Perioperative Exercise and Nutritional Optimisation Prehabilitation Before Surgery for Patients With Peritoneal Malignancy (PANO)

The PANO Trial: Perioperative Exercise and Nutrition Optimisation Prehabilitation in Cancer Patients With Peritoneal Malignancy

People who are diagnosed with cancer of the colon/rectum/appendix/ovaries that spreads into the lining of the tummy and some ovarian cancers or people with pseudomyxoma peritonei can often undergo intensive treatment including major surgery where chemotherapy is given whilst the person is having surgery - also known by doctors as surgery and hyperthermic intraperitoneal chemotherapy (HIPEC). Fitness for this surgery can improve if people undertake a prehabilitation programme at the time they get their diagnosis. To date, little research has focused on how exercise and nutrition support before surgery can help these patients during recovery. The aim of this study is to explore the use of exercise and nutritional support pre-treatment to enhance physical and psychological outcomes for patients.

Study Overview

• Status: Active, not recruiting
• Conditions: Ovarian Cancer; Colon Cancer; Appendix Cancer; Rectum Cancer; Peritoneal Malignancy
• Intervention / Treatment: Behavioral: Exercise; Behavioral: Nutrition

Detailed Description

The comparator in this study will be standard oncological care. Control patients will receive the same care as standard without the addition of a formal exercise and nutrition support programme. The pre-treatment (prehabilitation) programme will commence following diagnosis and continue up to the point of surgery and recommence for six weeks following surgery when deemed clinically fit to participate. Assessments will occur at baseline, pre-surgery, post-surgery, and 6 weeks later and a follow up... Mixed methods will be employed with patients taking part in self-report assessments, physical assessments, and qualitative interviews. The primary aim of the study is to assess the feasibility of the intervention and cardiorespiratory fitness pre-surgery. The secondary aims include assessing the effect of the intervention on physical health, psychological wellbeing, health-related quality of life, self-efficacy, nutrition, and serology markers. Exploratory aims also include post-operative morbidity, health economics analysis and qualitative interview of patient experience.

• Study Type: Interventional
• Enrollment (Actual): 36
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Aideen Scriney; Phone Number: 0879472033; Email: aidscriney@gmail.com
• Study Contact Backup: Name: Lorraine Boran, Dr.; Email: lorraine.boran@dcu.ie

Study Locations

• Ireland
  • Dublin, Ireland
    • Mater Misericordiae University Hospital
  • Dublin, Ireland
    • Dublin City University
  • Dublin, Ireland
    • Royal College of Surgeons , Ireland

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• age ≥18 years,
• multidisciplinary team referral for CRS-HIPEC for colorectal/appendix/ovarian peritoneal disease or pseudomyxoma peritonei (+/- completed neoadjuvant cancer treatment)
• WHO performance status ≤2.

Exclusion Criteria:

• inability to provide informed consent,
• impaired cognitive function with a reduced ability to either understand advice /instructions from or communicate with the research team,
• declined surgery,
• surgery in less than 2 weeks
• pregnancy or breastfeeding,
• inability to participate in the exercise training (unable to perform the 6 Minute Walk Test)
• absolute contraindications to exercise testing, veganism.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Health Services Research
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Intervention; Exercise: The exercise training program was designed to improve physical fitness prior to surgery and for a 6-week period after surgery once deemed fit. Nutrition: The nutritional arm consists of nutritional intervention tailored to the outcome of the nutritional screening.Participants will be asked to take part in a dietary food recall system called Foodbook24, and based on their dietary needs will be supported in nutritional optimisation.	Behavioral: Exercise; Standard Exercise Program- Participants will be invited to take part in a structured home, supervised, or both, exercise program while undergoing treatment and for a six-week period when deemed fit post-surgery.; Other Names: Tailored Exercise Prehabilitation Program; Behavioral: Nutrition; Participants will be screened for their nutritional health and tailored advice and education will be provided on an individualised basis. An online dietary recall tool will be used to track patients' dietary habits. This will occur from diagnosis until point of surgery and recommence for 6 weeks post-surgery once deemed physically fit.; Other Names: Nutritional Optimisation
No Intervention: Control; This group will receive standard oncological care and will receive no formal education of exercise or nutritional intervention.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Feasibility of Adherence to the Intervention	Prehabilitation fidelity in terms of the patient group adherence as measured by patient structured qualitative feedback and activity logs.	2-6 weeks pre surgery, 6 weeks post-surgery
Feasibility of participant retention to the Intervention	Prehabilitation fidelity in terms of the patient group retention as measured by patient screening and retention logs and monitoring of recruitment rates.	2-6 weeks pre-surgery, 6 weeks post-surgery
Feasibility of intervention effectiveness	Prehabilitation fidelity in terms of intervention effectiveness as measured by qualitative patient feedback at two timepoints. Monitoring of patient activity logs. Engagement with online and in-person exercise and nutritional intervention resources.	2-6 weeks pre-surgery, 6 weeks post-surgery
Change in Cardiorespiratory Fitness	Cardiorespiratory fitness using the 6-Minute Walk Test (6MWT) assessed at the pre-surgery time point. The 6MWT is performed with participants walking up and down a 20 m course marked by cones for 6 min under instruction to cover as much ground as possible. The number of laps completed is recorded. A standard set of instructions is used as per the European Respiratory Society guidelines. The 6MWT is a validated assessment of cardiorespiratory function in clinical populations.	2-6 weeks pre-surgery, 6 weeks post-surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Strength - The Handgrip Test	This is measured using a hand dynamometer. The test will be conducted in a standing position with the upper arm tight against the participant's trunk and the forearm at a right angle to the upper arm. If this is not possible the participant may sit in an upright chair or use their free hand to rest the dynamometer on a table to support the arm. The gripping handle will be set to a comfortable width to ensure the patient can rest the middle piece of the four fingers on the handle. The participant will be instructed to squeeze the handle with maximum force for a few seconds. The value on the scale will be recorded. The participant will complete two trials on each hand. The highest score will be accepted.	2-6 weeks pre-surgery, 6 weeks post-surgery
Change in Strength - The Stand to Sit Test	Participants will sit on a chair (height 43-45 cm) with arms crossed on their, and legs flat on the floor, parallel to each other, and approximately shoulder width apart. Participants will stand up and sit down 10 times as quickly as possible. Participants must not bounce off the chair when moving from a seated position to standing position. They must fully extend their legs on each stand. The time taken to perform 10 repetitions will be timed using a stopwatch. Participants will perform two trials and the best trial will be recorded as their score.	2-6 weeks pre-surgery, 6 weeks post-surgery
Change in Activity - 3-day ActivPAL3 triaxial accelerometer	Participants will be instructed to wear the device on the midpoint of the anterior aspect of the right thigh and attach using a film adhesive frame dressing. They will continue to wear this for three days continuously. They cannot wear the ActivPAL3 triaxial accelerometer during water activity periods.	2-6 weeks pre-surgery, 6 weeks post-surgery
Change in Psychological Stress	NCCN Distress Thermometer: To detect distress (psychosocial stress) with all stages of cancer. This is measured using a visual analogue scale like a thermometer to indicate a range from 0 (not loaded) to 10 (extreme pressure). Additional 36 items in five problem areas - practical family, emotional, spiritual, physical, are rated for distress and a score of 5 or higher is considered significant stress.	2-6 weeks pre-surgery, 6 weeks post-surgery
Change in Psychological Stress- Impact of Events Scale	This is a self-report measure of traumatic stress symptoms focused on intrusive thoughts and avoidant behaviours. Questions will be adapted to reflect the PM diagnosis specifically. Frequency of symptoms will be self-reported during the previous week using a 4 point scale from 0 (not at all) to 5 (often). Total scores range from 0 to 75 with higher scores indicative of greater cancer-related stress. Scores in the range of > 30 are reflective of clinically significant stress. Higher scores on an adapted IES are related to decreased immune function in breast cancer patients.	2-6 weeks pre-surgery, 6 weeks post surgery
Change in Cognitive Reserve-Cognitive Reserve Index (CR-IQ)	This questionnaire is a semi-structured interview with the patients that measures reserve in three parts: Education; Working-Activity, and Leisure time. Each sub-scale and total index score is correlated with age and expressed on a standardised scale.	2-6 weeks pre-surgery, 6 weeks post surgery
Change in Cognition- FACT-Cog	The Functional Assessment of Cancer Therapy- Cognition is a self-report 37 item questionnaire that assesses cancer related cognitive problems. Sub-scales include: Perceived cognitive impairments, impact of perceived cognitive impairments on QoL, Comments from others and perceived cognitive abilities.	2-6 weeks pre-surgery, 6 weeks post surgery
Change in Self-Efficacy	This is a 12 item Communication and Attitudinal Self-Efficacy scale for Cancer, and rates a patients' perceived ability to seek information, understand and engage in care, and maintain a positive attitude. Confidence level for each skill is rated on a 4 point scale with higher score indicative of higher self-efficacy.	2-6 weeks pre-surgery, 6 weeks post surgery
Change in Health Related Quality of Life (HrQoL)-EQ-5D-5L (5L)	This is a standardised and validated self-report measure describing health status. It is disease non-specific but applicable to cancer, with five dimensions (mobility, self-care, typical activities, pain, anxiety/depression) with three problem levels to rate (some to extremely problematic). The higher the index score, the higher the perceived health status.	2-6 weeks pre-surgery, 6 weeks post surgery
Change in Health Related Quality of Life (HrQoL)- FACT-G	This is a version of the Functional Assessment of Cancer Therapy is a 28-item self-report survey that measures quality of life; it has 5 sub-scales measures physical well-being (PWB), functional wellbeing (FWB), social/family wellbeing (SFWB), emotional wellbeing (EWB) and satisfaction with care. Self-ratings of all 5 subscales for the present moment and the preceding week are captured, computing an overall total score. Good Cronbach's for all five have been reported, and the higher the core the better the QoL.	2-6 weeks surgery, 6 weeks post surgery
Change in Nutritional Status-The Malnutrition Screening Tool	The Malnutrition Screening Tool (MST) is an easy to administer tool. It is based on recent appetite and weight loss and has been previously validated for use with oncology patients. The measure scores both "recent intake" and "recent weight loss". A total score of >2 indicates a risk of malnutrition.	2-6 weeks pre-surgery, 6 weeks post surgery
Change in Nutritional Status- Glasgow Prognostic Score	This measure of cancer prognosis is measured using serum markers CRP and Albumin. The score is used to measure the cancer prognosis. The score ranges from 0-2, with patients with a normal measure of CRP assigned a score of zero, and those with both elevated or reduced levels a score of 2.	2-6 weeks pre-surgery, 6 weeks post surgery
Change in Dietary Intake - Foodbook24	Foodbook24 is a Web-based, dietary tool consisting of a 24-hour dietary recall and food frequency questionnaire. Patients will provide dietary recall information about what they have eaten in the past 24 hours.	2-6 weeks pre-surgery, 6 weeks post surgery
Change in Nutritional Status- Blood Screening	Bloods should be ordered by clinician for Iron (Fe) analysis (identify anaemia) and CT scans of patients should be analysed for the identification of incidence of sarcopenia.	2-6 weeks pre-surgery, 6 weeks post surgery

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Post-operative Morbidity- Post-surgery Morbidity Score	This is an 18-item tool that addresses morbidity relevant to the post-surgical patient.	Day 2 post
Post-operative Morbidity- The Clavien-Dindo classification	This is a classification of surgical complications with seven grades. The Comprehensive Complication Index (CCI) sums all post-operative complications with their respective severities on a scale of 0 (no burden) to 100 (fatality).	Day 15 post
Post-Operative Morbidity- Comprehensive Complication Index	The Comprehensive Complication Index (CCI) sums all post-operative complications with their respective severities on a scale of 0 (no burden) to 100 (fatality).	Day 15 post
Post-Operative Morbidity - Length of Hospital Stay	Length of stay in hospital as a result of their operation.	Day 1-15 post surgery
Health Economic- Exploratory Analysis	An exploratory analysis will review healthcare resource use by individual participants and with locally determined unit cost calculate the healthcare cost related to the two interventions. The mean group difference in accumulated costs will be used in the cost-effectiveness analysis.	2-6 weeks pre surgery, 6 weeks post surgery
Serology Markers- Exploratory Analysis	Biomarkers will be analysed on a sub-group (n=20) of recruited participants. Serological markers of inflammation using a multiplexed ELISA approach will be measured. The Luminex system can measure up to 45 serum cytokines and markers of inflammation, including the inflammatory cytokine IL-6, which has been associated with increased PS and PA. Inflammatory markers will be assessed at baseline, pre-surgery and post-surgery and 6 weeks post. Blood samples are taken routinely pre and post-surgery but for the purpose of the study the two additional timepoints of baseline/consent and 6 weeks post will also be taken. Using this dynamic approach, we will be able to correlate a patient's inflammatory response with their outcome during their prehabilitation and after surgery.	2-6 weeks pre-surgery, 6 weeks post surgery
Qualitative Experience - Qualitative Patient Experience	Patients will also be asked whether they consent to take part in a short semi-structured phone interview with a member of the research team across two timepoints: pre surgery and 6 weeks post. The interviewer will ask the patients exploratory questions relating to four main topics: 1) Participants experiences and engagement with their care pathway (both control and intervention) 2) Perceptions of their emotional and physical preparation before surgery 3) Perceptions of their condition pre and post-surgery 4)Perceptions of physical and emotional symptoms pre and post-surgery.	2-6 weeks pre surgery- 6 weeks post surgery
Change in Smoking Status	Participants will be asked for their smoking status. If participants are active smokers who would like to cease smoking, they will be provided with the National Centre for Smoking Cessation and Training information support packages.	2-6 weeks pre surgery, 6 weeks post surgery

Collaborators and Investigators

• Sponsor: Dublin City University
• Collaborators: Royal College of Surgeons, Ireland; Mater Misericordiae University Hospital
• Investigators: Principal Investigator: Jurgen Mulsow, Mr., Mater Misericordiae University Hospital; Principal Investigator: Lisa Loughney, Dr., Royal College of Surgeons, Ireland; Principal Investigator: Lorraine Boran, Dr., Dublin City University

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2022
• Primary Completion (Estimated): June 1, 2024
• Study Completion (Estimated): August 1, 2024

Study Registration Dates

• First Submitted: February 15, 2022
• First Submitted That Met QC Criteria: March 23, 2022
• First Posted (Actual): March 31, 2022

Study Record Updates

• Last Update Posted (Actual): March 21, 2024
• Last Update Submitted That Met QC Criteria: March 20, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: Peritoneal Malignancy
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms; Cecal Diseases; Cecal Neoplasms; Neoplasms; Rectal Neoplasms; Appendiceal Neoplasms
• Other Study ID Numbers: COALESE/2021/103 (Other Grant/Funding Number: Irish Research Council)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No