Digital Home-Based Prehabilitation Before Surgery
Phase: NA
Conditions: Cancer Colorectal, Frailty, Surgery
Sponsor: Vestre Viken Hospital Trust

Digital Home-Based Prehabilitation before Surgery dHOPE) 
– PRESERVATION OF FUNCTIONAL STATUS IN PATIENTS UNDERGOING MAJOR CANCER SURGERY – 
 
 
STUDY PROTOCOL COVER PAGE – January 16th 2014 
 
 
NAME OF STUDY:  
 
Digital Home-Based Prehabilitation Before Surgery (dHOPE) 
PROTOCOL VERSION:   
Version January 16th 2024 
DATE:   
 
 
January 16th 2024 
CENTRAL CONTACT PERSON: 
Guro Kleve, MD/surgeon 
 
 
 
 
Researcher 
Email: gurok@vestreviken.no 
Phone: (+47) 32 80 30 00 
BACKUP CONTACT PERSON: 
Rune Ougland, MD PhD/surgeon 
 
 
 
 
Principal investigator 
Email: runoug@vestreviken.no  
Phone: (+47) 32 80 30 00 
 

 
 
    
 
1. Digital Home-Based Prehabilitation before Surgery (dHOPE) 
– PRESERVATION OF FUNCTIONAL STATUS IN PATIENTS UNDERGOING MAJOR CANCER SURGERY – 
2 INTRODUCTION 
Major cancer operations are associated with a significant risk of complications and irreversible or 
longstanding loss of function. Patients report that they value functional capacity and independence 
as much as survival. Traditional rehabilitation is hampered by being introduced at a time point when 
the patients’ reserves are at the lowest. Data strongly suggest that an effort to increase functional 
reserves before the challenge of surgery – prehabilitation – can prevent complications and 
readmissions and reduce hospital length-of-stay. Most importantly, it can prevent loss of functional 
capacity and independency. However, a key challenge to prehabilitation is patient compliance. The 
available data come from hospital-based prehabilitation programs requiring patients to commute on 
daily basis. This has low acceptance even in densely populated metropolitan areas. By transferring 
of the prehabilitation to the patients’ home, we will increase compliance, contribute to a future-
oriented digitalization of the healthcare system, and strengthen the link between the patients and the 
hospital – a process that will bolster vulnerable transitions and improve patient-hospital relationship. 
 
We will perform an RCT to scientifically test a digital home-based multimodal prehabilitation bundle 
to increase functional reserves in patients scheduled for major cancer surgery. We have called our 
study “Digital Home-Based Prehabilitation before Surgery – dHOPE”. The main goal of our project 
is to elucidate the functional outcome of the prehabilitation program, and to assess the patient 
perspective through structured questionnaires of the patients’ perception of their experience with the 
prehabilitation program (PREMs) and the effect on life-quality (HR-QoL). 
 
The project is multicenter and multidisciplinary and engage national- and international collaborators. 
We will perform an RCT to scientifically test different multimodal prehabilitation bundles to increase 
functional reserves in patients scheduled for major cancer surgery. The study is designed to compare 
a digital home-based program with a hospital-based program and no organized prehabilitation. We 
harvest blood samples at three time-points, and tumor specimens at the time of surgery. By 
combining surgical outcome, clinical data, high-throughput molecular biology and artificial 
intelligence we intend to identify biomarkers reliably predicting the patients’ individual pre-operative 
risk profile and outcome after surgery. The project harbors a clear innovation potential, and the digital 
platform can easily be spread and implemented by all Norwegian hospitals. 
 
Frailty is a syndrome characterized by increased vulnerability to stress, leading to increased risk of 
disability, morbidity and mortality. Moreover, people do not age at the same rate. Individuals with 
same chronological age display great differences in biological age and divergent frailty (Yang Cell 
2023; Levine Aging 2018). A task of the proposed study is to establish a biobank with blood- and 
tumor samples for molecular analyses in search of biomarkers that reliably reflect a measurable 
effect of prehabilitation on the frailty syndrome and the patients’ individual risk profile (López-Otín 
Figure 1: Illustration of the concept 
of how prehabilitation, in combination 
with ERAS, impact the patients’ 
functional capacity before and after 
an operation. Prehabilitation reduce 
patient frailty and increase functional 
reserves prior to surgery. This may 
reduce hospital length-of-stay and 
the need of community based health 
care and support after discharge, 
and our pilot study suggest that the 
patients’ experience measures and 
postoperative 
Quality-of-Life 
is 
significantly 
improved 
after 
the 
completion 
of 
a 
prehabilitation 
program (Kleve NGF-nytt 2022). 

 
 
2 
DIGITAL HOME-BASED PREHABILITATION BEFORE SURGERY - dHOPE 
16. januar 2024 
Cell 2023). We believe some patients will 
benefit from a prolonged prehabilitation 
scheme, while others are fit for surgery after 
a shorter program. Biomarkers reflecting the 
patients’ individual conditions are required 
to individualize the prehabilitation program 
according to the patients’ needs. We will do 
genetic, 
epigenetic 
and 
metabolomics 
analyses of blood and serum, and feed 
results from multi-omics analyses, clinical 
results and patient outcome into advanced 
machine learning algorithms to identify 
possible predictors of the patients’ condition 
and prognosis. In parallel to the data 
obtained from this study, our models can be 
pretrained on other biobanks (such as Dutch 
“Lifelines” 
or 
UK 
biobank) 
providing 
biomarkers and clinical outputs, allowing for 
high precision predictions and uncertainty 
measurements never achieved before. 
These analyses are done in collaboration 
with basic scientists at OUS (Oslo, Norway), 
Karolinska Institutet (Stockholm, Sweden) 
and PueroVita Biotechnology.  
2.1 EXPECTED IMPACT/BENEFIT 
Functional 
impairment 
predicts 
post-
operative complications and mortality in 
older adults operated for colorectal cancer 
(Kristjansson Crit Rev Oncol Hematol 2010; 
Ommundsen Europ Ger Med 2013), and 
numerous studies have confirmed the 
association 
between 
frailty 
and 
complications, slow functional recovery, and 
postoperative mortality, (Dale Ann Surg 
2014; Wilson Br J Anaesth 2010; Gillis 
Anesthesiology 2014). Furthermore, the risk 
of a permanent reduction in functional capacity after surgery increases with pre-existing comorbidity 
and functional impairment (Dronkers Anaesthesia 2013). Even following the implementation of 
Enhanced Recovery After Surgery (ERAS) protocols for major abdominal surgery (Lassen Clin Nutr 
2012; Mortensen Br J Surg 2014), and general optimization measures (Fearon Br J Surg 2013), 
major cancer operations are associated with a high rate of complications and constitute a severe 
impact on patients’ levels of function (Kleve NGF-nytt 2022; figure 1). Adding to short-term 
complications and protracted recovery are long-term functional impairment and fatigue and reduced 
health-related quality-of-life (HR-QoL). Malnutrition and sarcopenia (low muscle mass) are major 
causes of morbidity and mortality in advanced cancer patients (Antoun Annals of Oncol 2018). 
Sarcopenia is associated with increased treatment toxicities as well as reduced progression-free and 
overall survival (Prado Cancer Chem Pharm 2011; Malietzis Br J Surg 2016). Martin et al. found that 
a cohort of 1473 lung and gastrointestinal cancer patients exhibiting weight loss, low muscle mass 
and density survived 8.4 months, compared with 28.4 months in patients who had none of these 
characteristics (Martin J Clin Oncol 2013). Most patients emphasize that functional outcomes after 
treatment, such as the ability to live independently, are more important than survival (Fried N Engl J 
Med 2002; Akishita J Am Med Dir Assoc 2013). Furthermore, patients who do not recover swiftly 
after surgery may lose the opportunity of adjuvant anti-cancer treatment. Thus, finding ways to 
preserve functional status is paramount.  
 
Figure 
2: 
A 
schematic 
representation 
of 
the 
pathophysiology of frailty. There is a complex interplay 
between genetic predisposition and environmental factors that 
affect epigenetic and epitranscriptomic regulation in turn 
accelerating cellular damage and aging thus reducing 
functional reserves. The process can be counteracted by 
improved nutrition and daily exercise through a structured 
multimodal prehabilitation program (Clegg Lancet 2013). 

 
 
3 
DIGITAL HOME-BASED PREHABILITATION BEFORE SURGERY - dHOPE 
16. januar 2024 
The feasibility of multimodal prehabilitation is threatened by low compliance to hospital-based 
programs due to burdensome commuting even in central and metropolitan areas (Dunne Br J Surg 
2016).  Economical and logistical constraints in modern hospitals add to this. To build on the known 
benefits of hospital-based prehabilitation programs but at the same time overcome the challenge of 
known constraints and low acceptance to daily long-distance commuting in a vulnerable period for 
surgical cancer patients, a new approach to prehabilitation is warranted. Making the intervention 
digital, thus transfer of the prehabilitation program to the patients’ own homes, is an intriguing idea 
(Durrand Anaesthesia 2021; Barberan-Garcia Front Oncol 2021). In addition, modern surgery is 
continuously pushing limits. With an aging population, surgery is offered to the very old, even 
centenarians, and multimorbid patients. There is an increasing need for personalized prediction of 
risk and outcome, not only when regarding survival of surgery and cancer, but rather with respect to 
level of function, activities of daily life and life quality.  
 
3 HYPOTHESES, AIMS AND OBJECTIVES 
Environmental influence, such as sedentary lifestyle, socioeconomic adversity, and malnutrition in 
addition to yet unknown genetic and molecular factors, underlies development of the frailty 
syndrome. The addition of external stress, like major cancer surgery, may be the final straw that 
sends the patient over the edge and necessitates increased care (figure 2).  
 
Re-habilitation after surgery has been the traditional approach to counteract this unfavorable 
outcome but comes at a time where patients’ reserves are at their lowest. Conceptually, an 
intervention that predates the trauma, i.e. applied before the physiological stress of surgery is 
appealing and has been coined prehabilitation (Carli Curr Opin Clin Nutr Metab Care 2005). A 
multimodal prehabilitation program includes intensive and coached physical exercise and optimized 
nutritional intake coupled with smoking cessation, physiological support and correction of poly-
pharmacy. Indeed, such programs have repeatedly been shown to increase functional capacity 
(Bruns Colorectal Dis 2016; Hijazi Int J Surg 2017; Boukili Skand J Surg 2022), to reduce rate of 
complications in patients undergoing major abdominal surgery (Barberan-Garcia Ann Surg 2018; 
Heger J Gastrointest Surg 2019), to reduce unplanned readmissions (Barberan-Garcia Br J Anaesth 
2019), and to lower the costs (Howard J Am Coll Surg 2019). The benefits appear even in situations 
where ERAS care is already established, indicating that the benefits from prehabilitation comes as 
an addition to what ERAS offers. The observed improvement of functional capacity appears to 
depend on a concomitant increase in protein intake to allow for lean muscle anabolism (Gillis 
Gastroenterology 2018), and studies on physical exercise alone have shown conflicting results 
(Lemanu World J Surg 2013; Moran Surgery 2016). Hence, an important aspect is that 
complementary interventions such as physical exercise and nutritional counselling are warranted, to 
help sustain or rebuild muscle mass through increasing protein metabolism and decreasing 
catabolism (Al-Majid Biol Res Nurs 2008). 
 
We want to move the prehabilitation program to the patients’ homes by implementing a user-friendly 
digital platform with daily online real-time exercise together with a dedicated physiotherapist. To our 
knowledge, a digital home-based prehabilitation program is completely novel. A home-based 
approach spares the patients for time-consuming and laborious commuting to the hospital, and it 
represents a valuable future-oriented cost-effective digitalization of the health care system. Our long-
term ambition is to spread our digital model to all hospitals nationally and implement prehabilitation 
for all cancer patients.  
 
Hypothesis: A digital home-based prehabilitation program is not inferior to a hospital-based 
program in preventing loss of function in frail patients undergoing cancer surgery. 
Advanced analytics will provide personalized prediction of surgical outcome and post-
operative functional level and quality of life. 
Aim: 
Maintain functional capacity and protect quality-of-life for patients undergoing major 
cancer surgery using a defined prehabilitation program and develop biomarkers 
reflecting patients’ individual risk profile. 
Objective: 
Stratified randomization of patients to either digital home-based or hospital-based 
prehabilitation, or no organized prehabilitation (control group). Evaluate change in “six-
minute-walk-test” (6MWT) following prehabilitation (primary outcome). Decipher the 

 
 
4 
DIGITAL HOME-BASED PREHABILITATION BEFORE SURGERY - dHOPE 
16. januar 2024 
role of the epigenome, epitranscriptome and metabolome in relation to the surgical 
outcome, clinical data, and functional capacity. Utilize artificial intelligence in the multi-
omics integration and pathway analyses to identify biomarkers. 
Results: 
Development and implementation of a digital home-based prehabilitation program to 
improve outcome and maintain quality-of-life for patients after major cancer surgery. 
Novel blood biomarkers to predict outcome. 
 
Summarized: The primary goal of our project is to develop and implement a digital home-based 
prehabilitation program and use this setup in an RCT to compare digital home-based prehabilitation 
with hospital-based or non-organized. The secondary goal is to identify blood biomarkers reflecting 
the effect of prehabilitation on patient frailty and reliably report the patients’ individual risk profile to 
establish personalized prediction of outcome for patients treated for colorectal cancer.  
 
4 PROJECT METHODOLOGY 
The proposed project describes a three-armed, open-labelled parallel-group randomized controlled 
trial (RCT) between a control group (current practice) and two intervention groups: A digital home-
based prehabilitation bundle and a hospital-based prehabilitation bundle. Patients will be extensively 
tested at the hospital premises at three time points to assess functional capacity. Blood samples for 
biomarker analyses will be drawn at the same three time-points, and tumor specimens will be 
collected at time of surgery. Figure 3 illustrates the trial outline. Patients are randomized to one of 
three possible preoperative courses, and we do a stratified randomization to include the frail, or pre-
frail patients (based on “Frailty Index”) to ensure inclusion of individuals with presumed effect of 
prehabilitation. Postoperatively, all groups enter a standard rehabilitation program to isolate the 
effect of prehabilitation in the analyses.  
 
Patients are screened at the preoperative outpatient clinic and invited into the trial (included) if: 
 
Planned for major gastrointestinal cancer surgery  
 
Fluent in Norwegian and able to consent and to understand questionnaires 
 
They cannot participate (excluded) if:  
 
Inability to walk for six minutes or to rise independently from a chair 
 
Inability to comprehend exercise program or to comply with written and oral instructions 
 
Presence of a cardio-pulmonary condition that precludes exercise  
 
Living in very remote areas making a hospital-based intervention group impossible to implement  
 
Being without a permanent address 
 
Admittance to a hospital facility for > 50% of the time from diagnosis to surgery 
 
For both hospital-based and digital home-based prehabilitation groups: 
 
Psychological coaching and support  
 
Individualized nutritionist counselling  
 
Coached, structured and repeated daily exercises for three weeks prior to surgery  
Figure 3: Overview of project 
timeline. Included patients will 
undergo a set of functional test 
prior 
to 
randomization 
to 
establish a baseline level to 
which one can compare post-
prehabilitation 
and 
post-
operative results. Intervention 
will run for three weeks before 
surgery, 
and 
the 
enrolled 
patients will be tested again the 
day 
before 
the 
scheduled 
surgery. After the operation, the 
patients 
follow 
standard 
postoperative rehabilitation, and 
the final test is done 4-5 weeks 
after hospital discharge. 

 
 
5 
DIGITAL HOME-BASED PREHABILITATION BEFORE SURGERY - dHOPE 
16. januar 2024 
For intervention and control groups: 
 
Counsel for smoking cessation 
 
Polypharmacy optimization 
 
Standard information about planned surgery, risks and precautions 
 
Rehabilitation in the form of once daily exercise for 4-5 weeks postoperatively 
 
Details of the intervention groups:  
 
Nutritional optimization: A nutritionist will perform a structured interview, comprehensive nutrition 
assessment, and provide personalized dietary advice. The main goals are to avoid perioperative 
malnutrition and to ensure optimal protein intake to support exercise-induced anabolism, if 
required by nutritional support drinks. A daily protein intake of 1.2-2.0 g/kg will meet needs as 
outlined in surgical nutrition guidelines (Wischmeyer Anesth Analg 2018; Weimann Clin Nutr 
2017; Symons J Am Diet Assoc 2009; Witard Am J Clin Nutr 2014).  
 
Exercise:  Based on current guidelines and instructed by a dedicated physiotherapist, for 1 hour 
per day preoperatively to increase muscle strength, aerobic capacity and physical endurance. 
The digital home-based exercise will be done at home by the patients, with guidance by an 
online physiotherapist, while the hospital-based exercise will be done in groups at the hospital. 
Intensity will be based on the rate of perceived exertion using the Borg scale, a 15-graded scale 
ranging from very light to very hard. Resistance exercises will target upper/lower body, and 
abdominal muscles.  
 
Psychological coaching and support: Performed as one interview during inclusion, followed by 
weekly phone calls by a study nurse coordinator during the preoperative intervention, focusing 
on exercise, nutritional intake, motivation (and smoke cessation if applicable). 
 
Estimation of sample-size (figure 4): 
Patients are randomized to one of three 
possible preoperative courses, and we do a 
stratified randomization to include the frail, 
or pre-frail patients (based on “Frailty 
Index”) to ensure inclusion of individuals 
with presumed effect of prehabilitation. 
Sample size calculation is based on a two-
sample 
(repeat 
measure), 
two-sided 
comparison of mean changes after 4 weeks 
intervention 
compared 
with 
baseline. 
Based on data for the six-minute walk test 
(6MWT) from a pilot study, and from 
Montreal, on patients undergoing colorectal 
surgery (Li Surg Endosc 2013; Carli Br J 
Surg 2010), we will need 40 patients per 
group 
Expecting 
dropout 
of 
15 
% 
necessitates a total of 140 patients.  
 
4.1 DESIGN, METHODS, ANALYSES 
To carry out our purpose; we have defined the above-mentioned objective with connected work-
packages (WP1 and WP2. See below). 
 
Work-package 1: The primary outcome 
Patients with colorectal cancer will be called and informed about the project after colonoscopy. If 
they decide to participate in the study, they are included at the day evaluation by the multidisciplinary 
team (MDT) and tested extensively. All patients get guidance by specialists in nutrition and geriatric 
medicine (see above). Eligible patients are then randomized, and the intervention groups receive 1-
hour daily physical exercise, one group physical and one group digital. The physical group use 
“Pusterommet” while the digital group use the “Digitale Pusterommet”. “Pusterommene” are 
inventions by the organization “Aktiv mot Kreft”, and the project is in collaboration with them.  
 
Figure 4: Sample-size. Figure visualizing the randomization and 
two intervention groups relative to a control group. Two thirds of 
the enrolled patients will receive intervention (statistical 
significance level (alpha) of 0.05 and a power (1-beta) of 0.80). 

 
 
6 
DIGITAL HOME-BASED PREHABILITATION BEFORE SURGERY - dHOPE 
16. januar 2024 
Figure 5: Workflow of AI-based analysis of multi-omics data. Epigenetics, epitranscriptomics and metabolomics 
are integrated and analyzed using a knowledge graph approach to stratify disease endotypes, identify relevant 
pathways and ultimately identify endotype-specific biomarkers with predictive value of surgical outcome. 
Change in “six-minute-walk-test” (6MWT) is chosen as our primary outcome. We will measure the 
walking distance at inclusion, following the prehabilitation program and 4-5 weeks after surgery. 
6MWT is chosen as an indicator for functional capacity because several studies have published it to 
be significantly correlated with effect of prehabilitation (Boukili Skand J Surg 2022; Li Surg Endosc 
2013; Carli Br J Surg 2010). Moreover, the following parameters will be addressed: 
 
 Quality of life: Health-related-quality-of-life (HR-QoL) will be assessed by the EORTC QLQ C30, 
the EQ-5D and the QoR-15 tools focusing on aspects relating to functional status, emotional 
function, role function, pain and overall QoL 
 Patient-reported experience measures (PREMs) will be measured by GS-PEQ (Sjetne BMC 
Health Serv Res. 2011) to elucidate the patients’ perception of their experience with the 
prehabilitation program and health care system 
 Complications according to the Clavien-Dindo Classification 
 Use of nursing home facilities 4-5 weeks post-discharge 
 Changes in patient weight, energy- and protein intake 
 Aggregated length-of-stay (aLoS) within 30-days from surgery and 90-day mortality 
 Cost-effectiveness. This is a subtask within the field of health service research. We will estimate 
the resources used on the prehabilitation program and compare to resources saved by shorter 
aLoS, less use of nursing home facilities and less need of community healthcare services 
 
Work-package 2: The biomarkers 
 
Reversible modifications of DNA and RNA molecules, and proteomics/metabolomics, allow for rapid 
cellular adjustment to environmental changes, a concept well known from basic cancer research. We 
believe the same mechanisms plays a significant role in the patients’ adaption to the environmental 
change imposed by the prehabilitation program. We have recently portrayed the RNA modification 
status of the small non-coding RNA and elucidated their role in gene regulation (Su Nature Commun 
2022). In the proposed project we will use the same workflow to portray the modification status of 
DNA and RNA, and include metabolomic analyses, before and after the prehabilitation program, and 
after the surgical stress. There are evidence suggesting that a physical prehabilitation program affect 
tumor growth and metastasis (Verma Immunopharmacol Immunotoxicol 2009; Amirsasan Cancer 
Cell Int 2022). Thus, we will compare the molecular changes in blood samples with changes in tumor 
cells collected at the day of the operation. 

 
 
7 
DIGITAL HOME-BASED PREHABILITATION BEFORE SURGERY - dHOPE 
16. januar 2024 
To cope with the overwhelming amount of data generated by multi-omics, we will use advanced 
analytics and machine learning to map the relationships between the epigenome, epitranscriptome 
and metabolome in relation to the surgical outcome, clinical data, and functional capacity. To do so, 
several unsupervised multi-omics integration and pathway analysis approaches will be tested and 
subsequently evaluated based on the emerging endotypes of prehabilitation samples and control 
samples (figure 5). By combining endotyping from the multi-omic analyses with existing knowledge 
graphs, we will be able to better distinguish patient endotypes and identify novel biomarkers. We will 
query the graph both on the basis of embedding methodologies for similarity assessment, e.g. LINE 
(Tang Proceedings of the 24th International Conference on World Wide Web 2015: 1067–1077), and 
graph neural networks. The top candidates and candidate combinations will then be tested in 
subsequent studies. The AI-based analysis will be done by our collaborator Dr. Valentin Normand 
and his team, PueroVita Biotechnology. PueroVita Biotechnology aims to improve insight into aging 
biology and frailty to increase understanding of aging, and what one can do to counteract frailty 
(https://puerovita.ai/). 
4.2 PARTICIPANTS, ORGANIZATION AND COLLABORATIONS 
 
Name 
Role 
Key collaborators  
(curriculum vitae enclosed) 
Rune Ougland 
Bærum Hospital 
WP1/WP2: Project leader and principal supervisor 
Guro Kleve 
Bærum Hospital 
WP1/WP2: PhD student  
Marius Myrstad 
Bærum Hospital 
WP1: Co-supervisor  
Arne Klungland 
University of Oslo 
WP2: Co-supervisor  
Line Schjøtt-Iversen 
Diakonhjemmet Hospital 
WP1: Surgeon, participates in enrollment of patients and 
evaluation of results.  
Valentin Normand 
PueroVita Biotechnology 
WP2: Artificial intelligence. Development of algorithms for 
multi-omic and clinical integration and identify biomarkers. 
Juulia Jylhävä 
Karolinska Institutet 
WP2: Studies of aging-related frailty syndrome and 
epigenetics of aging including aging and frailty biomarkers. 
 
 
 
 
National 
collaborators 
Helle Aanesen 
Aktiv Mot Kreft 
WP1: CEO of “Aktiv mot Kreft». Experience in digital 
physical training, and exercise as part of cancer care. 
Marianne Helgheim  
Bærum Hospital 
WP1: Physiotherapist, in charge of the physical exercise 
provided to the patients in the intervention groups. 
Parasto Engene 
Bærum Hospital 
WP1: Registered dietitian. Provides personalized dietary 
advice in relation to cancer and major surgery. 
Marita Tegnander 
Bærum Hospital 
WP1: Cancer nurse, contributing in testing of the enrolled 
patients and has knowledge of all required methodology. 
 
 
 
 
International 
collaborators 
 
Cindy Neuzillet 
Curie Institute, St. Cloud 
 
WP1: Experience in digital prehabilitation of gastrointestinal 
cancer patients from rural areas.  
 
Zhangli Su 
University of Alabama 
 
WP2: Bioinformatics and artificial intelligence. Development 
of required algorithms. Multi-omics analyses. 

 
 
8 
DIGITAL HOME-BASED PREHABILITATION BEFORE SURGERY - dHOPE 
16. januar 2024 
4.3 PLAN FOR ACTIVITIES, VISIBILITY AND DISSEMINATION 
 
Users: The project will be carried out in collaboration with user groups and rapid dissemination of 
project results is expected. We will make the results of the study known to the patients and 
caregivers, and we will seek advice from our expert group of users to do this efficiently. Patients and 
caregivers may also be identified through the cancer coordinators, and we will use the network that 
we establish through this study to reach patients more efficiently.Community: The planning of the 
study will be carried out in cooperation with representatives from the municipality. As the study is 
multidisciplinary, we have the potential to spread the knowledge to a broad group of health 
professionals in the community. We will do this by arranging workshops for physiotherapists, cancer 
coordinators, and nurses. This educational process is an important part of the dissemination of 
knowledge about the effects of surgery on functional status and alertness towards preventing loss of 
function. After the study is completed, results will be presented at suitable conferences or other 
meetings. General public: Cancer is a disease with a high level of interest to the general public. The 
research team will reach out through social media, e.g. by blog posts, the effects of surgery on 
functional status, and how to prevent loss of function through exercise and nutrition. We aim to 
publish in national papers such as “Apollon” and “Khrono” as well as widely read scientific webpages 
such as www.forskning.no. We will collaborate with the Norwegian Cancer Society in order to inform 
the public as well as influence stakeholders such as public administration. We are presenting the 
proposed project during “Arendalsuka 2022” as an initiative by “Aktiv mot Kreft”. For the academic 
(and clinical) community: The primary audience of our results is scientists and clinicians working in 
the field, and we will publish our data in peer-reviewed scientific journals of high quality. Moreover, 
results will be presented at international conferences on surgery, geriatric medicine, oncology, 
geriatric oncology, physiotherapy, and nutrition. For clinicians in Norway, the experiences and results 
from the study will be presented in national journals such as “Tidsskrift for Den Norske Legeforening”, 
“Indremedisineren” and “Onkologisk forum”, and we aim for frequent lectures at various hospitals 
dealing with older cancer patients. We have already published a description of the project (Kleve 
NGF-nytt 2022). 
 
A project progress plan with milestones is suggested (figure 6).  
4.4 PLAN FOR IMPLEMENTATION 
Users: In our proposed project, we include PREMs (see pt 3.1/WP2 above) to elucidate the patient 
perspective and develop our prehabilitation program according to the patients’ needs and desires. 
We scientifically test a novel intervention with a generic potential for all cancer patients that need 
major surgery, or even extended radiation or chemotherapy regimens. A well-functioning digital 
home-based prehabilitation program is a non-invasive approach that preserves functional capacity 
and quality-of-life, reduces complications and dovetails with the wishes of cancer patients and needs 
of society. Avoiding unnecessary time spent in hospital before and after major surgery and an early 
established digital contact with healthcare providers is in full accordance with the expressed 
concerns voiced by the user representatives in the team. Our focus is on gastrointestinal cancer 
patients as this is our clinical field, but the model will be easily applicable to other fields of cancer 
surgery.  
 
Figure 6: Overview of 
project timeline. The 
figure is a schematic 
suggestion and changes 
may apply. For statistical 
reasons, WP1 can first 
be achieved once all 
patients are enrolled. 
WP2 may start earlier 
than indicated. Behind 
the 
gray 
shading 
is 
complementary projects. 

 
 
9 
DIGITAL HOME-BASED PREHABILITATION BEFORE SURGERY - dHOPE 
16. januar 2024 
Community: The project is performed in collaboration with community health care personnel: Cancer 
coordinating nurses and community-based physiotherapists and nutritionists, and hence has the 
potential to generate an increased local expertise that will outlast our project. Moreover, a digital 
platform for healthcare, and a community-driven home-based prehabilitation, will strengthen the 
interaction between “the treatment-triad” i.e. the hospital, the community, and the patients.  
 
General public: Implementation of a digital home-based platform for physiotherapy represents a 
future-oriented digitalization of the healthcare system enabling the community to reach out to a large 
number of users in a time- and cost-effective way, in line with the goals given by the government.  
 
For the academic community: Reversible RNA modifications allows for rapid cellular adjustment to 
environmental changes. This mechanism is known to play a substantial role in tumor-cell resistance 
against anti-cancer therapy. We believe the same family of molecules will reflect the cellular adaption 
to the environmental change a prehabilitation program represents. We have recently portrayed the 
RNA modifications of small non-coding RNA and elucidated their role in gene regulation (Su Nature 
Commun 2022). We will use the same workflow to portray the modifications status before and after 
the prehabilitation program, and after the surgical stress. We search for biomarkers reflecting the 
patients’ individual response to prehabilitation. This is to individualize the prehabilitation program as 
we believe some persons will benefit from a longer program, while a shorter one is sufficient for 
others. We aim to identify a panel of methylated RNAs that can serve as a useful screening tool in 
evaluation of operability of frail cancer patients. 
 
Risk assessment 
In this proposal, we combine high-risk/high-gain objectives with some very feasible ones. We have 
recently published two manuscripts using the described sequencing methodology. Thus, the high-
risk is associated with the positive outcome of WP2; namely identification of biomarkers reliably 
predicting the patients’ individual risk profile and treatment outcome. However, with adequate 
resources, we believe we possess all required facilities and expertise to successfully achieve our 
proposed results. Some of the proposed sub-projects are very challenging (development of artificial 
intelligence predictive algorithms). However, the project management underscore that the 
challenging high-risk work tasks are already partly developed (funded by other grants), and the 
proposed project will get support from personnel working on these complementary projects. 
Moreover, PueroVita Biotechnology has particular experience in analyses of aging and frailty and 
will be investing considerably of their own resources into this project. Thus, although the project is 
laborious, we consider it completely feasible to achieve. The schematic overview of the project plan 
includes complementary projects on epitranscriptomic cancer research (figure 6). The proposed 
project will be done according to this scheme. PueroVita has extensive knowledge into translating 
research into product, and has built many other platform systems and software. Any discoveries 
worth of patenting will be brought up to the UiO/OUS Inven2 technology transfer office. Of note; the 
project management currently holds 8 granted and pending patents as well as 4 licensed products.  
 
5 USER INVOLVEMENT 
The patients diagnosed and treated for colorectal cancer have provided information about the life 
with gastrointestinal cancer, including everyday problems and quality of life. This created the desire 
of doing something to improve their situation. Thus, in collaboration with the organization “Aktiv mot 
Kreft” we initiated a prehabilitation pilot project including 20 patients who were offered daily physical 
exercise, psychological coaching and dietary advice. These “pilot patients” have served as our user 
group, and we have discussed the development of the project with them. One of the patients has 
served as spokesman for the group, however, because of recent severe disease progression he is 
no longer capable to serve the role and we have not named him in the application form. Despite this 
very sad development, we have maintained communication with the patient group and designed the 
project according to their needs. Through several meetings between patients and clinical personnel 
we have collected suggestions and feedback of how to best proceed with our investigations. 
Patients, nurses, physiotherapists, secretaries, and doctors have all contributed with invaluable input 
regarding the challenges coming with the disease work-up and treatment. In our proposed project, 
we include PREMs to monitor the patients’ perspective and continuously develop our prehabilitation 
program according to their needs and desires. We have a dialogue with The Norwegian Cancer 

 
 
10 
DIGITAL HOME-BASED PREHABILITATION BEFORE SURGERY - dHOPE 
16. januar 2024 
Society and received results from their surveys which report that a significant number of cancer 
survivors want more information and supervision of how and what to do to participate in their 
treatment chain. When specifically interviewed about prehabilitation, more than 70% answer that 
they would have appreciated participation in a program such as ours.   
 
6 ETHICAL CONSIDERATIONS 
The project is approved by the Regional Ethical Committee (REC) (ref. no: 489036). Patients will be 
enrolled following written informed consent. Time of surgery will be postponed by 1 week for the 
intervention groups compared to the recommended “pakkeforløpstid”. However, multiple 
international studies report that this delay does not improve the risk, rather the contrary; if a 
prehabilitation program is followed, the risk is reduced. Except for the delay of surgery, the enrolled 
patients follow standard diagnostic work-up and treatment common for all patients with 
gastrointestinal cancer. However, the enrolled patients will have to use more time on examinations 
and testing. The patients in the intervention groups will be followed more closely and have more 
focus on exercise, diet and smoke cessation. We expect all patients to benefit from the program, 
however, we assume that those randomized to the intervention groups will benefit more than the 
control group. There will be no information given to the enrolled patients about the molecular 
analysis. Results from the proposed project will be published in peer-reviewed international journals. 
It will not be possible to identify the enrolled patients in the publications. GDPR limits sharing of raw 
data to third party databases, and any sharing of such data will only be possible after evaluation by 
REC and the local Data Protection Officer. The project does not impact the environment, lead to 
manipulation of individuals or society, have military consequences, or expose sensitive personal 
information. We have a system in place to support employees who might encounter ethical 
objections on the work floor.  
 
7 REFERENCES 
Al-Majid S, Waters H. Biol Res Nurs 2008; 10(1):7-20; Antoun S, Raynard B. Annals of Oncology 2018; 29(suppl_2):ii10-
ii17; Akishita M, Ishii S, Kojima T, et al. J Am Med Dir Assoc 2013; 14(7):479-84; Barberan-Garcia A, Ubre M, Roca J, 
et al. Ann Surg 2018; 267(1):50-56; Barberan-Garcia A, Ubre M, Pascual-Argente N, et al. Br J Anaesth 2019; Barberan-
Garcia A, Cano I, Bongers BC, et al. Front Oncol. 2021 Jun 17;11:662013; Boukili IE, Flaris AN, Mercier F, et al. Scand 
J Surg. 2022 Apr-Jun;111(2):14574969221083394; Bruns ER, van den Heuvel B, Buskens CJ, et al. Colorectal Dis 2016; 
18(8):O267-77; Carli F, Zavorsky GS. Curr.Opin.Clin.Nutr.Metab Care. 2005; 8(1):23-32; Clegg A, Young J, Iliffe S, et al. 
Lancet. 2013 Mar 2;381(9868):752-62; Dale W, Hemmerich J, Kamm A, et al. Ann Surg 2014; 259(5):960-5; Dronkers 
JJ, Chorus AM, van Meeteren NL, et al. Anaesthesia 2013; 68(1):67-73; Dunne DF, Jack S, Jones RP, et al. Br J Surg 
2016; 103(5):504-512; Durrand JW, Moore J, Danjoux G. Anaesthesia 2021 Nov 18; Fearon KC, Jenkins JT, Carli F, et 
al. Br.J.Surg. 2013; 100(1):15-27; Fried TR, Bradley EH, Towle VR, et al. N Engl J Med 2002; 346(14):1061-6; Gillis C, 
Li C, Lee L, et al. Anesthesiology 2014; 121(5):937-47; Gillis C, Buhler K, Bresee L, et al. Gastroenterology 2018; 
155(2):391-410.e4; Heger P, Probst P, Wiskemann J, et al. J Gastrointest Surg 2019; Hijazi Y, Gondal U, Aziz O. Int J 
Surg 2017; 39:156-162; Howard R, Yin YS, McCandless L, et al. J Am Coll Surg 2019; 228(1):72-80; Kleve G, Fetveit T, 
Ougland R. Prehabilitering før kreftkirurgi – the new kid on the block. NGF nytt 1/2022; Kristjansson SR, Nesbakken A, 
Jordhoy MS, et al. Crit Rev Oncol Hematol 2010; 76(3):208-17; Lassen K, Coolsen MM, Slim K, et al. Clin.Nutr. 2012; 
31(6):817-830; Lemanu DP, Singh PP, MacCormick AD, et al. World J Surg 2013; 37(4):711-20; Li C, Carli F, Lee L, et 
al. Surg Endosc. 2013 Apr;27(4):1072-82; Malietzis G, Currie AC, Athanasiou T, et al. Br J Surg 2016; 103(5):572-80; 
Martin L, Birdsell L, Macdonald N, et al. J Clin Oncol 2013; 31(12):1539-47; Moran J, Guinan E, McCormick P, et al. 
Surgery 2016; 160(5):1189-1201; Mortensen K, Nilsson M, Slim K, et al. Br.J.Surg. 2014:10; Ommundsen N, Kristjansson 
SR, Wyller TB. European Geriatric Medicine, Vol. 4: Elsevier Science, 2013. pp. S90; Prado CM, Lima IS, Baracos VE, et 
al. Cancer Chemother Pharmacol 2011; 67(1):93-101; Sjetne IS, Bjertnaes OA, Olsen RV, et al. BMC Health Serv Res. 
2011 Apr 21;11:88; Su Z, Monshaugen I, Wilson B, et al. Nat Commun. 2022 Apr 20;13(1):2165; Symons TB, Sheffield-
Moore M, Wolfe RR, et al. J Am Diet Assoc 2009; 109(9):1582-6; Weimann A, Braga M, Carli F, et al. Clin Nutr 2017; 
36(3):623-650; Wilson RJ, Davies S, Yates D, et al. Br J Anaesth 2010; 105(3):297-303; Wischmeyer PE, Carli F, Evans 
DC, et al. Anesth Analg 2018; 126(6):1883-1895; Witard OC, Jackman SR, Breen L, et al. Am J Clin Nutr 2014; 99(1):86-
95.