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Knight G.,Grand River Regional Cancer Center | Earle C.C.,Odette Cancer Center | Cosby R.,McMaster University | Coburn N.,Odette Cancer Center | And 3 more authors.
Gastric Cancer | Year: 2013

Background: Gastric cancer is a global health problem accounting for 10% of all new cancer cases and 12% of all cancer deaths worldwide. Many clinical trials and meta-analyses have explored the value of neoadjuvant or adjuvant chemotherapy and radiation therapy in gastric cancer; however, these studies have produced conflicting results. The purpose of this guidance document was to determine whether patients with resectable gastric cancer should receive neoadjuvant or adjuvant therapy in addition to surgery. Outcomes of interest were overall survival, disease-free survival, and adverse events. Methods: A systematic review was undertaken to inform recommendations regarding neoadjuvant and adjuvant therapy in resectable gastric cancer in Ontario, Canada. MEDLINE and EMBASE databases, as well as American Society of Clinical Oncology (ASCO) annual meeting proceedings and American Society for Therapeutic Radiology and Oncology (ASTRO) proceedings were systematically searched from 2002 to 2010. Oral fluoropyrimidine trials were excluded owing to the unavailability of these agents in North America. Results: Overall, 22 randomized controlled trials (RCTs), 13 meta-analyses, and two secondary analyses were included. The systematic review informed the development of a clinical practice guideline with the following recommendations. Postoperative 5-fluorouracil-based chemoradiotherapy based on the Macdonald approach or perioperative ECF (epirubicin, cisplatin, fluorouracil) chemotherapy based on the Cunningham/MAGIC (Medical Research Council Adjuvant Gastric Infusional Chemotherapy) approach are both acceptable standards of care in North America. Choice of treatment should be made on a case-by-case basis. Adjuvant chemotherapy is a reasonable option for those patients for whom the Macdonald and MAGIC protocols are contraindicated. All patients with resectable gastric cancer should undergo a pretreatment multidisciplinary assessment to determine the best plan of care. Conclusions: Overall survival in patients with resectable gastric cancer is significantly improved with the use of either postoperative chemoradiation (Macdonald approach) or perioperative ECF (MAGIC protocol). © 2012 The International Gastric Cancer Association and The Japanese Gastric Cancer Association. Source

Eisen A.,Sunnybrook Health science Center | Fletcher G.G.,McMaster University | Gandhi S.,Sunnybrook Health science Center | Mates M.,Kingston University | And 15 more authors.
Current Oncology | Year: 2015

The Breast Cancer Disease Site Group of Cancer Care Ontario identified the need for new guidelines for the adjuvant systemic therapy of early-stage breast cancer. The specific question to be addressed was “What is the optimal adjuvant systemic therapy for female patients with early-stage operable breast cancer, when patient and disease factors are considered?” A systematic review was prepared based on literature searches conducted using the medline and EMBASE databases for the period January 2008 to March 5, 2012, and updated to May 12, 2014. Guidelines were located from that search, from the Standards and Guidelines Evidence directory of cancer guidelines, and from the Web sites of major guideline organizations. The literature located was subdivided into the broad categories of chemotherapy, hormonal therapy, and therapy targeted to HER2 (human epidermal growth factor receptor 2). Although several of the systemic therapies discussed in this guideline can be considered in the neoadjuvant setting, the review focused on trials with rates of disease-free and overall survival as endpoints and thus excluded several trials that used pathologic complete response as a primary endpoint. Based on the systematic review, the working group drafted recommendations on the use of chemotherapy, hormonal therapy, and targeted therapy; based on their professional experience, they also drafted recommendations on patient and disease characteristics and recurrence risk. The literature review and draft recommendations were circulated to a consensus panel of medical oncologists who had expertise in breast cancer and who represented the regions of Ontario. Items without initial consensus were discussed at an in-person consensus meeting held in Toronto, November 23, 2012. The final recommendations are those for which consensus was reached before or at the meeting. Some of the key evidence was revised after the updated literature search. Evidence reviews for systemic chemotherapy, endocrine therapy, and targeted therapy for HER2- positive disease are reported in separate articles in this supplement. The full three-part 1-21 evidencebased series, including complete details of the development and consensus processes, can be found on the Cancer Care Ontario Web site at https://www. cancercare.on.ca/toolbox/qualityguidelines/disease site/breast-ebs. © 2015 Multimed Inc. Source

Escudier B.,Institute Gustave Roussy | Michaelson M.D.,Massachusetts General Hospital | Motzer R.J.,Sloan Kettering Cancer Center | Hutson T.E.,Sammons Cancer Center | And 12 more authors.
British Journal of Cancer | Year: 2014

Background:In the AXIS trial, axitinib prolonged progression-free survival (PFS) vs sorafenib in patients with advanced renal cell carcinoma (RCC) previously treated with sunitinib or cytokines.Methods:In post hoc analyses, patients were grouped by objective response to prior therapy (yes vs no), prior therapy duration (< vs ≥median), and tumour burden (baseline sum of the longest diameter < vs ≥median). PFS and overall survival (OS), and safety by type and duration of prior therapy were evaluated.Results:Response to prior therapy did not influence outcome with second-line axitinib or sorafenib. PFS was significantly longer in axitinib-treated patients who received longer prior cytokine treatment and sorafenib-treated patients with smaller tumour burden following sunitinib. Overall survival with the second-line therapy was longer in patients who received longer duration of prior therapy, although not significant in the sunitinib-to-axitinib sequence subgroup; OS was also longer in patients with smaller tumour burden, but not significant in the cytokine-to-axitinib sequence subgroup. Safety profiles differed modestly by type and duration of prior therapy.Conclusions:AXIS data suggest that longer duration of the first-line therapy generally yields better outcome with the second-line therapy and that lack of response to first-line therapy does not preclude positive clinical outcomes with a second-line vascular endothelial growth factor-targeted agent in patients with advanced RCC. © 2014 Cancer Research UK. Source

Gandhi S.,Sunnybrook Health science Center | Fletcher G.G.,McMaster University | Eisen A.,Sunnybrook Health science Center | Mates M.,Kingston University | And 3 more authors.
Current Oncology | Year: 2015

Background The Program in Evidence-Based Care (Kinston) of Cancer Care Ontario recently created an evidence-based consensus guideline on the systemic treatment of early breast cancer. The evidence for the guideline was compiled using a systematic review to answer the question “What is the optimal systemic therapy for patients with early-stage, operable breast cancer, when patient and disease factors are considered?” The question was addressed in three parts: cytotoxic chemotherapy, endocrine treatment, and human epidermal growth factor receptor 2 (HER2)– directed therapy. Methods For the systematic review, the MEDLINE and EMBASE databases were searched for the period January 2008 to May 2014. The Standards and Guidelines Evidence directory of cancer guidelines and the Web sites of major oncology guideline organizations were also searched. The basic search terms were “breast cancer” and “systemic therapy” (chemotherapy, endocrine therapy, targeted agents, ovarian suppression), and results were limited to randomized controlled trials (RCTS), guidelines, systematic reviews, and meta-analyses. Results Several hundred documents that met the inclusion criteria were retrieved. The Early Breast Cancer Trialists’ Collaborative Group meta-analyses encompassed many of the RCTS found. Several additional studies that met the inclusion criteria were retained, as were other guidelines and systematic reviews. Chemotherapy was reviewed mainly in three classes: anti-metabolite– based regimens (for example, cyclophosphamide– methotrexate–5-fluorouracil), anthracyclines, and taxane-based regimens. In general, single-agent chemotherapy is not recommended for the adjuvant treatment of breast cancer in any patient population. Anthracycline–taxane-based polychemotherapy regimens are, overall, considered superior to earliergeneration regimens and have the most significant impact on patient survival outcomes. Regimens with varying anthracycline and taxane doses and schedules are options; in general, paclitaxel given every 3 weeks is inferior. Evidence does not support the use of bevacizumab in the adjuvant setting; other systemic therapy agents such as metformin and vaccines remain investigatory. Adjuvant bisphosphonates for menopausal women will be discussed in later work. Conclusions The results of this systematic review constitute a comprehensive compilation of the high-level evidence that is the basis for the 2014 PEBC guideline on systemic therapy for early breast cancer. Use of cytotoxic chemotherapy is presented here; the results addressing endocrine therapy and HER2-targeted treatment, and the final clinical practice recommendations, are published separately in this supplement. © 2015 Multimed Inc. Source

Holly R.,University of Toronto | Holly R.,Durham Regional Cancer Center | Morton G.C.,University of Toronto | Sankreacha R.,University of Toronto | And 5 more authors.
Brachytherapy | Year: 2011

Purpose: To determine the magnitude of catheter displacement between time of planning and time of treatment delivery for patients undergoing high dose-rate (HDR) brachytherapy, the dosimetric impact of catheter displacement, and the ability to improve dosimetry by catheter readjustment. Methods and Materials: Twenty consecutive patients receiving single fraction HDR brachytherapy underwent kilovoltage cone-beam CT in the treatment room before treatment. If catheter displacement was apparent, catheters were adjusted and imaging repeated. Both sets of kilovoltage cone-beam CT image sets were coregistered off-line with the CT data set used for planning with rigid fusion of anatomy based on implanted fiducials. Catheter displacement was measured on both sets of images and dosimetry calculated. Results: Mean internal displacement of catheters was 11mm. This would have resulted in a decrease in mean volume receiving 100% of prescription dose (V 100) from the planned 97.6% to 77.3% (p<0.001), a decrease of the mean dose to 90% of the prostate (D 90) from 110.5% to 72.9% (p<0.001), and increase in dose to 10% of urethra (urethra D 10) from 118% to 125% (p=0.0094). Each 1cm of catheter displacement resulted in a 20% decrease in V 100 and 36% decrease in D 90. Catheter readjustment resulted in a final treated mean V 100 of 90.2% and D 90 of 97.4%, both less than planned. Mean urethra D 10 remained higher at126% (p=0.0324). Conclusions: Significantly, internal displacement of HDR catheters commonly occurs between time of CT planning and treatment delivery, even when only a single fraction is used. The adverse effects on dosimetry can be partly corrected by readjustment of catheter position. © 2011 American Brachytherapy Society. Source

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