Digital home-based multimodal prehabilitation of colorectal cancer patients prior to surgery (the dHOPE study): A non-inferiority clinical trial protocol

Guro Kleve^1,2Chiara Dalla Santa³Felicia Iselin Svensson Kristiansen^1,2,4Marita Tegnander¹Victoria Buch¹Cecilie Steen Hagemann⁵Marianne Helgheim⁵Parasto Engene⁵Henri Pesonen⁶Maiken Kojen Kleveland⁷Greta Lyster Hverven⁷Tormod Nilsen^8,9Mathyn Adrianus Marinus Vervaart^10,11Helle Aanesen¹²Kari Thune Uglane⁵Mona Bjelland¹³Raphaël Zory¹⁴Frédéric Chorin¹⁴Victoire Cardot-Ruffino^15,16Eva Ester Molina Beltran^15,16Cindy Neuzillet^15,16Mette Soerensen^17,18Juulia Jylhävä^19,20Irantzu Anzar³Valentin André Normand³Marius Myrstad⁵Arne Klungland^2,4Hilde Loge Nilsen^2,4Rune Ougland^1,4*

• ¹Department of Surgery, Bærum Hospital, Vestre Viken Hospital Trust, Drammen, Norway
• ²Centre for Embryology and Healthy Development (CRESCO), Department of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Oslo, Norway
• ³Applied Mathematics for Biomedical Research Institute, Ambr Institute AS, Oslo, Norway
• ⁴Centre for Embryology and Healthy Development (CRESCO), Department of Microbiology, Oslo University Hospital, Oslo, Norway
• ⁵Department of Internal Medicine, Bærum Hospital, Vestre Viken Hospital Trust, Drammen, Norway
• ⁶Department of Biostatistics, Faculty of Medicine, University of Oslo, Oslo, Oslo, Norway
• ⁷Department of Laboratory Medicine, Bærum Hospital, Vestre Viken Hospital Trust, Drammen, Norway
• ⁸Department of Sport Science and Physical Education, Faculty of Health and Sport Sciences, University of Agder, Kristiansand, Vest-Agder, Norway
• ⁹Department of Physical Performance, Norwegian School of Sport Sciences, Oslo, Norway
• ¹⁰Department of Health Management and Health Economics, University of Oslo, Oslo, Oslo, Norway
• ¹¹Clinical Trials Unit, Oslo University Hospital, Oslo, Norway
• ¹²AKTIV Against Cancer, Oslo, Norway
• ¹³Norwegian Cancer Society, Oslo, Norway
• ¹⁴Centre Hospitalier Universitaire de Nice, Clinique Gériatrique du Cerveau et du Mouvement, Université Côte d'Azur, Nice, Provence-Alpes-Côte d'Azur, France
• ¹⁵Molecular Oncology Team, UMR 144, Institut Curie, Paris, Ile-de-France, France
• ¹⁶Département d’Oncologie Médicale, Institut Curie, Paris, France
• ¹⁷Department of Clinical Genetics, Odense University Hospital, Odense, Denmark
• ¹⁸The Danish Twin Registry and Epidemiology, Biostatistics and Biodemography, Department of Public Health, University of Southern Denmark, Odense, Denmark
• ¹⁹Department of Medical Epidemiology and Biostatistics, Karolinska Institutet (KI), Solna, Stockholm, Sweden
• ²⁰Gerontology Research Center (GEREC), Faculty of Medicine and Health Technology, Tampere University, Tampere, Pirkanmaa, Finland

Background: Cancer surgery is associated with risk of complications and loss of function. Vulnerability factors, such as advanced age, malnutrition, smoking, comorbidity, frailty, and low socioeconomic status increase the risk. Lifestyle intervention prior to surgery, known as prehabilitation, often include physical activity, nutritional support, psychological coaching, and smoking cessation, increase functional reserves and reduce postoperative complications. Most importantly, it prevents loss of functional capacity and dependence. Methods: The dHOPE study is a three-armed, open-labelled, parallel-group randomized controlled trial (RCT) with non-inferiority design to compare a digital home-based prehabilitation program with a hospital-based program or no organized prehabilitation. In addition, the dHOPE study aims to identify measurable parameters reflecting the effect of prehabilitation, thus preparing for future personalization of the prehabilitation programs. Discussion: The feasibility of multimodal prehabilitation is threatened by low compliance to hospital-based programs due to burdensome commuting, even in central and metropolitan areas. In sparsely populated countries, this challenge is even more pronounced. To ensure equal healthcare to all citizens regardless of address or economic situation, there is a need to transfer the prehabilitation program to the patients' homes. Thus, the primary hypothesis of dHOPE is that a digital home-based program is not inferior to a hospital-based program. Moreover, given the patient diversity, prehabilitation must be personalized to meet individual profiles or needs. An exploratory subtask of dHOPE is to confirm the utility of clinical, genetic, and molecular factors in evaluating prehabilitation response ultimately to identify new biomarkers and develop medical software for individual risk stratification and development of personalized prehabilitation programs. Trial registration: Clinical Trials NCT06231576 (https://clinicaltrials.gov/).