95% CI: F.FF, G.GG; p = H.HHH). ORR was JJ.J% with Evo/Gem vs KK.K% with Placebo/Gem (p = L.LLL). Grade ≥3 adverse events (AEs) occurring in >5% of pts in treated with Evo/Gem were: TBC. Conclusions: The data from the MAESTRO trial will make an important contribution to our understanding of PDAC treatment. Clinical trial information: NCT01746979.
A western validation of a novel gastric cancer prognostic model using American data.
Authors: Goldner Bryan S. , Song Ki Jun , Son Taeil , Kim Hyoung-Il , Melstrom Laleh , Singh Gagandeep , Noh Sung Hoon , Fong Yuman , Woo Yanghee , Hyung Woo Jin 
Published: February 2017

2 Background: A novel prediction model, the Yonsei University Gastric Cancer Prediction Tool was developed by an international collaborative group (G6+) for accurate determination of 5-year overall survival of gastric cancer patients. This prediction model was created using a prospectively maintained single institution database of 12,399 patients and included clinically relevant factors not accounted for in the TNM staging system. This prediction model was validated using external data sets from Asia; its’ applicability in the American population has yet to be determined through a validated data set. Methods: Using the SEER dataset, 2014 release, all patients with gastric adenocarcinoma diagnosed between the years 2002 –2012 who underwent resection were selected. The following characteristics were selected for analysis: age, sex, gender, depth of tumor invasion, number of positive lymph nodes, total lymph nodes retrieved, presence of distant metastasis, extent of resection, and histology. These data were processed through a recently published prognostic nomogram to obtain concordance index (C-statistic) using the bootstrap method and calibration was assessed. This was compared to the current prognostic index, the TNM staging system. Results: A total of 26,019 possible patients were identified from the SEER database, years 2002-2012. Of these, 11,765 had complete datasets. Validation of the prognostication model revealed a C-statistic of 0.762 (95% CI 0.754-0.769). This is compared to the 7thTNM staging model, C-statistic 0.683 (95% CI 0.677-0.689). The new nomogram was found to be significantly more accurate with a p-value of < 0.001. Conclusions: Our study validates a novel prediction model for gastric cancer in the American patient population. Using this model, superior accuracy in prognosticating the 5-year survival of gastric cancer patients was confirmed in the western cohort strongly supporting its global applicability. This model also allows for inclusion of those who did not undergo adequate lymphadenectomy or who underwent a non-curative resection and can be a useful prediction tool for an increasing number of gastric cancer patients world-wide.
Obesity and mortality in patients with esophageal cancer: A systematic review and meta-analysis.
Authors: Gupta Arjun , Majumder Kaustav , Arora Nivedita , Singh Preet Paul , Singh Siddharth 
Published: February 2017

20 Background: Obesity influences incidence of esophageal cancer (EC) with contrasting impact on esophageal adenocarcinoma (EAC) and esophageal squamous cell carcinoma (ESC). However, it is unclear whether it influences mortality in patients with EC. We performed a systematic review and meta-analysis to assess the association between obesity and EC mortality. Methods: Through a systematic search of major databases and conference proceedings, up to June 2015, we identified observational studies reporting the association between obesity (premorbid body mass index [BMI] ≥ 30 kg/m2) and all-cause mortality in patients with EC. We estimated summary adjusted hazard ratio (aHR) with 95% confidence intervals (CI), comparing highest BMI category with reference category in each study using random effects model; heterogeneity was measured using the inconsistency index (I2). Results: We identified 8 studies (including 1 pooled cohort study) with 2,784,027 people, of whom 18% were obese. On meta-analysis, compared with EC patients with reference BMI, obese EC patients had aHR for mortality of 0.97 (95% CI, 0.66-1.43), with high heterogeneity (I2 = 88%) after pooling maximally adjusted HRs. On analyzing patients with EAC alone (3 studies), mortality aHR was 1.10 (95% CI, 0.43-2.82), with high heterogeneity (I2 = 95%). Data to separately analyze ESC or to perform subgroup analysis in males vs females, smokers vs never smokers and Asia Pacific vs Western populations was limited. Conclusions: Based on meta-analysis, obesity does not appear to be associated with mortality in patients with EC. However, high heterogeneity and limited data for subgroup analysis limits the interpretation of this analysis. Further prospective studies evaluating mortality in patients with established EC are needed to answer this question. [Table: see text]
Risk factor of thrombosis and impact on prognosis in patients with pancreatic cancer receiving chemotherapy.
Authors: Ishigaki Kazunaga , Nakai Yousuke , Isayama Hiroyuki , Hamada Tsuyoshi , Takahara Naminatsu , Mizuno Suguru , Mohri Dai , Kogure Hirofumi , Matsubara Saburo , Yamamoto Natsuyo , Tada Minoru , Koike Kazuhiko 
Published: February 2017

218 Background: Thromboembolism (TE) is common in cancer patients, and pancreatic cancer is reported to be highly associated with TE. The aim of this analysis is to clarify risk factors for TE and its clinical impact in pancreatic cancer patients. Methods: Data on consecutive pancreatic cancer patients receiving systemic chemotherapy between August 1999 and July 2015 were retrospectively studied. The diagnosis of TE was made on CT scan either performed for suspicious symptoms of TE or for evaluation of chemotherapy response, and TE was classified into two groups: arterial events including coronary artery disease (CAD), cerebrovascular disease and other artery thrombosis, and venous events including deep vein thrombosis/pulmonary embolism (DVT/PE), portal vein thrombosis (PVT) and IVC thrombosis. Overall survival and time to TE (TTE) were calculated by Kaplan-Meier analysis. Risk factors for TE development were analyzed using a Cox proportional hazards model. To evaluate the impact of TE on survival, multivariate analyses were performed using a time-dependent covariate multiple Cox model. Results: A total of 475 patients (195 female, a median age of 67 years) were analyzed. TE was identified in 57 patients (12%). Venous TE were 45 (79%) including DVT/PE 24(42%), IVC thrombosis 2 (4%), PVT 19 (33%). Arterial TE were 12 (21%) including cerebrovascular infarction 9 (16%), CAD 2 (4%) respectively. The median TTE was 169 days (95% CI, 75-203). Liver metastasis was the only significant risk factor for TE in the multivariate analysis (OR 2.01, 95%CI 1.12-3.47, P = 0.012). The median survival from TE development was 57 days (95% CI, 37-65) and TE was significantly associated with poor prognosis (HR 3.31, 95%CI 2.72-5.27, P< 0.01) in the time-dependent covariate analysis. Conclusions: TE was not uncommon in pancreatic cancer patients receiving chemotherapy and was associated with poor prognosis. Whether the prophylaxis for TE can improve survival should be further investigated, especially in high risk patients such as patients with liver metastasis.
Pancreatic squamous cell carcinoma: Epidemiology, clinicopathologic characteristics, and outcomes.
Authors: Makarova-Rusher Oxana V. , Ulahannan Susanna Varkey , Greten Tim F. , Duffy Austin G. 
Published: February 2017

220 Background: Although squamous metaplasia is commonly detected in pancreatic parenchyma, primary pancreatic squamous cell carcinoma (SCC) is a rare malignancy with unknown incidence and unclear prognosis. Methods: Using SEER-18 database primary code C25 in conjunction with histology codes for SCC (8052-8053, 8070-8078, 8083-8084) and for adenocarcinoma (AC) (8052-8053, 807-8078, 8083-8084), we identified cases diagnosed from 2000 to 2012. Age-adjusted incidence rates and trends over time were calculated. Patients with SCC were compared with AC by clinical features (TNM categories and histological differentiation), and 1-year and 2-year relative survival (RS) outcomes. Chi-square tests for categorical variables and t-tests for continuous variables were conducted. Kaplan-Meier method was used to estimate RS and Z-test was used to compare RS rates. SEERStat and GraphPad were used for analysis. Results: We identified 214 patients with microscopically confirmed SCC and 72,860 patients with AC. SCC constituted less than 1% of all cases of primary pancreatic cancer; however, age-adjusted incidence rates for this subtype tripled between 2000 and 2012. The annual percent increase of SCC incidence rate was 5.5%. Significant differences were observed by age, gender and race: older age groups, blacks and males had higher SCC incidence rates. Compared to AC, a greater proportion of patients with SCC had poorly differentiated histology (15.8% vs. 30.4%, p < 0.01). Similar to AC, the majority of patients with SCC had stage IV disease at diagnosis, 54.3% for AC vs. 56.4% SCC. The 1-year and 2-year relative survival rates were significantly lower in patients with SCC than AC. The 1-year relative survival rate was 15.8% (95%CI = 10.4-22.3) for SCC, compared with 24.7% (95%CI = 24.3-25.1) for AC, p < 0.001. Conclusions: Although primary squamous pancreatic carcinoma is a rare neoplasm, incidence rates for this subtype are markedly rising. Relative to adenocarcinoma, pancreatic squamous cell carcinoma is characterized by poorly differentiated histology and worse survival.