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Bar J.,Ottawa Hospital Cancer Center | Bar J.,Sheba Medical Center | Onn A.,Sheba Medical Center
Clinical Lung Cancer | Year: 2012

The epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) gefitinib and erlotinib have provided substantial benefits to patients with advanced non-small cell lung cancer (NSCLC). However resistance to these agents has emerged as a significant clinical issue; most patients who initially respond to treatment eventually experience relapse. The mechanisms underlying gefitinib and erlotinib resistance are multifactorial and several have been described. Clearly there is a need for novel and more effective therapies that can overcome resistance to the currently available TKIs. Several agents are in clinical development, including irreversible EGFR TKIs, inhibitors of the MET pathway, and others. In this review we discuss the various underlying mechanisms of gefitinib and erlotinib resistance and highlight the agents currently in clinical development that may have potential for overcoming this resistance. © 2012 Elsevier Inc. All rights reserved.

Tkachuk G.A.,University of Manitoba | Harris C.A.,Ottawa Hospital Cancer Center
Journal of Pain | Year: 2012

The aim of this study was to investigate the psychometric properties of an abbreviated version of the Tampa Scale for Kinesiophobia (TSK) in a clinical sample of patients with chronic pain. Chronic pain patients (n = 276) seeking treatment at an interdisciplinary treatment center completed self-report questionnaires including the TSK-13, and 2 tests of physical functioning. Four competing models of the TSK were tested using confirmatory factor analysis. Internal consistency was assessed, as were discriminant evidence of construct validity and concurrent criterion-related validity. Incremental validity was assessed with hierarchical multiple regressions controlling for pain severity. The analyses indicated that an 11-item, 2-factor structure best fit the data. The first factor, somatic focus, consisted of 5 items, while the second factor, activity avoidance, was comprised of 6 items. The TSK-11 scales demonstrated acceptable levels of internal consistency, as well as evidence of discriminant, concurrent criterion-related, and incremental validity. Somatic focus uniquely predicted perceived disability while activity avoidance uniquely predicted actual physical performance, controlling for pain severity. The 2-factor structure of the TSK-11 was found to be a brief, reliable, and valid measure of fear of movement/(re)injury for chronic pain patients. We recommend that the TSK-11 be used in future research and in clinical settings. Perspective: In this study, confirmatory factor analysis identified the 2-factor TSK-11 as the best fitting model of TSK factor structure. The TSK-11 is a brief, reliable, and valid measure of fear of movement/(re)injury for chronic pain patients. © 2012 by the American Pain Society.

Tanderup K.,Aarhus University Hospital | Tanderup K.,University of Aarhus | Beddar S.,University of Houston | Andersen C.E.,Technical University of Denmark | And 2 more authors.
Medical Physics | Year: 2013

In vivo dosimetry (IVD) has been used in brachytherapy (BT) for decades with a number of different detectors and measurement technologies. However, IVD in BT has been subject to certain difficulties and complexities, in particular due to challenges of the high-gradient BT dose distribution and the large range of dose and dose rate. Due to these challenges, the sensitivity and specificity toward error detection has been limited, and IVD has mainly been restricted to detection of gross errors. Given these factors, routine use of IVD is currently limited in many departments. Although the impact of potential errors may be detrimental since treatments are typically administered in large fractions and with high-gradient-dose-distributions, BT is usually delivered without independent verification of the treatment delivery. This Vision 20/20 paper encourages improvements within BT safety by developments of IVD into an effective method of independent treatment verification. © 2013 American Association of Physicists in Medicine.

Jarvis V.,Ottawa Hospital Cancer Center
Current Opinion in Supportive and Palliative Care | Year: 2014

Purpose of review The role of palliative care interventions in patients with nonmetastatic disease is unclear. Locally advanced breast cancer (LABC) is such a diagnosis that presents a platform to examine the relationship of symptom management while patients are receiving treatment with curative intent. Recent findings Overwhelming physical and psychological symptoms can affect women with LABC. Fungating lesions at the time of primary presentation remain a major challenge. Treatments specifically for the treatment of fungating lesions using new dressings, topical analgesics, buccal opioids, and old techniques such as larval therapy were explored. Summary LABC is a complex biosocial disease that requires a collaborative interdisciplinary approach to care. © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins.

Spaans J.N.,Ottawa Hospital Research Institute | Goss G.D.,Ottawa Hospital Research Institute | Goss G.D.,Ottawa Hospital Cancer Center | Goss G.D.,University of Ottawa
Frontiers in Oncology | Year: 2014

Our ability to detect and directly target the oncogenic alterations responsible for tumorproliferation has contributed significantly to the management of lung cancer in the last decade.The therapeutic efficacy of molecularly targeted therapy is, however, mainly limited to patientsharboring certain genetic mutations and is generally short-lived. Herein, we review primary andsecondary drug resistance using the most well-studied of the molecularly targeted agents, thetyrosine kinase inhibitors targeting the epidermal growth factor (EGF) receptor and theanaplastic lymphoma kinase (ALK) rearrangement, the current limitations of targeted therapiesand their consequences on the management of patients with lung cancer. © 2014 Spaans and Goss.

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