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Edmonton, Canada

Yee D.,11560 University Ave | Rathee S.,Cross Cancer Institute | Robinson D.,Cross Cancer Institute | Murray B.,Cross Cancer Institute
International Journal of Radiation Oncology Biology Physics | Year: 2011

Purpose: Small-cell lung cancer is considered to be relatively chemosensitive and radiosensitive. Small-cell tumor volume changes during concurrent chemoradiotherapy have not been quantified. The purpose of this work is to quantify small-cell lung tumor volume variations in limited-stage patients undergoing chemoradiotherapy. Methods and Materials: Eligible patients had pathologically confirmed limited-stage small-cell lung cancer, underwent concurrent chemoradiotherapy, and signed study-specific consent forms. Patients underwent serial chest computed tomography (CT) scans on a CT simulator with images acquired at the same phase of patients' respiratory cycle. Computed tomography scans were obtained at the time of planning CT scan and 3 times a week during radiotherapy (RT). Gross tumor volumes (GTVs) were contoured on each CT scan. Gross tumor volumes defined on each CT scan were analyzed for volume changes relative to pre-RT scans. Results: We obtained 104 CT scans (median, 11.5 scans per patient). The median tumor dose was 50 Gy. The median pre-RT GTV was 98.9 cm 3 (range, 57.8-412.4 cm 3). The median GTV at the final serial CT scan was 10.0 cm 3 (range, 4.2-81.6 cm 3). The mean GTV relative to pre-RT volume at the end of each RT week was 53.0% for Week 1, 29.8% for Week 2, 22.9% for Week 3, 19.5% for Week 4, and 12.4% for Week 5. Conclusions: Dramatic shrinkage of small-cell lung tumors occurred in patients undergoing chemoradiotherapy in this trial. Most of the observed GTV shrinkage occurred during the first week of RT. © 2011 Elsevier Inc. Source

Trinh L.,University of Alberta | Plotnikoff R.C.,University of Alberta | Plotnikoff R.C.,University of Newcastle | Rhodes R.E.,University of Victoria | And 2 more authors.
Mental Health and Physical Activity | Year: 2013

Background: Adverse health effects of sedentary behaviour on cancer risk and health outcomes in cancer survivors have been reported but few studies have examined quality of life (QoL) and no study has focused on kidney cancer survivors (KCS). The purpose of this study was to estimate the prevalence of sitting time among KCS and to determine any associations with QoL. Methods: All 1985 KCS diagnosed between 1996 and 2010 identified through a Canadian provincial Registry were mailed a survey that consisted of the modified domain-specific sitting time questionnaire, the Godin Leisure Time Exercise Questionnaire and several Functional Assessment of Cancer Therapy (FACT) QoL scales. Standard demographic and medical variables were also reported. Results: Completed surveys were received from 540 KCS. The mean hours of sitting time were 8.0 ± 4.7 for a work-day and 6.5 ± 3.8 for a non-work day. After adjustment for key covariates, analyses of covariance indicated that the only significant relationship was an unexpected positive association between sitting time on a work day and emotional well-being (p = 0.019). Moreover, the only variable to moderate these associations was age, with younger KCS under age 60 showing the expected negative associations between sitting time and physical and functional aspects of QoL. Conclusion: KCS sit for a significant amount of time on work days and non-work days, however, there were few associations with QoL. Future observational studies and randomized controlled trials are warranted to examine sitting time and health outcomes among KCS. Crown Copyright © 2012 Published by Elsevier Ltd. All rights reserved. Source

Fairchild A.,11560 University Ave | Straube W.,Imaged Guided Therapy Center | Laurie F.,Review Centre | Followill D.,University of Houston
International Journal of Radiation Oncology Biology Physics | Year: 2013

Central review of radiation therapy (RT) delivery within multicenter clinical trials was initiated in the early 1970s in the United States. Early quality assurance publications often focused on metrics related to process, logistics, and timing. Our objective was to review the available evidence supporting correlation of RT quality with clinical outcomes within cooperative group trials. A MEDLINE search was performed to identify multicenter studies that described central subjective assessment of RT protocol compliance (quality). Data abstracted included method of central review, definition of deviations, and clinical outcomes. Seventeen multicenter studies (1980-2012) were identified, plus one Patterns of Care Study. Disease sites were hematologic, head and neck, lung, breast, and pancreas. Between 0 and 97% of treatment plans received an overall grade of acceptable. In 7 trials, failure rates were significantly higher after inadequate versus adequate RT. Five of 9 and 2 of 5 trials reported significantly worse overall and progression-free survival after poor-quality RT, respectively. One reported a significant correlation, and 2 reported nonsignificant trends toward increased toxicity with noncompliant RT. Although more data are required, protocol-compliant RT may decrease failure rates and increase overall survival and likely contributes to the ability of collected data to answer the central trial question. © 2013 Elsevier Inc. Source

Valdez B.C.,University of Houston | Valdez B.C.,University of Texas M. D. Anderson Cancer Center | Li Y.,University of Houston | Murray D.,11560 University Ave | And 2 more authors.
Biochemical Pharmacology | Year: 2011

DNA alkylating agents alone or with ionizing radiation have been the preferred conditioning treatment in allogeneic hematopoietic stem cell transplantation (allo-HSCT). In search of less toxic alternatives, we hypothesized that combination of busulfan (Bu), fludarabine (Flu) and clofarabine (Clo) would provide superior efficacy. At low concentrations, these drugs show synergistic cytotoxicity in Bu-resistant AML KBM3/Bu2506 cells. Similar molecular responses were observed in other AML cell lines and in primary explanted AML cells. The [Clo + Flu + Bu] combination activates an intense DNA damage response through the ATM pathway, leading to cell cycle checkpoint activation and apoptosis. Phosphorylations of SMC1 and SMC3, and methylations of histones 3 and 4, are much more pronounced in cells exposed to [Clo + Flu + Bu] than [Clo + Flu], suggesting their relevance in the efficacy of the triple-drug combination. A possible mechanism for these observed synergistic effects involves the capability of [Clo + Flu] to induce histone methylations and subsequent chromatin remodeling, which may render the genomic DNA more accessible to Bu alkylation. The Bu-mediated DNA cross-linking may provide a feedback loop which perpetuates the DNA damage response initiated by [Clo + Flu] and commits the cells to apoptosis. Our results provide a conceptual mechanistic basis for exploring this triple-drug combination in pretransplant conditioning therapy for allo-HSCT. Source

Makis W.,11560 University Ave | Kurzencwyg D.,McGill University | Hickeson M.,McGill University
Clinical Imaging | Year: 2013

The aim of this study was to examine whether positron emission tomography (PET)/computed tomography (CT) can detect more cases of colorectal cancer (CRC) than serum carcinoembryonic antigen (CEA), both at initial staging and during surveillance for recurrence. A retrospective review of 639 CRC patients imaged with PET/CT was performed. PET/CT was superior to serum CEA in detecting CRC, identifying 2.5 times as many CRC at initial staging compared to serum CEA and 1.5 times as many CRC recurrences. The current guideline recommendations of utilizing PET/CT only in the context of a rising serum CEA will miss more than one third of all CRC recurrences. © 2013 Elsevier Inc. Source

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