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Effects of exercise prehabilitation and/or rehabilitation on health-related quality of life and fatigue in patients with non-small cell lung cancer undergoing surgery: A systematic review
Department of Clinical Epidemiology, VieCuri Medical Centre, Venlo, the NetherlandsDepartment of Epidemiology, Maastricht University Medical Centre, GROW School for Oncology and Reproduction, Maastricht, the Netherlands
Department of Nutrition and Movement Sciences, Nutrition and Translational Research in Metabolism (NUTRIM), Faculty of Health, Medicine and Life Sciences, Maastricht University, Maastricht, The NetherlandsDepartment of Surgery, Nutrition and Translational Research in Metabolism (NUTRIM), Faculty of Health, Medicine and Life Sciences, Maastricht University, Maastricht, The Netherlands
Department of Clinical Epidemiology, VieCuri Medical Centre, Venlo, the NetherlandsDepartment of Epidemiology, Maastricht University Medical Centre, GROW School for Oncology and Reproduction, Maastricht, the Netherlands
Duration of (p)rehabilitation in published studies may have been too short to achieve effects on HRQoL
•
There is heterogeneity of both physical exercise training programs and outcomes used to assess HRQoL
•
At least 4 weeks of moderate or high-intensity (p)rehabilitation seems to improve HRQoL
Abstract
Background
This systematic review aimed to appraise the current available evidence regarding the effects of exercise prehabilitation and rehabilitation on perceived health-related quality of life (HRQoL) and fatigue in patients undergoing surgery for non-small cell lung cancer (NSCLC).
Methods
Studies were selected according to Cochrane guidelines and assessed for methodological quality and therapeutic quality (the international CONsensus on Therapeutic Exercise aNd Training (i-CONTENT)). Eligible studies included patients with NSCLC performing exercise prehabilitation and/or rehabilitation and postoperative HRQoL and fatigue up to 90-days postoperatively.
Results
Thirteen studies were included. Exercise prehabilitation and rehabilitation significantly improved postoperative HRQoL in almost half of the studies (47%), although none of the studies demonstrated a decrease in fatigue. Methodological quality and therapeutic quality were poor in respectively 62% and 69% of the studies.
Conclusion
There was an inconsistent effect of exercise prehabilitation and exercise rehabilitation on improving HRQoL in patients with NSCLC undergoing surgery, with no effect on fatigue. Due to the low methodological and therapeutic quality of included studies, it was not possible to identify the most effective training program content to improve HRQoL and reduce fatigue. It is recommended to investigate the impact of a high therapeutic qualified exercise prehabilitation and exercise rehabilitation on HRQoL and fatigue in larger studies.
Netherlands Cancer Registry: Incidence of Lung Cancer in The Netherlands according to type of histology. Available from: http://cijfersoverkanker.nl. Accessed March 30, 2021.
Netherlands Cancer Registry: Richtlijn niet-kleincellig longcarcinoom. Published 2004. Updated June 3, 2020. Available from: http://cijfersoverkanker.nl. Accessed March 30, 2021.
], surgery is advised for relatively fit patients with operable early-stage NSCLC. About half of the patients is aged 70 years or older and this proportion is expected to increase due to aging [
]. Characteristics of patients with NSCLC are smoking-related comorbidities, frailty, poor physical performance status, and long-term physical inactivity [
Stage III Non-Small Cell Lung Cancer in the elderly: patient characteristics predictive for tolerance and survival of chemoradiation in daily clinical practice.
In addition, NSCLC and its treatment is often accompanied with physical and psychological symptoms. Pain, fatigue, insomnia, and/or mood disturbances are the four most commonly reported postoperative and distressing symptoms [
Effects of lung rehabilitation therapy in improving respiratory motor ability and alleviating dyspnea in patients with lung cancer after lobectomy: a clinical study.
]. This accounts especially for patients with NSCLC who are physically inactive and/or malnourished and therefore have a low physiological reserve capacity [
]. Prehabilitation (physical exercise training before surgery) and rehabilitation (physical exercise training after surgery) in patients with NSCLC are emerging disciplines, which may positively influence long-term HRQoL, fatigue, and exercise capacity [
Preoperative exercise halves the postoperative complication rate in patients with lung cancer: a systematic review of the effect of exercise on complications, length of stay and quality of life in patients with cancer.
Effects of prehabilitation and rehabilitation including a home-based component on physical fitness, adherence, treatment tolerance, and recovery in patients with non-small cell lung cancer: a systematic review.
], with a limited number and low quality of evidence of included trials. However, systematic evidence regarding the effects of exercise prehabilitation and rehabilitation on HRQoL and fatigue in patients with NSCLC is scarce. Therefore, the aim of this study was to systematically review the literature regarding the effects of exercise prehabilitation and rehabilitation on perceived HRQoL and fatigue in patients undergoing surgery for NSCLC.
2. Methods
Cochrane and PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines were followed. The study protocol was registered at PROSPERO (CRD42018087073).
2.1 Data sources and searches
Articles were systematically searched in PubMed and EMBASE till May 2022. Search terms were related to the research question, including patients with NSCLC performing (a combination of) preoperative and/or postoperative aerobic exercise training, resistance exercise training, and breathing exercises in whom HRQoL and fatigue were assessed (see Supplementary file 1). No filters were applied for study design, and date, as this could eliminate useful articles.
2.2 Study selection
Randomized and non-randomized controlled trials in patients with NSCLC, aged ≥18 years, in which of ≥95% patients with NSCLC underwent elective surgery were included. Search results were combined and duplicates removed. Two reviewers (E.D. and R.R. until March 2018, M.V. and E.D. until May 2022) independently assessed titles, abstracts, and full texts regarding eligibility. Studies were included when patients were diagnosed with stage I-III NSCLC and participated in a physical exercise training intervention (aerobic exercise training, resistance exercise training, and/or breathing exercises) before and/or after surgery, that evaluated the effect on HRQoL and/or fatigue. Furthermore, only randomized controlled trials (RCT), cohort studies, or pilot studies written in English or Dutch were included. Studies were excluded when the physical exercise training intervention was not described or when studies were case reports or systematic reviews. Discrepancies between the three reviewers (M.V., E.D., and R.R.) were discussed until consensus.
2.3 Assessment of methodological quality
Three reviewers (M.V., E.D., and R.R.) independently assessed the methodological quality of included studies by means of the Cochrane risk of bias tool for randomized controlled trials II (RoB2) [
]. The RoB2 reviews six domains and the ROBINS-I tool reviews seven domains. In the RoB2 tool, each item was rated as ‘high’, ‘low’, or ‘some’. In the ROBINS-I tool, each item was rated as ‘low’, ‘moderate’, serious', ‘critical’, or ‘no information’. Discrepancies were resolved by consensus. If no consensus was reached, a fourth person acted as an adjudicator (M.J.).
2.4 Therapeutic quality
Therapeutic quality of exercise prehabilitation programs was assessed independently by the same reviewers (M.V., E.D.) using the international Consensus on Therapeutic Exercise aNd Training (i-CONTENT) tool [
]. Using the i-CONTENT tool, the following eight items were substantively described: 1) patient selection, 2) dosage of the exercise program, 3) type of the exercise program, 4) qualified supervisor, 5) type and timing of outcome assessment, 6) safety of the exercise program, and 7) adherence to the exercise program. A score could be given as low or high risk for ineffectiveness on each of the seven items. An overall risk of ineffectiveness was calculated based on the weight per item that applies to estimate the content of an exercise prehabilitation and/or rehabilitation program. The used criteria for grading the overall risk of ineffectiveness are shown in Table 1.
Table 1Interpretation of therapeutic quality of exercise prehabilitation, rehabilitation program, or a combination of prehabilitation and rehabilitation for patients with NSCLC scheduled for surgery, based on the i-CONTENT tool [
A VO2peak < 20 mL/kg/min and/or a predicted postoperative VO2peak < 10 mL/kg/min for prehabilitation or other selection criteria with a clear rationale for prehabilitation and/or rehabilitation.
No preselection or selection (described).
2. Dosage of the exercise program
Intensity and duration of the physical exercise training program must be clearly described and/or based on existing literature relevant to the target population of operable patients with NSCLC and/or an adequate exercise test (e.g., steep ramp test, CPET).
Intensity and duration of the physical exercise training program is not (adequately) described and/or no physiological improvement can be expected due to a low training dosage (frequency, intensity, time).
3. Type of the exercise program
At least aerobic training with or without resistance training.
An intervention inconsistent with the goal of training therapy for patients undergoing surgery for lung cancer.
4. Qualified supervisor (if applicable)
Guidance of a physical therapist who is specialized in supervising adult clinical populations.
Supervision or guidance is not reported or supervision or guidance was provided by a professional other than a physical therapist.
5. Type and timing of outcome assessment
Follow-up for HRQoL and/or fatigue before and after exercise prehabilitation and/or before and after exercise rehabilitation.
Follow-up for HRQoL and/or fatigue was not clearly described.
6. Safety of the exercise program
Adverse events related to the exercise program are described and acceptable as would be expected in the studied population.
Adverse events related to the exercise program are higher than would be expected in the studied population or adverse events were not described.
7. Adherence to the exercise program
Adherence was determined separately for training frequency and deemed good in case of ≥80%.
Adherence to the training frequency was <80%.
Abbreviations: CPET = cardiopulmonary exercise test; HRQoL = health-related quality of life; i-CONTENT = the international Consensus on Therapeutic Exercise aNd Training; NSCLC = non = small cell lung cancer; VO2peak = oxygen uptake at peak exercise.
Information collected included the name of the first author, year of publication, number of participants, study design, used exercise intervention, age of participants, comorbidity, type of surgery, type and dosage of the exercise program (e.g., frequency, intensity, time, and type), qualified supervisor of the exercise program, type and timing of the outcome assessment, adherence to the physical exercise training sessions, and safety of the exercise program. The outcome measures HRQoL and fatigue were presented as reported in the original studies. A meta-analysis was intended to be performed by use of the Review Manager (version 5.4; Copenhagen: The Nordic Cochrane Centre, The Cochrane Collaboration, 2014).
3. Results
3.1 Study characteristics
3.1.1 Study selection
The PubMed and EMBASE search provided respectively 380 and 232 hits, and 247 hits were found through other sources. After removal of duplicates, there were 756 unique hits. The reasons for exclusion based on title, abstract, and full-text analyses are described in the PRISMA flow diagram (Fig. 1). After full-text review, thirteen studies [
Impact of one-week preoperative physical training on clinical outcomes of surgical lung cancer patients with limited lung function: a randomized trial.
Combined aerobic exercise and high-intensity respiratory muscle training in patients surgically treated for non-small cell lung cancer: a pilot randomized clinical trial.
Impact of one-week preoperative physical training on clinical outcomes of surgical lung cancer patients with limited lung function: a randomized trial.
Combined aerobic exercise and high-intensity respiratory muscle training in patients surgically treated for non-small cell lung cancer: a pilot randomized clinical trial.
]. A total of 633 patients with lung cancer were included (98% NSCLC), consisting of patients with (pathological) stage I (33%), II (14%), III (4%), IV (1%), I-II (28%), I-IIIa (3%), or unknown stage of disease (15%). The sample size ranged from 9 to 101 participants, with an overall age-range between 44 and 79 years. Medical treatment consisted of surgery (99%) [
Impact of one-week preoperative physical training on clinical outcomes of surgical lung cancer patients with limited lung function: a randomized trial.
Combined aerobic exercise and high-intensity respiratory muscle training in patients surgically treated for non-small cell lung cancer: a pilot randomized clinical trial.
]. General characteristics of the included studies are described in Table 2. A meta-analysis could not be performed due to a lack of accurate reporting of HRQoL and fatigue outcomes and heterogeneity of the content of physical exercise training programs in the included studies.
Fig. 1PRISMA flow diagram displaying the selection of studies and reasons for exclusion.
Impact of one-week preoperative physical training on clinical outcomes of surgical lung cancer patients with limited lung function: a randomized trial.
Combined aerobic exercise and high-intensity respiratory muscle training in patients surgically treated for non-small cell lung cancer: a pilot randomized clinical trial.
Impact of one-week preoperative physical training on clinical outcomes of surgical lung cancer patients with limited lung function: a randomized trial.
Combined aerobic exercise and high-intensity respiratory muscle training in patients surgically treated for non-small cell lung cancer: a pilot randomized clinical trial.
Impact of one-week preoperative physical training on clinical outcomes of surgical lung cancer patients with limited lung function: a randomized trial.
Combined aerobic exercise and high-intensity respiratory muscle training in patients surgically treated for non-small cell lung cancer: a pilot randomized clinical trial.
Combined aerobic exercise and high-intensity respiratory muscle training in patients surgically treated for non-small cell lung cancer: a pilot randomized clinical trial.
Impact of one-week preoperative physical training on clinical outcomes of surgical lung cancer patients with limited lung function: a randomized trial.
Combined aerobic exercise and high-intensity respiratory muscle training in patients surgically treated for non-small cell lung cancer: a pilot randomized clinical trial.
Impact of one-week preoperative physical training on clinical outcomes of surgical lung cancer patients with limited lung function: a randomized trial.
Combined aerobic exercise and high-intensity respiratory muscle training in patients surgically treated for non-small cell lung cancer: a pilot randomized clinical trial.
Impact of one-week preoperative physical training on clinical outcomes of surgical lung cancer patients with limited lung function: a randomized trial.
Combined aerobic exercise and high-intensity respiratory muscle training in patients surgically treated for non-small cell lung cancer: a pilot randomized clinical trial.
Combined aerobic exercise and high-intensity respiratory muscle training in patients surgically treated for non-small cell lung cancer: a pilot randomized clinical trial.
Impact of one-week preoperative physical training on clinical outcomes of surgical lung cancer patients with limited lung function: a randomized trial.
], with a training session duration between 30 and 90 min. All physical exercise training interventions were prescribed at a moderate or high training intensity. Supervision of the intervention was applied by physical therapists [
Impact of one-week preoperative physical training on clinical outcomes of surgical lung cancer patients with limited lung function: a randomized trial.
Impact of one-week preoperative physical training on clinical outcomes of surgical lung cancer patients with limited lung function: a randomized trial.
• Based on: NR • Program duration: 4 weeks Aerobic exercises: F: 3–5/week, I: 60–80% of CPET WRpeak, with reduction of intensity in case of a 1–10 Borg dyspnea scores ≥6, T: 30 min, T: Cycle ergometer Resistance exercises: F: 3–5/week, I: 2–3 kg, progressively increasing, T: 2 × 10–15 repetitions, T: gravity-resisted exercises
Consult by phone by the researchers
• HRQoL • HRQoL and fatigue: at baseline and after four weeks (before surgery)
Impact of one-week preoperative physical training on clinical outcomes of surgical lung cancer patients with limited lung function: a randomized trial.
• Based on: NR • Program duration: NR Aerobic exercises: F: 5/week, I-T: week 1: increasing duration and intensity from 20 min at 60% of CPET VO2peak to 30 min at 65% of CPET VO2peak, weeks 2 and 3: 4 sessions of 25–30 min at 60–65% of CPET VO2peak and 1 session of 20 min at the ventilatory anaerobic threshold. After week 3: 3 sessions of 60–65% of CPET VO2peak for 30–35 min, 1 threshold workout, and 1 interval workout per week, T: cycle ergometer
Exercise physiologist
• HRQoL and fatigue • HRQoL and fatigue: at baseline and after prehabilitation (before surgery)
≥18 years, at least one of the following: (a) FEV1 ≤80% of predicted value or BMI ≥30 or age ≥75 years or two or more co-morbidities identified in the Colinet Comorbidity Score
] • Program duration: NR Aerobic exercises: F: 3–5/week, I: interval training (1 min at high intensity (80% of CPET WRpeak) plus 4 min of active rest (performed at 50% of CPET WRpeak), T: 30 min, T: cycling Resistance exercises: F: 3–5/week, I: 25 repetition maximum test, T: 3 × 15 repetitions, T: six exercises using Thera bands and body mass for the large muscle groups Breathing exercises: F: 2/day, I: 80% of vital capacity, T: 6 cycles of 5 repetitions, T: incentive spirometry coach2
Physical therapist
• HRQoL • HRQoL: at baseline and after prehabilitation (before surgery)
PUREAIR protocol: randomized controlled trial of intensive pulmonary rehabilitation versus standard care in patients undergoing surgical resection for lung cancer.
• Based on: NR • Program duration: 12 weeks, 6–12 weeks after surgery Aerobic exercises: F: 2/week, I: 15 min on 80% of baseline mean walk speed on the 6MWT and increased at moderate intensity (Borg-score 4–10, somewhat hard), T: 90 min, T: treadmill Resistance exercises: F: NR, I: Borg-score 4–10, somewhat hard, T: 3 sets of 8–15 repetitions, T: major limb movement
Specialized physical therapist
• Feasibility and safety of delivering rehabilitation • HRQoL and fatigue: at the start of exercise prehabilitation and after exercise rehabilitation at 12 weeks
Combined aerobic exercise and high-intensity respiratory muscle training in patients surgically treated for non-small cell lung cancer: a pilot randomized clinical trial.
• Based on: NR • Program duration: 8 weeks, 6 weeks after surgery Aerobic exercises: F: 3/week, I: 60% of baseline WRpeak on the CPET, T: 30 min, T: cycle ergometer Breathing exercises: F: 3/week, 2/day, I: 50% of PImax and PEmax and adjusted weekly by 10 cm cm H2O, T: 5 sets of 10 repetitions, T: inspiratory and expiratory muscle trainer
Physical therapist
• HRQoL • HRQoL and fatigue: at the start of exercise rehabilitation and after exercise rehabilitation at 8 weeks
No adverse events
Combination of exercise prehabilitation and rehabilitation
• Based on: NR • Program duration: 9 weeks: ≤7 days preoperative and until 8 weeks postoperative Aerobic exercises: F: 5/week, I: moderate, T: 30 min, T: walking Resistance exercises: F: 3/week, I: moderate (1–10 Borg dyspnea scale 4–6, somewhat hard), T: 2 sets of 10–15 repetitions, T: major muscle groups
Specialized physical therapist
• Feasibility and safety of delivering prehabilitation and rehabilitation • HRQoL and fatigue: at baseline before prehabilitation (before surgery) and at 8 weeks after rehabilitation (after surgery)
] • Program duration: NR Aerobic exercises F: 1/day, I: a target heart rate (>60% of maximum heart rate), T: at least 20 min, T: walking, swimming, exercise classes or cycling Resistance exercises: F: 1/day, I: a target heart rate (>60% of maximum heart rate), T: 10 × 3 min per exercise, T: upper and lower limb
Physical therapist
• Postoperative pulmonary complications and length of hospital stay • HRQoL and fatigue: at baseline (before surgery) and 6 weeks after rehabilitation (after surgery)
No adverse events
Abbreviations: 1RM = one-repetition maximum; 6MWT = 6-min walk test; 6MWD = 6-min walk distance; BMI = body mass index; COPD = chronic obstructive pulmonary disease; CPET = cardiopulmonary exercise test; IG = intervention group; HRpeak = heart rate at peak exercise; HRQoL = health-related quality of life; ECOG = Eastern cooperative oncology group; FEV1 = forced expiratory volume in 1 s; FVC = forced vital capacity; NR = not reported; PImax = maximal inspiratory mouth pressure; PEmax = maximal expiratory mouth pressure; ppoDLCO = predicted postoperative diffusing capacity of the lung for carbon monoxide; ppoFEV1 = predicted postoperative forced expiratory volume in 1 s; SpO2 = peripheral oxygen saturation; UC = usual care; VO2peak = oxygen uptake at peak exercise; WRpeak = work rate at peak exercise.
Combined aerobic exercise and high-intensity respiratory muscle training in patients surgically treated for non-small cell lung cancer: a pilot randomized clinical trial.
Impact of one-week preoperative physical training on clinical outcomes of surgical lung cancer patients with limited lung function: a randomized trial.
] as having a high risk of bias. Often, studies showed an unclear description of the randomization process (n = 5), unclear assignment to intended interventions (n = 4), and poor adherence to the intended interventions (n = 6). Of the five included observational studies, four [
] a serious risk of bias. The latter was mainly caused by a high risk on the items confounding (n = 5), patient selection (n = 3), and a poor description of the intervention classification (n = 1).
Table 4Results of methodological quality according to the Cochrane risk of bias tool and the Robins-1 tool, and therapeutic quality according to the i- CONTENT tool.
Methodological quality (Cochrane risk of bias tool)
Impact of one-week preoperative physical training on clinical outcomes of surgical lung cancer patients with limited lung function: a randomized trial.
Combined aerobic exercise and high-intensity respiratory muscle training in patients surgically treated for non-small cell lung cancer: a pilot randomized clinical trial.
Impact of one-week preoperative physical training on clinical outcomes of surgical lung cancer patients with limited lung function: a randomized trial.
Combined aerobic exercise and high-intensity respiratory muscle training in patients surgically treated for non-small cell lung cancer: a pilot randomized clinical trial.
Methodological quality: low=low risk of bias, some= some concerns; high=high risk of bias, moderate=moderate risk of bias, serious=serious risk of bias.
Therapeutic quality: low=low risk of ineffectiveness; high=high risk of ineffectiveness.
a: Overall risk of ineffectiveness:
•Low risk of ineffectiveness: items 1, 2, 3, AND 7 scored a "low risk of ineffectiveness" AND ≥1 of the items 4, 5, 7 scored a "low risk of ineffectiveness".
•Some risk of ineffectiveness: items 1, 2, 3, AND 7 scored a "low risk of ineffectiveness" AND 1 of the items 4, 5, 7 scored a "low risk of ineffectiveness" OR 3 items with a score of "low risk of ineffectiveness" on item 1, 2, 3, and 7 AND ≥1 of the items 4, 5, 7 scored a "low risk of ineffectiveness".
•High risk of ineffectiveness: ≤2 items with a score of "low risk of ineffectiveness" on item 1, 2, 3, and 7.
Combined aerobic exercise and high-intensity respiratory muscle training in patients surgically treated for non-small cell lung cancer: a pilot randomized clinical trial.
Impact of one-week preoperative physical training on clinical outcomes of surgical lung cancer patients with limited lung function: a randomized trial.
] (62%) a high risk of ineffectiveness. Often, physical exercise training programs scored a high risk of ineffectiveness on the items patient selection (n = 9), description of the dosage of the physical exercise training program (n = 10), type and timing of the outcome assessment (n = 6), and low adherence to the program (n = 5).
3.2 Health-related quality of life and fatigue
Effects of exercise prehabilitation and/or rehabilitation on HRQoL and fatigue are shown in Table 5. HRQoL was the primary outcome in four studies [
Combined aerobic exercise and high-intensity respiratory muscle training in patients surgically treated for non-small cell lung cancer: a pilot randomized clinical trial.
Impact of one-week preoperative physical training on clinical outcomes of surgical lung cancer patients with limited lung function: a randomized trial.
]. The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C30 (EORTC QLQ- C30) questionnaire for HRQoL was used in nine studies [
Impact of one-week preoperative physical training on clinical outcomes of surgical lung cancer patients with limited lung function: a randomized trial.
Combined aerobic exercise and high-intensity respiratory muscle training in patients surgically treated for non-small cell lung cancer: a pilot randomized clinical trial.
Combined aerobic exercise and high-intensity respiratory muscle training in patients surgically treated for non-small cell lung cancer: a pilot randomized clinical trial.
Impact of one-week preoperative physical training on clinical outcomes of surgical lung cancer patients with limited lung function: a randomized trial.
HRQoL: EORTC-QLQ-C30 No statistically significant improvement Fatigue: EORTC-QLQ-C30 fatigue subscale No statistically but a clinically significant reduction
•
n = 20 (35%) (n = 6 lack of time, n = 6 not specified, n = 5 lack of interest about engaging in a research project, n = 3 high level of anxiety, n = 3 scheduled surgery within one week of consent, n = 1 clinical deterioration)
•
n = 3 (n = 2 clinical deteriorations, n = 1 psychological distress)
HRQoL: EORTC-QLQ-C30 A statistically significant improvement in the IG compared to UC, p=0.04 Fatigue: fatigue index No statistically significant reduction in the IG compared to UC
•
NR
•
IG: n = 3, (n = 1 acute COPD exacerbation, n = 2 worsening knee pain, n = 2 loss of motivation), UC: n = 0
Impact of one-week preoperative physical training on clinical outcomes of surgical lung cancer patients with limited lung function: a randomized trial.
HRQoL: EORTC QLQ-C30 A statistically significant improvement in emotional function in the IG compared to UC, p<0.01 Fatigue: fatigue index No statistically significant reduction in the IG compared to UC
HRQoL: FACT-L A statistically significant improvement in the lung cancer subscale after prehabilitation compared with baseline, p<0.01 Fatigue: FACT subscale for fatigue No statistically significant reduction after prehabilitation compared with baseline
•
n = 13 (n = 6 lack of interest, n = 2 already exercising, n = 2 work, n = 2 no transportation, n = 1 = languages)
HRQoL: SF-12 No statistically significant improvement in the IG compared to UC
•
NR
•
IG: n = 25 (n = 6 adjuvant treatment, n = 5 disease progression, n = 5 non primary lung neoplasm, n = 8 lost to follow-up, n = 1 other). UC: n = 30 (n = 15 adjuvant treatment, n = 2 disease progression, n = 3 non primary lung neoplasm, n = 9 lost to follow-up, n = 1 other)
•
90% of the patients had accomplished 80% session adherence
HRQoL: EORTC QLQ-C30 A statistically significant improvement on emotional function compared with before rehabilitation, p<0.01 Fatigue: EORTC-QLQ-C30 fatigue subscale No statistically significant reduction compared with before rehabilitation
•
n = 61 (n = 23 travel to far, n = 22 busy with personal affairs, n = 9 still hospital inpatient, n = 3 busy with work, n = 3 incorrect phone number, n = 1 do not want to participate)
•
n = 1 (unable to contact)
•
47% of the participants attended at least 70% of the scheduled supervised exercise sessions, total attendance rate was 53% (181/340 possible supervised sessions).
Combined aerobic exercise and high-intensity respiratory muscle training in patients surgically treated for non-small cell lung cancer: a pilot randomized clinical trial.
HRQoL: EORTC-QLQ-30 No statistically significant difference between the IG and UC A clinically significant improvement within the IG and UC Fatigue: EORTC-QLQ-C30 fatigue subscale No statistically significant reduction between the IG and UC
•
n = 19 (n = 2 postoperative complications, n = 4 no preoperative assessment, n = 6 declined to participate, n = 7 other reasons)
•
IG: n = 5 (n = 3 declined participations, n = 2 chemotherapy), UC: n = 8 (n = 5 declined participations, n = 2 chemotherapy, n = 1 postoperative complications)
•
>80% completion
Combination of exercise prehabilitation and exercise rehabilitation
HRQoL: EORTC-QLQ-30 A statistically significant improvement at 5 months postoperative compared with preoperative Fatigue: EORTC-QLQ-C30 fatigue subscale No statistically significant reduction
•
NR
•
Before surgery 32%, after surgery 79% (pain, lack of motivation and generally feeling unwell)
•
Median of 4 (range 1–7) sessions a week. 32% did not use the app postoperative
Abbreviations: EORTC-QLQ-30 = European for and of QLQ-C30; FACT = functional assessment of cancer therapy; FACT-L = functional assessment of cancer therapy of the lung; HRQoL = health-related quality of life; IG = intervention group; NR = not reported; NS = not significant; UC = usual care group.
Impact of one-week preoperative physical training on clinical outcomes of surgical lung cancer patients with limited lung function: a randomized trial.
] showed that exercise prehabilitation significantly improved HRQoL on the EORTC-QLQ-C30 lung cancer subscale. Other studies found a significantly higher overall HRQoL measured with the EORTC-QLQ-C30 [
Impact of one-week preoperative physical training on clinical outcomes of surgical lung cancer patients with limited lung function: a randomized trial.
Impact of one-week preoperative physical training on clinical outcomes of surgical lung cancer patients with limited lung function: a randomized trial.
Impact of one-week preoperative physical training on clinical outcomes of surgical lung cancer patients with limited lung function: a randomized trial.
Combined aerobic exercise and high-intensity respiratory muscle training in patients surgically treated for non-small cell lung cancer: a pilot randomized clinical trial.
] investigated the effect of exercise rehabilitation on HRQoL. The subscales ‘global quality of life’ and ‘emotional functioning’ of the EORTC-QLQ-C30 significantly improved during exercise rehabilitation [
Combined aerobic exercise and high-intensity respiratory muscle training in patients surgically treated for non-small cell lung cancer: a pilot randomized clinical trial.
] showed an improvement in HRQoL five months after combined exercise prehabilitation and rehabilitation compared to preoperative HRQoL. Fatigue was measured in both studies by the EORTC QLQ-C30 [
] in which there was no statistically significant effect of exercise prehabilitation and rehabilitation on fatigue.
4. Discussion
The aim of this systematic review was to appraise current available evidence regarding the effects of exercise prehabilitation and rehabilitation on perceived HRQoL and fatigue in patients undergoing surgery for NSCLC. Half of studies that applied exercise prehabilitation or exercise rehabilitation reported small statistically significant improvements in HRQoL, but in most studies this only concerned different subscales of the used questionnaire which make the clinical usefulness of the changes unclear. None of the studies reported a statistically significant decrease in fatigue. Due to the large heterogeneity of physical exercise training programs, the short intervention duration in some studies, the generally high risk of bias concerning methodological quality, and the high risk of ineffectiveness regarding therapeutic quality in most studies, the results of this systematic review must be interpreted with caution.
This is the first systematic review that examined the effect of exercise prehabilitation and/or rehabilitation on postoperative HRQoL and fatigue thereby accounting for the quality of the exercise intervention (i-CONTENT tool). Regardless of the risk of ineffectiveness score for the applied prehabilitation and/or rehabilitation programs, there was an inconsistent effect of exercise prehabilitation and/or rehabilitation on HRQoL. Heterogeneity across the items of the i-CONTENT tool, along with the risk of bias regarding HRQoL and fatigue, influences the certainty ratings supporting the efficacy and effectiveness of exercise prehabilitation and/or rehabilitation. Previous systematic reviews also reported a minimal improvement in HRQoL after prehabilitation and/or rehabilitation in patients with NSCLC undergoing surgery [
], which is possibly caused by the limited number and the low quality of evidence of included trials. In addition, in this systematic review, the duration of the exercise program was only one week in four studies [
Impact of one-week preoperative physical training on clinical outcomes of surgical lung cancer patients with limited lung function: a randomized trial.
] in which exercise training was performed by patients with NSCLC undergoing surgery, a duration of an exercise program of at least four weeks was recommended to improve HRQoL. Thus, those programs with a duration of merely one or two weeks might not be expected to improve HRQoL. In a previous study [
], it was reported that regained muscle mass associated with aging improved a patient's performance of activities of daily living, reduced cancer-related fatigue, and improved HRQoL after sixteen-weeks whole-body resistance training. Moreover, in a qualitative study [
] among patients with NSCLC, benefits of exercise rehabilitation were reported by participants such as improvements in muscle strength, aerobic fitness, and motivation, making sense of a goal that prevented boredom, feeling more prepared for future challenges, and improved ability to manage surgery-related symptoms. Most participants reported the exercise program to be feasible and to appreciate the individualized prescription and monitoring support from experienced physical therapists, as well as partly supervised exercises in a home-based setting [
]. Exercises or tools decreasing these symptoms are very important for both patients and clinicians to incorporate as goals in the exercise intervention [
A strength of this study was the use of i-CONTENT tool, leading to a more appropriate evaluation of the quality of the interventions next to methodological quality applied despite the heterogeneity of the used exercise programs [
]. Regarding study limitations, there was a large heterogeneity of physical exercise training programs and measures used to assess HRQoL (domains). Furthermore, there was a high risk of ineffectiveness of the exercise interventions (e.g., inadequate description or lack of supervision, personalization, objective monitoring of training intensity, monitoring of adherence) and a high risk of bias in many studies. The generally poor methodological and therapeutic quality of the included studies was mainly due to the non-description or incomplete description of the population, as well as the representativeness of the exercise intervention (e.g., frequency, intensity, type, time). There was considerable variation between studies concerning the type of surgery and the used outcome variables of HRQoL and fatigue questionnaires. This variation may have influenced the effects of exercise prehabilitation and/or rehabilitation on HRQoL and fatigue. Moreover, it should be mentioned that three studies took place at the same hospital in China [
]. This could have influenced expectations of researchers, physical therapists, (part of the) patients, methods, collection, and data analyses. As these three studies did not mention this potential overlap, it is important to raise awareness regarding both publication and reporting bias across these studies.
As mentioned earlier, the results of this systematic review must be interpreted with caution because of the heterogeneity of exercise programs and measures used to assess HRQoL and HRQoL domains, the high risk of ineffectiveness of the exercise interventions (e.g., caused by not describing or inserting of supervision, personalization, objective monitoring of exercise intervention and exercise intensity, training adherence), and the high risk of bias in many studies. Further research is required to investigate how to sustain positive effects of exercise over time and to determine essential attributes of exercise (mode, intensity, frequency, duration, timing) in patients with NSCLC, for an optimal effect on HRQoL and its subdomains.
5. Conclusion
There was an inconsistent effect of exercise prehabilitation and exercise rehabilitation on HRQoL in patients with NSCLC undergoing surgery, and no effect on fatigue. Due to the high risk of ineffectiveness of the exercise interventions, especially in case of a short duration of an exercise intervention, this systematic review cannot provide a definitive conclusion regarding the best form of exercises to improve HRQoL and reduce fatigue. It is recommended to investigate the impact of an exercise prehabilitation and/or rehabilitation program with high methodological and therapeutic quality (e.g., a duration of at least four weeks and a moderate- or high-exercise intensity) on HRQoL and fatigue in patients with NSCLC undergoing surgery in larger studies.
Funding statement
This study was supported by an unconditional research grant from the Research and Innovation Fund VieCuri (Fonds Wetenschap en Innovatie VieCuri, Venlo, the Netherlands). This study did not receive any specific grants from funding agencies in the public, commercial, or not-for-profit sectors.
Author contribution statement
Elisabeth J.M. Driessen: Study concepts, Data acquisition, Quality control of data and algorithms, Data analysis and interpretation, Manuscript preparation, Manuscript editing, Manuscript review, Robin J.E.F. Reinders: Study concepts, Data acquisition, Quality control of data and algorithms, Data analysis and interpretation, Manuscript preparation, Manuscript editing, Bart C. Bongers: Study concepts, Data analysis and interpretation, Manuscript preparation, Manuscript editing, Manuscript review, Maryska L.G. Janssen-Heijnen: Study concepts, Manuscript preparation, Janssen-Heijnen: Data analysis and interpretation, Manuscript editing, Manuscript review, Manuscript preparation, Melissa J.J. Voorn: Data acquisition, Quality control of data and algorithms, Data analysis and interpretation, Manuscript preparation, Manuscript editing, Manuscript review, V.E.M. van Kampen – van den Boogaart: Manuscript review
Data availability statement
The data underlying this article will be shared on reasonable request to the corresponding author.
Declaration of competing interest
The authors declare no conflict of interest.
Appendix A. Supplementary data
The following is the Supplementary data to this article:
Netherlands Cancer Registry: Incidence of Lung Cancer in The Netherlands according to type of histology. Available from: http://cijfersoverkanker.nl. Accessed March 30, 2021.
Netherlands Cancer Registry: Richtlijn niet-kleincellig longcarcinoom. Published 2004. Updated June 3, 2020. Available from: http://cijfersoverkanker.nl. Accessed March 30, 2021.
Stage III Non-Small Cell Lung Cancer in the elderly: patient characteristics predictive for tolerance and survival of chemoradiation in daily clinical practice.
Effects of lung rehabilitation therapy in improving respiratory motor ability and alleviating dyspnea in patients with lung cancer after lobectomy: a clinical study.
Preoperative exercise halves the postoperative complication rate in patients with lung cancer: a systematic review of the effect of exercise on complications, length of stay and quality of life in patients with cancer.
Effects of prehabilitation and rehabilitation including a home-based component on physical fitness, adherence, treatment tolerance, and recovery in patients with non-small cell lung cancer: a systematic review.
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