Jennifer J Knox

University Health Network, Toronto, Ontario, Canada

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Publications (114)489.43 Total impact

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    ABSTRACT: Background There is strong rationale to combine temsirolimus (TEM) with Bevacizumab (BEV) for patients with advanced HCC. Methods A modified two-stage Simon phase II trial was performed with plans to advance to stage 2 if more than 2 patients had confirmed PR or >18 patients were progression free at 6 months out of 25 in stage 1. Toxicity, PFS and overall survival were secondary endpoints. Eligible pts had advanced HCC, Child Pugh A liver status and no prior systemic therapy involving the VEGF or m-TOR targeted agents. Patients were treated with temsirolimus 25 mg IV on Days 1, 8, 15, and 22 of a 28 day cycle and bevacizumab 10 mg/kg IV on Days 1 and 15 of the cycle. Results Twenty-eight eligible patients were enrolled, 26 evaluable receiving a median of 6.5 cycles (range 1-18). Drug related toxicities were common including cytopenias, fatigue, mucositis, diarrhea and mild bleeds. Dose reductions or discontinuation of TEM were common. Accrual closed for presumed futility after interim analysis of the first 25 evaluable patients showed only one PR and 16/25 were progression-free at 6 months. However, the final data update in March 2013 demonstrated 4 confirmed PRs, a 5th unconfirmed PR and 16 /26 progression-free at 6 months. Median PFS and OS were 7 and 14 months respectively. Conclusion This first-line HCC trial evaluating the BEV/TEM doublet reports an ORR of 19 % and OS of 14 months which is favorable but requires further study at a more optimized dose and schedule.
    Investigational New Drugs 10/2014; · 3.50 Impact Factor
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    ABSTRACT: Objective To assess the efficacy and toxicity of abiraterone and docetaxel in men with metastatic castration-resistant prostate cancer (mCRPC) of age > 80 compared to younger men. Methods Retrospective chart review of 116 men treated with abiraterone and 378 men treated with docetaxel at Princess Margaret Cancer Centre. Categorical outcome measures including PSA response rate (PSA-RR) and incidence of toxic side-effects were compared using Fisher's exact test. Overall survival (OS) and biochemical progression free survival (bPFS) were analyzed using the Kaplan–Meier method and log-rank tests. Results Thirty-four (29%) and 50 (13%) of the men treated with abiraterone or docetaxel, respectively, were octogenarians. For abiraterone there were no significant differences in PSA-RR (42% vs. 39%), bPFS (4.7 vs. 4.4 months) or OS (14.0 vs 20.7 months) between octogenarians and younger men, respectively. Toxicity was mild with no significant differences between age groups. For men treated with docetaxel PSA-RR and OS did not differ between age groups (40% vs. 45% and 12.0 vs. 14.1 months, respectively). However, rates of febrile neutropenia were 16% and 7% for octogenarians and younger men, respectively (p = 0.048). This difference was observed despite greater use of lower dose intensity and weekly docetaxel in the elderly cohort, with 20% of them receiving lower than standard dose during their first cycle compared to 7% of younger men (p = 0.004). Conclusions Treatment outcome on abiraterone and docetaxel did not differ in patients over and under the age of 80, but febrile neutropenia was more common in octogenarians treated with docetaxel despite lower dose intensity.
    Journal of Geriatric Oncology 10/2014; · 1.12 Impact Factor
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    ABSTRACT: BACKGROUND Abiraterone acetate (AA), oral CYP17 inhibitor, is an active agent in the treatment of metastatic castrate-resistant prostate cancer (mCRPC).METHODS We (R.L.A and N.A) retrospectively evaluated outcome in 12 men who were re-treated with AA following prior treatment with AA at the Princess Margaret Cancer Centre.RESULTSAll men were heavily pre-treated for mCRPC with a median of four prior lines of therapy, one of which was AA (given either pre- or post-chemotherapy). Eleven out of 12 (92%) men stopped their first treatment course of AA due to progression and one stopped for financial reasons. Seven men had a PSA decrease ≥50% following their first AA treatment, of which three (46%) had a PSA decrease ≥50% to AA re-treatment. The responses to AA re-treatment were generally short-lived with a median biochemical progression-free survival of 2.3 months and median treatment duration of 3.2 months. No PSA responses to AA re-treatment were seen in five men who did not have an initial PSA response to AA.CONCLUSIONS Our data suggest that AA re-challenge may have limited benefit in select men with mCRPC, and warrants further formal research. Prostate © 2014 Wiley Periodicals, Inc.
    The Prostate 08/2014; · 3.84 Impact Factor
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    ABSTRACT: A multicenter, randomized phase II trial, RECORD-3, was conducted to compare first-line everolimus followed by sunitinib at progression with the standard sequence of first-line sunitinib followed by everolimus in patients with metastatic renal cell carcinoma.
    Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 07/2014;
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    ABSTRACT: The benefit of cytoreductive nephrectomy (CN) for overall survival (OS) is unclear in patients with synchronous metastatic renal cell carcinoma (mRCC) in the era of targeted therapy.
    European urology. 06/2014;
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    ABSTRACT: Background: The SWI/SNF chromatin remodeling complex is an important regulator of gene expression that has been linked to cancer development and outcome. Expression of Brahma (BRM), a critical catalytic subunit of SWI/SNF is lost in a variety of solid tumors. Two novel BRM promoter polymorphisms (BRM-741 and BRM-1321) have been correlated with BRM loss and elevated cancer risk in upper aerodigestive and lung cancer outcome. Objectives: We evaluated BRM polymorphisms and their role in the survival of esophageal cancer patients. Methods: 270 histologically-confirmed esophageal adenocarcinoma patients of all stages were evaluated. The two BRM polymorphisms utilized Taqman genotyping. Cox proportional hazards models adjusted for clinical prognostic variables and determined the association of polymorphisms with overall survival (OS) and progression free survival (PFS). Adjusted hazard ratio (aHR) and 95% confidence intervals (CI) were calculated. Results: Among our patients, 85% were male; the mean age was 63 years. 37% had stage IV advanced tumors. The median PFS was 12.9 months, while median OS was 20.8 months. After adjustment for known prognostic clinical variables, carrying homozygous variants of both BRM polymorphisms (double homozygotes) was associated with a worse outcome: aHR 2.207 (1.36-3.58, p=0.0014) for OS and aHR 2.467 (1.527-3.983, p=0.0002) for PFS. Conclusions: We report the initial association of BRM polymorphisms with survival in esophageal cancer. We plan to explore additional relationships and validate these findings in other datasets.
    ASCO 2013; 05/2014
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    ABSTRACT: Clinical data supporting the use of targeted agents for the treatment of metastatic renal cell carcinoma (RCC) are based predominantly on patients with clear cell histology. Little is known about the efficacy of these drugs in non-clear cell variants.
    European urology. 05/2014;
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    ABSTRACT: Background:Limited data exist on outcomes for metastatic renal cell carcinoma (mRCC) patients treated with multiple lines of therapy. Benchmarks for survival are required for patient counselling and clinical trial design.Methods:Outcomes of mRCC patients from the International mRCC Database Consortium database treated with 1, 2, or 3+ lines of targeted therapy (TT) were compared by proportional hazards regression. Overall survival (OS) and progression-free survival (PFS) were calculated using different population inclusion criteria.Results:In total, 2705 patients were treated with TT of which 57% received only first-line TT, 27% received two lines of TT, and 16% received 3+ lines of TT. Overall survival of patients who received 1, 2, or 3+ lines of TT were 14.9, 21.0, and 39.2 months, respectively, from first-line TT (P<0.0001). On multivariable analysis, 2 lines and 3+ lines of therapy were each associated with better OS (HR=0.738 and 0.626, P<0.0001). Survival outcomes for the subgroups were as follows: for all patients, OS 20.9 months and PFS 7.2 months; for those similar to eligible patients in the first-line ADAPT trial, OS 14.7 months and PFS 5.6 months; for those similar to patients in first-line TIVO-1 trial, OS 24.8 months and PFS 8.2 months; for those similar to patients in second-line INTORSECT trial, OS 13.0 months and PFS 3.9 months; and for those similar to patients in the third-line GOLD trial, OS 18.0 months and PFS 4.4 months.Conclusions:Patients who are able to receive more lines of TT live longer. Survival benchmarks provide context and perspective when interpreting and designing clinical trials.British Journal of Cancer advance online publication, 1 April 2014; doi:10.1038/bjc.2014.25 www.bjcancer.com.
    British Journal of Cancer 04/2014; · 5.08 Impact Factor
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    ABSTRACT: Approval of the mTOR inhibitors for the treatment of mRCC was based on efficacy in poor-risk patients in the first-line setting for temsirolimus and in vascular endothelial growth factor inhibitor-refractory patients for everolimus. We strove to characterize temsirolimus and everolimus use and effectiveness in the first-line setting. We performed a retrospective database analysis of mRCC patients who received mTOR inhibitors as first-line targeted therapy. The Kaplan-Meier product-limit method was used to estimate the distribution of progression-free survival (PFS) and overall survival (OS). We identified 127 mRCC patients who had received a first-line mTOR inhibitor. Temsirolimus was administered in 93 patients (73%) and everolimus in 34 patients (27%). The main reasons for choice of temsirolimus were poor-risk disease (38%), non-clear cell histology (27%), and clinical trial availability (15%), whereas clinical trial (82%) and non-clear cell histology (6%) drove everolimus selection. Of the temsirolimus and everolimus patients, 58% and 32% were poor-risk according to the International mRCC Database Consortium criteria, respectively. The median PFS and OS were 3.4 and 12.5 months and 4.8 and 15.9 months with temsirolimus and everolimus, respectively. Although limited by small numbers, this study characterizes a real-world, international experience with the use of mTOR inhibition in treatment-naive mRCC patients. Poor-risk RCC, non-clear cell histology, and clinical trials were the predominant reasons for mTOR inhibitor selection in the front-line setting. Because of the different patient populations in which they were administered, direct comparisons of the front-line efficacy of temsirolimus and everolimus cannot be made.
    Clinical Genitourinary Cancer 03/2014; · 1.43 Impact Factor
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    ABSTRACT: Brahma (BRM) has a key function in chromatin remodeling. Two germline BRM promoter insertion-deletion polymorphisms, BRM-741 and BRM-1321, have been previously associated with an increased risk of lung cancer in smokers and head and neck cancer. To further evaluate their role in cancer susceptibility particularly in early disease, we conducted a preplanned case-control study to investigate the association between the BRM promoter variants and stage I/II upper aerodigestive tract (UADT) cancers (i.e., lung, esophageal, head and neck), a group of early-stage malignancies in which molecular and genetic etiologic factors are poorly understood. The effects of various clinical factors on this association were also studied. We analyzed 562 cases of early-stage UADT cancers and 993 matched healthy controls. The double homozygous BRM promoter variants were associated with a significantly increased risk of early stage UADT cancers (adjusted odds ratio [aOR], 2.46; 95% confidence interval [CI], 1.7-3.8). This association was observed in lung (aOR, 2.61; 95% CI, 1.5-4.9) and head and neck (aOR, 2.75; 95% CI, 1.4-5.6) cancers, but not significantly in esophageal cancer (aOR, 1.66; 95% CI, 0.7-5.8). There was a nonsignificant trend for increased risk in the heterozygotes or single homozygotes. The relationship between the BRM polymorphisms and early-stage UADT cancers was independent of age, sex, smoking status, histology, and clinical stage. These findings suggest that the BRM promoter double insertion homozygotes may be associated with an increased risk of early-stage UADT cancers independent of smoking status and histology, which must be further validated in other populations.
    Cancer Medicine 02/2014;
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    ABSTRACT: To correlate metabolic response to neoadjuvant chemoradiotherapy (NACR) on FDG-PET/CT using PERCIST-based criteria to pathologic and clinical response, and survival in patients with locally advanced esophageal cancer (LAEC). Forty-five patients with LAEC underwent PET/CT at baseline and after NACR. Tumors were evaluated using PERCIST (PET response criteria in solid tumors)-based criteria including SUL, SUL tumor/liver ratio, % change in SUL. These parameters were compared to pathology regression grade (PRG), clinical response (including residual or new disease beyond the surgical specimen), and overall survival. On surgical pathology, there was complete or near-complete regression of tumor in 51.1 %, partial response in 42.2 %, and lack regression in 4.4 %. One patient (2.2 %) had progression of disease on imaging and did not undergo surgical resection. None of the baseline PET parameters had significant correlation to pathology regression grade or clinical response. On follow-up, a positive correlation was found between post-therapy SUL ratio, %∆ SUL and %∆ SUL ratio and clinical response (p = 0.025, 0.035, 0.030, respectively). A weak correlation was found between post-therapy SUL ratio to PRG (p = 0.049). A strong correlation was found between the metabolic response score and PRG (p = 0.002) as well as between metabolic response and clinical response (p < 0.001). PERCIST-based metabolic response assessment to NACR in LAEC may correlate with clinical outcome and survival.
    Annals of Nuclear Medicine 01/2014; · 1.41 Impact Factor
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    ABSTRACT: Abiraterone acetate (abiraterone) prolongs overall survival (OS) in patients with metastatic castration-resistant prostate cancer (mCRPC). This study's objective was to retrospectively identify factors associated with prostate-specific antigen (PSA) response to abiraterone and validate them in an independent cohort. We hypothesized that the neutrophil/lymphocyte ratio (NLR), thought to be an indirect manifestation of tumor-promoting inflammation, may be associated with response to abiraterone. All patients receiving abiraterone at the Princess Margaret (PM) Cancer Centre up to March 2013 were reviewed. The primary end point was confirmed PSA response defined as PSA decline ≥50% below baseline maintained for ≥3 weeks. Potential factors associated with PSA response were analyzed using univariate and multivariable analyses to generate a score, which was then evaluated in an independent cohort from Royal Marsden (RM) NHS foundation. A confirmed PSA response was observed in 44 out of 108 assessable patients (41%, 95% confidence interval 31%-50%). In univariate analysis, lower pre-abiraterone baseline levels of lactate dehydrogenase, an NLR ≤ 5 and restricted metastatic spread to either bone or lymph nodes were each associated with PSA response. In multivariable analysis, only low NLR and restricted metastatic spread remained statistically significant. A score derived as the sum of these two categorical variables was associated with response to abiraterone (P = 0.007). Logistic regression analysis on an independent validation cohort of 245 patients verified that this score was associated with response to abiraterone (P = 0.003). It was also associated with OS in an exploratory analysis. A composite score of baseline NLR and extent of metastatic spread is associated with PSA response to abiraterone and OS. Our data may help understand the role of systemic inflammation in mCRPC and warrant further research.
    Annals of Oncology 01/2014; · 7.38 Impact Factor
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    ABSTRACT: Targeted therapies in metastatic renal cell carcinoma (mRCC) have been approved based on registration clinical trials that have strict eligibility criteria. The clinical outcomes of patients treated with targeted agents but are ineligible for trials are unknown. mRCC patients treated with vascular endothelial growth factor-targeted therapy were retrospectively deemed ineligible for clinical trials (according to commonly used inclusion/exclusion criteria) if they had a Karnofsky performance status (KPS) <70%, nonclear-cell histology, brain metastases, hemoglobin ≤9 g/dl, creatinine >2× the upper limit of normal, corrected calcium ≥12 mg/dl, platelet count of <100 × 10(3)/uL, or neutrophil count <1500/mm(3). Overall, 768 of 2210 (35%) patients in the International Metastatic RCC Database Consortium (IMDC) were deemed ineligible for clinical trials by the above criteria. Between ineligible versus eligible patients, the response rate, median progression-free survival (PFS) and median overall survival of first-line targeted therapy were 22% versus 29% (P = 0.0005), 5.2 versus 8.6 months, and 12.5 versus 28.4 months (both P < 0.0001), respectively. Second-line PFS (if applicable) was 2.8 months in the trial ineligible versus 4.3 months in the trial eligible patients (P = 0.0039). When adjusted by the IMDC prognostic categories, the HR for death between trial ineligible and trial eligible patients was 1.55 (95% confidence interval 1.378-1.751, P < 0.0001). The number of patients that are ineligible for clinical trials is substantial and their outcomes are inferior. Specific trials addressing the unmet needs of protocol ineligible patients are warranted.
    Annals of Oncology 01/2014; 25(1):149-54. · 7.38 Impact Factor
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    ABSTRACT: Background Biliary tract cancers (BTCs) include intrahepatic (IHC), hilar, distal bile duct (DBD) and gallbladder carcinoma (GBC). Neutrophil/lymphocyte ratio (NLR), a marker of host inflammation, is prognostic in several cancers but has not been reviewed in large BTC series, or advanced BTC (ABTC) at diagnosis. Patients and methods Baseline demographics and NLR at diagnosis were retrospectively evaluated in 864 consecutive patients with BTC treated from January 1987 to December 2012. The association between NLR and overall survival (OS) was determined using a multivariable Cox proportional hazards model. Results Eight hundred and sixty-four patients were included in the analysis, of which 62% had ABTC and 38% had surgery with curative intent. Median age was 65 years, 444 (51%) were male and 727 (84%) had performance status (PS) ⩽2. A NLR ⩾3.0, PS >2, IHC primary, stage, lack of surgery, haemoglobin <110 g/L and albumin <40 g/L were associated with significantly worse OS on multivariable analysis. A NLR ⩾3.0 was an independent prognostic factor for OS for the entire cohort; median OS was 21.6 months versus 12.0 months for patients with NLR <3.0 versus NLR ⩾3.0 respectively (adjusted hazard ratio (HR)-1.26, 95% confidence interval (CI); 1.06–1.50, P = 0.01). NLR was also prognostic in patients with ABTC (HR-1.26, 95% CI; 1.02–1.56, P = 0.035) and hilar cancer: overall group (N = 149) (HR-1.70, 95% CI; 1.10–2.50, P = 0.01) and advanced group (N = 111) (HR-1.57, 95% CI; 1.04–2.44, P = 0.048). Conclusion Baseline NLR is a readily available and inexpensive prognostic biomarker in patients with BTC and likely warrants validation in large prospective clinical trials.
    European journal of cancer (Oxford, England: 1990) 01/2014; · 4.12 Impact Factor
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    ABSTRACT: Background Targeted therapy has become the mainstay of treatment for metastatic renal cell carcinoma (mRCC). The efficacy of this therapy in the older population is poorly understood. Patients and methods Data from patients with mRCC treated with first-line anti-VEGF therapy were collected through the International mRCC Database Consortium from 12 centers. Patient characteristics, data on second-line therapy, and outcomes, including treatment duration and overall survival, were evaluated using summary statistics and multivariate analysis. Results and limitations: 1,381 patients were treated with front-line targeted therapy; 144 (10%) were 75-years or older. 4% were favorable risk, 69% intermediate risk, and 27% poor risk as per Heng et al. JCO 2009 prognostic factors. The initial treatment for those ≥75-years was with sunitinib(n=98), sorafenib(n=35), bevacizumab(n=7), and AZD217(n=4). 23% of older patients and 39% of the younger patients went on to receive second-line therapy (p<0.0001). The overall response rate, median treatment duration and overall survival for the older vs. younger group were 18% vs. 25% (p=0.0975), 5.5months vs. 7.5months (p=0.1388) and 16.8months vs. 19.7months (p=0.3321), respectively. When adjusted for poor prognostic factors, age 75-years and above was not found to be associated with poorer overall survival (HR 1.002, 95%CI 0.781-1.285) or shorter treatment duration (HR 1.018, 95%CI 0.827-1.252). The retrospective study design was the primary limitation. Conclusions The use of advanced age as a selection criterion for targeted therapy requires further study, with data suggesting no clinically meaningful differences in overall response rate, treatment duration, and overall survival between older and younger age groups.
    Clinical Genitourinary Cancer 01/2014; · 1.43 Impact Factor
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    ABSTRACT: Background Targeted therapies improve survival in metastatic renal cell carcinoma (mRCC). However, survival patterns can be divergent and patients at the two extremes of the survival spectrum need to be characterized. Patients and Methods Data from 2161 patients included in the International mRCC Database Consortium (IMDC) were analyzed. We identified patients based on their duration of survival. Long-term survivors (LTS) were defined as overall survival (OS) ≥ 4 years and short-term survivors (STS) were patients with OS ≤ 6 months from the start of targeted therapy. Baseline characteristics including demographic, clinico-pathologic, and laboratory data were compared between LTS and STS. Treatment response by the RECIST criteria was summarized for the two survival groups. Results 152 patients were LTS and 218 were STS. Adverse clinical and laboratory prognostic factors previously described in the IMDC prognostic model were significantly more frequent in the STS group (p<0.0001). In the LTS group, 138 patients (91%) had non-progressive disease (non-PD) as best response to first-line targeted therapy, and 56 of 94 patients (60%) who received second-line therapy had non-PD. In the STS group, only 51 patients (23%) had non-PD on first-line therapy. None of 21 the patients who received second-line therapy had non-PD as best response. In LTS, the median duration of therapy was 23.6 months (range: 0.4, 81.8+) for first-line and 11.5 months (range: 0.6-45.7) for second-line compared to 2.0 and 0.8 months for the STS respectively. Conclusion Baseline prognostic criteria and absence of PD after first and second-line targeted therapy may characterize long-term survivors.
    Clinical Genitourinary Cancer 01/2014; · 1.43 Impact Factor
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    ABSTRACT: Background Approval of the mTOR inhibitors for the treatment of metastatic RCC was based on efficacy in poor risk patients in the first-line setting for temsirolimus and in VEGF inhibitor-refractory patients for everolimus. We strove to characterize temsirolimus and everolimus use and effectiveness in the first-line setting. Patients and Methods Retrospective database analysis of mRCC patients who received mTOR inhibitors as first-line targeted therapy. The Kaplan-Meier product-limit method was used to estimate the distributions of progression-free survival (PFS) and overall survival (OS). Results We identified 127 mRCC patients who had received a first-line mTOR inhibitor. Temsirolimus was administered in 73% and everolimus in 27%. The main reasons for choice of temsirolimus were poor risk disease (38%), non-clear cell histology (27%), and clinical trial availability (15%) whereas clinical trial (82%) and non-clear cell histology (6%) drove everolimus selection. Of the temsirolimus and everolimus patients, 58% and 32% were poor risk by IMDC criteria, respectively. The median PFS and OS were 3.4 and 12.5 months and 4.8 and 15.9 months with temsirolimus and everolimus respectively. While limited by small numbers, this study characterizes a real world, international experience with the use of mTOR inhibition in treatment-naïve metastatic RCC patients. Conclusions Poor-risk RCC, non-clear cell histology, and clinical trials were the predominant reasons for mTOR inhibitor selection in the front-line setting. Given the different patient populations in which they were administered, direct comparisons of the frontline efficacy of temsirolimus and everolimus cannot be made.
    Clinical Genitourinary Cancer 01/2014; · 1.43 Impact Factor
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    ABSTRACT: BACKGROUND: Inflammation may play an important role in cancer progression, and a high neutrophil-to-lymphocyte ratio (NLR) has been reported to be a poor prognostic indicator in several malignancies. Here we quantify the prognostic impact of this biomarker and assess its consistency in solid tumors. METHODS: A systematic review of electronic databases was conducted to identify publications exploring the association of blood NLR and clinical outcome in solid tumors. Overall survival (OS) was the primary outcome, and cancer-specific survival (CSS), progression-free survival (PFS), and disease-free survival (DFS) were secondary outcomes. Data from studies reporting a hazard ratio and 95% confidence interval (CI) or a P value were pooled in a meta-analysis. Pooled hazard ratios were computed and weighted using generic inverse-variance and random-effect modeling. All statistical tests were two-sided. RESULTS: One hundred studies comprising 40559 patients were included in the analysis, 57 of them published in 2012 or later. Median cutoff for NLR was 4. Overall, NLR greater than the cutoff was associated with a hazard ratio for OS of 1.81 (95% CI = 1.67 to 1.97; P < .001), an effect observed in all disease subgroups, sites, and stages. Hazard ratios for NLR greater than the cutoff for CSS, PFS, and DFS were 1.61, 1.63, and 2.27, respectively (all P < .001). CONCLUSIONS: A high NLR is associated with an adverse OS in many solid tumors. The NLR is a readily available and inexpensive biomarker, and its addition to established prognostic scores for clinical decision making warrants further investigation.
    J Natl Cancer Inst. 01/2014; 106(6):dju124.
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    ABSTRACT: Introduction Abiraterone (AA) is a CYP17 inhibitor that prolongs survival in men with metastatic castration-resistant prostate cancer (mCRPC). Data suggest similar pharmacokinetics of 250–500 mg of AA with high-fat meals (‘low-dose’) and 1000 mg in the fasting state (‘full-dose’). Ketoconazole (KT) is a less potent CYP17 inhibitor previously widely used in mCRPC. Objective To study outcomes of men with mCRPC treated with low-dose AA and/or with prior exposure to KT. Patients and methods Retrospective chart review of all men treated with AA at the Princess Margaret Cancer Centre between November 2009 and March 2013. Outcome measures were prostate-specific antigen response rate (PSA-RR), biochemical progression-free survival (bPFS), treatment duration and overall survival (OS). Associations between AA dose or prior KT and outcomes were assessed using chi-square test for PSA-RR and log-rank test for bPFS, treatment duration and OS. Results In total, 111 men who received AA were evaluable, of which 21 received low-dose AA and 23 received prior KT. There was a non-significant difference in PSA-RR (43% versus 32%, p = 0.37), but no significant differences in median bPFS, median treatment duration and median OS (18.7 versus 16.6 months, p = 0.25) in the full and low-dose cohorts respectively, and for those who received prior KT or not (PSA-RR 48% versus 38%, p = 0.4; median OS 24.2 versus 16.5 months, p = 0.066, respectively). Conclusions Low-dose AA or prior KT treatment were not associated with poorer outcome in men with mCRPC treated with AA. These observations may have implications for drug sequencing and dose in resource-limited settings.
    European Journal of Cancer. 01/2014;
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    ABSTRACT: Outcomes and prognosis of metastatic sarcomatoid renal cell carcinoma (sRCC) in the targeted-therapy era are not well described. This retrospective series of 230 patients with metastatic sRCC examined the role anti-VEGF agents as a treatment option. The validity of the IMDC prognostic model in patients with metastatic sRCC was confirmed. Sarcomatoid histology was found to be an independent factor for adverse prognosis. Background Sarcomatoid RCC (sRCC) is associated with poor prognosis. Data regarding outcome in the targeted therapy era is lacking. Methods Clinical, prognostic, and treatment parameters in mRCC patients with and without sarcomatoid histology treated with targeted therapy were retrospectively analyzed. Results 2,286 patients were identified (sRCC (n=230); non-sRCC (n=2,056)). sRCC patients had significantly worse IMDC prognostic criteria compared to non-sRCC (11% vs. 19% favorable risk, 49% vs. 57% intermediate risk, and 40% vs. 24% poor risk; p<0.0001). Time from original diagnosis to relapse (excluding synchronous metastatic disease) was shorter in the sRCC group (18.8 vs. 42.9 months; p<0.0001). There was no significant difference in the incidence of CNS metastases (6-8%) or underlying clear cell histology (87-88%). Greater than 93% of patients received VEGF inhibitors as first line therapy; objective response was less common in sRCC whereas primary refractory disease was more common (21% vs. 26% and 43% vs. 21%; p<0.0001, for both). sRCC patients had significantly less use of second- (p=0.018) and third-line (p<0.0001) systemic therapy. The median PFS / OS was 4.5 / 10.4 months in sRCC patients and 7.8 / 22.5 months in non-sRCC patients (p<0.0001 for both). Sarcomatoid histology was associated with a significantly worse PFS and OS after adjusting for individual IMDC risk factors in multivariable analysis (HR 1.5, p<0.0001 for both). Conclusions Patients with sRCC have a shorter time to relapse, worse baseline prognostic criteria, and worse clinical outcome to targeted therapy. Additional insight into the biology of sRCC is needed to develop alternative therapeutics.
    Clinical Genitourinary Cancer 01/2014; · 1.43 Impact Factor

Publication Stats

2k Citations
489.43 Total Impact Points

Institutions

  • 2005–2014
    • University Health Network
      • Department of Medical Oncology
      Toronto, Ontario, Canada
  • 2004–2014
    • The Princess Margaret Hospital
      Toronto, Ontario, Canada
    • University of Toronto
      • • Department of Surgery
      • • Department of Radiation Oncology
      Toronto, Ontario, Canada
  • 2010–2013
    • Dana-Farber Cancer Institute
      • Department of Medical Oncology
      Boston, MA, United States
  • 2009–2013
    • Tom Baker Cancer Centre
      Calgary, Alberta, Canada
  • 2012
    • Stanford University
      • Stanford Cancer Institute
      Stanford, CA, United States
  • 2011
    • London Health Sciences Centre
      London, Ontario, Canada
    • The University of Calgary
      Calgary, Alberta, Canada
    • Vancouver Prostate Centre
      Vancouver, British Columbia, Canada
  • 2007
    • Hospital Israelita Albert Einstein
      San Paulo, São Paulo, Brazil
  • 2006
    • Dalhousie University
      Halifax, Nova Scotia, Canada