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 Pilot Randomized Controlled Trial

The purpose of this study is 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).

Objectives: The objective of the study is to determine if a larger investigation of HIIT-based multimodal prehabilitation is feasible in AYA patients awaiting major ES surgery. Specific aims of the study are: 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 effect of prehabilitation on global health score, preoperative cardiorespiratory fitness, physical function, short-term perioperative outcomes, and patient-reported outcomes (e.g., symptom burden and health-care utilization). Methods: This pilot study is a phase I, two-arm randomized control trial to assess the feasibility of high-intensity interval training-based multimodal prehabilitation in newly diagnosed AYAs with ES. Patients will be randomized to either the prehabilitation group or the usual care group. Patients in the prehabilitation group will be prescribed both physical and psychological prehabilitation prior to undergoing major extremity sarcoma surgery (described below). The usual care group will be counseled to continue their current level of activity and given the information on exercise as outlined in the Cancer Care Ontario guidelines. Patients in the usual care group will also be given the same physical activity trackers and weekly exercise tracking logs as the patients in the prehabilitation group to eliminate the effect of activity tracking as an intervention itself and to facilitate descriptive comparisons of physical activity engagement between the groups. Feasibility (e.g., recruitment, safety, tolerability), clinical, fitness, patient-reported outcomes and health system utilization outcomes will be evaluated. Outcomes will be measured at baseline (T0), immediately preoperatively (T1), and postoperatively at one (T2), three (T3) and six (T4) months. Feasibility data will be collected via logs completed by the research coordinators (during recruitment and postoperative follow-up) and by the study lead / research assistants (during the intervention period in person (during each supervised exercise session) and via weekly patient phone calls (usual care group only)).

Preoperative Care, Exercise Therapy, Prehabilitation, Extremity Sarcoma, Adolescents and Young Adults

Facility and home-based multimodal prehabilitation (aerobic exercise training, resistance exercise training, mindfulness)

Self-directed physical activity and provision of Cancer Care Ontario's physical activity guidelines for cancer survivors

Physical Prehabilitation: Combination facility-/home-based exercise consisting of aerobic exercise (4-5 days/week (d/wk)), resistance exercise (2-3 d/wk), and daily mindfulness practice. Aerobic exercise Facility-based, high-intensity interval training (HIIT), 2 d/wk, 35 min/session, 4-min work and 3-min recovery period; cycle ergometer or arm ergometer (for those who cannot weight-bear) at 75% to 95% of baseline VO2peak Home-based, moderate-intensity continuous training (MICT), 2-3 d/wk, >=30 min/session, brisk walking (or equivalent) aiming to achieve a target HR of 40-70% of maximal HR Resistance exercise Home-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 Psychological Prehabilitation: Daily mindfulness practice, 20 min/session, and guided by audio file created at Mount Sinai Hospital

Defined as the percent of consenting patients based on the total number of otherwise eligible patients (OEP; patients meeting all study eligibility criteria) approached

Defined as the number and frequency of testing- and intervention-related serious adverse events (SAEs) according to the Common Terminology Criteria for Adverse Events

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

Defined as the percent of consenting patients who successfully complete baseline assessments based on the total number of consenting patients

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

Defined as the percent of patients who discontinue intervention participation prior to the planned end of the intervention period

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.

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)

Defined as the percent of exercise sessions completed based on the total number of sessions prescribed

Defined as the percent of psychological sessions completed based on the total number of sessions prescribed

Defined as the percent loss to follow-up (not completing follow-up assessments) for the PREHAB and UC groups, individually and overall

Primary exploratory outcome: European Organization for the Research and Treatment of Cancer (EORTC) QLC-C30

Baseline (T0), preoperative (T1), 1 month postoperative (T2), 3 months postoperative (T3), 6 months postoperative (T4)

Postoperative complication severity and frequency defined according to the Common Terminology Criteria for Adverse Events.

Baseline (T0), preoperative (T1), 1 month postoperative (T2), 3 months postoperative (T3), 6 months postoperative (T4)

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), 3 months postoperative (T3), 6 months postoperative (T4)

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), 3 months postoperative (T3), 6 months postoperative (T4)

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), 3 months postoperative (T3), 6 months postoperative (T4)

Baseline (T0), preoperative (T1), 1 month postoperative (T2), 3 months postoperative (T3), 6 months postoperative (T4)

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), 3 months postoperative (T3), 6 months postoperative (T4)

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), 3 months postoperative (T3), 6 months postoperative (T4)

Baseline (T0), preoperative (T1), 1 month postoperative (T2), 3 months postoperative (T3), 6 months postoperative (T4)

Baseline (T0), preoperative (T1), 1 month postoperative (T2), 3 months postoperative (T3), 6 months postoperative (T4)

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