Alessandro Brunelli

ERS/ESTS clinical guidelines on fitness for radical therapy in lung cancer patients (surgery and chemo-radiotherapy)

A collaboration of multidisciplinary experts on the functional evaluation of lung cancer patients has been facilitated by the European Respiratory Society (ERS) and the European Society of Thoracic Surgery (ESTS), in order to draw up recommendations and provide clinicians with clear, up-to-date guidelines on fitness for surgery and chemo-radiotherapy. The subject was divided into different topics, which were then assigned to at least two experts. The authors searched the literature according to their own strategies, with no central literature review being performed. The draft reports written by the experts on each topic were reviewed, discussed and voted on by the entire expert panel. The evidence supporting each recommendation was summarised, and graded as described by the Scottish Intercollegiate Guidelines Network Grading Review Group. Clinical practice guidelines were generated and finalised in a functional algorithm for risk stratification of the lung resection candidates, emphasising cardiological evaluation, forced expiratory volume in 1 s, systematic carbon monoxide lung diffusion capacity and exercise testing. Contrary to lung resection, for which the scientific evidences are more robust, we were unable to recommend any specific test, cut-off value, or algorithm before chemo-radiotherapy due to the lack of data. We recommend that lung cancer patients should be managed in specialised settings by multidisciplinary teams.

Physiologic Evaluation of the Patient With Lung Cancer Being Considered for Resectional Surgery: Diagnosis and Management of Lung Cancer, 3rd ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines

BACKGROUND This section of the guidelines is intended to provide an evidence-based approach to the preoperative physiologic assessment of a patient being considered for surgical resection of lung cancer. METHODS The current guidelines and medical literature applicable to this issue were identified by computerized search and were evaluated using standardized methods. Recommendations were framed using the approach described by the Guidelines Oversight Committee. RESULTS The preoperative physiologic assessment should begin with a cardiovascular evaluation and spirometry to measure the FEV1 and the diffusing capacity for carbon monoxide (Dlco). Predicted postoperative (PPO) lung functions should be calculated. If the % PPO FEV1 and % PPO Dlco values are both > 60%, the patient is considered at low risk of anatomic lung resection, and no further tests are indicated. If either the % PPO FEV1 or % PPO Dlco are within 60% and 30% predicted, a low technology exercise test should be performed as a screening test. If performance on the low technology exercise test is satisfactory (stair climbing altitude > 22 m or shuttle walk distance > 400 m), patients are regarded as at low risk of anatomic resection. A cardiopulmonary exercise test is indicated when the PPO FEV1 or PPO Dlco (or both) are < 30% or when the performance of the stair-climbing test or the shuttle walk test is not satisfactory. A peak oxygen consumption (V˙O2 peak) < 10 mL/kg/min or 35% predicted indicates a high risk of mortality and long-term disability for major anatomic resection. Conversely, a V˙O2 peak > 20 mL/kg/min or 75% predicted indicates a low risk. CONCLUSIONS A careful preoperative physiologic assessment is useful for identifying those patients at increased risk with standard lung cancer resection and for enabling an informed decision by the patient about the appropriate therapeutic approach to treating his or her lung cancer. This preoperative risk assessment must be placed in the context that surgery for early-stage lung cancer is the most effective currently available treatment of this disease.

Peak Oxygen Consumption During Cardiopulmonary Exercise Test Improves Risk Stratification in Candidates to Major Lung Resection

BACKGROUND The objective of this investigation was to assess the association of peak oxygen consumption (Vo(2)) with postoperative outcome in a prospective cohort of patients undergoing major lung resection for the treatment of lung cancer. METHODS Preoperative symptom-limited cardiopulmonary exercise testing (CPET) performed using cycle ergometry was conducted in 204 consecutive patients who had undergone pulmonary lobectomy or pneumonectomy. Peak Vo(2) was tested for possible association with postoperative cardiopulmonary complications and mortality. Logistic regression analysis, validated by a bootstrap analysis, was used to adjust for the effect of other perioperative factors. The role of peak Vo(2) in stratifying the surgical risk was further assessed in different groups of patients subdivided according to their cardiorespiratory status. RESULTS Logistic regression showed that peak Vo(2) was an independent and reliable predictor of pulmonary complications (p = 0.04). All six deaths occurred in patients with a peak Vo(2) of < 20 mL/kg/min (four deaths in patients with a peak Vo(2) of < 12 mL/kg/min). The mortality rate in this high-risk group was 10-fold higher (4 of 30 patients; 13%) compared to those with higher peak Vo(2) (p = 0.006). Compared to patients with a peak Vo(2) of > 20 mL/kg/min, those with a peak Vo(2) of < 12 mL/kg/min had 5-fold, 8-fold, 5-fold, and 13-fold higher rates, respectively, of total cardiopulmonary complications pulmonary complications, cardiac complications, and mortality. CONCLUSIONS The present study supports a more liberal use of CPET before lung resection compared to the current guidelines since this test can help in stratifying the surgical risk and optimizing perioperative care.

Tumours of the thymus: a cohort study of prognostic factors from the European Society of Thoracic Surgeons database

OBJECTIVES A retrospective database was developed by the European Society of Thoracic Surgeons, collecting patients submitted to surgery for thymic tumours to analyse clinico-pathological prognostic predictors. METHODS A total of 2151 incident cases from 35 institutions were collected from 1990 to 2010. Clinical-pathological characteristics were analysed, including age, gender, associated myasthenia gravis stage (Masaoka), World Health Organization histology, type of thymic tumour [thymoma, thymic carcinoma (TC), neuroendocrine thymic tumour (NETT)], type of resection (complete/incomplete), tumour size, adjuvant therapy and recurrence. Primary outcome was overall survival (OS); secondary outcomes were the proportion of incomplete resections, disease-free survival and the cumulative incidence of recurrence (CIR). RESULTS A total of 2030 patients were analysed for OS (1798 thymomas, 191 TCs and 41 NETTs). Ten-year OS was 0.73 (95% confidence interval 0.69-0.75). Complete resection (R0) was achieved in 88% of the patients. Ten-year CIR was 0.12 (0.10-0.15). Predictors of shorter OS were increased age (P < 0-001), stage [III vs I HR 2.66, 1.80-3.92; IV vs I hazard ratio (HR) 4.41, 2.67-7.26], TC (HR 2.39, 1.68-3.40) and NETT (HR 2.59, 1.35-4.99) vs thymomas and incomplete resection (HR 1.74, 1.18-2.57). Risk of recurrence increased with tumour size (P = 0.003), stage (III vs I HR 5.67, 2.80-11.45; IV vs I HR 13.08, 5.70-30.03) and NETT (HR 7.18, 3.48-14.82). Analysis using a propensity score indicates that the administration of adjuvant therapy was beneficial in increasing OS (HR 0.69, 0.49-0.97) in R0 resections. CONCLUSIONS Masaoka stages III-IV, incomplete resection and non-thymoma histology showed a significant impact in increasing recurrence and in worsening survival. The administration of adjuvant therapy after complete resection is associated with improved survival.

POSSUM scoring system as an instrument of audit in lung resection surgery

BACKGROUND The physiological and operative severity score for the enumeration of mortality and morbidity (POSSUM) is a scoring system that was validated in general surgery with the aim of being used as an instrument to evaluate surgical outcome. We applied POSSUM to a population of lung resection candidates to assess its capability to predict postoperative complications. METHODS Two hundred fifty lung resection candidates were prospectively evaluated from 1993 through 1996. The POSSUM value was entered along with other variables (sex, smoking history, type of resection, pulmonary function tests, arterial carbon dioxide, serum albumin level, total lymphocyte count, neoadjuvant chemotherapy and radiotherapy, and diabetes) in a multivariate analysis to identify independent predictors of postoperative morbidity. RESULTS Logistic regression analysis showed POSSUM was predictive of postoperative complications, showing no significant difference between predicted and observed morbidity (chi2 test, p > 0.05). CONCLUSIONS We think POSSUM can be appropriately used as a tool of surgical audit in lung resection operations.

The European Respiratory Society and European Society of Thoracic Surgeons clinical guidelines for evaluating fitness for radical treatment (surgery and chemoradiotherapy) in patients with lung cancer

The European Respiratory Society (ERS) and the European Society of Thoracic Surgeons (ESTS) established a joint task force with the purpose to develop clinical evidence-based guidelines on evaluation of fitness for radical therapy in patients with lung cancer. The following topics were discussed, and are summarized in the final report along with graded recommendations: Cardiologic evaluation before lung resection; lung function tests and exercise tests (limitations of ppoFEV1; DLCO: systematic or selective?; split function studies; exercise tests: systematic; low-tech exercise tests; cardiopulmonary (high tech) exercise tests); future trends in preoperative work-up; physiotherapy/rehabilitation and smoking cessation; scoring systems; advanced care management (ICU/HDU); quality of life in patients submitted to radical treatment; combined cancer surgery and lung volume reduction surgery; compromised parenchymal sparing resections and minimally invasive techniques: the balance between oncological radicality and functional reserve; neoadjuvant chemotherapy and complications; definitive chemo and radiotherapy: functional selection criteria and definition of risk; should surgical criteria be re-calibrated for radiotherapy?; the patient at prohibitive surgical risk: alternatives to surgery; who should treat thoracic patients and where these patients should be treated?

Evaluation of a new chest tube removal protocol using digital air leak monitoring after lobectomy: a prospective randomised trial

BACKGROUND The objective of this randomised trial was to assess the effectiveness of a new fast-track chest tube removal protocol taking advantage of digital monitoring of air leak compared to a traditional protocol using visual and subjective assessment of air leak (bubbles). METHODS One hundred and sixty-six patients submitted to pulmonary lobectomy for lung cancer were randomised in two groups with different chest tube removal protocols: (1) in the new protocol, chest tube was removed based on digitally recorded measurements of air leak flow; (2) in the traditional protocol, the chest tube removal was based on an instantaneous assessment of air leak during daily rounds. The two groups were compared in terms of chest tube duration, hospital stay and costs. RESULTS The two groups were well matched for several preoperative and operative variables. Compared to the traditional protocol, the new digital recording protocol showed mean reductions in chest tube duration (p=0.0007), hospital stay (p=0.007) of 0.9 day, and a mean cost saving of euro 476 per patient (p=0.008). In the new chest tube removal protocol, 51% of patients had their chest tube removed by the second postoperative day versus only 12% of those in the traditional protocol. CONCLUSIONS The application of a chest tube removal protocol using a digital drainage unit featuring a continuous recording of air leak was safe and cost effective. Although future studies are warranted to confirm these results in other settings, the use of this new protocol is now routinely applied in our practice.

Stair climbing test as a predictor of cardiopulmonary complications after pulmonary lobectomy in the elderly

BACKGROUND The objective of this study was to assess the role of a symptom-limited stair climbing test in predicting postoperative cardiopulmonary complications in elderly candidates for lung resection. METHODS A consecutive series of 109 patients more than 70 years of age who underwent pulmonary lobectomy for lung carcinoma from January 2000 through May 2003 formed the prospective database of this study. All patients in the analysis performed a preoperative symptom-limited stair climbing test. Univariate and multivariate analyses were performed to identify predictors of postoperative cardiopulmonary complications. RESULTS At univariate analysis, the patients with complications had a lower forced expiratory capacity percentage of predicted (p = 0.048), predicted postoperative forced expiratory volume in 1 second percentage of predicted (p = 0.049), climbed a lower height at preoperative stair climbing test (p = 0.0004), and presented a greater proportion of cardiac comorbiditiy with respect to the patients without complications (p = 0.02). After logistic regression analysis, significant predictors of postoperative complications resulted in the presence of a concomitant cardiac disease (p = 0.04) and a low height climbed preoperatively (p = 0.0015). CONCLUSIONS A symptom-limited stair climbing test was a safe and simple instrument capable of predicting cardiopulmonary complications in the elderly after lung resection.

The European Thoracic Database project: composite performance score to measure quality of care after major lung resection

BACKGROUND Performance measurement is an essential element of quality improvement initiatives. The objective of this study was to develop a composite performance score (CPS) incorporating processes and outcomes measures available in the European Society of Thoracic Surgeons (ESTS) Database and apply it to stratify performance of participating units. METHODS A total of 1656 major lung resections for malignant primary neoplastic disease were collected in the ESTS database from 2001 through 2003 and were analyzed. For the purpose of this study only data collected from units contributing more than 50 consecutive cases were included. Three quality domains were selected: preoperative care, operative care, and postoperative outcome. According to best available evidence the following measures were selected for each domain: preoperative care (% of predicted postoperative carbon monoxide lung diffusion capacity (ppoDLCO) measurement in patients with predicted postoperative forced expiratory volume in one second (ppoFEV1) <40%), operative care (% of systematic lymph node dissection), and outcomes (risk-adjusted cardiopulmonary morbidity and mortality rates). Morbidity and mortality risk models were developed by hierarchical logistic regression and validated by bootstrap analyses. Individual processes and outcomes scores were rescaled according to their standard deviations and summed to generate the CPS, which was used to rate units. RESULTS CPS ranged from -4.4 to 3.7. Individual scores were poorly correlated with each other. Two units were negative outliers and two positive outliers (outside 95% confidence limits). Compared to the rating obtained by using the risk-adjusted mortality rates, all units changed their positions when ranked by CPS. CONCLUSIONS The composite performance score methodology may support future peer-based organizational quality benchmarking initiatives and may be used for regulatory and credentialing purposes.

Recalibration of the Revised Cardiac Risk Index in Lung Resection Candidates

BACKGROUND The revised cardiac risk index (RCRI) has been proposed as a tool for cardiac risk stratification before lung resection. However, the RCRI was originally developed from a generic surgical population including a small group of thoracic patients. The objective of this study was to recalibrate the RCRI in candidates for major lung resections to provide a more specific instrument for cardiac risk stratification. METHODS One thousand six hundred ninety-six patients who underwent lobectomy (1,426) or pneumonectomy (270) in two centers between the years of 2000 and 2008 were analyzed. Stepwise logistic regression and bootstrap analyses were used to recalibrate the six variables comprising the RCRI. The outcome variable was occurrence of major cardiac complications (cardiac arrest, complete heart block, acute myocardial infarction, pulmonary edema, or cardiac death during admission). Only those variables with a probability of less than 0.1 in more than 50% of bootstrap samples were retained in the final model and proportionally weighted according to their regression estimates. RESULTS The incidence of major cardiac morbidity was 3.3% (57 patients). Four of the six variables present in the RCRI were reliably associated with major cardiac complications: cerebrovascular disease (1.5 points), cardiac ischemia (1.5 points), renal disease (1 point), and pneumonectomy (1.5 points). Patients were grouped into four classes according to their recalibrated RCRI, predicting an incremental risk of cardiac morbidity (p < 0.0001). Compared with the traditional RCRI, the recalibrated score had a higher discrimination (c indexes, 0.72 versus 0.62; p = 0.004). CONCLUSIONS The recalibrated RCRI can be reliably used as a first-line screening instrument during cardiologic risk stratification for selecting those patients needing further cardiologic testing from those who can proceed with pulmonary evaluation without any further cardiac tests.