bluuebunny/crossref_metadata_2025_split huggingface dataset:
Palliative reoperation for recurrent periampullary adenocarcinoma: Primum non nocere?
Authors: Boone Brian A. , Moser Arthur J. , Mock Brady K. , Johnson Paul J. , Dvorchik Igor , Zeh Herbert J. , Marsh J. Wallis 
Published: February 2017

257 Background: A majority of patients with periampullary cancer develop local or metastatic recurrence despite successful R0 resection. Many of these patients present with unresectable, symptomatic recurrence and selective surgical palliation is often considered. While the literature has addressed palliative surgery in primary periampullary cancer, no study has evaluated outcomes in recurrent disease. We examined the outcomes of surgical palliation for recurrent periampullary cancer. Methods: This is a retrospective study of patients who underwent palliative reoperation for recurrent periampullary cancer from 1990-2011. Morbidity and mortality was followed to 90 days. Complications were graded according to the Clavien-Dindo classification. Kaplan Meier was used to evaluate survival. Results: Fourteen patients underwent palliative reoperation following successful primary resection for periampullary adenocarcinoma. Indications for reoperation were small bowel obstruction (n=10, 71%), gastric outlet obstruction (2, 14.3%), spinal compression (1, 7.1%) and symptomatic pleural effusion (1, 7.1%). For patients undergoing abdominal reoperation, 2 (17%) underwent incomplete resection, 5 (42%) underwent bypass and 5 (42%) underwent lysis of adhesions. Median estimated blood loss was 100 mL. Median length of stay was 12 days. Postoperative complications affected 8 (57%) patients, with 75% ≥ Grade 3 complications. 3 (38%) patients died during their operative stay. 30 day and 90 day postoperative mortality were 43% and 86% respectively. Median survival was 45 days (range: 4-100). There was improved median survival in patients with an interval of more than 9 months prior to undergoing reoperation (57 vs. 11 days, p <0.05). There was no difference in survival based on pancreatic versus ampullary cancer (45 vs. 43 days, p=0.096), or local versus metastatic site of recurrence (57 vs. 34 days, p=0.30). Conclusions: Palliative reoperation for periampullary cancer recurrence is associated with high morbidity and dismal survival. Non-operative palliation should be strongly considered in patients who have undergone prior resection and present with symptomatic recurrence.
Safety and efficacy of resin 90Y-microspheres in 548 patients with colorectal liver metastases progressing on systemic chemotherapy.
Authors: Kennedy Andrew S. , Ball David , Cohen Steven J. , Cohn Michael , Coldwell Douglas M. , Drooz Alain , Ehrenwald Edward , Kanani Samir , Rose Steven C. , Nutting Charles W. , Moeslein Fred M , Savin Michael , Schirm Sabine , Putnam Samuel G. , Sharma Navesh K , Wang Eric 
Published: February 2017

264 Background: 90Y-microspheres (radioembolization) are administered via the hepatic artery following failure of one or more lines of fluoropyrimidine-based systemic chemotherapy, with or without biologic agents in colorectal carcinoma metastatic (mCRC) to the liver. Methods: A retrospective review of consecutively treated patients with mCRC from July 2002 to December 2011 at 11 U.S. institutions was conducted. Data on background characteristics, prior chemotherapy, surgery/ablation, radiotherapy, vascular procedures, 90Y treatment (SIR-Spheres; Sirtex Medical), subsequent adverse events (grade 3+) and survival were documented. Median follow-up was 8.5 mo. (IQR 4.3–15.6). Trends in the occurrence of adverse events for patients receiving 1, 2, or 3+ lines of systemic chemotherapy were evaluated by Fisher’s Exact. Kaplan Meier estimates compared the overall survival of patients across lines of chemotherapy. Results: A total of 548 patients were included; majority were male (61%), Caucasian (66%), mean age 61 years; received median of 2 (range 1–6) lines of chemotherapy prior to 90Y therapy. Median tumor/liver ratio at 90Y therapy was 15% (IQR 23%). Median 90Y activity administered was 1.18 GBq (IQR 0.48). Hospital stay duration was <24 hours for most cases (97.8%). The most common adverse events (grade 3+) following 90Y therapy included: abdominal pain 6.6% (n=36), GI ulceration 1.8% (10), nausea 1.5% (8), vomiting 1.6% (9), fatigue 6.0% (33), ascites 3.5% (19), hyperbilirubinemia 5.7% (31) and anorexia 1.1% (6). A comparison of 1, 2 and 3+ lines of chemotherapy versus grade 3+ adverse events to 3 months post-90Y therapy revealed no significant difference (p>0.05). Corresponding median survivals (95% CI) were 13.0 (10.5–14.6), 9.0 (7.8–11.0) and 8.1 (6.4–9.3) months, respectively (p<0.0001). Conclusions: 90Y microsphere therapy appears to have a favorable risk/benefit ratio in patients with mCRC who have failed prior systemic chemotherapy. These data show a clinically relevant survival benefit for 90Y therapy in patients not responding to chemotherapy, including those heavily pre-treated (3+ lines).
Effect of upregulation of ANGPT2 by DARPP-32 on angioenesis in gastric cancer.
Authors: Chen Zheng , Zhu Shoumin , Hong Jun , Belkhiri Abbes , El-Rifai Wael 
Published: February 2017

34 Background: Gastric cancer is the second most frequent cause of cancer-related death worldwide. We have previously shown that Dopamine and cAMP regulated phosphoprotein MW 32 kDa (DARPP-32) and its truncated form (t-DARPP) are overexpressed in two-thirds of gastric adenocarcinomas. Angiopoietin 2 (ANGPT2) -TIE2 signaling is a secreted protein that acts as a key regulator of adult vascular homeostasis and blood vessel formation. Methods: The expression of DARPP-32 in the multi-step carcinogenesis cascade was examined using IHC analysis on 533 samples. ANGPT2 mRNA level was detected by real-time quantitative polymerase chain reaction (PCR) in 30 gastric cancer tissue samples and 30 normal gastric tissues. DARPP-32 and t-DARPP were over expressed using stable and transient expression in AGS and MKN-28 gastric cancer cell lines, lacking endogenous DARPP-32 to investigate the induction of ANGPT2 by DARPP-32 and t-DARPP. Results: We found that ANGPT2 was higher expressed in cancer samples than normal tissues from RT-PCR. We also found gastric cancer tissue samples expressed higher DARPP-32 and t-DARPP mRNA than normal gastric tissues. Over expression of DARPP-32 and t-DARPP led to a significant increase of the mRNA and protein levels of ANGPT2 as compared to empty vector control. Consistent with these findings, the condition media from DARPP-32 and t-DARRP expressing cells showed high levels of secreted ANGPT-2. TNF-α treatment induced the levels of ANGPT2 further in DARPP-32 and t-DARPP expressing cells as compared to control. Of note, this increase in NF-κB activity was significantly higher in DARPP-32 and t-DARPP expressing cells as compared to control. To confirm the angiogenic potential, we used condition media from DARPP-32 and t-DARPP expressing AGS cells and demonstrated its ability to stimulate tube formation on human umbilical vein endothelial cells (HUVEC) models than the condition medium from control cells. Conclusions: Our results suggest that DARPP-32 and t-DARPP over expression may participate in the angiogenesis of gastric cancer. The in vitro studies indicate that DARPP-32 and t-DARPP play a role in up regulation of ANGPT2 in gastric cancer cells by enhancing the TNF-α induced activation of NF-κB signaling pathway.
Real-world comparative economics of a 12-gene assay for prognosis in stage II colon cancer.
Authors: Alberts Steven R. , Yu Tiffany , Behrens Robert J. , Renfro Lindsay Anne , Srivastava Geetika , Soori Gamini S. , Dakhil Shaker R. , Mowat Rex Bradford , Kuebler J. Phillip , Kim George P. , Mazurczak Miroslaw , Hornberger John C. 
Published: February 2017

391 Background: Prior economic analysis of a 12-gene assay (Oncotype DX), compared with patterns of care reported in the NCCN database of patients with stage II, T3, DNA mismatch repair proficient (MMR-P) colon cancer, predicted that the assay would save medical costs and improve patient well-being (Hornberger et al., Value Health, 2012). This study assessed the validity of those findings with actual adjuvant chemotherapy (aCT) recommendations. Methods: Outcomes and costs were estimated for patients with stage II, T3, MMR-P colon cancer using a Markov model. A study of 141 patients from 17 sites in the Mayo Clinic Cancer Research Consortium collected data on aCT recommended before and after knowledge of the 12-gene assay results (Srivastava et al. abstract). Quality-adjusted life years (QALY) and medical resource use after recurrence were computed using guideline-validated state-transition probability estimation methods. Risk of progression and incidence of adverse events with different aCT regimens were based on published literature. Drug and administration costs for aCT were obtained from 2012 Medicare fee schedules. One-way sensitivity analyses were conducted to evaluate parameter influence on economic impact. Results: After receiving the 12-gene assay results, physician recommendations in favor of aCT decreased 22% (95% CI 11%-32%; McNemar test p<0.001) from 73 (52%) to 42 (30%) patients. Oxaliplatin aCT and 5-FU monotherapy recommendations each declined 11%. Average aCT costs decreased $5,738 for drugs, $668 for administration, and $3,268 for adverse events management. Overall, average total direct medical costs decreased $4,203. The net effect on average patient well-being was a gain of 0.083 QALYs. Total medical costs are most influenced by change in aCT recommendations, 5-FU monotherapy efficacy, and oxaliplatin drug acquisition cost. Savings are expected to persist even if the cost of oxaliplatin dropped by >75% due to generic substitution. Conclusions: The 12-gene assayhas been shown to alter aCT recommendations for patients with stage II, T3, MMR-P colon cancer. This study provides real-world confirmation that these changes in aCT reduce direct medical costs and improve patient well-being.
Randomized phase II study of erlotinib (ERL) in two different schedules with concomitant modified XELOX in the first-line treatment of metastatic colorectal cancer (mCRC): Correlation with serial serum levels of amphiregulin (AMR) and transforming growth factor receptor-alpha (TGFa).
Authors: Chan Anthony T. C. , Chan Stephen Lam , Ho Wing Ming , Lau Wilson , Mo Frankie , Hui Edwin P. , Chan Charles , Poon Annette , Dattatray Rasalkar , Wong S. C. Cesar , To Ka Fai , King Ann Dorothy , Ahuja Anil Tejbhan , Ma Brigette 
Published: February 2017

425 Background: This study evaluated the feasibility of combining XELOX with erlotinib in a 2 different schedules, and the prognostic significance of serum AMR and TGFa in previously untreated mCRC. Methods: Eligible patients (Pt) were randomized to the ‘continuous’ arm (Arm CON) [ERL 100mg daily D1-21, oxaliplatin (Ox) 130mg/m2 D1, capecitabine (Xe) 825mg/m2 bd D1-14, q3w], or the ‘intermittent’ arm (Arm INT) [ERL 150mg daily at alternate day on D 1-14, then 150mg daily on D15-21, Ox 130mg/m2 on D1, Xe 750mg/m2bd on D1-14, in a q3w]. Serum levels of AMR, TGFa and CEA were determined serially. KRAS mutation was determined from archived tumors. Results: 60 pts were randomized and there was no difference in the baseline characteristics between the 2 arms. Of the 58 pts evaluated for response, the overall response rates (ORR) were 56.3% (Arm CON) and 66.3% (Arm INT). At a median follow-up of 2.8 yrs, the median overall survival (OS) of pts in Arm CON and Arm INT were 9 m (95% CI: 7.2-18m) and 10.3m (95% CI: 7.2-15.6 m) respectively. KRAS mutation (n = 44 tumors) status did not predict ORR or survival. Gr 3-4 toxicities occurred in 53.3% (Arm CON) and 46.7% (Arm INT) of pts. Multivariate analysis showed that elevated baseline serum TGFa and AMR were independent predictors of inferior PFS and OS, respectively. Post-treatment drop in serum TGFa was associated with shorter OS and PFS, while a drop in serum TGFa and a rise in serum AMR were associated with inferior PFS and OS, respectively. Conclusions: Although there was no statistical difference in the toxicity and efficacy of the 2 arms, the ORR from XELOX and intermittent ERL compared favorably with historic control. KRAS mutation status was not predictive. Serum TGFa and AMR have prognostic significance in this cohort and further prospective studies are warranted. Clinical trial information: NCT01243047.
Assessment of the quality of the pathological evaluation of total mesorectal excision specimens: Differences in evaluation between local pathologists and a review committee in the context of an improvement project.
Authors: Demetter Pieter , Vandendael Tamara , Sempoux Christine , Ectors Nadine , Cuvelier Claude , Nagy Nathalie , Hoorens Anne , Jouret-Mourin Anne ,   PROCARE
Published: February 2017

481 Background: Data on quality control of the pathologic evaluation of total mesorectal excision specimens are scarce. Differences between evaluation by local pathologists participating in PROCARE, a Belgian improvement project on rectal cancer, and a review panel were assessed. Methods: Based on photographic material and histopathology slides, a review committee of pathologists with a particular interest in colorectal pathology re-evaluated the mesorectal plane, the circumferential resection margin (CRM), the tumour differentiation grade, the (y)pT stage and the tumour regression grade (according to Dworak) in 444 cases (354 low anterior resection and 90 abdomino-perineal resection specimens). Results: The surgical plane was reported in 89% and the CRM in 88% of cases by the local pathologist. The median number of lymph nodes harvested in patients undergoing long-course neoadjuvant radiochemotherapy was 11, whereas this was 14 in the other patients. The review committee downgraded the surgical plane of 17% of patients from (intra)mesorectal to intramuscular, and upgraded it in 27% from intramuscular to (intra)mesorectal. Tumour differentiation grade, T stage and tumour regression grade differed between local pathologists and review committee in 15%, 10% and 38%, respectively. T stage was upgraded in 8% of cases, mainly from T2 to T3. Tumour regression was judged by the review panel to be less advanced in 15% of cases. Conclusions: Acknowledging some shortcomings (comparison between a photographical evaluation and an evaluation on a fresh specimen), this study gives a realistic view of clinical practice. There are differences in interpretation with regard to macroscopic and microscopic analysis of TME specimens. These findings indicate a need for more objective and reproducible criteria in histopathology. Being aware of this is a first step for improvement.
High pathologic response rate of hepatic colorectal cancer metastases (HCRM) following neoadjuvant bevacizumab (Bev)-based treatment (tx).
Authors: Pietrantonio Filippo , Coppa Jorgelina Clara , Miceli Rosalba , Milione Massimo , Perrone Federica , Fanetti Giuseppe , Christian Cotsoglou , Melotti Flavia , Di Bartolomeo Maria , Mazzaferro Vincenzo , Mariani Luigi , Pellegrinelli Alessio , Bertan Claudia , Biondani Pamela , De Braud Filippo G. 
Published: February 2017

529 Background: Pathologic response of HCRM to neoadjuvant tx is associated to better outcome. In retrospective analyses Bev-based tx improved tumor regression grade (TRG), while cetuximab (Cmab) increased RECIST response and R0 resections in prospective studies. The aim of this analysis was to assess the effect of Bev vs Cmab-based tx in terms of HCRM pathological response and outcome. Methods: Fifty-eight pts with HCRM were resected at National cancer Institute of Milan from 2007 to 2012 following Bev (n=30) or Cmab (n=28) based neoadjuvant tx. Pathological response was classified from TRG 1 for pathological complete response (pCR), to TRG5 for no response; TRG 1-3, for histological response; TRG 4-5 for scarce/no response (Rubbia-Brandt L, Ann Oncol 2007). Results: KRAS missing in 9 pts (3 Bev/6 Cmab), mutated in 18 pts (60%) in Bev vs 4 (14%) in Cmab group.Median number of resected metastases: 4.6 vs 3.9; mean TRG: 2.9 (2.2-4) in Bev vs 3.8 (3-5) in Cmab group (p=0.04 at Kruskal-Wallis test). Pathological response rate was higher for Bev vs Cmab (70% vs 39%; p=0.037 at Chi-square test). Bev also increased pCRs (20% vs 0%, p=0.024 at Fisher’s test). With generalized estimating equation for all resected nodules, mean TRG was lower in Bev vs Cmab group: 2.6 (2-4) vs 3.7 (3-4), p<0.001. At univariate analysis, no PFS and OS difference was observed according to tx. Multivariable Cox models shown below: Conclusions: Bev-based tx obtained an excellent pathological response rate, despite the high proportion of KRAS mutated tumors, and further prospective confirmation of these data is planned. [Table: see text]
Patient-reported outcomes from a phase III multicenter, randomized, double-blind, placebo-controlled trial of gefitinib versus placebo in esophageal cancer progressing after chemotherapy: Cancer Oesophagus Gefitinib (COG).
Authors: Dutton Susan J. , Blazeby Jane M. , Petty Russell D. , Mansoor Wasat , Thompson Joyce , Harrison Mark , Abbas Haider , Dahle-Smith Asa , Chatterjee Anirban , Falk Stephen , Garcia-Alonso Angel , Fyfe David Walter , Hubner Richard , Gamble Tina , Peachey Lynnda , Harvey Christine , Julier Patrick , Jankowski Janusz , Midgley Rachel , Ferry David R. ,   COG Collaborative Group
Published: February 2017

6 Background: There are no randomised trials of 2nd line chemotherapy for esophageal cancer. The phase III COG trial of gefitinib versus placebo in patients with esophageal cancer progressing after chemotherapy did not show significant overall survival (OS) benefit, however the trial incorporated patient reported outcomes (PRO) using validated tools. The PRO data are therefore critical to inform practice and the initial results are presented here. Methods: Adults with measurable/evaluable metastatic esophageal or types I/II junctional adeno or squamous cell carcinoma progressing after prior chemotherapy, with performance status 0-2 were randomised 1:1 to 500mg gefitinib (G) or placebo (P), treated until progression. Primary outcome: OS. Secondary outcomes include safety, PFS, PRO (assessed by EORTC QLQ-C30 and EORTC QLQ-OG25 at baseline 4, 8 and 12 weeks until progression) and predictive biomarkers. Pre-specified PRO domains were global quality of life, dysphagia, eating and odynophagia. Analysis by ANCOVA of change in PRO at 4 weeks adjusted for baseline. Results: 450 patients were recruited from 51 UK centres and no difference in OS was detected. There was evidence that PFS was better in the intervention arm (P 35 days, G 49 days; HR=0.795, 95%CI 0.66, 0.96, p=0.017). Questionnaire compliance rates were excellent at baseline (94%) and at 4 weeks (77%). Patients in the gefitinib arm reported significantly better social function (9.26; 95%CI 1.94 to 16.58; p=0.013) and significantly fewer problems with odynophagia (-8.61; 95%CI -14.49 to -2.73; p=0.004), constipation (-15.24; 95%CI -22.83 to -7.65; p=0.0001) and speech (-10.40; 95%CI -16.13 to -4.67; p=0.0004) than patients receiving placebo but more problems with diarrhoea (19.23; 95%CI 11.79 to 26.27; p<0.0001). All other PRO domains were similar between the two groups. Conclusions: Gefitinib did not improve overall survival in esophageal cancer patients after chemotherapy however there was significant PFS improvement and improvement in quality of life and palliation of symptoms albeit with an excess of diarrhoea. Clinical trial information: 29580179.
Phase II trial of miniDOX (reduced-dose docetaxel/oxaliplatin/capecitabine) in “suboptimal” patients with advanced gastric cancer (AGC): TTD 08-02.
Authors: Rivera Fernando , Massuti Bartomeu , Salcedo Matilde , Sastre Javier , Martínez-Galán Joaquina , Valladares-Ayerbes Manuel , Serrano Raquel , Garcia De Paredes Marisa , Tabernero Josep , Galan M. Carmen , Mozo Jose Luis Manzano , Diaz Rubio Eduardo , Conde Veronica , Reboredo Margarita , Vazquez Silvia , Layos Romero Laura , Pascual Francisco Javier Ramos , Aranda Enrique 
Published: February 2017

87 Background: Chemotherapy has improved overall survival (OS) in patients (p) with AGC and docetaxel (D), oxaliplatin (O) and capecitabine (X), have shown consistent activity in this setting. We defined "Suboptimal" p as those with PS ECOG-2 and/or weight loss 10-25% and/or age ≥70 years. This population is usually underrepresented in AGC clinical trials. Methods: We explored in 43 previously untreated "suboptimal" AGC p the "miniDOX" regimen (D: 40 mg/m2 iv, d1; O: 80 mg/m2 iv d1; C: 625 mg/m2 po bid, d1 to 21, every 21d; after 6 courses only C was maintained). D and O dose were allowed to be increased to 45 and 90 mg/m2 respectively (dose level +1) and to 50 and 100 mg/m2 (level +2) if less than grade 2 toxicity after the first 2 courses. One p that did not received any dose of chemotherapy, was included in the ITT efficacy analysis but not in the safety analysis. Primary endpoint was Response Rate (RR), Toxicity, Progression Free Survival (PFS) and OS were secondary objectives. Results: p characteristics: PS ECOG-2:12 p, Weigh loss 10-25%:23 p; median age 73.3 years (40-87); 32 males; locally advanced:8 p/metastatic:35 p; Primary site:Gastric 32 p/ EGJ 11; In 19 p the dose of D and O were increased to level +1 and in 8 of them to level +2. Worst toxicity per p (Grade 3-4): neutropenia: 5 p (3 of them with febrile neutropenia); pulmonary embolism (PE):4 p (3 of them suffered sudden death and the PE was suspected but not confirmed); diarrhea:9 p; paronychia:2 p; CVA:1 p; renal failure:1 p (this p suffered infection/bacteriemia without neutropenia and died); hand-foot syndrome:4 p and asthenia:5 p. Response: CR:1 p, PR:23 p (RR: 56%), SD:12 p, Progression:3 p, No determined:4 p; With a median follow-up of 27 months, 36 p have died (toxicity:4 p, progressive disease:32 p). Median and 1 year actuarial PFS and OS are 5.5 months/19% and 13.3 months/54% respectively. Conclusions: Although relevant the toxicity of miniDOX has been found, its activity is encouraging in "suboptimal" pts with AGC and this combination should be further investigated in this setting. Clinical trial information: NCT00733616.
Association of relapse in patients with esophageal and esophagogastric junction (E-EGJ) cancer with surgical stage after trimodality therapy (TMT): Implications for customized surveillance.
Authors: Campagna Maria-Claudia , Taketa Takashi , Correa Arlene M. , Sudo Kazuki , Blum Mariela A. , Wadhwa Roopma , Komaki Ritsuko , Lee Jeffrey H. , Bhutani Manoop S. , Weston Brian , Liao Zhongxing X. , Rice David C. , Swisher Stephen , Hofstetter Wayne Lewis , Ajani Jaffer A. 
Published: February 2017

95 Background: The surveillance strategy for E-EGJ cancer patients after TMT is currently not based on evidence and varies considerably. Literature does not provide guidance. Methods: Between 2000 and 2010, 579 patients with E-EGJ cancer who underwent TMT were analyzed. The type and timing of first relapse using 12-month intervals and their association the post-TMT surgical stage. Various statistical methods were utilized. Results: For 579 patients, the median follow-up time was 57.4 months (95% confidence interval [CI], 51.5-63.3 months). A total of 232 (40%) patients had a relapse. First relapses were: distant metastases (199 patients; 34.4%) and local-regional metastases (33 patients; 5.7%). Irrespective of the surgical stage, 95% of all relapses occurred within 36 months of surgery. The timing and frequency of relapses were significantly associated with the surgical stage (see Table; stage 0 or I vs. II or III; p= <0.001). Conclusions: Our data suggest that customization of surveillance is possible based on the surgical stage after TMT. These data can contribute to the development of an evidence-based surveillance strategy. [Table: see text]