Impact on Pulmonary Function in a Randomized Trial of Single-Fraction and Multifraction Stereotactic Body Radiation Therapy for Pulmonary Oligometastatic Disease: An Analysis of TROG 13.01 (SAFRON II).

PURPOSE: The TROG 13.01 (SAFRON II) trial was a phase 2 multicenter trial comparing single-fraction (SF) and multifraction (MF) stereotactic body radiation therapy. Patients with 1 to 3 peripheral pulmonary oligometastases were randomized 1:1 between 28 Gy in 1 fraction and 48 Gy in 4 fractions. There were no differences between arms in efficacy or toxicity. We performed an analysis to assess changes in pulmonary function tests (PFTs) between arms over time and assessed the effect of the number and total volume of targets on PFT change over time. METHODS AND MATERIALS: A linear mixed model was used to describe the PFTs by treatment arm over time. The effect of number and volume of targets on PFTs at 6 and 12 months was assessed by a simple linear model. RESULTS: Ninety patients were randomized; 87 were treated for 133 pulmonary oligometastases. Forty-four were randomized to the SF arm and 43 to the MF arm. There were no differences in absolute or relative PFT measures of forced expiratory volume in 1 second (FEV1), diffusing capacity of the lungs for carbon monoxide (DLCO), or forced vital capacity (FVC) between the 2 arms. At 12 months, there was a reduction in absolute DLCO from baseline (-1.7 mL/min/mm Hg [95% CI, -2.5 to -1.0]), relative DLCO (-5.5% [95% CI, -8.4% to -2.6%]), absolute FEV1 (-0.17 L [95% CI, -0.23 to -0.11]), and absolute FVC (-0.20 L [95% CI, -0.27 to -0.13]). In patients with multiple pulmonary targets, increase in target number (per lesion) was associated with a reduction in the absolute FEV1 at 6 months of -0.10 L (95% CI, -0.18 to -0.03; P = .007), FEV1 at 12 months of -0.10 L (95% CI, -0.20 to -0.01; P = .04), FVC at 6 months of -0.11 L (95% CI, -0.20 to -0.03; P = .014), and FVC at 24 months of -0.13 L (95% CI, -0.25 to -0.01; P = .036). Reduction in FEV1 was also seen per 10-mL increase in PTV at 12 months (-0.03 L [95% CI, -0.06 to -0.00], P = .036). The number of targets and PTV were not associated with DLCO. CONCLUSIONS: Treating multiple targets resulted in increased loss of FEV1 and FVC but not DLCO. There were no significant differences in PFT decline between SF and MF stereotactic body radiation therapy.

"Now is the time for institutions to be investing in growing exercise programs as part of standard of care": a multiple case study examining the implementation of exercise oncology interventions.

BACKGROUND: Implementation science seeks to systematically identify determinants, strategies, and outcomes within a causal pathway to help explain successful implementation. This process is applied to evidence-based interventions (EBIs) to improve their adoption, implementation, and sustainment. However, this method has not been applied to exercise oncology services, meaning we lack knowledge about implementing exercise EBIs in routine practice. This study aimed to develop causal pathways from the determinants, strategies (including mechanism of change), and implementation outcomes to explain exercise EBIs implementation in routine cancer care. METHODS: A multiple-case study was conducted across three healthcare sites in Australia. Sites selected had implemented exercise within routine care for people diagnosed with cancer and sustained the delivery of services for at least 12 months. Four data sources informed the study: semi-structured interviews with staff, document reviews, observations, and the Program Sustainability Assessment Tool (survey). Framework analysis was applied to understand the findings. The Implementation Research Logic Model was used to identify commonalities in implementation across sites and develop causal pathways. RESULTS: Two hundred and eighteen data points informed our findings. Across sites, 18 determinants and 22 implementation strategies were consistent. Sixteen determinants and 24 implementation strategies differed across sites and results of implementation outcomes varied. We identified 11 common pathways that when combined, help explain implementation processes. The mechanisms of implementation strategies operating within the pathways included (1) knowledge, (2) skills, (3) secure resources, (4) optimism, and (5) simplified decision-making processes associated with exercise; (6) relationships (social and professional) and support for the workforce; (7) reinforcing positive outcomes; (8) capability to action plan through evaluations and (9) interactive learning; (10) aligned goals between the organisation and the EBI; and (11) consumer-responsiveness. CONCLUSION: This study developed causal pathways that explain the how and why of successful implementation of exercise EBIs in cancer care. These findings can support future planning and optimisation activities by creating more opportunities for people with cancer to access evidence-based exercise oncology services. IMPLICATIONS FOR CANCER SURVIVORS: Understanding how to implement exercise within routine cancer care successfully is important so cancer survivors can experience the benefits of exercise.

Beyond Medical Care: How Different National Models of Care Impact the Experience of Adolescent and Young Adult Cancer Patients.

Patient experience is positively associated with clinical effectiveness, quality care, and patient safety. This study examines the experience of care of adolescents and young adult (AYA) cancer patients from Australia and the United States, allowing a comparison of patient experiences in the context of different national models of cancer care delivery. Participants (n = 190) were aged 15-29 years and received cancer treatment from 2014 to 2019. Australians (n = 118) were recruited nationally by health care professionals. U.S. participants (n = 72) were recruited nationally via social media. The survey included demographic and disease variables, and questions regarding medical treatment, information and support provision, care coordination, and satisfaction across the treatment pathway. Sensitivity analyses examined the possible contribution of age and gender. Most patients from both countries were satisfied or very satisfied with their medical treatment (chemotherapy, radiotherapy, and surgery). There were significant differences between countries in the provision of fertility preservation services, age-appropriate communication, and psychosocial support. Our findings suggest when a national system of oversight with both state and federal funding is implemented, as is the case in Australia but not in the United States, significantly more AYAs with cancer receive age-appropriate information and support services, and improved access to specialist services such as fertility care. A national approach with government funding and centralized accountability appears to be associated with substantial benefits for the well-being of AYAs undergoing cancer treatment.

Comparison of Changes in Pulmonary Function After Stereotactic Body Radiation Therapy Versus Conventional 3-Dimensional Conformal Radiation Therapy for Stage I and IIA Non-Small Cell Lung Cancer: An Analysis of the TROG 09.02 (CHISEL) Phase 3 Trial.

PURPOSE: The TROG 09.02 CHISEL trial compared conventional radiation therapy (CRT) with stereotactic body radiation therapy (SBRT) in patients with inoperable early-stage non-small cell lung cancer. Patients randomized to SBRT had less local failure and improved overall survival. This analysis reports differences in pulmonary function tests (PFTs) and the 6-minute walk test (SMWT) between patients who received SBRT and those who received CRT. METHODS AND MATERIALS: We analyzed the PFTs and SMWTs of all patients recruited to the CHISEL [trial. During this trial, patients underwent serial PFTs. Linear regression models were used to compare parameters between SBRT and CRT at 3 and 12 months after treatment. RESULTS: One hundred and one patients were enrolled; 33 patients were treated with CRT, 61 were treated with SBRT, and 7 did not receive treatment. Primary tumor size was similar between arms: SBRT 25 mm (standard deviation [SD], 9) and CRT 28 mm (SD, 9). On regression analysis, at 3 and 12 months, there was no evidence of a difference between arms in PFT decline or distance walked in the SMWT. Planning target volume size was significantly larger in the CRT arm, 142.79 cc (SD, 61.14), compared with the SBRT group, 46.15 cc (SD, 23.39). The mean biologically effective dose received by the target was significantly larger in the SBRT group, 125.92 Gy (SD, 21.58), compared with CRT, 65.49 Gy (SD, 6.32). Mean dose to the lungs minus the gross target volume incorporating motion was 8.9 Gy (SD, 2.34) in the CRT group and 4.37 Gy (SD, 1.42) in the SBRT group. CONCLUSIONS: Despite the considerably higher biologically effective doses delivered to the tumor in SBRT, there was no difference in decline in respiratory function observed between the 2 groups.

AYA 'Can-Sleep' programme: protocol for a stepped-care, cognitive behavioural therapy-based approach to the management of sleep difficulties in adolescents and young adults with cancer.

BACKGROUND: Sleep problems are reported in up to 50% of adolescents and young adults (AYA) with cancer. Cognitive behavioural therapy for insomnia (CBTi) is considered the gold-standard treatment. In the AYA population, CBTi is associated with improvements in insomnia, daytime sleepiness, fatigue and quality of life. In adults, stepped-care interventions can improve accessibility to CBTi. This study aims to evaluate the acceptability and feasibility of a stepped-care CBTi programme in AYA with cancer. METHODS AND ANALYSIS: AYA (target N = 80) aged 16-25 with a diagnosis of cancer will be screened using the Insomnia Severity Index (ISI) and Epworth Sleepiness Scale (ESS). When sleep difficulties are identified by the ISI and/or ESS, they will be screened for obstructive sleep apnoea and restless leg syndrome and referred to a sleep service if indicated. The remainder with sleep difficulties will be offered a stepped-care sleep programme including CBT self-management and coaching (first step). Participants will then be rescreened at 5 weeks, and those with ongoing sleep difficulties will be offered individualised CBT (second step). Recruitment and retention rates, adherence to intervention and time taken to deliver screening and intervention will be collected to assess the feasibility of the programme. AYA and clinicians will complete evaluation surveys to assess the acceptability of the AYA Can-Sleep programme. DISCUSSION: We seek to contribute to the evidence base regarding screening and treatment of sleep difficulties in the AYA population by implementing the AYA Can-Sleep programme and determining its feasibility and acceptability as an approach to care in an Adolescent & Young Adult Cancer Service.

Exercise recommendations and referral patterns of oncology professionals.

BACKGROUND: Exercise physiologists and physiotherapists can provide exercise interventions for cancer survivors; however, many do not access this support. Our primary aim explored referral habits to exercise professionals and attitudes of oncology professionals. Secondary aims explored fitness levels of oncology professionals and the relationship between fitness and exercise referral habits. METHODS: Oncology professionals (n = 67) attending a national cancer conference in Australia participated in this cross-sectional study (23% doctors, 11% nurses, 25% allied health, and 41% other). A subgroup (n = 49) completed a fitness assessment measuring aerobic fitness (3-minute step test), muscle strength (handgrip dynamometry), and body composition (waist-to-hip ratio). Oncology professionals in a position to refer patients to exercise professionals were assessed on their history of patient referrals. RESULTS: Sixty-seven of 750 eligible conference delegates participated (9% recruitment rate), of which 73% completed fitness assessments. Participants displayed above average physical activity and fitness levels with 60% meeting exercise guidelines. The majority (92%) agreed that exercise is important among cancer survivors to attenuate treatment-associated symptoms. Most understand the role of exercise physiologists (61%) and physiotherapists (64%) in cancer care. Seventy-three percent reported that referral to exercise professionals is optimal to increase exercise participation. Most (82%) oncology professionals who are able to refer patients to exercise professionals have self-reported doing so, while 91% recommended exercise themselves. Sixty-two percent were aware of evidence-based exercise guidelines. Fitness levels (p = 0.25), strength (p = 0.88), and physical activity (p = 0.33) did not impact referrals made to exercise professionals. CONCLUSION: There was high awareness exercise-oncology benefits and evidence-based guidelines existed among sampled participants. Oncology professionals understand the role of exercise professionals, reflected by high self-reported referral rates. Implementing referral pathways to exercise professionals in cancer care may facilitate improved patient outcomes.

Health-related quality of life, fatigue and health behaviours in Australian adolescent and young adult cancer survivors.

INTRODUCTION: Current knowledge of the long-term health behaviours and well-being of adolescent and yong adult (AYA) cancer survivors is limited. The aim of this study was to evaluate the health behaviours of AYA cancer survivors compared to Australian normative data and describe their health-related quality of life (HR-QoL) and levels of fatigue. METHOD: A cross-sectional online survey of participants aged 15-25 years at diagnosis and 2-7 years post treatment completion was conducted at a comprehensive cancer centre. Validated questionnaires assessed health behaviours and functioning including current physical activity (PA) levels, diet quality, fatigue (FACIT-F) and HR-QoL (AQoL-6D, Short Form 36v2 [SF-36v2]) were compared to Australian normative data. RESULTS: Ninety individuals completed the survey (26% response rate) with a mean age of 25.4 years and median time post treatment of 61 months (24-85 months). Compared to normative data, a higher proportion of AYA cancer survivors was consuming the recommended daily serves of fruit and vegetables (16.7% vs. 3.9%, p < .0001), had a lower presence of overweight or obesity (46.7% vs. 57.7%, p = .04) and lower percentage of current smokers (2.2% vs. 16.7%, p < .0001). However, AYA cancer survivors reported increased fatigue (t[df = 596] = -4.1, p < .0001) and reduced HR-QoL compared to normative data (t[df = 533] = 9.2, p < .0001) along with a higher proportion suffering from one or more chronic health conditions (65% vs. 40%, p < .0001). CONCLUSION: AYA cancer survivors from a single Australian institution, who were on average 5 years post treatment, exhibited better health behaviours compared to Australian normative data, but still below recommended guidelines. However, they continue to experience issues with fatigue and reduced HR-QoL, especially in those not meeting the PA guidelines.

A randomized controlled trial of a structured exercise intervention after the completion of acute cancer treatment in adolescents and young adults.

BACKGROUND: Cancer treatments are frequently associated with impaired physical fitness, quality of life (QOL), and fatigue, often persisting into survivorship.  Studies in older adults with cancer have demonstrated benefits from exercise; however, this has not been rigorously investigated in adolescents and young adults (AYA). The aim of this study was to determine whether a structured 10-week exercise intervention was associated with improved cardiorespiratory fitness (VO2peak ), fatigue, and QOL in AYA who have recently completed cancer treatment. METHOD: Forty-three AYA (median age 21 ± 6 years) were randomly assigned to an exercise group (n = 22) or a control group (n = 21). The exercise group received a structured 10-week exercise program comprising progressive aerobic and resistance exercise; the control arm received routine care. VO2peak was measured at baseline, 10 weeks, and six months. Fatigue and QOL were assessed by the FACIT fatigue scale and the PEDS QL, respectively. RESULTS: Mean VO2peak at baseline was 26.5 ± 7.2 mL.kg-1 .min-1 , which is substantially lower than population norms. The exercise group demonstrated significant improvement in VO2peak at 10 weeks compared with controls (33.8 ± 8.1 vs 29.6 ± 7.6 mL.kg-1 .min-1 , P = 0.0002), but by six months, the difference was no longer significant (32.9 ± 7.0 vs 30.9 ± 11.0 mL.kg-1 .min-1 , P = 0.21). There were no significant differences in fatigue or total QOL scores between groups. CONCLUSION: Cancer treatment is associated with reduced VO2peak in AYA. Improvement in VO2peak was accelerated by a 10-week exercise program; however, no significant benefit was observed in QOL or fatigue. The plateau in VO2peak at six months suggests that a maintenance exercise program may be beneficial.

i-Move, a personalised exercise intervention for patients with advanced melanoma receiving immunotherapy: a randomised feasibility trial protocol.

INTRODUCTION: There is increasing evidence demonstrating the benefits of exercise in counteracting cancer treatment-related fatigue. Immunotherapy is an established treatment for advanced melanoma, and is associated with fatigue in a third of patients. The safety and efficacy of exercise in counteracting treatment-related fatigue in patients with advanced melanoma receiving immunotherapy are yet to be determined. This study aims to assess the safety, adherence to and acceptability of a mixed-methods parallel-group, pilot randomised controlled trial of a personalised, 12-week semi-supervised exercise programme prescribed by an exercise physiologist (iMove) in 30 patients with stage IV melanoma scheduled to commence immunotherapy: single agent ipilimumab, nivolumab or pembrolizumab, or combination ipilimumab and nivolumab. The trial will be used to provide preliminary evidence of the potential efficacy of exercise for managing fatigue. METHODS AND ANALYSIS: Thirty participants will be recruited from a specialist cancer centre between May and September, 2019. Participants will be randomised 1:1 to receive iMove, or usual care (an information booklet about exercise for people with cancer). Feasibility data comprise: eligibility; recruitment and retention rates; adherence to and acceptability of exercise consultations, personalised exercise programme and study measures; and exercise-related adverse events. Patient-reported outcome measures assess potential impact of the exercise intervention on: fatigue, role functioning, symptoms and quality of life. Follow-up will comprise five time points over 24 weeks. Physical assessments measure physical fitness and functioning. ETHICS AND DISSEMINATION: This study was reviewed and approved by the Peter MacCallum Cancer Centre Human Research Ethics Committee (HREC/48927/PMCC-2019). The findings from this trial will be disseminated via conference presentations and publications in peer-reviewed journals, and by engagement with clinicians, media, government and consumers. In particular, we will promote the outcomes of this work among the oncology community should this pilot indicate benefit for patients. TRIAL REGISTRATION NUMBER: ACTRN12619000952145; Pre-results.

Clinical Oncology Society of Australia position statement on exercise in cancer care.

INTRODUCTION: Clinical research has established exercise as a safe and effective intervention to counteract the adverse physical and psychological effects of cancer and its treatment. This article summarises the position of the Clinical Oncology Society of Australia (COSA) on the role of exercise in cancer care, taking into account the strengths and limitations of the evidence base. It provides guidance for all health professionals involved in the care of people with cancer about integrating exercise into routine cancer care. Main recommendations: COSA calls for: exercise to be embedded as part of standard practice in cancer care and to be viewed as an adjunct therapy that helps counteract the adverse effects of cancer and its treatment; all members of the multidisciplinary cancer team to promote physical activity and recommend that people with cancer adhere to exercise guidelines; and best practice cancer care to include referral to an accredited exercise physiologist or physiotherapist with experience in cancer care. Changes in management as a result of the guideline: COSA encourages all health professionals involved in the care of people with cancer to: discuss the role of exercise in cancer recovery; recommend their patients adhere to exercise guidelines (avoid inactivity and progress towards at least 150 minutes of moderate intensity aerobic exercise and two to three moderate intensity resistance exercise sessions each week); and refer their patients to a health professional who specialises in the prescription and delivery of exercise (ie, accredited exercise physiologist or physiotherapist with experience in cancer care).

Structured exercise program prior to major cancer surgery improves cardiopulmonary fitness: a retrospective cohort study.

PURPOSE: To determine if cardiopulmonary exercise testing (CPET) was useful in predicting response to exercise in cancer patients preoperatively. A secondary aim was to explore if exercise was associated with improved postoperative outcomes. METHODS: A retrospective cohort study was performed on consecutive cancer patients from 2012 to 2014, referred for exercise prehabilitation and had two CPET preoperatively. RESULTS: Twenty-six patients were analysed. There was a significant overall increase in oxygen uptake at anaerobic threshold (AT) from 10.4 to 11.6 ml kg(-1) min(-1) (ΔAT = 1.2 ± 3.0 ml kg(-1) min(-1) [9 %]; p = 0.046); peak oxygen uptake (pVO2) from 16.0 to 17.7 ml kg(-1) min(-1) (ΔpVO2 = 1.7 ± 2.4 ml kg(-1) min(-1) [9 %]; p = 0.002); and pVO2/BSA from 658 to 726 ml min(-1) m(-2); (ΔpVO2/BSA = 68 ± 112.3 mL min(-1) m(2) [10 %]; p = 0.004). Fifty percent of patients were responders to exercise, defined as having >10 % increase in AT. Responders had a median increase in AT of 26 % [IQR 7 %, 45 %] with an absolute increase in AT of 2.5 ml kg(-1) min(-1) [IQR 1.1, 3.9] (p = 0.002) and a median increase in pVO2 of 22 % [IQR 11.5, 32.5 %] with an absolute increase in pVO2 of 3.8 ml.kg(-1).min(-1) [IQR 2.0, 5.7] (p < 0.001). Responders were more likely to have a lower baseline AT (9.1 ml kg(-1) min(-1); p = 0.002). CONCLUSIONS: Exercise improved cardiorespiratory fitness prior to major cancer surgery. Not all patients responded the same, with only 50 % of the study cohort being responders to exercise. A low AT, pVO2 and ratio of AT/pVO2 at baseline were good predictors of response to exercise, with a tendency for responders to suffer fewer major postoperative complications.

Low physical activity levels and functional decline in individuals with lung cancer.

OBJECTIVES: Physical activity has been infrequently measured objectively in non-small cell lung cancer (NSCLC). We aimed to investigate levels of physical activity, functional and patient reported outcomes at diagnosis and over six months in participants with recently diagnosed NSCLC and compare results with both physical activity guidelines and outcomes of similar-aged healthy individuals. METHODS: This prospective observational study assessed 50 individuals from three Australian tertiary hospitals with stage I-IIIB NSCLC at diagnosis, then 10 weeks and six months later. Thirty five healthy individuals without cancer were assessed once. Outcome measures included tri-axial accelerometery (number of steps per day), six minute walk distance (6MWD), muscle strength and questionnaires including health-related quality of life (HRQoL). RESULTS: Individuals with NSCLC were engaged in significantly less physical activity than similar-aged healthy individuals, with 60% not meeting physical activity guidelines. At diagnosis they had worse quadriceps strength, nutritional status and HRQoL. Over six months, participants with NSCLC experienced decline in self-reported physical activity, 6MWD and muscle strength, and worsening symptoms. CONCLUSION: At diagnosis individuals with NSCLC engage in less physical activity, are weaker and more depressed than healthy individuals and their self-reported physical activity declines over six months. Future studies are required to investigate the efficacy of interventions to increase physical activity.

The exercise programming preferences and activity levels of cancer patients undergoing radiotherapy treatment.

INTRODUCTION: Research has shown that patients who undergo regular physical activity during cancer treatment have significantly better physical functioning, cardiorespiratory fitness, psychological well-being and quality of life than those who do not. Despite the apparent value of exercise, few patients undertake regular physical activity during treatment and usually find it difficult to return to pre-treatment levels of activity following treatment completion. The purpose of this study was to compare pre-treatment versus on-treatment activity levels of outpatients receiving radiotherapy at a cancer centre in Australia and to identify patients' preferences and barriers to exercise during this time. METHODS: One hundred and twenty consecutive patients undergoing radical radiotherapy were approached. Ninety-two patients (77%) answered questions on medical and demographic variables, past and current activity levels and exercise counselling and programming preferences. RESULTS: Patients reported a decrease in the time spent exercising once radiotherapy treatment started and were less likely to engage in strenuous activities. Seventy-nine percent of patients reported that cancer and its treatments had affected their ability to exercise. Seventy-one percent wanted information about exercise during treatment and preferred to receive this information from an exercise specialist who is affiliated with the hospital. A home-based independent exercise program was preferred by 53% of patients but there was less consistency around when to begin an exercise program. CONCLUSIONS: The study indicates that a significant proportion of cancer patients undergoing radiotherapy want information, counselling and support regarding exercise and exercise programming.