bluuebunny/crossref_metadata_2025_split huggingface dataset:
Retrospective observational study: Bevacizumab (B) use and outcomes among metastatic colorectal cancer (mCRC) patients (pts) receiving care in the outpatient community in the United States.
Authors: Nadler Eric S. , Sail Kavita Rohidas , Chen Lei , Thompson Stephen F. , Kolodziej Michael A. 
Published: February 2017

547 Background: This study assessed utilization and outcomes of B use in mCRC pts receiving 1st- (1L) and 2nd-line (2L) treatment (Tx) in this setting. Methods: Data were abstracted primarily from US Oncology’s iKnowMed electronic medical record system. Multivariate Cox models were used for overall survival (OS) when testing differences between B and nonbiologic use. mCRC pts initiating 1L or 2L Tx from 1/1/07-6/30/09 were included. Cost of care was derived from outpatient claims data in US Oncology’s Claims Data Warehouse. Results: 1795 pts were identified in 1L setting, 615 in 2L, and 323 in both 1L and 2L; 90% of 1L and 87% of 2L pts received combination Tx. Most received biologics (73% 1L, 65% 2L); among these, most included B (1131/1179 [96%] 1L, 312/345 [90%] 2L). B was commonly combined with FOLFOX (665/1131 [59%]) in 1L and FOLFIRI (135/312 [43%]) in 2L. Results for B use are described as 1L and 2L, respectively. Mean (median) numbers of cycles were 9.1 (7.0) and 7.0 (5.0), and 23% (301/1321) and 34% (120/348) received ≤3 cycles. Mean (median) durations of use were 141 (113) and 108 (75.5) days; average doses across all cycles for B were 5.5 mg/kg and 5.7 mg/kg. Consistent with the literature, 1L B was associated with a 23% reduction in risk of mortality vs nonbiologics (HR=0.77; CI: 0.60-0.98; P=0.036); however, 2L B was not associated with risk of mortality reduction (HR=0.87; CI: 0.62-1.22; P=0.44). With 1L B-containing regimens, median OS was 546.5 days in pts who continued B in 2L (n=269), and 569 days (P=0.11) in pts who did not (n=28); median costs for 2L B vs non-B were $5155 vs $3867 (P=0.068). 1L OS observed in this study was less than 1L OS reported in the BRITE registry (660 days; 95% CI: 21.9-24.4 months [doi: 10.1634/theoncologist.2009-0071]). Conclusions: This study re-examines previously reported observations from the BRITE registry, but evaluates pts treated more recently and in both 1L and 2L settings. Our study did not show a significant survival advantage with prolonged use of B following progression. Further research is needed to confirm these findings. Research and editorial assistance was funded by sanofi-aventis U.S. LLC.
Multicenter phase Ib/II study of everolimus (RAD001) and tivozanib (AV-951) in patients with refractory, metastatic colorectal cancer.
Authors: Wolpin Brian M. , Ng Kimmie , Zhu Andrew X. , Abrams Thomas Adam , Enzinger Peter C. , McCleary Nadine , Meyerhardt Jeffrey A. , Schrag Deborah , Kwak Eunice Lee , Allen Jill N. , Bhargava Pankaj , Chan Jennifer A. , Goessling Wolfram , Blaszkowsky Lawrence Scott , Elliott Meaghan , Shellock Maria , Regan Eileen , Fuchs Charles S. 
Published: February 2017

560 Background: Everolimus (E) is an oral inhibitor of mTOR. Tivozanib (T) is a highly potent, selective, oral inhibitor of VEGF receptors-1, -2, and -3. Preclinical data suggest antitumor activity for this combination in colorectal cancer. We therefore performed a multicenter Phase Ib trial of E + T in patients (pts) with any refractory gastrointestinal (GI) malignancy, followed by a Phase II trial of E + T in pts with refractory, metastatic colorectal cancer (mCRC). Methods: Eligibility criteria: histologically confirmed, measurable disease; ECOG PS≤2; blood pressure ≤150/100; no venous thromboembolism within prior 6 months. Pts with mCRC must have received prior fluoropyrimidine, irinotecan, oxaliplatin, bevacizumab and anti-EGFR antibody (if KRAS wt). E was administered once daily continuously. T was administered once daily for 3 out of every 4 weeks. The Phase Ib study in pts with any GI malignancy followed a standard 3+3 design with 3 dose levels: (1) E 5 mg/d + T 1 mg/d; (2) E 10 mg/d + T 1 mg/d; (3) E 10 mg/d + T 1.5 mg/d. The Phase II study in pts with mCRC was a non-randomized, one-stage design with a primary endpoint of progression-free survival. Results: Between 02/10-12/10, 12 pts were enrolled to the Phase Ib study. Median age, 60 (39-81) years; male, 50%; ECOG PS 0/1/2, 42/58/0%; tumor types: esophagus 1, colorectal 11 pts. Dose limiting toxicities of grade 3 fatigue and grade 3 fatigue/ dehydration occurred in 2/6 pts on dose level 3. Grade 3/4 treatment-related adverse events in ≥10% of pts were dehydration, fatigue, headache, hyperglycemia, hypertension, and hypophosphatemia. The phase II study proceeded at the maximally tolerated dose (MTD) of E 10 mg/d and T 1 mg/d. Between 02/11-06/11, 40 pts with mCRC were enrolled to the phase II study. All but 1 pt received prior bevacizumab. Median age, 56 (35-81) years; male, 48%; ECOG PS 0/1/2, 45/53/2%. Treatment is ongoing. Conclusions: Among pts with refractory GI malignancies, the combination of Everolimus + Tivozanib was well-tolerated with MTD of E 10 mg/d and T 1 mg/d. A phase II trial has completed enrollment using these doses of E + T in pts with refractory mCRC; safety and efficacy data will be available for presentation.
Targeted therapies for metastatic colorectal cancer (mCRC): A systematic review of cost-effectiveness (CE).
Authors: Bentley Tanya G. , Broder Michael Samuel , Das Lopamudra , Ortendahl Jesse , Su Yun , Wagner Samuel 
Published: February 2017

583 Background: Currently three targeted agents are available for the treatment of mCRC. Making the right choice requires balancing efficacy, safety, quality of life, and, in cost-constrained systems, cost. This study aims to determine the most cost effective treatment in each line of therapy for mCRC through systematic review of published CE analyses (CEA). Methods: Literature was searched in Medline, Cancerlit, EMBASE, Cochrane, CINAHL, BIOSIS, Web of Science, Tufts CEA registry, ASCO and ASCO GI for CEAs of the three mCRC targeted agents, cetuximab, bevacizumab, and panitumumab. Manuscripts from 2004-2011 and abstracts from 2009-2011, published in English and considering payer/societal perspectives were included. Incremental CE ratios (ICERs) were converted to US$ using 2010 purchasing power parity. Results: 15 models from six countries were identified. Mean incremental costs per quality adjusted life year (QALY) and per life year (LY) gained are shown in the Table. All four models evaluating cetuximab in 1st line therapy, and only one of the six in 2nd+ line therapy, were done among biomarker selected KRAS wild type patients. Cetuximab’s cost effectiveness in 1st line therapy was driven by its ability to convert initially unresectable liver metastasis to resectable. Conclusions: Lower ICERs appear to be associated with the use of a predictive biomarker and / or a sub patient population that can benefit the most from a treatment. With the KRAS biomarker and its potential curative benefit in patients with initially unresectable liver metastasis, cetuximab appears to be the most cost-effective targeted agent in 1st line mCRC treatment. In 2nd or later lines, direct CEA between the three agents in comparable biomarker selected patients are needed to determine the most cost effective agent. [Table: see text]
Hepatic arterial embolization adopting polyvinyl alcohol microspheres preloaded with irinotecan versus systemic chemotherapy for hepatic metastases from colorectal cancer: A phase III clinical research trial of activity and quality of life.
Authors: Fiorentini Giammaria , Aliberti Camillo , Tilli Massimo , Coschiera Paolo , Mambrini Andrea , Giordani Paolo , Alessandroni Paolo , Benea Giorgio 
Published: February 2017

587 Background: Patients with liver metastases (LM) from colorectal cancer (CRC) have a severe prognosis with the 5-year survival of 25% after radical resection; for not operable metastases the survival is poor. Embolization using polyvinil alcohol microspheres loaded with IRI 200 mgr (D) is a feasible procedure. FOLFIRI (CT) is active for the treatment of CRC. We planned this phase III study to assess survival as primary endpoint to increase median survival (MS) by 40% at 2-y (HR=0.72). QoL, responses, progression-free survival (PFS) and safety are secondary endpoints. Methods: Between December 2006 and December 2008, 74 pts were randomized, 37 patients to D and 37 to CT. Two D patients had early progression and two CT patients refused. 70 cycles of D were administered in 35 pts, with a dose intensity (DI) of 99%, and 292 CT cycles were delivered to 35 pts with a DI of 90%. Results: At a median follow up of 30 months ( 18-42) we reported (D vs CT): MS 48% vs 28%, Response Rate 70% vs 20%, Acute Toxicity 70% vs 20%, Late Toxicity 20% vs 80%, QoL improvement 65% vs 25%, Costs for each pt: 7,000 vs 24,000 euro. Conclusions: D increased the 30-Months MS difference of 20% compared to CT. D improved responses, Performance Status and reduced costs. D reported higher immediate toxicity, mainly fever and abdominal pain, than CT. Late toxicity, mainly haematological, diarrhoea, asthenia and alopecia, was more common in CT. We conclude that D compared to CT increases survival and palliative results in patients with LM from CRC.
Relationship of the expression of IL-32 on NF-κB and p-p38 MAP kinase pathways in human esophageal cancer.
Authors: Yousif Nasser Ghaly , al-Amran Fadhil , Al-khirsani Hassan 
Published: February 2017

59 Background: Esophageal cancer is the seventh leading cause of cancer death in males in the United States, and a strong link has been demonstrated between inflammation and esophageal cancer. Interleukin (IL)-32 is a recently described proinflammatory cytokine characterized by the induction of nuclear factor NF-κB activation, the p38 MAPK also plays an important role in key cellular processes related to inflammation and cancer. We investigated whether the IL-32 expression may be involved in esophageal carcinogenesis through modulates the activity of NF-κB and p- p38 MAPK. Methods: Malignant esophageal and blood samples were obtained from 65 operable untreated patients, normal samples was obtained from 35 patients operated for other reasons as control. IL-32 expression, phosphorylated P38MAPK are visualized by immunohistochemistry, RT-PCR for IL-32 mRNA expression and for detected cytokines (TNF-α, IL-1 β, IL-6 and IL-8 ), NF-kB phosphorylation was analyzed by immunoblotting, ELISA for further detection IL-32 and cytokines concentration in the patients sera. Results: IL-32 expression was increased in malignant esophageal samples compared with control (P = 0.01),and mostly in adenocarcinomas type (76.7%) and (21%) in squamous cell carcinomas. IL-32 expression detected at the mRNA level (P = 0.007 vs. control), and its correlated with NF-κB activation (P = 0.003), and up-regulation of phospho p38MAPK (P= 0.004), and also increased in the cytokines concentration compared with the control samples. Conclusions: Understanding the pathway of IL-32 expression to stimulates the secretion cytokines via the activation of NF-κB and up-regulation of p- p38MAPK might be responsible in the esophageal carcinogenesis and used as tumor marker.
Metabolome analyses in human gastric cancer tissue using capillary electrophoresis time-of-flight mass spectrometry.
Authors: Terashima Masanori , Kusuhara Masatoshi , Kondo Junya , Tokunaga Masanori , Tanizawa Yutaka , Bando Etsuro , Kawamura Taiichi , Fujimori Tamaki , Yamamoto Hiroyuki , Ohashi Yoshiaki 
Published: February 2017

61 Background: In order to explore carcinogenic and prognostic biomarkers for gastric cancer, genomic, transcriptomic and proteomic approach had been extensively investigated. However, little information is possible for metabolomics profiles in gastric cancer. As cancer cells demonstrates distinguishable growth pattern from normal cells, presence of specific metabolic pathway in cancer cells is expected. Therefore, we investigated the metabolme profiles of gastric cancer tissue by capillary electrophoresis time-of-flight mass spectrometry (CE-TOFMS). Methods: Twenty seven patients with gastric cancer underwent gastrectomy were enrolled in this study. Cancer tissue and adjacent non-cancerous tissue were obtained from surgically resected sample and immediately frozen. Frozen tissues were homogenized and then applied to CF-TOFMS.The metabolomics data by CE-TOFMS were analyzed using principal component analysis (PCA) in order to compare the metabolic profiling of the non cancerous and the cancer tissues. Correlation between metabolic profile and clinicopathologic factors were also investigated. Results: A total of 245 metabolites were detected and quantified. In PCA, the first component separated the cancer tissue data from the non-cancerous tissue data. Metabolic data from cancer tissues showed severe heterogeneity. PCA based on the difference between cancer tissue and non-cancerous tissue revealed that metabolic profile of gastric cancer was classified into two groups. One cancer group (group 1) accumulated lactate and most amino acids excessively, and another group (group 2) didn’t. In group 1, the adenylate energy charge of the cancer tissues was maintained compared to that of the non-cancerous tissues.In comparison with clinicopathologic factors, only histological type demonstrated significant correlation with metabolic classification. Undifferentiated type was significantly predominant in group 2. Conclusions: Gastric cancer was classified into two groups by quantitative metabolome profiling. As this classification significantly correlated with histological type, existence of specific metabolic pathway related to histological type is suggested.
Potential of surgery and chemotherapy in patients with second metastatic recurrence after R0-resection of colorectal liver metastases.
Authors: Homayounfar Kia , Bleckmann Annalen , Conradi Lena , Sprenger Thilo , Niessner Martin , Lorf Thomas , Becker Heinz , Ghadimi Michael B. , Liersch Torsten 
Published: February 2017

644 Background: Surgical resection is the standard of care for resectable colorectal metastases (CRM). Preoperative chemotherapy allows assessment of tumorbiology and has been shown to convert approximately 30% of unresectable patients into secondary resectability. In patients with second metastatic recurrence (SMR), complete (R0) resection of all metastases seems to be accompanied with a survival benefit. The role of chemotherapy is unclear. Methods: Between 01/2001 and 31/08/2011 R0-resection could be achieved in 178 patients with liver only CRM at our institution. 103 patients developed SMR 10.4 ± 8.9 months after R0-resection of hepatic CRM. Of these, 79 patients had perioperative 5FU-based chemotherapy for treatment of the primary tumor and/or first liver metastases. Median follow-up from diagnosis of SMR was 21 (range 1-80) months. Results: SMR occurred in 80 patients at a single site (48x liver, 18x lung, 14x other) and in 23 patients at multiple sites (11x liver and lung, 7x including lung, 4x including liver, 1x other). 9 patients refused therapy and received best supportive care. 42 patients with single site recurrence were scheduled for primary surgery. R0-resection could be achieved in 26 patients (62%). 52 patients were treated with 8.1 ± 8 cycles of 5FU-based chemotherapy (5x 5FU/FS, 21x FOLFOX, 26x FOLFIRI) extended by the EGFR-antibody cetuximab (n=9) or the VEGF-antibody bevacizumab (n=18). 9 of these patients were scheduled for surgical exploration. R0-resection could be achieved in 5 patients with single site and 2 patients with multiple site recurrence. Morbidity and mortality rates for all operated patients were 16% and 0%, respectively. 5-years DFS rate for R0-resected patients was 20%. 5-years OS rate were 43% for R0-resected patients versus 11% for patients with R1/2 resection and palliative therapy (p<0.001). Conclusions: Surgical resection of SMR offers a survival benefit and became possible even in 7 of 52 patients (13%) initially treated by chemotherapy. Therefore, all therapeutic options should be used in patients with SMR to achieve R0-resection of CRM.
Should lymph node retrieval be a surgical quality indicator in colon cancer?
Authors: Musselman Reilly Patrick , Xie Mingyang , McLaughlin Kelsey , Moloo Husein , Boushey Robin P , Auer Rebecca Ann C 
Published: February 2017

648 Background: Adequate lymph node harvest is easily obtained and is necessary for proper staging of colorectal cancer, making it an attractive measure of surgical quality for policy makers. However, achieving an adequate lymph node harvest requires a multidisciplinary effort. The purpose of this study was to determine if it is appropriate to use this measure as a surgical quality indicator for individual surgeons. Methods: The study was undertaken at a high volume center with standardized colon cancer specimen processes. The charts of 1,138 consecutive segmental colon cancer surgeries performed between 2002 and 2008 were retrospectively analyzed. The primary outcome was inadequate lymph node retrieval for colon cancer surgery defined by fewer than 12 lymph nodes on pathology. Predictor variables were based on patient, surgeon, pathology and tumor related factors. Univariate analysis was performed on all potential predictor variables, followed by multivariate logistic regression. Results: 841 cases (69.0%) achieved adequate lymph node harvest, while 377 (31.0%) were inadequate. Factors on univariate analysis associated with inadequate lymph node harvest were specimen length (p<0.0001), tumor location (p<0.0001), and T-stage (0.0015), all of which remained significant multivariate logistic regression. The average specimen length differed by 3.6 cm between non-adequate and adequate specimens. When broken down by procedure, resection length did not vary significantly between high and low volume surgeons or between colorectal and non-colorectal surgeons. Furthermore when surgeons were ranked according to their success rate of >12 LN retrieval, there was no difference between surgeons in mean specimen length. Conclusions: In a high-volume, tertiary care centre that uses standardized practices for specimen processing, 31% of cases yielded fewer than 12 lymph nodes. Factors relating to the patient and tumor were the primary predictors of a successful outcome and there was no association between surgeon-related factor and adequate LN retrieval. Caution should be used when considering LN harvest as a surgical quality indicator for individual surgeons.
Dexamethasone as a means for controlling vascular pain caused by the administration of oxaliplatin via the peripheral vein and also for controlling oxaliplatin-induced hypersensitivity reactions.
Authors: Yoshida Yoichiro , Hoshino Seiichiro , Aisu Naoya , Shiwaku Hironari , Beppu Richiko , Tanimura Syu , Yamashita Yuichi 
Published: February 2017

662 Background: With the recent development of XELOX therapy involving oral administration of drug preparations, etc., implantation of a CV port can be now avoided. However, vascular pain (pain in the peripheral veins) occasionally requires switching of the drip infusion route during XELOX therapy. Some investigators reported that addition of steroids to oxaliplatin drip infusion is useful in controlling vascular pain. However, the pharmacological use of steroids can make oxaliplatin unstable due to the elevation of pH; further, the effectiveness of oxaliplatin in this therapy is unknown because of lack of published data. This study was undertaken to evaluate the effectiveness of dexamethasone (DEX) in infusion solution containing oxaliplatin for controlling vascular pain caused by the administration of oxaliplatin via the peripheral vein. Methods: The study included 47 patients (33 males and 14 females; median age, 64) who received XELOX + bevacizumab for metastatic colorectal cancer without implantation of a CV port. In all the patients, oxaliplatin (130 mg/m2) was administered in combination with DEX (6.6 mg) via the peripheral vein. Results: Vascular pain developed in 34 patients (72.3%), but it was transient. In only 1 of the 34 patients, the drip infusion route had to be switched to the opposite side because of vascular pain. No patients required CV port implantation. Grade 3 or higher hemotoxicity was noted in 14.9% of the patients, and grade 3 or higher nonhematological toxicity was noted in 21.2% of the patients. The response rate was 61.7%. Among 47 patients, no patients experienced hypersensitivity reactions to oxaliplatin. Conclusions: Addition of DEX to oxaliplatin drip infusion controlled vascular pain caused by the administration of oxaliplatin via the peripheral vein. The response rate to this therapy combined with the use of DEX suggests that DEX probably does not exert adverse effects on the therapy, ie, it does not affect the stability of oxaliplatin by elevating the pH. Furthermore, coinfusion of DEX to oxaliplatin may be a useful preventive method for oxaliplatin-induced hypersensitivity.
inSIRT trial: Single-center phase II study of yttrium-90 radioactive resin microspheres in the treatment of liver-predominant metastatic colorectal adenocarcinoma after failure of first-line combination chemotherapy.
Authors: Roeland Eric , Shimabukuro Kelly Anne , Fanta Paul Timothy , Rose Steven C. , Reid Tony R. 
Published: February 2017

685 Background: Liver metastases develop in half of colorectal cancer (CRC) cases and once metastatic ~90% die due to consequences from the hepatic metastases. We are evaluating the aggressive management of liver metastases through the incorporation of selective internal radiation therapy (SIRT) using yttrium-90 radioactive microspheres after evidence of progressive disease following first-line FOLFOX ± bevacizumab. Optimal timing for microsphere treatment relative to chemotherapy is not clearly established. We present preliminary data of a phase II study evaluating tumor response rates to SIRT following FOLFOX ± bevacizumab and prior to FOLFIRI. Methods: Subjects with predominant hepatic metastatic CRC despite first-line FOLFOX based therapy ± bevacizumab are eligible. Interventional radiology and nuclear medicine assess the liver lesions and the subject receives SIRT followed by second-line FOLFIRI (without bevacizumab) 4-6 weeks after the final SIRT. The primary objective is PFS at 6 mos and secondary objectives include: OS, tumor response rates, and toxicity. Results: To date, 8 metastatic CRC subjects have been treated and 9 subjects enrolled (goal 30 subjects). One subject was withdrawn due to progressive lung metastases. 4 of 8 subjects (50%) achieved PFS at 6 mos and average TTP is 6.7 mos (0.7-17.3 mos). Overall treatment has been well tolerated, but one possible study related SAE of liver failure occurred (subject 8). The OS endpoint has not been achieved. Conclusions: Historically, second-line FOLFIRI has achieved a 2.5 mos median PFS. In 8 subjects with liver predominant metastatic CRC, we have observed 50% PFS at 6 mos. These encouraging results demonstrate the utility of an innovative direct approach to metastatic CRC after failure of first-line combination chemotherapy. [Table: see text]