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Exercise intervention for patients surgically treated for Non-Small Cell Lung Cancer (NSCLC): A systematic review
Surgical Oncology, 1, 23, pages 17 - 30
Surgery remains the best curative option for appropriately selected patients with lung cancer. Evidence suggests that improving cardiovascular fitness and functional capacity can accelerate post-surgery recovery and reduce mortality. However, the effect of exercise intervention for patients surgically treated for Non-Small Cell Lung Cancer [NCSLC] has not been fully examined.
This review examines the literature regarding exercise intervention for patients who are surgically treated for NSCLC focussing on three key areas: methodological quality, intervention design (e.g. duration, frequency, type) and outcomes measured.
A search of Medline, EMBASE, CINAHL and PsychINFO was undertaken. Randomised Controlled Trials [RCTs] and non-RCTs including exercise training pre or post lung cancer resection were included. Descriptive characteristics were extracted and methodological quality assessed using Downs and Black appraisal checklist.
Twenty studies (eight RCT's) were included: nine pre-surgical, nine post-surgical and two pre to post-surgical. The quality of evidence is questionable with many limitations (e.g. small samples, inadequate allocation concealment and a lack of clear reporting on timing, adverse events and follow-up). Regarding design of exercise intervention and outcomes measured, there was much variation between studies producing a disparate set of data. An optimal programme is still to be determined; however, suggestions are made relating to type of exercise (i.e. mixing aerobic, resistance and breathing exercises). Preliminary work from this review suggests that exercise intervention compared with usual care both pre and post-surgery is associated with improved cardiopulmonary exercise capacity, increased muscle strength and reduced fatigue, post-operative complications and hospital length of stay. Results concerning pulmonary function, quality of life, and blood gas analysis were variable and inconsistent.
In order to implement exercise intervention appropriate for patients surgically treated for NCSLC, more high quality randomised controlled trials are required and more work concerning feasibility, acceptability and effectiveness of specific interventions on outcomes is warranted.
Keywords: Systematic review, Lung cancer, Oncology, Surgical, Exercise, Pulmonary rehabilitation.
Lung cancer is the second most common cancer in the UK and the leading cause of cancer death worldwide  and . It is frequently diagnosed at a late stage due to its initial asymptomatic course often leading to a poor prognosis. Lung cancer is histologically defined into two groups, Non-Small Cell Lung Cancer (NSCLC) and Small Cell Lung Cancer (SCLC). For patients diagnosed with NSCLC (approximately 85% of those diagnosed with lung cancer) survival rates remain much higher than for those diagnosed with SCLC  , in particular for those deemed eligible for tumour resection  . Surgical removal remains the best curative option for patients with early stage (stages I and II) NSCLC and for appropriately selected patients with locally advanced disease (stage IIIA)  .
At present approximately 11% of patients diagnosed with lung cancer are eligible for resection  , owing to the stage of disease, limited functional capacity and/or associated comorbidities  . However, with a government focus on the early detection of cancer and lung cancer screening programmes being trialled across the country, this may result in an increase in the number of patients with early stage disease, thus increasing the number of curative treatments being performed  . Despite the possibility of a cure, surgical resection is associated with significant morbidity, functional limitations and decreased Quality Of Life (QOL) post-surgery  and .
Cancer care is being directed toward developing interventions that improve overall functioning as well as longevity  . There has been a growing interest in the use of non-pharmacological interventions, such as exercise, both during and after cancer treatment. Exercise has been identified as a successful intervention to improve physical and psychological health in some cancer populations (mainly breast cancer)  . Furthermore, cardiopulmonary rehabilitation has been a key component in other pulmonary diseases such as Chronic Obstructive Pulmonary Disorder (COPD) and has been shown to be effective in reducing symptoms and minimising the exacerbation of disease  and .
The strongest evidence concerning exercise intervention for patients undergoing lung resection surgery is for patients with COPD. In this population exercise training has been shown to improve exercise capacity and Health Related Quality Of Life (HRQOL) and reduce symptoms such as dyspnoea, fatigue and depression  and . Cavalheri et al.  suggest however that although many patients with lung cancer will also have co-existing COPD the above effects of exercise training may not be applicable for two main reasons; firstly, patients with lung cancer that are eligible for surgery often have less severe COPD than those with COPD alone; and secondly, adjuvant treatment for lung cancer may affect the capability of patients to complete an exercise programme.
Of significance is that few exercise interventions have been developed specifically for people with lung cancer. In light of the anticipated changing landscape of lung cancer care, with the likelihood of an increase in the diagnosis of people with cancer at an early stage, exercise intervention for this population needs to be explored. This is of particular relevance to people undergoing surgical resection, who have potentially curative disease, yet currently experience significant symptom burden, decreased functioning and quality of life post-surgery  and . To enable exercise intervention for this population to be integrated into clinical practice, it is important to review the evidence and determine the optimal design of exercise intervention that will be feasible, acceptable and positively affect outcomes in a health care setting. To the authors knowledge there are currently no systematic reviews focussing on pre and post-operative exercise intervention for patient's treated surgically for lung cancer.
The objective of this review is to identify and examine the literature on exercise intervention for patients who are surgically treated for lung cancer in order to inform the design of future interventions. More specifically it aims to evaluate the quality of the evidence available, determine the most optimal design (type, frequency, intensity, duration and setting) of exercise intervention and examine the outcomes that have been measured.
- 1. What is the methodological quality of the studies to date that include exercise intervention for the surgically treated patient with lung cancer?
- 2. What designs of exercise intervention have been trialled and what aspects have been reported to be effective?
- 3. What outcomes have been measured and have they been affected by exercise intervention compared with patients receiving usual care?
This review has been carried out systematically and has been conducted in line with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statement guidelines  which aim at optimising the reporting of systematic reviews. A review protocol was developed prior to starting the review and followed vigilantly.
A comprehensive systematic search of the following electronic databases; Medline, EMBASE, CINAHL and PsychINFO, was undertaken. An outline of the search conducted on Ovid MEDLINE® is given in Fig. 1 [note that the suffix exp = exploded term, / = MeSH and mp. = title, abstract, original title, name of substance word, subject heading word, keyword heading word, protocol supplementary concept, rare disease supplementary concept, unique identifier (free text term)].
Reference lists of included studies were manually reviewed for additional relevant references and journal alerts were subscribed to.
Due to the nature of this area of research, in that it is a newly emerging field, both randomised and non-randomised studies were considered to acquire a complete understanding of the topic area. The key inclusion criterion was that all studies, regardless of design, had to include some form of physical exercise training for patients surgically treated for NSCLC. This review intended to include quantitative, qualitative and mixed method study designs. All poster abstracts and non-English full-text articles were excluded.
Studies that included participants that were diagnosed with resectable NSCLC were included in this review. Studies with <65% of the patient population were excluded to ensure a consistent sample.
Exercise intervention was defined as supervised or unsupervised inpatient, outpatient, community or home-based intervention including any type of exercise training applied to patients surgically treated for NSCLC.
All outcomes measured were recorded in this review.
Assessment of methodological quality
Two reviewers independently assessed the methodological quality of each study according to the Downs and Black quality appraisal checklist  . This checklist consists of 27 questions to evaluate both randomised and non-randomised studies, evaluating study reporting and internal and external validity.
The evaluations were cross-checked between two reviewers and the availability to go to a third reviewer was optional to resolve any disagreements. Studies were not excluded on the basis of methodological quality as it was the aim of this review to learn from the previous work in the field in order to inform future design of exercise intervention.
Studies that met the inclusion criteria were independently assessed and data regarding participants, intervention and all measured outcomes were extracted.
Synthesis of results
Due to the heterogeneity of exercise interventions, outcomes measured, tools used and the lack of robust RCT's, a systematic narrative review was conducted, opposed to a meta-analysis.
The initial search returned 1920 journal articles after duplicates had been removed. Three articles came from other sources (journal alerts) and were included in this review. After preliminary screening of titles 1850 articles were deemed to be irrelevant and were excluded leaving 68 studies to be retrieved. After reviewing retrieved abstracts, 32 articles were excluded (16 were reviews and 16 were non-English). Finally 36 full-text articles were reviewed and 25 fulfilled the inclusion criteria for this review of which 19 were original studies (one article reported two studies). Each reference list was screened for relevant studies however no new studies were included from this step. The search is current up to May 2013.
Of the 36 full-text articles that were reviewed reasons for exclusion included; i) not a published study (e.g. abstract from conference or study protocol (n = 8)) ii) the intervention did not include exercise training (n = 1) and iii) the study included <65% patient of the patient population (n = 2).
Study characteristics are presented in Table 1 . Of the 20 studies included in this review eight are RCTS's , , , , , , and  with participants randomised to either an exercise intervention or control group. Benzo et al.  report on two RCT's which have been included as two separate studies; however one of these studies (study 1) was stopped early due to poor recruitment. Two studies  and  report on non-randomised controlled trials and both used historical controls. The remaining ten studies were considered as Single Group Trials (SGT's), these studies observed a single cohort over the period of an intervention without including a control group. Hoffman et al.  and  report on one study that consisted of two phases.
|Reference (country)||Preoperative/post-operative||Study design||Population and treatment||Gender and age|
|Arbane et al. 2010 (UK)||POST||RCT||53 (control 26, Intervention 27), NSCLC, stage I–IV, 100% post-surgical (open thoracotomy or VATs)||28 male, mean age 64|
|Benzo et al. 2011 Study 1 (USA)||PRE||RCT||9 (control 4, Intervention 5), lung cancer resection by open thoracotmoy or VATs and moderate-severe COPD||NR|
|Benzo et al. 2011 study 2 (USA)||PRE||RCT||19 (control 9, Intervention 10), lung cancer resection by open thoracotmoy or VATs and moderate-severe COPD||9 male, mean age control = 72.0, intervention = 70.2|
|Bobbio et al. 2007 (Italy)||PRE||SGT||12, NCSLC stage I or II, VO2 max ≤15 ml/kg/min, Surgery – lobectomy||10 male, mean age 71|
|Cesario et al. 2007a (Italy)||POST||CT||25 (+186 control) NSCLC, Surgical (lateral musce sparing thoracotomy)||NR|
|Cesario et al. 2007b (Italy)||PRE||SGT||8, denied surgery on basis of poor pulmonary function but had favourable clinical staging (8 ended up having lobectomies) stage I-Iib||NR|
|Coats et al. 2013 (Quebec)||PRE||SGT||16 (only 13 analysed), under investigation for NSCLC (stage I–IV) awaiting surgical resection (n = 10)||5 male, 8 female, mean age 59 ± 9|
|Divisi et al. 2012 (Italy)||PRE||SGT||27, NSCLC stage I + COPD, not fit for surgery at baseline (functionally inoperable) but all had lobectomy post intervention||20 men, mean age 55|
|Granger et al. 2012 (Australia)||POST||RCT||15 (control 8, Intervention7), suspected lung cancer (those confirmed n = 10 (67%)), stage I-IV, Surgery all patients||53% male, mean age 65.5|
|Hoffman et al. 2013 (USA)||POST||SGT||7, post-surgical NSCLC stage I-IIIa||5 female, 2 male, mean age 64.6|
|Jones et al. 2007 (Canada)||PRE||SGT||25, suspected surgical lung cancer (NSCLC 65%) stage I-IIIA||70% female, mean age 65 ± 10|
|Jones et al. 2008 (USA)||POST||SGT||20, NSCLC stage I–IIIB, 80% surgery||53% male, mean age 62|
|Morano et al. 2012 (Brazil)||PRE||RCT||24 (12-PR, 12 CPT), NCSLC stage I–IIIA with pulmonary disease and impaired spirometry, surgical resection by thoracotomy or VATS (n = 21)||5 male in CPT and 4 male in PR, mean age 68.8 in CPT and 64.8 in PR|
|Peddle-McIntyre et al. 2011 (Canada)||POST||SGT||17, 94% NSCLC stage I-IIIB and limited stage SCLC, on average 3 and a half years post-surgical (82% surgical)||7 male, mean age 67|
|Pehlivan et al. 2011 (Turkey)||PRE -POST||RCT||60 (30 control, 30 intervention), NSCLC stage IA-IIIB, surgery (lobectomy/pneumonectomy)||NR, mean age Intervention group – 54.1, control group – 54.7|
|Reisenberg and Lubbe 2010 (Germany)||POST||SGT||45, NSCLC stage I-IIIB + SCLC (2 limited an 1 extensive), undergone treatment (88% surgical) time since last treatment no more than 14 days||gender NR, mean age 60.2|
|Sekine et al. 2005 (Japan)||PRE-POST||CT||22 + 60 historical control, NSCLC stage I–IV with COPD, thoracotomy||22 male in rehab (95.5%) and 55 male in control (91.7%), age (rehab – 70.4 ± 4.6, control – 69.0 ± 5.5)|
|Spruit et al. 2006 (Netherlands)||POST||SGT||10, NSCLC (n = 9), SCLC (n = 1) + impaired pulmonary function and exercise intolerance, 3 months following treatment, stage I–IIIB||8 male, mean age 65.5|
|Stigt et al. 2013 (Netherlands)||POST||RCT||57 (control = 26, intervention = 23), NSCLC resectable, thoracotomy 4 weeks post-discharge||91% male active group and 73% male control group, mean age active group – 63.6 ± 10.2, control – 63.2 ± 10.3|
|Wall 2000 (USA)||PRE||RCT||104, NSCLC I-IIIA surgery only (no chemo/radio therapy)||53.8% male, mean age 65|
Nine of the 20 studies included exercise intervention in the preoperative period , , , , , , , and  and nine in the post-operative period , , , , , , , , and , the remaining two studies  and  included exercise intervention from the preoperative period continuing over into the post-operative period and have been termed pre–post-operative studies in this review.
All 20 studies used quantitative designs and no qualitative work was found in the area. The views of patients and health professionals were not evident in the literature. Only three studies , , and  measured subjective variables (using a survey) looking at participants evaluation of the intervention.
In total, the 20 articles consisted of 575 participants, not including the 246 historical controls, making the average study size 28.75 participants (range = 7–104). The mean cohort age was 64.07 years across 17 of the studies, three studies  (study 1)  and  did not report age. All studies that reported gender recruited both male and female participants and the average male percentage of recruitment was 57.29% (range 29%–95.5%). Five studies  (study 1) , , , and  did not report on gender.
Stage of cancer
The majority of studies , , , , , , , , and  included patients with stage I to IIIA or IIIB disease. Four studies , , , and  included patients with up to stage IV disease, two studies  and  included patients with stage I–II disease and Divisi et al.  included patients with stage I disease only, however patients also had to have confirmed COPD. Four studies  (study 1 and 2)  and , did not report stage of disease however two of these studies  and  were post-operative studies and therefore patients would be considered operable stage disease.
Using the Downs and Black  quality assessment tool, consensus was reached for each article by two reviewers. Reviewers were not blinded to authors, institution or journal of publication. The overall methodological quality of studies was low mainly due to the small number of RCT's included. For studies that lacked a control group the main limitations (apart from lack of control, randomisation and blinding) included a lack of clear reporting on inclusion and exclusion criteria , , , and  and adverse events , , , , , and .
The results of the assessment of RCT's revealed that none of the studies were free from risk of bias. All eight studies were described as RCTs, but allocation concealment was only adequate in five studies , , , , and . Other forms of risk of bias included; an uncertainty about the blinding of outcome assessors , , , , and  and the timing of the outcome assessment after the intervention  (study 2); small sample sizes (n < 20)  (study 1 and 2)  with only two  and  reporting a power calculation; and three studies did not adequately report on losses to follow-up  (study 1)  and . Also, only three RCT's reported on adverse events  (study 1 and 2)  .
Intervention designs are summarised in Table 2 .
|Reference||Length of intervention||Duration of sessions||Exercise type||Intensity||Frequency||Supervised/unsupervised||Inpatient/outpatient||Group/individual||Education/smoking cessation|
|Arbane et al. 2011||12 weeks (+5 days)||Aerobic 5–10 mins1 for each component||Resistance (weights) + aerobic (walking, marching and recumbent bike)||60–80% MHR2||2×/day||Both||Both||Individual||NR3|
|Benzo et al. 2011 Study 1||4 weeks||NR – “used current guidelines for exercise prescription”||NR||NR||NR||NR||NR||NR||NR|
|Benzo et al. 2011 study 2||1 week||20 min lower extremity + upper extremity + strength exercises + breathing 20 mins + education||Aerobic (treadmill, step and arm ergometer) + resistance + breathing||Intensity that they felt “very confident” they could sustain||2×/day over 5 days||Supervised||NR||Individual||Education|
|Bobbio et al. 2008||4 weeks||1 1/2 h||Aerobic (cycling) + stretching + breathing (incentive spirometry) + resistance (weights)||5 min at 30% MWR4 followed by 30 min at 50% increased to 80%, weights NR||5×/week for 4 weeks||Supervised||Outpatient||Individual||Smoking cessation + optimisation of drugs|
|Cesario et al. 2007a||20 sessions||3 h||Aerobic (cycling, walking) + resistance + breathing||Aerobic 70–80% MWL5, resistance NR||5×/week||Supervised||Inpatient||NR||Education|
|Cesario et al. 2007b||4 weeks||3 h||Aerobic (cycling, walking) + breathing||Aerobic 80% MWL||5×/week||Supervised||Inpatient||NR||Education + smoking cessation|
|Coats et al. 2013||4 weeks||Aerobic 30mins + muscle strength exercises||Aerobic (walking and cycling) + resistance||60–80% PL6||3–5×/week||Both||Home-based||Individual||Weekly telephone calls|
|Divisi et al. 2012||4–6 weeks||1 1/2 h||Aerobic (cycling + walking) + breathing||70% MWR||6×/week||Supervised||NR||Individual||Diet advice, optimisation of drugs + smoking cessation|
|Granger et al. 2013||Post-surgery to discharge + 8 weeks outpatient||1 h||Aerobic (walking + cycling) + resistance (upper and lower) + stretching||HR7 85% maximum predicted||2×/day until discharge then twice weekly||Both||Both||Individual||Telephone calls|
|Hoffman et al. 2013||6 weeks (phase 2 + 10 weeks)||5 min per day progressing to 30 min||Aerobic + balance||Up to 60% HRR8||5×/week||Unsupervised||Home-based||Individual||Telephone calls|
|Jones et al. 2007||Until surgical resection, mean of 30 sessions||20–30 min + 5 min warm up and 5 min cool down||Aerobic (cycling)||60–100% baseline VO2 peak||5×/week on consecutive days||Supervised||Outpatient||Individual||NR|
|Jones et al. 2008||14 weeks||15–45 min increasing over 14 weeks||Aerobic (cycling)||60–100% PL||3×/week non-consecutive days||Supervised||Outpatient||Individual||NR|
|Morano et al. 2012||4 weeks||10 min increasing to 30 min + resistance training +10–30 min of IMT9||Strength and endurance + breathing + flexibility||80% max load and 20–60% IMT||5×/week||NR||NR||NR||Education|
|Peddle-McIntyre et al. 2012||10 weeks (28 sessions)||NR||Resistance + breathing + stretching||60% 1RM10 to progress to 85% 1RM||3×/week non-consecutive days||supervised||Outpatient||Individual||NR|
|Pehlivan et al. 2011||1 week pre-op until discharge||According to patients tolerance||Aerobic (walking on treadmill + wandering around the centre) + breathing||“Patients tolerance”||3×/day walking + 2×/day chest physiotherapy||Supervised||Inpatient||NR||NR|
|Reisenberg and Lubbe 2010||28 days||30 min per day interval training (3–5 min)||Aerobic (cycling)||Sub-maximal||Daily||Supervised||Inpatient||NR||NR|
|Sekine et al. 2005||Time of admission to operation (approx. 2 weeks)||Breathing 15 min 5×/day + pulmonary exercises for 30 min and walking more than 5000 steps every day||Breathing (incentive spirometry, abdominal breathing, huffing and coughing) + aerobic (walking)||NR||Daily (breathing 5× per day)||Both||Inpatient||NR||Smoking cessation|
|Spruit et al. 2006||8 weeks||40 min aerobic + weights +30 min of gymnastics||Aerobic (Cycling, walking) + resistance (weight training) + Gymnastics||Cycling 60% PL and walking at 80% PL, weights −60% 1RM||Daily||Supervised||Inpatient||Group of patients with COPD||NR|
|Stigt et al. 2013||12 weeks||1 h||Aerobic (Cycling) + resistance||60–80% PL||2×/week||Supervised||Outpatient||NR||NR|
|Wall 2000||Mean 7 days (range 1–20 days)||Walking 1 mile daily + stair climbing 40 steps per day + resistance – repeat 10 times 2×/day + breathing 5 times 2×/day||Aerobic (walking + stair climbing) + resistance + breathing||NR||Daily||Unsupervised||Home-based||Individual||NR|
Abbreviations: 1minutes, 2maximum heart rate, 3not reported, 4maximum work rate, 5maximum work load, 6peak load, 7heart rate, 8heart rate reserve, 9inspiratory muscle training, 10one repetition maximum.
Length of intervention
The majority (six out of nine) of pre-surgical studies focused on four weeks exercise intervention. Divisi et al.  started with a four week intervention but extended it by two weeks for nine patients who required further improvement before surgical resection.
Study 1 in Benzo et al.  found that four weeks of pre-surgical intervention was not feasible due to patients and health professionals' unwillingness to delay surgery. Benzo et al.  therefore carried out a second study which included a ten session exercise intervention to be completed over one week (twice daily). Studies conducted in the post-operative time period were mostly longer due to the time period available (ranged from four to sixteen weeks).
Type of exercise
All studies included aerobic activity (mainly walking and cycling) as part of the exercise intervention apart from one  which focused entirely on resistance exercise. Nine studies included breathing exercises  (study 2) , , , , , , , and  most commonly consisting of Inspiratory Muscle Training [IMT] and abdominal exercises.
Frequency of sessions ranged from two times per week to two sessions per day. Studies that included daily exercise sessions were mainly those where participants were inpatients , , , and . Most often the studies that included breathing exercises completed sessions numerous times a day  and  (study 2)  and .
Studies that included post-operative outpatient sessions delivered sessions mainly twice weekly and some advised further sessions unsupervised at home  and . The majority of home-based studies prescribed frequency in line with the current physical activity guidelines for adults (5 times per week)  .
Cardiovascular intensity ranged from 50 to 100% of varied measures of intensity (e.g. max work load, max heart rate, VO2 Peak) limiting the process of comparison. The majority of studies considered their programme to be of moderate intensity , , , , , , , , , , , and .
One study focused on light intensity exercise  and  and mentioned this to be highly feasible and acceptable. A further two studies did not report an exact intensity of exercise but instead asked patients to exercise at a pace they felt confident  (study 2) or according to the patients tolerance  .
Studies  (study 2) , , , , and including strength training generally reported an intensity of between 60 and 80% of one repetition maximum (1 Rep max) or at a level participants felt confident  .
Duration of session
The duration of each exercise session was not always easily determined due to the type of exercise performed. For example sessions that included resistance exercise focused more on repetitions rather than the time it took to perform the exercise. Although many studies  and  (study 2) , , , , and  reported accumulating 10–45 min of aerobic exercise throughout each session, other studies , , , , , , , , , and  reported longer sessions (e.g. 3 h) without a breakdown of minutes of exercise/rest.
The majority of studies (n = 17) reported supervised exercise sessions. However, six of these studies  (study 2) , , , , and  did not report who supervised the sessions. Supervision was mainly carried out by a physiotherapist, however, three studies , , and  were conducted by a rehabilitation team; two  and  by an exercise specialist; and one  by an exercise physiologist.
One study  reported using group exercise intervention where participants were entered into an inpatient rehabilitation group for patients with severe COPD.
Five studies included participants as outpatients , , , , and , three exclusively provided a home-based programme , , and  and six , , , , , and  reported participants to be inpatients. Four studies  (study 1 and 2)  and  did not report whether the participants were inpatients or outpatients. Two post-surgical studies  and  started exercise intervention in an inpatient setting and post-discharge prescribed home-based sessions.
Inclusion of control group
Ten studies  and  (Study 1 and 2) , , , , , , and  included control groups, with eight  and  (study 1 and 2) , , , , and  classified as RCT's and two  and  as controlled trials. In the majority of RCT's the control group received usual care and therefore received exactly the same treatment without the exercise intervention. Some studies included other intervention variables for the control group such as telephone intervention  , chest physiotherapy  and  and education  , thus reducing the ability to solely examine the effect of exercise intervention.
Other components to the rehabilitation programme
Although the main focus of studies was exercise intervention, some studies also involved other components to the rehabilitation programme. Four studies  (study 2) , , and  included education sessions on topics such as patients role in recovery, dietary advice, pulmonary pathophysiology, breathing techniques and relaxation/stress management. A further four studies , , , and  reported including smoking cessation. Finally, three studies , , and  used telephone calls to encourage adherence and observe patients' perceptions (barriers etc.) and progress.
The potential effect of each component (exercise, physiotherapy, diet advice, etc.) should be considered when interpreting results from these studies.
Outcomes measured are presented in Table 3 .
|Reference||Measurement (tool)||Time measured||Results|
|Arbane et al. 2011||Quadriceps strength (magnetic stimulation), exercise tolerance (6MWD1), QOL2 (EORTC-QLQ-LC133), hospital stay and POC4||Pre-op, 5 days and 12 weeks post-op||Quadriceps strength – significant fall in control group and non-significant improvement in intervention group at 5 days post-op, no significant difference at 12 weeks. Exercise tolerance – decreased in both groups at 5 days, returned to preoperative values in both groups at 12 weeks. QOL – no significant difference within subjects or between groups. Length of hospital stay – (mean 8.9 active and 11.0 control) and POC (2 in active and 3 in control) no significant differences between groups.|
|Benzo et al. 2011 Study 1||Hospital stay and POC||NR5||No differences were found in any outcome between groups – Study stopped prematurely (9 patients in 18 months)|
|Benzo et al. 2011 study 2||Hospital stay and POC||Post-op time NR||Patients in the PR6 arm had fewer days in hospital (p = 0.058), had fewer days needing a chest tube and lower incidence of prolonged chest tube.|
|Bobbio et al. 2008||Exercise tolerance (VO2max7, CPET8), hospital stay, POC, lung function||Baseline, last day of PR and post intervention||Exercise tolerance – VO2 max mean improvement 2.8 ml/kg/min (p = <0.01). VO2 max at AT9, work load capacity and oxygen pulse all significantly improved (p = <0.016, <0.001 and <0.007 respectively) at end of PR. 11 underwent surgery – median hospital stay 17.5 ± 14.8 days, 8 patients had POC. Pulmonary function – non-significant.|
|Cesario et al. 2007a||Exercise capacity (6MWD), pulmonary function (spirometry), blood gas analysis (radial artery)||Baseline, 1 month after discharge (intervention group at end of intervention)||Exercise capacity – Intervention group significantly increased 6MWD and Borg scale at rest and exertion improved. Blood gas – PH levels and Hb saturation during 6MWD increased. Pulmonary function – did not significantly change. Control group – spirometry values and 6MD decreased.|
|Cesario et al. 2007b||Exercise capacity (6MWD), pulmonary function (spirometry), POC||Before and after PR||Exercise capacity – 6MWD improved by 47.4%. Patients starting with the worst initial conditions received most benefit. Pulmonary function – FVC10 significantly increased, non-significant improvements for FEV111. All patients re-entered functional and clinical criteria for surgery and were operated on. Morbidity was 25% (2/8 – 1 post-op haemorrhage and 1 AF12).|
|Coats et al. 2013||Pulmonary function (spirometry), exercise capacity and oxygen consumption (incremental cycling exercise test, constant work rate cycle exercise, 6MWD), muscle strength (max voluntary contraction), QOL (sf-3613, EORTC-QLQ-30 + QLQ-LC13 and HADS14), feasibility and acceptability (recruitment rate, adherence, adverse events, subjective perception of obstacles)||Baseline and post intervention||Pulmonary function – no significant change. Exercise capacity – VO2 peak no significant change, constant work rate cycle duration significantly improved by 60%, 6MWD improved by 28 ± 29 m (p < 0.05). Isotime, VO2, carbon dioxide output, ventilation and respiratory exchange ratio were reduced post intervention. Muscle strength – strength of deltoid, triceps and hamstrings increased significantly (p = <0.05). Hand grip, biceps and quadriceps strength were not statistically significant. QOL – No significant improvements in QOL apart from depression. Feasibility and acceptability – completion rate 81%, no adverse events, mean adherence 125% and 83% for aerobic and strength respectively.|
|Divisi et al. 2012||Blood gas, exercise capacity (VO2 max, 6MWD, CPET), lung function (spirometry), post-op morbidity||Baseline and post intervention||Blood gas – significant increase in PaO2. Exercise capacity – VO2 max significantly increased (p = 0.00001) Pulmonary function – FEV1 significantly improved (p = 0.02). Post-op morbidity of 15%.|
|Granger et al. 2013||POC, hospital stay, safety (adverse events), feasibility (attendance), functional capacity (6MWT), functional mobility (TUG15) and HRQOL16 (SF-36, EORTC-QLQ-C30-L13)||Preoperative and 2 and 12 weeks post-op||POC and hospital stay – Patients in the PR arm had fewer days chest tube and lower incidence of prolonged chest tube, also PR arm had fewer days in hospital (close to being significant (p = 0.058). Safety – no adverse events. Feasibility – 71% delivered sessions. Functional capacity – intervention group improved 6MWT to a greater extent however TUG improved more in control group. HRQOL- non-significant.|
|Hoffman et al. 2013||Feasibility (recruitment rate – % eligible of those who were recruited who consented), adherence (% participating that adhered), safety (adverse events) acceptability (designed a questionnaire), Cancer Related Fatigue (BFI17 measure), perceived self-efficacy (questionnaire)||Pre-surgery, post-surgery baseline and weekly||Feasibility – 80% approached consented, 100% retention, adherence rate 96.6%, no adverse events. Acceptability – highly acceptable. Fatigue – decreased from baseline (post-surgery to week 4) and increased when patients started chemotherapy. Perceived self-efficacy – decreased from pre-surgery to post-surgery, gradually increased during the intervention for both walking and balance, perceived self-efficacy for managing fatigue decreased post-surgery but increased above pre-surgical baseline measurements at week 6. Phase 2 – 100% recruitment and retention, adherence declined from 96.6% in phase I to 87.6% at the end of phase II.|
|Jones et al. 2007||Exercise capacity (6MWT, CPET), pulmonary function (Spirometry), POC, adverse events, adherence||Baseline to pre-surgery||Exercise capacity – mean VO2 peak increased by 2.3 ml/kg/min (p = 0.002), 6MWD increased by 40 m (p = 0.003), for participants who attended >80% of prescribed classes VO2 peak and 6MWD increased by 3.3 ml/kg/min and 49 m respectively. Pre-surgical exercise capacity decreased post-surgery but not beyond baseline levels. Pulmonary function – non-significant results. POC – 35%. Adverse events – 2 reported. Adherence rate – 72%.|
|Jones et al. 2008||VO2 peak (CPET), QOL (FACT-L17, FACT-G18, TOI19), exercise adherence(attended/prescribed)||Baseline and post intervention||VO2 peak – no significant increase. QOL- significant favourable changes found for functional-wellbeing (p = 0.007) and fatigue (p = 0.03), TOI increased by 9 points (p = 0.03) others did not reach significance. Adherence – 85%.|
|Morano et al. 2012||Functional parameters (Spirometry, 6MWT, blood gas), hospital stay and POC||Assessed before and after intervention||Functional parameters – (baseline to 1 month) improved significantly in FVC (p = 0.02) and percentage predicted (p = 0.00), 6MWD was improved (p = 0.00), blood gas- non-significant. Patients in intervention group had fewer days in hospital (p = 0.04), needing a chest tube (0.03), lower incidence of POC (p = 0.01) and less POC.|
|Peddle-McIntyre et al. 2012||Feasibility (adherence, eligibility, recruitment rate), physical functioning (muscle strength [1RM20] and endurance [number of reps to exhaustion], get up and go test, sit to stand test, 6MWT), PRO's (QOL [Sf-36, FACT-L], fatigue [FACT-fatigue], sleep quality [PSQI21], dyspnoea [MRC dyspnoea scale], anxiety [Speilberger state anxiety scale] and depression [CES-D1022])||Baseline and post training||Feasibility – adherence 87%, 3 adverse events (2× shoulder pain and 1× back pain). Physical functioning – muscular strength significantly improved, 52% (leg press) and 42% (chest press), muscular endurance improved significantly for chest press (p = 0.001) and leg press (p = <0.001). Peak inspiratory muscle pressure increased (p < 0.001). Significant improvements in 6MWD (p = <0.001), number of chair stands, arm curls and up-and-go time (p < 0.001, <0.001 and 0.015 respectively). PRO's/QOL-borderline significant improvements for role physical (p = 0.072), bodily pain (p = 0.101) and physical health component (p = 0.92).|
|Pehlivan et al. 2011||Pulmonary function (spirometry), blood gas, exercise capacity (maximum walking distance), ventilation perfusion, hospital stay and POC||Baseline, post intervention (before surgery)||Pulmonary function did not differ between groups after IPT23 (before surgery) however significant improvements in FVC, FEV and DLCO24 (p = 0.003, 0.01 and p < 0.001 respectively) were found within the intervention group. Blood gas – increased PaO2 and decreased PaCO2 (p < 0.001), peripheral oxygen saturation was higher in the intervention group (p = 0.008). Exercise capacity – increased significantly in intervention group. Hospital length of stay was 5.4 and 9.66 in the intervention group and control group respectively (p < 0.001). POC – 5 in control, 1 in intervention group.|
|Reisenberg and Lubbe 2010||Exercise capacity (6MWT, bicycle ergometery test, heart rate variability), pulmonary function (body plethysmography), QOL (EORTC QLQ-C30, QLQ-LC13 and SF36) and fatigue (MFI-2027)||Baseline and end of intervention||Exercise capacity – significant increase in 6MWT (322 ± 11 to 385 ± 13 m, p < 0.001), cycling work load performance (68 ± 3 to 86 ± 4, p < 0.001), HRR28 was reduced. HR29 variability significantly increased (9.7 ± 1 to 12.9 ± 1, p < 0.002). Pulmonary function – significantly increased. QOL – significantly improved (48 ± 3 to 62 ± 2, p < 0.001) and reduced fatigue (66 ± 3 to 41 ± 4, p < 0.001).|
|Sekine et al. 2005||POC, blood gas and pulmonary function (spirometry)||Before and one month after operation||No significant differences between groups of POC or blood gases, however prolonged 02 therapy and tracheostomy more frequent in the control group. Post-operative hospital stay was significantly longer in control group (0.0003). Pulmonary function – FEV1 less diminished in intervention group (p = 0.023) however FVC remained similar between groups.|
|Spruit et al. 2006||Pulmonary function (spirometry), exercise capacity (6MWD and peak cycling load)||Baseline and 8 weeks||Pulmonary function – no change. Exercise capacity – 6 MWD significantly improved (median 145 m – 43.2% of baseline values, p = 0.002) – without significant changes in Borg symptom scales for dyspnoea and fatigue. Peak cycling load increased (median 26 W, 34.4% from baseline, p = 0.0078).|
|Stigt et al. 2013||QOL (SGRQ30, SF-36), pain (MPQ-DLV31), exercise capacity (6MWD), pulmonary function and feasibility of combining rehab with adjuvant chemotherapy (attendance rates)||Baseline, 1, 3, 6 months and 1 year follow-up – QOL and pain. Before surgery and 3 months after discharge – pulmonary function and exercise capacity||No significant differences in QOL, control group reported less limitations at 3 months compared to the intervention group (p = .03) – difference disappeared at 12 months. Pain – Intervention group reported significantly more pain after 3 and 6 months (p = 0.042 and p = 0.010 respectively). The use of analgesics at 3 months was higher in the intervention group compared with controls (p = 0.048), Exercise capacity – 6MWD was improved in the intervention group at 3 months compared with the control group (p = 0.024). Pulmonary function did not significantly differ between groups. Feasibility – dropout rates were quite high and even more for those who received adjuvant chemotherapy.|
|Wall 2000||Hope (HHI32) and power (PKPCT. VII33)||7–10 days pre-surgery, day before surgery, 4–6 days post-surgery (prior to patients receiving information about their final surgical pathology)||Power increased in intervention group while the non-exercise group decreased. Hope – no differences.|
Abbreviations: 1six minute walk distance, 2Quality Of Life, 3European Organization for Research and Treatment of Cancer Quality of Life Questionnaire, 4post-operative complication, 5not reported, 6pulmonary rehabilitation, 7maximum oxygen consumption, 8Cardio Pulmonary Exercise Test, 9anabolic threshold, 10forced vital capacity, 11forced expiratory volume in one second, 12atrial fibrillation, 13Short Form – 36 assessment,14Hospital Anxiety and Depression Scale, 15Timmed Up and GO test, 16Health Related Quality Of Life, 17Functional Assessment of Cancer Therapy scale Lung, 18Functional Assessment of Cancer Therapy scale General, 19Total Outcome Index, 20one Repetition Maximum, 21Pittsburgh Sleep Quality Index, 22Center for Epidemiologic Studies Depression Scale – 10, 23intensive physical therapy, 24diffusion lung capacity for carbon monoxide, 25partial pressure of oxygen, 26partial pressure of carbon dioxide, 27multi-dimensional fatigue inventory, 28heart rate reserve, 29heart rate, 30St George Respiratory Questionnaire, 31McGill Pain Questionnaire, 32Herth Hope Index, 33power as knowing participation in change test.
Exercise capacity was the most commonly measured outcome, measured in thirteen studies , , , , , , , , , , , , and . This was measured using the six Minute Walk Distance test (6MWD) and/or a Cardio Pulmonary Exercise Test (CPET) test to measure VO2 max or VO2 peak. A further two studies  and  used a peak cycling load test to measure bicycle ergometer performance (measured in Watts).
Of the studies that used the 6MWD test, all but one  reported a significant increase in distance measured from baseline to post intervention (increase of 28 m–377 m [range]). However, this study  focused on muscle strength. They found a deterioration in walking distance immediately post-surgery (which is consistent with other studies)  however did not find an improvement in distance from baseline to twelve weeks. This may be due to the intervention focus on strength training. However, adherence to exercise was not monitored at home making this result difficult to interpret.
Those using CPET reported exercise capacity (VO2 max and VO2 peak) to increase significantly in three out of five studies , , and , with VO2 max improving between 2.8 and 6.3 ml/kg/min and VO2 peak improving by 1.7 ml/kg/min. Also, peak cycling load was shown to increase significantly in both studies  and  by 27% and 34.4% respectively. The study  that showed the highest percentage of improvement was twice as long in the duration of intervention (eight weeks compared to four weeks, both inpatient, post-surgical studies). Studies which recruited patients who had impaired exercise capacity at baseline (VO2 max <15 ml/kg/mi) , , , and  showed the most improvement post exercise intervention.
Pulmonary function (FEV1 and FVC) was measured in ten studies , , , , , , , , , and , most commonly tested using spirometry with two studies also using body plethysmography  and . Diffusion Capacity (DLCO) was measured in four studies , , , and . The majority of studies indicated non-significant results for all pulmonary function measures , , , , , and  however, four studies , , , and  reported improved pulmonary function. Furthermore, although Sekine et al.  did not find significant improvements, they reported less diminished FEV1 post-surgery in the intervention group compared with the control group and would suggest that prophylactic pulmonary rehabilitation may prevent some of the decline seen in pulmonary function post-surgery.
Quality Of Life (QOL)
Out of the eight studies , , , , , , , and  that measured QOL there were conflicting results, with some studies reporting improvements  and  but the majority reporting no change , , , , , and . Generic QOL measures that often lack sensitivity to disease specific symptoms were used in the majority of studies. For example, the SF-36 health survey, not yet validated in the lung cancer population, was the most commonly used tool to measure QOL, used in five of the seven studies , , , , and .
Riesenberg and Lübbe's  28 day post-operative inpatient study was the only study to report consistent significant findings across the QOL variables (physical, role, emotional, cognitive and social functioning and decreased symptoms). Jones et al.  reported improvements in QOL but only for patients who did not receive adjuvant chemotherapy. Furthermore, Coats, Maltais, Simard et al.  considered depression under QOL. They found that although there were no significant changes in QOL measures, depression scores measured by the HADS were significantly decreased (p = <0.05).
Only nine studies , , , , , , , and  reported recording adverse events. One study  reported two patients experiencing an abnormal decline in systolic blood pressure (<20 mmHg) and another study  reported three events; one patient experienced lower back pain, another patient experienced exacerbation of shoulder arthritis and another experienced shoulder pain post-testing. The other seven studies reported no adverse events.
Feasibility was measured in seven studies , , , , , , and  monitoring; eligibility, recruitment rate, completion/retention rate, consent rate, delivered sessions and attendance/adherence rate.
Eligibility rate, measured in two studies  and , ranged from 10% to 81%. Recruitment rate was measured in all seven studies and ranged from 43% to 80% (mean = 60.6%). Completion/retention rate was reported in two studies  and  as 81% and 100% respectively. Adherence/attendance rate was measured in all seven studies and ranged from 72% to 125% (some reporting more sessions attended than prescribed). Stigt et al.  found that the attendance rate amongst patients being treated with adjuvant chemotherapy was lower, 43% (mean).
Of significance is that only three studies , , and  explored patients' perceptions regarding acceptability, each using a questionnaire developed by the research team. Perceived benefits were reported as: helped to start performing physical activities, improved dyspnoea, improved strength and having more energy  . The main obstacles reported were lack of time and difficulty of integrating the intervention into an already busy schedule of several medical appointments.
The only study to report major complications with feasibility and acceptability was Benzo et al.  (study 1) in which patients and health professionals were reluctant to delay surgery for four weeks; thus their subsequent study was designed as a one week pre-surgical intervention.
Length of hospital stay and post-operative complications (POCs)
Four out of five studies that included a control group and compared length of hospital stay showed significantly fewer days (on average 5 days less) in hospital for patients in the exercise intervention arm  (study 2) , , and . The study  that did not show significant difference between groups was one that focused on improving muscle strength.
Furthermore, out of the four studies , , , and  to report on post-operative complications (POCs), two  and  reported less POCs (such as atelectasis, dyspnoea and pneumonia) in the exercise group compared with the control group while the other two studies did not result in significant changes  and .
Fatigue was measured in five studies , , , , , and  by a range of different tools including; the Brief Fatigue Inventory (BFI); Perceived Self-Efficacy for Fatigue Self-Management (PSEFSM); FACT-an; FACT-fatigue; and the multi-dimensional fatigue inventory-20 (MFI-20) questionnaire.
Studies that measured pre to post-surgical data found that fatigue increased significantly between the pre-surgery to immediately post-surgery time point; however, significant reductions in fatigue were found from baseline to post-intervention in three , , and  out of five studies.
In comparison, two studies  and  did not find significant reductions in fatigue severity from baseline to post-intervention. However, one  focused entirely on resistance exercise training and the other  was a preoperative intervention, suggesting that participants may have not been experiencing high fatigue levels pre-treatment.
In relation to patients receiving adjuvant treatment, Hoffman et al.  found that the two participants who did not receive adjuvant treatment after surgery experienced lower levels of fatigue than those who were receiving adjuvant chemotherapy.
Three studies , , and  measured muscle strength. From the studies reviewed it can be suggested that muscle strength improved for patients who participated in resistance exercise. The only study that did not show a significant improvement reported a non-significant increase in the intervention group which was statistically significantly different to the significant decrease in muscle strength in the control group  . It would seem that in this study exercise intervention had a prophylactic effect, preventing the decline in muscle strength seen in the control group.
Of the four studies that measured blood gas analysis , , , and  the majority reported non-significant findings. Only one study showed significant increase in both PaCO2 and PaO2  also showing improved SaO2. This again was the study that recruited participants with poor pulmonary function further emphasising the possible amplified effect of exercise intervention in this particular population. Cesario et al.  was the only other study to show significant findings for increased PaO2.
Further outcomes from three original studies , , and  were reported in subsequent articles , , , and . These outcomes include; inflammatory markers  , correlates of adherence  , motivational outcomes  and oxidative status  .
Jones et al.  reported the effects of pre-surgical exercise training on systemic inflammatory markers. Findings indicated that exercise training resulted in a significant reduction in ICAM-1 however other markers did not significantly change.
Peddle et al.  report on correlates of adherence to supervised pre-surgical exercise training using the theory of planned behaviour. Results indicated that significant correlates of adherence to exercise were perceived behavioural control (p = 0.004) and subjective norm (p = 0.014).
Peddle-McIntyre et al.  reported on changes in motivational outcomes in a resistance based exercise intervention. After the intervention, significant increases in self-efficacy and perceived behavioural control were found. Intention was significantly lower post-intervention and significantly correlated to instrumental attitude, self-efficacy, perceived behavioural control and affective attitude. Post-intervention self-efficacy was significantly correlated with planning.
Finally, Jones et al.  examined the effects of aerobic training on oxidative status post-surgery. Concerning individual isomers, only two increased significantly (iPF (2-alpha)-III and iPF (2 alpha)-VI.
This systematic review aimed to synthesise all available evidence with regard to exercise intervention for patients who are surgically treated for NSCLC. The results illustrate the infancy of the field under study, with only twenty studies across the spectrum being considered eligible for this review, of which the majority of studies included were observational SGT's. Studies included various forms of exercise intervention and investigated a wide range of outcomes (using various measures) that produced a disparate set of data. This in itself is an important finding as it indicates a lack of consensus around the design of exercise intervention, the most desired outcomes to be measured and the appropriate outcome measures to be used.
The quality of studies included was variable and the findings are tempered by this fact. Quality assessment revealed an overall weak methodological quality of study design in the area. This is mainly due to the number of studies not including a control group; however this review has also revealed limitations in the available RCT evidence, most notably the small numbers, poor/limited reporting of methodology and outcome assessment. Future trials should focus on including a control group, adequate randomisation, significant numbers powered for the primary outcome, validated and appropriate assessment tools and blinding of outcome assessors throughout the study. Also clear reporting of age, gender and treatment of patients should be reported and the documentation of adverse events mandatory in studies in order for the context, safety and transferability of interventions to be assessed.
The heterogeneity of exercise intervention programmes reviewed made comparisons difficult and from the studies above it is not evident as to what the optimal exercise programme should be for this population. In particular a pre-surgical and post-surgical intervention should be considered separately mainly due to the time period available and the physical status of the patient in each setting.
Due to the relatively small time period from diagnosis to surgery, pre-surgical studies were generally shorter in duration and more frequent in prescribed sessions per week to enable maximum benefit. However one pre-surgical study  mentioned that their exercise programme may have worsened fatigue due to the intense and demanding nature of the intervention in a population that was deconditioned and suffered significant comorbidity. So far the majority of studies utilise the current physical activity guidelines for adults (5 times per week)  , however this may be adapted when more research is completed concerning patients undergoing specific cancer treatments.
It is evident that exercise intervention is influenced greatly by the setting of intervention. For example, inpatient studies included more frequent supervised sessions. It remains questionable if this would be feasible and acceptable in an outpatient setting as travel has been reported as one of the main barriers regarding cardiac rehabilitation  . Realistically due to financial circumstances outpatient or home-based studies may be more financially manageable in the longer term. A review by Dalal et al.  that looked at home-based versus centre based cardiac rehabilitation found that adherence to the programme was superior for those who received a home-based programme; they also conclude that this may be more cost effective.
In relation to delivery (supervised/unsupervised), structure (group/individual sessions), duration, intensity of sessions and length of intervention, it is not clear which may be most beneficial. However based on the evidence  from the area of cardiac rehabilitation, depending both on the stage of treatment and the individual's ability and willingness to participate in exercise, what can be suggested is that this should be considered on an individualised level, relating to particular patient desires and needs.
With regards to type of exercise, aerobic exercise in comparison to other forms of exercise, for example resistance exercise alone, would seem superior for improving outcomes such as exercise capacity (VO2 max); however with only one small single group trial [SGT]  focussing on resistance exercise, it is impossible to make true comparisons. As one would expect, the study  that focused on resistance exercises alone showed a significant improvement in muscle strength. Thus, the combination of resistance and aerobic exercise training may provide the optimal training programme for this population.
Although exercise intervention has been included as a core component in cardiac rehabilitation, participation rates remain low. Three main barriers have been identified in the literature regarding participation; service and system level barriers (e.g. physician recommendation and misconceptions about cardiac rehabilitation) practical barriers (e.g. transport and parking); and thirdly, personal barriers (e.g. perceptions of the ability to control the disease)  . Research into the development of similar interventions should consider these barriers from the offset which may help design more acceptable interventions.
Preliminary findings from this review would suggest that exercise intervention compared with usual care both pre and post-surgery is safe, feasible and acceptable and associated with increased exercise capacity, reduced POC and hospital stay, increased muscle strength and reduced fatigue. However the results concerning pulmonary function, QOL, and blood gas analysis are variable and inconsistent.
The increase in exercise capacity post intervention is not particularly surprizing, it is a well-established finding in patients with COPD  and reviews including other cancer populations  and . However what was recognised in this review was that studies which recruited patients who had impaired exercise capacity at baseline (VO2 max <15 ml/kg/mi) , , , and  were those receiving the most benefit from exercise intervention.
Exercise capacity is an important consideration in the decision-making process regarding the feasibility of surgical resection. VO2 peak is reported as one of the strongest independent predictors of surgical complications  and poor exercise capacity has been shown to be a major determinant of post-operative morbidity and mortality following lung resection surgery  and . Therefore interventions aimed at improving exercise capacity may, in turn, lower the risks associated with poor cardiopulmonary function. Interestingly reduced POC and length of hospital stay were found in the majority of pre-surgical intervention studies that measured these outcomes, affirming that they may be linked to increased exercise capacity.
Increased muscle strength and reduced fatigue are also promising findings. Muscle strength was improved particularly in studies that included resistance exercise, highlighting the need for a varied intervention. Regarding fatigue, results from this review and from a review by Cramp and Byron-Daniel  , looking at exercise intervention for the management of CRF, suggest that physical exercise can help to reduce fatigue both during and after treatment for cancer. However, the evidence is not sufficient to demonstrate the best type or intensity of exercise for reducing the symptom of fatigue.
Improvements in outcomes, in particular exercise capacity, together with no change in pulmonary function may be an unexpected finding at first sight, however this coincides with previous research in patients with other pulmonary diseases, for example, COPD  and  and restrictive disorders  . Overall the evidence is unclear as to how exercise may or may not improve pulmonary function in this population.
Regarding QOL, although the majority of results were non-significant, a few explanations were evident. Studies conducted in the preoperative period  and  may have found no change in QOL due to a possible ceiling effect. Of the three RCT's , , and  that measured QOL, all were post-operative interventions and found no significant differences in QOL between groups, however certain limitations must be emphasised in relation to this result. Arbane et al.  lacked reporting adherence to home-based exercise leaving the result open to scrutiny of how much exercise was undertaken, in Granger et al.'s  study the intervention group was significantly fitter at baseline, and finally, Stigt et al.  did not use a disease specific tool to measure QOL but instead used one designed for patients with COPD. Differences in tools (generic/specific), design of intervention and extent of surgery made comparisons and conclusions concerning QOL difficult. To clarify this matter, it is desirable that future studies use equal measurement instruments for which reliability and validity has been established in the relevant patient population.
From the wider literature it is clear that further outcomes should be explored that have not been included in the reviewed papers, such as; pain, breathlessness and fear of recurrence which have been reported to be some of the main outcomes that concern patients  and . Finally, missing from the literature was both the study of patient experience/beliefs and of long term follow-up on outcomes and recurrence. Therefore questions remain about the sustainability and long term effectiveness of exercise intervention.
The lack of qualitative evidence is a finding worth commenting and suggests that the present studies are ‘researcher led’ and the opinions of patients and health professionals have not been fully explored in the development stage of study design. The Medical Research Council (MRC) framework  for developing complex interventions suggests that in the development stage of an intervention it might be necessary to do some new primary research, for example interview key ‘stakeholders’, to ensure the intervention is appropriate for those involved. This reveals an area worth exploring to enhance and evaluate the design of exercise intervention; ensure it reflects the needs of those receiving the intervention; and so it can be implemented in clinical care.
This review has revealed that currently there is insufficient evidence to conclude what is the best design of exercise intervention for patients surgically treated for lung cancer. Further methodologically sound studies are urgently required to determine the optimal exercise intervention for this particular patient group. To facilitate comparison between studies and allow replication, it is essential that future studies clearly describe the content of the exercise intervention, adherence rates to the intervention and any possible adverse events, thus giving insight into the exercise dose received and safety of the intervention.
Study conception and design: Crandall.
Acquisition of data: Crandall.
Analysis and interpretation of data: Crandall, Maguire, Campbell.
Drafting of manuscript: Crandall.
Critical revision: Kearney, Maguire, Campbell.
Conflict of interest statement
The authors declare that they have no conflict of interest.
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a University of Dundee, School of Nursing and Midwifery, 11 Airlie Place, Dundee DD1 4HJ, Scotland, UK
b University of Surrey, School of Health and Social Care, Faculty of Health and Medical Sciences, Duke of Kent Building, Guildford GU2 7TE, Surrey, UK
c University of Dundee, Institute of Sport and Exercise, Dundee DD1 4HN, Scotland, UK
∗ Corresponding author. Tel./fax: +44 (0) 1382 388 533.
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