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Pignol J.-P.,Sunnybrook Health science Center | Olivotto I.,British Columbia Cancer Agency Vancouver Island Center
European journal of Clinical and Medical Oncology | Year: 2010

The majority of early-stage breast cancers are treated with breast-conserving surgery followed by adjuvant radiation treatment on the whole breast. Acute dermatitis is a frequent side-effect of adjuvant breast radiotherapy, and this treatment can also impair the long-term cosmetic result. Breast intensity-modulated radiation therapy (IMRT) is a technique that improves the radiation dose distribution in the breast, allowing the avoidance of ''hotspots''. To review current evidence that breast IMRT provides a patient benefit, a MedLine search was done to identify articles reporting on this technique. A total of 63 manuscripts reporting on breast IMRT were identified. Fifty-six articles present original research data; the majority (80%) reported on physics or dosimetry, a smaller number on clinical outcomes (15%), and on health sciences or radiobiology (5%). Eight articles reported clinical outcomes, with six being single-institution retrospective or prospective cohort from three centers in the USA, and two reporting prospective randomized controlled trials were from the UK and Canada. Combining all these data, the clinical outcomes of nearly 780 patients receiving breast IMRT have been reported and compared with 767 patients receiving standard wedged radiotherapy. There is level 1 evidence that breast IMRT reduces acute dermatitis from a Canadian, multicenter, randomized, double-blinded, clinical trial, and there is level 1 evidence that breast IMRT improves the long-term cosmetic results from a UK randomized clinical trial. Source


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. Source


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. Source


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. Source


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 Source

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