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PubMed | Hematologic Oncology, University of Modena and Reggio Emilia, Queen Elizabeth Health science Center, Center Hospitalier Of Luniversite Of Montreal Hopital Notre Dame and 7 more.
Type: Clinical Trial, Phase III | Journal: Blood | Year: 2015

The treatment of transformed indolent lymphoma (TRIL) often includes salvage chemotherapy (SC) and autologous stem cell transplant (ASCT). NCIC CTG LY12 is a randomized phase 3 trial comparing gemcitabine, dexamethasone, and cisplatin (GDP) with dexamethasone, cytarabine, and cisplatin (DHAP) before ASCT. This analysis compares the results of SC and ASCT for TRIL with de novo diffuse large B-cell lymphoma (DLBCL). Six-hundred nineteen patients with relapsed/refractory aggressive non-Hodgkin lymphoma were randomized to GDP or DHAP; 87 patients (14%) had TRIL and 429 (69%) had DLBCL. The response rate to SC was 47% in TRIL and 45% in DL (P = .81). Transplantation rates were similar: TRIL 53% and DL 52% (P = 1.0). With a median follow-up of 53 months, 4 year overall survival was 39% for TRIL and 41% for DL (P = .78); 4 year event-free survival (EFS) was 27% for TRIL and 27% for DL (P = .83). Post-ASCT, 4-year EFS was 45% for TRIL and 46% for DL. Histology (TRIL or DL) was not a predictor of any outcome in multivariate models. Patients with relapsed or refractory TRIL and DLBCL have similar outcomes with SC and ASCT; this therapy should be considered the standard of care for patients with TRIL who have received prior systemic chemotherapy. NCIC CTG LY12 is registered at ClinicalTrials.gov as #NCT00078949.


Fenkell L.,Aarhus University Hospital | Fenkell L.,Stronach Regional Cancer Center | Fenkell L.,Princess Margaret Hospital | Assenholt M.,Aarhus University Hospital | And 5 more authors.
International Journal of Radiation Oncology Biology Physics | Year: 2011

Purpose: Midline-blocked boost (MBB) fields are frequently used in the treatment of locally advanced cervical cancer. The purpose of this study was to evaluate the dose contribution from MBBs to tumor and organs at risk. Methods and Materials: Six patients with locally advanced cervical cancer (IIB-IIIB) treated with definitive chemoradiotherapy and magnetic resonance imaging (MRI)-guided brachytherapy were analyzed. A three-phase plan was modeled: 45 Gy (1.8 Gy per fraction) four-field box, 9 Gy (1.8 Gy per fraction) MBB (midline-shielded anteroposterior/posteroanterior fields), and intracavitary MRI-guided brachytherapy boost of 28 Gy (7 Gy per fraction). Midline shields 3, 4, and 5 cm wide were simulated for each patient. Brachytherapy and MBB plans were volumetrically summed. The rectum, sigmoid, and bladder minimum dose in the most exposed 2 cm3 of an organ at risk (D2 cc) and high-risk clinical target volume (HR-CTV) and intermediate-risk clinical target volume (IR-CTV) D90 and D100 were evaluated. The intended HR-CTV D90 was 85 Gy or greater, and the intended IR-CTV D90 was greater than 60 Gy. Results: After a 4-cm MBB, HR-CTV D90 remained lower than 85 Gy in all cases (mean, 74 Gy; range, 64-82 Gy). High-risk clinical target volume (85 Gy) coverage increased slightly from 73% (range, 64-82%) to 78% (range, 69-88%). Mean IR-CTV D90 increased from 56 Gy (range, 53-64 Gy) to 62 Gy (range, 59-67 Gy). Intermediate-risk clinical target volume 60-Gy dose coverage increased from 81% (range, 72-96%) to 96% (range, 90-100%). The mean volume irradiated to 85 Gy increased by 14 cm3 (range, 10-22 cm3), whereas the volume irradiated to 60 Gy increased from 276 cm3 (range, 185-417 cm 3) to 592 cm3 (range, 385-807 cm3). Bladder, rectum, or sigmoid D2 cc increased by more than 50% of the boost dose in 4 of 6 patients. Conclusions: Midline-blocked boosts contribute substantial dose to rectum, sigmoid, and bladder D2 cc. HR-CTV dose and 85-Gy coverage remain compromised in large tumors despite MBB. IR-CTV 60-Gy coverage improved at the expense of a considerable increase in volume of normal tissue irradiated to 60 Gy. © 2011 Elsevier Inc.


PubMed | Trillium Health Partners, McMaster University, Thunder Bay Regional Health science Center, Nursing and Psychosocial Oncology and 2 more.
Type: | Journal: Psycho-oncology | Year: 2016

Previous systematic reviews have found limited evidence for the effectiveness of pharmacological and psychological interventions for the management of depression in patients with cancer. This paper provides the first meta-analysis of newer collaborative care interventions, which may include both types of treatment, as well as integrated delivery and follow-up. Meta-analyses of pharmacological and psychological interventions are included as a comparison.A search of MEDLINE, EMBASE, PsycINFO, and the Cochrane Library from July 2005 to January 2015 for randomized controlled trials of depression treatments for cancer patients diagnosed with a major depressive disorder, or who met a threshold on a validated depression rating scale was conducted. Meta-analyses were conducted using summary data.Key findings included eight reports of four collaborative care interventions, eight pharmacological, and nine psychological trials. A meta-analysis demonstrated that collaborative care interventions were significantly more effective than usual care (standardized mean difference=-0.49, p=0.003), and depression reduction was maintained at 12months. By comparison, short-term (up to 12weeks), but not longer-term effectiveness was demonstrated for both pharmacological and psychological interventions.Collaborative care interventions have newly emerged as multidisciplinary care delivery models, which may result in more long-term depression remission. This review also updates previous findings of modest evidence for the effectiveness of both pharmacological and psychological interventions for threshold depression in cancer patients. Research designs focusing on combined treatments and delivery systems may best further the limited evidence-base for the management of depression in cancer.


Taremi M.,Princess Margaret Hospital | Taremi M.,University of Toronto | Taremi M.,VU University Amsterdam | Hope A.,Princess Margaret Hospital | And 16 more authors.
International Journal of Radiation Oncology Biology Physics | Year: 2012

Purpose: To present the results of stereotactic body radiotherapy (SBRT) for medically inoperable patients with Stage I non-small-cell lung cancer (NSCLC) and contrast outcomes in patients with and without a pathologic diagnosis. Methods and Materials: Between December 2004 and October 2008, 108 patients (114 tumors) underwent treatment according to the prospective research ethics board-approved SBRT protocols at our cancer center. Of the 108 patients, 88 (81.5%) had undergone pretreatment whole-body [18F]-fluorodeoxyglucose positron emission tomography/computed tomography. A pathologic diagnosis was unavailable for 33 (28.9%) of the 114 lesions. The SBRT schedules included 48 Gy in 4 fractions or 54-60 Gy in 3 fractions for peripheral lesions and 50-60 Gy in 8-10 fractions for central lesions. Toxicity and radiologic response were assessed at the 3-6-month follow-up visits using conventional criteria. Results: The mean tumor diameter was 2.4-cm (range, 0.9-5.7). The median follow-up was 19.1 months (range, 1-55.7). The estimated local control rate at 1 and 4 years was 92% (95% confidence interval [CI], 86-97%) and 89% (95% CI, 81-96%). The cause-specific survival rate at 1 and 4 years was 92% (95% CI, 87-98%) and 77% (95% CI, 64-89%), respectively. No statistically significant difference was found in the local, regional, and distant control between patients with and without pathologically confirmed NSCLC. The most common acute toxicity was Grade 1 or 2 fatigue (53 of 108 patients). No toxicities of Grade 4 or greater were identified. Conclusions: Lung SBRT for early-stage NSCLC resulted in excellent local control and cause-specific survival with minimal toxicity. The disease-specific outcomes were comparable for patients with and without a pathologic diagnosis. SBRT can be considered an option for selected patients with proven or presumed early-stage NSCLC. © 2012 Elsevier Inc.


Hodgson D.C.,University of Toronto | Charpentier A.-M.,University of Toronto | Ng A.,University of Toronto | Bahl G.,Nova Scotia Cancer Center | And 3 more authors.
International Journal of Radiation Oncology Biology Physics | Year: 2013

Purpose: Stereotactic radiosurgery (SRS) for brain metastases is a relatively well-studied technology with established guidelines regarding patient selection, although its implementation is technically complex. We evaluated the extent to which local availability of SRS affected the treatment of patients with brain metastases. Methods and Materials: We identified 3030 patients who received whole-brain radiation therapy (WBRT) for brain metastases in 1 of 7 cancer centers in Ontario. Clinical data were abstracted for a random sample of 973 patients. Logistic regression analyses were performed to identify factors associated with the use of SRS as a boost within 4 months following WBRT or at any time following WBRT. Results: Of 898 patients eligible for analysis, SRS was provided to 70 (7.8%) patients at some time during the course of their disease and to 34 (3.8%) patients as a boost following WBRT. In multivariable analyses, factors significantly associated with the use of SRS boost following WBRT were fewer brain metastases (odds ratio [OR] = 6.50), controlled extracranial disease (OR = 3.49), age (OR = 0.97 per year of advancing age), and the presence of an on-site SRS program at the hospital where WBRT was given (OR = 12.34; all P values were <.05). Similarly, availability of on-site SRS was the factor most predictive of the use of SRS at any time following WBRT (OR = 5.98). Among patients with 1-3 brain metastases, good/fair performance status, and no evidence of active extracranial disease, SRS was provided to 40.3% of patients who received WBRT in a hospital that had an on-site SRS program vs 3.0% of patients who received WBRT at a hospital without SRS (P<.01). Conclusions: The availability of on-site SRS is the factor most strongly associated with the provision of this treatment to patients with brain metastases and appears to be more influential than accepted clinical eligibility factors. © 2013 Elsevier Inc. All rights reserved.


Allibhai Z.,University of Toronto | Taremi M.,Stronach Regional Cancer Center | Bezjak A.,University of Toronto | Brade A.,University of Toronto | And 3 more authors.
International Journal of Radiation Oncology Biology Physics | Year: 2013

Purpose Stereotactic body radiation therapy for medically inoperable early-stage non-small cell lung cancer (NSCLC) offers excellent control rates. Most published series deal mainly with small (usually <4 cm), peripheral, solitary tumors. Larger tumors are associated with poorer outcomes (ie, lower control rates, higher toxicity) when treated with conventional RT. It is unclear whether SBRT is sufficiently potent to control these larger tumors. We therefore evaluated and examined the influence of tumor size on treatment outcomes after SBRT. Methods and Materials Between October 2004 and October 2010, 185 medically inoperable patients with early (T1-T2N0M0) NSCLC were treated on a prospective research ethics board-approved single-institution protocol. Prescription doses were risk-adapted based on tumor size and location. Follow-up included prospective assessment of toxicity (as per Common Terminology Criteria for Adverse Events, version 3.0) and serial computed tomography scans. Patterns of failure, toxicity, and survival outcomes were calculated using Kaplan-Meier method, and the significance of tumor size (diameter, volume) with respect to patient, treatment, and tumor factors was tested. Results Median follow-up was 15.2 months. Tumor size was not associated with local failure but was associated with regional failure (P=.011) and distant failure (P=.021). Poorer overall survival (P=.001), disease-free survival (P=.001), and cause-specific survival (P=.005) were also significantly associated with tumor size (with tumor volume more significant than diameter). Gross tumor volume and planning target volume were significantly associated with grade 2 or worse radiation pneumonitis. However, overall rates of grade ≥3 pneumonitis were low and not significantly affected by tumor or target size. Conclusions Currently employed stereotactic body radiation therapy dose regimens can provide safe effective local therapy even for larger solitary NSCLC tumors (up to 5.7 cm in tumor diameter or 100 cm3 in tumor volume) but are associated with more nonlocal failures as well as poorer survival. These observations suggest these patients may benefit from more extensive staging or consideration of adjuvant therapy. © 2013 The Authors. Published by Elsevier Inc. All rights reserved.


PubMed | Stronach Regional Cancer Center and British Columbia Cancer Agency
Type: Journal Article | Journal: Medical physics | Year: 2016

To present the dose per pulse dependence of various QA devices under Flattening Filter Free (FFF) conditions.Air and liquid filled ion chamber arrays, diode arrays, radiochromic film and optically stimulated luminescence detectors were investigated. All detectors were irradiated under similar conditions of varying dose per pulse on a TrueBeam linac. Dose per pulse was controlled by varying SSD from 70 to 160 cm providing a range from 0.5 to 3 mGy per pulse. MU rates of up to 2400 MU/min for 10X FFF and 1400 MU/min for the 6X FFF beam were used. Beam pulses were counted using the Profiler diode array and pulse timing was confirmed by examining linac node files. Delivered doses were calculated with the Eclipse treatment planning system.The detectors show a range of behaviors depending on the detector type, as expected. Diode arrays show up to 4% change in sensitivity (sensitivity increases with increasing dose per pulse) over the range tested. Air and liquid ion chambers arrays show a change in sensitivity of up to 3% (air) and 6% (liquid) (sensitivity decreases with increasing dose per pulse) while film and OSLD do not demonstrate a dependence on dose per pulse.Dependence of detector response on dose per pulse varies considerably depending on detector design. Interplay between dose per pulse and MU rate also exists for some detectors. Due diligence is required to characterize detector response prior to implementation of a QA protocol for FFF treatment delivery. During VMAT delivery, the MU rate may also vary dramatically within a treatment fraction. We intend to further investigate the implications of this for VMAT FFF patient specific quality assurance. T Karan and F Viel have received partial funding through the Varian Research program.


Chan E.H.,Stronach Regional Cancer Center | Ryan M.J.,Stronach Regional Cancer Center
Radiography | Year: 2016

Radiation therapy techniques for early stage Hodgkin's disease (HD) include simple parallel-opposed-pair (POP) and Intensity-Modulated Radiation Therapy (IMRT). This case report compared the dosimetry achieved with POP and IMRT by evaluating target volumes and organs at risk (OAR). It showed that the IMRT technique could be a valuable technique when treating HD. Optimal target coverage can be achieved while at the same time reducing dose given to critical structures such as lung and thyroid. © 2016 The College of Radiographers.


Abbas A.S.,Stronach Regional Cancer Center
Journal of applied clinical medical physics / American College of Medical Physics | Year: 2013

Recently, volumetric-modulated arc therapy (VMAT) has demonstrated the ability to deliver radiation dose precisely and accurately with a shorter delivery time compared to conventional intensity-modulated fixed-field treatment (IMRT). We applied the hypothesis of VMAT technique for the treatment of thoracic esophageal carcinoma to determine superior or equivalent conformal dose coverage for a large thoracic esophageal planning target volume (PTV) with superior or equivalent sparing of organs-at-risk (OARs) doses, and reduce delivery time and monitor units (MUs), in comparison with conventional fixed-field IMRT plans. We also analyzed and compared some other important metrics of treatment planning and treatment delivery for both IMRT and VMAT techniques. These metrics include: 1) the integral dose and the volume receiving intermediate dose levels between IMRT and VMATI plans; 2) the use of 4D CT to determine the internal motion margin; and 3) evaluating the dosimetry of every plan through patient-specific QA. These factors may impact the overall treatment plan quality and outcomes from the individual planning technique used. In this study, we also examined the significance of using two arcs vs. a single-arc VMAT technique for PTV coverage, OARs doses, monitor units and delivery time. Thirteen patients, stage T2-T3 N0-N1 (TNM AJCC 7th edn.), PTV volume median 395 cc (range 281-601 cc), median age 69 years (range 53 to 85), were treated from July 2010 to June 2011 with a four-field (n = 4) or five-field (n = 9) step-and-shoot IMRT technique using a 6 MV beam to a prescribed dose of 50 Gy in 20 to 25 F. These patients were retrospectively replanned using single arc (VMATI, 91 control points) and two arcs (VMATII, 182 control points). All treatment plans of the 13 study cases were evaluated using various dose-volume metrics. These included PTV D99, PTV D95, PTV V9547.5Gy(95%), PTV mean dose, Dmax, PTV dose conformity (Van't Riet conformation number (CN)), mean lung dose, lung V20 and V5, liver V30, and Dmax to the spinal canal prv3mm. Also examined were the total plan monitor units (MUs) and the beam delivery time. Equivalent target coverage was observed with both VMAT single and two-arc plans. The comparison of VMATI with fixed-field IMRT demonstrated equivalent target coverage; statistically no significant difference were found in PTV D99 (p = 0.47), PTV mean (p = 0.12), PTV D95 and PTV V9547.5Gy (95%) (p = 0.38). However, Dmax in VMATI plans was significantly lower compared to IMRT (p = 0.02). The Van't Riet dose conformation number (CN) was also statistically in favor of VMATI plans (p = 0.04). VMATI achieved lower lung V20 (p = 0.05), whereas lung V5 (p = 0.35) and mean lung dose (p = 0.62) were not significantly different. The other OARs, including spinal canal, liver, heart, and kidneys showed no statistically significant differences between the two techniques. Treatment time delivery for VMATI plans was reduced by up to 55% (p = 5.8E-10) and MUs reduced by up to 16% (p = 0.001). Integral dose was not statistically different between the two planning techniques (p = 0.99). There were no statistically significant differences found in dose distribution of the two VMAT techniques (VMATI vs. VMATII) Dose statistics for both VMAT techniques were: PTV D99 (p = 0.76), PTV D95 (p = 0.95), mean PTV dose (p = 0.78), conformation number (CN) (p = 0.26), and MUs (p = 0.1). However, the treatment delivery time for VMATII increased significantly by two-fold (p = 3.0E-11) compared to VMATI. VMAT-based treatment planning is safe and deliverable for patients with thoracic esophageal cancer with similar planning goals, when compared to standard IMRT. The key benefit for VMATI was the reduction in treatment delivery time and MUs, and improvement in dose conformality. In our study, we found no significant difference in VMATII over single-arc VMATI for PTV coverage or OARs doses. However, we observed significant increase in delivery time for VMATII compared to VMATI.


PubMed | Stronach Regional Cancer Center
Type: Journal Article | Journal: Medical physics | Year: 2017

Breast radiation therapy is associated with some risk of lung toxicity as well as cardiac toxicity for left-sided cases. Radiation doses to the lung and heart can be reduced by using the deep inspiration breath hold (DIBH) technique, in which the patient is simulated and treated during the deep inspiration phase of the breathing cycle. During DIBH, the heart is usually displaced posteriorly, inferiorly, and to the right, effectively expanding the distance between the heart and the breast/chest wall. As a result, the distance between the medial treatment field border and heart/lung is increased. Also, in a majority of DIBH patients, the air drawn into the thoracic cavity increases the total lung volume. The DIBH was discussed by an AAPM Task Group 10 years ago in the AAPM TG 76 report. However, DIBH is still not the standard of care in many clinics, which may be partially due to challenges associated with its implementation. Therefore, this seccion will focus primarily on how to clinically implement four different DIBH techniques: (1) Active Breathing Control, (2) Spirometric Motion Management, (3) 3D Surface Image-Guided, and (4) Self-held Breath Control with Respiratory Monitoring and Feedback Guidance.1. Describe the physical displacement of the heart and the change in lung volume during DIBH and discuss dosimetric consequences of those changes. 2. Provide an overview of the technical aspects. 3. Describe work flow for patient simulation and treatment. 4. Give an overview of commissioning and routine. 5. Provide practical tips for clinical implementation.

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