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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.

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.

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.

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.

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.

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