Tsoref D.,University of Toronto |
Welch S.,London Regional Cancer Program |
Lau S.,McGill University |
Tonkin K.,Cross Cancer Institute |
And 10 more authors.
Gynecologic Oncology | Year: 2014
Objective The phosphatidylinositol-3 kinase/serine-threonine kinase PI3K/AKT pathway is postulated to be central to cancer cell development. Activation of this pathway is believed to promote angiogenesis, protein translation and cell cycle progression. A large percentage of endometrial carcinomas have demonstrated mutations within this regulation pathway which result in constitutional activation. The downstream effector protein mammalian target of rapamycin (mTOR) acts as a critical checkpoint in cancer cell cycling and is a logical target for drug development. The efficacy and tolerability of the oral mTOR inhibitor ridaforolimus were evaluated in this study.Methods This phase II study evaluated the single agent tolerability and activity of oral ridaforolimus administered at a dose of 40 mg for 5 consecutive days followed by a 2 day break, in women with recurrent or metastatic endometrial carcinoma who had received no chemotherapy in the metastatic setting.Results 31 of 34 patients were evaluable. Three partial responses (8.8%) were observed with response duration ranging between 7.9 and 26.5 months. An additional 18 patients showed disease stabilization (52.9%) for a median duration of 6.6 months. Response rates were not affected by previous chemotherapy exposure. No correlation was found between response and mutation status.Conclusion Oral ridaforolimus was reasonably tolerated and demonstrated modest activity in women with recurrent or metastatic endometrial cancers. Potential synergy between mTOR inhibition, angiogenesis and hormonal pathways warrants ongoing evaluation.
Harris R.,Providence College |
Probst H.,Sheffield Hallam University |
Bolderston A.,Fraser Valley Cancer Center |
Faithfull S.,University of Surrey |
And 2 more authors.
Radiography | Year: 2012
Aim: The primary objective of the survey was to evaluate clinical skin care practice in radiotherapy departments across the United Kingdom. Methods and sample: A questionnaire containing sixty-one questions grouped into eight themed sections was developed and a link to an on-line survey, using the Survey Monkey™ tool, was e-mailed to all radiotherapy department managers in the United Kingdom (N=67). Each recipient was invited to provide one response per department. Key results: Fifty-four departments responded within the allocated timeframe giving a final response rate of 81%. Products and their use for skin conditions varied and some outdated and unfounded practices were still being used which did not always reflect the current evidence base. The amount of data routinely collected on skin toxicity was limited making it difficult to quantify the extent of skin morbidity following radiotherapy. Conclusion: The survey demonstrated variability in skin care practice in radiotherapy departments across the UK, with limited practice based on evidence or on skin toxicity measurement and monitoring. © 2011 The College of Radiographers.
PubMed | Sunnybrook Health science Center, Dr iss Murphy Cancer Center, Tom Baker Cancer Center, Fraser Valley Cancer Center and Cross Cancer Institute
Type: Journal Article | Journal: Canadian medical education journal | Year: 2015
To survey employment and training characteristics of Canadian radiation oncology training program graduates and foreign medical graduates with Canadian radiation oncology post-graduate education or specialist certification.A 38-question, web-based survey was distributed to radiation oncologists who completed specialty training between 2000-2010.Out of 256 radiation oncologists contacted, 148 completed the survey (58% response rate). Thirty-two respondents (22%) were foreign MD graduates. One-hundred and fifteen respondents (78%) undertook fellowship training after residency. Many Canadian MD graduates (77%) and foreign MD graduates (34%) had staff positions in Canada, while 11% of all respondents had staff positions outside Canada, and 21% did not have a commitment for staff employment. Of the 31 respondents without a staff position, 22 graduated from Canadian residency training in 2009 or 2010, and 21 had completed medical school training in Canada.The majority of respondents were successful in securing staff positions in Canada. A sizeable proportion extended training with fellowships. New graduates may have more difficulty in finding Canadian staff positions in radiation oncology in the near future. Implications for specialty training programs and for an improved national strategy for physician resource planning are discussed.
PubMed | McGill University, London Regional Cancer Program, Cross Cancer Institute, Cancer Center for the Southern Interior and 5 more.
Type: Clinical Trial, Phase II | Journal: Gynecologic oncology | Year: 2014
The phosphatidylinositol-3 kinase/serine-threonine kinase PI3K/AKT pathway is postulated to be central to cancer cell development. Activation of this pathway is believed to promote angiogenesis, protein translation and cell cycle progression. A large percentage of endometrial carcinomas have demonstrated mutations within this regulation pathway which result in constitutional activation. The downstream effector protein mammalian target of rapamycin (mTOR) acts as a critical checkpoint in cancer cell cycling and is a logical target for drug development. The efficacy and tolerability of the oral mTOR inhibitor ridaforolimus were evaluated in this study.This phase II study evaluated the single agent tolerability and activity of oral ridaforolimus administered at a dose of 40mg for 5 consecutive days followed by a 2day break, in women with recurrent or metastatic endometrial carcinoma who had received no chemotherapy in the metastatic setting.31 of 34 patients were evaluable. Three partial responses (8.8%) were observed with response duration ranging between 7.9 and 26.5months. An additional 18 patients showed disease stabilization (52.9%) for a median duration of 6.6months. Response rates were not affected by previous chemotherapy exposure. No correlation was found between response and mutation status.Oral ridaforolimus was reasonably tolerated and demonstrated modest activity in women with recurrent or metastatic endometrial cancers. Potential synergy between mTOR inhibition, angiogenesis and hormonal pathways warrants ongoing evaluation.
Schellenberg D.,Fraser Valley Cancer Center |
Quon A.,Stanford University |
Minn A.Y.,Stanford University |
Graves E.E.,Stanford University |
And 6 more authors.
International Journal of Radiation Oncology Biology Physics | Year: 2010
Purpose: This study analyzed the prognostic value of positron emission tomography (PET) for locally advanced pancreas cancer patients undergoing stereotactic body radiotherapy (SBRT). Patients and Methods: Fifty-five previously untreated, unresectable pancreas cancer patients received a single fraction of 25-Gy SBRT sequentially with gemcitabine-based chemotherapy. On the preradiation PET-CT, the tumor was contoured and the maximum standardized uptake value (SUVmax) and metabolic tumor burden (MTB) were calculated using an in-house software application. High-SUVmax and low-SUVmax subgroups were created by categorizing patients above or below the median SUVmax. The analysis was repeated to form high-MTB and low-MTB subgroups as well as clinically relevant subgroups with SUVmax values of <5, 5-10, or >10. Multivariate analysis analyzing SUVmax, MTB, age, chemotherapy cycles, and pretreatment carbohydrate antigen (CA)19-9 was performed. Results: For the entire population, median survival was 12.7 months. Median survival was 9.8 vs.15.3 months for the high- and low- SUVmax subgroups (p <0.01). Similarly, median survival was 10.1 vs. 18.0 months for the high MTB and low MTB subgroups (p <0.01). When clinical SUVmax cutoffs were used, median survival was 6.4 months in those with SUVmax >10, 9.5 months with SUVmax 5.0-10.0, and 17.7 months in those with SUVmax <5 (p <0.01). On multivariate analysis, clinical SUVmax was an independent predictor for overall survival (p = 0.03) and progression-free survival (p = 0.03). Conclusion: PET scan parameters can predict for length of survival in locally advanced pancreas cancer patients. Copyright © 2010 Elsevier Inc.
Butts C.,11560 University Avenue |
Maksymiuk A.,CancerCare Manitoba |
Goss G.,Ottawa Hospital |
Soulieres D.,University of Montréal |
And 8 more authors.
Journal of Cancer Research and Clinical Oncology | Year: 2011
Purpose: To present an updated survival analysis of an open-label, parallel-group, phase IIB trial of BLP25 liposome vaccine (L-BLP25) in patients with stage IIIB or IV non-small-cell lung cancer (NSCLC). Methods: Patients were randomized to either L-BLP25 plus best supportive care (BSC) or BSC alone. Patients in the L-BLP25 arm received subcutaneous vaccinations of L-BLP25 930 μg weekly for 8 weeks, followed by maintenance vaccinations at 6-week intervals. Results: Median survival time was 4.2 months longer in patients receiving L-BLP25 plus BSC (n = 88) than in those receiving BSC alone (n = 83; 17.2 months vs. 13.0 months, respectively; hazard ratio [HR] 0.745, 95% confidence interval [CI] 0.533-1.042). The 3-year survival rate was 31% in patients receiving L-BLP25 plus BSC and 17% in those receiving BSC (P = 0.035). In the stratified subset of patients with stage IIIB loco-regional (LR) disease, median survival time was 17.3 months longer in patients receiving L-BLP25 plus BSC (n = 35) than in those receiving BSC (n = 30; 30.6 months vs. 13.3 months, respectively; HR 0.548, 95% CI 0.301-0.999). In this subgroup, 3-year survival was 49% in patients receiving L-BLP25 plus BSC and 27% in those receiving BSC (P = 0.070). Conclusions: Confirming the initial results, further followup continues to show that survival time for patients with stage IIIB/IV NSCLC was longer with L-BLP25 plus BSC compared with BSC alone, with the greatest difference seen in patients with stage IIIB LR disease. © Springer-Verlag 2011.
Giassa M.,Simon Fraser University |
Khosla A.,Simon Fraser University |
Gray B.,Simon Fraser University |
Parameswaran A.,Simon Fraser University |
And 2 more authors.
Journal of Electronic Testing: Theory and Applications (JETTA) | Year: 2010
We present methodology and instrumentation used to carry out and log automated multiple electrical impedance measurements using multiplexed control. We also address the issue of measurement error introduced by the instrumentation, and demonstrate how we reduce these effects in our experiments. Finally, we present two potential applications for our automated electrical impedance analysis systems: tissue scanning and mapping via impedance measurements between arrays of electrodes, and materials testing of novel conductive polymer materials. © 2009 Springer Science+Business Media, LLC.
Warde P.,Princess Margaret Hospital |
Mason M.,University of Cardiff |
Ding K.,NCIC CTG |
Kirkbride P.,Weston Park Hospital |
And 15 more authors.
The Lancet | Year: 2011
Whether the addition of radiation therapy (RT) improves overall survival in men with locally advanced prostate cancer managed with androgen deprivation therapy (ADT) is unclear. Our aim was to compare outcomes in such patients with locally advanced prostate cancer. Patients with: locally advanced (T3 or T4) prostate cancer (n=1057); or organ-confined disease (T2) with either a prostate-specific antigen (PSA) concentration more than 40 ng/mL (n=119) or PSA concentration more than 20 ng/mL and a Gleason score of 8 or higher (n=25), were randomly assigned (done centrally with stratification and dynamic minimisation, not masked) to receive lifelong ADT and RT (65-69 Gy to the prostate and seminal vesicles, 45 Gy to the pelvic nodes). The primary endpoint was overall survival. The results presented here are of an interim analysis planned for when two-thirds of the events for the final analysis were recorded. All efficacy analyses were done by intention to treat and were based on data from all patients. This trial is registered at controlledtrials.com as ISRCTN24991896 and Clinicaltrials.gov as NCT00002633. Between 1995 and 2005, 1205 patients were randomly assigned (602 in the ADT only group and 603 in the ADT and RT group); median follow-up was 6·0 years (IQR 4·4-8·0). At the time of analysis, a total of 320 patients had died, 175 in the ADT only group and 145 in the ADT and RT group. The addition of RT to ADT improved overall survival at 7 years (74, 95 CI 70-78 vs 66, 60-70; hazard ratio [HR] 0·77, 95 CI 0·61-0·98, p=0·033). Both toxicity and health-related quality-of-life results showed a small effect of RT on late gastrointestinal toxicity (rectal bleeding grade >3, three patients (0·5) in the ADT only group, two (0·3) in the ADT and RT group; diarrhoea grade >3, four patients (0·7) vs eight (1·3); urinary toxicity grade >3, 14 patients (2·3) in both groups). The benefits of combined modality treatment - ADT and RT - should be discussed with all patients with locally advanced prostate cancer. Canadian Cancer Society Research Institute, US National Cancer Institute, and UK Medical Research Council. © 2011 Elsevier Ltd.
Kennecke H.,BC Cancer Agency |
Lim H.,BC Cancer Agency |
Woods R.,BC Cancer Agency |
McGahan C.E.,BC Cancer Agency |
And 3 more authors.
Radiotherapy and Oncology | Year: 2012
Background and purpose: This study compares the outcomes of patients with pathological (p) T3N0 rectal cancer treated with surgery alone (S), surgery and radiation (SR) or surgery, radiation and chemotherapy (SRC), in a population based setting. Materials: Three hundred and seven patients with operable, macroscopically resected pT3N0 rectal cancer referred to the BC Cancer Agency between 2000 and 2004 were segregated by treatment type: S (n = 65), SR (n = 97) and SRC (n = 145). Patient characteristics, 5-year locoregional recurrence (LRR) and disease-specific survival (DSS) were compared between treatment cohorts. Results: Median age differed significantly between S, SR and SRC patient cohorts: 76, 72 and 64 years respectively. Five-year LRR differed by treatment group, with 29% for S, 6.3% for SR and 3.84% for SRC patients. DSS was superior in SRC compared to S patients (hazard ratio = 0.31 [0.17, 0.60]). Co-morbidities and patient preference were most common reasons for omission of radiation. Conclusions: Unselected patients with pT3N0 rectal cancer not treated with peri-operative radiation experience a high rate of LRR and reduced DSS in comparison to patients treated with bimodality and trimodality therapies. Advanced age is significantly associated with omission of therapy in patients with early stage rectal cancer. © 2012 Elsevier Ireland Ltd. All rights reserved.
Randomized phase II study of modified FOLFOX-6 in combination with ramucirumab or icrucumab as second-line therapy in patients with metastatic colorectal cancer after disease progression on first-line irinotecan-based therapy
PubMed | The Ottawa Hospital Cancer Center, British Columbia Cancer Agency, McGill University, Atlantic Clinical Cancer Research Unit and 13 more.
Type: Journal Article | Journal: Annals of oncology : official journal of the European Society for Medical Oncology | Year: 2016
Icrucumab and ramucirumab are recombinant human IgG1 monoclonal antibodies that bind VEGF receptors 1 and 2 (VEGFR-1 and -2), respectively. This randomized phase II study evaluated the antitumor activity and safety of icrucumab and ramucirumab each in combination with mFOLFOX-6 in patients with metastatic colorectal cancer after disease progression on first-line therapy with a fluoropyrimidine and irinotecan.Eligible patients were randomly assigned to receive mFOLFOX-6 alone (mFOLFOX-6) or in combination with ramucirumab 8 mg/kg IV (RAM+mFOLFOX-6) or icrucumab 15 mg/kg IV (ICR+mFOLFOX-6) every 2 weeks. Randomization was stratified by prior bevacizumab therapy. The primary end point was progression-free survival (PFS). Secondary end points included overall survival (OS), tumor response, safety, and PK.In total, 158 patients were randomized, but only 153 received treatment (49 on mFOLFOX-6, 52 on RAM+mFOLFOX-6, and 52 on ICR+mFOLFOX-6). Median PFS was 18.4 weeks on mFOLFOX-6, 21.4 weeks on RAM+mFOLFOX-6, and 15.9 weeks on ICR+mFOLFOX-6 (RAM+mFOLFOX-6 versus mFOLFOX-6, stratified hazard ratio [HR] 1.116 [95% CI 0.713-1.745], P = 0.623; ICR+mFOLFOX-6 versus mFOLFOX-6, stratified HR 1.603 [95% CI 1.011-2.543], P = 0.044). Median survival was 53.6 weeks on mFOLFOX-6, 41.7 weeks on RAM+mFOLFOX-6, and 42.0 weeks on ICR+mFOLFOX-6. The most frequent adverse events reported on the ramucirumab arm (RAM+mFOLFOX-6) were fatigue, nausea, and peripheral sensory neuropathy; those on the icrucumab arm (ICR+mFOLFOX-6) were fatigue, diarrhea, and peripheral sensory neuropathy. Grade 3 serious adverse events occurred at comparable frequency across arms.In this study population, combining ramucirumab or icrucumab with mFOLFOX-6 did not achieve the predetermined improvement in PFS.NCT01111604.