Peter Strang

Bone-targeted radium-223 in symptomatic, hormone-refractory prostate cancer: a randomised, multicentre, placebo-controlled phase II study

BACKGROUND The alpha-emitter radium-223 ((223)Ra) is a bone-seeking radionuclide studied as a new treatment for patients with bone metastases from hormone-refractory prostate cancer. We aimed to study mature outcomes from a randomised, multicentre, phase II study of (223)Ra. METHODS Patients with hormone-refractory prostate cancer and bone pain needing external-beam radiotherapy were assigned to four intravenous injections of (223)Ra (50 kBq/kg, 33 patients) or placebo (31 patients), given every 4 weeks. Primary endpoints were change in bone-alkaline phosphatase (ALP) concentration and time to skeletal-related events (SREs). Secondary endpoints included toxic effects, time to prostate-specific-antigen (PSA) progression, and overall survival. All tests were done at a 5% significance level, based on intention to treat. FINDINGS Median relative change in bone-ALP during treatment was -65.6% (95% CI -69.5 to -57.7) and 9.3% (3.8-60.9) in the (223)Ra group and placebo groups, respectively (p<0.0001, Wilcoxon ranked-sums test). Hazard ratio for time to first SRE, adjusted for baseline covariates, was 1.75 (0.96-3.19, p=0.065, Cox regression). Haematological toxic effects did not differ significantly between two groups. No patient discontinued (223)Ra because of treatment toxicity. Median time to PSA progression was 26 weeks (16-39) versus 8 weeks (4-12; p=0.048) for (223)Ra versus placebo, respectively. Median overall survival was 65.3 weeks (48.7-infinity) for (223)Ra and 46.4 weeks (32.1-77.4) for placebo (p=0.066, log rank). The hazard ratio for overall survival, adjusted for baseline covariates was 2.12 (1.13-3.98, p=0.020, Cox regression). INTERPRETATION (223)Ra was well tolerated with minimum myelotoxicity, and had a significant effect on bone-ALP concentrations. Larger clinical trials are warranted to study (223)Ra on the prevention of SREs and on overall survival in patients with hormone-refractory prostate cancer. Bone-targeting properties of (223)Ra could also potentially be used for treating skeletal metastasis from other primary cancers.

A randomized, dose–response, multicenter phase II study of radium-223 chloride for the palliation of painful bone metastases in patients with castration-resistant prostate cancer

PURPOSE To investigate the dose-response relationship and pain-relieving effect of radium-223, a highly bone-targeted alpha-pharmaceutical. METHODS One hundred patients with castration-resistant prostate cancer (CRPC) and painful bone metastases were randomized to a single intravenous dose of 5, 25, 50 or 100 k Bq/kg radium-223. The primary end-point was pain index (visual analogue scale [VAS] and analgesic use), also used to classify patients as responders or non-responders. RESULTS A significant dose response for pain index was seen at week 2 (P = .035). At week 8 there were 40%, 63%, 56% and 71% pain responders (reduced pain and stable analgesic consumption) in the 5, 25, 50 and 100 k Bq/kg groups, respectively. On the daily VAS, at week 8, pain decreased by a mean of -30, -31, -27 and -28 mm, respectively (P = .008, P = .0005, P = .002, and P < . 0001) in these responders (post-hoc analysis). There was also a significant improvement in the brief pain inventory functional index for all dose-groups (P = .04, .01, .002 and .02, Wilcoxon signed rank test). Furthermore, a decrease in bone alkaline phosphatase in the highest dose-group was demonstrated (P = .0067). All doses were safe and well tolerated. CONCLUSION Pain response was seen in up to 71% of the patients with a dose response observed 2 weeks after administration. The highly tolerable side-effect profile of radium-223 previously reported was confirmed.

Spiritual thoughts, coping and ‘sense of coherence’ in brain tumour patients and their spouses

When a person is diagnosed with a life-threatening disease, existential questions are easily triggered. The aims of this study were to explore to what extent brain tumour patients and their next of kin were able to cope, understand and create meaning in their situation, to explore whether spirituality could be supportive and to analyse whether these concepts are related to Antonovskys concept of sense of coherence. Using a purposive sampling technique, 20 patients and 16 of their next of kin took part in tape-recorded interviews. A content and context analysis was performed using a hermeneutic approach. We found that comprehensibility was to a large extent constructed by the patients own thoughts and theories, despite an insecure situation. Manageability was achieved by active information-seeking strategies, by social support and by coping, including positive reinterpretation of the situation. Meaningfulness was central for quality of life and was created by close relations and faith, as well as by work. A crucial factor was whether the person had a ‘fighting spirit’ that motivated him or her to go on. As only three patients were believers, trust in God had generally been replaced by a belief and confidence in oneself, in science, in positive thinking and by closeness to nature. Sense of coherence as a concept can explain how exposed persons handle their situation. In its construction, sence of coherence integrates essential parts of the stress/coping model (comprehensibility, manageability) and of spirituality (meaning).

Death anxiety in brain tumour patients and their spouses.

When a person is diagnosed with a severe disease, it seems plausible that existential questions and death anxiety are easily intensified. The aims of this study were to explore whether this is the case, to what extent patients and their next of kin experience death anxiety, and how these experiences are expressed. Following a purposive sampling technique, 20 patients with brain tumours and 15 of their next of kin took part in interviews. A content and context analysis were performed using a hermeneutic approach, in order to identify and analyse main categories. Six main categories common to patients and their next of kin emerged during the process: (1) emotional reactions that could be related to death anxiety and included general anxiety, anguish, sadness, hope and despair; (2) existential fear, existential anxiety and existential pain; (3) contradictions; (4) trigger situations; (5) coping strategies related to death anxiety; and (6) new values for life. Besides these categories, a further category emerged, experiences characteristic of the next of kin. The study shows that both the patients and their next of kin are preoccupied with existential thoughts and death anxiety. The problems are easily overlooked as the death anxiety is not always expressed directly. Staff need to be more aware of these situations in order to provide existential support.

Next of kin’s experience of powerlessness and helplessness in palliative home care

Goals of workPowerlessness and helplessness have been very little studied. The aims of this study were (1) to describe what characterise such experiences and the meaning of them to next of kin of cancer patients in advanced palliative home care and (2) to make quantifications.Patients and methodsThe study design was cross-sectional and targeted next of kin during ongoing palliative home care and next of kin of patients who had died 3–9 months earlier; 233 next of kin responded (response rate 72%) to a postal questionnaire with both Likert-type and open-ended questions. The text responses were analysed with a combined qualitative and quantitative content analysis.Main resultsThirty-six percent of respondents stated that they had experienced powerlessness and/or helplessness every day or several times per week, whereas 33% had never had this experience during the palliative home care period. Powerlessness and helplessness concerned next of kin’s perception of the patient’s suffering, of the patient’s fading away and the next of kin’s own feelings of insufficiency and resulted in both physical and psychological symptoms, such as muscle tension, headache, loss of appetite, anxiety and depression. In addition, powerlessness and helplessness concerned also a deeper meaning with existential and social aspects, such as feelings of guilt, anger and loneliness.ConclusionsThe main findings provide tools for the practitioner to identify situations contributing to next of kin’s sense of powerlessness and helplessness. The findings are discussed in relation to the concepts of symptom control, communication of awareness and humans’ search for action.

The organization of hospital-based home care for terminally ill cancer patients: the Motala model

In 1977, the first palliative home care programme in Sweden, the Motala hospital-based home care, was established to provide a high level of medical care on a 24-hour basis, as an alternative and a replacement to hospital care. The current study summarizes the care and organizational needs of 179 consecutive terminally ill cancer patients treated during a 10-year period. Of the patients, 70% came from acute clinics. The median time of care was 36 days. The need for help with activities of daily living was a significant predictor of the length of survival, with the greatest difference between four or less compared to five or six items (p = 0.0006). Analgesics were needed by 96% of the patients, and 78% were provided with various facilities such as hospital beds. The input of family members as primary caregivers was essential for successful care, as were security factors such as easy availability of a nurse or doctor, at any time day or night, and an immediate, guaranteed hospital bed, if needed. As many as 89% of the patients who wished to live at home until death actually did so. We conclude that hospital-based home care according to the Motala model can replace hospital care for selected patients, but only if both the patient and the family approve.

EMOTIONAL AND SOCIAL ASPECTS OF CANCER PAIN

The emotional and social consequences of pain were studied in 93 consecutive in-patients, 44 males and 49 females, suffering from cancer-related pain. The methods used were Visual Analogue Scales (VAS), standardized interviews and comprehensive self-questionnaires. Forty-seven patients (51%) experienced certain or pronounced anxiety (4-6 or 7-9 on a 9-grade scale) because of their pain and 66 patients (71%) expressed depressive pain-associated symptoms, which had a high correlation with the intensity of their pain. Physical activities such as movements, dressing/undressing, washing, cooking were hampered in about 2/3 of the patients and mental activities such as reading were significantly disturbed in 48% of the cases. For every social activity listed in the questionnaires (hobbies, seeing friends, etc) most patients reported a decreased activity because of pain and in most cases the decrease correlated significantly with the intensity of the pain. The family roles had changed since the patient could not participate in a usual manner. The study underlines the profound consequences of pain: physical suffering, emotional distress, social handicap and altered family roles. Thus, pain control should be a high-priority matter in palliative care.

Cancer pain--a provoker of emotional, social and existential distress.

Although methods for controlling most cases of severe cancer pain exist, probably about 50% of patients still suffer from unnecessary, poorly controlled pain. Cancer pain has a substantial negative effect on mood, resulting in anxiety, depressive feelings and even suicidal thoughts and cognitive functions are disturbed. As cancer pain often originates from skeletal metastases, movements and daily activities (ADL) functions are restricted. Cancer pain is associated by the public with progressive disease and dying and is therefore a trigger of existential fears, for both patients and the public. Pain treatment and education are therefore high-priority matters with effects far beyond the physical suffering.

Differences in supporting families of dementia patients and cancer patients: a palliative perspective:

Objectives: To investigate what staff working in close contact with patients perceive as good support of families in dementia care as compared with support of families in palliative cancer care. Design and subjects: During four national courses on dementia care and one national course on palliative cancer care, 316 and 121 participants, respectively, responded to an open-ended question: In your experience, what are the two most important measures for supporting families of dementia patients/severely ill cancer patients? Sixty-one items were coded and allocated into 10 main categories and analysed with both a qualitative and quantitative approach. Results: The dominant items for both staff groups were to listen to the family member and to give information, although listening was significantly more often stressed in the palliative group (PB = 0.001). The staff in dementia care stressed significantly more the importance to form support groups for families (PB = 0.001), to offer respite care (PB = 0.001), to educate families (PB = 0.001) and to try to relieve the familys feeling of guilt (PB = 0.001). In the palliative staff group, the importance of being available (PB = 0.05), creating a sense of security (PB = 0.001) and supporting the family after the patients death (PB = 0.01) were significantly more focused on. Discussion: The respondents from the dementia staff group and from the palliative cancer group stressed the importance of supporting family members. However, the type of support needed partly differs because of the different trajectories in dementia compared with severe cancer phases.

Dying cancer patients’ experiences of powerlessness and helplessness

Goals of workExperiences of powerlessness and helplessness are closely linked to incurable diseases but seldom studied in patients with disseminated cancer. The aim is to explore the perception, experiences and significance of powerlessness and helplessness, to study triggering factors and to make quantifications.Materials and methodsOne hundred three patients, enrolled in four different palliative home-care settings, completed a questionnaire with both Likert-type questions and open-ended questions. The response rate was 58%, and background data was reported as frequencies, whereas the main material was analysed using a qualitative content analysis.Main resultsImpending death, symptoms, loss of control and autonomy, ignorance, isolation and uncertainty constituted the basis for powerlessness and helplessness, but each factor was reinforced by the occurrence of suddenness, high intensity and/or lengthiness. In total, 65% reported definite experiences of powerlessness and helplessness. These feelings also held a deeper meaning, involving aspects such as existential loneliness and hopelessness. They were ultimately caused by an incapacity to control feelings and cope with the situation related to the impending death. The results are discussed in relation to Cassel’s theory of suffering and existential psychology.