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Title: Physical performance and muscle mass in the assessment of sarcopenia and its association with receipt and completion of planned treatment in non-small cell lung cancer
Author: Collins, Jemima
ISNI:       0000 0004 7426 6338
Awarding Body: Cardiff University
Current Institution: Cardiff University
Date of Award: 2017
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Lung cancer is the third most common cancer in the United Kingdom, and the most common cancer worldwide, where approximately 1.61 million new cases are diagnosed every year. The prognosis is bleak as many present at advanced stages, despite advances in systemic anticancer-treatment, including targeted treatment. In the United Kingdom, at 5 years only 11-16% are still alive, with this proportion decreasing to approximately 5% at 10 years. Survival is dependent on many factors, one of which is whether or not treatment is received. In advanced lung cancer, survival was poorer in those who did not receive treatment, regardless of performance status (PS). However, many lung cancer patients who are initially considered eligible for treatment do not go on to receive it, as a result of declining physical function. The importance of receiving and subsequently completing treatment planned by the multidisciplinary team, as an endpoint, has been overlooked thus far, in favour of survival. Although survival is undoubtedly important, understanding factors which may be predictive of receipt and completion of treatment will enable better stratification of risks and benefits of treatment. Sarcopenia is a condition which is defined as depletion of muscle mass, and either poor physical performance or low muscle strength. It was originally recognised in the context of older people, but is also prevalent in many cancer groups. In non-small cell lung cancer (NSCLC), muscle mass depletion has been associated with poor survival, and potential increased risk of chemotherapy toxicity. However, in this context muscle mass is rarely assessed with physical function, and the latter may also have predictive potential. Whether or not bioelectrical impedance (BIA)-measured muscle mass is associated with treatment outcomes in NSCLC is also unclear. The overall aim of this thesis was to examine the value of muscle mass and physical performance measurements in predicting receipt and completion of treatment in NSCLC. Chapters 2 and 3 concern the primary and secondary aims of the thesis, as well as details of recruiting participants, the study protocol and techniques used. In chapter 4, the body composition of all participants, including muscle mass, fat mass and body mass index (BMI) was described. None of these parameters had any association with treatment receipt or completion. However, a subset analysis of muscle mass values from BIA compared with dual energy x-ray absorptiometry (DXA) values showed that BIA consistently overestimated DXA values. BIA-derived values consistent with sarcopenia were present in 19.4% of participants. Although individually sarcopenic participants had worse outcomes than their counterparts in surgery and chemotherapy groups, statistically this was not significant. In Chapter 5, the predictive value of nutritional status on receipt and completion of treatment is presented. Nutritional status parameters of weight loss, BMI, albumin, C-reactive protein and malnutrition universal screening tool (MUST) were evaluated for prediction of treatment-related outcomes. Weight loss of 10% or more was predictive of being less able to complete of treatment in all groups, as well as being less likely to receive chemotherapy. A higher CRP was associated with being less able to complete treatment in all groups, and a higher albumin associated with completion of 3 or more cycles of chemotherapy in the group planned for chemotherapy. BMI and MUST were not predictive of treatment outcomes. In Chapter 6, the predictive value of physical performance assessed by the Short Physical Performance Battery and its component parts was evaluated. In the chemotherapy group, totalSPPB, gait speed and sit-to-stand were all predictive of completion of more cycles of chemotherapy. We also found that for every unit increase in SPPB score, there was a 28.2% decrease in chemotherapy toxicity events. There was no relationship between muscle mass and SPPB score, and between SPPB score and PS. Chapter 7 investigates the relationship between both physician and patient-rated Eastern Cooperative Oncology Group (ECOG) and Karnofsky PS, and whether any of these are predictive of receipt or completion of treatment. PS between physician and patient was poorly correlated for both scores, but there was no tendency for the physician to over- or under-estimate patients’ scores. In terms of predicting completion of treatment in all groups, only patient-rated ECOG PS showed an association. However, in the chemotherapy group only, physician-rated ECOG PS was predictive of receipt of chemotherapy. The results of the chapters taken together demonstrate that PS which is currently used to evaluate NSCLC patients’ fitness for treatment is insufficient to predict receipt or completion of treatment. SPPB as a marker of physical performance shows promise as a simple bedside test for predicting chemotherapy completion, and may be able to predict risk of chemotherapy toxicity. Patient-rated PS as well as some nutritional status markers such as weight loss of 10% of more, CRP and albumin, could add to the robustness of future studies looking at creating a predictive model for treatment receipt and completion.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (M.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available