The effects of neoadjuvant chemoradiotherapy and an in-hospital exercise training programme on physical fitness and quality of life in locally advanced rectal cancer patients: a randomised controlled trial (The EMPOWER Trial)

Lisa Loughney, Malcolm A West, Helen Moyses, Andrew Bates, Graham J Kemp, Lesley Hawkins, Judit Varkonyi-Sepp, Shaunna Burke, Christopher P Barben, Peter M Calverley, Trevor Cox, Daniel H Palmer, Michael G Mythen, Michael P W Grocott, Sandy Jack, Fit4Surgery group, Lisa Loughney, Malcolm A West, Helen Moyses, Andrew Bates, Graham J Kemp, Lesley Hawkins, Judit Varkonyi-Sepp, Shaunna Burke, Christopher P Barben, Peter M Calverley, Trevor Cox, Daniel H Palmer, Michael G Mythen, Michael P W Grocott, Sandy Jack, Fit4Surgery group

Abstract

Background: The EMPOWER trial aimed to assess the effects of a 9-week exercise prehabilitation programme on physical fitness compared with a usual care control group. Secondary aims were to investigate the effect of (1) the exercise prehabilitation programme on psychological health; and (2) neoadjuvant chemoradiotherapy (NCRT) on physical fitness and psychological health.

Methods: Between October 2013 and December 2016, adults with locally advanced rectal cancer undergoing standardised NCRT and surgery were recruited to a multi-centre trial. Patients underwent cardiopulmonary exercise testing (CPET) and completed HRQoL questionnaires (EORTC-QLQ-C30 and EQ-5D-5L) pre-NCRT and post-NCRT (week 0/baseline). At week 0, patients were randomised to exercise prehabilitation or usual care (no intervention). CPET and HRQoL questionnaires were assessed at week 0, 3, 6 and 9, whilst semi-structured interviews were assessed at week 0 and week 9. Changes in oxygen uptake at anaerobic threshold (VO2 at AT (ml kg-1 min-1)) between groups were compared using linear mixed modelling.

Results: Thirty-eight patients were recruited, mean age 64 (10.4) years. Of the 38 patients, 33 were randomised: 16 to usual care and 17 to exercise prehabilitation (26 males and 7 females). Exercise prehabilitation significantly improved VO2 at AT at week 9 compared to the usual care. The change from baseline to week 9, when adjusted for baseline, between the randomised groups was + 2.9 ml kg -1 min -1; (95% CI 0.8 to 5.1), p = 0.011.

Conclusion: A 9-week exercise prehabilitation programme significantly improved fitness following NCRT. These findings have informed the WesFit trial (NCT03509428) which is investigating the effects of community-based multimodal prehabilitation before cancer surgery.

Trial registration: ClinicalTrials.gov NCT01914068 . Registered 1 August 2013.

Keywords: Exercise prehabilitation; Neoadjuvant cancer treatment; Physical fitness; Rectal cancer; Surgery.

Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Screening and recruitment algorithm
Fig. 2
Fig. 2
Changes in oxygen uptake at lactate threshold (ml kg−1 min −1) throughout the entire cancer journey: pre-NCRT, post-NCRT (baseline/week 0), week 3, 6 and 9 between the exercise group and the usual care control group

References

    1. Aaronson NK, Ahmedzai S, Bergman B, Bullinger M, Cull A, Duez NJ, Filiberti A, Flechtner H, Fleishman SB, Haes JCJM, Kaasa S, Klee M, Osoba D, Razavi D, Rofe PB, Schraub S, Sneeuw K, Sullivan M, Takeda F. The European Organization for Research and Treatment of Cancer QLQ-C30: a quality-of-life instrument for use in international clinical trials in oncology. J Natl Cancer Inst. 1993;85(5):365–376. doi: 10.1093/jnci/85.5.365.
    1. Belle V. Statistical rules of thumb. Chichester. West Sussex: Wiley; 2002.
    1. Boereboom CL, Phillips BE, Williams JP, Lund JN. A 31-day time to surgery compliant exercise training programme improves aerobic health in the elderly. Tech Coloproctol. 2016;20(6):375–382. doi: 10.1007/s10151-016-1455-1.
    1. Burke SM, Brunet J, Sabiston CM, Jack S, Grocott MP, West MA. Patients’ perceptions of quality of life during active treatment for locally advanced rectal cancer: the importance of preoperative exercise. Support Care Cancer. 2013;10:3345–3353. doi: 10.1007/s00520-013-1908-2.
    1. Carlisle J, Swart M. Mid-term survival after abdominal aortic aneurysm surgery predicted by cardiopulmonary exercise testing. Br J Surg. 2007;94(8):966–969. doi: 10.1002/bjs.5734.
    1. Du D, Su Z, Wang D, Liu W, Wei Z. Optimal interval to surgery after neoadjuvant chemoradiotherapy in rectal cancer: a systematic review and meta-analysis. Clin Colorectal Cancer. 2017;1:13–24.
    1. Dworak O, Keilholz L, Hoffmann A. Pathological features of rectal cancer after preoperative radiochemotherapy. Int J Color Dis. 1997;12(1):19–23. doi: 10.1007/s003840050072.
    1. Fanke AJ, Parekh H, Starr JS, Tan SA, Iqbal A, George TJ. Total neaodjuvant therapy: a shifting paradigm in locally advanced rectal cancer management. Clin Colorectal Cancer. 2018;17(1):1–12. doi: 10.1016/j.clcc.2017.06.008.
    1. Glimelius B, Pahlman L, Cervantes A, ESMO Guidelines Working Group. Rectal cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2010. 10.1093/annonc/mdq170.
    1. Grocott MP, Browne JP, Van der Meulen J, Matejowsky C, Mutch M, Hamilton MA, et al. The postoperative morbidity survey was validated and used to describe morbidity after major surgery. J Clin Epidemiol. 2007;60(9):919–928. doi: 10.1016/j.jclinepi.2006.12.003.
    1. Habr-Gama A, Perez RO, Sabbaga J, Nadalin W, São Julião GP, Gama-Rodrigues J. Increasing the rates of complete response to neoadjuvant chemoradiotherapy for distal rectal cancer: results of a prospective study using additional chemotherapy during the resting period. Dis Colon Rectum. 2009;52(12):1927–1934. doi: 10.1007/DCR.0b013e3181ba14ed.
    1. Heldens AFJM, Bongers BC, de Vos-Geelen J, van Meeteren NLU, Lenssen AF. Feasibility and preliminary effectiveness of a physical exercise training program during neoadjuvant chemoradiotherapy in individual patients with rectal cancer prior to major elective surgery. Eur J Surg Oncol. 2016;42(9):1322–1330. doi: 10.1016/j.ejso.2016.03.021.
    1. Kothmann E, Batterham AM, Owen SJ, Turley AJ, Cheesman M, Parry A, Danjoux G. Effect of short-term exercise training on aerobic fitness in patients with abdominal aortic aneurysms: a pilot study. Br J Anaesth. 2009;103(4):505–510. doi: 10.1093/bja/aep205.
    1. Lee CHA, Kong JC, Ismail H, Riedel B, Heriot A. Systematic review and meta-analysis of objective assessment of physical fitness in patients undergoing colorectal cancer surgery. Dis Colon Rectum. 2018;61(3):400–409. doi: 10.1097/DCR.0000000000001017.
    1. Levett DZH, Jack S, Swart M, Carlisle J, Wilson J, Snowden C, Riley M, Danjoux G, Ward SA, Older P, Grocott MPW, Perioperative Exercise Testing and Training Society (POETTS) Perioperative cardiopulmonary exercise testing (CPET): consensus clinical guidelines on indications, organisation, conduct, and physiological interpretation. Br J Anaesth. 2018;120(3):484–500. doi: 10.1016/j.bja.2017.10.020.
    1. Loughney L, West MA, Kemp GJ, Rossiter HB, Burke SM, Cox T, Barben CP, Mythen MG, Calverley P, Palmer DH, Grocott MPW, Jack S. The effects of neoadjuvant chemoradiotherapy and an in-hospital exercise training programme on physical fitness and quality of life in locally advanced rectal cancer patients (The EMPOWER Trial): study protocol for a randomised controlled trial. Trials. 2016;17(1):24. doi: 10.1186/s13063-015-1149-4.
    1. Loughney LA, West MA, Kemp GJ, Grocott MPW, Jack S. Exercise training interventions for people with cancer during cancer treatment before or after surgery. Cochrane Database Syst Rev. 2018. 10.1002/14651858.CD012280.
    1. Mavros MN, Athanasiou S, Gkegkes ID, Polyzos KA, Peppas G, Falagas ME. Do psychological variables affect early surgical recovery? PLoS One. 2011;6(5):e20306. doi: 10.1371/journal.pone.0020306.
    1. Meyerhardt JA, Giovannucci EL, Holmes MD, Chan AT, Chan JA, Colditz GA, Fuchs CS. Physical activity and survival after colorectal cancer diagnosis. J Clin Oncol. 2006;24(22):3527–3534. doi: 10.1200/JCO.2006.06.0855.
    1. Moran J, Wilson F, Guinan E, McCormick P, Hussey J, Moriarty J. Role of cardiopulmonary exercise testing as a risk-assessment method in patients undergoing intra-abdominal surgery: a systematic review. Br J Anaesth. 2016;116(2):177–191. doi: 10.1093/bja/aev454.
    1. Morielli AR, Boule NG, Usmani N, Joseph K, Tankel K, Severin D, et al. Predictors of adherence to aerobic exercise in rectal cancer patients during and after neoadjuvant chemoradiotherapy. Psychol Health Med. 2018;23(2):224–231. doi: 10.1080/13548506.2017.1344356.
    1. Morielli AR, Usmani N, Boule NG, Severin D, Tankel K, Nijjar T, et al. Exercise motivation in rectal cancer patients during and after neoadjuvant chemoradiotherapy. Support Care Cancer. 2016;24:2919–2926. doi: 10.1007/s00520-016-3110-9.
    1. Morielli AR, Usmani N, Boule NG, Severin D, Tankel K, Nijjar, et al. Exercise during and after neoadjuvant rectal cancer treatment (the EXERT trial): study protocol for a randomised controlled trial. Trials. 2018;19:35. doi: 10.1186/s13063-017-2398-1.
    1. Morielli AR, Usmani N, Boule NG, Tankel K, Severin, Nijjar, et al. A phase I study examining the feasibility and safety of an aerobic exercise intervention in patients with rectal cancer during and after neoadjuvant chemoradiotherapy. Oncol Nurs Forum. 2016;43(3):352–362. doi: 10.1188/16.ONF.352-362.
    1. Moug SJ, Mutrie N, Barry SJE, Mackay G, Steele RJC, Boachie C, Buchan C, Anderson AS. Prehabilitation is feasible in patients with rectal cancer undergoing neoadjuvant chemoradiotherapy and may minimize physical deterioration: results from the Rex trial. Color Dis. 2019;21(5):548–562. doi: 10.1111/codi.14560.
    1. NICE: National Institute for Health and Care Excellence: Colorectal cancer (update): preoperative radiotherapy ad chemoradiotherapy for rectal cancer. NICE guideline NG15 last updated January 2020.
    1. Nilsson PJ, van Etten B, Hospers GA, Pahlman L, van de Velde CJH, Beets-Tan RGH, et al. Short-course radiotherapy followed by neo-adjuvant chemotherapy in locally advanced rectal cancer--the RAPIDO trial. BMC Cancer. 2013;7:13–279.
    1. Patel UB, Blomqvist LK, Taylor F, George C, Guthrie A, Bees N, Brown G. MRI after treatment of locally advanced rectal cancer: how to report tumor response: the MERCURY experience. AJR. 2012;199(4):W486–W495. doi: 10.2214/AJR.11.8210.
    1. Patel UB, Taylor F, Blomqvist L, George C, Evans H, Tekkis P, Quirke P, Sebag-Montefiore D, Moran B, Heald R, Guthrie A, Bees N, Swift I, Pennert K, Brown G. Magnetic resonance imaging-detected tumor response for locally advanced rectal cancer predicts survival outcomes: MERCURY experience. J Clin Oncol. 2011;29(28):3753–3760. doi: 10.1200/JCO.2011.34.9068.
    1. Pearse RM, Moreno RP, Bauer P, Pelosi P, Metnitz P, Spies C, Vallet B, Vincent JL, Hoeft A, Rhodes A, European Surgical Outcomes Study (EuSOS) group for the Trials groups of the European Society of Intensive Care Medicine and the European Society of Anaesthesiology Mortality after surgery in Europe: a 7 day cohort study. Lancet. 2012;380(9847):1059–1065. doi: 10.1016/S0140-6736(12)61148-9.
    1. Peel AB, Thomas SM, Dittus K, Jones LW, Lakoski SG. Cardiorespiratory fitness in breast cancer patients: a call for normative values. J Am Heart Assoc. 2014;3(1):e000432. doi: 10.1161/JAHA.113.000432.
    1. Pucciarelli S, Gagliardi G, Maretto I, Lonardi S, Friso ML, Urso E, et al. Long-term oncologic results and complications after preoperative chemoradiotherapy for rectal cancer: a single-institution experience after a median follow-up of 95 months. Ann Surg Oncol. 2009;6:893–899. doi: 10.1245/s10434-009-0335-6.
    1. Rabin R, de Charro F. EQ-5D: a measure of health status from the EuroQol Group. Ann Med. 2001;33(5):337–343. doi: 10.3109/07853890109002087.
    1. Singh F, Galvao DA, Newton RU, Spry NA, Baker MK, Taaffe DR. Feasibility and preliminary efficacy of a 10-week resistance and aerobic exercise intervention during neoadjuvant chemoradiation treatment in rectal cancer patients. Inter Cancer Ther. 2018;17(3):952–595. doi: 10.1177/1534735418781736.
    1. Slade SC, Dionne CE, Underwood M, Buchbinder R. Consensus on Exercise Reporting Template (CERT): explanation and elaboration statement. Br J Sports Med. 2016;50(23):1428–1437. doi: 10.1136/bjsports-2016-096651.
    1. Snowden CP, Prentis JM, Anderson HL, Roberts DR, Randles D, Renton M, Manas DM. Submaximal cardiopulmonary exercise testing predicts complications and hospital length of stay in patients undergoing major elective surgery. Ann Surg. 2010;251(3):535–541. doi: 10.1097/SLA.0b013e3181cf811d.
    1. West MA, Asher R, Browning M, Minto G, Swart M, Richardson, et al. Validation of preoperative cardiopulmonary exercise testing-derived variables to predict in-hospital morbidity after major colorectal surgery. Br J Surg. 2016;103:744–742. doi: 10.1002/bjs.10112.
    1. West MA, Loughney L, Barben CP, Sripadam R, Kemp GJ, Grocott MP, et al. The effects of neoadjuvant chemoradiotherapy on physical fitness and morbidity in rectal cancer surgery patients. Eur J Surg Oncol. 2014;40(11):1421–1428. doi: 10.1016/j.ejso.2014.03.021.
    1. West MA, Loughney L, Lythgoe D, Barben CP, Sripadam R, Kemp GJ, et al. Effect of prehabilitation on objectively measured physical fitness after neoadjuvant treatment in preoperative rectal cancer patients: a blinded interventional pilot study. Br J Anaesth. 2014;114:244–251. doi: 10.1093/bja/aeu318.
    1. Wijeysundera DN, Pearse RM, Shulman MA, Abbott TEF, Torres E, Ambosta A, et al. Assessment of functional capacity before major non-cardiac surgery: an international, prospective cohort study. Lancet. 2018;10140:2631–2640. doi: 10.1016/S0140-6736(18)31131-0.
    1. Wilson RJ, Davies S, Yates D, Redman J, Stone M. Impaired functional capacity is associated with all-cause mortality after major elective intra-abdominal surgery. Br J Anaesth. 2010;105(3):297–303. doi: 10.1093/bja/aeq128.
    1. Wyrwicz L, Temnyk M, Spalek M. The addition of oxaliplatin increases pathological complete response: a meta-analysis of randomized controlled trials on radiochemotherapy in rectal cancer. Ann Oncol. 2016. 10.1093/annonc/mdw199.217.

Source: PubMed

赞助者和合作者

医疗条件

药物干预

3
订阅