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Results of surgical treatment of T4 non-small cell lung cancer

Results of surgical treatment of T4 non-small cell lung cancer Abstract Objective: Because of location and invasion of surrounding structures, the role of surgical treatment for T4 tumors remains unclear. Extended resections carry a high mortality and should be restricted for selected patients. This study clarifies the selection process in non-small cell T4 tumors with invasion of the mediastinum, recurrent nerve, heart, great vessels, trachea, esophagus, vertebral body, and carina, or with malignant pleural effusion. Methods: From 1977 through 1993, 89 patients underwent resection for primary non-small cell T4 carcinomas. Resection was regarded as complete in 34 patients (38.2%) and incomplete in 55 patients (61.8%). Actuarial survival time was calculated and risk factors for late death were identified. Results: Overall hospital mortality was 19.1% (n=17). Mean 5-year survival was 23.6% for all hospital survivors, 46.2% for patients with complete resection and 10.9% for patients with incomplete resection (P=0.0009). In patients with complete resection, mean 5-year survival for patients with invasion of great vessels was 35.7%, whereas mean 5-year survival for invasion of other structures was 58.3% (P=0.05). Age, mediastinal lymph node involvement, type of operative procedure, and postoperative radiotherapy did not significantly influence survival. Conclusion: In certain T4 tumors complete resection is possible, resulting in good mean 5-year survival especially for tumors with invasion of the trachea or carina. High hospital mortality makes careful patient selection imperative. Lung cancer, Surgery, Survival 1 Introduction Prognosis in carcinoma of the lung is influenced by the stage of the disease and consequently by the therapeutic potential. Surgical resection is the treatment of choice for stage I and stage II non-small cell lung cancer, but its role in stage III disease remains unclear [1]. Our previous studies have shown that complete resection will result in good survival in T3 bronchogenic carcinoma with chest wall involvement [2], and in lung tumors invading mediastinal structures, or the main bronchus [3]. These tumors are classified as stage IIB, or IIIA disease [4]. Stage IIIB non-small cell lung cancer can be divided into primary bronchogenic carcinoma invading adjacent structures (T4), or tumors with metastases to contralateral mediastinal, contralateral hilar, ipsilateral or contralateral scalene, or supraclavicular lymph node(s) (N3). T4 bronchogenic carcinomas are a heterogeneous group of locally advanced cancers. Generally, these T4 tumors are regarded as unresectable [5]. Treatment is palliative for the majority of the patients, ranging from supportive care to chemotherapy or radiotherapy. However, some studies about extended resection of T4 tumors have been published [6–10]; hospital morbidity and mortality are high but, in selected patients, surgery appears to be beneficial and radical resection of the tumor has a potential for cure in the absence of mediastinal lymph node metastases. The present report is a retrospective analysis of survival characteristics in 89 patients who underwent resection for T4 tumors with invasion of the mediastinum, recurrent nerve, heart, great vessels, trachea, esophagus, vertebral body and carina or with a malignant pleural effusion. 2 Materials and methods From 1977 through 1993, 2009 patients with bronchogenic carcinoma had a resection at our hospital. Of this group, 89 patients (4.4%) underwent operation for T4 non-small cell lung cancer (NSCLC) with invasion of the mediastinum, recurrent nerve, heart, great vessels [aorta, superior vena cava, proximal main pulmonary vessels (proximal defined as proxim to the pericard or at pericardial reflection)], trachea, esophagus, vertebral body, or carina, or with malignant pleural effusion at pathologic examination. Patients with distant metastases, synchronous tumors, superior sulcus tumors, a satellite tumor within the same lobe or recurrences were excluded. Resection was considered complete when (1) the surgeon was morally certain that all known disease was removed; (2) resection margins were histologically free; and (3) the highest mediastinal lymph node was negative by microscopy. Staging procedures included routine blood tests, thoracic computed tomography, ultrasonography of the upper abdomen, bronchoscopy, mediastinoscopy, and pulmonary function tests. Computed tomography of the brain or bone scintigraphy was performed only in case of clinical suspicion of metastatic disease. Patient characteristics are shown in Table 1 . Cervical mediastinoscopy was negative in 81 patients (91.0%), not performed in one patient (1.1%) and positive in seven patients (7.9%). These seven patients were operated because they only had one single positive lymph node at the ipsilateral tracheobronchial angle (n=4), or, because they were relatively young (46 and 51 years). In one patient the reason for thoracotomy could not be assessed retrospectively. One patient was pre-operatively diagnosed at bronchoscopy as having a carcinosarcoma in the main right bronchus. No cervical mediastinoscopy was performed. Frozen sections peroperatively showed a squamous cell carcinoma. Table 1 Open in new tabDownload slide Patient characteristics Table 1 Open in new tabDownload slide Patient characteristics The type of resection is shown in Table 2 . In four patients with bronchogenic carcinoma invading the right side of the mediastinum, a pneumonectomy (n=3) or lobectomy (n=1) included resection and reconstruction of the superior vena cava by a Goretex graft. Two patients had a lobectomy of the right upper lobe and a bypass of the superior vena cava. One patient had a lobectomy of the left upper lobe followed by a Dacron prothesis of the subclavian artery. In one patient with a pneumonectomy the tumor invaded the chest wall and an en bloc resection of the tumor and the chest wall was performed. Table 2 Open in new tabDownload slide Operative procedures Table 2 Open in new tabDownload slide Operative procedures A complete resection was achieved in 34 patients (38.2%). Resections were incomplete due to positive resection margins (n=39), positive lymph nodes (n=2), a combination of both (n=12) or malignant pleural effusion (n=2). The histological diagnosis was squamous cell carcinoma in 77 patients (86.5%), adenocarcinoma in 10 patients (11.2%), adenosquamous cell carcinoma in one patient (1.1%) and large cell carcinoma in one patient (1.1%). Cervical mediastinoscopy was false negative in 27 patients. Fourteen of these 27 patients had positive subaortic or para-aortic lymph nodes (n=11) or positive paraesophageal lymph nodes (n=3). All patients were staged as T4 because of involvement of the mediastinum, recurrent nerve, heart, great vessels, trachea, esophagus, vertebral body, or carina, or the presence of malignant pleural effusion (Table 3) . Invasion of the different great vessels and pTNM staging are shown in Tables 4 and 5 . Table 3 Open in new tabDownload slide Structures involved in T4 tumors Table 3 Open in new tabDownload slide Structures involved in T4 tumors Table 4 Open in new tabDownload slide Invasion of the different great vessels Table 4 Open in new tabDownload slide Invasion of the different great vessels Table 5 Open in new tabDownload slide pTNM staging Table 5 Open in new tabDownload slide pTNM staging Radiation therapy was given to 47 patients as adjuvant therapy. One patient with tumor invasion of the pulmonary artery was pre-operatively irradiated. Although he was judged to be inoperable, a palliative pneumonectomy was carried out some months later because of persistent complaints of dyspnea and the absence of distant metastases. Forty-six patients (51.7%) received radiotherapy postoperatively. Of these patients, 32 patients had an incomplete resection. In the group of patients with complete resection (n=14), seven patients were irradiated because they were staged as T4N2, the other seven patients received radiotherapy because of the bulk of the tumor or localization near great vessels or other major structures. One patient with a T4N2 tumor only received 1.200 cG radiation because she developed a pericardial effusion. Ten years after the operation she is still alive. Four patients (4.5%) received postoperative chemotherapy because of incomplete resection. Follow-up was completed as of August 2002. Follow-up data were obtained from hospital files and from questionnaires to referring pulmonary physicians and general practitioners. Follow-up about local recurrence and distant metastases was obtained in 96.6% of the patients. Survival was estimated from the date of operation, using the Kaplan–Meier survival analysis method [11]. Hospital deaths were excluded. Survival comparisons were analyzed by the log rank test [12]. The difference was considered statistically significant when the P value was less than 0.05. Incremental risk factors affecting survival were evaluated using Cox's proportional hazards model [13]. 3 Results Hospital mortality was 19.1% (pneumonectomy 18.3% [13/71], lobectomy 26.6% [4/15]). The mean age of these 17 patients was 64.4 years (51–77 years). Ten patients had undergone a pneumonectomy, two a carinal pneumonectomy, one an en bloc pneumonectomy, two a lobectomy and two a lobectomy with reconstruction of the superior vena cava. Of these 17 deceased patients, 13 had invasion of the great vessels (four left atrium and intrapericardial pulmonary vein, three intrapericardial pulmonary vein, three aorta, three superior vena cava), two invasion of the trachea and esophagus, one invasion of the trachea and one had tumor involvement of the vertebral column. Hospital deaths were due to cardiac arrest (n=5), sepsis (n=4), respiratory failure (n=3), hemoptysis (n=1), cerebral hemorrhage (n=1) and gastro-intestinal tract bleeding (n=1). Two patients died at home, 1 and 2 days, respectively, after their discharge from the hospital, but within 30 days of the operation. Mean 5-year survival was 19.1% for all patients (n=89) and 23.6% for hospital survivors (n=72). Complete resection was performed in 26 hospital survivors (36.1%) with a mean 5-year survival of 46.2%. The remaining 46 hospital survivors underwent an incomplete resection with a mean 5-year survival of 10.9% (P=0.0009) (Fig. 1) . Because of this significant difference in survival between patients with complete and incomplete resection, only the results of hospital survivors with complete resection were studied for the analysis of other prognostic factors. Fig. 1 Open in new tabDownload slide Mean 5-year survival in hospital survivors with complete resection (solid line) and incomplete resection (dashed line) (Cum, cumulative). Fig. 1 Open in new tabDownload slide Mean 5-year survival in hospital survivors with complete resection (solid line) and incomplete resection (dashed line) (Cum, cumulative). As for the N status, mean 5-year survival was 33.3% for three N0 patients, and 43.8% and 57.1% for 16 N1 and seven N2 patients, respectively (P>0.05). Regarding the T status, mean 5-year survival for patients with invasion of great vessels (n=14) was 35.7%, whereas mean 5-year survival for patients with invasion of other structures (n=12) was 58.3% (P=0.03) (Fig. 2) . Although patients with involvement of the carina or the trachea had a better mean 5-year survival (50.0%) than involvement of other structures (44.4%), the difference was not statistically significant. Fig. 2 Open in new tabDownload slide Mean 5-year survival after complete resection with invasion of great vessels (dashed line) and invasion of other structures (solid line) (Cum, cumulative). Fig. 2 Open in new tabDownload slide Mean 5-year survival after complete resection with invasion of great vessels (dashed line) and invasion of other structures (solid line) (Cum, cumulative). Of the 26 hospital survivors with complete resection, 24 patients had a squamous cell carcinoma with a mean 5-year survival of 45.8%. One patient with an adenocarcinoma died after 2 years and an other patient is still alive after 10 years. Mean 5-year survival for patients who underwent a pneumonectomy (n=23) was 43.5%, and for patients post lobectomy (n=3) 66.7% (P>0.05). Age and postoperative radiotherapy did not influence survival significantly. According to the multivariate analysis regarding age, sex, pTNM classification, histology and localization no significant prognostic factors were found in the group of patients with complete resection. Distant metastases developed in four of 26 hospital survivors with complete resection (15.4%), and one patient had a local recurrence (3.8%). Three patients had combined local and distant recurrence (11.5%). 4 Discussion Prognosis, surgical treatment and long-term survival of non-small cell bronchogenic carcinoma are closely related to the stage of the disease [1]. Stage IIIB non-small cell lung cancer has a 5-year survival rate of about 7%, and results of surgical treatment are poor [4,6,14]; however, some selected T4 tumors are potentially resectable, survival depending on completeness of resection, locoregional tumor invasion and lymph node metastases. These extended resections carry a high mortality and morbidity and make careful patient selection imperative. Hospital mortality varied between 5% and 20%, increasing after extended resections [15,16]. Our study also shows a substantial hospital mortality of 19.1%. Hospital mortality was related to invasion of the great vessels. Thirteen of 17 hospital deaths had tumor involvement of the aorta, superior vena cava or pulmonary veins. In this subset hospital mortality was 21.3% (13/61). Resectability of a tumor is influenced by pTNM staging. Our results of surgical treatment of T3 tumors with invasion of the chest wall, or with invasion of the mediastinal structures and/or localization in the main bronchus showed that complete resection was possible in 68.8% and 64.8%, respectively [2,3]. In T4 tumors, localization and invasion of adjacent structures often make complete resection impossible. A complete resection is vital [6,15]. In our series, mean 5-year survival for complete resections was 46.2%, for incomplete resections 10.9% (P<0.05). A complete resection could be performed in 34 patients (38.2%). This is higher than described by Martini et al. who had a complete resection rate of 18%. In that study none of the tumors invading the aorta, trachea or spine were resected [6]. However, other studies reported complete resection rates of 72% and 80%, respectively, for tumors invading great vessels or the carina [10,17]. Based on resectability criteria, Grunenwald divided stage IIIB tumors in two subcategories: potentially resectable (invasion of superior vena cava, carina, lower trachea, left atrium) and definitively non-resectable (malignant pleural effusion, invasion of the esophagus and vertebrae) [18]. Our study supports this classification. In the past, high post-operative morbidity and mortality and uncertain long-term survival have been associated with carinal surgery for bronchogenic carcinoma [19]. Respiratory failure after non-cardiogenic pulmonary edema or infection in the remaining lung and anastomotic dehiscence with bronchial fistula were the major postoperative problems and the main cause of the high operative mortality, varying from 11 to 27% in large series [8]. However, careful patient selection, much attention to surgical details and careful anesthetic management can lower the levels of surgical deaths. Recently, a postoperative mortality of 6.6–15% has been reported and pneumonectomy with tracheal sleeve resection is advocated by several surgeons with 5-year survival approaching 43% [7,16]. In our study, complete resection of tumors with invasion of the trachea or carina was 37.5% and 36.4%, respectively, while it was less for tumors with invasion of other structures and it had a favorable prognosis with a mean 5-year survival of 50.9%. Results of surgery for T4 tumors with invasion of the left atrium or great vessels are poor. Burt et al. reported no 5-year survivors in their series of 18 patients after resection for tumors extending into the vena cava superior [14], while Tsuchiya et al. found only two of 101 patients alive after 5 years [9]. However, recent advances in cardiovascular surgery offer possibilities for complete resection in cases of invasion of the great vessels, like aorta and superior vena cava [10,15]. Spaggiari et al. reported extended resections for tumors invading the superior vena cava with 5-year actuarial survival of 29%, with four of 25 patients alive at 5 years [10]. Hospital mortality was 12%, and a complete resection was achieved in 20 patients (i.e. 80%). This is high, but Doddoli et al. described the same results for completeness of resection and survival [17]. In our study 37.7% of the patients with invasion of the great vessels had a complete resection (n=14). This conforms with the results of Fukuse et al. [15]. There was no difference in completeness of resection between invasion of the aorta, superior vena cava and pulmonary vein. The results of complete resection in the group with invasion of the pulmonary artery were better, but this was a very small group. Mean 5-year survival was 35.7%. Traditionally, tumors invading vertebrae were considered as unresectable. We had no complete resection in both patients with involvement of the vertebral body. However, recent progress in spinal surgery has opened new possibilities. Induction treatment with total or partial vertebrectomy and pulmonary resection is feasible in selected patients with an estimated 5-year survival of 14% [20]. In most studies involvement of the esophagus precludes a complete resection [6,21]. We achieved a complete resection in three patients (25%), as only the muscular layer of the esophagus was involved by the tumor. Regarding lymph node involvement, mean 5-year survival was worse for N0 patients than for N1 and N2 patients. This finding is contradictory to our previous studies [2,3] in which mediastinal lymph node involvement worsens the prognosis. All three N0 patients in this series, however, had involvement of great vessels or the heart. Invasion of these structures carries a worse prognosis [6]. In the group of 16 N1 and seven N2 patients involvement of great vessels or the heart was present in nine and five patients, respectively. The remaining patients had involvement of the trachea (n=8), carina (n=4), mediastinum (n=4) or esophagus (n=3). Izbicki et al. also found no statistical significant differences in survival related to lymph node status in T4 tumors [22]. In their study, mean 3-year survival for six T4N0, seven T4N1 and 12 T4N2 patients was 0%, 53% and 16.6%, respectively. This suggests that in T4 tumors local invasion of surrounding structures may be more important for survival than lymph node involvement. But in both studies the number of patients is limited and other studies reported no long-term survivors in patients with T4N2 tumors [6,15,21]. Because of the poor results of surgical resection alone, multimodality treatment has surfaced as the treatment of choice in patients with stage III NSCLC [23]. However, it is still unclear which treatment modality (surgery, radiotherapy or a combination of both) will result in prolonged survival after neo-adjuvant chemotherapy. Recently, several trials have been conducted showing that some locally advanced, initially unresectable tumors become operable after induction chemotherapy [24,25]. Given our own results, and those reported by others [18,19,22] for patients presenting with T4 pathology, pre-operative work-up should establish the possibilities of complete resection using complete available modern imaging technology. If complete resection with appropriate reconstruction, is feasible, all patients, otherwise fit for surgery, should be operated on. Complete resection resulting in good mean 5-year survival is possible, especially for tumors invading the trachea or carina. Tumors with invasion of the esophagus, vertebrae and with malignant pleural effusion appear to be unresectable in most cases. The results of induction chemotherapy make us propose that presently multimodality treatment offers new possibilities to treat patients with T4 disease and a good performance status. We wish to thank Mrs Joke van der Sluis for her secretarial support. The study was supported by a grant from the Mr Willem Bakhuys Roozeboom Foundation References [1] Martini N. . Surgical treatment of non-small cell lung cancer by stage , Semin Surg Oncol , 1990 , vol. 6 (pg. 248 - 254 ) Google Scholar Crossref Search ADS PubMed WorldCat [2] Pitz C.C.M. , Brutel de la Rivière A. , Elbers H.R.J. , Westermann C.J.J. , van den Bosch J.M.M. . Surgical treatment of 125 patients with non-small cell lung cancer and chest wall involvement , Thorax , 1996 , vol. 51 (pg. 846 - 850 ) Google Scholar Crossref Search ADS PubMed WorldCat [3] Pitz C.C.M. , Brutel de la Rivière A. , Elbers H.R.J. , Westermann C.J.J. , van den Bosch J.M.M. . Results of resection of T3 non-small cell lung cancer invading the mediastinum or main bronchus , Ann Thorac Surg , 1996 , vol. 62 (pg. 1016 - 1020 ) Google Scholar Crossref Search ADS PubMed WorldCat [4] Mountain C.F. . Revisions in the international system for staging lung cancer , Chest , 1997 , vol. 111 (pg. 1710 - 1717 ) Google Scholar Crossref Search ADS PubMed WorldCat [5] Ginsberg R.J. , Vokes E.E. , Raben A. . Devita V.T. , Hellman S. , Rosenberg S.A. . Non-small cell lung cancer , Cancer. Principles and practice of oncology , 1997 Philadelphia Lippincott-Raven (pg. 858 - 911 ) Google Scholar Google Preview OpenURL Placeholder Text WorldCat COPAC [6] Martini N. , Yellin A. , Ginsberg R.J. , Bains M.S. , Burt M.E. , McCormack P.M. , Rusch V.W. . Management of non-small cell lung cancer with direct mediastinal involvement , Ann Thorac Surg , 1994 , vol. 58 (pg. 1447 - 1451 ) Google Scholar Crossref Search ADS PubMed WorldCat [7] Dartevelle P. , Macchiarini P. . Carinal resection for bronchogenic cancer , Semin Thorac Cardiovasc Surg , 1996 , vol. 8 (pg. 414 - 425 ) Google Scholar PubMed OpenURL Placeholder Text WorldCat [8] Van Raemdonck D.E. , Schneider A. , Ginsberg R.J. . Surgical treatment for higher stage non-small cell lung cancer , Ann Thorac Surg , 1992 , vol. 54 (pg. 999 - 1013 ) Google Scholar Crossref Search ADS PubMed WorldCat [9] Tsuchiya R. , Asamura H. , Kondo H. , Goya T. , Naruke T. . Extended resection of the left atrium, great vessels, or both for lung cancer , Ann Thorac Surg , 1994 , vol. 57 (pg. 960 - 965 ) Google Scholar Crossref Search ADS PubMed WorldCat [10] Spaggiari L. , Regnard J.F. , Magdeleinat P. , Jauffret B. , Puyo P. , Levasseur P. . Extended resections for bronchogenic carcinoma invading the superior vena cava system , Ann Thorac Surg , 2000 , vol. 69 (pg. 233 - 236 ) Google Scholar Crossref Search ADS PubMed WorldCat [11] Kaplan E.L. , Meier P. . Non-parametric estimation from incomplete observations , J Am Stat Assoc , 1958 , vol. 53 (pg. 457 - 481 ) Google Scholar Crossref Search ADS WorldCat [12] Peto R. , Peto J. . Asymptotically efficient rank invariant test procedures , J R Stat Soc (series A) , 1972 , vol. 135 (pg. 185 - 198 ) Google Scholar Crossref Search ADS WorldCat [13] Cox D.R. . Regression models and life tables , J R Stat Soc (series B) , 1972 , vol. 34 (pg. 187 - 202 ) OpenURL Placeholder Text WorldCat [14] Burt M.E. , Pomerantz A.H. , Bains M.S. , McCormack P.M. , Kaiser L.R. , Hilaris B.S. , Martini N. . Results of surgical treatment of stage III lung cancer invading the mediastinum , Surg Clin North Am , 1987 , vol. 67 (pg. 987 - 1000 ) Google Scholar Crossref Search ADS PubMed WorldCat [15] Fukuse T. , Wada H. , Hitomi S. . Extended operation for non-small cell lung cancer invading great vessels and left atrium , Eur J Cardiothorac Surg , 1997 , vol. 11 (pg. 664 - 669 ) Google Scholar Crossref Search ADS PubMed WorldCat [16] Mitchell J.D. , Mathisen D.J. , Wright C.D. , Wain J.C. , Donahue D.M. , Allan J.S. , Moncure A.C. , Grillo H.C. . Resection for bronchogenic carcinoma involving the carina: long-term results and effect of nodal status on outcome , J Thorac Cardiovasc Surg , 2001 , vol. 121 (pg. 465 - 471 ) Google Scholar Crossref Search ADS PubMed WorldCat [17] Doddoli C. , Rollet G. , Thomas P. , Ghez O. , Seree Y. , Giudicelli R. , Fuentes P. . Is lung cancer surgery justified in patients with direct mediastinal invasion? , Eur J Cardiothorac Surg , 2001 , vol. 20 (pg. 339 - 343 ) Google Scholar Crossref Search ADS PubMed WorldCat [18] Grunenwald D.H. . Surgery for advanced stage lung cancer , Semin Surg Oncol , 2000 , vol. 18 (pg. 137 - 142 ) Google Scholar Crossref Search ADS PubMed WorldCat [19] Rice T.W. , Blackstone E.H. . Radical resections for T4 lung cancer , Surg Clin North Am , 2002 , vol. 82 (pg. 573 - 587 ) Google Scholar Crossref Search ADS PubMed WorldCat [20] Grunenwald D.H. , Mazel C. , Girard P. , Veronesi G. , Spaggiari L. , Gossot D. , Debrosse D. , Caliandro R. , Le Guillou J.L. , Le Chavelier T. . Radical en bloc resection for lung cancer invading the spine , J Thorac Cardiovasc Surg , 2002 , vol. 123 (pg. 271 - 279 ) Google Scholar Crossref Search ADS PubMed WorldCat [21] Shirakusa T. , Kawahara K. , Iwasaki A. , Okabayashi K. , Shiraishi T. , Yoneda S. , Yoshinaga Y. , Matsuzoe D. , Watanabe K. . Extended operation for T4 lung carcinoma , Ann Thorac Cardiovasc Surg , 1998 , vol. 4 (pg. 110 - 118 ) Google Scholar PubMed OpenURL Placeholder Text WorldCat [22] Izbicki J.R. , Knoefel W.T. , Passlick B. , Habekost M. , Karg O. , Thetter O. . Risk analysis and long-term survival in patients undergoing extended resection of locally advanced lung cancer , J Thorac Cardiovasc Surg , 1995 , vol. 110 (pg. 386 - 395 ) Google Scholar Crossref Search ADS PubMed WorldCat [23] Johnson D.H. , Turrisi A.T. , Pass H.I. . Pass H.I. , Mitchell J.B. , Johnson D.H. , Turrisi A.T. . Combined modality treatment for locally advanced non-small cell lung cancer , Lung cancer: principles and practice , 1996 Philadelphia Lippincott-Raven (pg. 863 - 873 ) Google Scholar Google Preview OpenURL Placeholder Text WorldCat COPAC [24] Stamatis G. , Eberhardt W. , Stuben G. , Bildat S. , Dahler O. , Hillejan L. . Preoperative chemoradiotherapy and surgery for selected non-small cell lung cancer IIIB subgroups: long-term results , Ann Thorac Surg , 1999 , vol. 68 (pg. 1144 - 1149 ) Google Scholar Crossref Search ADS PubMed WorldCat [25] Pitz C.C.M. , Maas K.W. , Van Swieten H.A. , Brutel de la Rivière A. , Hofman P. , Schramel F.M.N.H. . Surgery as part of combined modality treatment in stage IIIB non-small cell lung cancer , Ann Thorac Surg , 2002 , vol. 74 (pg. 164 - 169 ) Google Scholar Crossref Search ADS PubMed WorldCat © 2003 Elsevier B.V. Elsevier B.V. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png European Journal of Cardio-Thoracic Surgery Oxford University Press

Results of surgical treatment of T4 non-small cell lung cancer

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Oxford University Press
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© 2003 Elsevier B.V.
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1010-7940
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Abstract

Abstract Objective: Because of location and invasion of surrounding structures, the role of surgical treatment for T4 tumors remains unclear. Extended resections carry a high mortality and should be restricted for selected patients. This study clarifies the selection process in non-small cell T4 tumors with invasion of the mediastinum, recurrent nerve, heart, great vessels, trachea, esophagus, vertebral body, and carina, or with malignant pleural effusion. Methods: From 1977 through 1993, 89 patients underwent resection for primary non-small cell T4 carcinomas. Resection was regarded as complete in 34 patients (38.2%) and incomplete in 55 patients (61.8%). Actuarial survival time was calculated and risk factors for late death were identified. Results: Overall hospital mortality was 19.1% (n=17). Mean 5-year survival was 23.6% for all hospital survivors, 46.2% for patients with complete resection and 10.9% for patients with incomplete resection (P=0.0009). In patients with complete resection, mean 5-year survival for patients with invasion of great vessels was 35.7%, whereas mean 5-year survival for invasion of other structures was 58.3% (P=0.05). Age, mediastinal lymph node involvement, type of operative procedure, and postoperative radiotherapy did not significantly influence survival. Conclusion: In certain T4 tumors complete resection is possible, resulting in good mean 5-year survival especially for tumors with invasion of the trachea or carina. High hospital mortality makes careful patient selection imperative. Lung cancer, Surgery, Survival 1 Introduction Prognosis in carcinoma of the lung is influenced by the stage of the disease and consequently by the therapeutic potential. Surgical resection is the treatment of choice for stage I and stage II non-small cell lung cancer, but its role in stage III disease remains unclear [1]. Our previous studies have shown that complete resection will result in good survival in T3 bronchogenic carcinoma with chest wall involvement [2], and in lung tumors invading mediastinal structures, or the main bronchus [3]. These tumors are classified as stage IIB, or IIIA disease [4]. Stage IIIB non-small cell lung cancer can be divided into primary bronchogenic carcinoma invading adjacent structures (T4), or tumors with metastases to contralateral mediastinal, contralateral hilar, ipsilateral or contralateral scalene, or supraclavicular lymph node(s) (N3). T4 bronchogenic carcinomas are a heterogeneous group of locally advanced cancers. Generally, these T4 tumors are regarded as unresectable [5]. Treatment is palliative for the majority of the patients, ranging from supportive care to chemotherapy or radiotherapy. However, some studies about extended resection of T4 tumors have been published [6–10]; hospital morbidity and mortality are high but, in selected patients, surgery appears to be beneficial and radical resection of the tumor has a potential for cure in the absence of mediastinal lymph node metastases. The present report is a retrospective analysis of survival characteristics in 89 patients who underwent resection for T4 tumors with invasion of the mediastinum, recurrent nerve, heart, great vessels, trachea, esophagus, vertebral body and carina or with a malignant pleural effusion. 2 Materials and methods From 1977 through 1993, 2009 patients with bronchogenic carcinoma had a resection at our hospital. Of this group, 89 patients (4.4%) underwent operation for T4 non-small cell lung cancer (NSCLC) with invasion of the mediastinum, recurrent nerve, heart, great vessels [aorta, superior vena cava, proximal main pulmonary vessels (proximal defined as proxim to the pericard or at pericardial reflection)], trachea, esophagus, vertebral body, or carina, or with malignant pleural effusion at pathologic examination. Patients with distant metastases, synchronous tumors, superior sulcus tumors, a satellite tumor within the same lobe or recurrences were excluded. Resection was considered complete when (1) the surgeon was morally certain that all known disease was removed; (2) resection margins were histologically free; and (3) the highest mediastinal lymph node was negative by microscopy. Staging procedures included routine blood tests, thoracic computed tomography, ultrasonography of the upper abdomen, bronchoscopy, mediastinoscopy, and pulmonary function tests. Computed tomography of the brain or bone scintigraphy was performed only in case of clinical suspicion of metastatic disease. Patient characteristics are shown in Table 1 . Cervical mediastinoscopy was negative in 81 patients (91.0%), not performed in one patient (1.1%) and positive in seven patients (7.9%). These seven patients were operated because they only had one single positive lymph node at the ipsilateral tracheobronchial angle (n=4), or, because they were relatively young (46 and 51 years). In one patient the reason for thoracotomy could not be assessed retrospectively. One patient was pre-operatively diagnosed at bronchoscopy as having a carcinosarcoma in the main right bronchus. No cervical mediastinoscopy was performed. Frozen sections peroperatively showed a squamous cell carcinoma. Table 1 Open in new tabDownload slide Patient characteristics Table 1 Open in new tabDownload slide Patient characteristics The type of resection is shown in Table 2 . In four patients with bronchogenic carcinoma invading the right side of the mediastinum, a pneumonectomy (n=3) or lobectomy (n=1) included resection and reconstruction of the superior vena cava by a Goretex graft. Two patients had a lobectomy of the right upper lobe and a bypass of the superior vena cava. One patient had a lobectomy of the left upper lobe followed by a Dacron prothesis of the subclavian artery. In one patient with a pneumonectomy the tumor invaded the chest wall and an en bloc resection of the tumor and the chest wall was performed. Table 2 Open in new tabDownload slide Operative procedures Table 2 Open in new tabDownload slide Operative procedures A complete resection was achieved in 34 patients (38.2%). Resections were incomplete due to positive resection margins (n=39), positive lymph nodes (n=2), a combination of both (n=12) or malignant pleural effusion (n=2). The histological diagnosis was squamous cell carcinoma in 77 patients (86.5%), adenocarcinoma in 10 patients (11.2%), adenosquamous cell carcinoma in one patient (1.1%) and large cell carcinoma in one patient (1.1%). Cervical mediastinoscopy was false negative in 27 patients. Fourteen of these 27 patients had positive subaortic or para-aortic lymph nodes (n=11) or positive paraesophageal lymph nodes (n=3). All patients were staged as T4 because of involvement of the mediastinum, recurrent nerve, heart, great vessels, trachea, esophagus, vertebral body, or carina, or the presence of malignant pleural effusion (Table 3) . Invasion of the different great vessels and pTNM staging are shown in Tables 4 and 5 . Table 3 Open in new tabDownload slide Structures involved in T4 tumors Table 3 Open in new tabDownload slide Structures involved in T4 tumors Table 4 Open in new tabDownload slide Invasion of the different great vessels Table 4 Open in new tabDownload slide Invasion of the different great vessels Table 5 Open in new tabDownload slide pTNM staging Table 5 Open in new tabDownload slide pTNM staging Radiation therapy was given to 47 patients as adjuvant therapy. One patient with tumor invasion of the pulmonary artery was pre-operatively irradiated. Although he was judged to be inoperable, a palliative pneumonectomy was carried out some months later because of persistent complaints of dyspnea and the absence of distant metastases. Forty-six patients (51.7%) received radiotherapy postoperatively. Of these patients, 32 patients had an incomplete resection. In the group of patients with complete resection (n=14), seven patients were irradiated because they were staged as T4N2, the other seven patients received radiotherapy because of the bulk of the tumor or localization near great vessels or other major structures. One patient with a T4N2 tumor only received 1.200 cG radiation because she developed a pericardial effusion. Ten years after the operation she is still alive. Four patients (4.5%) received postoperative chemotherapy because of incomplete resection. Follow-up was completed as of August 2002. Follow-up data were obtained from hospital files and from questionnaires to referring pulmonary physicians and general practitioners. Follow-up about local recurrence and distant metastases was obtained in 96.6% of the patients. Survival was estimated from the date of operation, using the Kaplan–Meier survival analysis method [11]. Hospital deaths were excluded. Survival comparisons were analyzed by the log rank test [12]. The difference was considered statistically significant when the P value was less than 0.05. Incremental risk factors affecting survival were evaluated using Cox's proportional hazards model [13]. 3 Results Hospital mortality was 19.1% (pneumonectomy 18.3% [13/71], lobectomy 26.6% [4/15]). The mean age of these 17 patients was 64.4 years (51–77 years). Ten patients had undergone a pneumonectomy, two a carinal pneumonectomy, one an en bloc pneumonectomy, two a lobectomy and two a lobectomy with reconstruction of the superior vena cava. Of these 17 deceased patients, 13 had invasion of the great vessels (four left atrium and intrapericardial pulmonary vein, three intrapericardial pulmonary vein, three aorta, three superior vena cava), two invasion of the trachea and esophagus, one invasion of the trachea and one had tumor involvement of the vertebral column. Hospital deaths were due to cardiac arrest (n=5), sepsis (n=4), respiratory failure (n=3), hemoptysis (n=1), cerebral hemorrhage (n=1) and gastro-intestinal tract bleeding (n=1). Two patients died at home, 1 and 2 days, respectively, after their discharge from the hospital, but within 30 days of the operation. Mean 5-year survival was 19.1% for all patients (n=89) and 23.6% for hospital survivors (n=72). Complete resection was performed in 26 hospital survivors (36.1%) with a mean 5-year survival of 46.2%. The remaining 46 hospital survivors underwent an incomplete resection with a mean 5-year survival of 10.9% (P=0.0009) (Fig. 1) . Because of this significant difference in survival between patients with complete and incomplete resection, only the results of hospital survivors with complete resection were studied for the analysis of other prognostic factors. Fig. 1 Open in new tabDownload slide Mean 5-year survival in hospital survivors with complete resection (solid line) and incomplete resection (dashed line) (Cum, cumulative). Fig. 1 Open in new tabDownload slide Mean 5-year survival in hospital survivors with complete resection (solid line) and incomplete resection (dashed line) (Cum, cumulative). As for the N status, mean 5-year survival was 33.3% for three N0 patients, and 43.8% and 57.1% for 16 N1 and seven N2 patients, respectively (P>0.05). Regarding the T status, mean 5-year survival for patients with invasion of great vessels (n=14) was 35.7%, whereas mean 5-year survival for patients with invasion of other structures (n=12) was 58.3% (P=0.03) (Fig. 2) . Although patients with involvement of the carina or the trachea had a better mean 5-year survival (50.0%) than involvement of other structures (44.4%), the difference was not statistically significant. Fig. 2 Open in new tabDownload slide Mean 5-year survival after complete resection with invasion of great vessels (dashed line) and invasion of other structures (solid line) (Cum, cumulative). Fig. 2 Open in new tabDownload slide Mean 5-year survival after complete resection with invasion of great vessels (dashed line) and invasion of other structures (solid line) (Cum, cumulative). Of the 26 hospital survivors with complete resection, 24 patients had a squamous cell carcinoma with a mean 5-year survival of 45.8%. One patient with an adenocarcinoma died after 2 years and an other patient is still alive after 10 years. Mean 5-year survival for patients who underwent a pneumonectomy (n=23) was 43.5%, and for patients post lobectomy (n=3) 66.7% (P>0.05). Age and postoperative radiotherapy did not influence survival significantly. According to the multivariate analysis regarding age, sex, pTNM classification, histology and localization no significant prognostic factors were found in the group of patients with complete resection. Distant metastases developed in four of 26 hospital survivors with complete resection (15.4%), and one patient had a local recurrence (3.8%). Three patients had combined local and distant recurrence (11.5%). 4 Discussion Prognosis, surgical treatment and long-term survival of non-small cell bronchogenic carcinoma are closely related to the stage of the disease [1]. Stage IIIB non-small cell lung cancer has a 5-year survival rate of about 7%, and results of surgical treatment are poor [4,6,14]; however, some selected T4 tumors are potentially resectable, survival depending on completeness of resection, locoregional tumor invasion and lymph node metastases. These extended resections carry a high mortality and morbidity and make careful patient selection imperative. Hospital mortality varied between 5% and 20%, increasing after extended resections [15,16]. Our study also shows a substantial hospital mortality of 19.1%. Hospital mortality was related to invasion of the great vessels. Thirteen of 17 hospital deaths had tumor involvement of the aorta, superior vena cava or pulmonary veins. In this subset hospital mortality was 21.3% (13/61). Resectability of a tumor is influenced by pTNM staging. Our results of surgical treatment of T3 tumors with invasion of the chest wall, or with invasion of the mediastinal structures and/or localization in the main bronchus showed that complete resection was possible in 68.8% and 64.8%, respectively [2,3]. In T4 tumors, localization and invasion of adjacent structures often make complete resection impossible. A complete resection is vital [6,15]. In our series, mean 5-year survival for complete resections was 46.2%, for incomplete resections 10.9% (P<0.05). A complete resection could be performed in 34 patients (38.2%). This is higher than described by Martini et al. who had a complete resection rate of 18%. In that study none of the tumors invading the aorta, trachea or spine were resected [6]. However, other studies reported complete resection rates of 72% and 80%, respectively, for tumors invading great vessels or the carina [10,17]. Based on resectability criteria, Grunenwald divided stage IIIB tumors in two subcategories: potentially resectable (invasion of superior vena cava, carina, lower trachea, left atrium) and definitively non-resectable (malignant pleural effusion, invasion of the esophagus and vertebrae) [18]. Our study supports this classification. In the past, high post-operative morbidity and mortality and uncertain long-term survival have been associated with carinal surgery for bronchogenic carcinoma [19]. Respiratory failure after non-cardiogenic pulmonary edema or infection in the remaining lung and anastomotic dehiscence with bronchial fistula were the major postoperative problems and the main cause of the high operative mortality, varying from 11 to 27% in large series [8]. However, careful patient selection, much attention to surgical details and careful anesthetic management can lower the levels of surgical deaths. Recently, a postoperative mortality of 6.6–15% has been reported and pneumonectomy with tracheal sleeve resection is advocated by several surgeons with 5-year survival approaching 43% [7,16]. In our study, complete resection of tumors with invasion of the trachea or carina was 37.5% and 36.4%, respectively, while it was less for tumors with invasion of other structures and it had a favorable prognosis with a mean 5-year survival of 50.9%. Results of surgery for T4 tumors with invasion of the left atrium or great vessels are poor. Burt et al. reported no 5-year survivors in their series of 18 patients after resection for tumors extending into the vena cava superior [14], while Tsuchiya et al. found only two of 101 patients alive after 5 years [9]. However, recent advances in cardiovascular surgery offer possibilities for complete resection in cases of invasion of the great vessels, like aorta and superior vena cava [10,15]. Spaggiari et al. reported extended resections for tumors invading the superior vena cava with 5-year actuarial survival of 29%, with four of 25 patients alive at 5 years [10]. Hospital mortality was 12%, and a complete resection was achieved in 20 patients (i.e. 80%). This is high, but Doddoli et al. described the same results for completeness of resection and survival [17]. In our study 37.7% of the patients with invasion of the great vessels had a complete resection (n=14). This conforms with the results of Fukuse et al. [15]. There was no difference in completeness of resection between invasion of the aorta, superior vena cava and pulmonary vein. The results of complete resection in the group with invasion of the pulmonary artery were better, but this was a very small group. Mean 5-year survival was 35.7%. Traditionally, tumors invading vertebrae were considered as unresectable. We had no complete resection in both patients with involvement of the vertebral body. However, recent progress in spinal surgery has opened new possibilities. Induction treatment with total or partial vertebrectomy and pulmonary resection is feasible in selected patients with an estimated 5-year survival of 14% [20]. In most studies involvement of the esophagus precludes a complete resection [6,21]. We achieved a complete resection in three patients (25%), as only the muscular layer of the esophagus was involved by the tumor. Regarding lymph node involvement, mean 5-year survival was worse for N0 patients than for N1 and N2 patients. This finding is contradictory to our previous studies [2,3] in which mediastinal lymph node involvement worsens the prognosis. All three N0 patients in this series, however, had involvement of great vessels or the heart. Invasion of these structures carries a worse prognosis [6]. In the group of 16 N1 and seven N2 patients involvement of great vessels or the heart was present in nine and five patients, respectively. The remaining patients had involvement of the trachea (n=8), carina (n=4), mediastinum (n=4) or esophagus (n=3). Izbicki et al. also found no statistical significant differences in survival related to lymph node status in T4 tumors [22]. In their study, mean 3-year survival for six T4N0, seven T4N1 and 12 T4N2 patients was 0%, 53% and 16.6%, respectively. This suggests that in T4 tumors local invasion of surrounding structures may be more important for survival than lymph node involvement. But in both studies the number of patients is limited and other studies reported no long-term survivors in patients with T4N2 tumors [6,15,21]. Because of the poor results of surgical resection alone, multimodality treatment has surfaced as the treatment of choice in patients with stage III NSCLC [23]. However, it is still unclear which treatment modality (surgery, radiotherapy or a combination of both) will result in prolonged survival after neo-adjuvant chemotherapy. Recently, several trials have been conducted showing that some locally advanced, initially unresectable tumors become operable after induction chemotherapy [24,25]. Given our own results, and those reported by others [18,19,22] for patients presenting with T4 pathology, pre-operative work-up should establish the possibilities of complete resection using complete available modern imaging technology. If complete resection with appropriate reconstruction, is feasible, all patients, otherwise fit for surgery, should be operated on. Complete resection resulting in good mean 5-year survival is possible, especially for tumors invading the trachea or carina. Tumors with invasion of the esophagus, vertebrae and with malignant pleural effusion appear to be unresectable in most cases. The results of induction chemotherapy make us propose that presently multimodality treatment offers new possibilities to treat patients with T4 disease and a good performance status. We wish to thank Mrs Joke van der Sluis for her secretarial support. The study was supported by a grant from the Mr Willem Bakhuys Roozeboom Foundation References [1] Martini N. . Surgical treatment of non-small cell lung cancer by stage , Semin Surg Oncol , 1990 , vol. 6 (pg. 248 - 254 ) Google Scholar Crossref Search ADS PubMed WorldCat [2] Pitz C.C.M. , Brutel de la Rivière A. , Elbers H.R.J. , Westermann C.J.J. , van den Bosch J.M.M. . Surgical treatment of 125 patients with non-small cell lung cancer and chest wall involvement , Thorax , 1996 , vol. 51 (pg. 846 - 850 ) Google Scholar Crossref Search ADS PubMed WorldCat [3] Pitz C.C.M. , Brutel de la Rivière A. , Elbers H.R.J. , Westermann C.J.J. , van den Bosch J.M.M. . Results of resection of T3 non-small cell lung cancer invading the mediastinum or main bronchus , Ann Thorac Surg , 1996 , vol. 62 (pg. 1016 - 1020 ) Google Scholar Crossref Search ADS PubMed WorldCat [4] Mountain C.F. . Revisions in the international system for staging lung cancer , Chest , 1997 , vol. 111 (pg. 1710 - 1717 ) Google Scholar Crossref Search ADS PubMed WorldCat [5] Ginsberg R.J. , Vokes E.E. , Raben A. . Devita V.T. , Hellman S. , Rosenberg S.A. . Non-small cell lung cancer , Cancer. Principles and practice of oncology , 1997 Philadelphia Lippincott-Raven (pg. 858 - 911 ) Google Scholar Google Preview OpenURL Placeholder Text WorldCat COPAC [6] Martini N. , Yellin A. , Ginsberg R.J. , Bains M.S. , Burt M.E. , McCormack P.M. , Rusch V.W. . Management of non-small cell lung cancer with direct mediastinal involvement , Ann Thorac Surg , 1994 , vol. 58 (pg. 1447 - 1451 ) Google Scholar Crossref Search ADS PubMed WorldCat [7] Dartevelle P. , Macchiarini P. . Carinal resection for bronchogenic cancer , Semin Thorac Cardiovasc Surg , 1996 , vol. 8 (pg. 414 - 425 ) Google Scholar PubMed OpenURL Placeholder Text WorldCat [8] Van Raemdonck D.E. , Schneider A. , Ginsberg R.J. . Surgical treatment for higher stage non-small cell lung cancer , Ann Thorac Surg , 1992 , vol. 54 (pg. 999 - 1013 ) Google Scholar Crossref Search ADS PubMed WorldCat [9] Tsuchiya R. , Asamura H. , Kondo H. , Goya T. , Naruke T. . Extended resection of the left atrium, great vessels, or both for lung cancer , Ann Thorac Surg , 1994 , vol. 57 (pg. 960 - 965 ) Google Scholar Crossref Search ADS PubMed WorldCat [10] Spaggiari L. , Regnard J.F. , Magdeleinat P. , Jauffret B. , Puyo P. , Levasseur P. . Extended resections for bronchogenic carcinoma invading the superior vena cava system , Ann Thorac Surg , 2000 , vol. 69 (pg. 233 - 236 ) Google Scholar Crossref Search ADS PubMed WorldCat [11] Kaplan E.L. , Meier P. . Non-parametric estimation from incomplete observations , J Am Stat Assoc , 1958 , vol. 53 (pg. 457 - 481 ) Google Scholar Crossref Search ADS WorldCat [12] Peto R. , Peto J. . Asymptotically efficient rank invariant test procedures , J R Stat Soc (series A) , 1972 , vol. 135 (pg. 185 - 198 ) Google Scholar Crossref Search ADS WorldCat [13] Cox D.R. . Regression models and life tables , J R Stat Soc (series B) , 1972 , vol. 34 (pg. 187 - 202 ) OpenURL Placeholder Text WorldCat [14] Burt M.E. , Pomerantz A.H. , Bains M.S. , McCormack P.M. , Kaiser L.R. , Hilaris B.S. , Martini N. . Results of surgical treatment of stage III lung cancer invading the mediastinum , Surg Clin North Am , 1987 , vol. 67 (pg. 987 - 1000 ) Google Scholar Crossref Search ADS PubMed WorldCat [15] Fukuse T. , Wada H. , Hitomi S. . Extended operation for non-small cell lung cancer invading great vessels and left atrium , Eur J Cardiothorac Surg , 1997 , vol. 11 (pg. 664 - 669 ) Google Scholar Crossref Search ADS PubMed WorldCat [16] Mitchell J.D. , Mathisen D.J. , Wright C.D. , Wain J.C. , Donahue D.M. , Allan J.S. , Moncure A.C. , Grillo H.C. . Resection for bronchogenic carcinoma involving the carina: long-term results and effect of nodal status on outcome , J Thorac Cardiovasc Surg , 2001 , vol. 121 (pg. 465 - 471 ) Google Scholar Crossref Search ADS PubMed WorldCat [17] Doddoli C. , Rollet G. , Thomas P. , Ghez O. , Seree Y. , Giudicelli R. , Fuentes P. . Is lung cancer surgery justified in patients with direct mediastinal invasion? , Eur J Cardiothorac Surg , 2001 , vol. 20 (pg. 339 - 343 ) Google Scholar Crossref Search ADS PubMed WorldCat [18] Grunenwald D.H. . Surgery for advanced stage lung cancer , Semin Surg Oncol , 2000 , vol. 18 (pg. 137 - 142 ) Google Scholar Crossref Search ADS PubMed WorldCat [19] Rice T.W. , Blackstone E.H. . Radical resections for T4 lung cancer , Surg Clin North Am , 2002 , vol. 82 (pg. 573 - 587 ) Google Scholar Crossref Search ADS PubMed WorldCat [20] Grunenwald D.H. , Mazel C. , Girard P. , Veronesi G. , Spaggiari L. , Gossot D. , Debrosse D. , Caliandro R. , Le Guillou J.L. , Le Chavelier T. . Radical en bloc resection for lung cancer invading the spine , J Thorac Cardiovasc Surg , 2002 , vol. 123 (pg. 271 - 279 ) Google Scholar Crossref Search ADS PubMed WorldCat [21] Shirakusa T. , Kawahara K. , Iwasaki A. , Okabayashi K. , Shiraishi T. , Yoneda S. , Yoshinaga Y. , Matsuzoe D. , Watanabe K. . Extended operation for T4 lung carcinoma , Ann Thorac Cardiovasc Surg , 1998 , vol. 4 (pg. 110 - 118 ) Google Scholar PubMed OpenURL Placeholder Text WorldCat [22] Izbicki J.R. , Knoefel W.T. , Passlick B. , Habekost M. , Karg O. , Thetter O. . Risk analysis and long-term survival in patients undergoing extended resection of locally advanced lung cancer , J Thorac Cardiovasc Surg , 1995 , vol. 110 (pg. 386 - 395 ) Google Scholar Crossref Search ADS PubMed WorldCat [23] Johnson D.H. , Turrisi A.T. , Pass H.I. . Pass H.I. , Mitchell J.B. , Johnson D.H. , Turrisi A.T. . Combined modality treatment for locally advanced non-small cell lung cancer , Lung cancer: principles and practice , 1996 Philadelphia Lippincott-Raven (pg. 863 - 873 ) Google Scholar Google Preview OpenURL Placeholder Text WorldCat COPAC [24] Stamatis G. , Eberhardt W. , Stuben G. , Bildat S. , Dahler O. , Hillejan L. . Preoperative chemoradiotherapy and surgery for selected non-small cell lung cancer IIIB subgroups: long-term results , Ann Thorac Surg , 1999 , vol. 68 (pg. 1144 - 1149 ) Google Scholar Crossref Search ADS PubMed WorldCat [25] Pitz C.C.M. , Maas K.W. , Van Swieten H.A. , Brutel de la Rivière A. , Hofman P. , Schramel F.M.N.H. . Surgery as part of combined modality treatment in stage IIIB non-small cell lung cancer , Ann Thorac Surg , 2002 , vol. 74 (pg. 164 - 169 ) Google Scholar Crossref Search ADS PubMed WorldCat © 2003 Elsevier B.V. Elsevier B.V.

Journal

European Journal of Cardio-Thoracic Surgery – Oxford University Press

Published: Dec 1, 2003

Keywords: Lung cancer Surgery Survival

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