MENOS4 trial: a multicentre randomised controlled trial (RCT) of a breast care nurse delivered cognitive behavioural therapy (CBT) intervention to reduce the impact of hot flushes in women with breast cancer: Study Protocol.

BACKGROUND: Women who have been treated for breast cancer may identify vasomotor symptoms, such as hot flushes and night sweats (HFNS), as a serious problem. HFNS are unpleasant to experience and can have a significant impact on daily life, potentially leading to reduced adherence to life saving adjuvant hormonal therapy. It is known that Cognitive Behavioural Therapy (CBT) is effective for the alleviation of hot flushes in both well women and women who have had breast cancer. Most women with breast cancer will see a breast care nurse and there is evidence that nurses can be trained to deliver psychological treatments to a satisfactory level, whilst also maintaining treatment fidelity. The research team will assess whether breast care nurses can effectively deliver a CBT intervention to alleviate hot flushes in women with breast cancer. METHODS: This study is a multi-centre phase III individually randomised controlled trial of group CBT versus usual care to reduce the impact of hot flushes in women with breast cancer. 120-160 women with primary breast cancer experiencing seven or more problematic HFNS a week will be randomised to receive either treatment as usual (TAU) or participation in the group CBT intervention plus TAU (CBT Group). A process evaluation using May's Normalisation Process Theory will be conducted, as well as practical and organisational issues relating to the implementation of the intervention. Fidelity of implementation of the intervention will be conducted by expert assessment. The cost effectiveness of the intervention will also be assessed. DISCUSSION: There is a need for studies that enable effective interventions to be implemented in practice. There is good evidence that CBT is helpful for women with breast cancer who experience HFNS, yet it is not widely available. It is not yet known whether the intervention can be effectively delivered by breast care nurses or implemented in practice. This study will provide information on both whether the intervention can effectively help women with hot flushes and whether and how it can be translated into routine clinical practice. TRIAL REGISTRATION: ISRCTN 12824632 . Registered 25-01-2017.

Influence of psychological response on breast cancer survival: 10-year follow-up of a population-based cohort.

The possibility that psychological response within a few weeks of a breast cancer diagnosis can influence the outcome of the disease is a contentious issue. Psychological response, including helplessness/hopelessness, fighting spirit and depression was assessed in early-stage breast cancer patients between 1 and 3 months post-diagnosis, in order to ascertain effect on cancer prognosis. Patients were followed up for a period of 10 years in order to clarify the effect of psychological response on disease outcome. After 10 years, there is a continuing effect of helplessness/hopelessness on disease-free survival (adjusted hazard ratio (HR) 1.53, 95% confidence interval (CI) 1.11-2.11) but not of depression (adjusted HR for overall survival for 'cases' 2.43, 95% CI 0.97-6.10). Longer follow-up also indicates that a high fighting spirit confers no survival advantage. The results showed that, in patients who were disease-free at 5 years, their baseline helpless/hopeless response still exerted a significant effect on disease-free survival beyond 5 (and up to 10) years. The effect is therefore maintained for up to 10 years of follow-up. Clinicians may wish to screen for helplessness around the time of diagnosis in order to target psychological care resources. Further large studies, with similarly prolonged follow-up, are needed to replicate this effect and clarify its mechanism of action.

Fractionation sensitivity and dose response of late adverse effects in the breast after radiotherapy for early breast cancer: long-term results of a randomised trial.

BACKGROUND AND PURPOSE: Unlike squamous carcinomas, breast adenocarcinoma may be as sensitive to fraction size as late dose-limiting normal tissues. If so, fewer larger fractions would be as safe and effective as regimens based on 2.0 Gy fractions. The first step is to test the effects of radiotherapy fractions >2.0 Gy on late normal tissue responses in the breast after tumour excision and radiotherapy for early breast cancer. PATIENTS AND METHODS: One thousand four-hundred and ten women with T1-3 N0-1 M0 invasive breast cancer were randomised between 1986-98 into one of three radiotherapy regimens after local tumour excision of early stage breast cancer; 50 Gy in 25 fractions (F) vs two dose levels of a test schedule giving 39 or 42.9 Gy in 13 F over 5 weeks. Fraction sizes were 2.0, 3.0 and 3.3 Gy, respectively. The primary endpoint was late change in breast appearance compared to post-surgical appearance scored from annual photographs blinded to treatment allocation. Secondary endpoints included palpable breast induration (fibrosis) and ipsilateral tumour recurrence. RESULTS: After a minimum 5-year follow up, the risk of scoring any change in breast appearance after 50 Gy/25 F, 39 Gy/13 F and 42.9 Gy/13 F was 39.6, 30.3 and 45.7%, from which an alpha/beta value of 3.6 Gy (95% CI 1.8-5.4) is estimated. The alpha/beta value for palpable breast induration was 3.1 Gy (95% CI 1.8-4.4). CONCLUSIONS: An alpha/beta value of around 3 Gy for late normal tissue changes in the breast is derived from the estimated equivalence of 41.6 Gy in 13 fractions and 50 Gy in 25 fractions over 5 weeks, in line with trial predictions.

TGFB1 polymorphisms are associated with risk of late normal tissue complications in the breast after radiotherapy for early breast cancer.

Recent studies suggest that normal tissue radiosensitivity is influenced by single nucleotide polymorphisms (SNPs) in certain genes. In order to seek a confirmation of these findings, this study investigated SNPs in genes TGFB1 (position -509, codon 10 and codon 25), SOD2 (codon 16), XRCC1 (codon 399), XRCC3 (codon 241), APEX (codon 148) and ATM (codon 1853) in 26 breast cancer patients with marked changes in breast appearance after radiotherapy and 26 matched controls. Statistically significant associations were found between the TGFB1 codon 10 Pro allele (P=0.005) as well as the TGFB1 position -509 T allele (P=0.018) and increased risk of altered breast appearance. No significant associations were found for the remaining SNPs.

Normal tissue complication probability (NTCP) parameters for breast fibrosis: pooled results from two randomised trials.

INTRODUCTION: The dose-volume effect of radiation therapy on breast tissue is poorly understood. We estimate NTCP parameters for breast fibrosis after external beam radiotherapy. MATERIALS AND METHODS: We pooled individual patient data of 5856 patients from 2 trials including whole breast irradiation followed with or without a boost. A two-compartment dose volume histogram model was used with boost volume as the first compartment and the remaining breast volume as second compartment. Results from START-pilot trial (n=1410) were used to test the predicted models. RESULTS: 26.8% patients in the Cambridge trial (5 years) and 20.7% patients in the EORTC trial (10 years) developed moderate-severe breast fibrosis. The best fit NTCP parameters were BEUD3(50)=136.4 Gy, γ50=0.9 and n=0.011 for the Niemierko model and BEUD3(50)=132 Gy, m=0.35 and n=0.012 for the Lyman Kutcher Burman model. The observed rates of fibrosis in the START-pilot trial agreed well with the predicted rates. CONCLUSIONS: This large multi-centre pooled study suggests that the effect of volume parameter is small and the maximum RT dose is the most important parameter to influence breast fibrosis. A small value of volume parameter 'n' does not fit with the hypothesis that breast tissue is a parallel organ. However, this may reflect limitations in our current scoring system of fibrosis.

Project 27/28: inquiry into quality of neonatal care and its effect on the survival of infants who were born at 27 and 28 weeks in England, Wales, and Northern Ireland.

OBJECTIVE: To identify variations in standards of neonatal care in the first week of life that might have contributed to deaths in infants who were born at 27 and 28 weeks' gestation. METHODS: A case-control study was conducted of infants who were born at 27 and 28 weeks' gestation in England, Wales, and Northern Ireland during a 2-year period. Cases were neonatal deaths; control subjects were randomly selected survivors at day 28. Main outcome measures were failures of prespecified standards of care or deficiencies in care reported by regional panels assessing anonymized medical records. RESULTS: Failures of standards of care relating to ventilatory support (adjusted odds ratio [OR]: 3.29; 95% confidence interval [CI]: 1.97-5.49), cardiovascular support (OR: 2.37; 95% CI :1.36-4.13), and thermal care (OR: 1.71; 95% CI: 1.21-2.43) were associated with neonatal death. Frequencies of unmet resuscitation standards (range: 3%-46%) and of delays in surfactant administration (range: 38%-40%) were similar in cases and control subjects. Panels identified significantly more deficiencies in all aspects of neonatal care in cases with the exception of the management of infection. Stratification by clinical condition of infants at birth showed a stronger association between overall standard of care and death when infants were in a good condition at birth. CONCLUSIONS: Our findings suggest an association between quality of neonatal care and neonatal deaths, most marked for early thermal care and ventilatory and cardiovascular support. Poor overall quality of care was more strongly associated with deaths when the infant was in a good condition at birth.

Nurse led follow up and conventional medical follow up in management of patients with lung cancer: randomised trial.

OBJECTIVE: To assess the effectiveness of nurse led follow up in the management of patients with lung cancer. DESIGN: Randomised controlled trial. SETTING: Specialist cancer hospital and three cancer units in southeastern England. PARTICIPANTS: 203 patients with lung cancer who had completed their initial treatment and were expected to survive for at least 3 months. INTERVENTION: Nurse led follow up of outpatients compared with conventional medical follow up. OUTCOME MEASURES: Quality of life, patients' satisfaction, general practitioners' satisfaction, survival, symptom-free survival, progression-free survival, use of resources, and comparison of costs. RESULTS: Patient acceptability of nurse led follow up was high: 75% (203/271) of eligible patients consented to participate. Patients who received the intervention had less severe dyspnoea at 3 months (P=0.03) and had better scores for emotional functioning (P=0.03) and less peripheral neuropathy (P=0.05) at 12 months. Intervention group patients scored significantly better in most satisfaction subscales at 3, 6, and 12 months (P<0.01 for all subscales at 3 months). No significant differences in general practitioners' overall satisfaction were seen between the two groups. No differences were seen in survival or rates of objective progression, although nurses recorded progression of symptoms sooner than doctors (P=0.01). Intervention patients were more likely to die at home rather than in a hospital or hospice (P=0.04), attended fewer consultations with a hospital doctor during the first 3 months (P=0.004), had fewer radiographs during the first 6 months (P=0.04), and had more radiotherapy within the first 3 months (P=0.01). No other differences were seen between the two groups in terms of the use of resources. CONCLUSION: Nurse led follow up was acceptable to lung cancer patients and general practitioners and led to positive outcomes.

Exploring nursing outcomes for patients with advanced cancer following intervention by Macmillan specialist palliative care nurses.

BACKGROUND: Little information exists about the outcomes from nursing interventions, and few studies report new approaches to evaluating the complex web of effects that may result from specialist nursing care. AIMS: The aim of this study was to explore nursing outcomes for patients with advanced cancer that may be identified as resulting from the care of a Macmillan specialist palliative care nurse. METHODS/INSTRUMENTS: Seventy-six patients referred to 12 United Kingdom Macmillan specialist palliative care nursing services participated in a longitudinal study of their care over 28 days. Patients were interviewed and completed the European Organization for Research on Treatment of Cancer Quality of Life Scale and the Palliative Care Outcomes Scale at referral, and 3, 7 and 28 days following referral to a Macmillan specialist palliative care nursing service. A nominated carer was interviewed at baseline and 28 days. Notes recorded by Macmillan specialist palliative care nurses in relation to each patient case were analysed. FINDINGS: Significant improvements in emotional (P = 0.03) and cognitive functioning (P = 0.03) were identified in changes in patients' European Organization for Research on Treatment of Cancer Quality of Life Scale scores, and in Palliative Care Outcomes Scale patient anxiety scores (P = 0.003), from baseline to day 7. Analysis of case study data indicated that overall positive outcomes of care from Macmillan specialist palliative care nursing intervention were achieved in 42 (55%) cases. STUDY LIMITATIONS: Sample attrition due to patients' deteriorating condition limited the value of data from the quality of life measures. The method developed for evaluating nursing outcomes using data from patient and carer interviews and nursing records was limited by a lack of focus on outcomes of care in these data sources. CONCLUSIONS: A method was developed for evaluating outcomes of nursing care in complex situations such as care of people who are dying. Positive outcomes of care for patients that were directly attributable to the care provided by Macmillan specialist palliative care nurses were found for the majority of patients. For a small number of patients, negative outcomes of care were identified.

Clinical nurse specialists in palliative care. Part 2. Explaining diversity in the organization and costs of Macmillan nursing services.

In the UK, the work of Macmillan clinical nurse specialists in palliative care is now well established. There has been little research, however, into the organizational context in which these nurses operate and the implications for the services they deliver. We report on a major evaluation of the service delivery, costs, and outcomes of Macmillan nursing services in hospital and community settings. The study was based on eight weeks of fieldwork in each of 12 selected services. Data are presented from semi-structured interviews, clinical records, and cost analysis. We demonstrate wide variation across several dimensions: location and context of the services; activity levels; management patterns; work organization and content; links with other colleagues; and resource use. We suggest that such variation is likely to indicate the existence of both excellent practice and suboptimal practice. In particular, our study highlights problems in how teamwork is conceptualized and delivered. We draw on recent organizational theories to make sense of the heterogeneous nature of Macmillan nursing services.

Clinical nurse specialists in palliative care. Part 3. Issues for the Macmillan Nurse role.

The remit and boundaries of the Macmillan Nursing role in the UK have been called into question recently by a number of policy-driven changes. The rapid appointment of tumour site-specific nurses and the development of posts for palliative medicine, stemming originally from the Calman-Hine recommendations for reorganizing cancer services, have created unparalleled challenges of adaptation to new working practices and procedures. The extent to which Macmillan Nurses are adapting to these new demands was addressed as part of a major evaluation study of UK Macmillan Nursing in 12 sites commissioned by the UK charity Macmillan Cancer Relief. This paper draws upon semi-structured interviews with Macmillan Nurses (n = 44) and their key colleagues (n = 47). We found that differences of expectation between Macmillan Nurses and their managers about the appropriate focus of their work lead to problems of role ambiguity and role conflict; that Macmillan Nurses lack resources with which to develop an educative and consultative role and yet substitute for inadequacies in skills and knowledge of other health care staff; and that problems are associated in co-working with newly appointed cancer site-specific nurses and palliative medicine colleagues. Macmillan Nursing has a crucial role to play in meeting the objectives in the NHS Cancer Plan. However, in order to ensure that their expertise is used efficiently and effectively, there is an urgent need to clarify the nature and scope of the Macmillan Nurse role, to attend to issues of team working and to improve the skills of nonspecialist staff in palliative care.

Clinical nurse specialists in palliative care. Part 1. A description of the MacMillan Nurse caseload.

Macmillan Nurses play a significant role in specialist palliative care services in the UK, providing direct and indirect services to patients with complex palliative care needs and to their families. Existing literature shows a developing understanding of the role; however, little detailed data exist regarding the clinical work that they undertake. This paper provides evidence from a major evaluation study, commissioned by Macmillan Cancer Relief. It reports the methods of data collection for the study and then goes on to use data from the evaluation to describe the caseload of Macmillan Nurses. Between September 1998 and October 1999, a team of researchers worked alongside 12 Macmillan teams for a period of 8 weeks with each team. Prospective data were gathered on all new referrals to the services within the 8-week period. This included demographic details, timing of referral, the nature and purpose of contacts, and interventions, recorded from case notes and Macmillan Nurse records. Where possible, a date of death was obtained for all patients. A total of 814 new patients were referred during the study period (range 45-114 per site). The most common reasons for referral were emotional care for the patient (57%), pain control (27%), and other physical symptoms (33%). Thirteen per cent of the patients referred to the services died within 1 week of referral while 40% died within 6 weeks; thus, a significant proportion of patient work is focused on care at the end of life. It is also noteworthy that one-third of patients were still alive, indicating that some patients are being cared for earlier in the illness trajectory. On average, each new patient referral received two or more 'face-to-face' visits and two follow-up phone calls within the 8-week period. It would appear that Macmillan Nurse teams have been successful in getting access to relevant patients. As with any service that provides a complex set of interventions, the Macmillan teams have to adapt and develop the services in each setting. Whilst it is clearly important for the development of a Macmillan service to be tailored to the local conditions, the evidence on diversity suggests that in some cases, stronger guidance, in partnership with both Macmillan Cancer Relief and core providers, may be justified.