Sir Peter MacCallum Department of Oncology - Theses
Permanent URI for this collection
Search Results
1 - 8 of 8
-
ItemFever and neutropenia in children with cancer: optimising clinical research and the delivery of care in Australia( 2017)Fever and neutropenia (FN) is the most common complication of childhood cancer treatment. Management traditionally involves hospital admission for antibiotics until resolution of fever and recovery of neutrophil count. However, children with FN are a heterogeneous group with varying risk of severe infection, and this approach over treats up to half of all episodes where risk of serious complications is low. Unlike FN management for adults, formal low-risk treatment strategies for children are not routinely employed. In Australia, little is known about the aetiology and management of FN in children and clinical decision rules (CDRs), designed to predict infection, have not been validated. These factors remain a critical barrier to implementing ambulatory-care programs for children with low-risk FN in this country. Such programs are safe, improve quality of life (QoL) and reduce healthcare expenditures. The overall aims of this thesis were to optimise clinical paediatric FN research; to advance our understanding of the assessment and management of FN in children with cancer in Australia; and to facilitate treatment that is tailored to the patient’s risk of infection. Each project addresses important evidence gaps, namely the absence of standardised paediatric FN research outcomes and definitions, the lack of a contemporary evaluation of FN management in Australia and the limited use of risk-based treatment algorithms. To optimise clinical paediatric FN research, Delphi survey methodology was used to achieve consensus on a set of core variables and outcomes that should be reported in all FN studies. This is the first time a paediatric-specific FN research framework has been developed and is the result of an international collaboration. Standardised FN research outcomes will reduce heterogeneity between studies, minimise reporting bias and enable research results to be compared, contrasted and combined. To advance our understanding of the management of FN in Australia, a national practice survey was conducted. There was clear evidence of heterogeneity in assessment, risk stratification and treatment of children with FN. The survey identified critical knowledge gaps and deviations from best practice, and the results will be used to inform guidelines, education and low-risk program implementation strategies. It also highlighted the necessity for validation studies to determine which CDRs are most appropriate for use in Australia. A series of studies were conducted to facilitate FN treatment that is tailored to the risk of infection. In a retrospective study, seven CDRs were validated, of which two exhibited the most clinically meaningful results. The accompanying economic evaluation highlights opportunities for substantial healthcare savings by reducing length of stay (LOS) for low-risk patients. The systematic review and meta-analysis of the predictive ability of novel biomarkers found that marked heterogeneity between studies limits firm conclusions, and further research is required. This thesis has addressed key evidence gaps and contributed new knowledge that will optimise clinical FN research and the delivery of FN care to children with cancer. It has informed the national Australian Predicting Infectious ComplicatioNs in Children with Cancer (PICNICC) project that will prospectively validate CDRs, identify novel biomarkers and evaluate the cost and QoL associated with standard FN treatment. It has also established a collaborative network that will ensure FN research continues in this country and results are translated into practice.
-
ItemThe role of nature in cancer patients' experiences of health and recovery( 2017)This thesis explores the role of nature in cancer patients’ experiences of health and recovery. Using a 2-Phase mixed-method approach, the investigation aimed to generate new theoretical understanding about cancer patients’ use of nature and how they find nature engagement helpful or not when confronting cancer diagnosis. The project’s translational focus was to produce expert recommendations for nature-based care opportunities in oncology contexts based on patient-reported data. First, a systematic literature review and meta-synthesis was conducted to describe the existing qualitative research evidence base relating to nature experiences and nature-based interventions for cancer populations specifically. The aim was to describe current knowledge about the role of nature in cancer patients’ lives. From eleven eligible publications, seven inter-related core themes were identified as follows: connecting with what is valued; being elsewhere, seeing and feeling differently; exploration, inner and outer excursions; home and safe; symbolism, understanding and communicating differently; benefitting from old and new physical activities; and, enriching aesthetic experiences. Next, an in-depth investigation of cancer patients’ own experiences with nature used primary data to develop a new Grounded Theory describing the underlying and intrapsychic mechanisms of cancer patients’ phenomenal nature experiences. Based on qualitative data collected from semi-structured interviews with 20 cancer patients (9 female), the resulting theory model explores the unique role nature plays when diagnosed with cancer. It constitutes a core category and two inter-related themes, which explain a normalization process in which patients moved towards a state of 'new-normal' (Core Category). Nature functioned in this process as a support structure that repositioned patients and nurtured their inner and outer capacities to respond and connect more effectively (Theme A). Once enabled and comforted, participants could engage survival and reconstructive manoeuvres and explore the consequences of cancer in their present lives and possible futures (Theme B). A dynamic relationship was shown between moving away while, simultaneously, advancing towards the cancer reality in order for patients to incorporate their cancer experiences into a shifting normality. From a place of comfort and safety, patients felt supported to deal differently and more creatively with the threat and demands of cancer diagnosis, treatment, and outlook. The descriptively rich interview data provided further insights into patients’ own recommendations for nature engagement in the oncology context, which were extracted from the transcriptions using deductive content analysis and were consolidated into patient recommendations for nature-based care opportunities. These incorporated using nature for vital sensory stimulation and engagement, using nature for personal space and freedom to enable private and social exploration, using views of nature for distraction and comfort, and accessing nature for physical activity and movement. Three critical factors were determined to avoid adverse experiences: determining appropriate health-care expenditure and resourcing on nature-based interventions, selection of appropriate nature-based design materials, and exercising caution around demanding nature engagement and harsh weather conditions. A questionnaire survey study was conducted following an environmental intervention in an oncology waiting room to assess patient, visitor, and staff responses to design changes, which included the addition of artificial plant materials. Based on 143 returned survey questionnaires consisting of 73 cancer patients, 13 staff, 52 carers, and five ‘other’, it was found that the environmental intervention positively impacted patients, staff, and carers’ perceptions of the oncology waiting room environment. Patients, staff, and carers mostly accepted artificial plants as an alternative design solution to real plants. Comments included positive appraisals and occasional adverse reactions to artificial plants. No significant differences were found between patient, staff, and carer reactions. Insights gleaned from the initial, exploratory phase formed the basis for a second phase investigation comprising an international online Delphi study. The aim was to solicit knowledge from relevant experts drawn from a range of healthcare practitioners, management, designers, and researchers to determine feasible opportunities for, and barriers to, providing helpful nature engagement in oncology settings. Two hundred potential panellists were identified and sent an invitation to participate. Thirty-eight experts were recruited who represented 7 countries: Australia (19), USA (8), UK (3), New Zealand (2), Canada (2), Denmark (3), and Sweden (1). This study followed a structured, iterative feedback process that queried and synthesized expert opinion. Cancer patients’ own recommendations, extracted from phase 1, were used as a starting point for the Delphi panel to brainstorm and develop their own ideas about appropriate nature-based opportunities in oncology settings and the barriers to their provision. In total, 250 separate suggestions for opportunities and 205 suggestions for barriers were collected. Further analysis condensed these into 55 unique items (35 opportunities, 20 barriers). The Delphi panel’s list of recommendations included “Window views from clinical areas onto nature […]” as the highest rated opportunity, and “Building design and site constraints […]” as the highest rated barrier to providing nature-based supports for oncology care. Finally, a synthesis of findings from the overall investigation, which constitutes six publications, is provided to summarize and outline the salient findings and discern the study’s limitations in order to suggest pathways for future research. This synthesis produced a conceptual framework consolidating new theoretical understanding and empirical content from patient and expert-reported data about nature-based care opportunities in the oncology setting. The thesis findings provide evidence for multiple uses of nature as a supportive aid in the cancer care context. Concrete recommendations have resulted to guide the application of nature based concepts in future oncology setting design and may be considered when developing additional supportive care services. The findings may assist healthcare practitioners, designers, researchers, and patients themselves to creatively and practically participate in future oncology care practice and design.
-
ItemBET bromodomain inhibition as combined apoptotic and immunomodulatory therapy for the treatment of MYC-driven lymphoma( 2017)Bromodomain and Extra-Terminal (BET) proteins are a conserved family of ‘epigenetic readers’ that bind to acetylated lysine residues on histone and non-histone proteins to modulate transcription. BET proteins are enriched at promoter and enhancer regions and recruit the positive transcription elongation factor b (P-TEFb) complex to activate RNA polymerase II. Anti-tumour responses elicited by BET inhibitors have been associated with the suppression of genes required for cellular proliferation and survival, including oncogenic transcription factors. Suppression of the proto-oncogene MYC was initially reported as a key mechanistic property of BET inhibitors, however more recent evidence suggests that additional target genes are mechanistically implicated. In this thesis, the Eμ-Myc model of aggressive B-cell lymphoma was utilized to investigate the full repertoire of genes modulated by JQ1 and their functional significance in mediating therapeutic responses. JQ1 did not suppress the expression of transgenic Myc in this model, allowing the determinants of apoptosis induction to be assessed, independently of changes in Myc expression. This apoptotic response was p53-independent and associated with modulation in the ratio of pro- and antiapoptotic Bcl-2 family members to favor activation of the intrinsic mitochondrial apoptotic pathway. Therapeutic administration of JQ1 to mice bearing Eμ-Myc lymphomas led to robust clinical responses, however, universal treatment failure was observed despite ongoing therapy. Using RNA-Seq, disease progression and secondary JQ1 resistance was found to be associated with RAS pathway activation and Bcl-2 upregulation. In addition, the efficacy of JQ1 was found to be dependent on an intact host immune system, where a 50% reduction in the survival advantage was observed upon transplantation into immune-deficient mice. Using RNA-Seq, the immune checkpoint ligand Cd274 (Pd-l1) was found to be potently suppressed by JQ1. Mechanistically, BET inhibition decreased Brd4 occupancy at the Cd274 promoter, leading to promoter-proximal pausing of RNA polymerase II, and loss of Cd274 mRNA production. Rapid epigenetic remodeling of the Cd274 locus in response to interferon gamma (IFN-γ) stimulation led to recruitment of Irf1, Brd4, RNA polymerase II, as well as increased local histone acetylation. Accordingly, BET inhibition suppressed constitutive and IFN-γ-induced PD-L1 expression in genetically diverse tumour models. Ectopic expression of PD-L1 in Eμ-Myc lymphomas was sufficient to reduce the efficacy of JQ1, demonstrating the significance of PD-L1 suppression to the observed therapeutic responses associated with BET inhibition. Finally, treatment of mice bearing Eμ-Myc lymphomas with JQ1 in combination with a checkpoint inhibitor (anti-PD-1) or immune stimulating antibody (anti-4-1BB/CD137) led to improved therapeutic responses. The results presented herein demonstrate the importance of MYC-independent apoptotic signaling to therapeutic responses associated with BET inhibition, as well as acquired drug resistance. In addition, these results demonstrated the ability of BET inhibitors to directly engage the host immune response during anti-cancer therapy. Finally, BET inhibitors can suppress oncogenic PD-L1 transcription for therapeutic gain, leading to augmented anti-tumour immunity. These studies establish a strong rationale for clinical investigation of BET inhibitors in combination with immune modulating therapies.
-
ItemThe role of Pim-1 in breast cancer metastasis( 2017)Breast cancer is the most common cancer in women. Despite advances in treatment options, the spread of breast cancer to distant organs (metastasis) remains the major cause of morbidity and mortality in breast cancer patients. This is attributed primarily to the impairment of function in affected organs. Thus, there remains a vital need for better-targeted treatments that more effectively inhibit the development or progression of metastases. Pim-1 is a serine/threonine survival kinase that has been implicated in the development of metastasis in several haematological and solid cancers. However, little is known about its role in breast cancer. In our laboratory, we previously identified Pim-1 as upregulated in brain metastatic 4T1Br4 syngeneic mouse cells and tumours compared to parental 4T1 cells. This led us to propose that Pim-1 may play a role in mediating breast cancer brain metastasis. Therefore, the overall objective of this project was to examine the expression and functional role of Pim-1 in breast cancer metastasis, with a focus on organ-specific metastasis. We interrogated public databases to show that Pim-1 expression is low to absent in normal breast tissue and increased in breast tumour tissue. Furthermore we show that the murine (4T1Br4) and human (MDA-MB-231Br) brain metastatic breast cancer cell lines and tumours demonstrate the highest expression of Pim-1 mRNA and protein. To investigate the function of Pim-1 in breast cancer metastasis we tested the impact of inhibiting Pim-1, either by gene knock down using short hairpin RNAs or the pharmacological inhibitor SGI-1776, on the ability of 4T1Br4 and MDA-MB-231Br cells to migrate and invade in vitro. 4T1Br4 cells displayed increased migration and invasion propensity after Pim-1 knock down and this was coupled with a decrease in β4 integrin expression. Conversely, MDA-MB-231Br cells showed a decreased ability to migrate and invade after Pim-1 KD, as well as decreased cell surface expression of β1 and β3 integrins. Treatment with SGI-1776 dose-dependently decreased the ability of both 4T1Br4 and MDA-MB-231Br cells to migrate and invade, decreased cell surface expression of β3 integrin in 4T1Br4 cells, and both β1 and β3 integrins in MDA-MB-231Br cells. To examine the effect of Pim-1 inhibition in vivo, we assessed the metastatic spread of Pim-1 knock down MDA-MB-231Br cells in an experimental metastasis assay. After intracardiac injection of Pim-1 knock down cells, we observed a reduction in the number of circulating tumour cells and decreased bone metastasis, indicating a functional role for Pim-1 in breast cancer metastasis to the bone. Data from brain metastasis in this model were inconclusive. In summary, results from this project highlight the importance of Pim-1 in breast cancer metastasis and provide evidence that Pim-1 contributes to the migration and invasion of breast cancer cells both in vitro and in vivo, possibly via regulation of integrin expression, and indicate that Pim-1 is a relevant therapeutic target for the treatment of metastatic breast cancer.
-
ItemInvestigating the functional biology of chimeric antigen receptor T cells( 2017)Despite the success of autologous chimeric antigen receptor (CAR) T cells to treat patients with refractory B cell acute lymphoblastic leukaemia, (ALL) and lymphoma, there are many aspects of CAR T cell biology that remains unknown. For this reason, this thesis explored whether the recognition of antigen via either antigen receptor (CAR vs endogenous T cell receptor (TCR)) affected the CAR-T cell immune synapse, receptor signalling and tumour target killing kinetics. By addressing this issue we aim to translate this new knowledge to the clinic and broaden the CAR T therapy success to patients with a wider range of cancer subtypes. To explore the above questions, a novel transgenic mouse (designated CAR.OT-I) was developed, in which CD8+ T cells co-expressed the OVA257-specific T cell receptor (TCR) and a second generation CAR with an scFv specific for human HER2. Chapter 3 of this thesis validated the model system and compared CTL activation from CAR.OT-I and OT-I mice. Chapter 4 used time-lapse and confocal microscopy to explore whether the killing kinetics of CAR.OTI CTL was different when stimulated via with OVA257-pulsed (TCR) or HER2-expressing tumour cells (CAR). This thesis showed for the first time, individual CAR.OT-I CTL killed multiple tumour cells (‘serial killing’) and detached faster from dying targets after CAR ligation. Furthermore, in chapter 5, the CAR immune synapse gross molecular structure was described for the first time. This disrupted immune synapse had Lck micro-clusters, poor actin clearance and no peripheral LFA-1 clustering. Finally, phosphoprotein signalling and Ca2+ flux studies revealed faster, stronger signalling initiated via CAR compared to TCR ligation. This observation was also correlated with faster recruitment of cytotoxic granules to the target cell after CAR ligation. Taken together, the chapter 5 data reveals the mechanisms whereby CAR ligation initiates rapid tumour killing and detachment (Chapter 4). Information from this body of work can be used to inform on the next generation of CAR designs and provides a baseline for comparing CAR and TCR killing events.
-
ItemPerforin biochemistry: function and dysfunction( 2016)Natural killer (NK) cells and cytotoxic T lymphocytes (CTLs), collectively referred to as cytotoxic lymphocytes (CLs), are responsible for clearing virus infected and cancerous cells. The predominant manner by which CLs do this is through the delivery of the pore forming protein, perforin, and pro-apoptotic granzymes that synergise to induce apoptosis in a conjugated target cell. Humans who inherit bi-allelic inactivating perforin mutations develop the immunoregulatory disease familial haemophagocytic lymphohistiocytosis (FHL) and/or haematological malignancies, demonstrating the critical importance of expressing functional perforin for the maintenance of immune homeostasis and tumour immune surveillance. While most disease associated perforin mutations are rare, 8-9% of the Caucasian population are carriers of polymorphism A91V (rs35947132, 272C>T). It has been suggested that >50% of individuals homozygous for the A91V allele develop FHL and/or cancer and that individuals heterozygous for A91V have an increased susceptibility to ALL. Despite its frequency and disease association, it remained unknown whether heterozygous inheritance of the A91V allele impairs human CL cytotoxicity and, more broadly, whether perforin is rate limiting in CL cytotoxicity. Here, it has been demonstrated that NK cells from healthy humans heterozygous for the A91V allele show an almost 50% reduction in cytotoxicity compared to individuals homozygous for WT perforin. This reduction in function was due to A91V perforin protein being misfolded within human primary NK cells. Moreover, it was also observed that heterozygous perforin knockout mouse CTLs showed an ~50% reduction in cytotoxicity. Taken together, these data demonstrate that perforin is indeed rate limiting for CLs cytotoxicity and therefore, individuals heterozygous for defective perforin alleles have impaired CL function. Although FHL predominantly presents shortly after birth, a subset of patients present at an age greater than three years, owing to the expression of misfolded perforin variants. Previous studies have shown that when transiently expressed in CTLs, perforin variants associated with late onset disease failed to traffic within CTLs and the cells remained non-functional. Therefore, it was unknown how patient CTLs expressing these variants could avoid FHL in infancy, and maintain a level of immune homeostasis for many years, or even decades. Here, it is shown that perforin variants associated with late onset disease can fold correctly and traffic within CTLs, and thus provide a significant level of cytotoxic function. However, this function was found to be lost if CTLs were cultured at an increased temperature (39 ̊C). Taken together, these data suggest that the CTLs of late onset FHL patients may have sufficient cytotoxicity to delay FHL onset in infancy. However, prolonged fever and, potentially, a more rapid exhaustion of the limited pool of correctly folded perforin mutants may result in the loss of CTL function, leading to FHL and cancer later in life. Prior to its secretion from the CL, the evolutionarily conserved C-terminal residues of perforin are proteolytically cleaved. The functional significance of C- terminal processing has remained controversial. Here it is shown that perforin enriched from human NK cell with an intact and glycosylated C-terminus was not cytotoxic. However, removal of the C-terminal glycan from the protein was found to completely restore function. As full-length deglycosylated perforin has wild type activity, these data suggest that C-terminal cleavage of perforin is permissive for cytotoxic function due to removal of an inhibitory N-linked glycan moiety at the C-terminus of the protein. These findings position the protease(s) responsible for perforin cleavage as critical to CL function. In summary, the studies described in this thesis have added to the understanding to how perforin mutations affect CL cytotoxicity and described a critical final step in perforin maturation. Together, these advancements in perforin biology may contribute to the treatment of disease arising from perforin deficiency and also define new factors critical for CL function and human health.
-
ItemCooperative tumourigenesis : analysis of novel tumour suppressors in ras oncogene driven epithelial tumours( 2015)Cancer is a cooperative process, involving mutations in multiple genes. Activation of a cancer-driving gene, the Ras small GTPase, via a mutation that locks Ras in the GTP-bound active form (RasV12), occurs in ~30% of human cancers. However, alone it is not sufficient for tumour formation. A loss of function screen previously performed in the vinegar fly, Drosophila melanogaster, identified 947 genes that potentiate RasV12-mediated tumourigenesis and metastasis (Zoranovic, et al. in prep.). This list has been narrowed down to 234 genes that 1) show increased tumourigenicity with RasV12 in vivo, 2) are in the top 100 genes down-regulated in human cancer, and 3) are known to regulate the cytoskeleton, polarity, adhesion or cell motility. This study has successfully confirmed involvement of autophagy-related genes Atg8a, Atg7 in regulating RasV12-mediated proliferation in the Drosophila eye epithelial tissue using the UAS/GAL4 system. The study identified the autophagy-related genes Atg1, Atg3, Atg4, Atg5, Atg6, Atg7, Atg8a, Atg12 and Atg101 that when knocked down cooperate with RasV12 and lead to increased tissue overgrowth in the Drosophila eye epithelium. Atg8a was chosen as the representative target gene to investigate this cooperation. It was observed that Atg8a cooperates with RasV12 through the Raf pathway. The role of p62 in this Ras-mediated cooperation with Atg8a was also examined and it was found that p62 levels increase in RasV12+ Atg8aRNAi expressing tissue in comparison with control. Investigations were also carried out to ascertain if knockdown of Atg genes cooperate with Ras through the JNK pathway. It was discovered that in the presence of oncogenic Ras, knock down of Atg8a increases the expression of the JNK target MMP1. The finding of this work could lead to use of this autophagy related genes as prognostic markers in Ras-driven oncogenesis and might reveal effective therapeutic targets to combat this deadly disease.
-
ItemExploring the nature and impact of taste dysfunction in people receiving chemotherapy( 2013)Self-reported ‘taste’ problems are common in people receiving chemotherapy and have implications for nutritional and psychosocial domains. Taste refers to the perception derived when chemical molecules stimulate taste receptor fields in the oral cavity whereas flavour perception involves at least three independent sensory systems including taste, smell and texture. Conflation of the terms taste and flavour contributes to clinician confusion and reduces the opportunity to develop effective strategies to address taste problems in cancer patients. The research reported in this thesis aimed to characterise the extent to which taste function and food hedonics contribute to the eating and drinking experience in people receiving chemotherapy and to investigate how this is managed in the clinical setting. There was a mixed methods approach to this program of research that was comprised of three separate studies, in two phases, designed to: Phase 1, qualitative 1. Describe current practice surrounding taste function and food hedonics in the clinical oncology setting (Study 1); 2. Understand the experience and consequences of altered taste function and food hedonics for people receiving chemotherapy (Study 2); and Phase 2, quantitative 3. Describe the patterns of altered taste function and food hedonics across the chemotherapy treatment trajectory (Study 3). In the Phase 1 studies, patient and clinician interviews were used to explore a) clinician practice regarding the management of taste problems and b) patient and carer descriptions, experiences and consequences of taste changes. This qualitative phase informed the quantitative phase of the research: a longitudinal study of 52 women receiving chemotherapy for breast cancer that assessed taste function, appetite and food liking six times from before chemotherapy to 2 months after chemotherapy and investigated whether changes in these outcomes were associated with dietary intake, nutritional status or social dining activity. Phase 1 findings demonstrated that ‘taste’ problems refer to a raft of issues related to the wider aspects of flavour including changes to the sense of smell or touch, or to problems with appetite or food liking. Clinicians have limited capacity to distinguish between these scenarios. These changes shaped what patients chose to eat, drink, cook and purchase, and influenced how they dined and how they felt. A need for new approaches to classifying and describing flavour problems was identified and a requirement for better quality information and evidence with which to guide patients was indicated. In Phase 2, patterns of taste and hedonic changes were characterised in an unprecedented fashion across the treatment trajectory. Findings from Phase 2 analyses showed taste function and food hedonics were adversely influenced with greatest change closest to chemotherapy administration, followed by a gradual return to baseline measures. Problems resolved by 2 months after completion of chemotherapy. Change from baseline in ability to correctly identify all tastants was significant early in the third chemotherapy cycle (difference = 18.2%; 95% CI = 2.7, 32.9; p = 0.02) and final chemotherapy cycle (difference = 19.6%; 95% CI = 3.0, 35.1; p = 0.02). Decreased liking of sweet food (chocolate) was observed in the early (d = 0.77; p = 0.002) and middle stages of the third chemotherapy cycle (d = 0.70; p = 0.003) and early in the final chemotherapy cycle (d = 0.89; p = 0.001). Appetite was significantly decreased from baseline early in both the third and final chemotherapy cycles (d = 1.02; p < 0.001 respectively). Associations were found between taste and hedonic changes and dietary intake, nutritional status and social dining. Change in ability to correctly identify tastants was associated with reduced energy intake (r = 0.32; p = 0.005) early in the third chemotherapy cycle. At this assessment point, decreased liking of a sweet food item was also associated with reduced energy intake (r = 0.35; p = 0.001). Appetite loss was associated with reduced energy (r = 0.35; p = 0.001) and protein intake (r = 0.36; p = 0.001) early in a chemotherapy cycle, decrease in BMI over the study period (r = 0.36; p = 0.001), and change in overall nutritional status as assessed by PG-SGA score (r = 0.18; p = 0.09). Early in the final chemotherapy cycle, small-sized but non-significant associations were seen between taste change and social dining episodes (r = 0.22, p = 0.09) and between appetite loss and social dining episodes (r = 0.18, p = 0.16). Clinicians are ill equipped to support patients who report taste problems due to an absence of assessment tools or classification symptoms to identify problems described colloquially as ‘taste’. An emerging taxonomy of taste arising from this research goes some way to address the need for a classification system linking patient language to specific sensory or hedonic disturbances. Research findings will be used to guide the development of more specific pre-chemotherapy education material for patients.