Pulmonary Resection And Intensive Rehabilitation
Condition: Lung Cancer
MeSH terms: Lung Neoplasms
Study type: Interventional

Summary: 
      Lung cancer is the leading cause of cancer death in males, and is increasing in females. Up
      to 73% of affected patients present with Chronic Obstructive Pulmonary Disease (COPD). Most
      lung cancer patients have an average survival of about 8 months from diagnosis. Lobectomy for
      initial stages has demonstrated higher survival rates, but only 15% to 25% are surgical
      candidates; unfortunately, cardiopulmonary impairment mainly due to coexisting COPD reduces
      this number and patients undergo medical treatment or marginal lung resection, with minor
      functional impact but possible ineffective control of disease.

      Furthermore, COPD is associated with increased postoperative morbidity and mortality, longer
      in-hospital stay, need for additional treatments, and a rise in sanitary costs.

      The investigators planned a randomised trial on surgical candidates to assess the effect of
      comprehensive pulmonary rehabilitation on functional and surgical outcomes, functioning, and
      Quality of Life (QoL).
    

Detailed description: 
      Preoperative pulmonary rehabilitation ameliorates functional parameters responsible for
      inoperability in COPD patients; candidates for surgery could benefit from this functional
      improvement in terms of wider possible lung resection and lower incidence of postoperative
      complication.

      Likewise, postoperative respiratory rehabilitation significantly improves respiratory
      function and exercise capacity in treated patients but the effect on long-term functioning
      and QoL is not known.

      Current studies present small-sized samples and short follow up. The impact of comprehensive
      rehabilitation on overall functioning, depression, pain, and QoL has only been reported for
      COPD patients. Moreover, the rate of anatomical resection and postoperative morbidity in
      compromised COPD patients treated with intensive rehabilitation has never before been
      reported in randomised trials.

      The investigators hypothesise that: comprehensive rehabilitation intervention in lung cancer
      patients eligible for surgical treatment may reduce pain, comorbidity (pneumonia and other
      pulmonary complications requiring further treatments), depression, and deconditioning and
      improve QoL 1 to 6 month after surgery; active lifestyle and regular follow up may reduce
      long-term quality of life decline; early pulmonary rehabilitation can improve lung function
      tests making proper surgical treatment with curative intent possible in patients affected by
      COPD otherwise treated medically or by marginal operations.

      Investigators have planned a randomised trial with 2 parallel arms: all patients with
      resectable (T1-2 N0-1) diagnosed or suspected lung cancer will be enrolled in the study at
      pre-operative interview with thoracic surgery consultant and then randomised by the physician
      data manager (T0). The Intervention Group (IG) will receive an overall rehabilitation
      treatment based on 10 sessions of pre-operative outpatient PR, early inpatient post-operative
      PR, and long-term exercise beginning 1 month after surgery and lasting for 15 sessions.
      Control Group (CG) will receive Standard Care (SC) based upon physiatrist counselling the day
      before surgery and early inpatient post-operative PR. Both groups will receive re-evaluation
      and, if necessary, optimization of COPD therapy before entering the study; final follow up
      will be at 6 months after surgery in both groups (T3), intermediate evaluations are planned
      immediately before surgery (T1) and 1 month after surgical treatment (T2).

      The 6 minutes walk test (6MWT) proved to correlate with functional status of patients with
      respiratory impairments; measurement of the impact of Pulmonary Rehabilitation (PR) on 6MWT
      is the primary outcome of our study. Investigators expect that this kind of treatment will
      improve exercise tolerance expressed by the 6MWT, assessed at T0, T1, T2 and T3 in IG. Values
      of 6MWT in CG will be assessed at T0 and T3 (T1 only if changes in therapy have occurred).

      It has been demonstrated that PR and educational therapy optimize respiratory function in
      COPD patients. Investigators will asses the changes in pulmonary function with Lung Function
      Tests (LFT): complete spirometry (static and dynamic volumes and Diffusing Capacity of Carbon
      Oxide) will be performed at T0, T1 e T3 in IC. The CG will be evaluated at T0 and T3 (T1 only
      if changes in therapy have occurred).

      COPD patients eligible for lung cancer surgery often undergo sub-lobar resection to preserve
      respiratory function; PR could reduce lung impairment and increase the rate of lobectomies in
      this subset of patients. By optimizing lung function, investigators expect a reduction in
      post-operative complications and length of hospital stay. This will be evaluated 1 month
      after surgery (T2).

      The therapeutic strategy of lung cancer is very complex; this causes both physical and
      psychological symptoms and significantly impairs patients' QoL. This important outcome will
      be assessed with Short-Form 12 questionnaire (SF12) at T0 and T3. Pain and depression will
      also be monitored with specific scales: the Numeric Rating Scale (NRS) for pain and the
      Hospital Anxiety and Depression Scale (HADS) to measure depression. Pain evaluations will be
      planned at T0, T2 and T3, depression at T0, T1 and T3.

      Since there are no published data for mean and standard deviations of 6MWT after lung surgery
      with or without treatment, Cohen's medium effect size (d=0.5) has been used to compute sample
      size (n=140).

      Normality for continuous variables will be assessed by Shapiro-Wilk test to decide the
      statistical technique to use. Thus, Student t will be used for normal variables, while
      Wilcoxon-Mann-Whitney test will be used for the others.

      Categorical variables (presence/absence of any complication) will be analyzed through 2x2
      tables and significance assessed with Chi-squared test. Risks will be described by Odds Ratio
      and related Confidence Interval.

      With regard to primary endpoint, IC is expected to improve 6MWT at 6 months by at least 25
      metres compared to CG. We also expect an improvement in postoperative outcome (less morbidity
      and shorter in-hospital stay) and long-term QoL, and in pain and depression levels.

      An overall 10% drop-out rate is estimated, due to factors like perioperative death or major
      complications and need for adjuvant treatments (which would overlap postoperative
      rehabilitation and deeply impact on results).

      Moreover, overall randomization could produce an imbalance between the two groups in some
      features; in presence of significant non-homogeneity of treated versus control arm,
      propensity score matching analysis will be applied to reduce bias due to confounding factors.
    

Intervention name(s): Pulmonary Rehabilitation; Standard care
Intervention type(s): Procedure; Procedure
Intervention description(s): The Intervention Group (IG) will receive an overall rehabilitation treatment based on 10 sessions of pre-operative outpatient PR, early inpatient post-operative PR, and long-term exercise beginning 1 month after surgery and lasting for 15 sessions; Control Group (CG) will receive Standard Care (SC) based upon physiatrist counselling the day before surgery and early inpatient post-operative PR.
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Supportive Care
Keywords: Lung Cancer; Surgery; COPD; Rehabilitation