British Columbia Cancer Agency Vancouver Cancer Center

Vancouver, Canada

British Columbia Cancer Agency Vancouver Cancer Center

Vancouver, Canada
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Qiu Y.,British Columbia Cancer Agency Vancouver Cancer Center | Moiseenko V.,British Columbia Cancer Agency Vancouver Cancer Center | Popescu I.A.,British Columbia Cancer Agency Vancouver Cancer Center | Duzenli C.,British Columbia Cancer Agency Vancouver Cancer Center
Medical Physics | Year: 2010

Purpose: To assess risk of secondary malignancy associated with peripheral doses from kV CBCT for gynecological patients undergoing IMRT and to compare doses to organs peripheral to the treated volume from kV Cone Beam with scatter and leakage doses from MV IMRT. Method and Materials: In field and peripheral doses for kV CBCT gynecologic studies were simulated by Monte Carlo code BEAMnrc and DOSXYZnrc. Dose‐mean lineal energy based quality factor for kV beam was calculated to account for the difference of relative biological effectiveness between kV CBCT beams and MV beams. Life time attributable risk of cancer incidence (LAR) and relative risk (RR) for bladder and colon for patients undergoing IMRT and daily CBCT were estimated based on the Monte Carlo simulated equivalent doses. Peripheral dose from image‐guided radiation therapy (IGRT) using kV CBCT was evaluated relative to the scatter and leakage doses from the Linac delivering the IMRT treatment. Results: The estimated quality factor for CBCT is about 1.3 times that of MV beams. With daily imaging over a 25 fraction IMRT treatment regimen with prescribed dose of 4500 cGy RRs of cancer incidence for bladder and colon are 21.2 and 3.4 of which the contribution from CBCT is 1.83 and 1.20. In the peripheral region the average CBCT dose is of the same order of magnitude as the leakage dose. Scatter doses from the IMRT treatment are however a factor of 5 higher than the CBCT peripheral doses and leakage doses. Conclusion: Even with daily kV CBCT the relative risk caused by CBCT is much lower than the risk from IMRT scattering in both in field and peripheral regions. Understanding the relative risks associated with the doses from these procedures is important for designing appropriate CBCT protocols. Conflict of Interest: Research supported by Varian Medical Systems. © 2010, American Association of Physicists in Medicine. All rights reserved.

Kollmannsberger C.,British Columbia Cancer Agency Vancouver Cancer Center | Daneshmand S.,British Columbia Cancer Agency Vancouver Cancer Center | So A.,British Columbia Cancer Agency Vancouver Cancer Center | Chi K.N.,British Columbia Cancer Agency Vancouver Cancer Center | And 4 more authors.
Journal of Clinical Oncology | Year: 2010

Purpose: The management of patients with a radiographic complete response after chemotherapy remains controversial. The current study assesses the outcome for a modern, unselected patient population with disseminated testicular cancer with particular emphasis on those achieving a radiographic complete remission to combination chemotherapy. Patients and Methods: All patients with disseminated nonseminoma seen between 1999 and 2007 at the British Columbia Cancer Agency (BCCA) as well as through the Oregon Testis Cancer Program were retrospectively reviewed. A total of 276 patients treated with combination chemotherapy were identified. A radiographic complete remission (CR) was defined as disappearance of all metastatic lesions or minimal residual tissue ≤ 1 cm. Results: One hundred sixty-one patients achieved a CR. Results for the total population and CR subset were as follows: International Germ Cell Cancer Consensus Group stage good/intermediate/poor 84%/5%/ 11% (CR subset, 94%/3%/3%), presence of teratoma in the primary tumor 40% (CR subset, 55%), relapses 13%, death from disease 3% (CR subset, 6% and 0%, respectively). Two of the total 10 relapses in the CR group occurred beyond 2 years. Eight of the 10 relapses in the CR group were treated surgically for teratoma alone, whereas two required salvage chemotherapy. Disease-specific survival for the CR group was 100% after a median follow-up of 52 months (range, 3 to 135 months). Conclusion: Modern risk-adapted systemic chemotherapy with or without surgery for current populations of patients with disseminated testicular nonseminoma results in superb outcomes. Patients with disseminated germ cell tumors who obtain a complete serologic remission and no or minimal radiographic residual can be safely observed without adjunctive regional surgery. © 2009 by American Society of Clinical Oncology.

Oechsle K.,University of Hamburg | Lorch A.,Justus Liebig University | Honecker F.,University of Hamburg | Kollmannsberger C.,British Columbia Cancer Agency Vancouver Cancer Center | And 4 more authors.
Oncology | Year: 2010

Objectives: We investigated the pattern of relapse after chemotherapy in patients with high-risk germ cell tumor (GCT) to critically review common follow-up procedures including close monitoring of serum tumor markers and radiologic procedures. Methods: 645 patients received first-line (434 patients) or salvage platinum-based (211 patients) high-dose chemotherapy in three multicenter trials. Retrospective analysis comprised 77 patients after first-line and 61 after salvage chemotherapy, who had achieved at least a partial remission but progressed afterwards. Results: At relapse, 24% of the patients presented with an isolated elevation in serum tumor markers, 26% with pathologic radiologic confirmation with negative tumor markers, and 42% with elevated tumor markers and radiologically confirmed progression. Relapse was detected by clinical symptoms in 8%. 46% relapsed within 3 months and 97% within 2 years. Relapse pattern did not correlate with tumor marker status or metastasis location prior to chemotherapy, line of chemotherapy, response status after chemotherapy or time point of relapse. Conclusion: In high-risk GCT patients, relapse after chemotherapy is detected either by tumor marker elevation alone, radiologic imaging alone or both, in one third each. Close monitoring including serum tumor markers, radiologic imaging and clinical examination appears warranted within the first 2 years. Copyright © 2010 S. Karger AG.

Kollmannsberger C.,British Columbia Cancer Agency Vancouver Cancer Center | Bjarnason G.,Sunnybrook Odette Cancer Center | Burnett P.,Vanderbilt University | Creel P.,Duke University | And 11 more authors.
Oncologist | Year: 2011

The multitargeted tyrosine-kinase inhibitor sunitinib has emerged as one of the standards of care for goodand intermediate-risk metastatic renal cell carcinoma. Although generally associated with acceptable toxicity, sunitinib exhibits a novel and distinct toxicity profile that requires monitoring and management. Fatigue, diarrhea, anorexia, oral changes, hand-foot syndrome and other skin toxicity, thyroid dysfunction, myelotoxicity, and hypertension seem to be the most common and clinically relevant toxicities of sunitinib. Drug dosing and treatment duration are correlated with response to treatment and survival. Treatment recommendations for hypertension have been published but, currently, no standard guidelines exist for the management of noncardiovascular side effects. To discuss the optimal management of noncardiovascular side effects, an international, interdisciplinary panel of experts gathered in November 2009. Existing literature on incidence, severity, and underlying mechanisms of side effects as well as on potential treatment options were carefully reviewed and discussed. On the basis of these proceedings and the thorough review of the existing literature, recommendations were made for the monitoring, prevention, and treatment of the most common noncardiovascular side effects and are summarized in this review. The proactive assessment and consistent and timely management of sunitinib-related side effects are critical to ensure optimal treatment benefit by allowing appropriate drug dosing and prolonged treatment periods. © AlphaMed Press.

Renouf D.J.,University of Toronto | Moore M.J.,University of Toronto | Hedley D.,University of Toronto | Gill S.,British Columbia Cancer Agency Vancouver Cancer Center | And 9 more authors.
Investigational New Drugs | Year: 2012

Aim: This phase I/II study of saracatinib in combination with gemcitabine in patients with advanced pancreatic cancer was conducted by the NCIC Clinical Trials Group. The aims were to define the recommended phase II dose (RP2D) of saracatinib when combined with gemcitabine, and assess the efficacy of this combination in advanced pancreatic cancer. Patients and Methods: Eligibility criteria included locally advanced or metastatic pancreatic adenocarcinoma and no prior chemotherapy. In phase I saracatinib was escalated in combination with gemcitabine (1000 mg/m 2) to determine the recommended phase II dose (RP2D). The study was then expanded to a single arm phase II trial using a Simon 2-stage design. The primary endpoint was objective tumor response (OR) plus stable disease ≥4 months (SD4) rate; if ≥8 patients had OR+SD4, the study would proceed to stage 2. Results: Thirteen patients were enrolled into the phase I portion of this study. Saracatinib 175 mg PO daily was chosen as the RP2D in combination with gemcitabine. Twenty-one additional patients were then enrolled at the RP2D (phase II). Of the 22 response evaluable patients treated at the RP2D, 9 patients (40.9%) had progressive disease, 6 patients (27.3%) had stable disease for less than 4 months, 5 patients (22.7%) had SD4, and 2 patients (9.1%) had a partial response to treatment. Objective criteria for continuing to stage 2 were thus not met and the trial was closed following the accrual of 34 patients. Conclusion: Saracatinib 175 mg daily in combination with gemcitabine is well tolerated but the combination did not improve efficacy over what would be expected from gemcitabine alone. © Springer Science+Business Media, LLC 2010.

Nichols C.,Virginia Mason Medical Center | Kollmannsberger C.,British Columbia Cancer Agency Vancouver Cancer Center
Hematology/Oncology Clinics of North America | Year: 2011

The development of effective chemotherapy has been the defining event in the history of testicular cancer treatment. The discovery of cisplatin-based chemotherapy created a massive inflection that sharply defined the relatively grim precisplatin era from the astonishing postcisplatin era. The ripple effects of this discovery continue today with the rewriting of management of early-stage germ cell tumors to surveillance-based programs. This article reviews the discovery, development, and delivery of cisplatin-based chemotherapy; expected outcomes of chemotherapy treatment; remaining controversies in primary chemotherapy treatment of disseminated disease; and practical management tips for delivery of bleomycin, etoposide, and cisplatin and after chemotherapy treatment. © 2011 Elsevier Inc.

Deasy J.O.,University of Washington | Moiseenko V.,British Columbia Cancer Agency Vancouver Cancer Center | Marks L.,University of North Carolina at Chapel Hill | Nam J.,University of North Carolina at Chapel Hill | Eisbruch A.,University of Michigan
International Journal of Radiation Oncology Biology Physics | Year: 2010

Publications relating parotid dose-volume characteristics to radiotherapy-induced salivary toxicity were reviewed. Late salivary dysfunction has been correlated to the mean parotid gland dose, with recovery occurring with time. Severe xerostomia (defined as long-term salivary function of <25% of baseline) is usually avoided if at least one parotid gland is spared to a mean dose of less than ≈20 Gy or if both glands are spared to less than ≈25 Gy (mean dose). For complex, partial-volume RT patterns (e.g., intensity-modulated radiotherapy), each parotid mean dose should be kept as low as possible, consistent with the desired clinical target volume coverage. A lower parotid mean dose usually results in better function. Submandibular gland sparing also significantly decreases the risk of xerostomia. The currently available predictive models are imprecise, and additional study is required to identify more accurate models of xerostomia risk. © 2010 Elsevier Inc. All rights reserved.

PubMed | British Columbia Cancer Agency Vancouver Cancer Center and Queen Alexandra Hospital
Type: Journal Article | Journal: Cureus | Year: 2015

In the pre-human papillomavirus (HPV) era, unilateral radiation therapy (URT) for tonsil cancer was associated with low contralateral failure rates and had less toxicity than bilateral radiation therapy (BRT). This study explores the validity of URT in HPV-positive tonsil cancers.Tonsil squamous cell carcinomas (SCC) treated (typically with 70 Gy radiation and Cisplatin-based chemotherapy) between 2001 and 2007 were reviewed. Retrospective p16 immunohistochemistry staining was undertaken. Baseline, treatment, and response data were collected.Of 182 patients, 78% were p16-positive, were younger (predominantly male), mostly former or non-smokers, and had a more advanced nodal stage. With a median follow-up of 68 months, contralateral recurrence (CLR) rates were low (3.5% p16-positive versus 2.5% p16-negative, p=0.63). Overall survival (OS) was 74% for p16-positive versus 54% for p16-negative subjects (p=0.01), but all other outcomes were similar. Analysis amongst only p16-positive subjects revealed URT was delivered to 37%, with CLR rates of 7.5% versus 1.1% for those treated with BRT, p=0.05. Of the four p16-positive subjects treated with URT who developed contralateral recurrences, three were managed with neck dissection (two disease-free and one died of lung metastases)and one received palliative radiation to the neck and distant metastatic site. All disease control and survival outcomes were similar between those treated with URT versus BRT.While CLRs remain rare overall, there appears to be a slightly increased rate among HPV-positive subjects treated with URT. However, overall outcomes do not appear to be impacted, suggesting that URT remains a reasonable approach in HPV-positive subjects.

PubMed | University of Chicago, University of Oslo, Sloan Kettering Cancer Center, Dana-Farber Cancer Institute and 9 more.
Type: | Journal: Clinical cancer research : an official journal of the American Association for Cancer Research | Year: 2016

Cisplatin is one of the most commonly used chemotherapy drugs worldwide and one of the most ototoxic. We sought to identify genetic variants that modulate cisplatin-associated ototoxicity (CAO).We performed a genome-wide association study (GWAS) of CAO using quantitative audiometry (4-12 kHz) in 511 testicular cancer survivors of European genetic ancestry. We performed polygenic modeling and functional analyses using a variety of publicly available databases. We used an electronic health record cohort to replicate our top mechanistic finding.One SNP, rs62283056, in the first intron of Mendelian deafness gene WFS1 (wolframin ER transmembrane glycoprotein) and an expression quantitative trait locus (eQTL) for WFS1 met genome-wide significance for association with CAO (P=1.4x10We show for the first time the role of WFS1 in CAO and document a statistically significant interaction between increasing cumulative cisplatin dose and rs62283056 genotype. Our clinical translational results demonstrate that pre-therapy patient genotyping to minimize ototoxicity could be useful when deciding between cisplatin-based chemotherapy regimens of comparable efficacy with different cumulative doses.

PubMed | University of Toronto, British Columbia Cancer Agency Vancouver Cancer Center, Cross Cancer Institute, Juravinski Cancer Center and Tom Baker Cancer Center
Type: Journal Article | Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology | Year: 2017

113 Background: The COU-AA-301 trial showed that abiraterone (AA), an oral cytochrome p450 CYP17 inhibitor, improved survival for men with mCRPC progressing after docetaxel. AA is now a standard treatment in this setting. In order to better understand the non-clinical trial experience with AA, we undertook a multicenter retrospective analysis of patients (pts) treated with AA.Consecutive pts with mCRPC from 5 tertiary cancer centers in Canada who had received AA post-docetaxel were identified using centralized pharmacy records for each center. Pts who received AA for approved indications or within expanded access programs were included. Demographics, prognostic factors, treatment outcomes and toxicity profiles were collected.One hundred and eighty seven pts, who initiated AA between Jan-2011 and Jun-2012, were included. Median age at diagnosis and AA start was 65 and 73 years. 73 (39%) pts had M1 disease at diagnosis. ECOG 0/1/2/3 was noted in 17/96/39/8 pts. Median PSA at AA start was 132 with a median PSAdt of 2.8 months. 54 (29%) pts received more than 1 prior course of chemotherapy. Median follow up was 20.5 months. Median survival from start of AA was 9.3 months (95% CI, 7.9-12.6). Regional results were: Alberta 14 months (95% CI, 13-18); BC 8.2 months (95% CI, 5.4-9.6); and Ontario 7.3 months (95% CI, 5.7-8.1). Median overall survival from date of mCRPC was 36 months (95% CI, 29-40); in Alberta this was 39 months (95% CI, 29-47); BC 26 months (95% CI, 18-41); and Ontario 33 months (95% CI, 25-41). AA was well tolerated with toxicities comparable to those seen in the trial population, with anemia and fatigue being the most common reported toxicity.This is one of the largest cohorts of men with mCRPC treated with AA in the non-clinical trial setting. Treatment outcomes corroborate with results reported in clinical trials, supporting the effectiveness of AA in an unselected population. A difference in survival outcomes between the different cancer regions can be attributed to differences in time to AA start. Future analyses to evaluate potential prognostic/predictive factors will be undertaken.

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