TY - JOUR

T1 - Neo-train

T2 - study protocol and feasibility results for a two-arm randomized controlled trial investigating the effect of supervised exercise during neoadjuvant chemotherapy on tumour response in patients with breast cancer

AU - Kjeldsted, Eva

AU - Ammitzbøll, Gunn

AU - Jørgensen, Lars Bo

AU - Lodin, Alexey

AU - Bojesen, Rasmus Dahlin

AU - Ceballos, Silvia Gonzalez

AU - Rosthøj, Susanne

AU - Lænkholm, Anne Vibeke

AU - Skou, Søren T.

AU - Jack, Sandy

AU - Gehl, Julie

AU - Dalton, Susanne Oksbjerg

N1 - Funding Information: The authors wish to thank the Danish Cancer Biobank and Region Zealand Biobank for the handling and storage of biological material, and the DIMA department at KMD A/S for the collaboration on management of physical activity data from the activity trackers (Vivosmart 4, Garmin International Inc., Olathe, KS, USA). We also wish to thank the exercise locations: (1) Department of Physiotherapy, Naestved-Slagelse-Ringsted Hospitals, Naestved; (2) Department of Physiotherapy and Occupational Therapy, Zealand University Hospital, Roskilde; (3) Department of Physiotherapy and Occupational Therapy, Holbaek Hospital, Holbaek; (4) Department of Physiotherapy, Naestved-Slagelse-Ringsted Hospitals, Slagelse/ Physiotherapy Centre Aktivt Velvaere, Slagelse; (5) Guldborgsund Municipal Rehabilitation Centre, Nykoebing Falster. Last, a special thanks to the clinicians who provided feedback in the design phase, and the patients with breast cancer who participated in the patient panel and the pilot study. Funding Information: This trial will be conducted as part of research activities in the Danish Research Centre for Equality in Cancer (COMPAS), which is supported by ‘Knæk Cancer’/Danish Cancer Society (grant no. R223-A13094-18-S68). The study also received funding from Krista and Viggo Petersen Foundation (grant no. 6030/2HAH/ks), Helsefonden (grant no. 21-B-0396), Dansk Kræftforskningsfond, Dagmar Marshall Fond, Aase og Ejnar Danielsens Fond (grant no. 21-10-0143), the Department of Clinical Oncology and Palliative Care, Zealand University Hospital, and Region Zealand. The funders have no role in the design, data collection, analyses or interpretation of the study. Publisher Copyright: © 2023, BioMed Central Ltd., part of Springer Nature.

PY - 2023/12

Y1 - 2023/12

N2 - Background: Prehabilitation with exercise interventions during neoadjuvant chemotherapy (NACT) is effective in reducing physical and psychosocial chemotherapy-related adverse events in patients with cancer. In preclinical studies, data also support a growth inhibitory effect of aerobic exercise on the tumour microenvironment with possible improved chemotherapy delivery but evidence in human patients is limited. The aim of the study here described is to investigate if supervised exercise with high-intensity aerobic and resistance training during NACT can improve tumour reduction in patients with breast cancer. Methods: This parallel two-armed randomized controlled trial is planned to include 120 women aged ≥ 18 years with newly diagnosed breast cancer starting standard NACT at a university hospital in Denmark (a total of 90 participants needed according to the power calculation and allowing 25% (n = 30) dropout). The participants will be randomized to usual care or supervised exercise consisting of high-intensity interval training on a stationary exercise bike and machine-based progressive resistance training offered three times a week for 24 weeks during NACT, and screening-based advice to seek counselling in case of moderate-severe psychological distress (Neo-Train program). The primary outcome is tumour size change (maximum diameter of the largest lesion in millimetre) measured by magnetic resonance imaging prior to surgery. Secondary outcomes include clinical/pathological, physical and patient-reported measures such as relative dose intensity of NACT, hospital admissions, body composition, physical fitness, muscle strength, health-related quality of life, general anxiety, depression, and biological measures such as intratumoural vascularity, tumour infiltrating lymphocytes, circulating tumour DNA and blood chemistry. Outcomes will be measured at baseline (one week before to 1–2 weeks after starting NACT), during NACT (approximately week 7, 13 and 19), pre-surgery (approximately week 21–29), at surgery (approximately week 21–30) and 3 months post-surgery (approximately 33–42 weeks from baseline). Discussion: This study will provide novel and important data on the potential benefits of supervised aerobic and resistance exercise concomitant to NACT on tumour response and the tumour microenvironment in patients with breast cancer, with potential importance for survival and risk of recurrence. If effective, our study may help increase focus of exercise as an active part of the neoadjuvant treatment strategy. Trial registration: The trial was registered at ClinicalTrials.gov (NCT04623554) on November 10, 2020.

AB - Background: Prehabilitation with exercise interventions during neoadjuvant chemotherapy (NACT) is effective in reducing physical and psychosocial chemotherapy-related adverse events in patients with cancer. In preclinical studies, data also support a growth inhibitory effect of aerobic exercise on the tumour microenvironment with possible improved chemotherapy delivery but evidence in human patients is limited. The aim of the study here described is to investigate if supervised exercise with high-intensity aerobic and resistance training during NACT can improve tumour reduction in patients with breast cancer. Methods: This parallel two-armed randomized controlled trial is planned to include 120 women aged ≥ 18 years with newly diagnosed breast cancer starting standard NACT at a university hospital in Denmark (a total of 90 participants needed according to the power calculation and allowing 25% (n = 30) dropout). The participants will be randomized to usual care or supervised exercise consisting of high-intensity interval training on a stationary exercise bike and machine-based progressive resistance training offered three times a week for 24 weeks during NACT, and screening-based advice to seek counselling in case of moderate-severe psychological distress (Neo-Train program). The primary outcome is tumour size change (maximum diameter of the largest lesion in millimetre) measured by magnetic resonance imaging prior to surgery. Secondary outcomes include clinical/pathological, physical and patient-reported measures such as relative dose intensity of NACT, hospital admissions, body composition, physical fitness, muscle strength, health-related quality of life, general anxiety, depression, and biological measures such as intratumoural vascularity, tumour infiltrating lymphocytes, circulating tumour DNA and blood chemistry. Outcomes will be measured at baseline (one week before to 1–2 weeks after starting NACT), during NACT (approximately week 7, 13 and 19), pre-surgery (approximately week 21–29), at surgery (approximately week 21–30) and 3 months post-surgery (approximately 33–42 weeks from baseline). Discussion: This study will provide novel and important data on the potential benefits of supervised aerobic and resistance exercise concomitant to NACT on tumour response and the tumour microenvironment in patients with breast cancer, with potential importance for survival and risk of recurrence. If effective, our study may help increase focus of exercise as an active part of the neoadjuvant treatment strategy. Trial registration: The trial was registered at ClinicalTrials.gov (NCT04623554) on November 10, 2020.

KW - Breast neoplasms

KW - High intensity interval training

KW - Neoadjuvant therapy

KW - Prehabilitation

KW - Preoperative exercise

KW - Treatment outcome

U2 - 10.1186/s12885-023-11284-5

DO - 10.1186/s12885-023-11284-5

M3 - Journal article

C2 - 37598196

AN - SCOPUS:85168330318

VL - 23

JO - B M C Cancer

JF - B M C Cancer

SN - 1471-2407

IS - 1

M1 - 777

ER -