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Hanna T.P.,Queens University | Richardson H.,Queens University | Richardson H.,National Cancer Institute of Canada | Peng Y.,Queens University | And 3 more authors.
Clinical Oncology | Year: 2012

Aims: To describe the use of adjuvant radiotherapy for endometrial cancer in Ontario, and identify factors associated with its use, and to determine whether variation in the use of radiation is associated with differences in survival. Materials and methods: This was a retrospective, population-based, cohort study of all patients who had a hysterectomy for endometrial cancer in Ontario between 1992 and 2003. We used multiple logistic regression to identify health system-related factors associated with the use of radiotherapy, while controlling for disease- and patient-related factors. Survival and cancer cause-specific survival were compared among regions of the province with higher and lower rates of use of radiotherapy. Results: The study population included a total of 9411 women with a median age of 63 years. Overall, 26.2% received adjuvant radiotherapy. Patients living further from regional cancer centres were slightly less likely to receive radiation (P = 0.02). Patients who had their surgery during longer prevailing waiting times for radiotherapy were less likely to receive radiation (P = 0.04). The use of radiotherapy varied widely from 18.0 to 34.3% among the catchment areas of provincial radiotherapy centres (P < 0.0001). In the overall population, there was no difference in survival among regions with higher and lower rates of use of radiotherapy. However, in the subgroup of cases with clear cell and serous carcinomas, both overall survival and cancer cause-specific survival were significantly lower in regions with lower rates of use of radiotherapy (P < 0.05). This difference remained significant after controlling for other factors (P < 0.05; hazard ratio 1.43; 95% confidence limits 1.06-1.93). Conclusions: Health system-related factors unrelated to patients' needs affect the use of adjuvant radiotherapy in Ontario. Lower rates of use of adjuvant radiotherapy are associated with lower rates of survival in patients with serous and clear cell carcinomas. © 2012 The Royal College of Radiologists.

Harbison C.T.,Bristol Myers Squibb | Horak C.E.,Bristol Myers Squibb | Ledeine J.-M.,Bristol Myers Squibb | Mukhopadhyay P.,Bristol Myers Squibb | And 12 more authors.
Archives of Pathology and Laboratory Medicine | Year: 2013

Context.-The therascreen KRAS RGQ polymerase chain reaction kit is being developed as a companion diagnostic to aid clinicians, through detection of KRAS mutations, in the identification of patients with metastatic colorectal cancer (mCRC) who are more likely to benefit from cetuximab. Objective.-To assess whether KRAS mutation status, determined by using the therascreen KRAS kit, is a predictive marker of cetuximab efficacy. Design.-Tissue samples were obtained from patients with mCRC treated on the National Cancer Institute of Canada Clinical Trials Group (NCIC CTG) CO.17 phase 3 study of cetuximab plus best supportive care (BSC) versus BSC alone. Tumor DNA samples were assessed for the presence of KRAS mutations by using the therascreen KRAS kit. Efficacy and safety were assessed to determine whether mutation status was predictive of outcomes. Results.-Evaluable samples were available from 453 patients (79.2%) enrolled in the NCIC CTG CO.17 trial. The KRAS wild-type subset represented 54.1% (245 of 453) of the evaluated population. Median overall survival of patients with KRAS wild-type tumors was 8.6 months among those who received cetuximab plus BSC and 5.0 months among patients who received BSC alone (hazard ratio [HR], 0.63; P.002). Among patients with KRAS mutant mCRC, no meaningful difference in overall survival was observed between arms (HR, 0.91; P.55). These results are consistent with a previous report that analyzed patient tumor samples by using bidirectional sequencing. Conclusions.-These data support the utility of the therascreen KRAS kit as a means of selecting patients who may benefit from cetuximab therapy.

Pedeutour F.,University of Nice Sophia Antipolis | Pedeutour F.,Nice University Hospital Center | Maire G.,Queens University | Pierron A.,University of Nice Sophia Antipolis | And 10 more authors.
Virchows Archiv | Year: 2012

While surgery is the usual treatment for localized well-differentiated and dedifferentiated liposarcomas (WDLPS/DDLPS), the therapeutic options for patients with advanced disease are limited. The classical antimitotic treatments are most often inefficient. The establishment of genetically characterized cell lines is therefore crucial for providing in vitro models for novel targeted therapies. We have used spectral karyotyping, fluorescence in situ hybridization with whole chromosome painting and locus-specific probes, and array-comparative genomic hybridization to identify the chromosomal and molecular alterations of a novel cell line established from a recurring sclerosing WDLPS. The karyotype was hypertriploid and showed multiple structural anomalies. All cells retained the presence of a giant marker chromosome that had been previously identified in the primary cell cultures. This giant chromosome contained high-level amplification of chromosomal regions 12q13-21 and lacked the alpha-satellite centromeric sequences associated with WDLPS/DDLPS. The 12q amplicon was large, containing 370 amplified genes. The DNA copy number ranged from 3 to 57. The highest levels of amplification were observed at 12q14.3 for GNS, WIF1, and HMGA2. We analyzed the mRNA expression status by real-time reverse transcription polymerase chain reaction for six genes from this amplicon: MDM2, HMGA2, CDK4, TSPAN31, WIF1, and YEATS4. mRNA overexpression was correlated with genomic amplification. A second amplicon originating from 10p11-14 was also present in the giant marker chromosome. The 10p amplicon contained 62 genes, including oncogenes such as MLLT10, previously described in chimeric fusion with MLL in leukemias, NEBL, and BMI1. © 2012 Springer-Verlag.

Jeon J.,Dana-Farber Cancer Institute | Jeon J.,Yonsei University | Sato K.,Dana-Farber Cancer Institute | Niedzwiecki D.,Duke University | And 14 more authors.
Clinical Colorectal Cancer | Year: 2013

Background The impact of physical activity on survival outcomes in patients with recurrent colon cancer has not been studied. We tested the association between the level of postdiagnosis physical activity and survival outcomes of patients with recurrent colon cancer. Patients and Methods We conducted a prospective observational study of 237 patients with stage III colon cancer who had recurrence of disease. Physical activity was measured approximately 6 months after the completion of therapy (14 months after surgical resection) but before detection of recurrent disease. The primary end point of the study was survival time after recurrence. Results The hazard ratio comparing patients who reported at least 18 metabolic equivalent task (MET) hours per week of physical activity with those engaging in < 3 MET hours per week was 0.71 (95% confidence interval, 0.46-1.11). Increasing total MET hours of physical activity per week was associated with a borderline statistical significance trend for improved survival after recurrence (P =.052). The benefit of physical activity on survival was not significantly modified by sex, body mass index (BMI), number of positive lymph nodes, age, baseline performance status, adjuvant chemotherapy regimen, or recurrence-free survival period. Conclusion To our knowledge, this is the first study investigating the association of physical activity with survival outcome of patients with recurrent colon cancer. Although the association exceeded our predefined P trend <.05 for statistical significance, these findings warrant further studies of physical activity in patients with recurrent colorectal cancer. © 2013 Elsevier Inc. All rights reserved.

Goss P.E.,Massachusetts General Hospital | Ingle J.N.,Mayo Medical School | Martino S.,Los Angeles Clinic and Research Institute | Robert N.J.,Virgina Cancer Specialists | And 10 more authors.
Annals of Oncology | Year: 2013

Background: MA17 showed improved outcomes in postmenopausal women given extended letrozole (LET) after completing 5 years of adjuvant tamoxifen. Patients and methods: Exploratory subgroup analyses of disease-free survival (DFS), distant DFS (DDFS), overall survival (OS), toxic effects and of life (QOL) in MA17 were performed based on menopausal status atquality breast cancer diagnosis. Results: At diagnosis, 877 women were premenopausal and 4289 were postmenopausal. Extended LET was significantly better than placebo (PLAC) in DFS for premenopausal [hazard ratio (HR) = 0.26, 95% confidence interval (CI) 0.13-0.55; P = 0.0003] and postmenopausal women (HR = 0.67; 95% CI 0.51-0.89; P = 0.006), with greater DFS benefit in those premenopausal (interaction P = 0.03). In adjusted post-unblinding analysis, those who switched from PLAC to LET improved DDFS in premenopausal (HR = 0.15; 95% CI 0.03-0.79; P = 0.02) and postmenopausal women (HR = 0.45; 95% CI 0.22-0.94; P = 0.03). Conclusions: Extended LET after 5 years of tamoxifen was effective in pre- and postmenopausal women at diagnosis, and significantly better in those premenopausal. Women premenopausal at diagnosis should be considered for extended adjuvant therapy with LET if menopausal after completing tamoxifen. © The Author 2012. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved.

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