Mechanical suppression of osteolytic bone metastases in advanced breast cancer patients: a randomised controlled study protocol evaluating safety, feasibility and preliminary efficacy of exercise as a targeted medicine.

BACKGROUND: Skeletal metastases present a major challenge for clinicians, representing an advanced and typically incurable stage of cancer. Bone is also the most common location for metastatic breast carcinoma, with skeletal lesions identified in over 80% of patients with advanced breast cancer. Preclinical models have demonstrated the ability of mechanical stimulation to suppress tumour formation and promote skeletal preservation at bone sites with osteolytic lesions, generating modulatory interference of tumour-driven bone remodelling. Preclinical studies have also demonstrated anti-cancer effects through exercise by minimising tumour hypoxia, normalising tumour vasculature and increasing tumoural blood perfusion. This study proposes to explore the promising role of targeted exercise to suppress tumour growth while concomitantly delivering broader health benefits in patients with advanced breast cancer with osteolytic bone metastases. METHODS: This single-blinded, two-armed, randomised and controlled pilot study aims to establish the safety, feasibility and efficacy of an individually tailored, modular multi-modal exercise programme incorporating spinal isometric training (targeted muscle contraction) in 40 women with advanced breast cancer and stable osteolytic spinal metastases. Participants will be randomly assigned to exercise or usual medical care. The intervention arm will receive a 3-month clinically supervised exercise programme, which if proven to be safe and efficacious will be offered to the control-arm patients following study completion. Primary endpoints (programme feasibility, safety, tolerance and adherence) and secondary endpoints (tumour morphology, serum tumour biomarkers, bone metabolism, inflammation, anthropometry, body composition, bone pain, physical function and patient-reported outcomes) will be measured at baseline and following the intervention. DISCUSSION: Exercise medicine may positively alter tumour biology through numerous mechanical and non-mechanical mechanisms. This randomised controlled pilot trial will explore the preliminary effects of targeted exercise on tumour morphology and circulating metastatic tumour biomarkers using an osteolytic skeletal metastases model in patients with breast cancer. The study is principally aimed at establishing feasibility and safety. If proven to be safe and feasible, results from this study could have important implications for the delivery of this exercise programme to patients with advanced cancer and sclerotic skeletal metastases or with skeletal lesions present in haematological cancers (such as osteolytic lesions in multiple myeloma), for which future research is recommended. TRIAL REGISTRATION: anzctr.org.au , ACTRN-12616001368426 . Registered on 4 October 2016.

Can exercise suppress tumour growth in advanced prostate cancer patients with sclerotic bone metastases? A randomised, controlled study protocol examining feasibility, safety and efficacy.

INTRODUCTION: Exercise may positively alter tumour biology through numerous modulatory and regulatory mechanisms in response to a variety of modes and dosages, evidenced in preclinical models to date. Specifically, localised and systemic biochemical alterations produced during and following exercise may suppress tumour formation, growth and distribution by virtue of altered epigenetics and endocrine-paracrine activity. Given the impressive ability of targeted mechanical loading to interfere with metastasis-driven tumour formation in human osteolytic tumour cells, it is of equal interest to determine whether a similar effect is observed in sclerotic tumour cells. The study aims to (1) establish the feasibility and safety of a combined modular multimodal exercise programme with spinal isometric training in advanced prostate cancer patients with sclerotic bone metastases and (2) examine whether targeted and supervised exercise can suppress sclerotic tumour growth and activity in spinal metastases in humans. METHODS AND ANALYSIS: A single-blinded, two-armed, randomised, controlled and explorative phase I clinical trial combining spinal isometric training with a modular multimodal exercise programme in 40 men with advanced prostate cancer and stable sclerotic spinal metastases. Participants will be randomly assigned to (1) the exercise intervention or (2) usual medical care. The intervention arm will receive a 3-month, supervised and individually tailored modular multimodal exercise programme with spinal isometric training. Primary endpoints (feasibility and safety) and secondary endpoints (tumour morphology; biomarker activity; anthropometry; musculoskeletal health; adiposity; physical function; quality of life; anxiety; distress; fatigue; insomnia; physical activity levels) will be measured at baseline and following the intervention. Statistical analyses will include descriptive characteristics, t-tests, effect sizes and two-way (group × time) repeated-measures analysis of variance (or analysis of covariance) to examine differences between groups over time. The data-set will be primarily examined using an intention-to-treat approach with multiple imputations, followed by a secondary sensitivity analysis to ensure data robustness using a complete cases approach. ETHICS AND DISSEMINATION: Ethics approval was obtained from the Human Research Ethics Committee (HREC) of Edith Cowan University and the Sir Charles Gairdner and Osborne Park Health Care Group. If proven to be feasible and safe, this study will form the basis of future phase II and III trials in human patients with advanced cancer. To reach a maximum number of clinicians, practitioners, patients and scientists, outcomes will be disseminated through national and international clinical, conference and patient presentations, as well as publication in high-impact, peer-reviewed academic journals. TRIAL REGISTRATION NUMBER: ACTRN 12616000179437.

Outbreak of sporotrichosis, Western Australia.

A cluster of sporotrichosis cases occurred in the Busselton-Margaret River region of Western Australia from 2000 to 2003. Epidemiologic investigation and mycologic culture for Sporothrix schenckii implicated hay initially distributed through a commercial hay supplier as the source of the out-break. Declining infection rates have occurred after various community measures were instigated.

Epidemiological features and control of an outbreak of scarlet fever in a Perth primary school.

Scarlet fever was associated with feared outbreaks and mortality in the 19th Century. It occurs sporadically in modern society and infection is readily treated with antibiotics. We report on a scarlet fever outbreak in children attending a primary school in Perth, Western Australia, in late 2003. A total of 13 cases were identified over a five week period. Six of the cases were pre-primary children (ages 4 to 5) from the same class of 26 children (attack rate 23.1%). Three of the remaining seven cases were older siblings of pre-primary cases who developed scarlet fever after their younger siblings. Screening of the children and teachers from the two pre-primary classes at the school yielded 12 positive pharyngeal swabs for group A Streptococcus. Emm-typing of the screening isolates indicated that a common strain was circulating within the outbreak pre-primary class, with four of six isolates identified as emm-type 3. The overall group A Streptococcus carriage rate in screened students in this class was 31.6 per cent and the carriage rate for emm-type 3 was 21.1 per cent. Carriers were treated with oral penicillin V to eradicate carriage and control the outbreak. No further cases of scarlet fever were reported after the treatment of pharyngeal carriers. Outbreaks of scarlet fever still occur in young children and identification and treatment of carriers may still be valuable.