Single-agent versus combination chemotherapy in patients with advanced non-small cell lung cancer and a performance status of 2 : prognostic factors and treatment selection based on two large randomized clinical trials

Purpose: Data from two randomized phase III trials were analyzed to evaluate prognostic factors and treatment selection in the first-line management of advanced non-small cell lung cancer patients with performance status (PS) 2. Patients and Methods: Patients randomized to combination chemotherapy (carboplatin and paclitaxel) in one trial and single-agent therapy (gemcitabine or vinorelbine) in the second were included in these analyses. Both studies had identical eligibility criteria and were conducted simultaneously. Comparison of efficacy and safety was performed between the two cohorts. A regression analysis identified prognostic factors and subgroups of patients that may benefit from combination or single-agent therapy. Results: Two hundred one patients were treated with combination and 190 with single-agent therapy. Objective responses were 37 and 15%, respectively. Median time to progression was 4.6 months in the combination arm and 3.5 months in the single-agent arm (p < 0.001). Median survival imes were 8.0 and 6.6 months, and 1-year survival rates were 31 and 26%, respectively. Albumin <3.5 g, extrathoracic metastases, lactate dehydrogenase ≥200 IU, and 2 comorbid conditions predicted outcome. Patients with 0-2 risk factors had similar outcomes independent of treatment, whereas patients with 3-4 factors had a nonsignificant improvement in median survival with combination chemotherapy. Conclusion: Our results show that PS2 non-small cell lung cancer patients are a heterogeneous group who have significantly different outcomes. Patients treated with first-line combination chemotherapy had a higher response and longer time to progression, whereas overall survival did not appear significantly different. A prognostic model may be helpful in selecting PS 2 patients for either treatment strategy. © 2009 by the International Association for the Study of Lung Cancer.

Incidental treatment effects of CBT on suicidal ideation and hopelessness

Background: Depression and alcohol misuse are among the most prevalent diagnoses in suicide fatalities. The risk posed by these disorders is exacerbated when they co-occur. Limited research has evaluated the effectiveness of common depression and alcohol treatments for the reduction of suicide vulnerability in individuals experiencing comorbidity. Methods: Participants with depressive symptoms and hazardous alcohol use were selected from two randomised controlled trials. They had received either a brief (1 session) intervention, or depression-focused cognitive behaviour therapy (CBT), alcohol-focused CBT, therapist-delivered integrated CBT, computer-delivered integrated CBT or person-centred therapy (PCT) over a 10-week period. Suicidal ideation, hopelessness, depression severity and alcohol consumption were assessed at baseline and 12-month follow-up. Results: Three hundred three participants were assessed at baseline and 12 months. Both suicidal ideation and hopelessness were associated with higher severity of depressive symptoms, but not with alcohol consumption. Suicidal ideation did not improve significantly at follow-up, with no differences between treatment conditions. Improvements in hopelessness differed between treatment conditions; hopelessness improved more in the CBT conditions compared to PCT and in single-focused CBT compared to integrated CBT. Limitations: Low retention rates may have impacted on the reliability of our findings. Combining data from two studies may have resulted in heterogeneity of samples between conditions. Conclusions: CBT appears to be associated with reductions in hopelessness in people with co-occurring depression and alcohol misuse, even when it is not the focus of treatment. Less consistent results were observed for suicidal ideation. Establishing specific procedures or therapeutic content for clinicians to monitor these outcomes may result in better management of individuals with higher vulnerability for suicide.

The impact of tobacco smoking on treatment for comorbid depression and alcohol misuse

Tobacco use is a major public health concern, and is associated with a number of mental illnesses as well as increased alcohol/other drug (AOD). Research into treatment for individuals experiencing such comorbidities is limited. Participants (n = 447) were those enrolled in the Depression and Alcohol Integrated and Single-focused Interventions project (Baker et al. 2010), and the Self Help for Alcohol/other drugs and DEpression project (Kay-Lambkin et al. Medical Journal of Australia 195:S44-S50, 2011a, Journal of Medical Internet Research 13(1):e11p11, b), who reported current depression and hazardous alcohol use at entry to the study. Smoking cessation was not targeted in, nor a goal of, treatment. After controlling for socioeconomic variables, tobacco use was not associated with higher levels of depressive symptoms at baseline; however heavy smokers (30+ cigarettes per day) consumed significantly more alcohol at baseline than did non-smokers (13 vs. 9 standard drinks per day). Baseline smoking severity did not impact on depression or alcohol use outcomes over a 12-month period. Reductions in tobacco use between baseline and 3-month follow-up were significantly associated with reductions in depression and alcohol consumption over the same time period. The study results suggest that tobacco use does not interfere with treatment for depression and alcohol use problems, and adds weight to the idea of considering specific treatment for tobacco use in the context of treatment for alcohol/other drug use.

Meta-analysis of individual patient data from randomized trials of chemotherapy plus cetuximab as first-line treatment for advanced non-small cell lung cancer

OBJECTIVES: Four randomized phase II/III trials investigated the addition of cetuximab to platinum-based, first-line chemotherapy in patients with advanced non-small cell lung cancer (NSCLC). A meta-analysis was performed to examine the benefit/risk ratio for the addition of cetuximab to chemotherapy. MATERIALS AND METHODS: The meta-analysis included individual patient efficacy data from 2018 patients and individual patient safety data from 1970 patients comprising respectively the combined intention-to-treat and safety populations of the four trials. The effect of adding cetuximab to chemotherapy was measured by hazard ratios (HRs) obtained using a Cox proportional hazards model and odds ratios calculated by logistic regression. Survival rates at 1 year were calculated. All applied models were stratified by trial. Tests on heterogeneity of treatment effects across the trials and sensitivity analyses were performed for all endpoints. RESULTS: The meta-analysis demonstrated that the addition of cetuximab to chemotherapy significantly improved overall survival (HR 0.88, p=0.009, median 10.3 vs 9.4 months), progression-free survival (HR 0.90, p=0.045, median 4.7 vs 4.5 months) and response (odds ratio 1.46, p<0.001, overall response rate 32.2% vs 24.4%) compared with chemotherapy alone. The safety profile of chemotherapy plus cetuximab in the meta-analysis population was confirmed as manageable. Neither trials nor patient subgroups defined by key baseline characteristics showed significant heterogeneity for any endpoint. CONCLUSION: The addition of cetuximab to platinum-based, first-line chemotherapy for advanced NSCLC significantly improved outcome for all efficacy endpoints with an acceptable safety profile, indicating a favorable benefit/risk ratio.

Circles of care : should community development redefine the practice of palliative care?

Specialist palliative care, within hospices in particular, has historically led and set the standard for caring for patients at end of life. The focus of this care has been mostly for patients with cancer. More recently, health and social care services have been developing equality of care for all patients approaching end of life. This has mostly been done in the context of a service delivery approach to care whereby services have become increasingly expert in identifying health and social care need and meeting this need with professional services. This model of patient centred care, with the impeccable assessment and treatment of physical, social, psychological and spiritual need, predominantly worked very well for the latter part of the 20th century. Over the last 13 years, however, there have been several international examples of community development approaches to end of life care. The patient centred model of care has limitations when there is a fundamental lack of integrated community policy, development and resourcing. Within this article, we propose a model of care which identifies a person with an illness at the centre of a network which includes inner and outer networks, communities and service delivery organisations. All of these are underpinned by policy development, supporting the overall structure. Adoption of this model would allow individuals, communities, service delivery organisations and policy makers to work together to provide end of life care that enhances value and meaning for people at end of life, both patients and communities alike.

The automation of radiotherapy treatment planning assessment

Aim The assessment of treatment plans is an important component in the education of radiation therapists. The establishment of a grade for a plan is currently based on subjective assessment of a range of criteria. The automation of assessment could provide a number of advantages including faster feedback, reduced chance of human error, and simpler aggregation of past results. Method A collection of treatments planned by a cohort of 27 second year radiation therapy students were selected for quantitative evaluation. Treatment sites included the bladder, cervix, larynx, parotid and prostate, although only the larynx plans had been assessed in detail. The plans were designed with the Pinnacle system and exported using the DICOM framework. Assessment criteria included beam arrangement optimisation, volume contouring, target dose coverage and homogeneity, and organ-at-risk sparing. The in-house Treatment and Dose Assessor (TADA) software1 was evaluated for suitability in assisting with the quantitative assessment of these plans. Dose volume data were exported in per-student and per-structure data tables, along with beam complexity metrics, dose volume histograms, and reports on naming conventions. Results The treatment plans were exported and processed using TADA, with the processing of all 27 plans for each treatment site taking less than two minutes. Naming conventions were successfully checked against a reference protocol. Significant variations between student plans were found. Correlation with assessment feedback was established for the larynx plans. Conclusion The data generated could be used to inform the selection of future assessment criteria, monitor student development, and provide useful feedback to the students. The provision of objective, quantitative evaluations of plan quality would be a valuable addition to not only radiotherapy education programmes but also for staff development and potentially credentialing methods. New functionality within TADA developed for this work could be applied clinically to, for example, evaluate protocol compliance.

Treatment for prevention of HIV transmission in a localised epidemic : the case for South Australia

Background: Discussion is currently taking place among international HIV/AIDS groups around increasing HIV testing and initiating earlier use of antiretroviral therapy (ART) among people diagnosed with HIV as a method to reduce the spread of HIV. In this study, we explore the expected epidemiological impact of this strategy in a small population in which HIV transmission is predominantly confined to men who have sex with men (MSM). Methods: A deterministic mathematical transmission model was constructed to investigate the impacts of strategies that increase testing and treatment rates, and their likely potential to mitigate HIV epidemics among MSM. Our novel model distinguishes men in the population who are more easily accessible to prevention campaigns through engagement with the gay community from men who are not. This model is applied to the population of MSM in South Australia. Results: Our model-based findings suggest that increasing testing rates alone will have minimal impact on reducing the expected number of infections compared to current conditions. However, in combination with increases in treatment coverage, this strategy could lead to a 59–68% reduction in the number of HIV infections over the next 5 years. Targeting men who are socially engaged with the gay community would result in the majority of potential reductions in incidence, with only minor improvements possible by reaching all other MSM. Conclusions: Investing in strategies that will achieve higher coverage and earlier initiation of treatment to reduce infectiousness of HIV-infected individuals could be an effective strategy for reducing incidence in a population of MSM.

Adverse breast cancer treatment effects: The economic case for making rehabilitative programs standard of care

Purpose: The purpose of this work was to evaluate the patient-borne financial cost of common, adverse breast cancer treatment-associated effects, comparing cost across women with or without these side-effects. Methods: 287 Australian women diagnosed with early-stage breast cancer were prospectively followed starting at six months post-surgery for 12 months, with three-monthly assessment of detailed treatment-related side effects and their direct and indirect patient costs attributable to breast cancer. Bootstrapping statistics were used to analyze cost data and adjusted logistic regression was used to evaluate the association between costs and adverse events from breast cancer. Costs were inflated and converted from 2002 Australian to 2014 US dollars. Results: More than 90% of women experienced at least one adverse effect (i.e. post-surgical issue, reaction to radiotherapy, upper-body symptoms or reduced function, lymphedema, fatigue or weight gain). On average, women paid $5,636 (95%CI: $4,694, $6,577) in total costs. Women with any one of the following symptoms (fatigue, reduced upper-body function, upper-body symptoms) or women who report ≥4 adverse treatment-related effects, have 1.5 to nearly 4 times the odds of having higher healthcare costs than women who do not report these complaints (p<0.05). Conclusions: Women face substantial economic burden due to a range of treatment-related health problems, which may persist beyond the treatment period. Improving breast cancer care by incorporating prospective surveillance of treatment-related side effects, and strategies for prevention and treatment of concerns (e.g., exercise) has real potential for reducing patient-borne costs.

Deliverable 2: Literature review on effectiveness of alcohol treatment and determining rehabilitation. Report to Austroads (SS1755)

Austroads called for responses to a tender to investigate options for rehabilitation in alcohol interlock programs. Following successful application by the Centre for Accident Research and Road Safety – Queensland (CARRS-Q), a program of work was developed. The project has four objectives: 1. Develop a matrix outlining existing policies in national and international jurisdictions with respect to treatment and rehabilitation programs and criteria for eligibility for interlock removal; 2. Critically review the available literature with a focus on evaluation outcomes regarding the effectiveness of treatment and rehabilitation programs; 3. Analyse and assess the strengths and weaknesses of the programs/approaches identified, and; 4. Outline options with an evidence base for consideration by licensing authorities.

Strengths and weaknesses analysis of alcohol treatment programs. Report to Austroads (SS1755)

Austroads called for responses to a tender to investigate options for rehabilitation in alcohol interlock programs. Following successful application by the Centre for Accident Research and Road Safety – Queensland (CARRS‐Q), a program of work was developed. The project has four objectives: 1. Develop a matrix outlining existing policies in national and international jurisdictions with respect to treatment and rehabilitation programs and criteria for eligibility for interlock removal; 2. Critically review the available literature with a focus on evaluation outcomes regarding the effectiveness of treatment and rehabilitation programs; 3. Analyse and assess the strengths and weaknesses of the programs/approaches identified; and, 4. Outline options with an evidence base for consideration by licensing authorities...

An fMRI investigation of semantic and phonological naming treatment in aphasia

Di�culty naming objects is one of the most common impairments in people with aphasia post-stroke, irrespective of aphasia classification (Goodglass & Wingfield, 1997). Thus, remediation of naming impairments is often a focus of treatment in the rehabilitation of language. Such treatments typically employ phonological or semantic approaches, or a combination of the two, in order to target the major cognitive components involved in word retrieval (Nickels,2002). Although individuals can show greater benefit from one approach over the other, the relationship between an individual’s locus of breakdown in word retrieval and response to a particular treatment approach remains unclear, and knowledge of the underlying neural mechanisms which may be responsible for successful treatment is scarce. The aim of this study was to examine brain activity associated with successful phonological and semantic based treatments for word retrieval using functional Magnetic Resonance Imaging fMRI).

The short-term impact of curative colorectal cancer treatment on physical activity, functional status and quality of life: A systematic review protocol

REVIEW QUESTION/OBJECTIVE The quantitative objectives are to identify the impact of curative colorectal cancer treatment (surgery or adjuvant therapy) on physical activity, functional status and quality of life within one year of treatment or diagnosis. INCLUSION CRITERIA Types of participants: This review will consider studies that include individuals aged 18 years and over who have been diagnosed with colorectal cancer. Types of intervention(s)/phenomena of interest: This review will consider studies that evaluate the impact of curative colorectal cancer treatment: surgery and/or adjuvant therapy. Types of outcomes: This review will consider studies that include the following outcome measures assessed within one year of diagnosis or treatment: Physical activity - any bodily movement produced by skeletal muscles resulting in energy expenditure. Physical activity is not exclusive to exercise; activities can also be walking, housework, occupational or leisure. Physical activity can be measured objectively using pedometers or accelerometers, or subjectively using self-reported measures. Functional status – measured as the capacity to perform all activities of daily living such as walking, showering, and eating; and instrumental activities of daily living such as (but not limited to) grocery shopping, housekeeping and laundry. Quality of life – defined as the individual meaning of mental, physical and psychosocial wellbeing, as measured by validated tools such as SF-36, EORTC-QLQ-C30, or FACT-C.

Can exploring natural recovery from substance misuse in psychosis assist with treatment? A review of current research

Substance misuse in people with psychosis presents significant problems, but trials of treatments to address it show little sustained advantage over control conditions. An examination of mechanisms underpinning unassisted improvements may assist in the refinement of co-morbidity treatments. This study reviewed existing research on natural recovery from substance misuse in people with psychosis. To address this issue, a systematic search identified only 7 articles that fulfilled the criteria. Their results suggest that people with psychosis report similar reasons to change as do non-psychotic groups, although they did not clarify whether the relative frequencies or priority orders were the same. Differences involved issues relating to the disorder and the functional problems faced by this group: receipt of treatment for mental health difficulties, worsening of mental health difficulties, and homelessness. The current research on reasons for change in people with psychosis is sparse and has significant limitations, and as yet it offers little inspiration for new treatments. A more fertile source may prove to be a detailed investigation of successful substance control strategies that are used in self-management by this group.

Strategies for the management and treatment of coal seam gas associated water

Coal seam gas (CSG) is a growing industry in Queensland and represents a potential major employer and deliverer of financial prosperity for years to come. CSG is a natural gas composed primarily of methane and is found trapped underground in coal beds. During the gas extraction process, significant volumes of associated water are also produced. This associated water could be a valuable resource, however, the associated water comprises of various salt constituents that make it problematic for beneficial use. Consequently, there is a need to implement various water treatment strategies to purify the associated water to comply with Queensland’s strict guidelines and to mitigate environmental risks. The resultant brine is also of importance as ultimately it also has to be dealt with in an economical manner. In some ways it can be considered that the CSG industry does not face a water problem, as this has inherent value to society, but rather has a “salt issue” to solve. This study analyzes the options involved in both the water treatment and salt recovery processes. A brief overview of the constituents present in Queensland CS water is made to illustrate the challenges involved and a range of treatment technologies discussed. Water treatment technologies examined include clarification (ballasted flocculation, dissolved air flotation, electrocoagulation), membrane filtration (ultrafiltration), ion exchange softening and desalination (ion exchange, reverse osmosis desalination and capacitance deionization). In terms of brine management we highlighted reinjection, brine concentration ponds, membrane techniques (membrane distillation, forward osmosis), thermal methods, electrodialysis, electrodialysis reversal, bipolar membrane electrodialysis, wind assisted intensive evaporation, membrane crystallization, eutectic freeze crystallization and vapor compression. As an entirety this investigation is designed to be an important tool in developing CS water treatment management strategies for effective management in Queensland and worldwide.

The Use of Mesenchymal Stromal Cells in the Treatment of Diseases of the Cornea

As a key component of the ocular surface required for vision, the cornea has been extensively studied as a site for cell and tissue-based therapies. Historically, these treatments have consisted of donor corneal tissue transplants, but cultivated epithelial autografts have become established over the last 15 years as a routine treatment for ocular surface disease. Ultimately, these treatments are performed with the intention of restoring corneal transparency and a smooth ocular surface. The degree of success, however, is often dependent upon the inherent level of corneal inflammation at time of treatment. In this regard, the anti-inflammatory and immuno-modulatory properties of mesenchymal stromal cells (MSC) have drawn attention to these cells as potential therapeutic agents for corneal repair. The origins for MSC-based therapies are founded in part on observations of the recruitment of endogenous bone marrow-derived cells to injured corneas, however, an increasing quantity of data is emerging for MSC administered following their isolation and ex vivo expansion from a variety of tissues including bone marrow, adipose tissue, umbilical cord and dental pulp. In brief, evidence has emerged of cultured MSC, or their secreted products, having a positive impact on corneal wound healing and retention of corneal allografts in animal models. Optimal dosage, route of administration and timing of treatment, however, all remain active areas of investigation. Intriguingly, amidst these studies, have emerged reports of MSC transdifferentiation into corneal cells. Clearest evidence has been obtained with respect to expression of markers associated with the phenotype of corneal stromal cells. In contrast, the evidence for MSC conversion to corneal epithelial cell types remains inconclusive. In any case, the conversion of MSC into corneal cells seems unlikely to be an essential requirement for their clinical use. This field of research has recently become more complicated by reports of MSC-like properties for cultures established from the peripheral corneal stroma (limbal stroma). The relationship and relative value of corneal-MSC compared to traditional sources of MSC such as bone marrow are at present unclear. This chapter is divided into four main parts. After providing a concise overview of corneal structure and function, we will highlight the types of corneal diseases that are likely to benefit from the anti-inflammatory and immuno-modulatory properties of MSC. We will subsequently summarize the evidence supporting the case for MSC-based therapies in the treatment of corneal diseases. In the third section we will review the literature concerning the keratogenic potential of MSC. Finally, we will review the more recent literature indicating the presence of MSC-like cells derived from corneal tissue.