Where is the Person in Symptom Cluster Research? The Experience of Symptom Clusters in Patients with Advanced Lung Cancer This thesis describes a three-year qualitative study which aimed to explore the experience of symptom clusters in patients with advanced lung cancer. The study employed a patient-focused approach utilising Interpretative Phenomenological Analysis (IPA) (Smith et al. 2009a). This methodology (IPA), informed by a contextual constructionist stance, was selected to explore the experience of symptom clusters, for its focus on the lived experience, the context and meanings which surround such experiences and its idiographic approach. Ten patients (a sample size which is the upper limit of the number of participants advocated for studies employing IPA (Smith et al. 2009b;Reid et al. 2005;Smith and Osborn 2004)) with advanced lung cancer took part in the study and data were collected using unstructured, in-depth interviews at two time points: on recruitment and three to five weeks later. Data were analysed using Interpretative Phenomenological Analysis, within the framework advocated by Smith and Osborn (2003). The study generated interesting and significant findings. The experience of symptom clusters in patients with advanced lung cancer was characterised by two super-ordinate themes: ‘The lived experience of symptom clusters and the role of context and meaning’ and ‘Symptom clusters and loss of sense of self’. The super-ordinate theme of ‘The lived experience of symptom clusters and the role of context and meaning’ in the first instance, illustrates that the participants in this study were experiencing symptom clusters and providing detail on the components, nature and patterning of the symptom clusters reported, particularly the way that one or two salient symptoms were commonly highlighted from all the other symptoms experienced. This super-ordinate theme also demonstrates the core role that context and meaning play in the lived experience of symptom clusters, with many of the participants in this study framing their experiences of symptom clusters within a fear of death, stigma and loss of sense of self. The second super-ordinate theme informing this thesis is ‘Symptom clusters and loss of sense of self’. This super-ordinate theme illustrates the impact of symptom clusters on the participants’ lives, and how this, in turn, impacted on their sense of self in a number of different ways. For some, their sense of self was compromised by the concurrent symptoms that they were experiencing, as they prevented them from undertaking roles and activities that they were accustomed to in the past. This super-ordinate theme also highlights the role of the body relative to the self, and describes how the participants’ sense of self was transiently lost during periods when they experienced symptom clusters of high severity. The findings presented also demonstrate the knock-on effect of loss of sense of self experienced, with the participants feeling like they were a burden due to their incapacitation, and at times hiding the multiple symptoms that they were experiencing, in a bid to protect their loved ones from their illness. In light of the loss of sense of self experienced, this super-ordinate theme also demonstrates how the participants employed various strategies in a bid to try and maintain a coherent and valued sense of self. The findings presented illustrate how the use of IPA facilitated the collection of data that provided an in-depth understanding of the complexity of the experience of symptom clusters in patients with advanced lung cancer, adding a unique contribution to this body of knowledge. The results of this study highlight the limitations of definitions that currently underpin the study of symptom clusters in patients with cancer and the current empirical base to date, particularly the way that they do not acknowledge the core role that context and meaning play in the lived experience of this phenomenon. This lack of recognition of these core elements of the patient experience of symptom clusters poses the risk of this body of research producing data that have limited relevance to the patient and therefore clinical practice. It is therefore proposed that the study of symptom clusters in patients with cancer needs to move away from the reductionist approach which currently dominates and to broaden its scope, to one that acknowledges the complexity of the experience of symptom clusters, the core role that context and meaning play in such experiences, and contributions that patient experience can make in advancing this important and emerging body of research.

Cancer is a set of complex genetic diseases driven by diverse genomic alterations. The genomic study of cancer has enabled the discovery of novel, targetable events in almost all cancer types and in turn, has led to the development of new, targeted cancer therapies benefiting patients; however, the recent explosion of genomic datasets has also resulted in huge lists of new oncogenic factors of unknown biological relevance, and uncertainty over how best to use the data appropriately to influence patient care. Some of the most pressing questions surround the use of statistical methods to identify actionable genomic alterations in cancer and the identification of driving oncogenes in the context of the genomic evolution of cancer cells, undergone before, during, and after prolonged treatment regimens.

Introduction: New treatments for stage IV (adv) NSCLC have emerged this past decade. Recent pharmacoeconomic research has focused on cost of treatment, comparative costs of therapies, and cost/cost effectiveness of adding a biologic to traditional therapy. Drug cost is thought to be a primary driver of cost change in NSCLC, yet to our knowledge, characterization of the direct cost of NSCLC has not been published since the new treatments have emerged in the guidelines. Our primary objective was to characterize the direct and segmented cost of adv NSCLC from 2000-9. We also want to determine cost impact of new therapies, and cost trend from 2000-9. Methods: This PharMetrics claims database study includes diagnosed NSCLC patients [greater than or equal to] 20 yo. Small cell lung cancer was excluded. Claims were divided into disease segments and time periods representative of changes in therapy ("pre" (2000-2), "transition" (2003-5), and "current" (2006-9) periods). Descriptive statistics (median, interquartile range (IQR)), chi-square test (nominal data), and Wilcoxan rank sum tests were performed on the data. To adjust for baseline confounders, multivariate least squares regression models were created. Results: Costs are reported as medians in terms of per patient per month (pppm). Overall monthly cost (n=969) was $10,281 pppm. Diagnosis cost $6,601 pppm, active treatment cost $9,287 pppm, and end-of life cost $12,215 pppm. There was no difference in cost between the “transition” (n=439) and “current” (n=503) periods overall or for any segment of disease. Comorbidities had no effect on cost. For patients receiving at least 5 months of active treatment medication (n=316) total median cost was $144,147 per patient ($9,371 pppm). Discussion: There was no difference in cost between the transition and current periods, in regards to either overall cost or segmented cost. The most expensive segment was end-of-life, with a median cost exceeding $12,000 pppm. Surprisingly, comorbidities had no effect on cost. Newer agents (biologics, TKIs, and pemetrexed) represent only a modest portion of cost, with a majority of cost for stage IV NSCLC comprised of non-drug costs. / text

published_or_final_version / Pathology / Master / Master of Philosophy

No description available.

The study aims to estimate the ability of different grouping techniques on categorical response. We try to find out how well do they work? Do they really find clusters when clusters exist? We use Cancer Problems in Living Scales from the ACS as our categorical data variables and lung cancer survivors as our studying group. Five methods of cluster analysis are examined for their accuracy in clustering on both real CPILS dataset and simulated data. The methods include hierarchical cluster analysis (Ward's method), model-based clustering of raw data, model-based clustering of the factors scores from a maximum likelihood factor analysis, model-based clustering of the predicted scores from independent factor analysis, and the method of latent class clustering. The results from each of the five methods are then compared to actual classifications. The performance of model-based clustering on raw data is poorer than that of the other methods and the latent class clustering method is most appropriate for the specific categorical data examined. These results are discussed and recommendations are made regarding future directions for cluster analysis research.

EGFR TKIs are standard therapy for advanced NSCLC. In order to define their role in early disease, we implemented a phase II trial of neoadjuvant gefitinib in clinical stage I NSCLC. Tumour shrinkage was seen in 43% of patients, with 11% achieving RECIST partial response (PR). Analysis of molecular markers showed EGFR TKD mutations in 17% of cases, being the only associated with PR. For the first time we defined the histopathological response of NSCLC to these agents, characterized by reduction in tumour cellularity and proliferative index as well as presence of non-mucinous BAC histology. Clinical PR tumours also presented large areas of stromal fibrosis with presence of focal residual tumour. In a characterization of intracellular signalling response, EGFR dephosphorylation in the residues Y1068 and Y1173 was not concordant and only the former was significantly reduced. pAkt Ser473/Akt and Thr308/Akt ratios were significantly reduced but observed among both, clinical responders and resistant patients. Interestingly, reduction in pEGFR Y1068 was significantly associated with increase in tumour cellularity (p=0.047), Ki-67 index (p=0.018) and tumour growth (p=0.019) with a residual perinuclear localization been detected, suggesting a novel mechanism of resistance involving receptor internalization. Finally, we determined that the EGFR protein remains stable up to one hour of post resection ischemia but two to three tumour samples are necessary for an adequate tumour representation. Furthermore, EGFR cytoplasmic compartment presented the best association with clinical response in our cohort. Taking all together, we were able to generate the first clinical trial exploring the use of an EGFR TKI in early NSCLC, characterizing for the first time the histopathological and signalling responses to these agents with an evidence of a potential novel mechanism of resistance. Finally, we observed that multiple samples collection for an adequate tumour representation, and assessment of the cytoplasmic compartment, are warrant.

EGFR TKIs are standard therapy for advanced NSCLC. In order to define their role in early disease, we implemented a phase II trial of neoadjuvant gefitinib in clinical stage I NSCLC. Tumour shrinkage was seen in 43% of patients, with 11% achieving RECIST partial response (PR). Analysis of molecular markers showed EGFR TKD mutations in 17% of cases, being the only associated with PR. For the first time we defined the histopathological response of NSCLC to these agents, characterized by reduction in tumour cellularity and proliferative index as well as presence of non-mucinous BAC histology. Clinical PR tumours also presented large areas of stromal fibrosis with presence of focal residual tumour. In a characterization of intracellular signalling response, EGFR dephosphorylation in the residues Y1068 and Y1173 was not concordant and only the former was significantly reduced. pAkt Ser473/Akt and Thr308/Akt ratios were significantly reduced but observed among both, clinical responders and resistant patients. Interestingly, reduction in pEGFR Y1068 was significantly associated with increase in tumour cellularity (p=0.047), Ki-67 index (p=0.018) and tumour growth (p=0.019) with a residual perinuclear localization been detected, suggesting a novel mechanism of resistance involving receptor internalization. Finally, we determined that the EGFR protein remains stable up to one hour of post resection ischemia but two to three tumour samples are necessary for an adequate tumour representation. Furthermore, EGFR cytoplasmic compartment presented the best association with clinical response in our cohort. Taking all together, we were able to generate the first clinical trial exploring the use of an EGFR TKI in early NSCLC, characterizing for the first time the histopathological and signalling responses to these agents with an evidence of a potential novel mechanism of resistance. Finally, we observed that multiple samples collection for an adequate tumour representation, and assessment of the cytoplasmic compartment, are warrant.

1. INTRODUCTION Lung cancer is the most common malignancy in the world and accounts for 1.09 million new cases with 972 000 deaths per year. In Lithuania too, lung cancer is the most commonly diagnosed cancer in men with nearly 1500 new cases each year. Lung cancer is five times more common in men than in women. At present, most patients who receive an initial diagnosis of lung cancer have advanced stage disease (stage IV – 30.2%), making cure with currently available therapies unlikely. The main prognostic information with regard to survival is associated with the biological characteristics of the primary tumour (histological subtype, aggressiveness, differentiation, etc.), the extent of spread to regional or distant lymph nodes or to the other structures, and the operability of the patient (age, function of residual lung, co-morbidity). Because the outcome is associated with the histological subtype and stage of the lung cancer at the diagnosis, there has been persistent interest in designing and testing various radiological methods for early detection of lung cancer. Chest radiography, computed tomography (CT), magnetic resonance imaging (MRI) can not only identify specific features in lung nodules, but add important information about the localisation, size and extent of the primary tumour (T), detect invasion of major mediastinal structures and chest wall, and locoregional (N) and distal spread of the tumour. Although theoretically features such as nodal shape... [to full text]

Background: Randomized controlled trials (RCTs) are the gold standard for assessing the efficacy of a medical treatment. However, the efficacy demonstrated by trials does not automatically translate into a comparable level of effectiveness in the real world. RCTs may vary from routine clinical practice in several ways; the patients themselves, the delivery of the treatment, and the collateral care provided during treatment. Phase IV studies that assess outcomes of a treatment in the real-world provide a mechanism for assessing treatment effectiveness. Objectives: The objectives of this study were to: describe the characteristics of patients receiving standard, first-line, palliative, platinum-doublet chemotherapy (PPDC) for non-small cell lung cancer (NSCLC) in routine care; describe the effectiveness of PPDC in terms of wellbeing and symptom control; identify patient characteristics associated with change in wellbeing with treatment; and compare reported treatment efficacy to the effectiveness observed in the current study. Methods: This study was a retrospective cohort study of patients treated at Ontario’s Regional Cancer Centres (RCCs). Patients’ Edmonton Symptom Assessment System (ESAS) scores were used to describe patients’ symptomatic status and wellbeing. The proportions of patients whose wellbeing improved, remained stable or deteriorated at two months were calculated. Using logistic regression, patient and disease characteristics were assessed for association with change in wellbeing at two months (dichotomized as improved/stable and deteriorated). In comparing trial results to this study, adjustments were made for differences in case mix. Results: Patients’ median age was 65, 55% were male and the majority had stage IV disease and adenocarcinoma histology. Patients’ baseline wellbeing and symptomatic status varied widely. 61.3% (95% CI: 55.8 – 66.6%) of patients had improved or stable wellbeing at two months. Histology and baseline wellbeing score were associated with change in wellbeing at two months. The case mix adjusted estimates of the proportion of improved/stable patients (60.0% (95% CI 54.5 – 65.3) and 60.5% (95% CI 54.9 – 65.6)) were consistent with the proportion of patients achieving general quality of life improvement or stabilization in RCTs (55% and 63%). Conclusion: The effectiveness of PPDC delivered in Ontario’s RCCs is consistent with that expected based on the results of RCTs. / Thesis (Master, Community Health & Epidemiology) -- Queen's University, 2012-04-23 11:53:33.491