An exploration of testicular cancer survivors' experience of ejaculatory dysfunction following retroperitoneal lymph node dissection-a sub-study of the PREPARE clinical trial.

PURPOSE: Ejaculatory dysfunction secondary to retrograde ejaculation or anejaculation is a complication of retroperitoneal lymph node dissection (RPLND) for survivors of testicular cancer. We explored survivors' experiences of ejaculatory dysfunction following RPLND. METHODS: In a sub-study of a single-arm phase 2 clinical trial (ACTRN12622000537752/12622000542796), participants reporting ejaculatory dysfunction ≥ 6 months following RPLND were invited to complete semi-structured interviews. Purposive sampling was used. Interviews continued until thematic saturation occurred, and codebook thematic analysis of interviews was performed. RESULTS: Of 58 individuals recruited to the trial, 33 (57%) reported ejaculatory dysfunction. Of these, 32 (97%) agreed to interview and 15 participated. Participants interviewed had median age 34 years (range 24-66), 12 (80%) in a long-term relationship with median time from surgery 36 months (range 11-112). Three overarching themes were identified. The first reflected the value of RPLND despite ejaculatory dysfunction. The second illuminated the impact(s) of ejaculatory dysfunction closely mapped to life stage, with flow-on impacts to fertility, sex, psychological wellbeing and communication. The third reflected information needs. Fertility was a substantial source of concern for some participants. Ejaculatory dysfunction had no effect on sex for some, whilst for others, sex was less pleasurable. Some reported benefits. Few reported ejaculatory dysfunction challenged masculinity, confidence, or self-esteem. CONCLUSIONS: Future research should examine interventions to reduce distress related to fertility, challenged masculinity and body image. IMPLICATIONS FOR CANCER SURVIVORS: Whilst most participants considered ejaculatory dysfunction to have little impact on their sexual function and relationships, some reported significant difficulties varying by life stage and relationship status.

The impact of COVID-19 on cancer patients, their carers and oncology health professionals: A qualitative study.

OBJECTIVE: Cancer patients, carers and oncology health professionals have been impacted by the COVID-19 pandemic in many ways, but their experiences and psychosocial responses to the pandemic are still being explored. This study aimed to document the experience of Australians living with cancer, family carers, and Oncology health professionals (HPs) when COVID-19 first emerged. METHODS: In this qualitative study, participants (cancer patients currently receiving treatment, family carers and HPs) completed a semi-structured interview exploring their experiences of COVID-19 and the impact it had on cancer care. Participants also completed the Hospital Anxiety and Depression Scale (patients) and the Depression, Anxiety and Stress Scale (carers and HPs) to assess emotional morbidity. Thematic analysis was undertaken on qualitative data. RESULTS: 32 patients, 16 carers and 29 HPs participated. Qualitative analysis yielded three shared themes: fear and death anxiety, isolation, and uncertainty. For HPs, uncertainty incorporated the potential for moral distress and work-stress. Patients and carers scoring high on anxiety/depression measures were more likely to have advanced disease, expressed greater death anxiety, talked about taking more extreme precautionary measures, and felt more impacted by isolation. CONCLUSION: Cancer and COVID-19 can have compounding psychological impacts on all those receiving or giving care. PRACTICE IMPLICATIONS: Screening for distress in patients, and burnout in HPs, is recommended. Increased compassionate access and provision of creative alternatives to face-to-face support are warrented.

What happens to cancer survivors attending a structured cancer survivorship clinic? Symptoms, quality of life and lifestyle changes over the first year at the Sydney Cancer Survivorship Centre clinic.

BACKGROUND: Sydney Cancer Survivorship Centre (SCSC) clinic provides multidisciplinary care after primary adjuvant treatment, with ~ 40% of attendees continuing follow-up with SCSC. METHODS: SCSC survivors completed measures of symptoms, quality-of-life and lifestyle factors at initial visit (T1), first follow-up (T2) and 1 year (T3). Analyses used mixed effect models, adjusted for age, sex and tumour type. RESULTS: Data from 206 survivors (2013-2019) were included: 51% male; median age 63 years; tumour types colorectal 68%, breast 12%, upper gastrointestinal 12%, other 8%. Mean time from: T1 to T2, 3.6 months; T1 to T3, 11.8 months. Mean weight remained stable, but 45% (35/77) of overweight/obese survivors lost weight from T1 to T3. Moderately-intense aerobic exercise increased by 63 mins/week at T2, and 68 mins/week T3. Proportion meeting aerobic exercise guidelines increased from 20 to 41%. Resistance exercise increased by 26 mins/week at T2. Global quality-of-life was unchanged from T1 to T2, improving slightly by T3 (3.7-point increase), mainly in males. Mean distress scores were stable, but at T3 the proportion scoring 4+/10 had declined from 41 to 33%. At T3, improvements were seen in pain, fatigue and energy, but > 20% reported moderate-severe fatigue, pain or sleep disturbance. Proportion reporting 5+ moderate-severe symptoms declined from 35% at T1 to 26% at T3, remaining higher in women. CONCLUSIONS: Survivors attending SCSC increased exercise by 3 months, and sustained it at 1 year. Most overweight/obese survivors avoided further weight gain. Survivors had relatively good quality-of-life, with improvement in many symptoms and lifestyle factors at 1 year.

Dose intensity in anthracycline-based chemotherapy for metastatic breast cancer: mature results of the randomised clinical trial ANZ 9311.

PURPOSE: The separate impacts of dose and dose intensity of chemotherapy for metastatic breast cancer remain uncertain. The primary objective of this trial was to compare a short, high-dose, intensive course of epirubicin and cyclophosphamide (EC) with a longer conventional dose regimen delivering the same total dose of chemotherapy. METHODS: This open label trial randomised 235 women with metastatic breast cancer to receive either high-dose epirubicin 150 mg/m2 and cyclophosphamide 1500 mg/m2 with filgrastim support every 3 weeks for 3 cycles (HDEC) or standard dose epirubicin 75 mg/m2 and cyclophosphamide 750 mg/m2 every 3 weeks for 6 cycles (SDEC). Primary outcomes were time to progression, overall survival and quality of life. RESULTS: In 118 patients allocated HDEC 90% of the planned dose was delivered, compared to 96% in the 117 participants allocated SDEC. There were no significant differences in the time to disease progression (5.7 vs. 5.8 months, P = 0.19) or overall survival (14.5 vs. 16.5 months, P = 0.29) between HDEC and SDEC, respectively. Patients on HDEC reported worse quality of life during therapy, but scores improved after completion to approximate those reported by patients allocated SDEC. Objective tumour response was recorded in 33 (28%) on HDEC and 42 patients (36%) on SDEC. HDEC produced more haematologic toxicity. CONCLUSION: For women with metastatic breast cancer, disease progression, survival or quality of life were no better with high-dose intensity compared to standard dose EC chemotherapy. Australian Clinical Trials Registry registration number ACTRN12605000478617.

Health concerns of cancer survivors after primary anti-cancer treatment.

PURPOSE: Cancer survivors experience significant health concerns compared to the general population. Sydney Survivorship Clinic (SSC) is a multi-disciplinary clinic aiming to help survivors treated with curative intent manage side effects, and establish a healthy lifestyle. Here, we determine the health concerns of survivors post-primary treatment. METHODS: Survivors completed questionnaires assessing symptoms, quality of life (QOL), distress, diet, and exercise before attending SSC, and a satisfaction survey after. Body mass index (BMI), clinical findings and recommendations were reviewed. Descriptive statistical methods were used. RESULTS: Overall, 410 new patients attended SSC between September 2013 and April 2018, with 385 survivors included in analysis: median age 57 years (range 18-86); 69% female; 43% breast, 31% colorectal and 19% haematological cancers. Median time from diagnosis, 12 months. Common symptoms of at least moderate severity: fatigue (45%), insomnia (37%), pain (34%), anxiety (31%) and with 56% having > 5 moderate-severe symptoms. Overall, 45% scored distress ≥ 4/10 and 62% were rated by clinical psychologist as having 'fear of cancer recurrence'. Compared to population mean of 50, mean global QOL T-score was 47.2, with physical and emotional well-being domains most affected. Average BMI was 28.2 kg/m2 (range 17.0-59.1); 61% overweight/obese. Only 31% met aerobic exercise guidelines. Overall, 98% 'agreed'/'completely agreed' attending the SSC was worthwhile, and 99% would recommend it to others. CONCLUSION: Distress, fear of cancer recurrence, fatigue, obesity and sedentary lifestyle are common in cancer survivors attending SSC and may best be addressed in a multi-disciplinary Survivorship Clinic to minimise longer-term effects. This model is well-rated by survivors.

Psycho-oncology in Australia: a descriptive review.

Australia has a thriving Psycho-Oncology research and clinical community. In this article, the Australian health system in which Psycho-Oncology is embedded is described. Clinical Psycho-Oncology services are outlined, in terms of their composition, processes and reach. The development of the internationally ground-breaking Australian Psychosocial guidelines for the care of adults with cancer is described. Two large Psycho-Oncology organisations which are strongly linked to mainstream Oncology organisations are discussed: the Australian Psycho-Oncology Society (OzPos, a primarily clinician-led and focused organisation) and the Psycho-Oncology Co-operative Research Group (PoCoG, a national cancer clinical trial group). OzPos is a special interest group within the Clinical Oncology Society of Australia, while PoCoG is one of 14 cancer clinical trial groups funded by the national government. It is these strong connections with major multidisciplinary cancer organisations, and a culture of collaboration and co-operation, that have made Psycho-Oncology grow and thrive in Australia. Examples of large collaborative programs of Psycho-Oncology research are provided, as well as the mechanisms used to achieve these outcomes.

Impact of physical activity on fatigue and quality of life in people with advanced lung cancer: a randomized controlled trial.

BACKGROUND: Physical activity (PA) improves fatigue and quality of life (QOL) in cancer survivors. Our aim was to assess whether a 2-month PA intervention improves fatigue and QOL for people with advanced lung cancer. METHODS: Participants with advanced lung cancer, Eastern Cooperative Oncology Group performance status (PS) ≤2, >6 months life expectancy, and ability to complete six-min walk test, were stratified (disease stage, PS 0-1 versus 2, centre) and randomized (1:1) in an open-label study to usual care (UC) (nutrition and PA education materials) or experimental intervention (EX): UC plus 2-month supervised weekly PA and behaviour change sessions. Assessments occurred at baseline, 2, 4, and 6 months. The primary endpoint was fatigue [Functional Assessment of Cancer Therapy-Fatigue (FACT-F) questionnaire] at 2 months. The study was designed to detect a difference in mean FACT-F subscale score of 6. Analysis was intention-to-treat using linear mixed models. RESULTS: We recruited 112 patients: 56 (50.4%) were randomized to EX, 55(49.5%) to UC; 1 ineligible. Male 55%; median age 64 years (34-80); 106 (96%) non-small cell lung cancer; 106 (95.5%) stage IV. At 2, 4 and 6 months, 90, 73 and 62 participants were assessed, respectively, with no difference in attrition between groups. There were no significant differences in fatigue between the groups at 2, 4 or 6 months: mean scores at 2 months EX 37.5, UC 36.4 (difference 1.2, 95% CI - 3.5, 5.8, P = 0.62). There were no significant differences in QOL, symptoms, physical or functional status, or survival. CONCLUSIONS: Adherence to the intervention was good but the intervention group did not increase their PA enough compared to the control group, and no difference was seen in fatigue or QOL. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry No. ACTRN12609000971235.

Assessing the impact of a program for late surgical intervention in early-blind children.

OBJECTIVE: Many blind children in the developing world are unable to obtain timely treatment due to lack of financial and medical resources. Can public health programs that identify and treat such children several years after the onset of blindness enhance their quality of life? The notion that visual development is subject to an early 'critical period' argues against this possibility. However, there are inadequate empirical data from humans on this issue. To address this need, we examined the quality of life of children living in India and who were treated for early-onset blindness (before one year of age), due to cataracts or corneal opacities. STUDY DESIGN: Survey study. METHODS: As part of an ongoing scientific effort named Project Prakash, we screened over 40,000 children in rural northern India to identify those suffering from early-onset blindness. They were provided eye surgeries in a tertiary care ophthalmic center in New Delhi. We subsequently surveyed 64 Prakash children, ranging in age from 5 to 22 years and obtained their responses on a multi-dimensional quality of life questionnaire. RESULTS: Nearly all of the subjects indicated that their quality of life had improved after treatment. Children reported marked enhancement in their mobility, independence, and safety, and also in social integration. Surprisingly, we found no significant correlations between quality of life metrics and factors such as age at treatment, gender, time since treatment, and pre-surgery and post-surgery acuity. CONCLUSIONS: A key question for public health policy makers is whether a program of surgical intervention for older blind children is likely to be beneficial, or if the resources are better spent on rehabilitation via vocational training and assistive devices. The marked improvements in quality of life we find in our data strongly argue for the provision of surgical care regardless of a child's age.

Statistical controversies in cancer research: using standardized effect size graphs to enhance interpretability of cancer-related clinical trials with patient-reported outcomes.

Patient reported outcomes (PROs) are becoming increasingly important in cancer studies, particularly with the emphasis on patient centered outcome research. However, multiple PROs, using different scales, with different directions of favorability are often used within a trial, making interpretation difficult. To enhance interpretability, we propose the use of a standardized effect size graph, which shows all PROs from a study on the same figure, on the same scale. Plotting standardized effects with their 95% confidence intervals (CIs) on a single graph clearly showing the null value conveys a comprehensive picture of trial results. We demonstrate how to create such a graph using data from a randomized controlled trial that measured 12 PROs at two time points. The 24 effect sizes and CIs are shown on one graph and clearly indicate that the intervention is effective and sustained.

Fatigue in people with localized colorectal cancer who do and do not receive chemotherapy: a longitudinal prospective study.

BACKGROUND: Fatigue is associated with cancer and chemotherapy and may be sustained. Here, we describe a prospective longitudinal study evaluating fatigue and putative mechanisms in people with colorectal cancer (CRC). PATIENTS AND METHODS: People with localized CRC completed the Functional Assessment of Cancer Treatment-Fatigue (FACT-F) questionnaire at baseline (before chemotherapy, if given), 6, 12, and 24 months. Healthy controls (HCs) were assessed at the first three time points. Fatigue was defined by standardized FACT-F scores ≤68/100. Quality-of-life (QoL, assessed by the FACT-G questionnaire), affective, and cognitive symptoms were evaluated. Associations were sought between fatigue, baseline factors, and blood tests (including hemoglobin, cytokines, and sex hormones). Regression analyses, Fisher's exact tests, and Wilcoxon rank-sum tests assessed levels of fatigue at each time point and change in fatigue from baseline. A repeated-measures analysis investigated prognostic factors of fatigue across all time points. RESULTS: A total of 289 subjects with localized CRC (173 received chemotherapy) and 72 HCs were assessed. More CRC patients had fatigue than HCs at baseline (52% versus 26%, P < 0.001). Fatigue was increased in the chemotherapy (CTh) group at 6 months [CTh+ 70% versus CTh- 31% (P < 0.001), HCs 22%] and remained more common at 12 [CTh+ 44% versus CTh- 31% (P = 0.079)] and 24 months [CTh+ 39% versus CTh- 24% (P = 0.047)]. There was no significant difference between those not receiving chemotherapy and HCs at follow-up assessments. Fatigue was associated with poor QoL, affective and cognitive symptoms, but not consistently with cytokine levels. Predictors for sustained fatigue were baseline fatigue, treatment group, cognitive and affective symptoms, poorer QoL, and comorbidities. CONCLUSIONS: CRC patients have more fatigue than HCs at baseline. Fatigue peaks immediately after adjuvant chemotherapy, but remains common for 2 years in those who receive chemotherapy. Cognitive and affective symptoms, QoL, comorbidities, chemotherapy, and baseline fatigue predict for longer term fatigue.

Radiation therapy for people with cancer: what do written information materials tell them?

This study aimed to compare and contrast the contents of different types of written patient information about radiotherapy, namely (1) hospital radiotherapy departments vs. cancer control organisations and (2) generic vs. tumour-specific materials. A coding framework, informed by existing patients' information needs literature, was developed and applied to 54 radiotherapy information resources. The framework comprised 12 broad themes; cancer diagnosis, general information about radiotherapy, treatment planning, daily treatment, side effects, self-care management, external radiotherapy, internal radiotherapy, impact on daily activities, post-treatment, psychosocial health and other content, such as a glossary. Materials produced by cancer organisations contained significantly more information than hospital resources on diagnosis, general radiotherapy information, internal radiotherapy and psychosocial health. However, hospital materials provided more information about treatment planning, daily treatment and the impact on daily activities. Compared to generic materials, tumour-specific resources were superior in providing information about diagnosis, daily treatment, side effects, post-treatment and psychosocial health. Information about internal radiotherapy, prognosis and chronic side effects were poorly covered by most resources. Collectively, hospital and cancer organisation resources complement each other in meeting patients' information needs. Identifying ways to consolidate different information sources could help comprehensively address patients' medical and psychosocial information needs about radiotherapy.

Patients' perceptions of health-related quality of life during and after adjuvant radiotherapy for T1N0M0 breast cancer.

AIMS: The effects of radiotherapy on health-related quality of life (HRQOL) may influence decisions about adjuvant radiotherapy after breast-conserving surgery. We sought women's ratings of HRQOL during and after radiotherapy. MATERIALS AND METHODS: Women completed HRQOL measures before, during and after adjuvant radiotherapy for node-negative, hormone receptor-positive breast cancers that were less than 2 cm in size. Acute and late toxicities were rated by clinicians. RESULTS: There were 161 participants with a median age of 58 years (range 34-82). Mean scores for most aspects of HRQOL worsened only slightly during radiotherapy and improved to baseline levels or better within a few months. The symptoms rated as most distressing were: difficulty sleeping (29%), fatigue (23%), breast discolouration (21%), uncertainty about the future (18%), feeling sad or depressed (18%), feeling anxious or worried (19%). Most rated their experience as better (39%) or much better (28%) than expected. Grade 3 toxicities were rare (5% acute, 1% late) with no grade 4 toxicities. CONCLUSIONS: Radiotherapy was associated with transient and generally mild impairments in a few aspects of HRQOL. Concerns about adverse effects on HRQOL should not weigh heavily on decisions about adjuvant breast radiotherapy.

Cognitive function and fatigue after diagnosis of colorectal cancer.

BACKGROUND: Cognitive impairment and fatigue have been associated with cancer and its treatment. We present baseline data from a large longitudinal study that evaluates cognitive function, fatigue, and potential underlying mechanisms following diagnosis of colorectal cancer (CRC). PATIENTS AND METHODS: We evaluated CRC patients with stage I-III disease before or after surgery, participants with limited metastatic disease and healthy controls (HC). Neuropsychological evaluation included clinical and computerised tests. Participants completed questionnaires for fatigue and quality of life (QOL)-(FACT-F), anxiety/depression, and cognitive symptoms (FACT-Cog). Ten cytokines, clotting factors, sex hormones, carcinoembryonic antigen (CEA), and apolipoprotein E genotype were evaluated. Primary end points were cognitive function on clinical tests evaluated by a Global Deficit score (GDS) and fatigue. Associations between test results, demographic, and disease related factors were explored. RESULTS: We assessed 291 participants with early-stage disease [median age 59 (23-75) years, 63% men], 72 with metastatic disease, and 72 HC. Using GDS, 45% (126/281) of participants with early-stage CRC had cognitive impairment versus 15% (11/72) of HC (odds ratio 4.51, 95% confidence interval 2.28-8.93; P < 0.001), with complex processing speed, attention/working memory, and verbal learning efficiency being most affected. Women with early-stage CRC had greater cognitive impairment than men [55/105 (52%) versus 71/176 (40%), P < 0.050]. Cognitive symptoms were self-reported by 21% (59/286) of early-stage patients versus 17% (12/72) of HC; fatigue by 52% (149/287) of early-stage patients and 26% (19/72) of HC (P < 0.0001). Women reported more fatigue than men (P = 0.003). Fatigue, QOL, anxiety/depression, and cognitive symptoms were associated with each other (r = 0.43-0.71), but not with neuropsychological performance. Most cytokines were elevated in cancer patients. Cognitive function was not associated with cytokines, sex hormones, clotting factors, CEA, or apolipoprotein E genotype. CONCLUSIONS: The incidence of cognitive impairment was three to five times higher in CRC patients than HC, with women having higher impairment rates than men. The cognitive impairment profile suggests dysfunction primarily in fronto-subcortical brain systems. TRIAL REGISTRATION: NCT00188331.

Are radiation oncologists aware of health literacy among people with cancer treated with radiotherapy?

Health literacy skills are important for people affected by cancer as they are exposed to complex treatment and follow-up care information. This study aimed to (1) explore radiation oncologists' understandings and awareness of health literacy among patients with a reasonable command of English; (2) gain insight into oncologists' views regarding health literacy; and (3) identify techniques oncologists employ to communicate to different literacy populations. We conducted semi-structured interviews with 26 radiation oncologists. Four key themes were identified: (1) identifying a patient's literacy level; (2) perceived impact of literacy; (3) challenges and strategies to communicating concepts and supporting decision-making; and (4) suggested improvements to the health system. Participants described subjectively assessing a person's literacy level by monitoring the types of questions asked; analysing the language used; examining non-verbal behaviour, and considering a person's socio-economic situation. Participants reported the challenges of discussing the subtleties of cancer treatments with lower literacy groups such as the benefits and risks of treatment options and clinical trials, and tended to provide the basic facts to facilitate understanding. Radiation oncologists acknowledged the importance of health literacy in oncology, and employed a number of techniques to tailor their communication to different literacy populations. Further research is needed to address the challenges faced by oncologists when interacting with different literacy groups.

Molecular markers of response and toxicity to FOLFOX chemotherapy in metastatic colorectal cancer.

BACKGROUND: To investigate three genetic alterations (TP53 mutation, Kras mutation and microsatellite instability (MSI)) and three polymorphisms (methylene tetrahydrofolate reductase (MTHFR) C677T, excision repair cross complementing group 1 (ERCC1)-118 and X-ray repair cross complementing group 1 (XRCC1)-399) for their ability to predict response, survival and toxicity to FOLFOX first line chemotherapy in the treatment of metastatic colorectal cancer (mCRC). METHODS: Tumour tissues from 118 mCRC patients who underwent FOLFOX treatment from three successive phase II trials were evaluated for mutations in TP53 (exons 5-8) and Kras (codons 12 and 13) and for MSI using PCR-based analysis. Genotyping for common single nucleotide polymorphisms in the MTHFR (codon 677), ERCC1 (codon 118) and XRCC1 (codon 399) genes was also carried out using PCR techniques. These genetic markers were correlated with clinical response, survival and toxicity to treatment. RESULTS: Patients with the T allele of ERCC1-118 showed significantly worse progression-free survival in univariate analysis (HR=2.62; 95% CI=1.14-6.02; P=0.02). None of the genetic alterations or polymorphisms showed significant association with clinical response to FOLFOX. The MTHFR, ERCC1 and XRCC1 polymorphisms showed no associations with overall haematological, gastrointestinal or neurological toxicity to FOLFOX, although MTHFR 677 TT genotype patients showed a significantly higher incidence of grade 3 or 4 diarrhoea (26%) compared with CC or CT genotype patients (6%, P=0.02). CONCLUSIONS: The ERCC1-118 and MTHFR C677T polymorphisms were associated with progression and severe diarrhoea, respectively, after FOLFOX treatment in mCRC. Although our findings require confirmation in large prospective studies, they reinforce the concept that individual genetic variation may allow personalized selection of chemotherapy to optimize clinical outcomes.

Mice lacking beta-adrenergic receptors have increased bone mass but are not protected from deleterious skeletal effects of ovariectomy.

Activation of beta2-adrenergic receptors inhibits osteoblastic bone formation and enhances osteoclastic bone resorption. Whether beta-blockers inhibit ovariectomy-induced bone loss and decrease fracture risk remains controversial. To further explore the role of beta-adrenergic signaling in skeletal acquisition and response to estrogen deficiency, we evaluated mice lacking the three known beta-adrenergic receptors (beta-less). Body weight, percent fat, and bone mineral density were significantly higher in male beta-less than wild-type (WT) mice, more so with increasing age. Consistent with their greater fat mass, serum leptin was significantly higher in beta-less than WT mice. Mid-femoral cross-sectional area and cortical thickness were significantly higher in adult beta-less than WT mice, as were femoral biomechanical properties (+28 to +49%, P < 0.01). Young male beta-less had higher vertebral (1.3-fold) and distal femoral (3.5-fold) trabecular bone volume than WT (P < 0.001 for both) and lower osteoclast surface. With aging, these differences lessened, with histological evidence of increased osteoclast surface and decreased bone formation rate at the distal femur in beta-less vs. WT mice. Serum tartrate-resistance alkaline phosphatase-5B was elevated in beta-less compared with WT mice from 8-16 wk of age (P < 0.01). Ovariectomy inhibited bone mass gain and decreased trabecular bone volume/total volume similarly in beta-less and WT mice. Altogether, these data indicate that absence of beta-adrenergic signaling results in obesity and increased cortical bone mass in males but does not prevent deleterious effects of estrogen deficiency on trabecular bone microarchitecture. Our findings also suggest direct positive effects of weight and/or leptin on bone turnover and cortical bone structure, independent of adrenergic signaling.

The Colon Health and Life-Long Exercise Change trial: a randomized trial of the National Cancer Institute of Canada Clinical Trials Group.

BACKGROUND: Observational studies indicate that physical activity (PA) is strongly associated with improved disease outcomes in colon cancer survivors, but a randomized controlled trial is needed to determine whether the association is causal and whether new policies to promote exercise are justified. PURPOSE: The co.21 Colon Health and Life-Long Exercise Change (challenge) trial undertaken by the National Cancer Institute of Canada Clinical Trials Group (NCIC CTG) is designed to determine the effects of a structured pa intervention on outcomes for survivors of high-risk stage II or III colon cancer who have completed adjuvant therapy within the previous 2-6 months. METHODS: Trial participants (n = 962) will be stratified by centre, disease stage, body mass index, and performance status, and will be randomly assigned to a structured pa intervention or to general health education materials. The pa intervention will consist of a behavioural support program and supervised pa sessions delivered over a 3-year period, beginning with regular face-to-face sessions and tapering to less frequent face-to-face or telephone sessions. The primary endpoint is disease-free survival. Important secondary endpoints include multiple patient-reported outcomes, objective physical functioning, biologic correlative markers, and an economic analysis. SUMMARY: Cancer survivors and cancer care professionals are interested in the potential role of PA to improve multiple disease-related outcomes, but a randomized controlled trial is needed to provide compelling evidence to justify changes in health care policies and practice.

Somatostatin receptor expression, tumour response, and quality of life in patients with advanced hepatocellular carcinoma treated with long-acting octreotide.

Octreotide may extend survival in hepatocellular carcinoma (HCC). Forty-one per cent of HCCs have high-affinity somatostatin receptors. We aimed to determine the feasibility, safety, and activity of long-acting octreotide in advanced HCC; to identify the best method for assessing somatostatin receptor expression; to relate receptor expression to clinical outcomes; and to evaluate toxicity. Sixty-three patients with advanced HCC received intramuscular long-acting octreotide 20 mg monthly until progression or toxicity. Median age was 67 years (range 28-81 years), male 81%, Child-Pugh A 83%, and B 17%. The aetiologies of chronic liver disease were alcohol (22%), viral hepatitis (44%), and haemochromatosis (6%). Prior treatments for HCC included surgery (8%), chemotherapy (2%), local ablation (11%), and chemoembolisation (6%). One patient had an objective partial tumour response (2%, 95% CI 0-9%). Serum alpha-fetoprotein levels decreased more than 50% in four (6%). Median survival was 8 months. Thirty four of 61 patients (56%) had receptor expression detected by scintigraphy; no clear relationship with clinical outcomes was identified. There were few grade 3 or 4 toxicities: hyperglycaemia (8%), hypoglycaemia (2%), diarrhoea (5%), and anorexia (2%). Patients reported improvements in some symptoms, but no major changes in quality of life were detected. Long-acting octreotide is safe in advanced HCC. We found little evidence of anticancer activity. A definitive randomised trial would identify whether patients benefit from this treatment in other ways.