Lifestyle guidelines for managing adverse effects on bone health and body composition in men treated with androgen deprivation therapy for prostate cancer: an update.

BACKGROUND: Men treated with androgen deprivation therapy (ADT) for prostate cancer are prone to multiple treatment-induced adverse effects, particularly with regard to a deterioration in bone health and altered body composition including decreased lean tissue mass and increased fat mass. These alterations may partially explain the marked increased risk in osteoporosis, falls, fracture and cardiometabolic risk that has been observed in this population. METHODS: A review was conducted that assessed standard clinical guidelines for the management of ADT-induced adverse effects on bone health and body composition in men with prostate cancer. RESULTS: Currently, standard clinical guidelines exist for the management of various bone and metabolic ADT-induced adverse effects in men with prostate cancer. However, an evaluation of the effectiveness of these guidelines into routine practice revealed that men continued to experience increased central adiposity, and, unless pharmacotherapy was instituted, accelerated bone loss and worsening glycaemia occurred. CONCLUSIONS: This review discusses the current guidelines and some of the limitations, and proposes new recommendations based on emerging evidence regarding the efficacy of lifestyle interventions, particularly with regard to exercise and nutritional factors, to manage ADT-related adverse effects on bone health and body composition in men with prostate cancer.

How calls from carers, friends and family members of someone affected by cancer differ from those made by people diagnosed with cancer; analysis of 4 years of South Australian Cancer Council Helpline data.

PURPOSE: The purpose of this study is to determine how people diagnosed with cancer who call the Cancer Council Helpline in South Australia differ from carers/family/friends (caregivers) who call. METHOD: Descriptive, retrospective audit of calls from people who contacted Cancer Council Helpline in South Australia between 16 April 2009 and 16 April 2013 who were diagnosed with cancer (n = 5766) or were the caregivers (n = 5174) of a person with cancer. RESULTS: Caregivers were more likely to be female (p < 0.001); younger in age (p < 0.001); call regarding cancer that was metastasised/widespread/advanced, terminal or at an unknown stage (p < 0.001) and phone requesting general cancer information or emotional support (p < 0.001). This group was more distressed (p < 0.001) but less likely (p = 0.02) to be offered and/or accept referrals to counselling than people diagnosed with cancer who called. Follow-up care was required by 63.5 % of caregivers and 73.1 % of people with cancer according to distress management guidelines; 8.5 and 15.3 %, respectively, accepted referrals to internal services. The most frequently discussed topic for both groups was emotional/psychological concerns. There were no differences in remoteness of residence or call length between groups. CONCLUSIONS: Caregivers represented different demographic groups than people diagnosed with cancer who called this helpline. The two groups phoned for different issues, at different stages of disease progression, displayed different levels of distress and, therefore, may benefit from services being tailored to meet their unique needs. These results also demonstrate the capacity of helplines to complement other health services and confirm that callers to cancer helplines exhibit high levels of distress.

'First, do no harm': managing the metabolic impacts of androgen deprivation in men with advanced prostate cancer.

Androgen deprivation therapy (ADT) is a standard systemic treatment for men with prostate cancer. Men on ADT may be elderly and have comorbidities that are exacerbated by ADT, such as cardiovascular disease, diabetes, obesity, sedentary lifestyle and osteoporosis. Studies on managing the impacts of ADT have focused on men with non-metastatic disease, where ADT is given for a limited duration. However, some men with advanced or metastatic prostate cancer will achieve long-term survival with palliative ADT and therefore also risk morbidity from prolonged ADT. Furthermore, ADT is continued during the use of other survival-prolonging therapies for men with advanced disease, and there is a general trend to use ADT earlier in the disease course. As survival improves, management of the metabolic effects of ADT becomes important for maintaining both quality and quantity of life. This review will outline the current data, offer perspectives for management of ADT complications in men with advanced prostate cancer and discuss avenues for further research.

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.

Psychosocial factors impacting on life transitions among young adults with type 2 diabetes: an Australian - Danish qualitative study.

BACKGROUND: Type 2 diabetes (T2DM) prevalence is increasing rapidly worldwide with a significant increase in young adults. There is limited information about psychosocial and service needs of this group. AIM: To explore similarities and differences in how psychosocial factors impact on Australian and Danish young adults with T2DM and to identify unmet support needs during life transitions. METHOD: A qualitative approach was adopted using thematic content analysis of 26 in-depth semi-structured interviews. An inductive descriptive content analysis was undertaken using a comparative coding system. FINDINGS: Eligible participants were from Australia (12) and Denmark (14), aged 19-42 years who had T2DM for more than 10 months. In general, they reported diabetes management was difficult during transitions and diabetes self-care routines had to change to accommodate life changes. The underpinning sense of 'uncertainty' initiated by life transitions caused guilt that often resulted in low self-worth, anxiety and depression, which in turn had a negative impact on social and professional relationships. The participants emphasised the importance of connectedness to social networks, particularly with T2DM peers, and the need for flexible access to health professionals, age-specific tailored support and lower costs for Australians. Australian participants were more concerned than Danish participants about the cost associated with diabetes care and their ability to stay employed; hence, they were reluctant to disclose diabetes at work. CONCLUSION: T2DM had a similar impact on life transitions of Australian and Danish young adults with T2DM, suggesting health care needs to encompass managing life transitions. Participants had to cope with uncertainty and the impact of people's responses to diabetes, particularly at work and in relationships. Health professionals are urged to integrate these factors in care plans and education, which must be individualised and focus on the psychosocial aspects that operate during life transitions.

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 18 years 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.

Mapping the information resources available to patients with colorectal cancer.

The objectives of this study were to identify gaps in information provision along the colorectal cancer (CRC) treatment pathway as provided by health services within the North Eastern Metropolitan Integrated Cancer Service in Victoria Australia; to evaluate the information and recommend consistent, high quality health information resources; and to recommend strategies to improve delivery of patient information. A random sample of health professionals (n= 47) from various disciplines at eight health service sites participated in semi-structured interviews regarding the types of information they provided to CRC patients. Information items were mapped against a published CRC patient management framework and evaluated. A total of 193 information items were collected with 24 items specific to CRC. Gaps in information provision were evident in the community, at diagnosis, in clinics, when treatment was determined and when completed. The quality of information delivery to CRC patients across the public health sites was variable. Resources were often unavailable, out of date and inaccessible in other languages. Results indicate a need to improve health information availability and resource delivery to all CRC patients across different health services particularly at diagnosis and after treatment. Further research is required to determine patient preferences for information about CRC.

How acceptable is a referral and telephone-based outcall programme for men diagnosed with cancer? A feasibility study.

The objective of this study was to determine the feasibility and acceptability of a referral and outcall programme from a telephone-based information and support service, for men newly diagnosed with colorectal or prostate cancer. A block randomized controlled trial was performed involving 100 newly diagnosed colorectal and prostate cancer patients. Patients were referred to the Cancer Information Support Service (CISS) through clinicians at diagnosis. Clinicians were randomized into one of three conditions. Active referral 1: specialist referral with four CISS outcalls: (1)

Selection of GM2, fucosyl GM1, globo H and polysialic acid as targets on small cell lung cancers for antibody mediated immunotherapy.

Glycolipids GM2, GD2, GD3, fucosyl GM1, sialyl Lewis a (sLe(a)) and globo H, and polysialic acid on embryonal NCAM, are cell-surface antigens expressed on small cell lung cancer (SCLC) biopsy specimens. They are all candidates for inclusion in a polyvalent, antibody-inducing vaccine or for adoptive therapy with monoclonal antibodies (mAbs) against SCLC. To identify the minimum optimal combination of target antigens on SCLC and to confirm that antibodies against this combination might be able to mediate complement activation and lysis in the majority of cases, we tested ten SCLC cell lines with fluorescence activated cell sorter (FACS) and complement dependent cytotoxicity (CDC) assays using mAbs against these seven target antigens individually or pooled in different combinations. We find that (1) none of these mAbs demonstrated strong FACS reactivity with more than 6 of the 10 cell lines, (2) no mAb had strong CDC reactivity with more than 4 of the cell lines, (3) when the mAbs were pooled, nine cell lines were strongly positive by FACS and nine cell lines were strongly positive by CDC, and (4) mAbs against GM2, FucGM1, globo H and polysialic acid was the minimum optimal combination for inducing FACS reactivity. The addition of mAbs against sLe(a), GD2 and GD3 had no additional impact by FACS and only minimal additional impact in CDC assays. H345, the only cell line that had less than 30% CDC with the four mAb pool was strongly positive by FACS. To understand the lack of correlation between FACS and CDC in the case of H345, the ten cell lines were screened for expression of complement resistance factors CD55 and CD59. Three cell lines were strongly positive for CD55 and eight were strongly positive for CD59. Overall, no correlation was seen between expression of either of these factors on the ten cell lines and sensitivity to CDC. In the case of H345 however, complement resistance of H345 is demonstrated to be mediated primarily by CD59, and in the presence of mAb against CD59, the four mAb MEM-43 pool induced strong (94%) CDC. CD59 inhibits membrane attack complex formation but not activation of earlier complement components. Consequently, all ten cell lines are good targets for complement activation by the four antibody pool and for elimination by effector mechanisms including complement mediated inflammation and opsonization. These findings support our plan to develop a tetravalent vaccine against SCLC targeting GM2, fucosyl GM1, globo H and polysialic acid.

Quality of care for women presenting with benign breast conditions.

The aim of the study was to investigate the management of women with benign breast problems. A consecutive sample of women (n = 194) was assessed who presented to public or private sector providers. The main reasons for referral were breast lumps (62%); 56% of women who attended the public sector did not receive any recommendation compared to 40% who attended the private sector and clinical/general practitioner reviews were recommended to more women in the private sector (54%). Reasons for the discrepancy between public and private patients require further investigation.

Clinical results using biochemotherapy as a standard of care in advanced melanoma.

Phase II studies of biochemotherapy in metastatic melanoma patients have reported response rates of 47-63%. Even though these were highly selected patients, we were intrigued by these promising response rates and began using this regimen as standard care in advanced melanoma patients. We report the results of the first 65 patients with AJCC stage IV melanoma (n = 57) or unresectable stage III (n = 8) melanoma treated with concurrent biochemotherapy at Memorial Hospital. Treatment was repeated every 3 weeks and patients were assessed for antitumour effects after every other cycle. The overall response rate among the 63 patients evaluable for response was 29% (three complete responses, 15 partial responses). The median duration of responses was 3.7 months. The response rate among previously treated and previously untreated patients was 6% and 38%, respectively. The estimated median survival for all patients was 8.5 months; the median survival for previously untreated patients was 9.2 months. Tumour response did not correlate with survival. Our experience, which is a retrospective evaluation, does not provide support for the routine use of biochemotherapy as standard treatment. The low response rate among previously treated patients indicates that biochemotherapy is not useful as second-line therapy.

Knowledge, attitudes and experience associated with testing for prostate cancer: a comparison between male doctors and men in the community.

BACKGROUND: Debate about testing for prostate cancer using prostate-specific antigen (PSA) and digital rectal examination (DRE) continues. The evidence of benefit from screening for prostate cancer using PSA tests is inconclusive, and it is unclear how PSA can be used most effectively in the detection of prostate cancer. Given the lack of consensus, it is important that consumers understand the issues in a way that will permit them to decide whether or not to have a test and, if symptomatic, how their condition is managed. AIMS: To compare prostate cancer knowledge, attitudes and testing experiences reported by male doctors and men in the community, despite the lack of evidence of a benefit. METHODS: The primary method for ascertaining the attitudes of male doctors (MD) was a telephone survey, with some doctors electing to complete a written survey. Each MD was selected, at random, from a register of male practitioners aged > or = 49 years of age. A total of 266 MD participated in the survey. The community sample (CS) was accessed using a telephone survey. Five hundred male Victorian residents aged > or = 49 years of age participated in the study. RESULTS: Knowledge - Overall, 55% of the CS indicated correctly that prostate disease is sometimes cancer, compared to 83% of MD. Attitudes - Fifty-five per cent of MD believed men should be tested for prostate disease at least every 2 years, compared to 68% of men in the CS. Testing experience - Forty-five per cent of MD had been tested for prostate cancer in the past, and 92% of those tests were reported as negative. In the CS, 56% had been tested for prostate cancer in the past, and 78% of the results were reported as negative. The significant independent predictors of having had a prostate test among MD were: (i) age (> or = 60 years; odds ratio (OR): 1.59; 95% confidence intervals (CI): 1.30-1.88) and (ii) positive attitudes towards regular testing for prostate cancer (OR: 2.27; 95% CI: 1.98-2.56). The significant independent predictors for the CS were: (i) age (> or = 60 years; OR: 1.65; 95% CI: 1.40-1.89), (ii) being married (OR: 1.30; 95% CI: 1.00-1.60), (iii) knowledge that prostate disease was sometimes cancer (OR: 1.46; 95% CI: 1.26-1.66) and (iv) positive attitudes towards regular testing for prostate cancer (OR: 2.12; 95% CI: 1.90-2.34). CONCLUSIONS: The results highlight that testing for prostate cancer is widespread in the community and in the medical profession. Further research should be undertaken to identify how to help men make fully informed decisions about prostate cancer testing.

Knowledge, attitudes and self-care practices related to sun protection among secondary students in Australia.

The aim of this research was to ascertain changes in sun-related knowledge, attitudes and self-care practices among Australian secondary school students between 1993 and 1996. Two cross-sectional surveys of sun-related attitudes, beliefs and behavior of young people aged 12-17 years of age, were conducted in 1993 and 1996. Over 80% of adolescents at both time periods knew about the issues related to skin cancer prevention, frequency of burning and burning on cloudy days. Adolescent attitudes had shifted positively in the areas of staying inside in 1996 [relative risk (RR): 1.13; 95% confidence interval (CI): 1.09-1.17] and staying under shade in 1996 (RR: 1.16; 95% CI: 1.13-1.18). Desire for a moderate or dark tan was lower in 1996 (45%) than in 1993 (50%). Respondents reported that they were less likely to wear brief clothing to get a suntan in 1996 (RR: 0.81; 95% CI: 0.78-0.84) and were significantly more likely to stay in the shade in 1996 (RR: 1.19; 95% CI: 1.16-1.23). We conclude that there has been a shift in attitudes towards use of shade and avoidance of unnecessary exposure, and away from use of sunscreens and sunglasses. The results suggest that adolescents may be more ready to accept structural changes that move desired activities out of the sun.

Antibody-dependent cell-mediated cytotoxicity can be induced by MUC1 peptide vaccination of breast cancer patients.

Human polymorphic epithelial mucin (PEM, MUC1) is a high molecular weight transmembrane glycoprotein expressed on the apical cell surface of glandular epithelium and is over-expressed and hypo-glycosylated in adenocarcinomas. The extracellular part of the molecule consists mainly of a variable number of 20 amino acid repeats that contain cryptic epitopes exposed in malignancy. The objective of our study was to determine whether humanized MUC1 MAbs and Abs induced by vaccination of breast cancer patients with MUC1 peptides can effect an antibody-dependent cell-mediated cytotoxicity (ADCC). An in vitro assay has been set up in which the breast tumor cell line ZR-75-1 is used as target and PBMC of healthy donors as effector cells. Different target and effector cells, as well as various MUC1 MAbs were tested to optimize the efficacy of the in vitro assay. The humanized MAb HuHMFG-1, which recognizes the PDTR sequence in the MUC1 tandem repeat, induced a strong cell-mediated cytotoxicity. Nine MUC1-expressing tumor cell lines, including 3 bone marrow-derived cell lines, as well as 2 MUC1-transfected cell lines were susceptible to different extent to MUC1 Ab-dependent killing. Large variations in the killing capacity of PBMC from healthy donors were found. The NK cells were the essential effector cells for the MUC1 Ab-dependent killing. Plasma samples with induced high levels of MUC1 Ab were obtained from breast cancer patients repeatedly immunized with a KLH-conjugated 33-mer or 106-mer MUC1 tandem repeat. Pre- and post-vaccinated plasma samples of these patients were compared in the ADCC assay and it could be clearly demonstrated that the induced MUC1 Abs can effect tumor cell killing. MUC1 Ab-dependent cell-mediated tumor cell killing may occur in vivo and the ADCC assay can be applied to monitor MUC1 vaccination trials.

The effectiveness of callback counselling for smoking cessation: a randomized trial.

AIMS: The development of acceptable, widely available and effective smoking cessation methods is central to public health strategy for tobacco control. We examined the effectiveness of a telephone callback counselling intervention, compared to the provision of self-help resources alone. METHODS: Participants were 998 smokers calling a state-wide "Quitline" service randomly allocated to either callback counselling or ordinary care. The callback condition consisted of a series of brief counselling calls at strategic times in addition to ordinary care. The number of calls varied according to caller needs, and most occurred generally just before the person's quit day and in the week or two after it. The service was delivered by trained telephone counsellors. RESULTS: At the 3-month follow-up, significantly more participants in the callback group (24%) reported that they were quit, compared to those in the usual care comparison group (13%). The difference in point prevalence of smoking declined to 6% by the 12-month follow-up. Using sustained abstinence there was a significant benefit of callback counselling at 12-month follow-up. Treating dropouts as smokers reduced the overall magnitude of the effects somewhat. The benefit of callbacks was to marginally increase quit attempts and to significantly reduce relapse. CONCLUSION: Our findings are consistent with those of other studies demonstrating benefits of callback telephone counselling to facilitate cessation. Such counselling provides a flexible, relatively inexpensive and widely available form of cessation service. It appears to encourage a greater proportion of quit attempts and to reduce the rate of relapse among those quitting. Further research is required to determine ways to enhance effectiveness, particularly studies of how to reduce relapse.

Immunization of metastatic breast cancer patients with a fully synthetic globo H conjugate: a phase I trial.

The carbohydrate antigen globo H commonly found on breast cancer cells is a potential target for vaccine therapy. The objectives of this trial were to determine the toxicity and immunogenicity of three synthetic globo H-keyhole limpet hemocyanin conjugates plus the immunologic adjuvant QS-21. Twenty-seven metastatic breast cancer patients received five vaccinations each. The vaccine was well tolerated, and no definite differences were observed among the three formulations. Serologic analyses demonstrated the generation of IgM antibody titers in most patients, with minimal IgG antibody stimulation. There was significant binding of IgM antibodies to MCF-7 tumor cells in 16 patients, whereas IgG antibody reactivity was observed in a few patients. There was evidence of complement-dependent cytotoxicity in several patients. Affinity column purification supported the specificity of IgM antibodies for globo H. On the basis of these data, globo H will constitute one component of a polyvalent vaccine for evaluation in high-risk breast cancer patients.

Keyhole limpet hemocyanin conjugate vaccines against cancer: the Memorial Sloan Kettering experience.

Passively administered and actively induced antibodies have been associated with the eradication of circulating tumor cells and micrometastases in mice and humans. We have identified a series of cell surface carbohydrate and peptide antigens on melanomas, sarcomas, and cancer of the breast, prostate. ovary, and lung tissues. We found that breaking tolerance toward these tumor antigens was best achieved using vaccines containing antigens chemically conjugated to keyhole limpet hemocyanin (KLH) plus a potent immunological adjuvant (QS-21). To date, by using this approach to vaccination. antibodies have been induced in patients against glycolipid antigens GM2, GD2, GD3, FucosylGM1, Globo H, and Lewis Y, and glycoprotein (mucin) antigens Tn, sialyl Tn. TF, and MUC1. More recently, in a comparative study we investigated the T cell response induced by MUCI-KLH conjugates. Although a MUC1-specific T cell response was not consistently detected in any patient, the role of KLH in orienting the cytokine environment was crucial. We were able to confirm that KLH in these conjugate vaccines induces a Th1 T cell response as demonstrated by the high anti-KLH INF-gamma secretion and the IgGI and IgG3 subclasses of this high titer IgG antibodies induced. Clinical trials using KLH conjugated glycolipid and glycoprotein vaccines, are currently ongoing. These range from phase I/II single antigens trials with glycosilated MUC1, polysialic acid, synthetic Fucosyl GMI and GD2, to phase II trials with a polyvalent vaccine containing six or seven antigens. Randomized phase II trials with polyvalent vaccines are planned for initiation in 2001-2002 in patients with ovarian, breast, and prostate cancer.