Prehabilitation to Improve Cancer Surgery Outcomes in AYA Patients With Extremity Sarcomas (PICaSO-ES)

Prehabilitation to Improve Cancer Surgery Outcomes in AYA Patients With Extremity Sarcomas (PICaSO-ES): A Proof-of-Concept Trial

The purpose of this study was to evaluate the feasibility of a multimodal prehabilitation intervention intended to optimize postoperative recovery in adolescents and young adults (AYAs) diagnosed with soft tissue and bone-based sarcomas of the upper and lower extremities (extremity sarcomas; ES).

Study Overview

• Status: Completed
• Conditions: Osteosarcoma; Sarcoma,Soft Tissue
• Intervention / Treatment: Behavioral: Multimodal prehabilitation

Detailed Description

Objectives:

This objective of this study was to investigate the feasibility of multimodal prehabilitation for adolescents and young adults (AYAs) diagnosed with soft tissue and bone-based sarcomas of the upper and lower extremities (extremity sarcomas; ES) and explore its effects on measurements of health-related quality of life, physical function, length of hospital stays, and post-operative complications. Specific aims of the study included:

• To determine the feasibility of conducting a larger phase II investigation of HIIT-based multimodal prehabilitation according to three primary criteria, including (i) recruiting >=50% of otherwise eligible patients (OEP; i.e., patients meeting all eligibility criteria), (ii) no patient experiences a testing-related or an intervention-related serious adverse event (SAE), and (iii) patients achieve an exercise intervention adherence rate of >=70%.
• To further determine the feasibility of conducting a larger phase II investigation of HIIT-based multimodal prehabilitation according to the secondary feasibility criteria.
• To explore the preliminary effects of prehabilitation on measures of short-term perioperative outcomes including health-related quality of life, physical function, length of hospital stays, and post-operative complications.

Methods:

A single-arm, proof-of-concept trial design was informed by the ORBIT model of behavioural treatment development. Mixed methods were employed to obtain relevant context for investigating the feasibility of multimodal prehabilitation in newly diagnosed AYAs with ES within the circumstances of the COVID-19 pandemic.

Participants underwent virtual multimodal prehabilitation before undergoing major extremity sarcoma surgery. This program encompassed personalized exercise, nutrition, and stress management support delivered by a registered kinesiologist, registered dietitian, and clinical psychologist, respectively. The interventions were designed to enhance physical and psychological resilience to stress, with the objective of improving recovery outcomes and mitigating the risk of adverse events.

Feasibility (e.g., recruitment, safety, tolerability), physical function, and patient-reported outcomes were measured at baseline (T0), immediately preoperatively (T1), and one month postoperatively (T2).

Feasibility data and field notes were collected by the research coordinators (during recruitment and postoperative follow-up) and by the study lead / research assistants during the intervention period. A postoperative interview explored experiences with prehabilitation into explore the feasibility and practical considerations of virtual prehabilitation for adolescents and young adults with extremity sarcomas.

• Study Type: Interventional
• Enrollment (Actual): 7
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5G2C4
      • University Health Network

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 39 years (Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• ≥18 years and <40 years of age at diagnosis
• Fluent in English
• Able to comply with study and follow-up procedures contained within the consent form
• Pathologically or radiologically confirmed diagnosis of a soft-tissue or osteosarcoma of the upper or lower extremities
• Soft-tissue or osteosarcoma must be considered operable
• Patients of all weight bearing states will be eligible
• Expected LOS ≥ 5 days as calculated by the validated American College of Surgeons Surgical Risk Calculator
• >14 days between time of randomization and time of expected surgery
• Patient written, informed consent obtained according to ICH GCP guidelines and local regulations
• Medical clearance to participate in the study from either the primary treating surgeon (JW, PF) or oncologist (AG)

Exclusion Criteria:

• Planned resection of bony pelvis or major lower extremity neurovascular structures

• Significant comorbidity including any of the following:

  • Canadian Cardiovascular Society class III/IV coronary disease
  • New York Heart Association class III/IV congestive heart failure
  • Neurologic or musculoskeletal disorder prohibiting exercise
  • Major neuropsychiatric disorder
• High-risk or presence of pathological fracture

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Multimodal Prehabilitation; Facility and home-based multimodal prehabilitation (aerobic exercise training, resistance exercise training, nutrition support, stress management and mindfulness training)

Behavioral: Multimodal prehabilitation; Multimodal Prehabilitation; Aerobic exerciseHome-based, high-intensity interval training (HIIT), 2 days/weekHome-based, moderate-intensity continuous training (MICT), 2-3 days/week; Resistance exerciseHome-based, moderate-intensity resistance training, 2-3 d/wk, all major muscle groups (working around tumour-related deficits), 8-10 exercises, 12-15 repetitions, resistance bands and body weight based; NutritionProtein intake 1.2-1.5 g/kg body weight/day in compliance with European Society for Clinical Nutrition and Metabolism (ESPEN) guidelines; Stress managementDaily mindfulness practice, 20 min/session, guided by audio file created at Mount Sinai Hospital

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Patient recruitment rate (feasibility target: >=50% of eligible participants)	Defined as the percent of consenting patients based on the total number of otherwise eligible patients (OEP; patients meeting all study eligibility criteria) approached	Initiation through end of study recruitment at 12 months
Testing- and intervention-related serious adverse events (feasibility target: none)	Defined as the number and frequency of testing- and intervention-related serious adverse events (SAEs) according to the Common Terminology Criteria for Adverse Events	Initiation through end of pre-operative testing
Patient exercise adherence (feasibility target: >=70% of prescribed)	Defined as relative dose intensity as the percent of total dose of exercise performed relative to the total planned dose prescribed and quantified according to metabolic equivalents	Initiation through end of study intervention period

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Patient identification rate (feasibility target: >=50% of OEP)	Defined as the average number of OEP identified each month	Initiation through end of study recruitmentat 12 months
Baseline assessment rate (feasibility target: >=90% of consenting participants)	Defined as the percent of consenting patients who successfully complete baseline assessments based on the total number of consenting patients	Initiation through end of study recruitment at 12 months
Pretreatment intensity modification (feasibility target: <=25% of participants)	Defined as the percent of sessions which required pre-exercise modification of the target exercise intensity due to a pre-exercise screening indication (e.g., fatigue, pain)	Initiation through end of study intervention period
Intervention window (feasibility target: >=21 days)	Defined as the average elapsed time (in days) between diagnosis and extremity sarcoma surgery	Initiation through end of study intervention period
Testing- and intervention-related non-serious adverse events (feasibility target: <20% of sessions)	Defined as the number and frequency of testing- and intervention-related non-serious adverse events (nSAEs) according to the Common Terminology Criteria for Adverse Events	Initiation through end of pre-operative testing
Testing performance (feasibility target: >=95% completion of tests)	Defined as percent completion physical testing at baseline and follow-up	Initiation through end of pre-operative testing
Testing modality adaptations (descriptive)	Defined as the percent of all tests which are adapted for functional or safety reasons	Initiation through end of pre-operative testing
Training modality adaptations (descriptive)	Defined as the percent of all exercise sessions which are adapted for functional or safety reasons	Initiation through end of study intervention period
Permanent treatment discontinuation (feasibility target: <=15% of participants)	Defined as the percent of patients who discontinue intervention participation prior to the planned end of the intervention period	Initiation through end of study intervention period
Treatment interruption (feasibility target: <=15% of participants)	Defined as the percent of patients who miss ≥3 consecutive sessions within the intervention period	Initiation through end of study intervention period
Dose modification (feasibility target: <=25% of participants)	Defined as the percent of exercise sessions requiring a dose reduction during training (i.e., intensity or duration) relative to the total number of sessions completed. Total number of exercise sessions with a reduction in intensity or a reduction in duration will be combined into the numerator when calculating the percentage of affected sessions.	Initiation through end of study intervention period
Early session termination (feasibility target: <=25% of participants)	Defined as the percent of exercise sessions requiring unplanned early termination	Initiation through end of study intervention period
Physical prehabilitation compliance (feasibility target: >=70% of prescribed)	Defined as the percent of exercise sessions completed based on the total number of sessions prescribed	Initiation through end of study intervention period
Mindfulness prehabilitation compliance (feasibility target: >=70% of prescribed)	Defined as the percent of psychological sessions completed based on the total number of sessions prescribed	Initiation through end of study intervention period
Attrition (feasibility target: <=20% loss to follow-up)	Defined as the percent loss to follow-up (not completing follow-up assessments), individually and overall	Study initiation through end of 1 month postoperative (T2)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Length of stay	Average postoperative hospitalization period	1 month postoperative (T2)
Functional capacity	Total distance traveled during six-minute walk test	Baseline (T0), preoperative (T1)
Global health score	Primary exploratory outcome: European Organization for the Research and Treatment of Cancer (EORTC) QLC-C30	Baseline (T0), preoperative (T1), 1 month postoperative (T2)
Postoperative complications	Postoperative complication severity and frequency defined according to the Common Terminology Criteria for Adverse Events.	1 month postoperative (T2)
Physical activity behavior (subjective)	Godin Leisure-time Exercise Questionnaire	Baseline (T0), preoperative (T1), 1 month postoperative (T2)
Health-related quality of life	EQ-5D; All 5 items are rated on a 1 to 3 scale with higher numbers reflecting worse outcomes.	Baseline (T0), preoperative (T1), 1 month postoperative (T2)
Symptom burden	Edmonton Symptom Assessment Scale (ESAS); All 10 items are rated on a 0 to 10 scale with higher numbers reflecting worse outcomes.	Baseline (T0), preoperative (T1), 1 month postoperative (T2)
Anxiety and depression	Hospital Anxiety and Depression Scale (HADS); All 14 items are rated on a 0 to 3 scale with higher numbers reflecting worse outcomes.	Baseline (T0), preoperative (T1), 1 month postoperative (T2)
Fatigue	Functional Assessment of Chronic Illness Therapy-Fatigue scale (FACIT-F); All 13 items are rated on a 0 to 4 scale with higher numbers reflecting worse outcomes.	Baseline (T0), preoperative (T1), 1 month postoperative (T2)
Impact on work	Work Limitations Questionnaire	Baseline (T0), preoperative (T1), 1 month postoperative (T2)
Social support	Medical Outcomes Study Social Support Scale (SF-20); All item scores transformed into 0 to 100 scales with higher scores reflecting better outcomes.	Baseline (T0), preoperative (T1), 1 month postoperative (T2)
Relationships	Experiences in Close Relationships scale (ECR); All 36 items rated on a 1 to 7 scale with higher scores reflecting worse outcomes.	Baseline (T0), preoperative (T1), 1 month postoperative (T2)
Extremity function	Toronto Extremity Salvage Score (upper or lower)	Baseline (T0), preoperative (T1), 1 month postoperative (T2)
Disease burden	Musculoskeletal Tumor Society score	Baseline (T0), preoperative (T1), 1 month postoperative (T2)

Collaborators and Investigators

• Sponsor: University Health Network, Toronto
• Collaborators: MOUNT SINAI HOSPITAL
• Investigators: Principal Investigator: Daniel R Santa Mina, PhD, University of Toronto; University Health Network

Study record dates

Study Major Dates

• Study Start (Actual): February 2, 2022
• Primary Completion (Actual): April 26, 2023
• Study Completion (Actual): April 26, 2023

Study Registration Dates

• First Submitted: January 22, 2020
• First Submitted That Met QC Criteria: January 28, 2020
• First Posted (Actual): January 30, 2020

Study Record Updates

• Last Update Posted (Estimated): December 27, 2023
• Last Update Submitted That Met QC Criteria: December 20, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Keywords: Prehabilitation; Preoperative Care; Exercise Therapy; Adolescents and Young Adults; Extremity Sarcoma
• Additional Relevant MeSH Terms: Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Bone Tissue; Neoplasms, Connective Tissue; Sarcoma; Osteosarcoma
• Other Study ID Numbers: 18-5901; 18-0226 (Other Identifier: Toronto Academic Health Sciences Network)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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