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Heng D.Y.C.,University of Calgary | Wells J.C.,University of Calgary | Rini B.I.,Cleveland Clinic | Beuselinck B.,University Hospitals Leuven | And 16 more authors.
European Urology | Year: 2014

Background The benefit of cytoreductive nephrectomy (CN) for overall survival (OS) is unclear in patients with synchronous metastatic renal cell carcinoma (mRCC) in the era of targeted therapy. Objective To determine OS benefit of CN compared with no CN in mRCC patients treated with targeted therapies. Design, setting, and participants Retrospective data from patients with synchronous mRCC (n = 1658) from the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) were used to compare 982 mRCC patients who had a CN with 676 mRCC patients who did not. Outcome measurements and statistical analysis OS was compared and hazard ratios (HRs) adjusted for IMDC poor prognostic criteria. Results and limitations Patients who had CN had better IMDC prognostic profiles versus those without (favorable, intermediate, or poor in 9%, 63%, and 28% vs 1%, 45%, and 54%, respectively). The median OS of patients with CN versus without CN was 20.6 versus 9.5 mo (p < 0.0001). When adjusted for IMDC criteria to correct for imbalances, the HR of death was 0.60 (95% confidence interval, 0.52-0.69; p < 0.0001). Patients estimated to survive <12 mo may receive marginal benefit from CN. Patients who have four or more of the IMDC prognostic criteria did not benefit from CN. Data were collected retrospectively. Conclusions CN is beneficial in synchronous mRCC patients treated with targeted therapy, even after adjusting for prognostic factors. Patients with estimated survival times <12 mo or four or more IMDC prognostic factors may not benefit from CN. This information may aid in patient selection as we await results from randomized controlled trials. Patient summary We looked at the survival outcomes of metastatic renal cell carcinoma patients who did or did not have the primary tumor removed. We found that most patients benefited from tumor removal, except for those with four or more IMDC risk factors. © 2014 Published by Elsevier B.V. on behalf of European Association of Urology.


Abouassaly R.,Case Western Reserve University | Fossa S.D.,University of Oslo | Giwercman A.,Skåne University Hospital | Kollmannsberger C.,Vancouver Cancer Center | And 3 more authors.
European Urology | Year: 2011

Context: Testicular cancer patients are often diagnosed at a young age, and because of the advances in the treatment of this disease, the vast majority have a normal life expectancy after therapy. Thus, recognition of the long-term sequelae of treatment (ie, surgery, radiation therapy, and chemotherapy) is particularly important in these patients. Objective: To review the adverse effects and the risk of secondary malignancy in long-term survivors of testicular cancer. Evidence acquisition: We conducted a Medline search to identify original articles and reviews on the long-term effects of testicular cancer treatment. Although the search included articles from January 1948 to February 2011, the majority of the included articles were published in the last two decades. Evidence synthesis: All studies examining the long-term sequelae of treatment in testicular cancer are retrospective in nature, with most classified as cohort, case-control, and/or epidemiologic studies. Given that no standardized method of reporting long-term complications exists, evidence synthesis is limited. Conclusions: Recent evidence suggests an increased risk of cardiovascular disease, neurotoxicity, and mild reductions in renal function in survivors of testicular cancer. Treatment of testicular malignancy can also negatively affect gonadal function and fertility and has been shown to result in an increased risk of solid malignancy and leukemia. © 2011 European Association of Urology.


Tyldesley S.,Vancouver Cancer Center | Delaney G.,University of New South Wales | Foroudi F.,Peter MacCallum Cancer Center | Barbera L.,Odette Cancer Center | And 2 more authors.
International Journal of Radiation Oncology Biology Physics | Year: 2011

Purpose: Estimates of the need for radiotherapy (RT) using different methods (criterion based benchmarking [CBB] and the Canadian [C-EBEST] and Australian [A-EBEST] epidemiologically based estimates) exist for various cancer sites. We compared these model estimates to actual RT rates for lung, breast, and prostate cancers in British Columbia (BC). Methods and Materials: All cases of lung, breast, and prostate cancers in BC from 1997 to 2004 and all patients receiving RT within 1 year (RT1Y) and within 5 years (RT 5Y) of diagnosis were identified. The RT1Y and RT 5Y proportions in health regions with a cancer center for the most recent year were then calculated. RT rates were compared with CBB and EBEST estimates of RT needs. Variation was assessed by time and region. Results: The RT1Y in regions with a cancer center for lung, breast, and prostate cancers were 51%, 58%, and 33% compared with 45%, 57%, and 32% for C-EBEST and 41%, 61%, and 37% for CBB models. The RT5Y rates in regions with a cancer center for lung, breast, and prostate cancers were 59%, 61%, and 40% compared with 61%, 66%, and 61% for C-EBEST and 75%, 83%, and 60% for A-EBEST models. The RT1Y rates increased for breast and prostate cancers. Conclusions: C-EBEST and CBB model estimates are closer to the actual RT rates than the A-EBEST estimates. Application of these model estimates by health care decision makers should be undertaken with an understanding of the methods used and the assumptions on which they were based. © 2011 Elsevier Inc.


Bhandare N.,University of Florida | Moiseenko V.,Vancouver Cancer Center | Song W.Y.,University of California at San Diego | Morris C.G.,University of Florida | And 2 more authors.
International Journal of Radiation Oncology Biology Physics | Year: 2012

Purpose: To investigate the incidence of severe dry eye syndrome (DES) after external beam radiotherapy for head-and-neck cancer and its dependence on the parameters relevant to external beam radiotherapy. Methods and Materials: The present retrospective study included 78 patients treated for primary extracranial head-and-neck tumors between 1965 and 2000, whose lacrimal apparatus/entire globe was exposed to fractionated external beam radiotherapy. The dose received by the major lacrimal gland was used for analysis. The end point of the present study was the ophthalmologic diagnosis of severe DES leading to vision compromise. Results: Of the 78 patients, 40 developed severe DES leading to visual compromise. The incidence of DES increased steadily from 6% at 35-39.99 Gy to 50% at 45-49.99 Gy and 90% at 60-64.99 Gy. With a mean of 0.9 years (range, 1 month to 3 years), the latency of DES was observed to be a function of the total dose and the dose per fraction. On univariate and multivariate analysis, the total dose (p <.0001 and p <.0001, respectively) and dose per fraction (p ≤.0001 and p =.0044, respectively) were significant. However, age, gender, and the use of chemoradiotherapy were not. The actuarial analysis indicated a 5-year probability of freedom from DES of 93% for doses <45 Gy, 29% for 45-59.9 Gy, and 3% doses ≥60 Gy. A logistic normal tissue complication probability model fit to our data obtained a dose of 34 and 38 Gy corresponding to a 5% and 10% incidence of DES. Conclusion: With a dose of 34 Gy corresponding to a 5% incidence of DES, the risk of severe DES increased, and the latency decreased with an increase in the total dose and dose per fraction to the lacrimal gland. The effect of chemoradiotherapy and hyperfractionation on the risk of DES needs additional investigation. Copyright © 2012 Elsevier Inc. Printed in the USA. All rights reserved.


Schneider B.P.,Indiana University | Gray R.J.,Dana-Farber Cancer Institute | Radovich M.,Indiana University | Shen F.,Indiana University | And 16 more authors.
Clinical Cancer Research | Year: 2013

Purpose: Clinically validated biomarkers for anti-angiogenesis agents are not available. We have previously reported associations between candidate VEGFA single-nucleotide polymorphisms (SNP) and overall survival (OS) in E2100. The associations between tumor VEGFA amplification and outcome are evaluated here. Experimental Design: E2100 was a phase III trial comparing paclitaxel with or without bevacizumab for patients with metastatic breast cancer. FISH to assess gene amplification status for VEGFA was conducted on paraffin-embedded tumors from 363 patients in E2100. Evaluation for association between amplification status and outcomes was conducted. Results: Estrogen receptor (ER)+ or progesterone receptor (PR)+ tumors were less likely to have VEGFA amplification than ER/PR- tumors (P = 0.020). VEGFA amplification was associated with worse OS (20.2 vs. 25.3 months; P = 0.013) in univariate analysis with a trend for worse OS in multivariate analysis (P = 0.08). There was a significant interaction between VEGFA amplification, hormone receptor status, and study arm. Patients with VEGFA amplification and triple-negative breast cancers (TNBC) or HER2 amplification had inferior OS (P = 0.047); amplification did not affect OS for those who were ER+ or PR+ and HER2-. Those who received bevacizumab with VEGFA amplification had inferior progression-free survival (PFS; P= 0.010) and OS (P = 0.042); no association was seen in the control arm. Test for interaction between study arm and VEGFA amplification with OS was not significant. Conclusion: VEGFA amplification in univariate analysis was associated with poor outcomes; this was particularly prominent in HER2+ or TNBCs. Additional studies are necessary to confirm the trend for poor OS seen on multivariate analysis for patients treated with bevacizumab. © 2012 American Association for Cancer Research.


Rennie H.,Abbotsford Cancer Center | MacKenzie G.,Vancouver Cancer Center
Journal of Cancer Education | Year: 2010

A psychosocial oncology learning needs assessment was developed and offered online to cancer care providers in a variety of settings across all health regions in British Columbia. The purpose was to better understand the psychosocial learning needs of cancer care providers and to use this knowledge to shape continuing education priorities. Respondents' preferred learning formats, access to technology and barriers to accessing psychosocial learning opportunities were also assessed. Cancer care providers including radiation therapists, social workers, dieticians, pharmacists, physicians and nurses in both community and agency settings were surveyed. Two hundred and sixtyseven people completed the survey. Key learning needs identified included cultural aspects of care, symptom management, treating the anxious patient, self-care for the professional, care of elderly patients, basic cancer-related medical issues surrounding care and ethics. Community respondents indicated more needs than agency respondents. On-site training was the most preferred learning format, and time constraints were the biggest barrier to accessing learning opportunities. Participants had access to technology. Next steps include conducting key informant and focus group interviews to determine if interest in a learning need is the same as a relevant knowledge and practice gap. This research suggests that cancer care providers are interested in learning more about the psychosocial issues related to cancer care. © Springer 2010.


Morris W.J.,Vancouver Cancer Center | Morris W.J.,University of British Columbia | Spadinger I.,Vancouver Cancer Center | Keyes M.,Vancouver Cancer Center | And 6 more authors.
Brachytherapy | Year: 2014

Purpose: To examine the relationship between whole prostate dose metrics and disease-free survival (DFS) after 125I low-dose-rate prostate brachytherapy (LDR-PB). Methods and Materials: Data for the first 2000 LDR-PB monotherapy implants were extracted from a database containing patient, tumor, dosimetric, and outcomes information. By National Comprehensive Cancer Network criteria, half (n=1006) had low-risk disease and half (n=990) had intermediate-risk disease (four had high-risk disease). Most patients (58.4%) and 75.3% of intermediate-risk patients received 3 months neoadjuvant and 3 months concomitant androgen deprivation therapy (ADT). Univariate and multivariate analyses were conducted using recognized prognostic factors and the whole prostate dose metrics D90 (the minimum dose received by 90% of the postimplant CT-based prostate volume) and V100 (the percent of the postimplant CT-based prostate volume that received at least 100% of the prescription dose). Results: The median followup is 5years (maximum, 12.5years); the 5-, 7-, and 10-year actuarial DFS estimates are 96.0%, 94.4%, and 93.0%, respectively. Of the recognized prognostic factors, only pretreatment prostate-specific antigen (p=0.012) and Gleason sum (p=0.010) were predictive of DFS. When analyzed as continuous variables, dose metrics were not predictive of DFS. However, most nonsignificant trends favored higher doses, and D90 values <130Gy were predictive of an increased risk of recurrence in the non-ADT subset (N=833; log rank, p=0.018). Conclusions: Although D90 values of <130Gy were predictive of an increased risk of recurrence in the non-ADT subset, neither D90 nor V100, when used as continuous variables, was predictive of DFS when applied to the entire cohort or in the subset analysis. This observation informs us that dose metrics are not equivalent to oncologic end points and must be calibrated against DFS for each physician and each institution offering LDR-PB. © 2014 American Brachytherapy Society.


Keyes M.,Vancouver Cancer Center | Macaulay C.,British Columbia Cancer Agency | Hayes M.,British Columbia Cancer Agency | Korbelik J.,British Columbia Cancer Agency | And 2 more authors.
International Journal of Radiation Oncology Biology Physics | Year: 2013

Purpose: To explore whether DNA ploidy of prostate cancer cells determined from archived transrectal ultrasound-guided biopsy specimens correlates with disease-free survival. Methods and Materials: Forty-seven failures and 47 controls were selected from 1006 consecutive low- and intermediate-risk patients treated with prostate 125I brachytherapy (July 1998-October 2003). Median follow-up was 7.5 years. Ten-year actuarial disease-free survival was 94.1%. Controls were matched using age, initial prostate-specific antigen level, clinical stage, Gleason score, use of hormone therapy, and follow-up (all P nonsignificant). Seventy-eight specimens were successfully processed; 27 control and 20 failure specimens contained more than 100 tumor cells were used for the final analysis. The Feulgen-Thionin stained cytology samples from archived paraffin blocks were used to determine the DNA ploidy of each tumor by measuring integrated optical densities. Results: The samples were divided into diploid and aneuploid tumors. Aneuploid tumors were found in 16 of 20 of the failures (80%) and 8 of 27 controls (30%). Diploid DNA patients had a significantly lower rate of disease recurrence (P=.0086) (hazard ratio [HR] 0.256). On multivariable analysis, patients with aneuploid tumors had a higher prostate-specific antigen failure rate (HR 5.13). Additionally, those with "excellent" dosimetry (V100 >90%; D90 >144 Gy) had a significantly lower recurrence rate (HR 0.25). All patients with aneuploid tumors and dosimetry classified as "nonexcellent" (V100 <90%; D90 <144 Gy) (5 of 5) had disease recurrence, compared with 40% of patients with aneuploid tumors and "excellent" dosimetry (8 of 15). In contrast, dosimetry did not affect the outcome for diploid patients. Conclusions: Using core biopsy material from archived paraffin blocks, DNA ploidy correctly classified the majority of failures and nonfailures in this study. The results suggest that DNA ploidy can be used as a useful marker for aggressiveness of localized prostate cancer. A larger study will be necessary to further confirm our hypothesis. © 2013 Elsevier Inc.


Nouranian S.,University of British Columbia | Mahdavi S.S.,University of British Columbia | Spadinger I.,Vancouver Cancer Center | Morris W.J.,Vancouver Cancer Center | And 2 more authors.
IEEE Transactions on Medical Imaging | Year: 2015

Low-dose-rate brachytherapy is a radiation treatment method for localized prostate cancer. The standard of care for this treatment procedure is to acquire transrectal ultrasound images of the prostate in order to devise a plan to deliver sufficient radiation dose to the cancerous tissue. Brachytherapy planning involves delineation of contours in these images, which closely follow the prostate boundary, i.e., clinical target volume. This process is currently performed either manually or semi-automatically, which requires user interaction for landmark initialization. In this paper, we propose a multi-atlas fusion framework to automatically delineate the clinical target volume in ultrasound images. A dataset of a priori segmented ultrasound images, i.e., atlases, is registered to a target image. We introduce a pairwise atlas agreement factor that combines an image-similarity metric and similarity between a priori segmented contours. This factor is used in an atlas selection algorithm to prune the dataset before combining the atlas contours to produce a consensus segmentation. We evaluate the proposed segmentation approach on a set of 280 transrectal prostate volume studies. The proposed method produces segmentation results that are within the range of observer variability when compared to a semi-automatic segmentation technique that is routinely used in our cancer clinic. © 2014 IEEE.


Simpson D.R.,University of California at San Diego | Song W.Y.,University of California at San Diego | Moiseenko V.,Vancouver Cancer Center | Rose B.S.,University of California at San Diego | And 3 more authors.
International Journal of Radiation Oncology Biology Physics | Year: 2012

Purpose: To test the hypothesis that increased bowel radiation dose is associated with acute gastrointestinal (GI) toxicity in cervical cancer patients undergoing concurrent chemotherapy and intensity-modulated radiation therapy (IMRT), using a previously derived normal tissue complication probability (NTCP) model. Methods: Fifty patients with Stage I-III cervical cancer undergoing IMRT and concurrent weekly cisplatin were analyzed. Acute GI toxicity was graded using the Radiation Therapy Oncology Group scale, excluding upper GI events. A logistic model was used to test correlations between acute GI toxicity and bowel dosimetric parameters. The primary objective was to test the association between Grade ≥2 GI toxicity and the volume of bowel receiving ≥45 Gy (V 45) using the logistic model. Results: Twenty-three patients (46%) had Grade ≥2 GI toxicity. The mean (SD) V 45 was 143 mL (99). The mean V 45 values for patients with and without Grade ≥2 GI toxicity were 176 vs. 115 mL, respectively. Twenty patients (40%) had V 45 >150 mL. The proportion of patients with Grade ≥2 GI toxicity with and without V 45 >150 mL was 65% vs. 33% (p = 0.03). Logistic model parameter estimates V50 and γ were 161 mL (95% confidence interval [CI] 60-399) and 0.31 (95% CI 0.04-0.63), respectively. On multivariable logistic regression, increased V 45 was associated with an increased odds of Grade ≥2 GI toxicity (odds ratio 2.19 per 100 mL, 95% CI 1.04-4.63, p = 0.04). Conclusions: Our results support the hypothesis that increasing bowel V 45 is correlated with increased GI toxicity in cervical cancer patients undergoing IMRT and concurrent cisplatin. Reducing bowel V 45 could reduce the risk of Grade ≥2 GI toxicity by approximately 50% per 100 mL of bowel spared. © 2012 Elsevier Inc. All rights reserved.

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