Concurrent cisplatin/etoposide plus 3D-conformal radiotherapy followed by surgery for stage IIB (superior sulcus T3N0)/III non-small cell lung cancer yields a high rate of pathological complete response.

INTRODUCTION

Optimal preoperative treatment of stage IIB (Pancoast)/III non-small cell lung cancer (NSCLC) remains undetermined and a subject of controversy. The goal of our study is to confirm feasibility and pathological response rates after induction chemoradiation (CRT) in our community-based treatment center.

PATIENTS AND METHODS

Patients were selected according to functional and resectability criteria. Induction treatment comprised 3D conformal 4500 cGy radiotherapy delivered to the primary tumor and pathologic hilar and/or mediastinal lymph nodes on CT scan with an extra-margin of 1-1.5 cm. Concurrent chemotherapy regimen was cisplatinum 20mg/m2 d1-d5 and etoposide 50mg/m2 d1-d5, d1-5 d29-33. Within 3-4 weeks after CRT completion, operability was re-assessed accordingly. Surgery was performed 4-6 weeks after CRT completion in patients (pts) deemed resectable. Inoperable pts were referred for a 20-25 Gy boost +/-1 extra-cycle of cisplatinum+etoposide.

RESULTS

From 1996 to 2005, 107 pts were initially selected for treatment and received induction chemoradiation (stage IIB-Pancoast 18, IIIA 58 and IIIB 31, squamous cell carcinoma 48%, adenocarcinoma 44%, large-cell undifferentiated carcinoma 14%). After preoperative evaluation, 72 pts (67%) had a thoracotomy (pneumonectomy 21, lobectomy 45, bilobectomy 5) and all but one (unresectable tumor) had a macroscopic complete resection. During the 3-month postoperative time, five patients (6.9%) died, four after pneumonectomy (right 3, left 1). The analysis of tumoral samples showed a pathological complete response rate or microscopic residual foci of 39.5%. Median follow-up time was 22.3 months (survivors: 36.8 months), 2-year and 3-year overall survival rates were 55% and 40%, respectively (median=26.7 months) for all the intention-to-treat population (n=107), 62% and 51% (median=36.5 months) for 71 resected pts, 41% and 16% for 36 non-resected pts (median=19.1 months). On multivariate analysis, surgical resection and tumoral necrosis >50% (or pathological complete response) were the most pertinent predictive factors of the risk of death (hazard ratio=0.50 and 0.48, p=0.006 and 0.038, respectively).

CONCLUSION

Surgery was feasible after induction chemoradiation, particularly lobectomy in PS 0-1, stage IIB (Pancoast)/III NSCLC pts but pneumonectomy carries a high risk of postoperative death (particularly, right pneumonectomy). Pathological response to induction chemoradiation was complete in 39.5% of patients and was a significant predictive factor of overall survival.