HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Abstract Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Personal Folders Download to citation manager Author home page(s): Paul De Leyn Johan Vansteenkiste Dirk Van Raemdonck Permission Requests Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by De Leyn, P. Articles by Lerut, T. Search for Related Content PubMed PubMed Citation Articles by De Leyn, P. Articles by Lerut, T.

Eur J Cardiothorac Surg 1999;15:608-614
© 1999 Elsevier Science NL

Result of induction chemotherapy followed by surgery in patients with stage IIIA N2 NSCLC: importance of pre-treatment mediastinoscopy

^a Department of Thoracic Surgery, University Hospital Gasthuisberg, Catholic University, Heretraat 49, B-3000 Leuven, Belgium
^b Department of Pulmonology, University Hospital Gasthuisberg, Catholic University, Heretraat 49, B-3000 Leuven, Belgium

Received 12 October 1998; received in revised form 27 January 1999; accepted 10 February 1999.

Corresponding author. Tel.: +32-16346820; fax: +32-16346821
e-mail: paul.deleyn{at}uz.kuleuven.ac.be

	Abstract

Top Abstract 1. Introduction 2. Patients and methods... 3. Results 4. Discussion 4. Uncited References Appendix A. Conference... References

 
Objective: Data from the literature indicate that chemotherapy prior to resection may improve the results. However, only few and conflicting data are reported regarding the correlation between downstaging of mediastinal nodes and outcome. The aim of this study was to look at the correlation between downstaging, survival and pre-treatment staging. Material and methods: Between March 1995 and August 1998, 46 consecutive patients with pathology proven N2 disease were treated with three cycles of vindesine-ifosfamide-platinum (VIP). All patients underwent a rigorously performed cervical mediastinoscopy. Patients with at least partial response (n=26) were surgically explored. Results: The clinical response rate to chemotherapy was 57% (26 patients). Resection was complete in 23 patients (88.5%). Pneumonectomy was performed in 16 patients. In 11 patients (42.9%) the mediastinal nodes (which were positive at mediastinoscopy) had become negative (downstaging group). The projected 2-year survival of resected patients is 41%. Patients with downstaging of nodes had no better survival compared to patients with no downstaging. Patients with involved subcarinal nodes at mediastinoscopy and patients with involvement of more than one level had a worse survival. Conclusion: Surgery in N2-patients responsive to induction chemotherapy resulted in a high complete resectability rate. Findings at pre-treatment mediastinoscopy proved to be the most important prognostic factor.

Key Words: Carcinoma • Non-small cell lung • Combined modality treatment • Induction chemotherapy • Lung surgery • N2-disease

	1. Introduction

Top Abstract 1. Introduction 2. Patients and methods... 3. Results 4. Discussion 4. Uncited References Appendix A. Conference... References

 
The involvement of mediastinal lymph nodes (MLN) in patients with potentially resectable non-small cell lung cancer (NSCLC) is a very important prognostic factor. Patients with involved ipsilateral mediastinal or subcarinal lymph nodes (N2 disease) diagnosed preoperatively have a low complete resectability rate and a 5-year survival rate of only 9% [8,11,18,25]. Because of this important impact on prognosis, the new TNM classification has recently been modified [13]. Patients with N2 disease are still classified in stage IIIA while patients with T3N0 or T3N1 disease have been migrated into stage IIB.

In patients with N2 disease, induction chemotherapy followed by resection has been shown to be beneficial in 3 small randomized studies [17,21,22] and several phase II studies. However, review of the literature reveals that the pre-treatment staging was often non-invasive with patients believed to have N2 disease on CT findings only [24]. Enlarged nodes on CT scan are inflammatory in 50% of the cases [5] and these patients can in fact have N0 disease with a much better prognosis. Another striking point is the heterogeneity of the groups. Induction chemotherapy was often administered for stage IIIA tumours on the basis of T3N0 or T3N1 disease. These patients have a far better prognosis than patients with N2 disease, especially if the T3 factor is caused by resectable chest wall invasion.

The aim of this study is to evaluate the results of surgery after induction chemotherapy in a homogenous group of patients with N2 disease, proven by a meticulously performed invasive mediastinal staging. The effect of downstaging, the number and level of involved nodes at mediastinoscopy, and other different prognostic factors on survival are evaluated.

	2. Patients and methods

Top Abstract 1. Introduction 2. Patients and methods... 3. Results 4. Discussion 4. Uncited References Appendix A. Conference... References

 
Between March 1995 and August 1998, patients with potentially operable NSCLC with histological proven N2 disease were entered in this prospective study. Distant metastasis were excluded according to standard guidelines [9]. Since 1998, positron emission tomography (PET) scan was also routinely used in these patients.

As mediastinoscopy is essential to rule out contralateral disease (N3 disease) and because we were interested to evaluate the effect of the number and type of levels involved at mediastinoscopy on survival, we included only these patients who underwent cervical mediastinoscopy in our hospital. During this procedure, the upper right and left paratracheal nodes, the lower right and left paratracheal nodes, and the subcarinal nodes were extensively biopsied and labelled separately [4]. In patients with left upper lobe tumours with clinical suspicion of positive nodes in the paraaortic level or in the aortopulmonary window, a left anterior mediastinotomy was performed in case of negative cervical mediastinoscopy.

Inclusion criteria for induction chemotherapy were: age 70 or less, WHO performance status less than 2, bi-dimensionally measurable disease, no previous radio- or chemotherapy, no previous malignancies. Base line organ functions had to be normal. After combined treatment, patients were followed every 3 months with a thorough clinical examination, biological tests, a chest X-ray, and other imaging studies as clinically indicated or necessary to assess the site of recurrence. The cause of death was determined in all cases.

Tumours were staged according to the revised version of TNM staging, published in August 1997 [15,16].

2.1. Chemotherapy
Three courses of chemotherapy were given, except in cases with obvious progression during treatment. Cisplatinum 40 mg/m² was given on day 1, 30 mg/m² on days 2 and 3. Ifosfamide 1200 mg/m² was given on days 1, 2 and 3. Vindesine 3 mg/m² (max 5 mg) was given weekly during the first cycle and every 2 weeks in cycles 2 and 3. More detailed information on the induction scheme and its morbidity has been published by our respiratory oncology group [26].

Response was assessed at the weekly tumour round by clinicians and a staff member in thoracic radiology, by comparing the bi-dimensionally measurable lesions on a thoracic CT-scan before and 2–4 weeks after the last chemotherapy. The usual criteria for definition of response were followed [14].

2.2. Surgery
Patients with at least partial response underwent surgery with systematic mediastinal lymph node dissection [27].

Resection was defined complete in case of removal of all tumour at the primary site and lymph nodes, with the resection margin negative, and the highest mediastinal lymph nodes free of tumour.

Adjuvant thoracic radiotherapy (a total dose of 56 gy in 28 daily fractions) was given to patients with persistent N2 disease in the resected specimen.

2.3. Statistics
Survival was calculated from the time of diagnosis to the date of death or last date of follow-up for surviving patients. Survival curves were calculated by the Kaplan–Meier product-limit method and compared using the log rank test statistic.

	3. Results

Top Abstract 1. Introduction 2. Patients and methods... 3. Results 4. Discussion 4. Uncited References Appendix A. Conference... References

 
3.1. Patients
Between March 1995 and August 1998, 46 patients with histology proven NSCLC with N2 disease were entered in this prospective study. Partial or complete clinical response to chemotherapy was found in 26 patients (57%, Fig. 1) .

View larger version (10K): [in this window] [in a new window]   Fig. 1. Flow chart of 46 patients with N2 disease proven by invasive mediastinal staging performed at our hospital.

There were no postoperative deaths. The mean hospital stay was 13.6 days (±10.7) except for one patient in which prolonged ventilation was necessary because of pneumonia with respiratory insufficiency (120 days). Other complications were pneumonia and respiratory insufficiency requiring prolonged (>48 h) ventilation in another two patients, atrial fibrillation in two patients, prolonged air leak in two patients and recurrent nerve palsy in one patient. There were no bronchial fistulae.

3.3. Effect of chemotherapy on downstaging.
The results of the pathological examination of the resected specimens are shown in Table 2. In eleven patients (42.3%), no tumour was found in any of the mediastinal lymph nodes. Complete pathological response (pT0N0) was seen in only one patient (3.8%). In two patients, the tumour in the lung was completely sterilized while the mediastinal nodes remained positive. Pathological T staging was: pT0 in three patients, pTl in 11 patients, pT2 in 9 patients and pT3 in three patients.

View larger version (8K): [in this window] [in a new window]   Fig. 2. Overall survival after resection in responding patients treated with induction chemotherapy for N2 disease.

View larger version (10K): [in this window] [in a new window]   Fig. 3. Survival in patients with persistent N2 disease compared with those patients with downstaging in the mediastinal nodes of the resection specimen in responding patients treated with induction chemotherapy for N2 disease.

View larger version (11K): [in this window] [in a new window]   Fig. 4. Survival after resection in responding patients treated with induction chemotherapy for N2 disease. Effect of number of subcarinal lymph nodes at mediastinoscopy.

	4. Discussion

Top Abstract 1. Introduction 2. Patients and methods... 3. Results 4. Discussion 4. Uncited References Appendix A. Conference... References

In our study with VIP induction, the response to chemotherapy was 57%, which is comparable to the figure previously described by our group [26]. This clinical response rate is somewhat lower than reported in other studies which use other chemotherapy schemes [12]. Using induction chemoradiotherapy response rates up to 88% [13] and 89% [28] are reported. In a recent study using induction chemoradiotherapy, a pathological complete response of 26% has been reported [6].

We have only explored those patients with at least partial response on chemotherapy (n=26). Some groups have, in an attempt to salvage as many patients as possible explored patients with stable disease. However, when we review the literature [24], pathological complete response is very exceptional in clinically non-responding patients.

Complete resection, which was defined as removal of all known disease with no involvement of the margins of resection, nor of the highest mediastinal lymph nodes was possible in 23 patients (88.5%). The complete resection rate in the literature varies between 65 and 94%. This high resectability in our study is explained by the fact that we explored only patients with radiographic response to the induction treatment. In the study by Elias et al. [7], complete resection was statistically significant higher in patients with radiographic response compared to patients with stable disease.

During thoracotomy, pulmonary resection with systematic nodal dissection was performed. In the majority of those patients (61.5%) a pneumonectomy needed to be performed. When the tumour is located in the upper lobe, a lobectomy with mediastinal lymphadenectomy is performed. We believe that covering of the bronchial stump after pneumonectomy (mainly on right side) is essential to prevent bronchial fistulae.

The 2-year survival in our study was 41% with a median survival of 20 months. We have to keep in mind that this survival rate is obtained only for the subselected group of 26 responding patients. Although mediastinal nodal dissection is easier and more extensive to perform on the right side, no difference in survival was found between left or right sided tumours. Patients in which the tumour was cleared by lobectomy had a better survival when compared to patients with pneumonectomy. In three of these patients, pre-treatment staging showed that pneumonectomy would be necessary, but after induction treatment the tumour could be resected by lobectomy. All three patients are alive without evidence of disease.

Pathologic complete response (PCR), as defined by no viable tumour in resected specimen (primary tumour and dissected nodes) is an important endpoint associated with event free survival. In reported series, the incidence of PCR ranges from 0 to 18%. In the retrospective study of Memorial Sloan Kettering Cancer Center [19], patients with PCR had a progression-free survival of 45% at 5 years. In our series, only one patient (3.8%) had no viable tumour after three cycles of VIP.

Downstaging (mediastinal nodes negative in patients when previously involved) could be an important prognostic factor for resectability and long-term survival although many trials are unevaluable for this analysis as detailed mediastinal staging is not routinely performed and reported. In our study, downstaging in patients responsive to chemotherapy (n=26) occurred in 11 patients (42.3%). This is lower when compared to the study of Elias (71%) in which cisplatinum, Leukovorin and 5-FU was given [7] but comparable with the study of Kim et al. [10]. In this study, downstaging was described in 41%. To our surprise, patients with downstaging had no better survival compared to patients in which the mediastinal nodes remained positive. In the study of Elias et al., patients with downstaging showed a trend (but not statistically significant) to better survival. Chella [3] reported no difference in survival in pN2 and pN0 patients. In the Southwest Oncology group trial 88-05 [1], 126 patients with stage IIIA (N2) or stage IIIB (N3 or T4) were treated with preoperative chemoradiotherapy. The strongest predictor of event-free survival in this study was the absence of involved mediastinal nodes at the time of surgery.

In our study, the effect of pathological downstaging was not a significant prognostic factor on long-term survival. We have no clear explanation for this finding. A possible explanation could be that only patients with response to chemotherapy were explored in our series. Another possible explanation is the use of high-dose postoperative radiotherapy in patients with remaining viable tumour in the mediastinal nodes of the resection specimen. This has, however, been done in most of the studies. Conformation of this finding might have considerable implications for the future. According to our preliminary results, patients with persistent mediastinal disease might have a similar survival.

In two patients, the tumour in the lung was completely sterilized while the mediastinal nodes remained positive, which stresses the need that mediastinal nodal dissection should be performed in all patients.

In all patients in this series, meticulous cervical mediastinoscopy was performed at our hospital. This allows analysis of the correlation between downstaging and mediastinoscopic findings on survival. A very important prognostic factor for survival was the result of cervical mediastinoscopy performed before the onset of induction chemotherapy. Patients in which the subcarinal nodes were positive at mediastinoscopy, had a significantly lower survival with no patients alive at 2 years. Patients with more than one nodal level involved at mediastinoscopy, also had a significantly lower survival when compared to patients with only one nodal level involved.

We conclude that surgery after induction chemotherapy can be performed with acceptable morbidity. To our surprise, downstaging of the mediastinal nodes was not a prognostic factor in this analysis while the findings of cervical mediastinoscopy before the onset of induction chemotherapy proved to be of critical importance. Larger studies are needed to evaluate the impact of staging procedures and surgical resection of surgery in this group of patients.

	4. Uncited References

Top Abstract 1. Introduction 2. Patients and methods... 3. Results 4. Discussion 4. Uncited References Appendix A. Conference... References

 
Author, these references are not cited in the text. Please add or delete from reference list. [2].

	Footnotes

 
Presented at the 12th Annual Meeting of the European Association for Cardio-thoracic Surgery, Brussels, Belgium, September 20–23, 1998.

	Appendix A. Conference discussion

Top Abstract 1. Introduction 2. Patients and methods... 3. Results 4. Discussion 4. Uncited References Appendix A. Conference... References

 
Dr T. Grodzki (Szczecin, Poland): I have one doubt about those disappearing carcinomas in N2 disease, because the number of 32% N2 lymph nodes which were finally concluded with absence of malignant cells is a little bit too high. Did you do the histologic findings with the cytokeratin reaction or another specific monoclonal antibody's reaction, because the result seems a little bit false.

Dr De Leyn: Excuse me, I did not understand the question.

Dr. Grodzki: I wonder why 45% of first N2 disease at the end has appeared to be N1 or N0 disease?

Dr. De Leyn: All patients had N2 disease proven by cervical mediastinoscopy before the onset of chemotherapy. Then they received chemotherapy. After chemotherapy downstaging may occur. This means that these nodes, which were positive, become negative because of the chemotherapy. In the literature this varies from 40 to 70%.

Dr. Grodzki: Yes, but you have indicated that downstaging has no influence on 5-year survival, so it seems to confirm the thesis that the downstaging was a little bit false. So my question is, what techniques of histologic examination were used to prove the absence of malignant cells?

Dr. De Leyn: Well, we did not do immunohistology, we just did routine histology.

Dr. P. Van Schil (Edegem, Belgium): I have a rather similar question and one comment. In contrast to previous studies, you did not find a better survival when there was a downstaging to N0 or N1 disease. Do you have an explanation for that? My comment is that a definite answer, whether surgery or radiotherapy is better after response to induction chemotherapy, can only come from large phase 3 studies. There is currently a study from the EORTC trying to answer that. In this study, patients who have a response to induction chemotherapy with proven N2 disease beforehand, are randomized between surgical treatment and radiotherapy. I would encourage the audience to participate in that study because we need quite a lot of patients, as this is a prospective randomized study.

Dr. De Leyn: I fully agree that it is very remarkable that we found no effect. When you look through the literature, there is an article published by Chella, which also found no difference. In previous studies, not all patients had cervical mediastinoscopy, and there are only a few groups which are looking at the effect of downstaging of mediastinal nodes. I fully agree that it is difficult to understand and we have to do more extensive studies to see if indeed surgery is necessary.

Dr A. End (Vienna, Austria): Could you comment on your

postoperative adjuvant therapy?

Dr De Leyn: When we found persistent N2 disease, these patients received radiotherapy up to 56 gray. This could be an explanation as to why we did not find an effect of downstaging on survival.

Dr A. Brutel de la Riviere (Nieuwegein, The Netherlands): When do you determine the operative strategy? I mean, do you determine the resection planned before the chemotherapy is started or after you have noted response and, therefore, surgery is, in your view, possible?

Dr De Leyn: In our center, all patients are shown on a multidisciplinary group, and induction chemotherapy is given when we think, as surgeons, that the tumour is resectable. If you ask, are you going to do a lobectomy when initially findings had shown that the tumour could only be cleared by a pneumonectomy, that is a difficult question. Initially, we always did what we should have done before, chemotherapy. During the last months, if the tumour has decreased that much, we will try to do a less extended resection, if it is possible. We found a good survival in these patients with lobectomy. So it seems that you can do a less extended resection.

	References

Top Abstract 1. Introduction 2. Patients and methods... 3. Results 4. Discussion 4. Uncited References Appendix A. Conference... References

 

1. Albain K.S., Rusch V.W., Crowley J.J. Concurrent cisplatinletoposide 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]
2. Burkes R.L., Ginsberg R.J., Shepherd F.A., Blackstein M.E., Goldberg M.E., Waters P.F., Patterson G.A., Todd T., Pearson F.G., Cooper J.D., Jones D., Lockwodd G. Induction chemotherapy with mitomycin, vindesin, and cisplatinum for stage III unresectable non-small-cell lung cancer: Results of the Toronto phase II trial. J Clin Oncol 1992;10:580-586.[Abstract/Free Full Text]
3. Chella A., Lucchi M., Ribechini A., Silvano G., Mussi A., Janni A., Angeletti C.A. Pre-operative chemotherapy for stage IIIA (N2) non small cell lung cancer. Eur J Surg Oncol 1995;21:393-397.[Medline]
4. De Leyn P., Vansteenkiste J., Cuypers P., Deneffe G., Van Raemdonck D., Coosemans W., Verschakelen J., Lerut T. Role of cervical mediastinoscopy in staging of non-small cell lung cancer without enlarged mediastinal lymph nodes on CT scan. Eur J Cardio-thorac Surg 1997;12:706-712.[Abstract]
5. Dillemans B., Deneffe G., Verschakelen J., Decramer M. Value of computed tomography and mediastinoscopy in preoperative evaluation of mediastinal nodes in non-small cell lung cancer. Eur J Cardio-thorac Surg 1994;8:37-42.[Abstract]
6. Eberhardt W., Wilke H., Stamatis G., Stuschke M., Harstrick A., Menker H., Krause B., Mueller M.R., Stahl M., Flasshove M., Budach V., Greschuchna D., Kietzko N., Sack H., Seeber S. Preoperative chemotherapy followed by concurrent radiotherapy based on hyperfractionated accelerated radiotherapy and definitive surgery in locally advanced non-small-cell lung cancer: mature results of a ophase II trial. J Clin Oncol 1998;16:622-634.[Abstract]
7. Elias A.D., Skarin A.T., Leong T., Mentzer S., Strauss G., Lynch T., Shulman L., Jacobs C., Abner A., Baldini E.H., Frei E., Sugarbaker D.J. Neoadjuvant therapy for surgically staged IIIA N2 non-small cell lung cancer (NSCLC). Lung Cancer 1997;17:147-161.[Medline]
8. Funatsu T., Matsubaru Y., Hatakenaka R., Kosaba S., Yasuda Y., Ikeda S. The role of mediastinoscopic biopsy in preoperative assessment of lung cancer. J Thorac Cardiovasc Surg 1992;104:1688-1695.[Abstract]
9. Goldstraw P., Rocmans P., Ball D., Barthelemy N., Bonner J., Carette M., Choi N., Emani B., Grunenwald D., Hazuka M. Pretreatment minimal staging for non-small-cell lung cancer: an updated consensus report. Lung Cancer; 11(Suppl 1994;3:1-4.
10. Kim D.H., Lynch T.J., Mentzer S.J. Multimodality therapy of patients with stage IIIA. N2 non-small-cell lung cancer. J Thorac Cardiovasc Surg 1993;106:696-702.
11. Martini N., Flehinger B.J. The role of surgery in N2 lung cancer. Surg Clin North Am 1987;67:1037-1049.[Medline]
12. Martini N., Kris M.G., Flehinger B.J., Gralla R.J., Bains M.S., Burt M.E., Heelan R., McCormack P.M., Pisters K.M.W., Rigas J.R., Rusch V.W., Ginsberg R.J. Preoperative chemotherapy for stage lila (N2) lung cancer: the Sloan–Kettering experience with 136 patients. Ann Thorac Surg 1993;55:1365-1374.[Abstract]
13. Mathisen D.J., Wain J.C., Wright C., et al. Assessment of preoperative accelerated radiotherapy and chemotherapy in stage IIIA (N2) non-small-cell lung cancer. J Thorac Cardiovasc Surg 1996;111:123-131.[Abstract/Free Full Text]
14. Miller A.B., Hoogstraten B., Staquet M., Winkler A. Reporting results of cancer treatment. Cancer 1981;47:207-214.[Medline]
15. Mountain C.F., Dresler C.M. Regional lymph node classification for lung cancer staging. Chest 1997;111:1718-1723.[Abstract/Free Full Text]
16. Mountain C.F. Revisions in the International System for Staging Lung Cancer. Chest 1997;111:17107.
17. Pass H.I., Progrebniak H.W., Steinberg S.M., Mulshine J., Minna J. Randomized trial of neoadjuvant therapy for lung cancer: interim analysis. Ann Thoracic Surg 1992;53:992-998.[Abstract]
18. Pearson F.G., Delarue N.C., Ilves R., Todd T.R.J., Cooper J.D. Significance of positive superior mediastinal nodes identified at mediastinoscopy in patients with resectable cancer of the lung. J Thorac Cardiovasc Surg 1982;83:1-11.[Medline]
19. Pisters K.M.W., Kris M.G., Gralla R.J., Zaman M.B., Heelan R.T., Martini N. Pathologic complete response in advanced non-small-cell lung cancer following preoperative chemotherapy: implications for the design of future non-small-cell lung cancer combined modality trials. J of Clin Oncol 1993;11:1757-1762.[Abstract/Free Full Text]
20. Pujol J.L., Hayot M., Rouanet P., Le Chevalier T., Michel F.B. Long-term results of neoadjuvant ifosfamide, cisplatinum, and etoposide combination in locally advanced non-small cell lung cancer. Chest 1994;106:1451-1455.[Abstract/Free Full Text]
21. Rosell R., Gomez-Codina J., Camps C., Maestre J., Padille J., Canto A., Mate J.L., Li S., Roig J., Olazabal A., Canella M., Ariza A., Skacel Z., Morera-Prat J., Abat A. 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]
22. Roth J.A., Fossella F., Komaki R., Ryan M.B., Putnam J.B., Lee J.S., Dhingra H., De Caro L., Chasen M., McGavran M., Atkinson E.N., Hong W.K. A randomized trial comparing perioperative chemotherapy and surgery with surgery alone in resectable stage IIIA non-small-cell lung cancer. J Natl Cancer Inst 1994;86:673-680.[Abstract/Free Full Text]
23. Takita H., Blumenson L.E., Raghavan D. Neoadjuvant chemotherapy of stage IIIA and B lung carcinoma using the PACCO regimen. J Surg Oncol 1995;59:147-150.[Medline]
24. Vansteenkiste J., De Leyn P., Deneffe G., Menten J., Lerut T., Demedts M. Present status of induction treatment for N2 non-small cell lung cancer: A review. Eur J Cardio-thorac Surg 1998;13:1-12.[Abstract/Free Full Text]
25. Vansteenkiste J.F., De Leyn P.R., Deneffe G.J., Stalpaert G., Nackaerts K.L., Lerut T.E., Demedts M.G. 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]
26. Vansteenkiste J.F., De Leyn P.R., Deneffe G.J., Lievens Y.N., Nackaerts K.L., Van Raemdonck D.E., van der Schueren E. Lerut. Th., Demedts, M.G. Vindesine-ifosfamide-platinum (VIP) induction chemotherapy in surgically staged IIIA-N2 non-small-cell lung cancer: A prospective study. Ann Oncol 1998;9:261-267.
27. Vansteenkiste J.F., Stroobants S.G., De Leyn P.R., Dupont P.J., Bogaert J., Maes A., Deneffe G., Nackaerts K.L., Verschakelen J.A., Lerut T.E., Mortelmans L.A., Demedts M.G. Lymph node staging in non-small-cell lung cancer with FDG-PET Scan: a prospective study on 690 lymphnode stations from 68 patients. J Clin Oncol 1998;16:2142-2149.[Abstract]
28. Weitberg A.B., Yashar J., Glicksman A.S., et al. Combined modality therapy for stage IIIA non-small-cell carcinoma of the lung. Eur J Cancer 1993;29A:511-515.

This article has been cited by other articles:

				V. Steger, T. Walles, B. Kosan, T. Walker, T. Kyriss, S. Veit, J. Dippon, and G. Friedel Trimodal Therapy for Histologically Proven N2/3 Non-Small Cell Lung Cancer: Mid-Term Results and Indicators for Survival. Ann. Thorac. Surg., June 1, 2009; 87(6): 1676 - 1683. [Abstract] [Full Text] [PDF]

				C. Dooms, E. Verbeken, S. Stroobants, K. Nackaerts, P. De Leyn, and J. Vansteenkiste Prognostic Stratification of Stage IIIA-N2 Non-Small-Cell Lung Cancer After Induction Chemotherapy: A Model Based on the Combination of Morphometric-Pathologic Response in Mediastinal Nodes and Primary Tumor Response on Serial 18-Fluoro-2-Deoxy-Glucose Positron Emission Tomography J. Clin. Oncol., March 1, 2008; 26(7): 1128 - 1134. [Abstract] [Full Text] [PDF]

				S. Mizuguchi, N. Nishiyama, T. Iwata, T. Nishida, N. Izumi, T. Tsukioka, K. Inoue, M. Kameyama, and S. Suehiro Clinical Value of Serum Cytokeratin 19 Fragment and Sialyl-Lewis X in Non-Small Cell Lung Cancer Ann. Thorac. Surg., January 1, 2007; 83(1): 216 - 221. [Abstract] [Full Text] [PDF]

				J. L. Port, R. J. Korst, P. C. Lee, M. A. Levin, D. E. Becker, R. Keresztes, and N. K. Altorki Surgical Resection for Residual N2 Disease After Induction Chemotherapy Ann. Thorac. Surg., May 1, 2005; 79(5): 1686 - 1690. [Abstract] [Full Text] [PDF]

				M. K. Ferguson Optimal management when unsuspected N2 nodal disease is identified during thoracotomy for lung cancer: cost-effectiveness analysis J. Thorac. Cardiovasc. Surg., December 1, 2003; 126(6): 1935 - 1942. [Abstract] [Full Text] [PDF]

				D. Lardinois, A. Horsch, T. Krueger, M. Dusmet, and H.-B. Ris Mediastinal reinforcement after induction therapy and pneumonectomy: comparison of intercostal muscle versus diaphragm flaps Eur. J. Cardiothorac. Surg., January 1, 2002; 21(1): 74 - 78. [Abstract] [Full Text] [PDF]

				N. Novoa, G. Varela, and M.F. Jimenez Morbidity after surgery for non-small cell lung carcinoma is not related to neoadjuvant chemotherapy Eur. J. Cardiothorac. Surg., October 1, 2001; 20(4): 700 - 704. [Abstract] [Full Text] [PDF]

This Article Abstract Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Personal Folders Download to citation manager Author home page(s): Paul De Leyn Johan Vansteenkiste Dirk Van Raemdonck Permission Requests Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by De Leyn, P. Articles by Lerut, T. Search for Related Content PubMed PubMed Citation Articles by De Leyn, P. Articles by Lerut, T.