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J Thorac Cardiovasc Surg 2001;121:403
© 2001 The American Association for Thoracic Surgery


Letters to the Editor

Persistence of viable tumor cells after radiation and chemotherapy for stage IIIB non–small cell lung cancer: An early marker of treatment failure

Fabrice Andre, MD, Dominique Grunewald, MD, Thierry Le Chevalier, MD

Department of Medicine
Institut Gustave Roussy
39 rue C. Desmoulins 94805 Villejuif, France

To the Editor:

Results of radiation and chemotherapy given for stage III non–small cell lung cancer (NSCLC) are particularly disappointing because the 5-year overall survival ranges from 3% to 17%.Go Go 1,2 A randomized trial showed that local control of the disease was maintained in only 17% of these patients at 1 year.Go 2 In the same trial, chemotherapy decreased the rate of distant metastasis from 65% to 47%. This decrease was not associated with a relevant improvement in survival because of the lack of locoregional control. Since this time, locoregional control has been considered to be a major problem for stage IIIB NSCLC. On the basis of these data, some groups have proposed surgery after radiation and chemotherapy.Go Go 3-5 These studies report promising results, but interpretation of these phase II trials is difficult inasmuch as 5-year overall survival of stage IIIB NSCLC is heterogeneous. A method is therefore required to interpret phase II trials of postinduction surgery in patients with stage IIIB NSCLC. We propose to evaluate surgery in patients whose stage IIIB NSCLC was not controlled with radiation and chemotherapy alone. In this setting, surgery would be considered as an "early salvage treatment." An early marker of radiation and chemotherapy failure is needed. The persistence of tumor cells in the thorax after radiation and chemotherapy could be this marker but has never been validated in a prospective study.

We have evaluated the outcome of 63 patients with stage IIIB NSCLC treated with radiation and chemotherapy and having viable tumor cells in the bronchoscopic biopsy sample after treatment. Patients were included in a randomized trial whose results have been previously reported.Go 2 Patients were treated with 3 cycles of chemotherapy (cisplatin, vindesine, lomustine, and cyclophosphamide) followed by thoracic radiotherapy (65 Gy). The disease was restaged after treatment by means of a computed tomographic scan and bronchoscopy. After a minimum follow-up of 5 years, the 3-year and 5-year overall survivals were 3% (95% confidence interval: 0%-10%) and 1% (95% confidence interval: 0%-8%), respectively. Objective tumor response did not affect the long-term outcome.

This report shows that the persistence of viable tumor cells in the bronchoscopic biopsy specimen after radiation and chemotherapy is an early marker of treatment failure and death, even when a clinical tumor response is achieved. Considering these data, we propose to evaluate postinduction surgery in this subgroup of patients. Obtaining a significant 5-year overall survival in this subset of patients would mean that surgery is an efficient salvage procedure for stage IIIB NSCLC.

12/8/111203

doi:10.1067/mtc.2001.111203

References

  1. Dillman RO, Herndon J, Seagren SL, et al. Improved survival in stage III non–small cell lung cancer: seven year follow-up of the CALGB8433 trial. J Natl Cancer Inst 1996;88:1210-5.[Abstract/Free Full Text]
  2. Arriagada R, Le Chevalier T, Quoix E, et al. ASTRO plenary: effect of chemotherapy on locally advanced non–small cell lung carcinoma: a randomized study of 353 patients. Int J Radiat Oncol Biol Phys 1991;20:1183-90.[Medline]
  3. Albain KS, Rush VW, Crowley JJ, et al. Concurrent cisplatin/etoposide plus chest radiotherapy followed by surgery for stage IIIA (N2) and stage IIIB non small cell lung cancer: mature results of a SWOG phase II study 8805. J Clin Oncol 1995;13:1880-92.[Abstract/Free Full Text]
  4. Eberhardt W, Wilke H, Stamatis G, et al. Preoperative chemotherapy followed by concurrent chemoradiation therapy based on hyperfractionated accelerated radiotherapy and definitive surgery in locally advanced non–small lung cancer: mature results of a phase II study. J Clin Oncol 1998;16:622-34.[Abstract]
  5. Thomas M, Rube C, Semik M, et al. Impact of preoperative bimodality induction including twice-daily radiation therapy on tumor regression and survival in stage III non small cell lung cancer. J Clin Oncol 1999;17:1185.[Abstract/Free Full Text]



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