J Thorac Cardiovasc Surg 2004;128:489-490
© 2004 The American Association for Thoracic Surgery
Assessing the value of neoadjuvant chemoradiotherapy and pathologic downstaging in the treatment of non–small cell lung cancer
Rolando M. D'Angelillo, MD,
Lucio Trodella, MD,
Sara Ramella, MD
Department of Radiotherapy, Università Cattolica S. Cuore, Rome, Italy
To the Editor:
We read with great interest the article by Machtay and colleagues,1 which underlines the feasibility of trimodality treatment (concurrent chemoradiation followed by surgical intervention) in the cure of locally advanced non–small cell lung cancer (LA-NSCLC) and suggest the use of pathologic downstaging as a predictor for long-term survival.
Several studies have explored the combined trimodality treatment: in the ESSEN2 and SWOG3 trials, patients have been treated with cisplatin plus etoposide (the same drugs used in this study for 22 patients) with a similar radiation dose (45 Gy). They reported a rate of acute toxicity similar to that reported in this article, with esophageal toxicities as the most frequent. Esophageal toxicity could correlate with the adopted radiotherapy volumes, which include the bilateral mediastinal nodal regions independently by their involvement. New data from RTOG trials4 suggest moving the elective nodal irradiation focalizing to the gross tumor volume. In our recent published report,5 exploring a combined modality treatment with limited irradiation volume, we have reported a grade 3 esophageal toxicity rate of 1.1%.
Moreover, surgical-related mortality, as the authors stated, could be attributed to the type of operation, pneumonectomy, more than to induction protocol. Also, data from neoadjuvant chemotherapy support these findings.6
Today, lymph node clearance7 and pathologic downstaging have been proposed as surrogate endpoints for neoadjuvant treatment in LA-NSCLC. Data from SAKK and the University of Pennsylvania agree to group together pathologic stage I and II (or pN0-1) disease as a predictor of overall survival and event-free or local recurrence-free survival. If we look at the Memorial Sloan Kettering data on 470 patients treated with neoadjuvant therapy,8 the multivariate analysis shows us a statistically significant difference in term of the relative rate of deaths between pathologic stage 0 and stage II to IV disease. No differences have been reported between pathologic stage 0 and stage I disease. According to this and our analysis, we share the hypothesis to use pathologic downstaging to stage 0 to stage I as a direct indicator of the effectiveness of any multimodality approach to LA-NSCLC.
Finally, 2 more issues regarding pathologic downstaging have to be underlined: its value as a predictor of distant recurrence and disease-free survival. In our analysis we have found a direct effect of downstaging on these parameters that stress the importance of local control on lung cancer, generally considered a systemic disease, and the ability of surgical intervention to achieve an eradication of lung carcinoma.
This last consideration could directly affect the quality of life of patients according to the following syllogism: "no cancer, no treatment; no treatment, no side effect"—and no doctors, too.
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References
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- Machtay M, Lee JH, Stevenson JP, et al. Two commonly used neoadjuvant chemoradiotherapy regimens for locally advanced stage III non-small cell lung carcinoma. long-term results and associations with pathologic response. J Thorac Cardiovasc Surg. 2004;127(1):108-113.[Abstract/Free Full Text]
- 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-cell lung cancer. mature results of a phase II trial. J Clin Oncol. 1998;16(2):622-634.[Abstract]
- Albain KS, Rusch VW, Crowley JJ, et al. 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. J Clin Oncol. 1995;13(8):1880-1892.[Abstract/Free Full Text]
- Emami B, Mirkovic N, Scott C, et al. The impact of regional nodal radiotherapy (dose/volume) on regional progression and survival in unresectable non-small cell lung cancer. an analysis of RTOG data. Lung Cancer. 2003;41(2):207-214.[Medline]
- Trodella L, Granone P, Valente S, et al. neoadjuvant concurrent radiochemotherapy in locally advanced (IIIA-IIIB) non-small cell lung cancer. long term results according to downstaging. Ann Oncol. 2004;15:389-396.[Abstract/Free Full Text]
- Martin J, Ginsberg RJ, Abolhoda A, et al. Morbidity and mortality after neoadjuvant therapy for lung cancer. the risks of right pneumonectomy. Ann Thorac Surg. 2001;72(4):1149-1154.[Abstract/Free Full Text]
- Martin J, Ginsberg RJ, Venkatraman ES, et al. Long-term results of combined-modality therapy in resectable non-small-cell lung cancer. J Clin Oncol. 2002;20(8):1989-1995.[Abstract/Free Full Text]
- Betticher DC, Hsu Schmitz SF, Totsch M, 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. Clin Oncol. 2003;21(9):1752-1759.
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