Identifying Mediators of Exercise-induced Tumor Microenvironment Remodeling to Enhance Primary Chemotherapy Response (IMPROVE-Ovarian)

Participants who opt-in to the exercise intervention will be in this arm. The intervention will include a tele-health delivered exercise program (resistance and aerobic exercise) lasting 9-12 weeks concurrent with their neoadjuvant chemotherapy.

The exercise intervention will last approximately 9-12 weeks, running concurrently with their neoadjuvant chemotherapy, and will include resistance training two times per week and aerobic exercise 3-5 times per week. The prescribed exercise will be personalized based on the participant's baseline functionality and will be adjusted as needed throughout their participation based on any disease or chemotherapy-related side effect.

The UC group will not receive any intervention during study participation and will undergo usual medical treatment. There is no intervention for this arm. They will be provided with a welcome packet with basic study information and educational materials on exercise during cancer treatment and their research participation will be surveillance-based assessments only during the duration of the study.

The UC group will not receive any intervention during study participation and undergo usual medical treatment and surveillance during the duration of the study.

Acceptability will be defined as ≥60% of women approached for study participation will agree to participate and opt in to the exercise intervention.

Exercise adherence will be calculated as the proportion of completed exercise sessions over the number of prescribed sessions.

Feasibility will be defined as ≥60% adherence to the prescribed exercise intervention.

Cardiorespiratory fitness will be measured using the six minute walk test. The 6MWT is an objective evaluation of functional exercise capacity. Its results are highly correlated with those of the 12-minute walk test from which it was derived and with those of cycle ergometer or treadmill-based exercise tests.

Lower body strength will be evaluated using the 30 second chair stand test. The participant is seated in the middle of the chair, back straight, feet approximately shoulder width apart and placed on the floor. Arms are crossed at the wrists and held against the chest. At the signal "go," the participant rises to a full body stand and then returns to the initial seated position. The participant is encouraged to complete as many full stands as possible within 30 seconds.

Cardiorespiratory fitness will be measured with the 2-minute step test. Participants will be marching in place for 2 minutes and are encouraged to use a chair for balance or do the assessment seated if standing is too difficult. They should be lifting their legs about 6 inches off the ground, as if they were stepping onto a curb from the road. The tester will count the number of times the participant raises their right leg off the ground.

The TUG evaluates lower body strength, balance, and agility. The patient sits in a chair and on the command "go", the patient rises from the chair, walks 3 meters at a self-selected pace, turns around an obstacle, walks back to the chair and sits down. Test results may also be quantified assessing the time (seconds) needed to complete the assessment.

Maximum capacity to squeeze with each hand may be assessed using a hand grip dynamometer. Each hand may be assessed three times.

The SPPB is a short battery of performance tests of lower extremity functioning. The tests measure gait speed, standing balance, and lower extremity strength and power. To test gait speed, patients are instructed to walk an 4-meter walking course at their usual pace with assistive devices if needed. Three progressively more challenging positions are used to test balance (bipedal [feet next to each other], semi-tandem [one foot slightly in front of the other], and full tandem [one foot in front of the other]). To test lower extremity strength, patients are asked to stand up and sit down five times as quickly as possible and are timed from the initial sitting position to the final standing position at the end of the fifth stand. The scores for the overall assessment is the sum of the scores of each of the subtests. The scores for the individual subtests on their own are not research validated data points.

Min = 0; Max = 12; higher score = better performance

The SARC-F questionnaire is a short 5-item battery containing observational assessments that is a rapid diagnostic test for sarcopenia. There are 5 SARC-F components: Strength, Assistance with walking, Rise from a chair, Climb Stairs, and Falls.

Min = 0; Max = 10; higher score = higher risk for sarcopenia

The Edmonton Frail Scale is a reliable measure for frailty that is easy to use, captures the multidimensional aspects of fatigue, and presents the level of frailty along a continuum so that change over time can be captured. The semi-structured interview collects data across 9 frailty domains: cognition, general health status, functional independence, social support, medication use, nutrition, mood, continence, and functional performance. Scores fall within one of 5 categories (not frail, vulnerable, mild frailty, moderate frailty, severe frailty) and range from 0 (not frail) to 17 (severe frailty).

Min = 0; Max = 17; higher score = higher frailty risk

The Fried Frailty Index is a short battery of physical performance tests and observational assessments that evaluate phenotypic frailty. The index evaluates weight loss in the past year, weakness via grip strength, self-reported fatigue, gait speed, and self-reported physical activity levels. The score for the index is the sum of the scores of each of the measured items listed above. The scores for the individual items on their own are not research validated data points.

Min = 0; Max = 5; higher score = higher frailty risk

QoL may be assessed with the validated 30-item self-assessment questionnaire of the European Organization for Research and Treatment of Cancer (EORTC QLQ-C30, version 3.0). It includes five multi- item functional scales (physical, role, emotional, cognitive, and social function), three multi-item symptom scales (fatigue, pain, nausea/vomiting), and six single items assessing further symptoms (dyspnea, insomnia, appetite loss, constipation, diarrhea) and financial difficulties. Scores are derived according to the EORTC scoring manual.

All of the scales and single-item measures range in score from 0 to 100. A high scale score represents a higher response level.

Thus, a high score for a functional scale represents a high/healthy level of functioning, a high score for the global health status/QoL represents a high QoL, but a high score for a symptom scale/item represents a high level of symptomatology/problems.

Ovarian cancer specific QoL may be further assessed with the validated 28-item self-assessment questionnaire of the European Organization for Research and Treatment of Cancer (EORTC QLQ-OV28). It includes seven multi-item symptom and functional scales (abdominal/gastrointestinal symptoms, peripheral neuropathy, other chemotherapy side effects, hormonal/menopausal symptoms, body image, attitude to disease treatment, and sexual functioning). Scores are derived according to the EORTC scoring manual.

All of the scales and single-item measures range in score from 0 to 100. A high scale score represents a higher response level.

Thus, a high score for a functional scale represents a high/healthy level of functioning, a high score for the global health status/QoL represents a high QoL, but a high score for a symptom scale/item represents a high level of symptomatology/problems.

Fatigue may be assessed with the Multidimensional Fatigue Inventory (MFI) which is a 20-item, multidimensional self-assessment questionnaire. It covers five different dimensions of fatigue (general, physical, reduced activity, reduced motivation, and mental). Scores are derived by summing the answers (five-stage scale) of the appropriate items.

Min = 20; Max = 100; higher score = less fatigue

Physical activity patterns during a patient's leisure time may be assessed using the Godin Leisure Time Exercise questionnaire. The questionnaire asks patients to recall, during a seven-day period, the frequency to which they participated in strenuous, moderate, and mild exercise. The Godin questionnaire is short and easy to complete.

Min = 0; Max = none; higher score = more activity

Cognitive function may be measured by the 8-item PROMIS questionnaire. The questionnaire assesses patient-perceived cognitive deficits including mental acuity, concentration, verbal and nonverbal memory, verbal fluency, and perceived changes in these cognitive functions.

Min = 8; Max = 40; higher score = better cognitive function

The Patient-Generated Subjective Global Assessment (PG-SGA) is a patient-reported instrument for assessment of nutrition status in patients with cancer. The PG-SGA short form is completed by patients and screens for nutritional risk and deficit.

Min = 0, Max = 36; higher score = worse nutrition status

The BPI is a 9-item, self-assessment questionnaire that has been largely validated. The BPI measures both the intensity of pain (sensory dimension) and interference of pain in the participant's life (reactive dimension). It also asks the participant about pain relief, pain quality, and participant perception of the cause of pain.

Pain Severity: Min = 0; Max = 40; higher score = higher pain severity Pain Interference: Min = 0; Max = 7; higher score = higher pain interference

The FIM is a 4-item measure used to measure and compare participant feasibility of an intervention. This will only be completed by those in the EX group.

Min = 4; Max = 20; higher score = higher intervention feasibility

The AIM is a 4-item measure used to measure and compare participant acceptability of an intervention. This will only be completed by those in the EX group.

Min = 4; Max = 20; higher score = higher intervention acceptability

The PRO-CTCAE is a patient-reported outcome measure developed to evaluate symptomatic toxicity in patients on cancer clinical trials. The PRO-CTCAE item library contains 124 items representing 78 symptomatic toxicities. Specific items will be selected to create an individualized form specific to this study population. The questions ask first about the presence of different symptoms, then, if the symptom is present, follow up questions will automatically populate asking about the severity and/or interference for that particular symptom. The PRO-CTCAE will be used to design the weekly Ecological Momentary Assessments.

Symptom Frequency: Min = 0; Max = 44; higher score = higher symptom frequency Symptom Severity: Min = 0; Max = 60; higher score = higher symptom severity Symptom Interference: Min = 0; Max = 56; higher score = higher symptom interference