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Exploring the Effect of Exercise Physiology Intervention Among Adolescent and Young Adults Diagnosed With Cancer

Murnane, Andrew, MaApplSci, Grad Dip, AEP1; Thompson, Kate, MASW, BA, BSW2; Mancuso, Sam G., PhD (Clinical Psychology)3; Lewin, Jeremy, MBBS (hons), FRACP, GradCert AHW4; Orme, Lisa M., MBBS, FRACP5

doi: 10.1097/01.REO.0000000000000134

Background: Exercise in the adult oncology setting has proven to be an effective intervention in improving patients' physical condition and mental health and reducing treatment side effects; however, its role in the adolescent and young adult (AYA) population is less well understood. This study aimed to explore the effects of an exercise physiology (EP) intervention on the functional capacity of AYA diagnosed with malignancy.

Methods: A prospective, single-institution cohort study was conducted of all AYA patients who were referred to the EP service and participated in baseline and postintervention assessment. Patients were provided with an individualized exercise program aimed at improving functional capacity as measured by the Six-Minute Walk Test, maximum push-ups, arm curls, and Sit-to-Stand Test, and a hand-held dynamometer was used to measure limb strength.

Results: Fifty-one patients were included in the analysis, with predominant histological subgroups being sarcoma (37%) and lymphoma (26%). Thirty-seven percent of patients completed the program while on treatment and 63% were posttreatment. For those on treatment, there were significant improvement between baseline and postintervention strength assessments in sit-to-stand, push-ups, and arm curls, with robust effect sizes (Cohen's dR) ranging from small (dR = −0.02, U3 = 49%) to large (dR = 1.05, U3 = 85%). For posttreatment AYA, there were differences between all baseline and postintervention functional and strength assessments, with effect sizes ranging from small (dR = 0.30, U3 = 61.8%) to large (dR = 1.29, U3 = 90.1%).

Conclusion: An individualized exercise intervention had a positive effect on AYA cancer patients' physical performance both while undergoing treatment and posttreatment. Future randomized controlled trials are required to validate these findings.

1Exercise Physiologist, ONTrac at Peter Mac Victorian Adolescent and Young Adult Cancer Service, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia

2Program Manager, ONTrac at Peter Mac Victorian Adolescent and Young Adult Cancer Service, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia

3Senior Research Assistant, ONTrac at Peter Mac Victorian Adolescent and Young Adult Cancer Service, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia; and Research Fellow, Department of Psychiatry, The University of Melbourne, Parkville, Victoria, Australia

4Department of Medical Oncology, Peter MacCallum Cancer Centre, and Medical Director, ONTrac at Peter Mac Victorian Adolescent & Young Adult Cancer Service, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia and Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, Australia

5Paediatric and Adolescent Oncologist, Children's Cancer Centre, Royal Children's Hospital, Parkville, Australia and Medical Oncologist, Sarcoma Service ONTrac at Peter Mac Victorian Adolescent & Young Adult Cancer Service, Peter MacCallum Cancer Centre, Melbourne, Australia

Correspondence: Andrew Murnane, ONTrac at Peter Mac, Peter MacCallum Cancer Centre, Locked Bag 1 A'Beckett St, Melbourne, VIC 8006, Australia (

The authors declare no conflicts of interest.

In Australia, approximately 1000 adolescents and young adults (AYA) aged 15 to 25 years are diagnosed with cancer each year.1 Advances in cancer treatment will now see between 73% and 82% of these young people surviving beyond 5 years2,3 such that an increasing number of AYA are living many decades with the physical and psychosocial sequelae of their cancer and its treatment.4–11 It is increasingly recognized that AYA cancer survivors have unique care and support needs compared with younger children and older adults.12–15 It is the complexity of this life stage that is now recognized as influencing the poorer long-term health outcomes of AYA in comparison with survivors of childhood cancer and their healthy peers.5,9,11,16,17 These significant challenges can contribute to long-term chronic health problems and general difficulty in building productive and meaningful lives after cancer.4 Therefore, it is essential to understand health-related behaviors in the AYA cancer population, identify those at greatest risk of negative outcomes, understand influencing factors, and promote behaviors that enhance long-term physical, social, and emotional well-being.18,19

Studies from the adult and pediatric oncology setting have shown that exercise can improve patients' physical functioning, reduce treatment-related side effects (eg, fatigue), and contribute to positive mental health/overall well-being both on treatment and in survivorship.20–26 However, the role of exercise in the AYA cancer population is less well understood. The limited research in AYA has found that although AYA have a keen interest in tailored exercise information from an exercise physiologist or specialist, this service is rarely provided.18,27–29 Research has also shown that AYA are known to experience a higher prevalence of chronic conditions than healthy peers and siblings, including cardiovascular disease, hypertension, diabetes, and obesity, all of which are potentially modifiable through regular exercise.5,9,11,16,17 Despite the importance of exercise and its potential role in preventive medicine, less than half of AYA patients meet public health exercise guidelines posttreatment.18,27,28 It is therefore possible that access to exercise physiology (EP) services and the provision of advice and support around the benefits of exercise and healthy living may improve long-term health outcomes and prevent other associated chronic diseases.18,28,30 Thus, the aim of the study was to assess changes in functional capacity among adolescents and young adult cancer patients who had completed an EP prescribed intervention.

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Design and Setting

A prospective, single-institution cohort study was undertaken at a large specialist oncology facility in Melbourne, Australia. Participants were recruited from all patients referred for EP intervention within the ONTrac at Peter Mac Victorian Adolescent and Young Adult Cancer Service (ONTrac at Peter Mac), a statewide cancer service for 15- to 25-year-olds diagnosed with cancer in the state of Victoria. The study was approved by the local Human Research Ethics Committee (15/28L).

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Patient Population

Eligible patients were aged between 15 and 25 years at the time of diagnosis and referred to the EP service between May 28, 2013, and April 23, 2014, inclusive. Patients were included if they completed baseline functional assessment, exercise intervention (8-12 weeks in duration), and postintervention functional assessment. Patients in the off-treatment group had completed cancer therapy within the past 2 to 8 weeks prior to baseline assessment. Patients in the on-treatment group completed baseline assessment, exercise intervention, and postintervention assessment while undergoing cancer therapy.

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Recruitment Procedure and Study Procedures

All patients referred to the ONTrac at Peter Mac were screened and triaged for supportive care services by a member of the multidisciplinary team. Patients referred for EP underwent baseline functional assessment as part of standard care. Assessment measures chosen for each patient depended upon performance status, cancer diagnosis, cancer treatment, symptoms, and preexisting comorbidities. All functional assessment measures along with individualized exercise prescription (and progression) and supervised exercise sessions were carried out by accredited exercise physiologists and student exercise physiologists. All patients started their program with an individual assessment by the EP service and included full medical history assessment (current diagnosis and past medical history), medications, current and past exercise levels, precautions and contradictions to exercise, functional assessment, and goal setting (short-, mid-, and long-term).

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Exercise Intervention

Each patient was prescribed an individualized moderate-intensity exercise program, including a combination of aerobic, strength training, and flexibility exercises as per ACSM guidelines.31 Patients completed 3 to 5 training sessions per week, which lasted for 20 to 60 minutes in duration, with each program lasting 8 to 12 weeks in duration. Patients had a minimum of 1 supervised session per week at the hospital gym with the EP to progress and/or adjust the exercise intervention/training load as clinically indicated. Patients were also prescribed a home exercise program that consisted of walking program 2 to 3 days per week and strength training exercises 1 day per week.

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Supervised Exercise Session

All supervised exercise sessions were carried out at the specialist cancer center gym. The program was undertaken one to one, with each session beginning with a 3-minute warm-up on an exercise bike, followed by aerobic training program (exercise bike or treadmill), resistance training program, and ending with a 3-minute cooldown on the exercise bike, followed by stretching of the major muscle groups.

The aerobic component of the exercise program consisted of interval training and lasted for 15 to 30 minutes in duration. Heart rate (HR) was monitored throughout the session, with HR range maintained between 50% and 80% of predicated HRmax (monitored using a pulse oximeter). Participants were also asked regularly throughout session rating of perceived exertion on Borg's scale, with the aim to maintain intensity between 12 and 15 (out of 20) throughout the training session.

The strength training component of the exercise program consisted of 5 to 7 upper- and lower-limb exercises of the major muscle groups and started at 2 sets of 10 repetitions. Strength training exercises incorporated body weight exercises, dumbbells, and barbells. Initial progression of the program was increasing the number of repetitions per set from 10 to 12 to 15. Once this was achieved, the number of sets was increased from 2 to 3. Following the increase in sets, weight was added to further resistance.

For participants who had completed treatment, the exercise program was progressed each week of the intervention. For participants currently undergoing treatment, clinical reasoning was used to adjust exercise intensity depending on the treatment symptoms and side effects experienced by participant and therefore it was not expected that program intensity increased each week.

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Functional Assessment Measures

Functional outcome measures were undertaken at baseline assessment and then repeated postexercise intervention. Anthropometric measurements included weight, height, and body mass index (BMI). Participant aerobic capacity and endurance were assessed using the Six-Minute Walk Test (6MWT).31–33 A Powertrack-II Commander 1500 hand-held dynamometer was used to measure strength of knee extensor, ankle dorsiflexor, and shoulder abductor muscles. An isometric muscle contraction was assessed for each muscle group, and the highest force achieved over a 5-second duration was recorded. Lower-limb muscle endurance was assessed using the 30-second Sit-to-Stand Test, and upper-limb muscle endurance was assessed using the 30-Second Arm Curl Test and the maximal Push-up Test.34,35

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Demographic and Patient-Reported Characteristics

Demographic data collected from patient medical records included age, sex, and place of residence; medical data collected from participant medical records included cancer histological type and stage, treatment modalities, treatment status (in progress or treatment completed). Patient-reported data were collected at both baseline and postintervention assessment included, current exercise levels (type, duration, frequency, and intensity), which were then compared with the WHO physical activity guidelines and classified as follows: sufficient (≥150 min/wk), insufficient (1-149 min/wk), or sedentary (0 min/wk).36

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Statistical Analysis

Data were analyzed using R version 3.4.2. Means and standard deviations were calculated for continuous variables, and frequencies were measured for categorical variables. For between-group comparisons of baseline demographic variables, the χ2 test with Fisher's exact test was used for categorical variables, whereas t tests were used for continuous variables.

Preliminary analyses indicated that the data contained outliers. Therefore, we compared baseline and postintervention physical and psychosocial functioning outcomes using a paired permutation test.37 We calculated a robust version of Cohen's d (dR) effect size based on 20% trimmed means and Winsorized variances.38 For clinical utility, we converted dR to Cohen's U3 measure of nonoverlap, which reflects the proportion of postintervention scores that are greater than the mean preintervention scores.

In the absence of normative and clinical significance change data for AYA cancer populations for the 6MWT, we used the reliable change index (RCI) based on the standard error of measurement (SEM) calculated from the present data.39 This approach can demonstrate that baseline to postintervention change is reliably beyond any error in measurement. We used the modified Jacobson and Truax formula reported in Speer and Greenbaum.40 RCI scores greater than 1.96 indicate reliable change in the positive direction (improvement), whereas scores lower then −1.96 indicate reliable change in the negative direction (deterioration). RCI scores that fall between −1.96 and 1.96 indicate no (reliable) change. Therefore, a patient is said to have changed reliably from baseline to postintervention by analyzing a function of the standard deviation of the 6MWT and its test-retest reliability. Given the presence of outliers in both baseline and postintervention 6MWT scores, we used 20% trimmed means, Winsorized standard deviations, and Winsorized test-rest correlation (r = 0.71 for the on-treatment group and r = 0.66 for the posttreatment group) when calculating the SEM. The SEM was 21.60 and 26.50 for the on-treatment and posttreatment groups, respectively.

Chi-square tests were used to examine between-group differences for the 6MWT RCI. If the χ2 test was statistically significant, the adjusted standardized residual (ASR) was examined to determine whether the observed cell frequency statistically differed from the expected cell frequency. The ASR takes into account both the number of comparisons and the sample size and reports a more accurate difference between the observed and expected counts than between the unadjusted standardized residuals.41 The observed frequency is significantly greater than the expected frequency if the ASR is greater than 1.96 (P < .05), whereas the observed frequency is significantly less than the expected frequency if the ASR is less than −1.96 (P < .05).

The marginal homogeneity test (MHT) was used to compare changes in the proportion of exercise levels (sedentary vs insufficient vs sufficient) from baseline to postintervention. Separate analyses were conducted for the off-treatment and on-treatment groups.

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Study Profile

Between the period May 28, 2013, and April 23, 2014, inclusive, 167 patients were referred to ONTrac at Peter Mac. Of the 87 triaged to EP, 36 (41%) patients were excluded: 16 (18%) received only general exercise information guidance and advice; 13 (15%) completed only baseline assessment; and 7 (8%) completed postintervention assessment outside of the 8- to 12-week period (baseline to postintervention assessment). As a result, 51 patients were included in the analysis (Figure 1).

Fig. 1

Fig. 1

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Participant Characteristics

Demographic and medical characteristics of study participants are summarized in Table 1. The mean age of study participants was 21.2 years (SD = 2.7 years; range, 15-25 years) and 31 (61%) were male. The mean BMI of participants was 23.7 kg/m² (SD = 3.9; range, 17.7-36.8). The most common cancer diagnoses were sarcoma (n = 19; 39%), lymphoma (n = 13; 27%), and leukemia (n = 7; 14%). Common treatment modalities undertaken included chemotherapy-only (n = 15; 29%); chemotherapy and other (n = 28; 55%); and surgery ± radiotherapy (n = 8; 16%).



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Functional Outcome Measures

Table 2 presents the baseline and postintervention functional assessment. For the on-treatment group, there were significant differences between baseline and postintervention scores for sit-to-stand, push-ups, left and right arm curls, left shoulder abductions, and left dorsiflexion. The effect sizes for these differences ranged from small (dR = −0.02, U3 = 49%) to large (dR = 1.05, U3 = 85%). The pre- and postintervention mean distance on the 6MWT was 496 m (SD = 40.4) and 494 m (SD = 40.0), respectively (d = −0.02, U3 = 49%).



For patients posttreatment, there were significant differences between baseline and postintervention assessment, with most notable improvement seen in the 6MWT, Sit-to-Stand Test, Push-up Test, and arm curls (Table 2). The effect sizes ranged from small (dR = 0.30, U3 = 62%) to large (dR = 1.29, U3 = 90%). The pre- and postintervention mean distance on the 6MWT was 485 m (SD = 45.5) and 570 m (SD = 38.9), respectively (dR = 1.29, U3 = 90%).

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Reliable Change Index for the 6MWT

In the 6MWT, for the on-treatment group, conditions of 2 participants (11%) reliably deteriorated, 15 (79%) did not reliably change, and 2 (11%) reliably improved. In the posttreatment group, condition of 1 participant (4%) reliably deteriorated, 12 (40%) did not reliably change, and 17 (61%) reliably improved on the 6MWT.

There was a significant association between treatment status (on-treatment vs posttreatment) and changes on the observed 6MWT from baseline to postintervention (

= 8.01, P = .006). The ASRs indicated that relative to the on-treatment group, more patients posttreatment reliably improved (ASR = 2.83, P = .005) than expected. In addition, compared with the on-treatment group, fewer patients in the posttreatment group did not experience reliable change than expected (2.63, P = .009).

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Exercise Levels

The baseline exercise levels for the on- and posttreatment groups are shown in Table 3. There was no significant association between treatment status and baseline exercise levels. For both groups, almost all patients were either sedentary or had insufficient exercise levels.



For the on-treatment group, there were 0 (0%) sedentary patients, 14 (74%) with insufficient exercise levels, and 5 (26%) with sufficient exercise levels at postintervention. The MHT indicated that there was a significant increase in the proportion of patients with sufficient exercise levels from baseline to follow-up (

= 8.0, P = .018).

For the off-treatment group, there was 1 (3%) sedentary patient, 13 (41%) with insufficient exercise levels, and 18 (56%) with sufficient exercise levels at postintervention. The MHT test showed that there was a significant increase in the proportion of patients with sufficient exercise levels from baseline to follow-up (

= 20.9, P < .001).

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This study examined the physical performance of AYA with cancer who had undertaken an EP intervention in a multidisciplinary AYA oncology service. Given the expected differences between patients on-treatment and posttreatment, analysis of the EP intervention was separated to where patients were in their management. During treatment, the aim of an exercise prescription is to maintain function, limit treatment-related side effects, and prevent deconditioning of the individual.24,42 Posttreatment, the aim of an exercise program is to restore functional capacity and promote the return to normal everyday activities.42,43 With this in mind, our pilot data support the use of EP intervention in both phases and the positive effect it had on increasing patients exercise levels, along with meeting the exercise prescription goals of maintaining function during treatment and increased functional capacity posttreatment completion.

Prior to EP intervention, baseline testing showed that both the on-treatment and posttreatment groups showed early signs of deconditioning. Mean 6MWT distance in our sample ranged from 485 to 496 m, scores that are surprisingly similar to those reported by elderly presurgical lung cancer patients (540 m)44 and stage I-lII lung cancer patients who are within 6 months of treatment completion (499 m).45 A similar pattern was observed in patients' Chair-stand and Arm Curl Test scores, which were below normal range scores by 60- to 64-year-olds,34 and highlights the extent of deconditioning experienced by our younger cohort. One reason for this deconditioning is low levels of physical activity and exercise that were undertaken by patients prior to EP assessment. Within our sample, almost all patients at baseline failed to meet weekly exercise recommendations (Table 3).36 However, at the conclusion of the EP intervention, more than half of the off-treatment group and more than a quarter of patients who were undergoing treatment were participating in recommended levels of exercise at follow-up, showing a significant increase in the proportion of patients undertaking sufficient levels of exercise. This highlights the valuable role an EP intervention can play in helping people reengage in exercise after a diagnosis of cancer.

For patients who were undergoing cancer treatment, the EP intervention achieved the goal of maintaining patients' functional capacity and limiting the effects of deconditioning, with mean 6MWT distance results showing a small improvement in walk distance (11 m) with similar small improvements in lower-limb and upper-limb muscle strength and endurance tests. This highlights that AYA cancer patients currently undergoing treatment can be prescribed exercise during this time and it can be effective when appropriately tailored to meet the individual needs of the patient.21,42 Nonetheless, additional investigation is required to inquire whether early EP intervention for AYA patients undergoing treatment can play a role in preventing functional decline and positively impact treatment-related side effects.

Posttreatment, the EP intervention resulted in significant improvements in the 6MWT distance, a measure of cardiorespiratory fitness, as well as significant improvements in muscle strength and endurance as measured by the Push-up Test, arm curls, and sit to stand, indicating increased upper and lower extremity strength. The improvement of 89.5 m on the 6MWT is larger than the 27.5 m reported in a recent meta-analysis by Swartz et al46 in cancer survivors and the minimal important difference in lung cancer patients, which is reported to be between 22 and 42 m.47 This provides evidence that appropriately prescribed exercise posttreatment completion may optimize the recovery process and assist in cancer patients returning to premorbid levels of activity.42,43

While this study is the first to report on physical performance measures within the Australian AYA oncology setting, it does have a number of limitations. As a result of the study design, it cannot be determined whether changes in physical performance were due to the EP intervention or reflected the normal recovery process, particularly for those who are posttreatment. Patients also indicated through the screening and triaging process of the service were a self-selecting population keen to engage with EP and therefore they may have been motivated to exercise and as a result improve their functional strength and endurance. Larger, randomized controlled trails are needed in this area, particularly during the off-treatment phase to determine the effect exercise has on the recovery process as opposed to what may be considered the normal recovery process.

The aforementioned limitations notwithstanding, our findings may have several implications to clinical practice. An exercise intervention for patients during treatment may prevent the normal deconditioning that is expected during this time by maintaining or increasing their physical activity levels. For individuals who have completed their cancer treatment, an exercise intervention may accelerate their recovery process and return to premorbid levels of functioning. However, as there is very little evidence addressing these factors, no evidence-based exercise guidelines exist that facilitate optimal health, quality of life, and longevity in AYA cancer patients. Without post–cancer treatment rehabilitation, there is a potential risk of this population developing long-term late effects or comorbidities that may impact on survival, overall quality of life, and ability to reengage into society via work and education.16,18,45 Although AYA represent a small number of those with all cancer diagnoses, the long-term health implications for this group are disproportionate and therefore they may require specialist exercise intervention to reverse cancer and treatment-related deconditioning.

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We identified that an individualized exercise intervention may have a positive effect on AYA cancer patients' physical performance, both while undergoing treatment and during the posttreatment phase. While this study adds to the evidence supporting exercise interventions within AYA cancer patients, additional research is required, including prospective randomized studies that incorporate broader health-related quality-of-life measures alongside cost-effectiveness, variation in program formats, and timing of interventions.

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Adolescent and Young Adult Functional Capacity; Exercise

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