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Chicago Ridge, IL, United States

Von Mehren M.,Chase Medical | Rankin C.,Southwest Oncology Group | Goldblum J.R.,Cleveland Clinic | Demetri G.D.,Dana-Farber Cancer Institute | And 5 more authors.
Cancer | Year: 2012

BACKGROUND: Patients with advanced soft tissue sarcomas (STS) have limited therapeutic options. Sorafenib (BAY 43-9006) is a multitargeted tyrosine kinase inhibitor of raf, vascular endothelial growth factor receptors 1 (VEGFR1) through 3, platelet-derived growth factor B, fms-like tyrosine kinase 3, and c-kit, and some of these may be relevant in STS. METHODS: The authors tested sorafenib at a dose of 400 mg twice daily in patients with advanced vascular sarcoma (VS), high-grade liposarcomas, and leiomyosarcomas who had received 0 or 1 previous regimens for advanced disease. RESULTS: Fifty-one patients were accrued to the study, and 37 were evaluable for toxicity and response. There were no unexpected side effects and no confirmed responses. The median progression-free survival was 3 months, and the median overall survival was 17 months. Six of 8 patients in the VS cohort had prolonged clinical benefit (stable disease or better), resulting in a median progression-free survival of 5 months compared with 2 to 3 months for the patients who had liposarcoma and leiomyosarcomas. CONCLUSIONS: Sorafenib at the dose and schedule studied did not result in any responses in the VS, liposarcoma, or leiomyosarcoma cohort according to Response Evaluation Criteria in Solid Tumors. © 2011 American Cancer Society.

Sinicrope F.A.,North Central Cancer Treatment Group | Foster N.R.,North Central Cancer Treatment Group | Yothers G.,National Surgery Adjuvant Breast and Bowel Project | Benson A.,Eastern Cooperative Oncology Group | And 6 more authors.
Cancer | Year: 2013

BACKGROUND: Although obesity is an established risk factor for developing colon cancer, its prognostic impact and relation to patient sex in colon cancer survivors remains unclear. METHODS: The authors examined the prognostic and predictive impact of the body mass index (BMI) in patients with stage II and III colon carcinoma (N = 25,291) within the Adjuvant Colon Cancer Endpoints (ACCENT) database. BMI was measured at enrollment in randomized trials of 5-fluorouracil-based adjuvant chemotherapy. Association of BMI with the time to recurrence (TTR), disease-free survival (DFS), and overall survival (OS) were determined using Cox regression models. Statistical tests were 2-sided. RESULTS: During a median follow-up of 7.8 years, obese and underweight patients had significantly poorer survival compared with overweight and normal-weight patients. In a multivariable analysis, the adverse prognostic impact of BMI was observed among men but not among women (Pinteraction =.0129). Men with class 2 and 3 obesity (BMI ≥35.0 kg/m2) had a statistically significant reduction in DFS (hazard ratio [HR], 1.16; 95% confidence interval [CI], 1.01-1.33; P =.0297) compared with normal-weight patients. Underweight patients had a significantly shorter TTR and reduced DFS (HR, 1.18; 95% CI, 1.09-1.28; P <.0001) that was more significant among men (HR, 1.31; 95% CI, 1.15-1.50; P <.0001) than among women (HR, 1.11; 95% CI, 1.01-1.23; P =.0362; Pinteraction =.0340). BMI was not predictive of a benefit from adjuvant treatment. CONCLUSIONS: Obesity and underweight status were associated independently with inferior outcomes in patients with colon cancer who received treatment in adjuvant chemotherapy trials. © 2013 American Cancer Society.

Khandanpour C.,University of Montreal | Khandanpour C.,University of Duisburg - Essen | Khandanpour C.,Universitatsklinikum Essen | Thiede C.,Universitatsklinikum Carl Gustav Carus | And 25 more authors.
Blood | Year: 2010

The GFI1 gene encodes a transcriptional repressor, which regulates myeloid differentiation. In the mouse, Gfi1 deficiency causes neutropenia and an accumulation of granulomonocytic precursor cells that is reminiscent of a myelodysplastic syndrome. We report here that a variant allele of GFI1 (GFI136N) is associated with acute myeloid leukemia (AML) in white subjects with an odds ratio of 1.6 (P < 8 x 10-5). The GFI1 36N variant occurred in 1806 AML patients with an allele frequency of 0.055 compared with 0.035 in 1691 healthy control patients in 2 independent cohorts. We observed that both GFI1 variants maintain the same activity as transcriptional repressors but differ in their regulation by the AML1/ETO (RUNX1/RUNX1T1) fusion protein produced in AML patients with a t(8;21) translocation. AML1/ETO interacts and colocalizes with the more common GFI1 36S form in the nucleus and inhibits its repressor activity. However, the variant GFI136N protein has a different subnuclear localization than GFI136S. As a consequence, AML1/ETO does not colocalize with GFI1 36N and is unable to inhibit its repressor activity. We conclude that both variants of GFI1 differ in their ability to be regulated by interacting proteins and that the GFI136N variant form exhibits distinct biochemical features that may confer a predisposition to AML. © 2010 by The American Society of Hematology.

Tsao M.-S.,A+ Network | Sakurada A.,Ontario Cancer Institute | Aviel-Ronen S.,A+ Network | Ludkovski O.,Ontario Cancer Institute | And 8 more authors.
Journal of Thoracic Oncology | Year: 2011

PURPOSE: Patients with non-small cell lung carcinoma with epidermal growth factor receptor (EGFR) mutations may have a more favorable prognosis and greater response to chemotherapy. The effect of EGFR mutation and gene copy on patients with early-stage non-small cell lung carcinoma receiving adjuvant chemotherapy has not been reported. PATIENTS AND METHODS: Tumor samples from NCIC Clinical Trials Group JBR.10, an adjuvant trial of vinorelbine/cisplatin adjuvant chemotherapy [ACT] versus observation (OBS), were analyzed for EGFR mutation by multiple sensitive methods and copy number by fluorescent in situ hybridization. Their prognostic and predictive roles were explored in correlation with survival. RESULTS: Mutation results were available in 221 OBS and 215 ACT and fluorescent in situ hybridization results in 159 OBS and 163 ACT patients. Mutations were identified in 43 (27 OBS and 16 ACT) patients (36 sensitizing exon 19 deletions or L858R mutations). Compared with wild-type, sensitizing mutations were not significantly prognostic in OBS patients (hazard ratio [HR]: 0.79, 95% confidence interval [CI]: 0.38-1.63, p = 0.53). Although the presence of sensitizing mutations resulted in relatively greater benefit in ACT patients (HR: 0.44, 95% CI: 0.11-1.70, p = 0.22) compared with wild-type patients (HR: 0.78, 95% CI: 0.58-1.06, p = 0.12), this quantitative difference was not significant (interaction p = 0.50). Similarly, high EGFR copy was neither significantly prognostic nor predictive, although quantitatively it was associated with greater benefit from ACT. CONCLUSIONS: Trends toward longer survival and a greater benefit from chemotherapy were observed in patients with exon 19/21 mutations and high EGFR copy, although the differences were not statistically significant. The interpretation of the results was limited by the low EGFR mutation rate in this study of mainly white patients. Copyright © 2010 by the international Association fot the Study of lung Cancer.

Kornblith A.B.,Cancer and Leukemia Group B | Mirabeau-Beale K.,Harvard University | Lee H.,Massachusetts General Hospital | Goodman A.K.,Massachusetts General Hospital | And 3 more authors.
Journal of Psychosocial Oncology | Year: 2010

This study described the long-term adjustment of 42 ovarian cancer survivors diagnosed with advanced-stage disease with no evidence of recurrence, a mean of 6.1 years postdiagnosis. 64% of survivors' mental health was at or above the norm of medical outpatients (Mental Health Inventory-17). No patients reported post-traumatic stress disorder at a diagnosable level (Post-Traumatic Stress Disorder (PTSD) Checklist-Civilian). The majority of survivors ( 75%) reported a positive impact of cancer on their lives (Impact of Cancer Scale) and excellent social support (Medical Outcomes Study Social Support Survey). However, a subset of survivors reported needing more help than was received regarding emotional problems (28.9%). Copyright © Taylor & Francis Group, LLC.

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