Sobral-Filho R.G.,University of Victoria |
Brito-Silva A.M.,University of Victoria |
Isabelle M.,British Columbia Cancer Agency Vancouver Island Center |
Isabelle M.,Gloucestershire Hospitals NHS Foundation Trust |
And 4 more authors.
Chemical Science | Year: 2017
Fine-tuned gold and silver nanoshells were produced via an entirely reformulated synthesis. The new method yielded ultramonodisperse samples, with polydispersity indexes (PI) as low as 0.02 and narrow extinction bands suited for multiplex analysis. A library of nanoshell samples with localized surface plasmon resonances (LSPR) spanning across the visible range was synthesized. Hyperspectral analysis revealed that the average scattering spectrum of 100 nanoshells matched closely to the spectrum of a single nanoshell, indicating an unprecedented low level of nanoparticle-to-nanoparticle variation for this type of system. A cell labeling experiment, targeting different subcellular compartments in MCF-7 human breast cancer cells, demonstrated that these monodisperse nanoparticles can be used as a multiplex platform for single cell analysis at the intracellular and extracellular level. Antibody-coated gold nanoshells targeted the plasma membrane, while silver nanoshells coated with a nuclear localization signal (NLS) targeted the nuclear membrane. A fluorescence counterstaining experiment, as well as single cell hyperspectral microscopy showed the excellent selectivity and specificity of each type of nanoparticle for its designed subcellular compartment. A time-lapse photodegradation experiment confirmed the enhanced stability of the nanoshells over fluorescent labeling and their capabilities for long-term live cell imaging. © The Royal Society of Chemistry.
Pere H.,University of Paris Descartes |
Montier Y.,University of Paris Descartes |
Bayry J.,University of Paris Descartes |
Quintin-Colonna F.,University of Paris Descartes |
And 20 more authors.
Blood | Year: 2011
Regulatory T cells (Tregs) may impede cancer vaccine efficacy in hematologic malignancies and cancer. CCR4 antagonists, an emergent class of Treg inhibitor, have been shown to block recruitment of Tregs mediated by CCL22 and CCL17. Our aim was to demonstrate the ability of a CCR4 antagonist (a small chemical molecule identified in silico) when combined with vaccines to break peripheral tolerance controlled by Tregs, a prerequisite for the induction of CD8+ T cells against self Ags. Immunization of transgenic or normal mice expressing tumor-associated self Ags (Her2/neu, OVA, gp100) with a CCR4 antagonist combined with various vaccines led to the induction of effector CD8+ T cells and partial inhibition of tumor growth expressing self Ags in both prophylactic and therapeutic settings. The CCR4 antagonist was more efficient than cyclophosphamide to elicit anti-self CD8+ T cells. We also showed that the population of Tregs expressing CCR4 corresponded to memory (CD44high) and activated (ICOS+) Tregs, an important population to be targeted to modulate Treg activity. CCR4 antagonist represents a competitive class of Treg inhibitor able to induce functional anti-self CD8+ T cells and tumor growth inhibition when combined with vaccines. High expression of CCR4 on human Tregs also supports the clinical development of this strategy. © 2011 by The American Society of Hematology.
Volumetric Modulated Arc Therapy Improves Dosimetry and Reduces Treatment Time Compared to Conventional Intensity-Modulated Radiotherapy for Locoregional Radiotherapy of Left-Sided Breast Cancer and Internal Mammary Nodes
Popescu C.C.,British Columbia Cancer Agency Vancouver Island Center |
Olivotto I.A.,British Columbia Cancer Agency Vancouver Island Center |
Olivotto I.A.,University of British Columbia |
Beckham W.A.,British Columbia Cancer Agency Vancouver Island Center |
And 7 more authors.
International Journal of Radiation Oncology Biology Physics | Year: 2010
Purpose: Volumetric modulated arc therapy (VMAT) is a novel extension of conventional intensity-modulated radiotherapy (cIMRT), in which an optimized three-dimensional dose distribution may be delivered in a single gantry rotation. VMAT is the predecessor to RapidArc (Varian Medical System). This study compared VMAT with cIMRT and with conventional modified wide-tangent (MWT) techniques for locoregional radiotherapy for left-sided breast cancer, including internal mammary nodes. Methods and Materials: Therapy for 5 patients previously treated with 50 Gy/25 fractions using nine-field cIMRT was replanned with VMAT and MWT. Comparative endpoints were planning target volume (PTV) dose homogeneity, doses to surrounding structures, number of monitor units, and treatment delivery time. Results: For VMAT, two 190° arcs with 2-cm overlapping jaws were required to optimize over the large treatment volumes. Treatment plans generated using VMAT optimization resulted in PTV homogeneity similar to that of cIMRT and MWT. The average heart volumes receiving >30 Gy for VMAT, cIMRT, and MWT were 2.6% ± 0.7%, 3.5% ± 0.8%, and 16.4% ± 4.3%, respectively, and the average ipsilateral lung volumes receiving >20 Gy were 16.9% ± 1.1%, 17.3% ± 0.9%, and 37.3% ± 7.2%, respectively. The average mean dose to the contralateral medial breast was 3.2 ± 0.6 Gy for VMAT, 4.3 ± 0.4 Gy for cIMRT, and 4.4 ± 4.7 Gy for MWT. The healthy tissue volume percentages receiving 5 Gy were significantly larger with VMAT (33.1% ± 2.1%) and IMRT (45.3% ± 3.1%) than with MWT (19.4% ± 3.7%). VMAT reduced the number of monitor units by 30% and the treatment time by 55% compared with cIMRT. Conclusions: VMAT achieved similar PTV coverage and sparing of organs at risk, with fewer monitor units and shorter delivery time than cIMRT. Crown Copyright © 2010.
West N.R.,British Columbia Cancer Agency |
West N.R.,University of Victoria |
Milne K.,British Columbia Cancer Agency |
Truong P.T.,British Columbia Cancer Agency Vancouver Island Center |
And 7 more authors.
Breast Cancer Research | Year: 2011
Introduction: Infiltration of breast tumors by tumor-infiltrating lymphocytes (TIL) has been associated with sensitivity to anthracycline-based chemotherapy. However, it is unclear whether this is true within the estrogen receptor-alpha (ER)-negative subset of breast tumors that frequently manifest high TIL levels.Methods: The association of TIL with short-term and long-term clinical response to anthracycline-based therapy was assessed in two independent ER-negative breast cancer cohorts in which patients were categorized as TIL-high or TIL-low. We defined an eight-gene lymphocyte mRNA expression signature (including CD19, CD3D, CD48, GZMB, LCK, MS4A1, PRF1, and SELL) and used unsupervised hierarchical clustering to examine the association between TIL and short-term response to neoadjuvant chemotherapy in a previously published cohort of ER-negative tumors (n = 113). We also examined the association between TIL and long-term chemotherapeutic efficacy in a second cohort of ER-negative tumors (n = 255) with longer than 6 years of median follow-up by using tissue microarrays and immunohistochemistry (IHC) for detection of CD3, CD8, CD4, CD20, and TIA-1.Results: In patients with ER-negative tumors treated with neoadjuvant anthracycline-based chemotherapy, pathologic complete responses (pCRs) were achieved by 23 (74%) of 31 TIL-high patients and 25 (31%) of 80 TIL-low patients (odds ratio (OR), 6.33; 95% confidence interval (CI), 2.49 to 16.08; P < 0.0001). Multivariate logistic regression with standard clinicopathologic features demonstrated that only tumor size (P = 0.037) and TIL status (P = 0.001) were independent predictors of anthracycline response. In the second cohort, adjuvant anthracycline-based therapy was associated with increased disease-free survival (DFS) only in patients with high levels of intraepithelial CD3 +TIL (P = 0.0023). In contrast, outcomes after CMF treatment (cyclophosphamide, methotrexate, and fluorouracil) showed no association with CD3 status. In both cohorts, cytotoxic T-cells were the primary TIL subtype associated with anthracycline sensitivity. Finally, TIL significantly predicted anthracycline sensitivity for both the Her2-positive and triple-negative tumor phenotypes.Conclusions: ER-negative breast cancers with high levels of TIL have heightened sensitivity to anthracycline-based chemotherapy, as assessed by the immediate response to neoadjuvant therapy and long-term outcome following adjuvant therapy. Investigations of TIL-based predictive tests to identify patients likely to benefit from anthracycline-based treatments are warranted. © 2011 West et al.; licensee BioMed Central Ltd.
Popescu C.C.,British Columbia Cancer Agency Vancouver Island Center |
Beckham W.A.,British Columbia Cancer Agency Vancouver Island Center |
Beckham W.A.,University of Victoria |
Patenaude V.V.,British Columbia Cancer Agency Vancouver Island Center |
And 4 more authors.
Journal of Applied Clinical Medical Physics | Year: 2013
The purpose of this study was to compare the dosimetry of CG-Darc with three-dimensional conformal radiation therapy (3D CRT) and volumetric-modulated arc therapy (RapidArc) in the treatment of breast cancer with APBI. CG-Darc plans were generated using two tangential couch arcs combined with a simultaneous noncoplanar gantry arc. The dynamic couch arc was modeled by consecutive IMRT fields at 10° intervals. RapidArc plans used a single partial arc with an avoidance sector, preventing direct beam exit into the thorax. CG-Darc and RapidArc plans were compared with 3D CRT in 20 patients previously treated with 3D CRT (group A), and in 15 additional patients who failed the dosimetric constraints of the Canadian trial and of NSABP B-39/RTOG 0413 for APBI (group B). CG-Darc resulted in superior target coverage compared to 3D CRT and RapidArc (V95%: 98.2% vs. 97.1% and 95.7%). For outer breast lesions, CG-Darc and RapidArc significantly reduced the ipsilateral breast V50% by 8% in group A and 15% in group B (p < 0.05) as compared with 3D CRT. For inner and centrally located lesions, CG-Darc resulted in significant ipsilateral lung V10% reduction when compared to 3D CRT and RapidArc (10.7% vs. 12.6% and 20.7% for group A, and 15.1% vs. 25.2% and 27.3% for group B). Similar advantage was observed in the dosimetry of contralateral breast where the percent maximum dose for CG-Darc, 3D CRT, and RapidArc were 3.9%, 6.3%, and 5.8% for group A and 4.3%, 9.2%, and 6.3% for group B, respectively (p
Campbell W.G.,University of Victoria |
Wells D.M.,British Columbia Cancer Agency Vancouver Island Center |
Jirasek A.,University of British Columbia
IFMBE Proceedings | Year: 2015
A new method is introduced for evaluating the radiation-induced polymer distributions in polymer gel dosimeters. Destructive backscatter-based readout (DBBR) involves the careful slicing and scanning of dosimeters using dual chromatic scans (e.g., red and blue). Spectral differences in scatter attenuation coefficients cause blue light to be more likely to be scattered by polymers than red light. Comparing the intensities of backscattered red and blue photons allows one to evaluate polymer density. Two polymer gel dosimeters were irradiated, sliced and scanned using the DBBR method. Scans of central slices in two different irradiation patterns were acquired using a flatbed scanner, and [‘blue channel’ – ‘red channel’] images were used to measure polymer distributions. DBBR scan results were then compared against dose distributions calculated by treatment planning software, and select regions of interest from each scan allowed for a quantitative comparison between DBBR values and dose. For comparison, reconstructions were also obtained for the same dosimeters (prior to their destruction) using a fan-beam optical computed tomography scanner. © Springer International Publishing Switzerland 2015.
Lightstone A.W.,University of Toronto |
Tsao M.,University of Toronto |
Basran P.S.,British Columbia Cancer Agency Vancouver Island Center |
Chan G.,University of Toronto |
And 4 more authors.
Technology in Cancer Research and Treatment | Year: 2012
Patients receiving fractionated intensity-modulated radiation therapy (IMRT) for brain tumors are often immobilized with a thermoplastic mask; however, masks do not perfectly re-orient the patient due to factors including the maximum pressure which can be applied to the face, deformations of the mask assembly, patient compliance, etc. Consequently, ~3-5 mm PTV margins (beyond the CTV) are often recommended. We aimed to determine if smaller PTV margins are feasible using mask immobilization coupled with 1) a gantry mounted CBCT image guidance system and 2) position corrections provided by a full six-degree of freedom (6-DOF) robotic couch. A cohort of 34 brain tumor patients was treated with fractionated IMRT. After the mask set-up, an initial CBCT was obtained and registered to the planning CT. The robotic couch corrected the misalignments in all 6-DOF and a pre-treatment verification CBCT was then obtained. The results indicated a repositioning alignment within our threshold of 1.5 mm (3D). Treatment was subsequently delivered. A post-treatment CBCT was obtained to quantify intra-fraction motion. Initial, pre-treatment and post-treatment CBCT image data was analyzed. A total of 505 radiation fractions were delivered to the 34 patients resulting in ~1800 CBCT scans. The initial median 3D (magnitude) set-up positioning error was 2.60 mm. Robotic couch corrections reduced the 3D median error to 0.53 mm prior to treatment. Intra-fraction movement was responsible for increasing the median 3D positioning error to 0.86 mm, with 8% of fractions having a 3D positioning error greater than 2 mm. Clearly CBCT image guidance coupled with a robotic 6-DOF couch dramatically improved the positioning accuracy for patients immobilized in a thermoplastic mask system; however, such intra-fraction motion would be too large for single fraction radiosurgery. ©Adenine Press (2012).
Popescu C.C.,British Columbia Cancer Agency Vancouver Island Center
Journal of applied clinical medical physics / American College of Medical Physics | Year: 2013
The purpose of this study was to compare the dosimetry of CG-Darc with three-dimensional conformal radiation therapy (3D CRT) and volumetric-modulated arc therapy (RapidArc) in the treatment of breast cancer with APBI. CG-Darc plans were generated using two tangential couch arcs combined with a simultaneous noncoplanar gantry arc. The dynamic couch arc was modeled by consecutive IMRT fields at 10° intervals. RapidArc plans used a single partial arc with an avoidance sector, preventing direct beam exit into the thorax. CG-Darc and RapidArc plans were compared with 3D CRT in 20 patients previously treated with 3D CRT (group A), and in 15 additional patients who failed the dosimetric constraints of the Canadian trial and of NSABP B-39/RTOG 0413 for APBI (group B). CG-Darc resulted in superior target coverage compared to 3D CRT and RapidArc (V95%: 98.2% vs. 97.1% and 95.7%). For outer breast lesions, CG-Darc and RapidArc significantly reduced the ipsilateral breast V50% by 8% in group A and 15% in group B (p < 0.05) as compared with 3D CRT. For inner and centrally located lesions, CG-Darc resulted in significant ipsilateral lung V10% reduction when compared to 3D CRT and RapidArc (10.7% vs. 12.6% and 20.7% for group A, and 15.1% vs. 25.2% and 27.3% for group B). Similar advantage was observed in the dosimetry of contralateral breast where the percent maximum dose for CG-Darc, 3D CRT, and RapidArc were 3.9%, 6.3%, and 5.8% for group A and 4.3%, 9.2%, and 6.3% for group B, respectively (p < 0.05). CG-Darc achieved superior target coverage while decreasing normal tissue dose even in patients failing APBI dose constraints. Consequently, this technique has the potential of expanding the use of APBI to patients currently ineligible for such treatment. Modification of the RapidArc algorithm will be necessary to link couch and gantry rotation with variable dose rate and, therefore, enable the use of CG-Darc in clinical practice.
Bush K.,British Columbia Cancer Agency Vancouver Island Center |
Gagne I.M.,British Columbia Cancer Agency Vancouver Island Center |
Zavgorodni S.,British Columbia Cancer Agency Vancouver Island Center |
Ansbacher W.,British Columbia Cancer Agency Vancouver Island Center |
Beckham W.,British Columbia Cancer Agency Vancouver Island Center
Medical Physics | Year: 2011
Purpose: The dosimetric accuracy of the recently released Acuros® XB advanced dose calculation algorithm (Varian Medical Systems, Palo Alto, CA) is investigated for single radiation fields incident on homogeneous and heterogeneous geometries, and a comparison is made to the analytical anisotropic algorithm (AAA). Methods: Ion chamber measurements for the 6 and 18 MV beams within a range of field sizes (from 4.0×4.0 to 30.0×30.0 cm 2) are used to validate Acuros® XB dose calculations within a unit density phantom. The dosimetric accuracy of Acuros® XB in the presence of lung, low-density lung, air, and bone is determined using BEAMnrc/DOSXYZnrc calculations as a benchmark. Calculations using the AAA are included for reference to a current superposition/convolution standard. Results: Basic open field tests in a homogeneous phantom reveal an Acuros® XB agreement with measurement to within ±1.9% in the inner field region for all field sizes and energies. Calculations on a heterogeneous interface phantom were found to agree with Monte Carlo calculations to within ±2.0% (σ MC =0.8%) in lung (ρ =0.24 g cm -3) and within ±2.9% (σ MC =0.8%) in low-density lung (ρ =0.1 g cm -3). In comparison, differences of up to 10.2% and 17.5% in lung and low-density lung were observed in the equivalent AAA calculations. Acuros® XB dose calculations performed on a phantom containing an air cavity (ρ =0.001 g cm -3) were found to be within the range of ±1.5% to ±4.5% of the BEAMnrc/DOSXYZnrc calculated benchmark (σ MC =0.8%) in the tissue above and below the air cavity. A comparison of Acuros® XB dose calculations performed on a lung CT dataset with a BEAMnrc/DOSXYZnrc benchmark shows agreement within ±2%/2mm and indicates that the remaining differences are primarily a result of differences in physical material assignments within a CT dataset. Conclusions: By considering the fundamental particle interactions in matter based on theoretical interaction cross sections, the Acuros® XB algorithm is capable of modeling radiotherapy dose deposition with accuracy only previously achievable with Monte Carlo techniques. © 2011 American Association of Physicists in Medicine.
PubMed | British Columbia Cancer Agency Vancouver Island Center
Type: Clinical Trial | Journal: British journal of haematology | Year: 2015
Splenic marginal zone lymphoma (SMZL) accounts for less than 2% of all non-Hodgkin lymphomas. We identified 107 cases diagnosed with SMZL between 1985 and 2012 from the British Columbia Cancer Agency Centre for Lymphoid Cancer and Lymphoma Pathology Databases. Patient characteristics were: median age 67 years (range 30-88), male 40%, stage IV 98%, splenomegaly 93%, bone marrow involvement 96%, peripheral blood involvement 87%. As initial treatment, 52 underwent splenectomy (10 with chemotherapy), 38 chemotherapy alone (21 chemoimmunotherapy containing rituximab, 1 rituximab alone), two antivirals for hepatitis C, and 15 were only observed. The 10-year overall survival for first-line splenectomy versus chemotherapy was 61% and 42%, respectively [Hazard Ratio (HR) 048, 95% confidence interval (CI) 026-088, P = 0017]. The 10-year failure-free survival (FFS) after first-line splenectomy vs chemotherapy was 39% and 14%, respectively (HR 048, 95% CI 028-080, P = 0004). Among the 38 patients who received first-line chemotherapy, FFS was similar between those receiving rituximab (n = 22) and those who did not (n = 16) (HR 064, 95% CI 031-134, P = 0238). Fifteen patients transformed to aggressive lymphoma with median time to transformation of 35 years (range 6 months to 12 years) and the 10-year transformation rate was 18%. In conclusion, splenectomy remains a reasonable treatment for patients with SMZL.