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Olson R.A.,Cancer Agency Center for the North | Olson R.A.,University of Northern British Columbia | Olson R.A.,University of British Columbia | Tiwana M.S.,Cancer Agency Center for the North | And 12 more authors.
International Journal of Radiation Oncology Biology Physics | Year: 2014

Purpose There is abundant evidence that a single fraction (SF) of palliative radiation therapy (RT) for bone metastases is equivalent to more protracted and costly multiple fraction courses. Despite this, there is low utilization of SFRT internationally. We sought to determine the utilization of SFRT in a population-based, publicly funded health care system. Methods and Materials All consecutive patients with bone metastases treated with RT during 2007 to 2011 in British Columbia (BC) were identified. Associations between utilization of SFRT and patient and provider characteristics were investigated. Results A total of 16,898 courses of RT were delivered to 8601 patients. SFRT was prescribed 49% of the time. There were positive relationships among SFRT utilization and primary tumor group (P<.001; most commonly in prostate cancer), worse prognosis (P<.001), increasing physician experience (P<.001), site of metastases (P<.001; least for spine metastases), and area of training (P<.001; most commonly for oncologists trained in the United Kingdom). There was wide variation in the prescription of SFRT across 5 regional cancer centers, ranging from 25.5% to 73.4%, which persisted after controlling for other, potentially confounding factors (P<.001). Conclusions The large variability in SFRT utilization across BC Cancer Agency (BCCA) cancer centers suggests there is a strong cultural effect, where physicians' use of SFRT is influenced by their colleagues' practice. SFRT use in BC was similar to that in other Canadian and western European reports but strikingly higher than in the United States. Further work is needed to standardize SFRT prescribing practices internationally for this common indication for RT, with the potential for huge health system cost savings and substantial improvements in patients' quality of life. © 2014 Elsevier Inc. All rights reserved.


Bergman A.M.,Cancer Agency Vancouver Center | Gete E.,Cancer Agency Vancouver Center | Duzenli C.,Cancer Agency Vancouver Center | Teke T.,Cancer Agency Center for Southern Interior
Journal of Applied Clinical Medical Physics | Year: 2014

A Monte Carlo (MC) validation of the vendor-supplied Varian TrueBeam 6 MV flattened (6X) phase-space file and the first implementation of the Siebers-Keall MC MLC model as applied to the HD120 MLC (for 6X flat and 6X flattening filter-free (6X FFF) beams) are described. The MC model is validated in the context of VMAT patient-specific quality assurance. The Monte Carlo commissioning process involves: 1) validating the calculated open-field percentage depth doses (PDDs), profiles, and output factors (OF), 2) adapting the Siebers-Keall MLC model to match the new HD120-MLC geometry and material composition, 3) determining the absolute dose conversion factor for the MC calculation, and 4) validating this entire linac/MLC in the context of dose calculation verification for clinical VMAT plans. MC PDDs for the 6X beams agree with the measured data to within 2.0% for field sizes ranging from 2 × 2 to 40 × 40 cm2. Measured and MC profiles show agreement in the 50% field width and the 80%-20% penumbra region to within 1.3 mm for all square field sizes. MC OFs for the 2 to 40 cm2 square fields agree with measurement to within 1.6%. Verification of VMAT SABR lung, liver, and vertebra plans demonstrate that measured and MC ion chamber doses agree within 0.6% for the 6X beam and within 2.0% for the 6X FFF beam. A 3D gamma factor analysis demonstrates that for the 6X beam, > 99% of voxels meet the pass criteria (3%/3 mm). For the 6X FFF beam, > 94% of voxels meet this criteria. The TrueBeam accelerator delivering 6X and 6X FFF beams with the HD120 MLC can be modeled in Monte Carlo to provide an independent 3D dose calculation for clinical VMAT plans. This quality assurance tool has been used clinically to verify over 140 6X and 16 6X FFF TrueBeam treatment plans.


Lefresne S.,Cancer Agency Vancouver Center | Berthelet E.,Cancer Agency Vancouver Center | Cashman R.,Cancer Agency Vancouver Center | Levy K.,Cancer Agency Vancouver Center | And 5 more authors.
Supportive Care in Cancer | Year: 2015

Purpose: The Vancouver Rapid Access (VARA) clinic aimed to deliver urgent palliative radiotherapy (RT) and holistic care to patients with newly diagnosed incurable lung cancer. The purpose of this paper is to describe the 9-month pilot phase of the clinic and to compare its efficacy to standard practice.Methods: A multidisciplinary team performed the initial consult, and if appropriate, the patient received RT the same day and was connected with supportive services as required. Patient and treatment details were prospectively collected. A retrospective chart review of similar patients in standard practice 1 year prior to VARA was performed. Variables compared between VARA and standard practice included RT wait times and supportive service referrals.Results: During the pilot phase, 58 patients were assessed. Forty percent were inpatients, and 62 % had an ECOG 2 or higher. Fifty-four patients received RT; the majority (72 %) received RT on the same day as their consultation, compared to 41 % in standard practice (p < 0.001). The most common sites treated were the bone (42 %), lung (34 %), and brain (14 %). More than half of VARA patients (54 %) were referred to an additional health service such as home care nursing compared to 31 % of standard practice patients (p = 0.01). The VARA clinic decreased the proportion of patients double-booked into an oncologists schedule from 23 to 13 % (p < 0.001).Conclusions: The VARA clinic has improved wait times for palliative RT, increased patient access to supportive services, and improved the workload for lung radiation oncologists. This clinic could serve as a model for other patients with incurable cancer. © 2014, Springer-Verlag Berlin Heidelberg.


Whelan T.J.,McMaster University | Olivotto I.A.,Tom Baker Cancer Center | Olivotto I.A.,Cancer Agency Vancouver Island Center | Parulekar W.R.,Queen's University | And 20 more authors.
New England Journal of Medicine | Year: 2015

Background Most women with breast cancer who undergo breast-conserving surgery receive wholebreast irradiation. We examined whether the addition of regional nodal irradiation to whole-breast irradiation improved outcomes. Methods We randomly assigned women with node-positive or high-risk node-negative breast cancer who were treated with breast-conserving surgery and adjuvant systemic therapy to undergo either whole-breast irradiation plus regional nodal irradiation (including internal mammary, supraclavicular, and axillary lymph nodes) (nodalirradiation group) or whole-breast irradiation alone (control group). The primary outcome was overall survival. Secondary outcomes were disease-free survival, isolated locoregional disease-free survival, and distant disease-free survival. Results Between March 2000 and February 2007, a total of 1832 women were assigned to the nodal-irradiation group or the control group (916 women in each group). The median follow-up was 9.5 years. At the 10-year follow-up, there was no significant between-group difference in survival, with a rate of 82.8% in the nodal-irradiation group and 81.8% in the control group (hazard ratio, 0.91; 95% confidence interval [CI], 0.72 to 1.13; P = 0.38). The rates of disease-free survival were 82.0% in the nodal-irradiation group and 77.0% in the control group (hazard ratio, 0.76; 95% CI, 0.61 to 0.94; P = 0.01). Patients in the nodal-irradiation group had higher rates of grade 2 or greater acute pneumonitis (1.2% vs. 0.2%, P = 0.01) and lymphedema (8.4% vs. 4.5%, P = 0.001). Conclusions Among women with node-positive or high-risk node-negative breast cancer, the addition of regional nodal irradiation to whole-breast irradiation did not improve overall survival but reduced the rate of breast-cancer recurrence. © 2015 Massachusetts Medical Society.


Chin E.,University of British Columbia | Chin E.,Cancer Agency Vancouver Center | Loewen S.K.,University of British Columbia | Loewen S.K.,Cancer Agency Vancouver Center | And 3 more authors.
Physics in Medicine and Biology | Year: 2013

Four-dimensional volumetric modulated arc therapy (4D VMAT) is a treatment strategy for lung cancers that aims to exploit relative target and tissue motion to improve organ at risk (OAR) sparing. The algorithm incorporates the entire patient respiratory cycle using 4D CT data into the optimization process. Resulting treatment plans synchronize the delivery of each beam aperture to a specific phase of target motion. Stereotactic body radiation therapy treatment plans for 4D VMAT, gated VMAT, and 3D VMAT were generated on three patients with non-small cell lung cancer. Tumour motion ranged from 1.4-3.4 cm. The dose and fractionation scheme was 48 Gy in four fractions. A B-spline transformation model registered the 4D CT images. 4D dose volume histograms (4D DVH) were calculated from total dose accumulated at the maximum exhalation. For the majority of OARs, gated VMAT achieved the most radiation sparing but treatment times were 77-148% longer than 3D VMAT. 4D VMAT plan qualities were comparable to gated VMAT, but treatment times were only 11-25% longer than 3D VMAT. 4D VMAT's improvement of healthy tissue sparing can allow for further dose escalation. Future study could potentially adapt 4D VMAT to irregular patient breathing patterns. © 2013 Institute of Physics and Engineering in Medicine.


Liu Z.,University of British Columbia | Li Y.,University of British Columbia | Lozada J.,University of British Columbia | Pan J.,Cancer Agency Vancouver Center | And 3 more authors.
Journal of Labelled Compounds and Radiopharmaceuticals | Year: 2012

A rapid, single step, aqueous 18F-labeling method that proceeds under mild conditions to provide radiotracers in high radiochemical yield and at high specific activity represents a long-standing challenge. Arylboronates capture aqueous 18F-fluoride ion in buffered pH 2-3 at moderate temperature to provide a highly polar 18F-ArBF3 - anion. Similarly, 19F-18F isotope exchange on a 19F-ArBF3 - should create an 18F-ArBF3 -. We hypothesized that this reaction would proceed in volumes that would be amenable to the high levels of 18F-activity used in clinical hospitals. In order to measure both radiochemical and chemical yields, along with specific activity, we linked an alkyne-19F-ArBF3 - to rhodamine azide by standard click chemistry to afford a precursor Rh-19F-ArBF 3 -. This precursor was aliquoted in portions of 50 nmol and lyophilized for on-demand use. Using robotic manipulators in a hot cell, we combined >29.6 GBq (800 mCi) and 50 nmol of the Rh-19F-ArBF 3 - in aqueous dimethylformamide at buffered pH 2-3. Following mild heating (40 °C) for 10-15 min, the reaction was quenched and analyzed. We observed radiochemical yields of 50% and specific activities of nearly 555 GBq/μmol (15 Ci/μmol). Similar radiochemical yields and slightly lower specific activities were also obtained with ~400 mCi (n = 2). With radiochemical yields in the hundreds of millicuries and specific activities that are 3-10-fold higher than most radiotracers, this method is very attractive method for preparing clinically useful radiotracers. Moreover, the ability to produce tracers at extraordinarily high specific activities expands the distribution time window from production labs to distant positron emission tomography scanners. Copyright © 2012 John Wiley & Sons, Ltd. The specific activity of most 18F-radiotracers is limited to ~6 Ci/μmol while labeling is often cumbersome due fluoride's lack of reactivity in water. With 800 mCi, an aryltrifluoroborate is 18F-labeled by isotope exchange at 30-40° C, buffered pH 2-3 in yields of 50% at specific activities of ~15 Ci/μmol in 10-15 minutes. To measure such high specific activity we took advantage of a pendant Rhodamine which now provides for 18F-labeled fluorophores at extraordinarily high specific activity in one step. Copyright © 2012 John Wiley & Sons, Ltd.


Gaudet M.,Cancer Agency Vancouver Center | Hamm J.,Center for Population Oncology and Outcomes | Aquino-Parsons C.,Cancer Agency Vancouver Center
Gynecologic oncology | Year: 2014

The objective of this study was to determine if women with a history of Cervical Intraepithelial Neoplasia grades 2 and 3 (CIN2 and CIN3) are at increased long-term risk for developing non-cervix HPV-related malignancies. Women diagnosed with CIN2 or CIN3 between 1980 and 2005 were identified from the British Columbia (BC) Cancer Agency Cervical Cancer Screening Program's database. These patients' records were then cross-referenced with the BC Cancer Registry for diagnosis of vulvar, vaginal, anal or head and neck (HN) cancers during the period subsequent to their diagnosis of CIN. Standardized incidence ratios (SIR) were generated according to expected rates of each cancer. 54,320 women with a diagnosis of CIN2 or CIN3 were identified between 1985 and 2005. The crude incidence rate for non-cervix HPV-related cancers was 35.4 per 100,000 person-years (8.6 for vagina, 17.6 for vulva, 3.7 for anal canal and 5.5 for HN). The SIR was 1.9 (95% CI 1.3-2.7) for all non-cervix cancers, 6.7 (95% CI: 3.0-12.8) for vagina, 2.9 (95% CI: 1.7-4.6) for vulva, 1.8 (95% CI: 0.4-4.7) for anal canal, and 0.6 (95% CI: 0.2-1.4) for HN. There were statistically significant increases in anal cancers for years 5-9 and in HN cancers for years 0.5-5. BC women with a history of CIN2 or CIN3 are at relatively high risk of developing non-cervical HPV-related malignancies. The findings of this study suggest that interventions such as vaccination against high-risk HPV or long-term screening for these other cancers should be evaluated. Crown Copyright © 2014. Published by Elsevier Inc. All rights reserved.


Kennecke H.,Cancer Agency Vancouver Center | Chen L.,University of British Columbia | Blanke C.D.,Cancer Agency Vancouver Center | Cheung W.Y.,Cancer Agency Vancouver Center | And 2 more authors.
Current Oncology | Year: 2013

Background The survival benefit for single-agent anti-epidermal growth factor receptor (EGFR) therapy compared with combination therapy with irinotecan in KRAS wildtype (wt) metastatic colorectal cancer (mcrc) patients in the third-line treatment setting is not known. The objective of the present study was to describe the characteristics of, and to compare survival outcomes in, two cohorts of patients treated with either singleagent panitumumab or combination therapy with cetuximab and irinotecan. Methods The study enrolled patients with KRAS wt mcrc previously treated with both irinotecan and oxaliplatin who had received either panitumumab or combination cetuximab-irinotecan before April 1, 2011, at the BC Cancer Agency (BCCA). Patients were excluded if they had received anti-egfr agents in earlier lines of therapy. Data were prospectively collected, except for performance status (PS), which was determined by chart review. Information about systemic therapy was extracted from the bcca Pharmacy Database. Results Of 178 eligible patients, 141 received panitumumab, and 37 received cetuximab-irinotecan. Compared with patients treated with cetuximab-irinotecan, panitumumab-treated patients were significantly older and more likely to have an Eastern Cooperative Oncology Group (ECOG) ps of 2 or 3 (27.7% vs. 2.7%, p = 0.001). Other baseline prognostic variables and prior and subsequent therapies were similar. Median overall survival was 7.7 months for the panitumumab group and 8.3 months for the cetuximab-irinotecan group. Multivariate analysis demonstrated that survival outcomes were similar regardless of the therapy selected (hazard ratio: 1.28; p = 0.34). An ECOG PS of 2 or 3 compared with 0 or 1 was the only significant prognostic factor in this treatment setting (hazard ratio: 3.37; p < 0.01). Conclusions Single-agent panitumumab and cetuximab-irinotecan are both reasonable third-line treatment options, with similar outcomes, for patients with chemoresistant mcrc. © 2013 Multimed Inc.


Chin E.,University of British Columbia | Otto K.,Cancer Agency Vancouver Center
Medical Physics | Year: 2011

Purpose: A novel 4D volumetric modulated arc therapy (4D-VMAT) planning system is presented where radiation sparing of organs at risk (OARs) is enhanced by exploiting respiratory motion of tumor and healthy tissues. Methods: In conventional radiation therapy, a motion encompassing margin is normally added to the clinical target volume (CTV) to ensure the tumor receives the planned treatment dose. This results in a substantial increase in dose to the OARs. Our 4D-VMAT algorithm aims to reduce OAR dose by incorporating 4D volumetric target and OAR motions directly into the optimization process. During optimization, phase correlated beam samples are progressively added throughout the full range of gantry rotation. The resulting treatment plans have respiratory phase-optimized apertures whose deliveries are synchronized to the patient's respiratory cycle. 4D-VMAT plans reduce dose to the OAR by: (1) eliminating the motion margin, (2) selectively redistributing OAR dose over the OAR volume, and (3) timing larger dose contributions (MU) to respiratory phases where greater separations between the target and OAR occur. Our 4D-VMAT algorithm was tested by simulating a variety of tumor motion amplitudes (0.5-2 cm) in the superior/inferior and anterior/posterior directions. 4D-VMAT's performance was compared against 3D-VMAT, gated VMAT and dynamic multileaf collimator (DMLC) ideal-tracking VMAT. Results: Results show that OAR sparing of 4D-VMAT was greater than 3D-VMAT in all cases due to the smaller PTV margin. Compared to DMLC ideal-tracking VMAT, 4D-VMAT's OAR sparing is superior only when the relative distance between the PTV and OAR is changing. For gated VMAT, results compared to 4D-VMAT are phantom dependent. There was negligible difference in plan qualities for the tested case of motion along the anterior/posterior axis. For motions along the superior/inferior axis, gated VMAT's narrow beam-on window reduces the OAR volume directly irradiated by the linac but also allows higher dose accumulation in the exposed OAR. In contrast, 4D-VMAT can reduce the OAR volume exposed to high doses but at the cost of redistributing the OAR dose over a larger volume. Finally for 4D-VMAT, an increase in tumor motion no longer resulted in greater irradiation of the OAR as seen in conventional 3D radiation therapy. OAR dose levels were preserved for increasing target motion along the anterior/posterior axis. For increasing superior/inferior motion, the volume of OAR exposed to high doses actually decreased due to dose redistribution. Conclusions: Our investigation demonstrated that the 4D-VMAT system has the potential to improve radiation therapy of periodically moving tumors over 3D-VMAT, gating or tracking methods. © 2011 American Association of Physicists in Medicine.


Teke T.,University of British Columbia | Bergman A.M.,Cancer Agency Vancouver Center | Kwa W.,Cancer Agency Vancouver Center | Gill B.,Cancer Agency Vancouver Center | And 2 more authors.
Medical Physics | Year: 2010

Purpose: A Monte Carlo (MC) based QA process to validate the dynamic beam delivery accuracy for Varian RapidArc™ (Varian Medical Systems, Palo Alto, CA) using Linac delivery log files (DynaLog) is presented. Using DynaLog file analysis and MC simulations, the goal of this article is to (a) confirm that adequate sampling is used in the RapidArc optimization algorithm (177 static gantry angles) and (b) to assess the physical machine performance [gantry angle and monitor unit (MU) delivery accuracy]. Methods: Ten clinically acceptable RapidArc treatment plans were generated for various tumor sites and delivered to a water-equivalent cylindrical phantom on the treatment unit. Three Monte Carlo simulations were performed to calculate dose to the CT phantom image set: (a) One using a series of static gantry angles defined by 177 control points with treatment planning system (TPS) MLC control files (planning files), (b) one using continuous gantry rotation with TPS generated MLC control files, and (c) one using continuous gantry rotation with actual Linac delivery log files. Monte Carlo simulated dose distributions are compared to both ionization chamber point measurements and with RapidArc TPS calculated doses. The 3D dose distributions were compared using a 3D gamma-factor analysis, employing a 3%/3 mm distance-to-agreement criterion. Results: The dose difference between MC simulations, TPS, and ionization chamber point measurements was less than 2.1%. For all plans, the MC calculated 3D dose distributions agreed well with the TPS calculated doses (gamma-factor values were less than 1 for more than 95% of the points considered). Machine performance QA was supplemented with an extensive DynaLog file analysis. A DynaLog file analysis showed that leaf position errors were less than 1 mm for 94% of the time and there were no leaf errors greater than 2.5 mm. The mean standard deviation in MU and gantry angle were 0.052 MU and 0.355°, respectively, for the ten cases analyzed. Conclusions: The accuracy and flexibility of the Monte Carlo based RapidArc QA system were demonstrated. Good machine performance and accurate dose distribution delivery of RapidArc plans were observed. The sampling used in the TPS optimization algorithm was found to be adequate. © 2010 American Association of Physicists in Medicine.

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