9 results on '"Chia, Stephen"'
Search Results
2. Understanding adjuvant endocrine therapy persistence in breast Cancer survivors
- Author
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Lambert, Leah K., Balneaves, Lynda G., Howard, A. Fuchsia, Chia, Stephen K., and Gotay, Carolyn C.
- Published
- 2018
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3. Effect of continuous statistically standardized measures of estrogen and progesterone receptors on disease-free survival in NCIC CTG MA.12 Trial and BC Cohort
- Author
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Chapman, Judith-Anne W, Nielsen, Torsten O, Ellis, Matthew J, Bernard, Phillip, Chia, Stephen, Gelmon, Karen A, Pritchard, Kathleen I, Maitre, Aurelie Le, Goss, Paul E, Leung, Samuel, Shepherd, Lois E, and Bramwell, Vivien H C
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- 2013
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4. A phase-I study of lapatinib in combination with foretinib, a c-MET, AXL and vascular endothelial growth factor receptor inhibitor, in human epidermal growth factor receptor 2 (HER-2)-positive metastatic breast cancer.
- Author
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Chia, Stephen K., Ellard, Susan L., Mates, Mihaela, Welch, Stephen, Mihalcioiu, Catalin, Miller Jr, Wilson H., Gelmon, Karen, Lohrisch, Caroline, Kumar, Vikaash, Taylor, Sara, Hagerman, Linda, Goodwin, Rachel, Tao Wang, Shingo Sakashita, Tsao, Ming S., Eisenhauer, Elizabeth, Bradbury, Penelope, Miller, Wilson H Jr, Wang, Tao, and Sakashita, Shingo
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BREAST cancer ,LAPATINIB ,HER2 protein ,VASCULAR endothelial growth factor receptors ,MET receptor ,PHARMACOKINETICS - Abstract
Background: The mechanisms of resistance to anti-human epidermal growth factor receptor 2 (HER 2) therapies are unclear but may include the tyrosine-protein kinase Met (c-Met), vascular endothelial growth factor (VEGF) and AXL pathways. Foretinib is an inhibitor of c-Met, VEGF receptor 2 (VEGFR-2), platelet-derived growth factor receptor beta (PDGFRB), AXL, Fms-like tyrosine kinase 3 (FLT3), angiopoiten receptor (TIE-2), RET and RON kinases. This phase Ib study sought to establish the associated toxicities, pharmacokinetics (PK) and recommended phase II doses (RP2D) of foretinib and lapatinib in a cohort of HER-2-positive patients with metastatic breast cancer (MBC).Methods: Women with HER-2 positive MBC, Performance status (PS 0-2), and no limit on number of prior chemotherapies or lines of anti-HER-2 therapies were enrolled. A 3 + 3 dose escalation design was utilized. Four dose levels were intended with starting doses of foretinib 30 mg and lapatinib 750 mg orally once a day (OD) on a 4-weekly cycle. Assessment of c-MET status from the primary archival tissue was performed.Results: We enrolled 19 patients, all evaluable for toxicity assessment and for response evaluation. Median age was 60 years (34-86 years), 95% were PS 0-1, 53% were estrogen receptor-positive and 95% had at least one prior anti-HER-2-based regimen. The fourth dose level was reached (foretinib 45 mg/lapatinib 1250 mg) with dose-limiting toxicities of grade-3 diarrhea and fatigue. There was only one grade-4 non-hematological toxicity across all dose levels. There were no PK interactions between the agents. A median of two cycles was delivered across the dose levels (range 1-20) with associated progression-free survival of 3.2 months (95% CI 1.61-4.34 months). By immunohistochemical assessment with a specified cutoff, none of the 17 samples tested were classified as positive for c-Met.Conclusions: The RP2D of the combined foretinib and lapatinib is 45 mg and 1000 mg PO OD, respectively. Limited activity was seen with this combination in a predominantly unselected cohort of HER-2-positive patients with MBC. [ABSTRACT FROM AUTHOR]- Published
- 2017
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5. Mapping the FACT-G cancer-specific quality of life instrument to the EQ-5D and SF-6D.
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Teckle, Paulos, McTaggart-Cowan, Helen, Van der Hoek, Kim, Chia, Stephen, Melosky, Barb, Gelmon, Karen, and Peacock, Stuart
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ONCOLOGY ,CANCER patients ,CANCER education ,CANCER treatment ,MATHEMATICAL models - Abstract
Objective To help facilitate economic evaluations of oncology treatments, we mapped responses on cancer-specific instrument to generic preference-based measures. Methods Cancer patients (n = 367) completed one cancer-specific instrument, the FACT-G, and two preference-based measures, the EQ-5D and SF-6D. Responses were randomly divided to form development (n = 184) and cross-validation (n = 183) samples. Relationships between the instruments were estimated using ordinary least squares (OLS), generalized linear models (GLM), and censored least absolute deviations (CLAD) regression approaches. The performance of each model was assessed in terms of how well the responses to the cancerspecific instrument predicted EQ-5D and SF-6D utilities using mean absolute error (MAE) and root mean squared error (RMSE). Results Physical, functional, and emotional well-being domain scores of the FACT-G best explained the EQ-5D and SF-6D. In terms of accuracy of prediction as measured in RMSE, the CLAD model performed best for the EQ-5D (RMSE = 0.095) whereas the GLM model performed best for the SF-6D (RMSE = 0.061). The GLM predicted SF-6D scores matched the observed values more closely than the CLAD and OLS. Conclusion Our results demonstrate that the estimation of both EQ-5D and SF-6D utility indices using the FACT-G responses can be achieved. The CLAD model for the EQ-5D and the GLM model for the SF-6D are recommended. Thus, it is possible to estimate quality-adjusted life years for economic evaluation from studies where only cancer-specific instrument have been administered. [ABSTRACT FROM AUTHOR]
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- 2013
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6. Cost-effectiveness of MRI for breast cancer screening in BRCA1/2 mutation carriers.
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Pataky, Reka, Armstrong, Linlea, Chia, Stephen, Coldman, Andrew J., Kim-Sing, Charmaine, McGillivray, Barbara, Scott, Jenna, Wilson, Christine M., and Peacock, Stuart
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BREAST cancer diagnosis ,MEDICAL screening ,COST effectiveness ,MAGNETIC resonance imaging of cancer ,MAMMOGRAMS ,BRCA genes ,WOMEN ,BREAST tumor diagnosis ,RESEARCH ,GENETIC mutation ,RESEARCH methodology ,EARLY detection of cancer ,MAGNETIC resonance imaging ,EVALUATION research ,MEDICAL cooperation ,COMPARATIVE studies ,RESEARCH funding ,BREAST tumors ,PROBABILITY theory ,QUALITY-adjusted life years - Abstract
Background: Women with mutations in BRCA1 or BRCA2 are at high risk of developing breast cancer and, in British Columbia, Canada, are offered screening with both magnetic resonance imaging (MRI) and mammography to facilitate early detection. MRI is more sensitive than mammography but is more costly and produces more false positive results. The purpose of this study was to calculate the cost-effectiveness of MRI screening for breast cancer in BRCA1/2 mutation carriers in a Canadian setting.Methods: We constructed a Markov model of annual MRI and mammography screening for BRCA1/2 carriers, using local data and published values. We calculated cost-effectiveness as cost per quality-adjusted life-year gained (QALY), and conducted one-way and probabilistic sensitivity analysis.Results: The incremental cost-effectiveness ratio (ICER) of annual mammography plus MRI screening, compared to annual mammography alone, was $50,900/QALY. After incorporating parameter uncertainty, MRI screening is expected to be a cost-effective option 86% of the time at a willingness-to-pay of $100,000/QALY, and 53% of the time at a willingness-to-pay of $50,000/QALY. The model is highly sensitive to the cost of MRI; as the cost is increased from $200 to $700 per scan, the ICER ranges from $37,100/QALY to $133,000/QALY.Conclusions: The cost-effectiveness of using MRI and mammography in combination to screen for breast cancer in BRCA1/2 mutation carriers is finely balanced. The sensitivity of the results to the cost of the MRI screen itself warrants consideration: in jurisdictions with higher MRI costs, screening may not be a cost-effective use of resources, but improving the efficiency of MRI screening will also improve cost-effectiveness. [ABSTRACT FROM AUTHOR]- Published
- 2013
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7. Understanding adjuvant endocrine therapy persistence in breast Cancer survivors
- Author
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Lambert, Leah K, Balneaves, Lynda G, Howard, A. Fuchsia, Chia, Stephen K, and Gotay, Carolyn C
- Subjects
3. Good health - Abstract
Background: Adjuvant endocrine therapy (AET) significantly decreases the risk of breast cancer recurrence and mortality. Notwithstanding the demonstrated efficacy of AET, 31–73% of breast cancer survivors do not persist with AET. The purpose of this study was to explore breast cancer survivors’ experiences and perspectives of persisting with AET and to identify the psychosocial and healthcare system factors that influence AET persistence. Methods: Informed by interpretive descriptive methodology and relational autonomy theory, individual interviews were conducted with 22 women diagnosed with early-stage breast cancer who had been prescribed AET. These participants also completed a demographic form and a survey that assessed their perceived risk of recurrence. Interviews were analysed using inductive thematic and constant comparative analysis to iteratively compare data and develop conceptualizations of the relationships among data. Descriptive statistics were used to summarize the quantitative data. Results: The personal, social, and structural factors found to influence AET persistence included AET side effects, perception of breast cancer recurrence risk, medication and necessity beliefs, social support, the patient-provider relationship, and the continuity and frequency of follow-up care. For most women, over time, the decision-making process around AET persistence became a balancing act between quality of life and quantity of life. The interplay between the personal, social, and structural factors was complex and the weight women placed on some factors over others influenced their AET persistence or non-persistence. Conclusion: Expanding our understanding of the factors affecting breast cancer survivors’ AET persistence from their perspective is the first step in developing efficacious, patient-centered interventions aimed at improving AET persistence. In order to improve AET persistence, enhanced symptom management is required, as well as the development of supportive care strategies that acknowledge the values and beliefs held by breast cancer survivors while reinforcing the benefits of AET, and addressing women’s reasons for non-persistence. Improved continuity of health care and patient-healthcare provider communication across oncology and primary care settings is also required. The development and evaluation of supportive care strategies that address the challenges associated with AET experienced by breast cancer survivors hold the potential to increase both women’s quality and quantity of life.
8. Evaluating the predictive value of biomarkers for efficacy outcomes in response to pertuzumab- and trastuzumab-based therapy: an exploratory analysis of the TRYPHAENA study.
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Schneeweiss, Andreas, Chia, Stephen, Hegg, Roberto, Tausch, Christoph, Deb, Rahul, Ratnayake, Jayantha, McNally, Virginia, Ross, Graham, Kiermaier, Astrid, and Cortés, Javier
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ANTINEOPLASTIC agents ,ANTHROPOMETRY ,BREAST tumors ,MONOCLONAL antibodies ,GENETIC mutation ,PROGNOSIS ,TUMOR markers ,TUMOR classification ,TREATMENT effectiveness - Abstract
Introduction: Molecular markers that predict responses to particular therapies are invaluable for optimization of patient treatment. The TRYPHAENA study showed that pertuzumab and trastuzumab with chemotherapy was an efficacious and tolerable combination for patients with human epidermal growth factor receptor 2 (HER2)-positive breast cancer in the neoadjuvant setting. We analyzed whether particular biomarkers correlated with the responses observed and therefore may predict outcomes in patients given pertuzumab plus trastuzumab.Methods: We describe the analysis of a panel of biomarkers including HER2, human epidermal growth factor receptor 3 (HER3), epidermal growth factor receptor (EGFR), phosphatase and tensin homolog (PTEN), and phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) by qRT-PCR, immunohistochemistry (IHC), fluorescence in situ hybridization (FISH), enzyme-linked immunosorbent assay (ELISA), and PCR-based mutational analyses as appropriate. For each marker analyzed, patients were categorized into 'low' (generally below median) or 'high' (generally above median) subgroups at baseline and post-treatment.Results: Correlation of marker subgroups with the achievement of a pathological complete response (pCR) (ypT0/is) was analyzed. HER2 protein and mRNA expression levels were associated with pCR rate in two of the three study arms and the pooled analyses. Correlations of biomarker status with pCR occurred in one individual arm only and the pooled analyses with EGFR and PTEN; however, interpretation of these results is limited by a strong imbalance in patient numbers between the high and low subgroups and inconsistency between arms. We also found no association between expression levels of TOP2A and pCR rate in either the anthracycline-containing or free arms of TRYPHAENA.Conclusions: According to these analyses, and in line with other analyses of pertuzumab and trastuzumab in the neoadjuvant setting, we conclude that HER2 expression remains the only marker suitable for patient selection for this regimen at present.Trial Registration: The TRYPHAENA study was registered with ClinicalTrials.gov, NCT00976989, on September 14 2009. [ABSTRACT FROM AUTHOR]- Published
- 2014
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9. The ability of cancer-specific and generic preference-based instruments to discriminate across clinical and self-reported measures of cancer severities.
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Teckle P, Peacock S, McTaggart-Cowan H, van der Hoek K, Chia S, Melosky B, and Gelmon K
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- Analysis of Variance, Female, Humans, Male, Middle Aged, Quality of Life, Self Disclosure, Statistics, Nonparametric, Surveys and Questionnaires, Breast Neoplasms pathology, Colorectal Neoplasms pathology, Lung Neoplasms pathology, Psychometrics instrumentation, Severity of Illness Index
- Abstract
Objective: To evaluate the validity of cancer-specific and generic preference-based instruments to discriminate across different measures of cancer severities., Methods: Patients with breast (n = 66), colorectal (n = 57), and lung (n = 61) cancer completed the EORTC QLQ-C30 and the FACT-G, as well as three generic instruments: the EQ-5D, the SF-6D, and the HUI2/3. Disease severity was quantified using cancer stage, Eastern Cooperative Oncology Group Performance Status (ECOG-PS) score, and self-reported health status. Comparative analyses confirmed the multi-dimensional conceptualization of the instruments in terms of construct and convergent validity., Results: In general, the instruments were able to discriminate across severity measures. The instruments demonstrated moderate to strong correlation with each other (r = 0.37-0.73). Not all of the measures could discriminate between different groups of disease severity: the EQ-5D and SF-6D were less discriminative than the HUI2/3 and the cancer-specific instruments., Conclusion: The cancer-specific and generic preference-based instruments demonstrated to be valid in discriminating across levels of ECOG-PS scores and self-reported health states. However, the usefulness of the generic instruments may be limited if they are not able to detect small changes in health status within cancer patients. This raises concerns regarding the appropriateness of these instruments when comparing different cancer treatments within an economic evaluation framework.
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- 2011
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