Does Dose Matter? Effect of Two Different Neoadjuvant Protocols in Advanced NSCLC

Abstract

Background For stage III, NSCLC neoadjuvant protocols have been intensified up to full dose protocols but up till now the effect of more intensive protocols in a trimodal setting could not be compared directly because of different selection criteria or experience of involved facilities in different studies or multicenter studies. We analyzed our experience with two different neoadjuvant protocols, consistent selection criteria, and surgical teams over 17-year time period.

Method Single-center retrospective study in 159 patients concerning survival, recurrence, and downstaging effect.

Results Overall median survival was 32 months, with 26 months for protocol 1, and 35 months for protocol 2, respectively. Hospital mortality was 5%. Log-rank test showed significant difference between the protocols for UICC-downstaging-effect, ypT-stage, ypN-stage, and ypUICC-stage, respectively, but only ypN-stage and ypUICC-stage were significant risk factors for survival using Cox regression.

Conclusion The median survival benefit of 9 months is evident but (probably still) not significant. The more aggressive protocol 2 shows a significant better downstaging effect concerning N- and UICC-stage if R0-resection can be achieved. Insofar dose does matter!

Keywords

airway (includes related subject matter) - chemotherapy - lung cancer treatment (surgery medical)

• References

• 1 Rosell R, Gomez-Codina J, Camps C , et al. 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
• 2 Roth JA, Fossella F, Komaki R , et al. 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 (9) 673-680
• 3 Steger V, Walles T, Kosan B , et al. Trimodal therapy for histologically proven N2/3 non-small cell lung cancer: mid-term results and indicators for survival. Ann Thorac Surg 2009; 87: 1676-1683
• 4 Friedel G, Budach W, Dippon J , et al. Phase II trial of a trimodality regimen for stage III non-small-cell lung cancer using chemotherapy as induction treatment with concurrent hyperfractionated chemoradiation with carboplatin and paclitaxel followed by subsequent resection: a single-center study. J Clin Oncol 2010; 28: 942-948
• 5 Junker K, Langner K, Klinke F, Bosse U, Thomas M. Grading of tumor regression in non-small cell lung cancer : morphology and prognosis. Chest 2001; 120 (5) 1584-1591
• 6 Albain KS, Swann RS, Rusch VW , et al. Radiotherapy plus chemotherapy with or without surgical resection for stage III non-small-cell lung cancer: a phase III randomised controlled trial. Lancet 2009; 374: 379-3866
• 7 Robinson LA, Ruckdeschel JC, Wagner Jr H , et al. Treatment of non-small cell lung cancer-stage IIIA: ACCP evidence-based clinical practice guidelines (2nd edition). Chest 2007; 132: 243S-265S
• 8 Jett JR, Schild SE, Keith RL , et al. Treatment of non-small cell lung cancer, stage IIIB: ACCP evidence-based clinical practice guidelines (2nd edition). Chest 2007; 132: 266S-276S
• 9 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 Throc Surg 1999; 68: 1144-1149
• 10 Friedel G, Hruska D, Budach W , et al. Neoadjuvant chemoradiotherapy of stage III non-small-cell lung cancer. Lung Cancer 2000; 30: 175-185
• 11 Bauman JE, Mulligan MS, Martins RG, Kurland BF, Eaton KD, Wood DE. Salvage lung resection after definitive radiation (>59 Gy) for non-small cell lung cancer: surgical and oncologic outcomes. Ann Thorac Surg 2008; 86 (5) 1632-1638
• 12 Cerfolio RJ, Bryant AS, Jones VL , et al. Pulmonary resection after concurrent chemotherapy and high dose (60Gy) radiation for non-small cell lung cancer is safe and may provide increased survival. Eur J Cardiothorac Surg 2009; 35: 718-723
• 13 Sonett JR, Suntharalingam M, Edelman MJ , et al. Pulmonary resection after curative intent radiotherapy (>59 Gy) and concurrent chemotherapy in non-small-cell lung cancer. Ann Thorac Surg 2004; 78: 1200-1205
• 14 Hampel M, Dally I, Walles T , et al. Impact of neo-adjuvant radiochemotherapy on bronchial tissue viability. Eur J Cardiothorac Surg 2010; 37: 461-466
• 15 Fowler WC, Langer CJ, Curran WJ , et al. Postoperative complications after combined neoadjuvant treatment of lung cancer. Ann Thorac Surg 1993; 55: 986-989
• 16 Deutsch M, Crawford J, Leopold K , et al. Phase II study of neoadjuvant chemotherapy and radiation therapy with thoracotomy in the treatment of clinically staged IIIA non-small cell lung cancer. Cancer 1994; 74 (4) 1243-1252