Poster Presentation 29th Australian and New Zealand Bone and Mineral Society Annual Scientific Meeting 2019

Targeted mechanical loading of stable sclerotic and osteolytic vertebral bone metastases is safe for patients with advanced prostate or breast cancer. (#188)

Nicolas Hart 1 2 3 4 , Robert U Newton 1 4 5 , Nigel A. Spry 4 6 , Kynan T. Feeney 1 3 4 7 , Christobel Saunders 5 7 8 , Daphne Tsoi 1 3 4 7 , Dennis R. Taaffe 1 4 5 , Andrew D. Redfern 6 8 , Raphael Chee 1 4 6 9 , Tim Clay 7 9 , Hilary Martin 8 , Daniel A. Galvão 1 4
  1. School of Medical and Health Science, Edith Cowan University, Perth, Australia
  2. Western Australian Bone Research Collaboration, Perth, WA, Australia
  3. School of Medicine, University of Notre Dame Australia, Perth, WA, Australia
  4. Exercise Medicine Research Institute, Edith Cowan University, Perth, WA, Australia
  5. School of Exercise and Nutrition Science, University of Queensland, Brisbane, QLD, Australia
  6. School of Medicine, University of Western Australia, Perth, WA, Australia
  7. St John of God Hospital, Perth, WA, Australia
  8. Fiona Stanley Hospital, Perth, WA, Australia
  9. Genesis Cancer Care, Perth, WA, Australia

Background:
Bone is the most common location for metastatic prostate and breast carcinomas, with skeletal lesions identified in over 80% of patients in the advanced stages, dysregulating bone metabolism in favour of excess mineralisation (sclerotic) or porosity (osteolytic). Preclinical studies demonstrate the utility of mechanical loads to suppress tumour growth and promote skeletal preservation at metastatic bone sites [1]. The safety of a mechanical loading program in human patients with bone metastases has yet to be established [2,3].  

Methods:
40 men with prostate cancer and sclerotic bone metastases, and 40 women with breast cancer and osteolytic bone metastases were recruited. All patients had structurally stable bone disease as per Taneichi [4] and Mirels [5]. Supervised exercise was provided three days per week (for 12 weeks) at an exercise clinic with accredited exercise physiologists, consisting of resistance and high-intensity aerobic training that avoided bone lesion sites, additional to targeted isometric exercise focusing on spinal lesion sites [2,3]. A further two home-based isometric trunk muscle loading sessions was provided after two weeks. Safety was assessed as per CTCAE reporting criteria.

Results:
36 prostate cancer (90%) and 32 breast cancer patients (80%) completed the full exercise program. Withdrawn patients were due to changes in cancer treatment (9/12), or significant treatment toxicities (3/12) while on-study. Median 5.5 skeletal lesions per patient (range: 1 to 16), with a high overall bone metastatic burden (552 lesions in 80 patients). There were no skeletal adverse events (vertebral compressions, increases in bone pain, or fragility fractures), and no serious adverse events attributable to exercise. 12 minor adverse events (Grade ≤ 2; shoulder bursitis and knee pain) were reported, but were aggravations of pre-existing conditions only.

Conclusion:
Supervised and targeted isometric mechanical loading of sclerotic and osteolytic spinal metastases embedded within a modular multi-modal exercise program (otherwise avoiding lesion sites) is safe and feasible for advanced prostate and breast cancer patients.

  1. Lynch ME et al. In vivo tibial compression decreases osteolysis and tumour formation in a human metastatic breast cancer model. Journal of Bone and Mineral Research. 2013. 28(11):2357-67.
  2. Hart NH et al. 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. Trials. 2018. 19(1):695.
  3. Hart NH et al. Can exercise suppress tumour growth in advanced prostate cancer patients with sclerotic bone metastases? A randomised, controlled study protocol examining feasibility, safety and efficacy. BMJ Open. 2017. 7(5):e014458.
  4. Jawad MU et al. In brief: classifications in brief: Mirels’ classification: metastatic disease in long bones and impending pathologic fracture. Clinical Orthopaedics and Related Research. 2010. 468(10):2825.
  5. Taneichi H, et al. Risk factors and probability of vertebral body collapse in metastases of the thoracic and lumbar spine. Spine. 1997. 22(3):239-245.