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


     

Ann Thorac Surg 2008;86:228-233. doi:10.1016/j.athoracsur.2008.01.019
© 2008 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):
Nicola Santelmo
Xavier Ducrocq
Jean-Marie Wihlm
Gilbert Massard
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 Mansour, Z.
Right arrow Articles by Massard, G.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Mansour, Z.
Right arrow Articles by Massard, G.
Related Collections
Right arrow Lung - cancer
Right arrowRelated Article

Original Articles: General Thoracic

Persistent N2 Disease After Induction Therapy Does Not Jeopardize Early and Medium Term Outcomes of Pneumonectomy

Ziad Mansour, MDa, Evgenia A. Kochetkova, MD, PhDa, Nicola Santelmo, MDa, Xavier Ducrocq, MDa, Elisabeth Quoix, MD, PhDb, Jean-Marie Wihlm, MDa, Gilbert Massard, MDa,*

a Thoracic Surgery Service, Strasbourg University Hospital, Strasbourg, France
b Department of Pulmonology, Strasbourg University Hospital, Strasbourg, France

Accepted for publication January 7, 2008.

* Address correspondence to Dr Massard, Service de Chirurgie Thoracique, Hôpitaux Universitaires de Strasbourg, 67091 Strasbourg, France (Email: gilbert.massard{at}chru-strasbourg.fr).


   Abstract
Top
 Abstract
Introduction
 Patients and Methods
 Results
 Comment
 References
 
Background: Operative management of patients with persistent N2 disease after induction therapy is still debated.

Methods: One hundred fifty-three consecutive patients underwent pneumonectomy from January 1999 until July 2005; 28 patients (18.3%) had persistent N2 disease after induction therapy (group 1), 32 patients (20.9%) had pathologic stage N0 or N1 after induction therapy (group 2), and 93 patients (60.8%) with pathologic N2 disease underwent immediate surgery (group 3). Short-term end points were operative mortality at 30 and 90 days and major complications. Long-term end points were 5-year survival and disease-free survival rates.

Results: Demographics of the three groups were similar (age, sex, side of operation, type of chemotherapy, smoking status, and comorbidity such as coronary artery disease, diabetes, and chronic obstructive pulmonary disease). Thirty-day postoperative mortality was 10.7% in group 1, 3.1% in group 2 (p = 0.257), and 4.3% in group 3 (p = 0.201); 90-day postoperative mortality was 10.7% in group 1, 12.5% in group 2 (p = 0.577), and 9.7% in group 3 (p = 0.558). Incidence of major postoperative complications was similar. Five-year survival rate was 32.2% (median, 28 months; 95% confidence interval, 7 to 43) in group 1, 34.8% (median, 27 months; 95% confidence interval, 7 to 47) in group 2 (p = 0.685), and 12.4% (median, 15 months; 95% confidence interval, 11 to 19) in group 3 (p = 0.127). No statistical difference was found in terms of 5-year event-free survival, or regarding the side of pneumonectomy.

Conclusions: Our results suggest that pneumonectomy is justified in patients with persistent N2 disease after induction chemotherapy.


   Introduction
Top
 Abstract
 Introduction
Patients and Methods
 Results
 Comment
 References
 
Adequate management of patients with stage N2 non–small cell lung cancer has been a matter of relentless debate for at least four decades. The different prognostic factors and treatment strategies have been widely described [1–14]. Unsuspected N2 disease discovered during surgery is credited with a better prognosis than clinically evident N2 disease [10, 15–18]; skip metastases at the mediastinal level have a less disastrous prognosis than combined node involvement at the N1 and N2 levels [19–22].

A new era has begun with the advent of neoadjuvant therapies. Some controlled trials have demonstrated an important survival advantage in favor of induction chemotherapy followed by surgery compared with surgery alone [23–25]. Consequently, induction chemotherapy has been declared as the gold standard in patients with biopsy-proven or even suspected N2 disease, although the French multicenter trial conducted by Depierre and colleagues [26] did not demonstrate an advantage for the N2 category. Some more recent publications suggested that there is a survival benefit for patients with N2 disease who have been staged down by induction chemotherapy; on the other hand, prognosis might be dismal for those who have persistent N2 disease [27, 28].

The final question is whether induction chemotherapy might increase the operative risk. Several evaluations on series including all types of surgery conclude that there is no increased complication rate; the French controlled trial confirmed this impression. However, some alarming papers have drawn attention to a potential increase of operative mortality after pneumonectomy [29, 30], in particular right pneumonectomy after induction chemotherapy, which has been pointed out as a particularly dreadful operation, with an observed 3 months' mortality of close to 25%. Consequently, the legitimacy of pneumonectomy after induction therapy, especially on the right side, has become a question of everyday practice in oncology rounds, particularly if the patient has persistent N2 disease.

The purpose of this study was to review early and long-term results after pneumonectomy in patients with persistent N2 disease, and to compare them with the results of two other groups: those who were N0 or N1 after induction therapy, and those with pN2 disease who underwent immediate surgery.


   Patients and Methods
Top
 Abstract
 Introduction
 Patients and Methods
Results
 Comment
 References
 
This study was approved by the Institutional Review Board of Strasbourg University Hospital. This study being retrospective without disclosure of patients' identities, no individual consent was needed.

Data Collection
Three hundred six patients underwent a pneumonectomy between January 1999 and July 2005. Their records were retrospectively reviewed. Requested data were complete in all but 8 cases; the latter were excluded from the study. One hundred forty-five patients had immediate surgery and happened to have postoperative N0 or N1 status; they were also excluded. The remaining 153 patients were included in the present study. Their records were screened for patients' demographics and postoperative short and long-term results. When necessary, patients' physicians and families were contacted to retrieve the latest follow-ups. January 1, 2007, was chosen to be the follow-up deadline. Demographic data included age, sex, weaning from tobacco, pulmonary function tests, preoperative comorbidities (coronary artery disease, diabetes), preoperative chemotherapy and its type when performed, side of pneumonectomy, and postoperative pathologic staging. A patient was considered as suffering from chronic obstructive pulmonary disease (COPD) when forced expiratory volume in 1 second was less than 80% of predicted or when the ratio of forced expiratory volume in 1 second to forced vital capacity was less than 70%. Postoperative data included the in-hospital complications and their type, deaths on postoperative day 30 and on postoperative day 90, the administration of adjuvant radiation or chemotherapy, the occurrence of local or distant progression if any, and death during follow-up.

The whole cohort was divided into three groups: group 1 included those who received induction chemotherapy and still had persistent N2 disease (n = 28, 18.3%), group 2 included those who received induction chemotherapy and had pathologic stage N0 or N1 (n = 32, 20.9%), and group 3 included those who underwent surgery alone and happened to have a pathologic N2 disease (n = 93, 60.8%). Induction chemotherapy consisted typically of three cycles of a platinum-based drug (cisplatin or carboplatin) associated with vinorelbine (n = 17), gemcitabine (n = 9), or docetaxel (n = 7), or other associations depending on the referral oncology department.

Inclusion and Exclusion Criteria and Details on Staging Procedures
Pneumonectomy was indicated preoperatively each time the preoperative radiologic findings showed an invasion to the hilum or to the fissures. When these exploratory examinations did not show the above-mentioned findings and we discovered them intraoperatively, pneumonectomy was also performed. All pneumonectomy decisions were made after being sure that the predicted postoperative forced expiratory volume in 1 second is greater than 30% of the predicted normal value.

From the beginning of the study period, induction chemotherapy was available for administration to all the included patients. It was performed according to the referring oncology departments' protocols. At the beginning of the study, this treatment modality was less popular, and some patients did not receive it. It was used more frequently as time passed, until the end of the study period.

Initial pretreatment nodal staging was mainly based on computed tomographic scan, using the usual definition of cN2 when the smallest diameter is larger than 10 mm. Only those patients primarily referred to our group underwent staging mediastinoscopy if N2 or N3 was clinically suspected. Positron-emission spectroscopy scanning has become available at our institution only at the end of 2003; positron-emission spectroscopy–positive nodes were subjected to mediastinoscopy, whereas a negative mediastinal positron-emission spectroscopy was accepted as cN0. We did not use positron-emission spectroscopy scanning for restaging.

Our institutional strategy is to attempt a resection after induction therapy in all patients except those who show progressive disease. Therefore, restaging after induction relied once more on simple contrast-enhanced computed tomographic scan. As persistent N2 disease was not thought to be a contraindication to surgery, no redo mediastinoscopy has been performed in the present cohort.

Pneumonectomy was not performed whenever the operative exploration showed less tumoral invasion than suspected, and each time it was performed there was an unexpected mediastinal invasion precluding complete resection.

Operative Details
Patients were operated on by one of the department's three thoracic surgeons through a muscle-sparing anterolateral or axillary thoracotomy, or a non–muscle-sparing posterolateral thoracotomy. The same team of anesthesiologists managed the patients; a thoracic peridural anesthesia was performed whenever possible. Complete lymph node resection was performed in all patients as described previously [31]: on the right side, it included upper mediastinal nodes (levels 2, 4, and 10), subcarinal nodes (levels 7 and 8), and pulmonary ligament (level 9); on the left side we dissected the paraaortic nodes (levels 5 and 6), subaortic nodes up to the tracheobronchial angle (levels 10 and 4), subcarinal nodes, and pulmonary ligament. The bronchial suture was preferentially made with a stapling device. We routinely covered the bronchial stump after right-sided pneumonectomy; our preferred technique is a pericardial fat pad placed below the superior vena cava. The chest was systematically drained with a single tube connected to a balanced drainage system and kept in place for 48 hours. Patients stayed in the surveillance unit for at least 48 hours before being transferred to the ward.

Statistics
We performed comparisons between group 1 and group 2, then between group 1 and group 3. Group 1 was considered as the reference group.

Demographic data and results of both groups were compared using SPSS 11.5 for Windows software (SPSS Inc, Chicago, IL). Pearson's {chi}2 test or Fisher's exact test when needed were used to compare proportions, and Student's t test was used to compare means. Data were reported as mean ± standard deviation or as proportions. Survival estimates were made with the Kaplan–Meier model; the log-rank test was used to compare survival curves of each subset. A probability value less than 0.05 was considered as significant.


   Results
Top
 Abstract
 Introduction
 Patients and Methods
 Results
Comment
 References
 
Patient Population
One hundred fifty-three consecutive patients who had received induction chemotherapy or were presenting with pathologic N2 disease underwent pneumonectomy for non–small cell lung cancer at our institution from January 1999 until July 2005. Twenty-eight patients (18.3%) have undergone preoperative chemotherapy before pneumonectomy and still had persistent N2 disease (group 1), and 2 other patients underwent preoperative radiation therapy; postoperatively, 3 patients received combined adjuvant radiation and chemotherapy, 3 patients received exclusive adjuvant chemotherapy, 16 patients received exclusive adjuvant radiation therapy, and 6 received no adjuvant treatment. Thirty-two patients (20.9%) have undergone preoperative chemotherapy before pneumonectomy and had no persistent N2 disease (group 2), of whom 4 patients underwent preoperative radiation therapy. Postoperatively, no patient received combined adjuvant therapy, 5 patients received exclusive adjuvant chemotherapy, 3 patients received exclusive adjuvant radiotherapy, and 24 received no adjuvant treatment. Ninety-three patients (60.8%) underwent pneumonectomy without preoperative radiation or chemotherapy (group 3) and had a pathologic N2 disease, of whom 25 had postoperative combined radiation and chemotherapy, 6 had exclusive postoperative chemotherapy, 33 had exclusive postoperative radiation therapy, and 14 had no adjuvant treatment.

Preoperative demographic variables were statistically similar (Table 1). There was no statistical difference in the distribution of induction chemotherapy regimens administered to groups 1 and 2 (data not shown). Postoperative adjuvant treatments were administered more in group 1 than in group 2, but there was no statistical difference in the distribution of postoperative adjuvant treatments when comparing group 1 with group 3 (Table 2).


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

  		Table 1 Demographics
 

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

  		Table 2 Postoperative Distribution of Adjuvant Treatments
 
Short-Term Outcomes
Thirty-day and 90-day mortality rates as well as short-term severe complications are shown in Table 3. There were no statistically significant differences between groups 1 and 2, or between groups 1 and 3 either in terms of 30- and 90-day mortality rates or in incidences of empyema, bronchopleural fistula, or acute respiratory distress syndrome.


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

  		Table 3 Short-Term Outcomes
 
The comparison among the three groups did not show any statistical difference; this was true for every short-term variable (data not shown).

The side of the pneumonectomy had no impact on short-term outcomes when pooling groups 1 and 2 at one time, and when pooling groups 1 and 3 at another time (data not shown).

Long-Term Outcomes
There was a total follow-up period of 3,300 patient-months, with a mean of 21.57 ± 18.4 months per patient. Living patients at the follow-up deadline were 11 of 28 (39.29%) in group 1, 14 of 32 (43.75%) in group 2, and 18 of 93 (19.35%) in group 3. Five-year survival rate was 32.2% (median, 28 months; 95% confidence interval, 7 to 43) in group 1, 34.8% (median, 27 months; 95% confidence interval, 7 to 47) in group 2 (p = 0.685), and 12.4% (median, 15 months; 95% confidence interval, 11 to 19) in group 3 (p = 0.127). The comparison among the survival curves of the three groups did not show any statistical difference (p = 0.051; Fig 1).


Figure 1
View larger version (22K):
[in this window]
[in a new window]

  		Fig 1. Survival curves of each of the three subsets. (Group 1 [solid line] = pN2-positive patients after induction chemotherapy; Group 2 [short-and-long dashed line] = pN2-negative patients after induction chemotherapy; Group 3 [evenly dashed line] = pN2-positive patients with exclusive surgery.)

 
During the follow-up period, progression-free patients were 15 of 28 (53.57%) in group 1, 19 of 32 (59.37%) in group 2, and 39 of 93 (41.94%) in group 3. Five-year disease-free survival rate was 43.3% (median, 18 months; 95% confidence interval, 0 to 41) in group 1, 48.3% (median, 30 months) in group 2 (p = 0.480), and 23.3% (median, 12 months; 95% confidence interval, 9 to 15) in group 3 (p = 0.336). The comparison among the survival curves of the three groups did not show any statistical difference (p = 0.12; Fig 2).


Figure 2
View larger version (23K):
[in this window]
[in a new window]

  		Fig 2. Disease-free survival curves of each of the three subsets. (Group 1 [solid line] = pN2-positive patients after induction chemotherapy; Group 2 [short-and-long dashed line] = pN2-negative patients after induction chemotherapy; Group 3 [evenly dashed line] = pN2-positive patients with exclusive surgery.)

 
The test statistics for equality of survival distributions for the side of pneumonectomy adjusted for N2 status after induction chemotherapy (thus comparing groups 1 and 2) and then adjusted for the induction chemotherapy status in N2 disease (thus comparing groups 1 and 3) showed that the side of pneumonectomy had no influence either on the long-term survival (Table 4) or on the long-term disease-free survival (Table 5).


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

  		Table 4 Five-Year Survival Rates Depending on the Side of the Pneumonectomy
 

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

  		Table 5 Five-Year Disease-Free Survival Rates Depending on the Side of the Pneumonectomy
 

   Comment
Top
 Abstract
 Introduction
 Patients and Methods
 Results
 Comment
References
 
The results of the present study may be summarized as follows: (1) induction chemotherapy did not jeopardize postoperative outcome, (2) operative risk was not increased in patients with persistent N2 disease after induction chemotherapy, (3) long-term outcome of patients with persistent N2 disease was superior to that of those with N2 disease having undergone immediate surgery, and (4) the side of the pneumonectomy had no influence on outcomes.

Evaluation of postoperative mortality and morbidity after pneumonectomy after induction chemotherapy remains controversial. Most publications dealing with induction chemotherapy did not take into consideration the type of resection. Some alarming reports have pointed out a considerable increase of operative deaths, especially if the evaluation is made at 3 months [30]. In particular, right pneumonectomy led to a 90-day death rate of close to 25% [29, 30]. These reports contrast with some less pessimistic series, including our previously published results [32]: the latter showed no significant increase of operative mortality, and no significant difference with respect to the side of operation. However, all these evaluations have been made on a retrospective basis, so that the level of evidence is low.

Justification of surgery of N2 disease based on long-term results has also been a matter of debate. During the 1980s and early 1990s, North American authors have considered that the dismal prognosis could not legitimize surgical management, and patients were referred to medical therapies. On the other hand, European groups recommended surgery with radical lymph node dissection and followed by radiation therapy, which warranted an 18% survival rate at 5 years [26]. However, many reports highlight only subgroups with improved prognosis, which are not representative of the whole category; thus, a more optimistic prognosis may be expected in patients with unsuspected N2 discovered at the time of operation, N2 limited to a single node or station, skip-metastases, location of the primary tumor, and so forth.

Although it is well recognized that a complete resection is preferable to an incomplete resection, the consideration of the quality of surgery is a recent advent. We speculate that the extent of lymph node resection has an important part in long-term survival. In many former studies, exploration of the mediastinal nodes was either nonsystematic or relied on simple sampling. There is a bulk of evidence that complete node dissection improves staging by detecting unsuspected N2 nodes, such as skip metastases for instance [33, 34]. A negative positron-emission spectroscopy scan does not rule out the presence of microscopic N2 disease. It is obvious that the resection would be incomplete without removing these diseased nodes. A cooperative North American trial has demonstrated that lymph node dissection has no significant adverse effect. Finally, we recently found evidence that lymph node dissection may improve long-term survival also: after a first nonrandomized observation [35], the beneficial effect on survival has been confirmed by a randomized trial [34] and by a meta-analysis defining a hazard ratio of 0.78 [36]. These data allow us to hypothesize that even in patients with persistent N2 disease, a complete resection based on anatomic lung or lobar resection combined with a radical lymph node dissection may achieve an acceptable long-term result.

The role of neoadjuvant chemotherapy in N2 disease remains also controversial. Initial trials demonstrated a large survival benefit. On the other hand, the trial conducted by Depierre and colleagues [26] included a considerably larger sample size and concluded that induction chemotherapy is beneficial in stages N0 and N1, but not in stage N2. Two further studies by Bueno and associates [27] and Betticher and coworkers [28] concluded that there is a survival advantage limited to the patients having been staged down. Our results suggest that persistent N2 disease after induction therapy is less detrimental than N2 disease managed with immediate surgery. A possible factor might be compliance with treatment: adjuvant therapy after pneumonectomy is certainly hampered by a poor tolerance of treatment owing to postoperative fatigue.

Adequate decision for treatment of persistent N2 disease after induction therapy raises major ethical issues, especially if pneumonectomy is required. On the one hand, is it reasonable to subject a patient to a high-risk procedure when long-term prognosis is poor? Can we refuse to undertake a curative operation that might warrant long-term survival? Our results are clearly in favor of an aggressive management: induction chemotherapy did not jeopardize postoperative outcome of pneumonectomy, including those patients with persistent N2 disease; median survival in patients with persistent N2 disease was satisfactory and higher than in patients with N2 disease undergoing immediate surgery.

This original study is a retrospective one, having the limitations of all retrospective studies. A limited number of patients, especially in groups 1 and 2, made the adjustment of the survival rates on postoperative therapy of these two groups impossible. Patients were referred to our department from different oncology facilities after having received or not induction chemotherapy according to different therapeutic algorithms.

We think that the actual study may serve as a basis to a multicenter prospective investigation of induction chemotherapy followed by surgery in patients with histologically proven N2 disease, with or without proven downstaging after induction chemotherapy.


   References
Top
 Abstract
 Introduction
 Patients and Methods
 Results
 Comment
 References
 

  1. Yukinori S, Miyamoto H, Yamazaki A, et al. Prognostic significance of metastasis to the highest mediastinal lymph node in nonsmall cell lung cancer Ann Thorac Surg 2006;81:292-297.[Abstract/Free Full Text]
  2. Martin L, Correa A, Hofstetter W, et al. The evolution of treatment outcomes for resected stage IIIA non-small lung cancer over 16 years at a single institution J Thorac Cardiovasc Surg 2005;130:1601-1610.[Abstract/Free Full Text]
  3. Inoue M, Sawabata N, Takeda S, Ohta M, Ohno Y, Maeda H. Results of surgical intervention for p-stage IIIA (N2) non-small cell lung cancer: acceptable prognosis predicted by complete resection in patients with single N2 disease with primary tumor in the upper lobe J Thorac Cardiovasc Surg 2004;127:1100-1106.[Abstract/Free Full Text]
  4. Ichinose Y, Kato H, Koike T, et al. Completely resected stage IIIA non-small cell lung cancer: the significance of primary tumor location and N2 station J Thorac Cardiovasc Surg 2001;122:803-808.[Abstract/Free Full Text]
  5. Ichinose Y, Kato H, Koike T, et al. Overall survival and local recurrence of 406 completely resected stage IIIa-N2 non-small cell lung cancer patients: questionnaire survey of the Japan Clinical Oncology Group to plan for clinical trials Lung Cancer 2001;34:29-36.[Medline]
  6. Suzuki K, Nagai K, Yoshida J, Nishimura M, Takahashi K, Nishiwaki Y. The prognosis of surgically resected N2 non-small cell lung cancer: the importance of clinical N status J Thorac Cardiovasc Surg 1999;118:145-153.[Abstract/Free Full Text]
  7. Asamura H, Nakayama H, Kondo H, Tsuchiya R, Naruke T. Lobe-specific extent of systematic lymph node dissection for non-small cell lung carcinomas according to a retrospective study of metastasis and prognosis J Thorac Cardiovasc Surg 1999;117:1102-1111.[Abstract/Free Full Text]
  8. Vansteenkiste J, De Leyn P, Deneffe G, et al. Survival and prognostic factors in resected N2 non-small cell lung cancer: a study of 140 cases Ann Thorac Surg 1997;63:1441-1450.[Abstract/Free Full Text]
  9. Debevec M, Bitenc M, Vidmar S, et al. Postoperative radiotherapy for radically resected N2 non-small-cell lung cancer: randomized clinical study 1988–1992 Lung Cancer 1996;14:99-107.[Medline]
  10. Goldstraw P, Mannam G, Kaplan D, Michail P. Surgical management of non-small-cell lung cancer with ipsilateral mediastinal node metastasis (N2 disease) J Thorac Cardiovasc Surg 1994;107:19-28.[Abstract/Free Full Text]
  11. Miller D, McManus K, Allen M, et al. Results of surgical resection in patients with N2 non-small cell lung cancer Ann Thorac Surg 1994;57:1095-1101.[Abstract]
  12. Watanabe Y, Shimizu J, Oda M, et al. Aggressive surgical intervention in N2 non-small cell lung cancer of the lung Ann Thorac Surg 1991;51:253-261.[Abstract]
  13. Régnard J, Magdeleinat P, Azoulay D, et al. Results of resection for bronchogenic carcinoma with mediastinal lymph node metastases in selected patients Eur J Cardiothorac Surg 1991;5:583-587.[Abstract]
  14. Kawano R, Hata E, Ikeda S, Sakaguchi H. Micrometastasis to lymph nodes in stage I left lung cancer patients Ann Thorac Surg 2002;73:1558-1562.[Abstract/Free Full Text]
  15. Nakanishi R, Osaki T, Nakanishi K, et al. Treatment strategy for patients with surgically discovered N2 stage IIIA non-small cell lung cancer Ann Thorac Surg 1997;64:342-348.[Abstract/Free Full Text]
  16. De Leyn P, Schoonooghe P, Deneffe G, et al. Surgery for non-small cell lung cancer with unsuspected metastasis to ipsilateral or subcarinal nodes (N2 disease) Eur J Cardiothorac Surg 1996;10:649-655.[Abstract]
  17. Van Klaveren R, Festen J, Otten H, Cox A, De Graaf R, Lacquet L. Prognosis of unsuspected but completely respectable N2 non-small cell lung cancer Ann Thorac Surg 1993;56:300-304.[Abstract]
  18. Ferguson M. Optimal management when unsuspected N2 nodal disease is identified during thoracotomy for lung cancer: cost-effectiveness analysis J Thorac Cardiovasc Surg 2003;126:1935-1942.[Abstract/Free Full Text]
  19. Riquet M, Assouad J, Bagan P, et al. Skip mediastinal lymph node metastasis and lung cancer: a particular N2 subgroup with a better prognosis Ann Thorac Surg 2005;79:225-233.[Abstract/Free Full Text]
  20. Prenzel K, Mönig S, Sinning J, et al. Role of skip metastasis to mediastinal lymph nodes in non-small cell lung cancer J Surg Oncol 2003;82:256-260.[Medline]
  21. Gunlunoglu Z, Solak O, Metin M, Gurses A. The prognostic significance of skip mediastinal lymphatic metastasis in resected non-small cell lung cancer Eur J Cardiothorac Surg 2002;21:595(letter).[Free Full Text]
  22. Yoshino I, Yokoyam H, Yano T, et al. Skip metastasis to the mediastinal lymph nodes in non-small cell lung cancer Ann Thorac Surg 1996;62:1021-1025.[Abstract/Free Full Text]
  23. Roth J, Atkinson E, Fossella F, et al. Long-term follow-up of patients enrolled on a randomized trial comparing perioperative chemotherapy and surgery with surgery alone in respectable stage IIIA non-small-cell lung cancer Lung Cancer 1998;21:1-6.[Medline]
  24. Rosell R, Gómez-Codina J, Camps C, et al. A randomized trial comparing preoperative chemotherapy plus surgery with surgery alone in patients with non-small-cell lung cancer N Engl J Med 1994;330:153-158.[Abstract/Free Full Text]
  25. Pass HI, Pogrebniak HW, Steinberg SM, Mulshine J, Minna J. Randomized trial of neoadjuvant therapy for lung cancer: interim analysis Ann Thorac Surg 1992;53:992-998.[Abstract]
  26. Depierre A, Milleran B, Maro-Sibilot D, et al. Preoperative chemotherapy followed by surgery compared with primary surgery in respectable stage I (except T1N0), II, and IIIa non-small-cell lung cancer J Clin Oncol 2001;20:247-253.
  27. Bueno R, Richard W, Swanson S, et al. Nodal stage after induction therapy in stage IIIA lung cancer determines patient survival Ann Thorac Surg 2000;70:1826-1831.[Abstract/Free Full Text]
  28. Betticher DC, Hsu Schmitz SF, Tötsch M, et al. Mediastinal lymph node clearance after docetaxel-cisplatin neoadjuvant chemotherapy is prognostic of survival in patients with IIIA p N2 non-small-cell lung cancer: a multicenter phase II trial J Clin Oncol 2003;21:1752-1759.[Abstract/Free Full Text]
  29. Martin J, Ginsberg R, Abolhoda A, et al. Morbidity and mortality after neoadjuvant therapy for lung cancer: the risks of right pneumonectomy Ann Thorac Surg 2001;72:1149-1154.[Abstract/Free Full Text]
  30. Doddoli C, Barlesi F, Trousse D, et al. One hundred consecutive pneumonectomies after induction therapy for non-small lung cancer: an uncertain balance between risks and benefits J Thorac Cardiovasc Surg 2005;130:416-425.[Abstract/Free Full Text]
  31. Massard G, Ducrocq X, Kochetkova EA, Riquet M, Porhanov V. Sampling or node dissection for intraoperative staging of lung cancer: a multricentric cross-sectional study Eur J Cardiothorac Surg 2006;30:164-167.[Abstract/Free Full Text]
  32. Mansour Z, Kochetkova EA, Ducrocq X, et al. Induction chemotherapy does not increase the operative risk of pneumonectomy! Eur J Cardiothorac Surg 2007;31:181-185.[Abstract/Free Full Text]
  33. Doddoli C, Aragon A, Barlesi F, et al. Does the extent of lymph node dissection influence outcome in patients with stage I non-small cell lung cancer? Eur J Cardiothorac Surg 2005;27:680-685.[Abstract/Free Full Text]
  34. Wu YL, Huan ZF, Wang SY, Yang XN, Ou W. A randomized trial of systematic nodal dissection in respectable non-small cell lung cancer Lung Cancer 2002;36:1-6.[Medline]
  35. Keller SM, Adak S, Wagner H, et al. Mediastinal lymph node dissection improves survival in patients with stages II and IIIa non-small cell lung cancer Ann Thorac Surg 2000;70:358-366.[Abstract/Free Full Text]
  36. Wright G, Manser RL, Byrnes G, Hart D, Campbell DA. Surgery for non-small cell lung cancer: systematic review and metaanalysis of randomized controlled trials Thorax 2006;61:597-603.[Abstract/Free Full Text]

Related Article

Invited Commentary
Pierre-Emmanuel Falcoz
Ann. Thorac. Surg. 2008 86: 233-234. [Extract] [Full Text] [PDF]



This article has been cited by other articles:


Home page
 Ann. Thorac. Surg.Home page
A. W. Kim, L. P. Faber, W. H. Warren, S. Basu, S. C. Wightman, J. A. Weber, P. Bonomi, and M. J. Liptay
Pneumonectomy after chemoradiation therapy for non-small cell lung cancer: does "side" really matter?
Ann. Thorac. Surg., September 1, 2009; 88(3): 937 - 943.
[Abstract] [Full Text] [PDF]

Home page
 Ann. Thorac. Surg.Home page
H. M. Klomp and I. Kappers
Is Pneumonectomy Justified in Patients With Locally Advanced NSCLC and Persistent N2 Disease After Induction Chemotherapy?
Ann. Thorac. Surg., March 1, 2009; 87(3): 990 - 991.
[Full Text] [PDF]

Home page
 Ann. Thorac. Surg.Home page
P.-E. Falcoz
Invited Commentary
Ann. Thorac. Surg., July 1, 2008; 86(1): 233 - 234.
[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):
Nicola Santelmo
Xavier Ducrocq
Jean-Marie Wihlm
Gilbert Massard
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 Mansour, Z.
Right arrow Articles by Massard, G.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Mansour, Z.
Right arrow Articles by Massard, G.
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