ATS
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

Ann Thorac Surg 2009;88:1732-1735. doi:10.1016/j.athoracsur.2009.06.088
© 2009 The Society of Thoracic Surgeons
This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to Personal Folders
Right arrow Download to citation manager
Right arrow Author home page(s):
Patrick Bagan
Emmanuel Brian
Antoine Dujon
Marc Riquet
Right arrow Permission Requests
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Bagan, P.
Right arrow Articles by Riquet, M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Bagan, P.
Right arrow Articles by Riquet, M.
Related Collections
Right arrow Lung - cancer
Right arrowRelated Article

Original Articles: General Thoracic

Induction Chemotherapy Before Sleeve Lobectomy for Lung Cancer: Immediate and Long-Term Results

Patrick Bagan, MDa,c, Pascal Berna, MDa, Emmanuel Brian, MDa, Flora Crockett, MDa, Françoise Le Pimpec-Barthes, MD, PhDa, Antoine Dujon, MDb, Marc Riquet, MD, PhDa,*

a Department of Thoracic Surgery, Georges Pompidou European Hospital, Paris University, Paris, France
b Cedre Surgical Center, Boisguillaume, France
c Department of Thoracic and Vascular Surgery, Victor Dupouy Hospital, Argenteuil, France

Accepted for publication June 25, 2009.

* Address correspondence to Dr Riquet, service de Chirurgie Thoracique, Hôpital Européen Georges Pompidou, 20-40 rue Leblanc, Paris, 75015, France (Email: marc.riquet{at}egp.aphp.fr).


GENERAL THORACIC SURGERY: The Annals of Thoracic Surgery CME Program is located online at http://cme.ctsnetjournals.org. To take the CME activity related to this article, you must have either an STS member or an individual non-member subscription to the journal.

 

   Abstract
Top
 Abstract
Introduction
 Material and Methods
 Results
 Comment
 References
 
Background: Induction chemotherapy does not increase the morbidity and mortality rates of bronchoplastic procedures, but the long-term efficiency remains unclear. The purpose of this retrospective study was to analyze the impact of chemotherapy on resectability and long-term survival.

Methods: From 1984 to 2005, 159 consecutive patients with non–small cell lung cancer underwent sleeve lobectomy without (n = 117) or with induction chemotherapy (n = 42). Indications for chemotherapy were N2 lymph node involvement (n = 15), T3 or T4 tumor invasion with doubtful resectability (n = 13), need for tumor size reduction (n = 8), lung function precluding pneumonectomy (n = 4), and brain metastasis (n = 2). None of the patients received induction radiation therapy. We studied tumor characteristics and immediate and long-term results in both groups.

Results: Clinical stage III was predominant in the induction chemotherapy group whereas stage II was predominant in the surgery-only group. Complication rates in the induction chemotherapy group and in the surgery-only group were 23.8% and 24.7%, respectively. We observed a greater rate of 1-month-delay smoking cessation before surgery in the induction chemotherapy group (40% versus 22%). The 5-year survival rates were 65.4% in the surgery-only group and 73.4% in the induction chemotherapy group (p = 0.5). The tumor size in the induction chemotherapy group was lower (17.5 versus 30.6 mm; p = 0.01), which reflected the positive impact of chemotherapy on sleeve resection feasibility.

Conclusions: Induction chemotherapy before sleeve lobectomy achieves good long-term results. Tumor reduction and limited resection feasibility seemed to be increased, which justify further prospective trials.

Bronchial sleeve lobectomy (SL) was first introduced by Sir Clement Price-Thomas in 1947, and Allison performed the first SL for a bronchogenic carcinoma in 1954 (as referenced in [1–3]). Bronchoplastic techniques are currently the procedures of choice in anatomically suitable patients [2]. Bronchoplastic procedures are reported to be performed in 3% to 13% of the patients diagnosed with a resectable bronchopulmonary malignant tumor [1, 3–8]. A recent meta-analysis comparing the results of SL and pneumonectomy concluded that SL offers better long-term survival and quality of life than pneumonectomy [9]. Sleeve lobectomy after induction chemotherapy has not been demonstrated to be associated with an additional risk of postoperative complications, but results on long-term survival have not yet been evaluated [10, 11]. The reasons leading to perform pneumonectomy rather than SL are mainly the tumor size of lung cancer in N0 patient and the presence of extralobar lymph node involvement (N1) that precludes fissural and hilar dissection [3]. The purpose of this study was to retrospectively review the impact of induction chemotherapy on tumor characteristics and long-term survival in patients undergoing sleeve resection in comparison with those who underwent SL without induction chemotherapy.


   Material and Methods
Top
 Abstract
 Introduction
 Material and Methods
Results
 Comment
 References
 
Between January 1984 and December 2005, 222 consecutive patients underwent a bronchoplastic procedure with (n = 204) or without (n = 18) parenchymal resection (Table 1). The patients with non–small cell lung cancer (NSCLC; n = 159) were the basis of our study. During this study period, 1,077 patients underwent pneumonectomy for NSCLC. Data were collected retrospectively and analyzed from the hospital database, hospital charts, referring physicians, and patients. The study was approved by the institutional review board, which granted a waiver of the need for patient consent. The preoperative workup included physical examination, chest radiography, computed tomography (CT) of the chest and upper abdomen, CT imaging of the brain, positron emission tomography scan (PET scan) in recent years, pulmonary function testing, and ventilation-perfusion scanning. Fiberoptic bronchoscopy was performed for endobronchial staging. Mediastinoscopy was performed when CT showed mediastinal nodes larger than 10 mm in diameter or when PET scan showed mediastinal fixation. All patients underwent double-lumen endotracheal intubation. A posterolateral thoracotomy was performed. To avoid pneumonectomy, bronchoplastic procedure was always attempted in anatomically suitable patients. Circumferential bronchial resection was performed to obtain margins distant from the tumor. Specimens of the resection margins were checked by intraoperative frozen section to ensure complete resection. Patients with a positive margin underwent pneumonectomies or bilobectomies and were excluded from the study. Bronchial anastomoses were performed using interrupted 4-0 sutures and were checked for air leaks by inflating the lung while submersed in saline solution. A complete mediastinal lymphadenectomy was always performed since the beginning of the study period in 1984. Flexible bronchoscopy was performed at the end of the procedures to ensure the patency of anastomosis and to suction blood and secretions. Every effort was made to extubate the patients in the operating room. Fiberoptic bronchoscopy was performed routinely before hospital discharge or when atelectasis or anastomotic complications were suspected. Tumor resection was considered complete when the resection margins were free of disease.


View this table:
[in this window]
[in a new window]

  		Table 1 Patients' Clinical Characteristics
 
Among the 159 NSCLC patients, 42 patients received neoadjuvant chemotherapy (group IC) and 117 underwent surgery without induction therapy (group S; Table 2). Indications for chemotherapy were N2 lymph node involvement in 15 patients, T3 or T4 tumor invasion with doubtful resectability in 13 patients, need for tumor size reduction in 8 patients, lung function precluding pneumonectomy in 4 patients, and brain metastasis in 2 patients. Different chemotherapy protocols were used during the study period but were always platinum-based. The associated drugs were gemcitabine (n = 12), vinorelbine (n = 10), paclitaxel (n = 7), and miscellaneous (n = 13). The patients received two cycles (n = 16), three cycles (n = 15), or more (4 to 6 cycles, n = 7). None of the patients received induction radiation therapy. Operative mortality was defined as death within 30 days of surgery or during the hospitalization. Adjuvant therapy was in performed in 15 patients in group IC (chemotherapy, n = 6; chemotherapy and radiotherapy, n = 3; radiotherapy, n = 6) and in 34 patients in group S (chemotherapy, n = 7; chemotherapy and radiotherapy, n = 23; radiotherapy, n = 4). Follow-up was completed up to January 2009 or to the date of death for all patients. Mean follow-up duration was 83 months (range, 36 to 250 months).


View this table:
[in this window]
[in a new window]

  		Table 2 Postoperative Results After Surgery in Patients With Non–Small Cell Lung Cancer
 
Statistical analysis was obtained by introducing the data into computerized software (SEM, Anticancer Centre Jean Perrin, Clermont-Ferrand, France). Survival probabilities were estimated by the Kaplan-Meier method. Statistical comparisons among survival distributions were made using the log-rank test. Univariate analysis of prognostic factors was performed using the {chi}2 test. Statistical significance was found for any probability value less than 0.05.

The characteristics compared between these two groups were tumor diameter, postoperative complication rate, long-term survival, cancer recurrence, and cancer-related death. Survival of patients in group IC was also compared with patients who underwent bilobectomy and pneumonectomy after chemotherapy.


   Results
Top
 Abstract
 Introduction
 Material and Methods
 Results
Comment
 References
 
There were 166 men and 56 women with a mean age of 57 ± 11 years. Patient characteristics are depicted in Table 1. Postoperative results are detailed in Table 2.

Response to Induction Therapy
The examination of operative specimens revealed that 12 patients (28%) in the IC group had a complete response to induction therapy (ypT0N0), 26 patients (61%) had a partial response (>50%), and 4 patients (11%) had a poor response (20% to 50%). The comparison of the tumor size on operative specimen revealed a significative difference in favor of group IC (mean diameter in IC group, 17.5 ± 16.4 mm versus mean diameter in S group, 30.6 ± 21.3 mm; p = 0.01).

Operative Morbidity and Mortality
Postoperative complications occurred in 46 patients. Overall operative mortality and morbidity rates were 1.3% and 19.3%, respectively. A total of 22 (9.9%) patients presented with severe respiratory complications (pneumonia, respiratory failure, bronchial fistula, or stenosis). Overall operative morbidity was higher in the group of patients with a history of current smoking or recent smoking cessation. Induction therapy did not increase mortality (group IC, 1.7% versus group S, 2.3%) owing to postpneumonia respiratory failure in all cases. The rate of postoperative complications appeared slightly lower but not significantly (group S, 24.7% versus group IC, 23.8%; p = 0.66). The rate of 1-month-delay smoking cessation before surgery was higher in group IC than in group S (40% versus 22%). Major anastomotic complications were observed in 3 patients in group S (1 bronchopleural fistula and 2 severe stenoses treated by endoscopic dilatation) but not in group IC.

Survival
Five-year survival (Fig 1) was not significantly different between both groups despite a tendency to better survival after induction chemotherapy (median overall survival of 43.1 months versus 33.5 months) whatever the N status. There was a tendency to more cancer-related deaths in group S (19.6%) than in group IC (11.9%), and the local recurrence rates were similar in both groups. In group S, adjuvant therapy performed in 34 patients did not modify long-term survival (5-year survival of 58.5% versus 69% without adjuvant therapy).


Figure 1
View larger version (16K):
[in this window]
[in a new window]

  		Fig 1. Five-year survival of patients who underwent sleeve lobectomy after induction chemotherapy (curve 1) and primary sleeve lobectomy (curve 2).

 
Survival of patients in group IC was significantly better than survival of patients (n = 197) who underwent postinduction therapy pneumonectomy during the study period (5-year survival, 33.3%; p = 0.00065) but was not statistically different from patients (n = 22) who underwent postinduction bilobectomy (5-year survival, 58%; p = 0.15; Fig 2).


Figure 2
View larger version (21K):
[in this window]
[in a new window]

  		Fig 2. Five-year survival of patients who underwent sleeve lobectomy after induction therapy (curve 1), bilobectomy after induction therapy (curve 2), and pneumonectomy after induction therapy (curve 3).

 

   Comment
Top
 Abstract
 Introduction
 Material and Methods
 Results
 Comment
References
 
Bronchoplastic resections are more technically challenging than pneumonectomy. Sleeve lobectomy, the most performed bronchoplastic resection, results in lower operative mortality rates than pneumonectomy. Tedder and colleagues [1] reported a meta-analysis of sleeve resections and found that 30-day mortality was 5.5%, incidence of pneumonia was 10%, and incidences of bronchopleural fistula and bronchovascular fistula were 3% and 2.5%, respectively. The surgeon must balance the known mortality and morbidity of pneumonectomy (especially right pneumonectomy) with the growing body of evidence of better survival regarding bronchoplastic resections after induction therapy [3–5, 10–13].

Induction therapy appeared beneficial for increasing the feasibility of lobectomy performance in nonresectable patients and in patients unable to tolerate pneumonectomy. The resections became possible because of response to chemotherapy in 90% of our patients. It implied a significant tumor size reduction mainly observed in cN0 patients. Tumors were also classified ypT0 in 25% of group IC. The suggestion of induction chemotherapy in N0 patients that we previously proposed as a means for increasing SL feasibility seems to be confirmed by these results [3].

Sleeve lobectomy could be performed safely with minimal bronchial complications. Postoperative complication rate was lower in group IC than in group S probably because of the long smoke-free preoperative period more frequently obtained in the IC group. It is demonstrated that the delay between smoking cessation and surgery may influence pulmonary complications after lung resection [14]. The relatively low rate of anastomotic complications was probably related in our series to both the absence of residual tumor at the bronchial margin and associated induction radiotherapy. These are the significant factors of anastomotic complications reported in recent series studying post-SL complications [15–17].

Our long-term results support statements formulated by Martin-Ucar and colleagues [18] about interest of tumor reduction in view of pneumonectomy avoidance and lung parenchyma preservation. The long-term consequences of pneumonectomy such as mediastinal shift with postpneumonectomy syndrome, right ventricular dysfunction owing to high pulmonary vascular resistance, and postpneumonectomy empyema are prevented by SL [18]. We observed that downstaging the tumor by induction chemotherapy allowed lung-sparing resection and significantly improved long-term survival.

Moreover, pneumonectomy can be avoided even in a nonfunctioning lung caused by tumoral obstruction. Sleeve lobectomy may permit restoring the function of the remaining lobe by removing endobronchial tumor. It may also ameliorate the perfusion of a poorly functioning lung by relieving vascular constriction induced by the main or remaining lobe bronchus obstruction. In both cases, SL may result in lung function improvement [19].

In conclusion, this study emphasizes that induction chemotherapy before SL achieves good long-term results. Tumor reduction obtained in locally advanced clinical stages allows replacement of pneumonectomy by SL without increasing the risks of pulmonary and bronchial complications.


   References
Top
 Abstract
 Introduction
 Material and Methods
 Results
 Comment
 References
 

  1. Tedder M, Anstadt MP, Tedder SD, Lowe JE. Current morbidity, mortality, and survival after bronchoplastic procedures for malignancy Ann Thorac Surg 1992;54:387-391.[Abstract/Free Full Text]
  2. Deslauriers J, Gregoire J, Jacques LF, Piraux M, Guojin L, Lacasse Y. Sleeve lobectomy versus pneumonectomy for lung cancer: a comparative analysis of survival and sites or recurrences Ann Thorac Surg 2004;77:1152-1156.[Abstract/Free Full Text]
  3. Bagan P, Berna P, Pereira JC, et al. Sleeve lobectomy versus pneumonectomy: tumor characteristics and comparative analysis of feasibility and results Ann Thorac Surg 2005;80:2046-2050.[Abstract/Free Full Text]
  4. Takeda S, Maeda H, Koma H, et al. Comparison of surgical results after pneumonectomy and sleeve lobectomy for non-small cell lung cancer. Trends over time and 20-year institutional experience. Eur J Cardiothorac Surg 2006;29:276-280.[Free Full Text]
  5. Kim YT, Kang CH, Sung SW, Kim JH. Local control of disease related to lymph node involvement in non-small cell lung cancer after sleeve lobectomy compared with pneumonectomy Ann Thorac Surg 2005;79:1153-1161.[Abstract/Free Full Text]
  6. Mezzetti M, Panigalli T, Giuliani L, Raveglia F, Lo Giudice F, Meda S. Personal experience in lung cancer sleeve lobectomy and sleeve pneumonectomy Ann Thorac Surg 2002;73:1736-1739.[Abstract/Free Full Text]
  7. Ferguson MK, Karrison T. Does pneumonectomy for lung cancer adversely influence long-term survival? J Thorac Cardiovasc Surg 2000;119:440-448.[Abstract/Free Full Text]
  8. Okada M, Yamagishi H, Satake S, Matsuoka H, Miyamoto Y, Yoshimura M. Survival related to lymph node involvement in lung cancer after sleeve lobectomy compared with pneumonectomy J Thorac Cardiovasc Surg 2001;121:399-400.[Free Full Text]
  9. Ferguson MK, Lehman AG. Sleeve lobectomy or pneumonectomy: optimal management strategy using decision analysis techniques Ann Thorac Surg 2003;76:1782-1788.[Abstract/Free Full Text]
  10. Rendina EA, Venuta F, De Giacomo T, Flaishman I, Fazi P, Ricci C. Safety and efficacy of bronchovascular reconstruction after induction therapy J Thorac Cardiovasc Surg 1997;114:830-837.[Abstract/Free Full Text]
  11. Veronesi G, Solli PG, Leo F, et al. Low morbidity of bronchoplastic procedures after chemotherapy for lung cancer Lung Cancer 2002;36:91-97.[Medline]
  12. Ohta M, Sawabata N, Maeda H, Matsuda H. Efficacy and safety of tracheobronchoplasty after induction therapy for locally advanced lung cancer J Thorac Cardiovassc Surg 2003;125:96-100.[Abstract/Free Full Text]
  13. Mehran RJ, Deslauriers J, Piraux M, Beaulieu M, Guimont C, Brisson J. Survival related to nodal status after sleeve resection for lung cancer J Thorac Cardiovasc Surg 1994;107:576-583.[Abstract/Free Full Text]
  14. Nakagawa M, Tanaka H, Tsukuma H, Kishi Y. Relationship between the duration of the preoperative smoke-free period and the incidence of postoperative pulmonary complications after pulmonary surgery Chest 2001;120:705-710.[Abstract/Free Full Text]
  15. Burfeind WR, D'Amico TA, Toloza EM, Wolfe WG, Harpole DH. Low morbidity and mortality for bronchoplastic procedures with and without induction therapy Ann Thorac Surg 2005;80:418-422.[Abstract/Free Full Text]
  16. Yatsuyanagi E, Hirata S, Yamazaki K, Sasajima T, Kubo K. Anastomotic complications after bronchoplastic procedures for nonsmall cell lung cancer Ann Thorac Surg 2000;70:396-400.[Abstract/Free Full Text]
  17. Rea F, Marulli G, Schiavon M, et al. A quarter of a century experience with sleeve lobectomy for non-small cell lung cancer Eur J Cardiothorac Surg 2008;34:488-492.[Abstract/Free Full Text]
  18. Martin-Ucar AE, Chaudhuri N, Edwards JG, Waller DA. Can pneumonectomy for non-small cell lung cancer can be avoided?. An audit of parenchymal sparing lung surgery. Eur J Cardiothorac Surg 2002;21:601-605.[Abstract/Free Full Text]
  19. Bagan P, Le Pimpec-Barthes F, Badia A, Crockett F, Dujon A, Riquet M. Bronchial sleeve resections: lung function resurrecting procedure Eur J Cardiothorac Surg 2008;34:484-487.[Abstract/Free Full Text]

Related Article

Invited Commentary
Hans Hoffmann
Ann. Thorac. Surg. 2009 88: 1736. [Extract] [Full Text] [PDF]



This article has been cited by other articles:


Home page
 Eur J Cardiothorac SurgHome page
A. Gomez-Caro, M. Boada, N. Reguart, N. Vinolas, F. Casas, and L. Molins
Sleeve lobectomy after induction chemoradiotherapy
Eur J Cardiothorac Surg, January 4, 2012; (2012) ezr184v1.
[Abstract] [Full Text] [PDF]

Home page
 Eur J Cardiothorac SurgHome page
J. Schirren, M. Eberlein, A. Fischer, and S. Bolukbas
The role of sleeve resections in advanced nodal disease
Eur J Cardiothorac Surg, November 1, 2011; 40(5): 1157 - 1164.
[Abstract] [Full Text] [PDF]

Home page
 Eur J Cardiothorac SurgHome page
M. Riquet and A. Arame
Editorial comment: Sleeve lobectomy: time for setting the record straight
Eur J Cardiothorac Surg, November 1, 2011; 40(5): 1163 - 1164.
[Full Text] [PDF]

Home page
 Ann. Thorac. Surg.Home page
E. Martinod, D. M. Radu, K. Chouahnia, A. Seguin, A. Fialaire-Legendre, P.-Y. Brillet, M.-D. Destable, G. Sebbane, S. Beloucif, D. Valeyre, et al.
Human Transplantation of a Biologic Airway Substitute in Conservative Lung Cancer Surgery
Ann. Thorac. Surg., March 1, 2011; 91(3): 837 - 842.
[Abstract] [Full Text] [PDF]

Home page
 Eur J Cardiothorac SurgHome page
A. Gomez-Caro, S. Garcia, N. Reguart, E. Cladellas, P. Arguis, M. Sanchez, and J. M. Gimferrer
Determining the appropriate sleeve lobectomy versus pneumonectomy ratio in central non-small cell lung cancer patients: an audit of an aggressive policy of pneumonectomy avoidance
Eur J Cardiothorac Surg, March 1, 2011; 39(3): 352 - 359.
[Abstract] [Full Text] [PDF]

Home page
 Ann. Thorac. Surg.Home page
H. Hoffmann
Invited Commentary
Ann. Thorac. Surg., December 1, 2009; 88(6): 1736 - 1736.
[Full Text] [PDF]

This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to Personal Folders
Right arrow Download to citation manager
Right arrow Author home page(s):
Patrick Bagan
Emmanuel Brian
Antoine Dujon
Marc Riquet
Right arrow Permission Requests
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Bagan, P.
Right arrow Articles by Riquet, M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Bagan, P.
Right arrow Articles by Riquet, M.
Related Collections
Right arrow Lung - cancer
Right arrowRelated Article

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
ANN THORAC SURG ASIAN CARDIOVASC THORAC ANN EUR J CARDIOTHORAC SURG
J THORAC CARDIOVASC SURG ICVTS ALL CTSNet JOURNALS