Patient expectations and preferences for follow-up after treatment for lung cancer: a pilot study

Introduction

There is no robust evidence to indicate the most appropriate models of follow-up care for patients who have completed treatment for lung cancer. This pilot study aimed to assess expectations and preferences for follow-up care in a sample of patients who had completed treatment for lung cancer.

Method

Thirty-one patients who had completed treatment for primary lung cancer were recruited. A 13 item self-report survey was developed to elicit patient's preferences and expectations for follow-up. Participants completed the developed survey and clinical and demographic variables were collected.

Results

Factors scored as extremely important by over 80% of respondents focused on care coordination: Being able to see the same doctor or health care professional at each visit (24/83%); Knowing which doctor or nurse to contact if queries arise between follow-up appointments (23/82%); and Knowing the patient can book an appointment or contact a health care professional involved in their care regarding health concerns between visits (25/89%). Patients were supportive of nurse-led follow-up when offered in the context of a model of shared care (21/78%).

Conclusion

This study offers new insight into the expectations and preferences for follow-up of patients with lung cancer, with participants indicated preference for intensive follow-up after the completion of treatment.

Validation of the needs assessment for advanced lung cancer patients (NA-ALCP)

Objective: The Needs Assessment for Advanced Cancer Patients (NA-ACP) is a 132-item self-report questionnaire designed to assess the seven needs domains of patients with advanced, incurable cancer. This study aimed to evaluate the short derivative form of that questionnaire with advanced lung cancer patients.

Methods: Item factor loadings, item test–retest data and response distributions were used to retain or reject items from the original NA-ACP scale. This resulted in 38 items being maintained, preserving the original subscales. The response scale was simplified following feedback from patients. 108 people with advanced lung cancer completed the shortened NA-ALCP along with measures of psychological distress (HADS, DT) and quality of life (EORTC QLQ-C30). A-priori predictions were made for divergent and convergent validity.

Results: Internal consistency coefficients were satisfactory for six of seven subscales, range 0.71–0.95. Correlations between NA-ALCP and HADS, DT and EORTC-QLQ-C30 provided support for 11 of the 22 divergent (r = 0.13–0.27) and convergent predictions (r = 0.45–0.71).

Conclusions: Subscales of the NA-ALCP demonstrated internal reliability consistent with the original scale. Results provided supporting evidence for divergent and convergent validity. This study indicates that the NA-ALCP is psychometrically robust, easily understood and one-quarter the length of the original version

Psychological impact of receiving genetic risk information for breast cancer, with and without lifestyle information

The psychological impact of receiving hypothetical genetic risk information for breast cancer, with and without lifestyle information, was investigated. The psychological responses included in the study were drawn from three theories of behaviour change and included perceived risk, beliefs in health behaviours, motivations to change health behaviours, and use of coping strategies. Vignettes were used to present hypothetical risk information to 198 female university students. Results indicated that lifestyle information had an impact on psychological measures, in particular, increased beliefs in health behaviours, increased motivation for exercise, and decreased rational problem solving. Suggestions for future research are discussed.

Lung cancer: challenges and solutions for supportive care intervention research

Lung cancer is the leading cause of cancer death. It is associated with a high level of morbidity, particularly fatigue, pain, breathlessness, and coughing. These symptoms can have a substantial impact on psychosocial functioning. It is critical to have effective interventions demonstrated to improve quality of life particularly for those with advanced disease. However there is a paucity of high quality intervention research to guide practice in this area. This article discusses the challenges in conducting supportive care research in this group, including the patient's level of literacy in English, poor performance status, rapidly fluctuating health status, and familial or professional “gate-keeping.” Many of these challenges can be overcome by broadening eligibility criteria, permitting some flexibility in relation to recruitment and data collection procedures, working closely with the treatment team, involving the patient's family, minimizing practical difficulties associated with intervention delivery, and reducing study burden in other ways, such as limiting the amount of data collected from the patient and shortening follow-up time intervals. We explore these potential solutions drawing on the experience of conducting a randomized controlled trial of a support intervention for people with lung cancer and their family.

The metabolic syndrome and cancer: is the metabolic syndrome useful for predicting cancer risk above and beyond its individual components?

AIMS: The metabolic syndrome (MetS) is a risk factor for cancer. However, it is not known if the MetS confers a greater cancer risk than the sum of its individual components, which components drive the association, or if the MetS predicts future cancer risk. MATERIALS AND METHODS: We linked 20,648 participants from the Australian and New Zealand Diabetes and Cancer Collaboration with complete data on the MetS to national cancer registries and used Cox proportional hazards models to estimate associations of the MetS, the number of positive MetS components, and each of the five MetS components separately with the risk for overall, colorectal, prostate and breast cancer. Hazard ratios (HR) and 95% confidence intervals (95%CI) are reported. We assessed predictive ability of the MetS using Harrell's c-statistic. RESULTS: The MetS was inversely associated with prostate cancer (HR 0.85; 95% CI 0.72-0.99). We found no evidence of an association between the MetS overall, colorectal and breast cancers. For those with five positive MetS components the HR was 1.12 (1.02-1.48) and 2.07 (1.26-3.39) for overall, and colorectal cancer, respectively, compared with those with zero positive MetS components. Greater waist circumference (WC) (1.38; 1.13-1.70) and elevated blood pressure (1.29; 1.01-1.64) were associated with colorectal cancer. Elevated WC and triglycerides were (inversely) associated with prostate cancer. MetS models were only poor to moderate discriminators for all cancer outcomes. CONCLUSIONS: We show that the MetS is (inversely) associated with prostate cancer, but is not associated with overall, colorectal or breast cancer. Although, persons with five positive components of the MetS are at a 1.2 and 2.1 increased risk for overall and colorectal cancer, respectively, and these associations appear to be driven, largely, by elevated WC and BP. We also demonstrate that the MetS is only a moderate discriminator of cancer risk.

Oral administration of iron-saturated bovine lactoferrin-loaded ceramic nanocapsules for breast cancer therapy and influence on iron and calcium metabolism

We determined the anticancer efficacy and internalization mechanism of our polymeric-ceramic nanoparticle system (calcium phosphate nanocores, enclosed in biodegradable polymers chitosan and alginate nanocapsules/nanocarriers [ACSC NCs]) loaded with iron-saturated bovine lactoferrin (Fe-bLf) in a breast cancer xenograft model. ACSC-Fe-bLf NCs with an overall size of 322±27.2 nm were synthesized. In vitro internalization and anticancer efficacy were evaluated in the MDA-MB-231 cells using multicellular tumor spheroids, CyQUANT and MTT assays. These NCs were orally delivered in a breast cancer xenograft mice model, and their internalization, cytotoxicity, biodistribution, and anticancer efficacy were evaluated. Chitosan-coated calcium phosphate Fe-bLf NCs effectively (59%, P≤0.005) internalized in a 1-hour period using clathrin-mediated endocytosis (P≤0.05) and energy-mediated pathways (P≤0.05) for internalization; 3.3 mg/mL of ACSC-Fe-bLf NCs completely disintegrated (~130-fold reduction, P≤0.0005) the tumor spheroids in 72 hours and 96 hours. The IC50 values determined for ACSC-Fe-bLf NCs were 1.69 mg/mL at 10 hours and 1.62 mg/mL after 20 hours. We found that Fe-bLf-NCs effectively (P≤0.05) decreased the tumor size (4.8-fold) compared to the void NCs diet and prevented tumor recurrence when compared to intraperitoneal injection of Taxol and Doxorubicin. Receptor gene expression and micro-RNA analysis confirmed upregulation of low-density lipoprotein receptor and transferrin receptor (liver, intestine, and brain). Several micro-RNAs responsible for iron metabolism upregulated with NCs were identified. Taken together, orally delivered Fe-bLf NCs offer enhanced antitumor activity in breast cancer by internalizing via low-density lipoprotein receptor and transferrin receptor and regulating the micro-RNA expression. These NCs also restored the body iron and calcium levels and increased the hematologic counts.

Development of a conceptual model of cancer caregiver health literacy.

Caregivers play a vital role in caring for people diagnosed with cancer. However, little is understood about caregivers' capacity to find, understand, appraise and use information to improve health outcomes. The study aimed to develop a conceptual model that describes the elements of cancer caregiver health literacy. Six concept mapping workshops were conducted with 13 caregivers, 13 people with cancer and 11 healthcare providers/policymakers. An iterative, mixed methods approach was used to analyse and synthesise workshop data and to generate the conceptual model. Six major themes and 17 subthemes were identified from 279 statements generated by participants during concept mapping workshops. Major themes included: access to information, understanding of information, relationship with healthcare providers, relationship with the care recipient, managing challenges of caregiving and support systems. The study extends conceptualisations of health literacy by identifying factors specific to caregiving within the cancer context. The findings demonstrate that caregiver health literacy is multidimensional, includes a broad range of individual and interpersonal elements, and is influenced by broader healthcare system and community factors. These results provide guidance for the development of: caregiver health literacy measurement tools; strategies for improving health service delivery, and; interventions to improve caregiver health literacy.

Unmet needs and depression among carers of people newly diagnosed with cancer

AIMS: The aims of this analysis were to examine levels of unmet needs and depression among carers of people newly diagnosed with cancer and to identify groups who may be at higher risk, by examining relationships with demographic characteristics. METHODS: One hundred and fifty dyads of people newly diagnosed with cancer and their carers, aged 18years and older, were recruited from four Australian hospitals. People with cancer receiving adjuvant cancer treatment with curative intent, were eligible to participate. Carers completed the Supportive Care Needs Survey-Partners & Caregivers (SCNS-P&C45), and both carers and patients completed the Centre of Epidemiologic-Depression Scale (CES-D). RESULTS: Overall, 57% of carers reported at least one, 37% at least three, 31% at least five, and 15% at least 10 unmet needs; the most commonly endorsed unmet needs were in the domains of information and health care service needs. Thirty percent of carers and 36% of patients were at risk of clinical depression. A weak to moderate positive relationship was observed between unmet needs and carer depression (r=0.30, p<0.001). Carer levels of unmet needs were significantly associated with carer age, hospital type, treatment type, cancer type, living situation, relationship status (in both uni- and multi-factor analysis); person with cancer age and carer level of education (in unifactor analysis only); but not with carer gender or patient gender (in both uni- and multi-factor analyses). CONCLUSION: Findings highlight the importance of developing tailored programmes to systematically assist carers who are supporting patients through the early stages of cancer treatment.

Chemosensory science in the context of cancer treatment: implications for patient care

Introduction: This collaborative commentary brings together both clinical and sensory science perspectives in an effort to explain the mechanisms of cancer treatment and the ensuing implications for the sensorium. Strategy: This paper makes the distinction between food hedonics and true chemosensory effects in the cancer context and describes the adverse effects cancer and its treatment have on the eating and drinking experience, including gastronomic, nutritional and emotional implications. Results from a prospective breast cancer cohort study, conducted by an interdisciplinary team of nurses, medical oncologists, dietitians and sensory science researchers shed new light on specific sensory symptomatology associated with chemotherapy treatment and the implications this has for informing reliable pre-treatment patient education. Findings: Two conceptual models are posed as frameworks for better understanding the determinants and consequences of altered eating and drinking experiences during chemotherapy, as well as the link between patient-reported symptoms and chemosensory or hedonic disturbances. Discussion: Application of evidence of cancer treatment and its sensory effects in the patient treatment context continues to be a challenge for cancer clinicians, especially where standardised testing of taste and smell function are not able to be practically administered. Conclusions: Recommendations are made for further research and practice pursuits to underpin improved food enjoyment and dietary quality throughout the cancer trajectory. Clinician education of sensory science is also encouraged.

EpCAM aptamer mediated cancer cell specific delivery of EpCAM siRNA using polymeric nanocomplex

BACKGROUND: Epithelial cell adhesion molecule (EpCAM) is overexpressed in solid tumors and regarded as a putative cancer stem cell marker. Here, we report that employing EpCAM aptamer (EpApt) and EpCAM siRNA (SiEp) dual approach, for the targeted delivery of siRNA to EpCAM positive cancer cells, efficiently inhibits cancer cell proliferation. RESULTS: Targeted delivery of siRNA using polyethyleneimine is one of the efficient methods for gene delivery, and thus, we developed a novel aptamer-PEI-siRNA nanocomplex for EpCAM targeting. PEI nanocomplex synthesized with EpCAM aptamer (EpApt) and EpCAM siRNA (SiEp) showed 198 nm diameter sized particles by dynamic light scattering, spherical shaped particles, of 151 ± 11 nm size by TEM. The surface charge of the nanoparticles was -30.0 mV using zeta potential measurements. Gel retardation assay confirmed the PEI-EpApt-SiEp nanoparticles formation. The difference in size observed by DLS and TEM could be due to coating of aptamer and siRNA on PEI nanocore. Flow cytometry analysis revealed that PEI-EpApt-SiEp has superior binding to cancer cells compared to EpApt or scramble aptamer (ScrApt) or PEI-ScrApt-SiEp. PEI-EpApt-SiEp downregulated EpCAM and inhibited selectively the cell proliferation of MCF-7 and WERI-Rb1 cells. CONCLUSIONS: The PEI nanocomplex fabricated with EpApt and siEp was able to target EpCAM tumor cells, deliver the siRNA and silence the target gene. This nanocomplex exhibited decreased cell proliferation than the scrambled aptamer loaded nanocomplex in the EpCAM expressing cancer cells and may have potential for EpCAM targeting in vivo.

Iron-free and iron-saturated bovine lactoferrin inhibit survivin expression and differentially modulate apoptosis in breast cancer

BACKGROUND: Iron binding, naturally occurring protein bovine lactoferrin (bLf) has attracted attention as a safe anti-cancer agent capable of inducing apoptosis. Naturally, bLf exists partially saturated (15-20%) with Fe(3+) however, it has been demonstrated that manipulating the saturation state can enhance bLf's anti-cancer activities. METHODS: Apo-bLf (Fe(3+) free) and Fe-bLf (>90% Fe(3+) Saturated) were therefore, tested in MDA-MB-231 and MCF-7 human breast cancer cells in terms of cytotoxicity, proliferation, migration and invasion. Annexin-V Fluos staining was also employed in addition to apoptotic protein arrays and Western blotting to determine the specific mechanism of bLf-induced apoptosis with a key focus on p53 and inhibitor of apoptosis proteins (IAP), specifically survivin. RESULTS: Apo-bLf induced significantly greater cytotoxicity and reduction in cell proliferation in both cancer cells showing a time and dose dependent effect. Importantly, no cytotoxicity was detected in normal MCF-10-2A cells. Both forms of bLf significantly reduced cell invasion in cancer cells. Key apoptotic molecules including p53, Bcl-2 family proteins, IAP members and their inhibitors were significantly modulated by both forms of bLf, though differentially in each cell line. Most interestingly, both Apo-bLf and Fe-bLf completely inhibited the expression of survivin protein (key IAP), after 48 h at 30 and 40 nM in cancer cells. CONCLUSIONS: The capacity of these forms of bLf to target survivin expression and modulation of apoptosis demonstrates an exciting potential for bLf as an anti-cancer therapeutic in the existing void of survivin inhibitors, with a lack of successful inhibitors in the clinical management of cancer.

Hierarchical gene selection and genetic fuzzy system for cancer microarray data classification

This paper introduces a novel approach to gene selection based on a substantial modification of analytic hierarchy process (AHP). The modified AHP systematically integrates outcomes of individual filter methods to select the most informative genes for microarray classification. Five individual ranking methods including t-test, entropy, receiver operating characteristic (ROC) curve, Wilcoxon and signal to noise ratio are employed to rank genes. These ranked genes are then considered as inputs for the modified AHP. Additionally, a method that uses fuzzy standard additive model (FSAM) for cancer classification based on genes selected by AHP is also proposed in this paper. Traditional FSAM learning is a hybrid process comprising unsupervised structure learning and supervised parameter tuning. Genetic algorithm (GA) is incorporated in-between unsupervised and supervised training to optimize the number of fuzzy rules. The integration of GA enables FSAM to deal with the high-dimensional-low-sample nature of microarray data and thus enhance the efficiency of the classification. Experiments are carried out on numerous microarray datasets. Results demonstrate the performance dominance of the AHP-based gene selection against the single ranking methods. Furthermore, the combination of AHP-FSAM shows a great accuracy in microarray data classification compared to various competing classifiers. The proposed approach therefore is useful for medical practitioners and clinicians as a decision support system that can be implemented in the real medical practice.

Overcoming acquired drug resistance in colorectal cancer cells by targeted delivery of 5-FU with EGF grafted hollow mesoporous silica nanoparticles

Acquired drug resistance (ADR) can be developed in colorectal cancer cells after 5-fluorouracil (5-FU) treatment and diminish the effectiveness of chemotherapy. In this work, acquired 5-FU resistance in the colorectal cancer cell line SW480 was obtained with the up-regulation of dihydropyrimidine dehydrogenase (DPYD) gene expression which can convert 5-FU to its inactive metabolite. To overcome ADR in colorectal cancer, hollow mesoporous silica nanoparticles (HMSNs) grafted with epidermal growth factor (EGF) were used as nanocarriers to deliver 5-FU to colorectal cancer cells with acquired drug resistance. The effect and mechanism of 5-FU loaded EGF grafted HMSNs (EGF-HMSNs-5-FU) in overcoming acquired drug resistance in SW480/ADR cells were studied. The EGF-HMSNs were demonstrated to be specifically internalized in EGFR overexpressed SW480/ADR cells via a receptor-mediated endocytosis and can escape from endo-lysosomes. The EGF-HMSNs-5-FU exhibited much higher cytotoxicity on SW480/ADR cells than HMSNs-5-FU and free 5-FU while the plain HMSNs did not show significant cytotoxicity. The mechanism of EGF-HMSNs-5-FU in overcoming drug resistance in SW480/ADR cells could be attributed to the specific internalization of EGF-HMSNs-5-FU in EGFR overexpressed cells which can lead to high intracellular drug accumulation and cause cell death through S phase arrest.

Responses and relationship dynamics of men and their spouses during active surveillance for prostate cancer: health literacy as an inquiry framework

BACKGROUND: Early stage prostate cancer patients may be allocated to active surveillance, where the condition is observed over time with no intervention. Living with a cancer diagnosis may impose stress on both the men and their spouses. In this study we explore whether the scores of and verbal responses to a Health Literacy Questionnaire can be used to identify individuals in need of information and support and to reveal differences in perception and understanding in health related situations within couples. METHODS: We used the nine-domain Health Literacy Questionnaire (HLQ) as a framework to explore health literacy in eight couples where the men were on active surveillance for prostate cancer progression. Scores were calculated for each domain for both individuals. For each couple differences in scores were also calculated and related to the informants' self-reported experiences and reflections in relation to participating in an active surveillance program. Also an inductive analysis was performed to identify themes in the responses and these themes were compared to those of HLQ. RESULTS: The men tended to score higher than their spouses. There was no consistent relation between scores and the reported experiences and reflections. However, some interesting patterns emerged, e.g. in two of the three couples with the largest within couple differences in HLQ scores, responses revealed discrepancies in how the men and their spouses perceived their situation. Also, three themes emerged which related to six of the HLQ domains, i.e. involvement of spouses and other people around the men; support from and interaction with healthcare professionals; and use of the Internet for information retrieval. CONCLUSIONS: Using the HLQ as an interview framework provided insight into the differences within couples and provided new perspectives on their experiences, including their contact with health professionals and the patient-spouse interaction when dealing with prostate cancer. The HLQ used as a dialogue tool may be an adjunct to assist healthcare providers to understand the need for support and information of men with prostate cancer on active surveillance and the dynamics within couples.

Hidden Markov models for cancer classification using gene expression profiles

This paper introduces an approach to cancer classification through gene expression profiles by designing supervised learning hidden Markov models (HMMs). Gene expression of each tumor type is modelled by an HMM, which maximizes the likelihood of the data. Prominent discriminant genes are selected by a novel method based on a modification of the analytic hierarchy process (AHP). Unlike conventional AHP, the modified AHP allows to process quantitative factors that are ranking outcomes of individual gene selection methods including t-test, entropy, receiver operating characteristic curve, Wilcoxon test and signal to noise ratio. The modified AHP aggregates ranking results of individual gene selection methods to form stable and robust gene subsets. Experimental results demonstrate the performance dominance of the HMM approach against six comparable classifiers. Results also show that gene subsets generated by modified AHP lead to greater accuracy and stability compared to competing gene selection methods, i.e. information gain, symmetrical uncertainty, Bhattacharyya distance, and ReliefF. The modified AHP improves the classification performance not only of the HMM but also of all other classifiers. Accordingly, the proposed combination between the modified AHP and HMM is a powerful tool for cancer classification and useful as a real clinical decision support system for medical practitioners.