Molecular biology: the key to personalised treatment in radiation oncology?

We know considerably more about what makes cells and tissues resistant or sensitive to radiation than we did 20 years ago. Novel techniques in molecular biology have made a major contribution to our understanding at the level of signalling pathways. Before the “New Biology” era, radioresponsiveness was defined in terms of physiological parameters designated as the five Rs. These are: repair, repopulation, reassortment, reoxygenation and radiosensitivity. Of these, only the role of hypoxia proved to be a robust predictive and prognostic marker, but radiotherapy regimens were nonetheless modified in terms of dose per fraction, fraction size and overall time, in ways that persist in clinical practice today. The first molecular techniques were applied to radiobiology about two decades ago and soon revealed the existence of genes/proteins that respond to and influence the cellular outcome of irradiation. The subsequent development of screening techniques using microarray technology has since revealed that a very large number of genes fall into this category. We can now obtain an adequately robust molecular signature, predicting for a radioresponsive phenotype using gene expression and proteomic approaches. In parallel with these developments, functional magnetic resonance imaging (fMRI) and positron emission tomography (PET) can now detect specific biological molecules such as haemoglobin and glucose, so revealing a 3D map of tumour blood flow and metabolism. The key to personalised radiotherapy will be to extend this capability to the proteins of the molecular signature that determine radiosensitivity.

Patient selection for oncology phase I trials: a multi-institutional study of prognostic factors.

PURPOSE The appropriate selection of patients for early clinical trials presents a major challenge. Previous analyses focusing on this problem were limited by small size and by interpractice heterogeneity. This study aims to define prognostic factors to guide risk-benefit assessments by using a large patient database from multiple phase I trials. PATIENTS AND METHODS Data were collected from 2,182 eligible patients treated in phase I trials between 2005 and 2007 in 14 European institutions. We derived and validated independent prognostic factors for 90-day mortality by using multivariate logistic regression analysis. Results The 90-day mortality was 16.5% with a drug-related death rate of 0.4%. Trial discontinuation within 3 weeks occurred in 14% of patients primarily because of disease progression. Eight different prognostic variables for 90-day mortality were validated: performance status (PS), albumin, lactate dehydrogenase, alkaline phosphatase, number of metastatic sites, clinical tumor growth rate, lymphocytes, and WBC. Two different models of prognostic scores for 90-day mortality were generated by using these factors, including or excluding PS; both achieved specificities of more than 85% and sensitivities of approximately 50% when using a score cutoff of 5 or higher. These models were not superior to the previously published Royal Marsden Hospital score in their ability to predict 90-day mortality. CONCLUSION Patient selection using any of these prognostic scores will reduce non-drug-related 90-day mortality among patients enrolled in phase I trials by 50%. However, this can be achieved only by an overall reduction in recruitment to phase I studies of 20%, more than half of whom would in fact have survived beyond 90 days.

The impact of specialized oncology nursing on patient supportive care outcomes

Meeting the supportive care needs of cancer patients remains a challenge to cancer care systems around the world. Despite significant improvements in the organization of medical care of patients with cancer, numerous surveys of cancer populations demonstrate that significant proportions of patients fail to have their supportive care needs met. One possible solution is the introduction of a care coordinator role using oncology nursing to help ensure that patients' physical, psychological, and social support needs are addressed. Although having face validity, there is little empirical evidence on the effects of nurse-led supportive care coordinator roles on patient reported supportive care outcomes. In this article the authors present the results of a prospective longitudinal cohort study of 113 patients referred to a community-based specialist oncology nursing program. Using validated instruments they found significant improvements in patient-reported outcomes in key supportive care domains: unmet needs, quality of life, and continuity of care, as well as a shift in patterns of health resource utilization from acute care settings to the community over the course of the intervention. The results of this study are important in supporting the design and development of controlled trials to examine provider roles in the coordination of supportive cancer care. Copyright © Taylor & Francis Group, LLC.

Bolivian health and social care professionals' experiences of decision-making in oncology and palliative care

In the UK, end-of-life care strategies recommend patients and families are involved in decision making around treatment and care. In Bolivia, such strategies do not exist, and access to oncology services depends on finance, geography, education and culture. Compared to more developed countries, the delivery of oncology services in Latin America may result in a higher percentage of patients presenting with advanced incurable disease. The objective of this study was to explore decision-making experiences of health and social care professionals who cared for oncology and palliative care patients attending the Instituto Oncológico Nacional, Cochabamba (Bolivia). Patients were predominantly from the Quechua tradition, which has its own ethnic diversity, linguistic distinctions and economic systems. Qualitative data were collected during focus groups. Data analysis was conducted using Interpretative Phenomenological Analysis. Three interrelated themes emerged: (i) making sense of structures of experience and relationality; (ii) frustration with the system; and (iii) the challenges of promoting shared decision making. The study uncovered participants' lived experiences, emotions and perceptions of providing care for Quechua patients. There was evidence of structural inequalities, the marginalisation of Quechua patients and areas of concern that social workers might well be equipped to respond to, such as accessing finances for treatment/care, education and alleviating psychological or spiritual suffering.

Evaluating Many Treatments and Biomarkers in Oncology: A New Design

There is a pressing need for more-efficient trial designs for biomarker-stratified clinical trials. We suggest a new approach to trial design that links novel treatment evaluation with the concurrent evaluation of a biomarker within a confirmatory phase II/III trial setting. We describe a new protocol using this approach in advanced colorectal cancer called FOCUS4. The protocol will ultimately answer three research questions for a number of treatments and biomarkers: (1) After a period of first-line chemotherapy, do targeted novel therapies provide signals of activity in different biomarker-defined populations? (2) If so, do these definitively improve outcomes? (3) Is evidence of activity restricted to the biomarker-defined groups? The protocol randomizes novel agents against placebo concurrently across a number of different biomarker-defined population-enriched cohorts: BRAF mutation; activated AKT pathway: PI3K mutation/absolute PTEN loss tumors; KRAS and NRAS mutations; and wild type at all the mentioned genes. Within each biomarker-defined population, the trial uses a multistaged approach with flexibility to adapt in response to planned interim analyses for lack of activity. FOCUS4 is the first test of a protocol that assigns all patients with metastatic colorectal cancer to one of a number of parallel population-enriched, biomarker-stratified randomized trials. Using this approach allows questions regarding efficacy and safety of multiple novel therapies to be answered in a relatively quick and efficient manner, while also allowing for the assessment of biomarkers to help target treatment.

Does vicarious traumatisation affect oncology nurses?:A literature review

It is widely documented that nurses experience work-related stress [Quine, L., 1998. Effects of stress in an NHS trust: a study. Nursing Standard 13 (3), 36-41; Charnley, E., 1999. Occupational stress in the newly qualified staff nurse. Nursing Standard 13 (29), 32-37; McGrath, A., Reid, N., Boore, J., 2003. Occupational stress in nursing. International Journal of Nursing Studies 40, 555-565; McVicar, A., 2003. Workplace stress in nursing: a literature review. Journal of Advanced Nursing 44 (6), 633-642; Bruneau, B., Ellison, G., 2004. Palliative care stress in a UK community hospital: evaluation of a stress-reduction programme. International Journal of Palliative Nursing 10 (6), 296-304; Jenkins, R., Elliott, P., 2004. Stressors, burnout and social support: nurses in acute mental health settings. Journal of Advanced Nursing 48 (6), 622-631], with cancer nursing being identified as a particularly stressful occupation [Hinds, P.S., Sanders, C.B., Srivastava, D.K., Hickey, S., Jayawardene, D., Milligan, M., Olsen, M.S., Puckett, P., Quargnenti, A., Randall, E.A., Tyc, V., 1998. Testing the stress-response sequence model in paediatric oncology nursing. Journal of Advanced Nursing 28 (5), 1146-1157; Barnard, D., Street, A., Love, A.W., 2006. Relationships between stressors, work supports and burnout among cancer nurses. Cancer Nursing 29 (4), 338-345]. Terminologies used to capture this stress are burnout [Pines, A.M., and Aronson, E., 1988. Career Burnout: Causes and Cures. Free Press, New York], compassion stress [Figley, C.R., 1995. Compassion Fatigue. Brunner/Mazel, New York], emotional contagion [Miller, K.I., Stiff, J.B., Ellis, B.H., 1988. Communication and empathy as precursors to burnout among human service workers. Communication Monographs 55 (9), 336-341] or simply the cost of caring (Figley, 1995). However, in the mental health field such as psychology and counselling, there is terminology used to captivate this impact, vicarious traumatisation. Vicarious traumatisation is a process through which the therapist's inner experience is negatively transformed through empathic engagement with client's traumatic material [Pearlman, L.A., Saakvitne, K.W., 1995a. Treating therapists with vicarious traumatization and secondary traumatic stress disorders. In: Figley, C.R. (Ed.), Compassion Fatigue: Coping with Secondary Traumatic Stress Disorder in Those Who Treat the Traumatized. Brunner/Mazel, New York, pp. 150-177]. Trauma not only affects individuals who are primarily present, but also those with whom they discuss their experience. If an individual has been traumatised as a result of a cancer diagnosis and shares this impact with oncology nurses, there could be a risk of vicarious traumatisation in this population. However, although Thompson [2003. Vicarious traumatisation: do we adequately support traumatised staff? The Journal of Cognitive Rehabilitation 24-25] suggests that vicarious traumatisation is a broad term used for workers from any profession, it has not yet been empirically determined if oncology nurses experience vicarious traumatisation. This purpose of this paper is to introduce the concept of vicarious traumatisation and argue that it should be explored in oncology nursing. The review will highlight that empirical research in vicarious traumatisation is largely limited to the mental health professions, with a strong recommendation for the need to empirically determine whether this concept exists in oncology nursing.

Tele-Supervised FES-Assisted Exercise for Hemiplegic Upper Limb

Stroke survivors often have upper limb (UL) hemiparesis, limiting their ability to perform activities of daily life (ADLs). Intensive, task-oriented exercise therapy (ET) can improve UL function, but motivation to perform sufficient ET is difficult to maintain. Here we report on a trial in which a workstation was deployed in the homes of chronic stroke survivors to enable tele-coaching of ET in the guise of computer games. Participants performed 6 weeks of 1 hour/day, 5 days/week ET. Hand opening and grasp were assisted with functional electrical stimulation (FES). The primary outcome measure was the Action Research Arm Test (ARAT). Secondary outcome measures included a quantitative test of UL function performed on the workstation, grasp force measurements and transcranial magnetic stimulation (TMS). Improvements were seen in the functional tests, but surprisingly, not in the TMS responses. An important finding was that participants commencing with intermediate functional scores improved the most.

CONCLUSIONS: 1) Daily, tele-supervised FES-ET in chronic stroke survivors is feasible with commercially-available technology. 2) The intervention can significantly improve UL function, particularly in people who start with an intermediate level of function. 3) Significant improvements in UL function can occur in the absence of changes in TMS responses.