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Journal of Clinical Oncology, Vol 13, 1880-1892, Copyright © 1995 by American Society of Clinical Oncology

ARTICLES

Concurrent cisplatin/etoposide plus chest radiotherapy followed by surgery for stages IIIA (N2) and IIIB non-small-cell lung cancer: mature results of Southwest Oncology Group phase II study 8805

KS Albain, VW Rusch, JJ Crowley, TW Rice, AT Turrisi 3rd, JK Weick, VA Lonchyna, CA Presant, RJ McKenna and DR Gandara
Loyola University Medical Center, Maywood, IL, USA.

PURPOSE: To assess the feasibility of concurrent chemotherapy and irradiation (chemoRT) followed by surgery in locally advanced non-small- cell lung cancer (NSCLC) in a cooperative group setting, and to estimate response, resection rates, relapse patterns, and survival for stage subsets IIIA(N2) versus IIIB. PATIENTS AND METHODS: Biopsy proof of either positive N2 nodes (IIIAN2) or of N3 nodes or T4 primary lesions (IIIB) was required. Induction was two cycles of cisplatin and etoposide plus concurrent chest RT to 45 Gy. Resection was attempted if response or stable disease occurred. A chemoRT boost was given if either unresectable disease or positive margins or nodes was found. RESULTS: The median follow-up time for 126 eligible patients [75 stage IIIA(N2) and 51 IIIB] was 2.4 years. The objective response rate to induction was 59%, and 29% were stable. Resectability was 85% for the IIIA(N2) group eligible for surgery and 80% for the IIIB group. Reversible grade 4 toxicity occurred in 13% of patients. There were 13 treatment-related deaths (10%) and 19 others (15%) died of causes not related to toxicity or tumor. Of 65 relapses, 11% were only locoregional and 61% were only distant. There were 26 brain relapses, of which 19 were the sole site or cause of death. There was no survival difference (P = .81) between stage IIIA(N2) versus stage IIIB (median survivals, 13 and 17 months; 2-year survival rates, 37% and 39%; 3-year survival rates, 27% and 24%). The strongest predictor of long-term survival after thoracotomy was absence of tumor in the mediastinal nodes at surgery (median survivals, 30 v 10 months; 3-year survival rates, 44% v 18%; P = .0005). CONCLUSION: This trimodality approach was feasible in this Southwest Oncology Group (SWOG) study, with an encouraging 26% 3-year survival rate. An Intergroup study is currently being conducted to determine whether surgery adds more to the risk or to the benefit of chemoRT.
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D. C. Betticher, S.-F. Hsu Schmitz, M. Totsch, E. Hansen, C. Joss, C. von Briel, R. A. Schmid, M. Pless, J. Habicht, A. D. Roth, et al.
Mediastinal Lymph Node Clearance After Docetaxel-Cisplatin Neoadjuvant Chemotherapy Is Prognostic of Survival in Patients With Stage IIIA pN2 Non-Small-Cell Lung Cancer: A Multicenter Phase II Trial
J. Clin. Oncol., May 1, 2003; 21(9): 1752 - 1759.
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S. S. Leong, E. H. Tan, K. W. Fong, E. Wilder-Smith, Y. K. Ong, B. C. Tai, L. Chew, S. H. Lim, J. Wee, K. M. Lee, et al.
Randomized Double-Blind Trial of Combined Modality Treatment With or Without Amifostine in Unresectable Stage III Non-Small-Cell Lung Cancer
J. Clin. Oncol., May 1, 2003; 21(9): 1767 - 1774.
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L. J. Wirth, J. Lucca, P. Ostler, P. Fidias, C. Lynch, P. A. Janne, R. S. Herbst, B. E. Johnson, D. J. Sugarbaker, D. J. Mathisen, et al.
Induction Docetaxel and Carboplatin Followed by Weekly Docetaxel and Carboplatin with Concurrent Radiotherapy, then Surgery in Stage III Non-Small Cell Lung Cancer: A Phase I Study
Clin. Cancer Res., May 1, 2003; 9(5): 1698 - 1704.
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A. Granetzny, E. Striehn, U. Bosse, W. Wagner, O. Koch, U. Vogt, P. Froeschle, and F. Klinke
A phase II single-institution study of neoadjuvant stage IIIA/B chemotherapy and radiochemotherapy in non-small cell lung cancer
Ann. Thorac. Surg., April 1, 2003; 75(4): 1107 - 1112.
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K. Nagai, R. Tsuchiya, T. Mori, H. Tada, Y. Ichinose, T. Koike, and H. Kato
A randomized trial comparing induction chemotherapy followed by surgery with surgery alone for patients with stage IIIA N2 non-small cell lung cancer (JCOG 9209)
J. Thorac. Cardiovasc. Surg., February 1, 2003; 125(2): 254 - 260.
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M. Ohta, N. Sawabata, H. Maeda, and H. Matsuda
Efficacy and safety of tracheobronchoplasty after induction therapy for locally advanced lung cancer
J. Thorac. Cardiovasc. Surg., January 1, 2003; 125(1): 96 - 100.
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J. R. Jett, W. J. Scott, M. P. Rivera, and W. T. Sause
Guidelines on Treatment of Stage IIIB Non-small Cell Lung Cancer
Chest, January 1, 2003; 123(1_suppl): 221S - 225S.
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S. G. Spiro and J. C. Porter
Lung Cancer--Where Are We Today?: Current Advances in Staging and Nonsurgical Treatment
Am. J. Respir. Crit. Care Med., November 1, 2002; 166(9): 1166 - 1196.
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E. E. Vokes, J. E. Herndon II, J. Crawford, K. A. Leopold, M. C. Perry, A. A. Miller, and M. R. Green
Randomized Phase II Study of Cisplatin With Gemcitabine or Paclitaxel or Vinorelbine as Induction Chemotherapy Followed by Concomitant Chemoradiotherapy for Stage IIIB Non-Small-Cell Lung Cancer: Cancer and Leukemia Group B Study 9431
J. Clin. Oncol., October 15, 2002; 20(20): 4191 - 4198.
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F. Venuta, E. A. Rendina, T. De Giacomo, E. Mercadante, F. Francioni, F. Pugliese, M. Moretti, and G. F. Coloni
Nd:YAG laser resection of lung cancer invading the airway as a bridge to surgery and palliative treatment
Ann. Thorac. Surg., October 1, 2002; 74(4): 995 - 998.
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K. S. Albain, J. J. Crowley, A. T. Turrisi III, D. R. Gandara, W. B. Farrar, J. I. Clark, K. R. Beasley, and R. B. Livingston
Concurrent Cisplatin, Etoposide, and Chest Radiotherapy in Pathologic Stage IIIB Non-Small-Cell Lung Cancer: A Southwest Oncology Group Phase II Study, SWOG 9019
J. Clin. Oncol., August 15, 2002; 20(16): 3454 - 3460.
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A. Cyjon, M. Nili, G. Fink, M. R. Kramer, E. Fenig, J. Sandbank, A. Sulkes, and E. Rakowsky
Advanced non-small cell lung cancer: induction chemotherapy and chemoradiation before operation
Ann. Thorac. Surg., August 1, 2002; 74(2): 342 - 347.
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C. C.M. Pitz, K. W. Maas, H. A. V. Swieten, A. Brutel de la Riviere, P. Hofman, and F. M.N.H. Schramel
Surgery as part of combined modality treatment in stage IIIB non-small cell lung cancer
Ann. Thorac. Surg., July 1, 2002; 74(1): 164 - 169.
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C. D. Wright, M. T. Menard, J. C. Wain, D. M. Donahue, H. C. Grillo, T. J. Lynch, N. C. Choi, and D. J. Mathisen
Induction chemoradiation compared with induction radiation for lung cancer involving the superior sulcus
Ann. Thorac. Surg., May 1, 2002; 73(5): 1541 - 1544.
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J. Martin, R. J. Ginsberg, E. S. Venkatraman, M. S. Bains, R. J. Downey, R. J. Korst, M. G. Kris, and V. W. Rusch
Long-Term Results of Combined-Modality Therapy in Resectable Non-Small-Cell Lung Cancer
J. Clin. Oncol., April 15, 2002; 20(8): 1989 - 1995.
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C. Pottgen, W. Eberhardt, S. Bildat, G. Stuben, G. Stamatis, L. Hillejan, S. Sohrab, H. Teschler, S. Seeber, H. Sack, et al.
Induction chemotherapy followed by concurrent chemotherapy and definitive high-dose radiotherapy for patients with locally advanced non-small-cell lung cancer (stages IIIa/IIIb): a pilot phase I/II trial
Ann. Onc., March 1, 2002; 13(3): 403 - 411.
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D. H. Grunenwald, C. Mazel, P. Girard, G. Veronesi, L. Spaggiari, D. Gossot, D. Debrosse, R. Caliandro, J.-L. Le Guillou, and T. Le Chevalier
Radical en bloc resection for lung cancer invading the spine
J. Thorac. Cardiovasc. Surg., February 1, 2002; 123(2): 271 - 279.
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J.F. Vansteenkiste
Imaging in lung cancer: positron emission tomography scan
Eur. Respir. J., February 1, 2002; 19(35_suppl): 49S - 60s.
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L. Voltolini, L. Luzzi, C. Ghiribelli, P. Paladini, M. Di Bisceglie, and G. Gotti
Results of induction chemotherapy followed by surgical resection in patients with stage IIIA (N2) non-small cell lung cancer: the importance of the nodal down-staging after chemotherapy
Eur. J. Cardiothorac. Surg., December 1, 2001; 20(6): 1106 - 1112.
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K. Junker, K. Langner, F. Klinke, U. Bosse, and M. Thomas
Grading of Tumor Regression in Non-small Cell Lung Cancer : Morphology and Prognosis
Chest, November 1, 2001; 120(5): 1584 - 1591.
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D. H. Grunenwald, F. Andre, C. Le Pechoux, P. Girard, C. Lamer, A. Laplanche, M. Tarayre, R. Arriagada, and T. Le Chevalier
Benefit of surgery after chemoradiotherapy in stage IIIB (T4 and/or N3) non-small cell lung cancer
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J. Martin, R. J. Ginsberg, A. Abolhoda, M. S. Bains, R. J. Downey, R. J. Korst, T. L. Weigel, M. G. Kris, E. S. Venkatraman, and V. W. Rusch
Morbidity and mortality after neoadjuvant therapy for lung cancer: the risks of right pneumonectomy
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J. R. Roberts, C. Eustis, R. Devore, D. Carbone, H. Choy, and D. Johnson
Induction chemotherapy increases perioperative complications in patients undergoing resection for non-small cell lung cancer
Ann. Thorac. Surg., September 1, 2001; 72(3): 885 - 888.
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F. Venuta, E. A. Rendina, T. De Giacomo, E. Mercadante, A. M. Ciccone, M. T. Aratari, M. Moretti, and G. F. Coloni
Endoscopic treatment of lung cancer invading the airway before induction chemotherapy and surgical resection
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J.F. Vansteenkiste and S.G. Stroobants
The role of positron emission tomography with 18F-fluoro-2-deoxy-D-glucose in respiratory oncology
Eur. Respir. J., April 1, 2001; 17(4): 802 - 820.
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M. P. Siegenthaler, K. M. Pisters, K. W. Merriman, J. A. Roth, S. G. Swisher, G. L. Walsh, A. A. Vaporciyan, W. R. Smythe, and J. B. Putnam Jr
Preoperative chemotherapy for lung cancer does not increase surgical morbidity
Ann. Thorac. Surg., April 1, 2001; 71(4): 1105 - 1112.
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V. W. Rusch, D. J. Giroux, M. J. Kraut, J. Crowley, M. Hazuka, D. Johnson, M. Goldberg, F. Detterbeck, F. Shepherd, R. Burkes, et al.
Induction chemoradiation and surgical resection for non-small cell lung carcinomas of the superior sulcus: Initial results of Southwest Oncology Group Trial 9416 (Intergroup Trial 0160)
J. Thorac. Cardiovasc. Surg., March 1, 2001; 121(3): 472 - 483.
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F. W. Grannis Jr, F. Andre, T. Le Chevalier, and D. Grunenwald
Subclassification of N2 Non-Small-Cell Lung Cancer
J. Clin. Oncol., February 15, 2001; 19(4): 1228 - 1229.
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F. Andre, D. Grunewald, and T. Le Chevalier
Persistence of viable tumor cells after radiation and chemotherapy for stage IIIB non-small cell lung cancer: An early marker of treatment failure
J. Thorac. Cardiovasc. Surg., February 1, 2001; 121(2): 403 - 403.
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E. E. Vokes
Induction Chemotherapy Followed by Concomitant Chemoradiotherapy for Non-Small Cell Lung Cancer
Oncologist, February 1, 2001; 6(2008): 25 - 27.
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J. A. Hayman, M. K. Martel, R. K. Ten Haken, D. P. Normolle, R. F. Todd III, J. F. Littles, M. A. Sullivan, P. W. Possert, A. T. Turrisi, and A. S. Lichter
Dose Escalation in Non-Small-Cell Lung Cancer Using Three-Dimensional Conformal Radiation Therapy: Update of a Phase I Trial
J. Clin. Oncol., January 1, 2001; 19(1): 127 - 136.
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R. Bueno, W. G. Richards, S. J. Swanson, M. T. Jaklitsch, J. M. Lukanich, S. J. Mentzer, and D. J. Sugarbaker
Nodal stage after induction therapy for stage IIIA lung cancer determines patient survival
Ann. Thorac. Surg., December 1, 2000; 70(6): 1826 - 1831.
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F. Andre, D. Grunenwald, J.-P. Pignon, A. Dujon, J. L. Pujol, P. Y. Brichon, L. Brouchet, E. Quoix, V. Westeel, and T. Le Chevalier
Survival of Patients With Resected N2 Non-Small-Cell Lung Cancer: Evidence for a Subclassification and Implications
J. Clin. Oncol., August 16, 2000; 18(16): 2981 - 2989.
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N. Van Zandwijk, E. F. Smit, G. W. P. Kramer, F. Schramel, S. Gans, J. Festen, A. Termeer, N. J. J. Schlosser, C. Debruyne, D. Curran, et al.
Gemcitabine and Cisplatin as Induction Regimen for Patients With Biopsy-Proven Stage IIIA N2 Non-Small-Cell Lung Cancer: A Phase II Study of the European Organization for Research and Treatment of Cancer Lung Cancer Cooperative Group (EORTC 08955)
J. Clin. Oncol., July 14, 2000; 18(14): 2658 - 2664.
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Y. Ohta, Y. Tanaka, T. Hara, M. Oda, S.-i. Watanabe, J. Shimizu, and Y. Watanabe
Clinicopathological and biological assessment of lung cancers with pleural dissemination
Ann. Thorac. Surg., April 1, 2000; 69(4): 1025 - 1029.
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G. M. Strauss
Role of Chemotherapy in Stages I to III Non-small Cell Lung Cancer*
Chest, December 1, 1999; 116(suppl_3): 509S - 516S.
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M. Stuschke, W. Eberhardt, C. Pottgen, G. Stamatis, H. Wilke, G. Stuben, F. Stoblen, H. H. Wilhelm, H. Menker, H. Teschler, et al.
Prophylactic Cranial Irradiation in Locally Advanced Non-Small-Cell Lung Cancer After Multimodality Treatment: Long-Term Follow-Up and Investigations of Late Neuropsychologic Effects
J. Clin. Oncol., September 1, 1999; 17(9): 2700 - 2700.
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J. R. Roberts, R. Bueno, and D. J. Sugarbaker
Multimodality Treatment of Malignant Superior Vena Caval Syndrome
Chest, September 1, 1999; 116(3): 835 - 837.
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J. R. Sonett, M. J. Krasna, M. Suntharalingam, J. Schuetz, L. A. Doyle, R. Lilenbaum, and Z. Gamliel
Safe pulmonary resection after chemotherapy and high-dose thoracic radiation
Ann. Thorac. Surg., August 1, 1999; 68(2): 316 - 320.
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K. Suzuki, K. Nagai, J. Yoshida, M. Nishimura, K. Takahashi, and Y. Nishiwaki
THE PROGNOSIS OF SURGICALLY RESECTED N2 NON-SMALL CELL LUNGCANCER: THE IMPORTANCE OF CLINICAL N STATUS
J. Thorac. Cardiovasc. Surg., July 1, 1999; 118(1): 145 - 153.
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P. De Leyn, J. Vansteenkiste, G. Deneffe, D. Van Raemdonck, W. Coosemans, and T. Lerut
Result of induction chemotherapy followed by surgery in patients with stage IIIA N2 NSCLC: importance of pre-treatment mediastinoscopy
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