Neo-train: 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

Eva Kjeldsted, Gunn Ammitzbøll, Lars Bo Jørgensen, Alexey Lodin, Rasmus Dahlin Bojesen, Silvia Gonzalez Ceballos, Susanne Rosthøj, Anne-Vibeke Lænkholm, Søren T Skou, Sandy Jack, Julie Gehl, Susanne Oksbjerg Dalton, Eva Kjeldsted, Gunn Ammitzbøll, Lars Bo Jørgensen, Alexey Lodin, Rasmus Dahlin Bojesen, Silvia Gonzalez Ceballos, Susanne Rosthøj, Anne-Vibeke Lænkholm, Søren T Skou, Sandy Jack, Julie Gehl, Susanne Oksbjerg Dalton

Abstract

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.

Keywords: Breast neoplasms; High intensity interval training; Neoadjuvant therapy; Prehabilitation; Preoperative exercise; Treatment outcome.

Conflict of interest statement

The authors declare no competing interests.

© 2023. BioMed Central Ltd., part of Springer Nature.

Figures

Fig. 1
Fig. 1
Study design of the Neo-Train randomized controlled trial (RCT). Abbreviations: HIIT: high-intensity interval training; MRI: magnetic resonance imaging; NACT: neoadjuvant chemotherapy; PRT: progressive resistance training
Fig. 2
Fig. 2
Exercise program in the Neo-Train randomized controlled trial. The sessions supervised by a physiotherapist will be offered to the exercise group three times weekly for 24 weeks from 1–2 weeks after starting neoadjuvant chemotherapy to breast surgery in groups of up to three participants
Fig. 3
Fig. 3
Schedule of enrolment, intervention, and assessments of the Neo-Train randomized controlled trial according to the Standard Protocol Items: Recommendations for Intervention Trials (SPIRIT) Diagram. *Enrolment and allocation will be performed between one week before to 1–2 weeks after starting neoadjuvant chemotherapy. The baseline assessment will always be completed prior to allocation (randomization). **Additional assessments of tumour size by magnetic resonance imaging and clinical breast examination may be performed depending on the individual treatment response. Abbreviations: DT: Distress Thermometer; FACT-B: Functional Assessment of Cancer Therapy - Breast Cancer scale; GAD-7: Generalised Anxiety Disorder 7-item; GSES: General Self-Efficacy Scale; NACT: neoadjuvant chemotherapy; PHQ-9: Patient Health Questionnaire-9; 1RM: one-repetition maximum

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