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Ann Thorac Surg 2001;72:1149-1154
© 2001 The Society of Thoracic Surgeons

Original article: general thoracic

Morbidity and mortality after neoadjuvant therapy for lung cancer: the risks of right pneumonectomy

Jocelyne Martin, MDa, Robert J. Ginsberg, MDa, Amir Abolhoda, MDa, Manjit S. Bains, MDa, Robert J. Downey, MDa, Robert J. Korst, MDa, Tracey L. Weigel, MDa, Mark G. Kris, MDb, Ennapadam S. Venkatraman, PhDc, Valerie W. Rusch, MDa

a Thoracic Service, Department of Surgery, New York, New York, USA
b Thoracic Oncology Service, Department of Medicine, New York, New York, USA
c Biostatistics Service, Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, New York, USA

Address reprint requests to Dr Rusch, Memorial Sloan-Kettering Cancer Center, 1275 York Ave, New York, NY 10021
e-mail: ruschv{at}mskcc.org

Presented at the Poster Session of the Thirty-seventh Annual Meeting of The Society of Thoracic Surgeons, New Orleans, LA, Jan 29–31, 2001.


   Abstract
Top
 Abstract
Introduction
 Patients and methods
 Results
 Comment
 References
 
Background. The risks of complications in patients undergoing thoracotomy after neoadjuvant therapy for nonsmall cell lung cancer remain controversial. We reviewed our experience to define it further.

Methods. All patients undergoing thoracotomy after induction chemotherapy from 1993 through 1999 were reviewed. Univariate and multivariate methods for logistic regression model were used to identify predictors of adverse events.

Results. Induction chemotherapy included mitomycin, vinblastine, and cisplatin (179 patients), carboplatin and paclitaxel (152 patients), and other combinations (139 patients). Eighty-five patients (18%) received preoperative radiation. Operations were pneumonectomy (97 patients), lobectomy (297 patients), lesser resection (18 patients), and exploration only (58 patients). Total mortality was 7 of 297 (2.4%) and 11 of 97 (11.3%) for all lobectomies and pneumonectomies, respectively, but mortality was 11 of 46 (23.9%) for right pneumonectomy. Complications developed in 179 patients (38%). By multiple regression analysis, right pneumonectomy (p = 0.02), blood loss (p = 0.01), and forced expiratory volume in one second (percent predicted) (p = 0.01) predicted complications. No factor emerged to explain this high right pneumonectomy mortality rate.

Conclusions. Pulmonary resection after neoadjuvant therapy is associated with acceptable overall morbidity and mortality. However, right pneumonectomy is associated with a significantly increased risk and should be performed only in selected patients.


   Introduction
Top
 Abstract
 Introduction
Patients and methods
 Results
 Comment
 References
 
The use of induction chemotherapy before the surgical resection of locally advanced nonsmall cell lung cancer (NSCLC) is now common, and is even being tested in early-stage tumors [1]. The objectives of combined modality therapy are to improve resectability, and increase survival by treating micrometastatic disease. Although neoadjuvant therapy is well accepted, the risk of postoperative complications in patients undergoing thoracotomy after such treatment remains controversial. Previous studies have reported morbidity and mortality rates ranging from 20% to 60%, and 0% to 20%, respectively [2–7]. However, many of these series included only small numbers of patients with stage III disease. Therefore, we sought to determine the incidence of surgical morbidity and mortality after induction chemotherapy or chemoradiation for resectable NSCLC at our institution, and to identify factors that predict adverse postoperative events.


   Patients and methods
Top
 Abstract
 Introduction
 Patients and methods
Results
 Comment
 References
 
Subjects and data collected
Clinical information was obtained through a detailed retrospective review of the medical records of all patients who received induction chemotherapy or chemoradiation for potentially resectable NSCLC and then underwent thoracotomy at Memorial Sloan-Kettering Cancer Center, New York, NY. The data recorded included demographic information, smoking history and medical comorbidities (hypertension, coronary artery disease, heart failure, arrhythmia, diabetes, steroid dependence, and renal insufficiency). Information about the extent of disease evaluation and the prechemotherapy clinical stage were collected, as were the results of pulmonary function tests, ventilation-perfusion scans, electrocardiograms, echocardiograms and stress tests. Details of the neoadjuvant treatment and of the surgical procedure were recorded. The final pathologic stage was classified according to the 1997 International System for Staging Lung Cancer [8], and the completeness of resection was defined using standard criteria. A complete resection, classified as R0, was defined as pathologic demonstration of negative tissue margins and an assessment by the surgeon that all detectable disease had been removed. Patients who had a complete gross resection in whom positive margins were found on final pathologic review were classified as having a microscopic incomplete resection, or R1. Gross residual disease after attempted resection was classified as R2.

Morbidity and mortality data were also retrieved from the charts. All complications occurring during the hospitalization were recorded and categorized as minor or major. Pneumonia, respiratory failure requiring intubation for greater than 48 hours, adult respiratory distress syndrome, bronchial stump leak, empyema, reoperation for bleeding, myocardial infarction, heart failure, arrhythmia requiring treatment, renal failure requiring dialysis, cerebrovascular accident, sepsis, or pulmonary embolism were considered major complications. Mortality was recorded as in-hospital mortality when it occurred during the same hospitalization as the operation, or as late mortality when it was related to the operation but occurred after the initial hospital discharge.

Statistical methods
Potential factors contributing to morbidity were examined first in univariate analyses. Most of the variables were tested by Pearson’s or Kendall’s Tau’s correlation coefficients to determine whether the potential risk factors were truly independent predictors. Then a multivariate logistic regression analysis was performed. Because of the small number of deaths, univariate and multivariate analyses were not undertaken to predict mortality. Fisher’s exact test was used to assign the significance of the association between the type of resection and mortality. Statistical analyses were completed using SPSS 10.0 statistical software (Statistical Product and Service Solutions; SPSS Inc, Chicago, IL).


   Results
Top
 Abstract
 Introduction
 Patients and methods
 Results
Comment
 References
 
Demographics
The details of patient demographic information are shown in Table 1. From January 1, 1993 through December 31, 1999, 470 patients (208 women, 262 men) with a median age of 59 years (range, 25 to 82 years) underwent a thoracotomy after induction chemotherapy or chemoradiation for NSCLC at the Memorial Sloan-Kettering Cancer Center, New York, NY. There was a median of 65 operations performed annually (range, 51 to 80). Six patients (1.3%) had a prior ipsilateral lung resection. Although most patients were former or current smokers, preoperative pulmonary function tests showed on average only a moderate degree of impairment. Medical comorbidities were common, occurring in approximately half the patients, and included most frequently hypertension (24.7%), angina or past myocardial infarction (12.1%), or diabetes (7.9%). The majority of patients (70.4%) had clinical stage III NSCLC before induction therapy. Of 330 patients (70.2%) who had a mediastinoscopy, N2 disease was proven in 247 patients (52.6%).


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  		Table 1. Demographic Information: 470 Patients From 1993 Through 1999

 
Neoadjuvant therapy regimens
The majority of patients were treated off protocol and more than half were referred for surgical resection after receiving induction therapy at other hospitals. The chemotherapy regimen consisted of mitomycin, vinblastine, and cisplatin (MVP) in 179 patients (38.1%), carboplatin and paclitaxel (CT) in 152 patients (32.3%), and other combinations in 139 patients (29.6%). Eighty-five patients (18.1%) also received preoperative radiation, with a median dose of 50 Gy (range, 10 to 72 Gy). In 27 patients, documentation of the dose delivered could not be obtained. The median time between the end of chemotherapy and operation was 43.5 days (range, 6 to 453 days).

Surgical resection information
Information about the operations performed is shown in Table 2. The most common operation was a lobectomy (63.2%). Pneumonectomies were performed on 20.6% of patients, and explorations only on 12.3% of patients. Extended resections, defined as resections of the chest wall, pericardium, major vessels, vertebral bodies, or diaphragm, were performed on 102 patients (21.7%). In general, patients undergoing all forms of pulmonary resection were carefully managed by perioperative fluid restriction. No routine monitoring by Swan-Ganz or central venous catheter was used, and intensive hemodynamic measurements were not generally available for analysis. An R0, complete resection, was achieved in 78.1% of patients; an R1 was achieved in 7.9% of patients; an R2 was achieved in 1.7% of patients; and no resection was done in 12.3% of patients. Twenty-two patients (4.7%) received intraoperative brachytherapy. Adenocarcinoma was the predominant tumor histology that occurred in 263 patients (56.0%), whereas squamous cell carcinoma was seen in 124 patients (26.4%), large cell carcinoma in 53 patients (11.3%), and NSCLC, not otherwise specified, in 30 patients (6.4%).


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  		Table 2. Resection Information (n = 470)

 
Mortality
The overall mortality was 3.8% (18 of 470). In-hospital deaths occurred in 12 patients, and deaths after initial discharge occurred in 6 patients (during periods ranging from 21 to 95 days after the operation). The relationship between mortality and the type of surgical resection is shown in Table 3. Pneumonectomy, and especially right pneumonectomy, was significantly associated with mortality as compared with all other types of resection (p < 0.001; Fisher’s exact test). Ten of the 179 patients who received MVP as induction treatment died (5.59%); and there were 8 deaths among the 291 patients who received any other type of chemotherapy (2.75%) (p = 0.140; Fisher’s exact test).


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  		Table 3. Mortality (n = 18 of 470 [3.8%])

 
Mortality occurred in seven standard right pneumonectomies, three intrapericardial, and one extrapleural pneumonectomy. The causes of deaths related to right pneumonectomy were respiratory failure and adult respiratory distress syndrome [6] for the in-hospital mortalities. Other causes of death were respiratory failure and adult respiratory distress syndrome [1], bronchopleural fistula [1], respiratory failure believed to be associated with pulmonary toxicity caused by mitomycin [1], empyema [1], and atrial fibrillation with cerebrovascular accident [1] that occurred after initial discharge.

The forced expiratory volume in one second (FEV1) (percent predicted) for the right pneumonectomy patients who died was not statistically different than the FEV1 (percent predicted) for those who survived (0.738 and 0.781, respectively; p = 0.537). Seven of the 21 right pneumonectomy patients (33.3%) who received MVP as induction treatment died; 4 of the 25 patients (16%) who received other types of chemotherapy died (p = 0.2981; Fisher’s exact test). Ten of the 11 right pneumonectomy patients did not receive induction radiation, and the radiation status is unknown for 1 patient.

Morbidity
Complications developed in 179 patients (38.1%). Table 4 shows the morbidity by procedure. The most common complications are shown in Table 5. Respiratory was the most common complication, and the second most common was cardiac arrhythmia.


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  		Table 4. Total Morbidity by Procedure (n = 179 of 470 [38.1%])

 

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  		Table 5. Common Complications

 
In univariate analyses, the factors significantly associated with an increased risk of complications were a low FEV1 (percent predicted), a right pneumonectomy, an extended resection, a delayed extubation, the length of operation, and increased blood loss. Blood loss was significantly correlated to an extended resection, a delayed extubation, and a longer operation (p < 0.001, p = 0.005, and p < 0.001, respectively). By multivariate analysis, right pneumonectomy, increased blood loss, and low FEV1 (percent predicted) were significant predictors of higher morbidity. The results of these analyses are shown in Table 6.


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  		Table 6. Factors Predicting Complications

 

   Comment
Top
 Abstract
 Introduction
 Patients and methods
 Results
 Comment
References
 
Before the advent of combined modality therapy for NSCLC, the Lung Cancer Study Group reviewed their experience with 2,200 resections for lung cancer and reported a 30-day mortality of 3.7% [9]. The mortality rates for pneumonectomy and lobectomy were 6.2% and 2.9%, respectively. Similarly, at Memorial Sloan-Kettering Cancer Center, Nagasaki and colleagues [10] reported 6% and 2% postoperative mortality rates for pneumonectomy and lobectomy. After induction chemotherapy operative mortality rates of 2.5% to 8% were reported [1, 2, 5]. When concurrent radiotherapy is added to induction chemotherapy, the reported rates varied from 0 to 23% [4, 6, 7]. However, most studies included only a small number of patients. A trial of induction chemoradiation by the Southwest Oncology Group reported a postoperative mortality rate of 7.9% [11]. This study included many pneumonectomies and extended resections. The range of reported mortality rates may reflect varying criteria for patient selection, differences in type and dose of induction therapy, the experiences of oncologists and surgeons involved, and, in some instances, different definitions of postoperative mortality.

Although our study is limited by its retrospection, it has allowed us to analyze the outcome of a very large number of patients treated in a relatively uniform manner. Radiation and chemotherapy were frequently administered at outside institutions but operations and postoperative follow-up were carried out at our institution, in a homogeneous manner within a single surgical group. Our overall surgical mortality of 3.8% compares favorably with previous studies reports in which patients were not given any induction therapy. Our results are also similar with those reported by Deslauriers and colleagues [12], in which 25% of the patients were in trials involving neoadjuvant or adjuvant therapy.

With respect to morbidity, postoperative complication rates in the range of 30% are reported both in studies in which patients did not receive induction therapy and in studies in which they did [11–13]. The most common complications are cardiorespiratory. Our total morbidity was 38.1%, but our major complication rate is 26.6%, which is very similar to that of previous studies. Therefore the impact of induction therapy on the overall morbidity rate does not seem to be significant.

Right pneumonectomy is known to be associated with a higher morbidity and mortality. In 1989, the M.D. Anderson Cancer Center reported an operative mortality rate of 12% for right pneumonectomy as compared with 1% for left pneumonectomy [14]. Also before the era of induction therapy, the Brigham and Women’s Hospital reported that right-sided resections were associated with an increased risk of major complications, especially dysrhythmias [15]. In the previously cited Southwest Oncology Group study [11], 6 of the 8 postoperative deaths followed pneumonectomies, but the side of resections was not reported. Thus our 23.9% mortality rate for right pneumonectomy exceeds that usually reported in patients not receiving induction therapy, but there is little previous information regarding this issue after combined modality therapy. One notable point is that almost half of the deaths after right pneumonectomy in our study occurred after initial discharge from the hospital. We performed statistical analyses to characterize patients with right pneumonectomy who died or developed complications as compared with those who did not. No demographic, clinical, functional, or surgical variables thus far explain the high operative risk of this patient subset.

Our analyses showed that the FEV1 (percent predicted) significantly predicts morbidity. As seen in Table 6, the DLCO (percent predicted) approaches significance as a predictor by univariate analysis. Further analyses showed that the FEV1 (percent predicted) is very linearly correlated with the DLCO (percent predicted) (coefficient = 0.445; p less than 0.001), which explains why only the FEV1 (percent predicted) is a significant predictor factor in the multivariate model. Within the confines of this retrospective study, it has not been possible to define an absolute cutoff point for the FEV1 (percent predicted) in which most complications became unavoidable. Analyses have been performed using the values of FEV1 (percent predicted) as a continuous variable. In clinical practice, the postoperative predicted FEV1 and DLCO (ppoFEV1 and ppoDLCO) derived from a quantitative ventilation-perfusion scan and the preoperative pulmonary function tests are considered potential predictors of complications [16]. Unfortunately, the combined results of a ventilation-perfusion scan and of complete pulmonary function tests could only be retrieved for 63 patients in this retrospective study. Only 17 of these patients developed complications. Therefore, the role of ppoFEV1 and ppoDLCO in predicting morbidity and mortality could not be assessed in our study. This should be investigated in future prospective studies. Other factors previously suggested as important by some authors [17, 18], including the amount of perioperative fluid administration and surgical techniques, should be assessed in future studies. These factors cannot be accurately evaluated in a retrospective study.

In summary, pulmonary resection after induction chemotherapy or chemoradiation can generally be performed with acceptable morbidity and mortality. Our data suggest that patients should be carefully selected for operation especially with respect to their pulmonary function, and that intraoperative blood loss should be minimized. In our experience, right pneumonectomy is associated with a significantly increased risk of postoperative morbidity and mortality, and therefore, should be performed very selectively only when no alternative resection is possible. The precise role of bronchial or vascular sleeve resection, or both, after induction therapy, advocated by some authors as an alternative to pneumonectomy [19], has not been fully defined yet. The etiology of respiratory failure, which is the main cause of mortality after right pneumonectomy, remains unclear from our analyses and warrants further investigation in prospective studies.


   References
Top
 Abstract
 Introduction
 Patients and methods
 Results
 Comment
 References
 

  1. Pisters K.M.W., Ginsberg R.J., Giroux D.J., et al. Induction chemotherapy before surgery for early-stage lung cancer: a novel approach. J Thorac Cardiovasc Surg 2000;119:429-439.[Abstract/Free Full Text]
  2. Roberts J.R., DeVore R.F., Carbone D.P., et al. Neoadjuvant chemotherapy increases perioperative complications in patients undergoing resection for NSCLC. Proc Am Soc Clin Oncol 1999;18:465a.
  3. Rusch V.W., Albain K.S., Crowley J.J., et al. Surgical resection of stage IIIA and stage IIIB non-small-cell lung cancer after concurrent induction chemotherapy. A Southwest Oncology Group trial. J Thorac Cardiovasc Surg 1993;105:97-106.[Abstract]
  4. Fowler W.C., Langer C.J., Curran W.J., Jr, Keller S.M. Postoperative complications after combined neoadjuvant treatment of lung cancer. Ann Thorac Surg 1993;55:986-989.[Abstract]
  5. Martini N., Kris M.G., Flehinger B.J., et al. Preoperative chemotherapy for stage IIIa (N2) lung cancer: the Sloan-Kettering experience with 136 patients. Ann Thorac Surg 1993;55:1365-1374.[Abstract]
  6. Sonett J.R., Krasna M.J., Suntharalingam M., et al. Safe pulmonary resection after chemotherapy and high-dose thoracic radiation. Ann Thorac Surg 1999;68:316-320.[Abstract/Free Full Text]
  7. Bonomi P, Faber LP, Warren W, et al. Postoperative bronchopulmonary complications in stage III lung cancer patients treated with preoperative paclitaxel-containing chemotherapy and concurrent radiation. Semin Oncol 1997;24:S12–123-9.
  8. Mountain C.F. Revisions in the International System for Staging Lung Cancer. Chest 1997;111:1710-1717.[Abstract/Free Full Text]
  9. Ginsberg R.J., Hill L.D., Eagan R.T., et al. Modern thirty-day operative mortality for surgical resections in lung cancer. J Thorac Cardiovasc Surg 1983;86:654-658.[Abstract]
  10. Nagasaki F., Flehinger B.J., Martini N. Complications of surgery in the treatment of carcinoma of the lung. Chest 1982;82:25-29.[Abstract/Free Full Text]
  11. Albain K.S., Rusch V.W., Crowley J.J., et al. Concurrent cisplatin/etoposide plus chest radiotherapy followed by surgery for stages IIIA (N2) and IIIB non-small-cell lung cancer: mature results of Southwest Oncology Group phase II study 8805. J Clin Oncol 1995;13:1880-1892.[Abstract/Free Full Text]
  12. Deslauriers J., Ginsberg R.J., Piantadosi S., Fournier B. Prospective assessment of 30-day operative morbidity for surgical resections in lung cancer. Chest 1994;106:329S-330S.[Medline]
  13. Duque J.L., Ramos G., Castrodeza J., et al. Early complications in surgical treatment of lung cancer: a prospective, multicenter study. Ann Thorac Surg 1997;63:944-950.[Abstract/Free Full Text]
  14. Wahi R., McMurtrey M.J., DeCaro L.F., et al. Determinants of perioperative morbidity and mortality after pneumonectomy. Ann Thorac Surg 1989;48:33-37.[Abstract]
  15. Harpole D.H., Jr, Liptay M.J., DeCamp M.M., Jr, Mentzer S.J., Swanson S.J., Sugarbaker D.J. Prospective analysis of pneumonectomy: risk factors for major morbidity and cardiac dysrhythmias. Ann Thorac Surg 1996;61:977-982.[Abstract/Free Full Text]
  16. Ferguson M.K., Reeder L.B., Mick R. Optimizing selection of patients for major lung resection. J Thorac Cardiovasc Surg 1995;109:275-283.[Abstract/Free Full Text]
  17. Patel R.L., Townsend E.R., Fountain S.W. Elective pneumonectomy: factors associated with morbidity and operative mortality. Ann Thorac Surg 1992;54:84-88.[Abstract]
  18. Anderson T.M., Miller J.I. Use of pleura, azygos vein, pericardium, and muscle flaps in tracheobronchial surgery. Ann Thorac Surg 1995;60:729-733.[Abstract/Free Full Text]
  19. Rendina E.A., Venuta F., De Giacomo T., Flaishman I., Fazi P., Ricci C. Safety and efficacy of bronchovascular reconstruction after induction chemotherapy for lung cancer. J Thorac Cardiovasc Surg 1997;114:830-837.[Abstract/Free Full Text]

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Eur. J. Cardiothorac. Surg., June 1, 2006; 29(6): 896 - 901.
[Abstract] [Full Text] [PDF]

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 Ann. Thorac. Surg.Home page
A. Brunelli, F. Xiume', M. Al Refai, M. Salati, R. Marasco, and A. Sabbatini
Gemcitabine-Cisplatin Chemotherapy Before Lung Resection: A Case-Matched Analysis of Early Outcome
Ann. Thorac. Surg., June 1, 2006; 81(6): 1963 - 1968.
[Abstract] [Full Text] [PDF]

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 J. Thorac. Cardiovasc. Surg.Home page
R. J. Battafarano
Optimal management of patients with non-small cell lung cancer with ipsilateral mediastinal lymph node metastases
J. Thorac. Cardiovasc. Surg., June 1, 2006; 131(6): 1227 - 1228.
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 Am. J. Respir. Crit. Care Med.Home page
O. Schussler, M. Alifano, H. Dermine, S. Strano, A. Casetta, S. Sepulveda, A. Chafik, S. Coignard, A. Rabbat, and J.-F. Regnard
Postoperative Pneumonia after Major Lung Resection
Am. J. Respir. Crit. Care Med., May 15, 2006; 173(10): 1161 - 1169.
[Abstract] [Full Text] [PDF]

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M. Dancewicz, J. Kowalewski, and J. Peplinski
Factors associated with perioperative complications after pneumonectomy for primary carcinoma of the lung
Interactive CardioVascular and Thoracic Surgery, April 1, 2006; 5(2): 97 - 100.
[Abstract] [Full Text] [PDF]

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 ChestHome page
H. Sugimura and P. Yang
Long-term Survivorship in Lung Cancer: A Review.
Chest, April 1, 2006; 129(4): 1088 - 1097.
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 Ann. Surg. Oncol.Home page
E. D. Bernstein, S. M. Herbert, and N. H. Hanna
Chemotherapy and Radiotherapy in the Treatment of Resectable Non-Small-Cell Lung Cancer
Ann. Surg. Oncol., March 1, 2006; 13(3): 291 - 301.
[Abstract] [Full Text] [PDF]

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 J. Thorac. Cardiovasc. Surg.Home page
M. de Perrot, E. Fadel, O. Mercier, S. Mussot, A. Chapelier, and P. Dartevelle
Long-term results after carinal resection for carcinoma: Does the benefit warrant the risk?
J. Thorac. Cardiovasc. Surg., January 1, 2006; 131(1): 81 - 89.
[Abstract] [Full Text] [PDF]

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 J. Thorac. Cardiovasc. Surg.Home page
L. W. Martin, A. M. Correa, W. Hofstetter, W. K. Hong, R. Komaki, J. B. Putnam Jr, D. C. Rice, W. R. Smythe, S. G. Swisher, A. A. Vaporciyan, et al.
The evolution of treatment outcomes for resected stage IIIA non-small cell lung cancer over 16 years at a single institution
J. Thorac. Cardiovasc. Surg., December 1, 2005; 130(6): 1601 - 1610.
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F. Barlesi, L. Boyer, C. Doddoli, S. Antoniotti, P. Thomas, and P. Auquier
The Place of Patient Satisfaction in Quality Assessment of Lung Cancer Thoracic Surgery
Chest, November 1, 2005; 128(5): 3475 - 3481.
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Y. Matsubara, S.-i. Takeda, and T. Mashimo
Risk Stratification for Lung Cancer Surgery: Impact of Induction Therapy and Extended Resection
Chest, November 1, 2005; 128(5): 3519 - 3525.
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 Eur. J. Cardiothorac. Surg.Home page
F. Barlesi, C. Doddoli, J.-P. Torre, R. Giudicelli, P. Fuentes, P. Thomas, and P. Astoul
Comparative prognostic features of stage IIIAN2 and IIIB non-small-cell lung cancer patients treated with surgery after induction therapy
Eur. J. Cardiothorac. Surg., October 1, 2005; 28(4): 629 - 634.
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P. Van Schil, J. Van Meerbeeck, G. Kramer, T. Splinter, C. Legrand, G. Giaccone, C. Manegold, and N. van Zandwijk
Morbidity and mortality in the surgery arm of EORTC 08941 trial
Eur. Respir. J., August 1, 2005; 26(2): 192 - 197.
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W. R. Burfeind Jr, T. A. D'Amico, E. M. Toloza, W. G. Wolfe, and D. H. Harpole
Low Morbidity and Mortality for Bronchoplastic Procedures With and Without Induction Therapy
Ann. Thorac. Surg., August 1, 2005; 80(2): 418 - 422.
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E. Perrot, B. Guibert, P. Mulsant, S. Blandin, I. Arnaud, P. Roy, L. Geriniere, and P.-J. Souquet
Preoperative Chemotherapy Does Not Increase Complications After Nonsmall Cell Lung Cancer Resection
Ann. Thorac. Surg., August 1, 2005; 80(2): 423 - 427.
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