{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,15]],"date-time":"2025-12-15T19:39:34Z","timestamp":1765827574148,"version":"build-2065373602"},"reference-count":70,"publisher":"BMJ","issue":"5","funder":[{"DOI":"10.13039\/501100001170","name":"Cancer Council Western Australia","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001170","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Exercise and Sport Science Australia"}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["BMJ Open"],"accepted":{"date-parts":[[2017,3,20]]},"published-print":{"date-parts":[[2017,5]]},"abstract":"<jats:sec>\n                  <jats:title>Introduction<\/jats:title>\n                  <jats:p>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\u2013paracrine 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.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods and analysis<\/jats:title>\n                  <jats:p>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 \u00d7 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.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Ethics and dissemination<\/jats:title>\n                  <jats:p>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.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Trial registration number<\/jats:title>\n                  <jats:p>ACTRN 12616000179437.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1136\/bmjopen-2016-014458","type":"journal-article","created":{"date-parts":[[2017,5,30]],"date-time":"2017-05-30T20:10:21Z","timestamp":1496175021000},"page":"e014458","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":20,"title":["Can exercise suppress tumour growth in advanced prostate cancer patients with sclerotic bone metastases? A randomised, controlled study protocol examining feasibility, safety and efficacy"],"prefix":"10.1136","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2794-0193","authenticated-orcid":false,"given":"Nicolas H","family":"Hart","sequence":"first","affiliation":[{"name":"Exercise Medicine Research Institute, Edith Cowan University, Perth, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert U","family":"Newton","sequence":"additional","affiliation":[{"name":"Exercise Medicine Research Institute, Edith Cowan University, Perth, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nigel A","family":"Spry","sequence":"additional","affiliation":[{"name":"Exercise Medicine Research Institute, Edith Cowan University, Perth, Australia"},{"name":"Department of Radiation Oncology, Sir Charles Gairdner Hospital, Perth, Australia"},{"name":"Department of Radiation Oncology, Genesis CancerCare, Perth, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dennis R","family":"Taaffe","sequence":"additional","affiliation":[{"name":"Exercise Medicine Research Institute, Edith Cowan University, Perth, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Suzanne K","family":"Chambers","sequence":"additional","affiliation":[{"name":"Exercise Medicine Research Institute, Edith Cowan University, Perth, Australia"},{"name":"Menzies Health Institute Queensland, Griffith University, Gold Coast, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kynan T","family":"Feeney","sequence":"additional","affiliation":[{"name":"Exercise Medicine Research Institute, Edith Cowan University, Perth, Australia"},{"name":"Department of Medical Oncology, St John of God Hospital, Perth, Australia"},{"name":"School of Medicine, University of Notre Dame Australia, Perth, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David J","family":"Joseph","sequence":"additional","affiliation":[{"name":"Exercise Medicine Research Institute, Edith Cowan University, Perth, Australia"},{"name":"Department of Radiation Oncology, Sir Charles Gairdner Hospital, Perth, Australia"},{"name":"Department of Radiation Oncology, Genesis CancerCare, Perth, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrew D","family":"Redfern","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Fiona Stanley Hospital, Perth, Australia"},{"name":"School of Medicine and Pharmacology, University of Western Australia, Perth, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tom","family":"Ferguson","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Fiona Stanley Hospital, Perth, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel A","family":"Galv\u00e3o","sequence":"additional","affiliation":[{"name":"Exercise Medicine Research Institute, Edith Cowan University, Perth, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"239","published-online":{"date-parts":[[2017,5,30]]},"reference":[{"key":"2025101811005498000_7.5.e014458.1","doi-asserted-by":"crossref","first-page":"7554","DOI":"10.1158\/0008-5472.CAN-05-1317","article-title":"Prostate cancer cells promote osteoblastic bone metastases through wnts","volume":"65","author":"Hall","year":"2005","journal-title":"Cancer Res"},{"key":"2025101811005498000_7.5.e014458.2","doi-asserted-by":"publisher","DOI":"10.1002\/jcb.10662"},{"key":"2025101811005498000_7.5.e014458.3","doi-asserted-by":"publisher","DOI":"10.1038\/nrc867"},{"key":"2025101811005498000_7.5.e014458.4","doi-asserted-by":"publisher","DOI":"10.1023\/A:1015599831232"},{"key":"2025101811005498000_7.5.e014458.5","doi-asserted-by":"publisher","DOI":"10.1038\/nrendo.2010.227"},{"key":"2025101811005498000_7.5.e014458.6","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-06-1007"},{"key":"2025101811005498000_7.5.e014458.7","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2010.05.038"},{"key":"2025101811005498000_7.5.e014458.8","doi-asserted-by":"publisher","DOI":"10.1038\/nrc1528"},{"key":"2025101811005498000_7.5.e014458.9","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1186\/1471-2407-11-517","article-title":"Efficacy and safety of a modular multi-modal exercise program in prostate cancer patients with bone metastases: a randomized controlled trial","volume":"11","author":"Galv\u00e3o","year":"2011","journal-title":"BMC Cancer"},{"key":"2025101811005498000_7.5.e014458.10","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1038\/pcan.2013.22","article-title":"Safety and efficacy of resistance exercise in prostate cancer patients with bone metastases","volume":"16","author":"Cormie","year":"2013","journal-title":"Prostate Cancer Prostatic Dis"},{"key":"2025101811005498000_7.5.e014458.11","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-06-0931"},{"key":"2025101811005498000_7.5.e014458.12","doi-asserted-by":"publisher","DOI":"10.1002\/1097-0142(20000615)88:12+<2989::AID-CNCR14>3.0.CO;2-Q"},{"key":"2025101811005498000_7.5.e014458.13","doi-asserted-by":"publisher","DOI":"10.1016\/j.eururo.2004.08.016"},{"key":"2025101811005498000_7.5.e014458.14","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2010.31.5226"},{"key":"2025101811005498000_7.5.e014458.15","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2005.06.085"},{"key":"2025101811005498000_7.5.e014458.16","doi-asserted-by":"publisher","DOI":"10.1007\/s11864-008-0065-1"},{"key":"2025101811005498000_7.5.e014458.17","doi-asserted-by":"publisher","DOI":"10.1016\/j.suronc.2013.01.004"},{"key":"2025101811005498000_7.5.e014458.18","doi-asserted-by":"crossref","first-page":"485","DOI":"10.1186\/1471-2407-14-485","article-title":"Pain response of resistance training of the paravertebral musculature under radiotherapy in patients with spinal bone metastases-a randomized trial","volume":"14","author":"Rief","year":"2014","journal-title":"BMC Cancer"},{"key":"2025101811005498000_7.5.e014458.19","doi-asserted-by":"crossref","first-page":"294","DOI":"10.1002\/cncr.28396","article-title":"Mediators of the resistance and aerobic exercise intervention effect on physical and general health in men undergoing androgen deprivation therapy for prostate cancer","volume":"120","author":"Buffart","year":"2014","journal-title":"Cancer"},{"key":"2025101811005498000_7.5.e014458.20","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1007\/s11556-012-0114-4","article-title":"Exercise medicine for prostate cancer","volume":"10","author":"Newton","year":"2013","journal-title":"European Review of Aging and Physical Activity"},{"key":"2025101811005498000_7.5.e014458.21","doi-asserted-by":"publisher","DOI":"10.1007\/s00520-013-2103-1"},{"key":"2025101811005498000_7.5.e014458.22","doi-asserted-by":"publisher","DOI":"10.1016\/j.jsams.2009.03.002"},{"key":"2025101811005498000_7.5.e014458.23","doi-asserted-by":"publisher","DOI":"10.1016\/j.ctrv.2013.06.007"},{"key":"2025101811005498000_7.5.e014458.24","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2009.23.2488"},{"key":"2025101811005498000_7.5.e014458.25","doi-asserted-by":"publisher","DOI":"10.1038\/sj.pcan.4500975"},{"key":"2025101811005498000_7.5.e014458.26","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/djv040"},{"key":"2025101811005498000_7.5.e014458.27","unstructured":"Hoffman P . Exercise training, tumour metabolism, tumour-host interaction and lactate shuttle theory. Front Pharmacol 2014."},{"key":"2025101811005498000_7.5.e014458.28","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbi.2012.05.001"},{"key":"2025101811005498000_7.5.e014458.29","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1093\/jnci\/dju042","article-title":"Therapeutic properties of aerobic training after a cancer diagnosis: more than a one-trick pony?","volume":"106","author":"Jones","year":"2014","journal-title":"J Natl Cancer Inst"},{"key":"2025101811005498000_7.5.e014458.30","doi-asserted-by":"publisher","DOI":"10.1152\/japplphysiol.01575.2011"},{"key":"2025101811005498000_7.5.e014458.31","doi-asserted-by":"publisher","DOI":"10.1158\/1940-6207.CAPR-12-0416"},{"key":"2025101811005498000_7.5.e014458.32","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0089680"},{"key":"2025101811005498000_7.5.e014458.33","doi-asserted-by":"publisher","DOI":"10.1038\/bjc.2014.662"},{"key":"2025101811005498000_7.5.e014458.34","doi-asserted-by":"publisher","DOI":"10.1038\/sj.pcan.4500991"},{"key":"2025101811005498000_7.5.e014458.35","doi-asserted-by":"publisher","DOI":"10.1016\/j.eururo.2013.09.041"},{"key":"2025101811005498000_7.5.e014458.36","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2407-9-419"},{"key":"2025101811005498000_7.5.e014458.37","doi-asserted-by":"crossref","first-page":"306","DOI":"10.1038\/ncpuro1104","article-title":"Can exercise ameliorate the increased risk of cardiovascular disease and diabetes associated with ADT?","volume":"5","author":"Galv\u00e3o","year":"2008","journal-title":"Nat Clin Pract Urol"},{"key":"2025101811005498000_7.5.e014458.38","doi-asserted-by":"publisher","DOI":"10.1111\/1754-9485.12115"},{"key":"2025101811005498000_7.5.e014458.39","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2407-12-432"},{"key":"2025101811005498000_7.5.e014458.40","doi-asserted-by":"publisher","DOI":"10.1016\/j.juro.2011.05.055"},{"key":"2025101811005498000_7.5.e014458.41","doi-asserted-by":"crossref","first-page":"256","DOI":"10.1111\/bju.12646","article-title":"Can supervised exercise prevent treatment toxicity in patients with prostate cancer initiating androgen-deprivation therapy: a randomised controlled trial","volume":"115","author":"Cormie","year":"2015","journal-title":"BJU Int"},{"key":"2025101811005498000_7.5.e014458.42","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1186\/s13058-014-0413-y","article-title":"Physical activity and telomere length in early stage breast cancer survivors","volume":"16","author":"Garland","year":"2014","journal-title":"Breast Cancer Res"},{"key":"2025101811005498000_7.5.e014458.43","doi-asserted-by":"publisher","DOI":"10.1097\/MCO.0b013e32834121b1"},{"key":"2025101811005498000_7.5.e014458.44","doi-asserted-by":"publisher","DOI":"10.1249\/MSS.0b013e31817c92aa"},{"key":"2025101811005498000_7.5.e014458.45","doi-asserted-by":"publisher","DOI":"10.1155\/2015\/153561"},{"key":"2025101811005498000_7.5.e014458.46","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.24539"},{"key":"2025101811005498000_7.5.e014458.47","doi-asserted-by":"crossref","first-page":"697","DOI":"10.1007\/s10585-014-9660-7","article-title":"Living in shear: platelets protect cancer cells from shear induced damage","volume":"31","author":"Egan","year":"2014","journal-title":"Clin Exp Metastasis"},{"key":"2025101811005498000_7.5.e014458.48","doi-asserted-by":"crossref","first-page":"518","DOI":"10.1007\/s13238-014-0057-9","article-title":"Mechanomics: an emerging field between biology and biomechanics","volume":"5","author":"Wang","year":"2014","journal-title":"Protein Cell"},{"key":"2025101811005498000_7.5.e014458.49","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1016\/j.addr.2014.08.009","article-title":"Biomechanical forces in the skeleton and their relevance to bone metastasis: biology and engineering considerations","volume":"79-80","author":"Lynch","year":"2014","journal-title":"Adv Drug Deliv Rev"},{"key":"2025101811005498000_7.5.e014458.50","doi-asserted-by":"crossref","first-page":"2357","DOI":"10.1002\/jbmr.1966","article-title":"In vivo tibial compression decreases osteolysis and tumor formation in a human metastatic breast cancer model","volume":"28","author":"Lynch","year":"2013","journal-title":"J Bone Miner Res"},{"key":"2025101811005498000_7.5.e014458.51","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1016\/j.jmbbm.2012.09.002","article-title":"Localized sclerotic bone response demonstrated reduced nanomechanical creep properties","volume":"17","author":"Chen","year":"2013","journal-title":"J Mech Behav Biomed Mater"},{"key":"2025101811005498000_7.5.e014458.52","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejca.2014.07.002"},{"key":"2025101811005498000_7.5.e014458.53","first-page":"1","article-title":"Imaging of spinal metastatic disease","volume":"2011","author":"Shah","year":"2011","journal-title":"Int J Surg Oncol"},{"key":"2025101811005498000_7.5.e014458.54","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1155\/2012\/893193","article-title":"Modern detection of prostate cancer's Bone Metastasis: Is the Bone Scan Era Over?","volume":"2012","author":"Tombal","year":"2012","journal-title":"Adv Urol"},{"key":"2025101811005498000_7.5.e014458.55","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2006.01.015"},{"key":"2025101811005498000_7.5.e014458.56","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0006896","article-title":"Hypoxia and TGF-beta drive breast cancer bone metastases through parallel signaling pathways in tumor cells and the bone microenvironment","volume":"4","author":"Dunn","year":"2009","journal-title":"PLoS One"},{"key":"2025101811005498000_7.5.e014458.57","first-page":"620","article-title":"Segmental musculoskeletal examinations using Dual-Energy X-Ray absorptiometry (DXA): Positioning and analysis considerations","volume":"14","author":"Hart","year":"2015","journal-title":"J Sports Sci Med"},{"key":"2025101811005498000_7.5.e014458.58","unstructured":"An on . QDR for windows XP reference manual. Bedford, M.A: Hologic Inc, 2014."},{"key":"2025101811005498000_7.5.e014458.59","doi-asserted-by":"crossref","first-page":"1379","DOI":"10.1249\/MSS.0000000000000897","article-title":"Musculoskeletal asymmetry in football athletes: a product of limb function over time","volume":"48","author":"Hart","year":"2016","journal-title":"Med Sci Sports Exerc"},{"key":"2025101811005498000_7.5.e014458.60","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1186\/1471-2407-14-67","article-title":"Feasibility of isometric spinal muscle training in patients with bone metastases under radiation therapy - first results of a randomized pilot trial","volume":"14","author":"Rief","year":"2014","journal-title":"BMC Cancer"},{"key":"2025101811005498000_7.5.e014458.61","doi-asserted-by":"publisher","DOI":"10.1097\/00003677-200101000-00006"},{"key":"2025101811005498000_7.5.e014458.62","unstructured":"Hopkins WG . A scale of magnitudes for effect statistics. SportScience 2002 http:\/\/www.sportsci.org\/resource\/stats\/effectmag.html (accessed 15 Jan 2016)."},{"key":"2025101811005498000_7.5.e014458.63","doi-asserted-by":"publisher","DOI":"10.4103\/2229-3485.83221"},{"key":"2025101811005498000_7.5.e014458.64","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2288-13-92"},{"key":"2025101811005498000_7.5.e014458.65","doi-asserted-by":"publisher","DOI":"10.3109\/0284186X.2012.742564"},{"key":"2025101811005498000_7.5.e014458.66","doi-asserted-by":"publisher","DOI":"10.1097\/PPO.0000000000000096"},{"key":"2025101811005498000_7.5.e014458.67","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pcbi.1002983"},{"key":"2025101811005498000_7.5.e014458.68","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2015.06.006"},{"key":"2025101811005498000_7.5.e014458.69","first-page":"626","article-title":"Effects of exercise on angiogenesis and apoptosis-related molecules, quality of life, fatigue and depression in breast cancer patients","volume":"22","author":"Ergun","year":"2013","journal-title":"Eur J Cancer Care"},{"key":"2025101811005498000_7.5.e014458.70","doi-asserted-by":"crossref","first-page":"258","DOI":"10.1038\/nrurol.2016.46","article-title":"Enhancing active surveillance of prostate cancer: the potential of exercise medicine","volume":"13","author":"Galv\u00e3o","year":"2016","journal-title":"Nat Rev Urol"}],"container-title":["BMJ Open"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/bmjopen-2016-014458","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,18]],"date-time":"2025-10-18T18:01:08Z","timestamp":1760810468000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmjopen.bmj.com\/lookup\/doi\/10.1136\/bmjopen-2016-014458"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,5]]},"references-count":70,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2017,5,30]]},"published-print":{"date-parts":[[2017,5]]}},"alternative-id":["10.1136\/bmjopen-2016-014458"],"URL":"https:\/\/doi.org\/10.1136\/bmjopen-2016-014458","relation":{},"ISSN":["2044-6055","2044-6055"],"issn-type":[{"type":"print","value":"2044-6055"},{"type":"electronic","value":"2044-6055"}],"subject":[],"published":{"date-parts":[[2017,5]]}}}