Results of Trimodality Therapy in Patients with Stage IIIA (N2-bulky) and Stage IIIB Non–Small-cell Lung Cancer

Jian Li; Chun-Hua Dai; Li-Chao Yu; Ping Chen; Xiao-Qin Li; Shun-Bing Shi; Jing-Rong Wu

Disclosures

Clin Lung Cancer. 2009;10(5) 

In This Article

Abstract and Introduction

Abstract

Background: The survival rates for stage IIIA and stage IIIB non–small-cell lung cancer (NSCLC) are extremely poor with single-treatment modalities such as radiation therapy or surgery. The purpose of this study is to assess tolerability, response, surgical resectability, and survival of chemotherapy followed by chemoradiation therapy, and then followed by surgery in patients with stage IIIA (N2-bulky) or stage IIIB NSCLC.
Patients and methods: Forty-eight patients with stage IIIA (N2-bulky) or stage IIIB (T4 N1-2 M0) NSCLC received 2 cycles of chemotherapy with cisplatin, mitomycin, and vindesine, subsequent radiation therapy (45 Gy, twice-daily 1.5 Gy) with simultaneous low-dose cisplatin and vindesine, followed by surgery.
Results: Forty-five patients completed induction chemoradiation therapy. Thirty-three patients (68.8%) had clinical response to induction treatment. Thirty-nine patients underwent a thoracotomy, with a complete resection rate of 62.5% (30/48). The pathologic response rate was 60% (27/45), with complete pathologic response of 8 patients. The median survival time for the total group of 48 patients was 23 months, with 3- and 5-year survival rates of 41.7% and 31.8%, respectively. Multivariate analysis showed that complete resection and pathologic response in surgical specimens were independent predictors of survival (P = .048 and P = .022).
Conclusion: Preoperative sequence of chemotherapy followed by concurrent chemoradiation therapy is an effective approach in patients with stage IIIA (N2-bulky) and IIIB (T4 N1-2 M0) NSCLC. The operation after induction chemoradiation therapy should be performed in carefully selected patients with surgically resectable diseases. The patients who achieved complete resection and with pathologic response of tumor can benefit from surgery following induction chemoradiation therapy.

Introduction

Non–small-cell lung cancer (NSCLC) accounts for approximately 80%-85% of all cases of lung cancer, and 45% of patients present with stage IIIA and stage IIIB disease.[1] Despite continuous progress, locally advanced stage IIIA and IIIB NSCLC still represents a therapeutic challenge. The chances of a cure offered by a single therapeutic option (chemotherapy, radiation therapy, surgery) are extremely poor. Stage IIIA NSCLC is a heterogeneous disease. Patients diagnosed with stage IIIA NSCLC fall into 3 groups: patients with T3 N1 or microscopic N2 disease; patients with clinical N2 disease diagnosed preoperatively, with imaging or surgical procedures; patients with multiple station bulky-N2 involvement.[2] Patients with stage IIIB disease are considered inoperable and are usually treated with chemoradiation therapy.[3] Although there is consensus to treat patients with IIIA N2-bulky in the same group as locally advanced IIIB disease, and to treat with primary surgical resection patients with minimal N2 involvement,[4] there is still no agreement about the best approach to NSCLC patients with stage IIIA N2-bulky disease diagnosed preoperatively. Some data have shown that survival in patients with stage IIIA (N2) and stage IIIB NSCLC is improved by the addition of chemotherapy to radiation therapy and/or surgery.[5–9] Investigators have focused on an early intensification of preoperative treatment by bimodality induction, including chemotherapy as well as radiation therapy before surgery.[8–14] However, whether stage IIIA N2-bulky disease should be treated together with selected patients with stage IIIB NSCLC, with a combination of chemotherapy and radiation therapy, followed by surgery (trimodality treatment), is still debated. The main objectives of the present phase II study were to assess the feasibility and toxicity of chemotherapy followed by chemoradiation therapy before operation and to evaluate clinical response, resection rate, and survival by a trimodality therapy in patients with stage IIIA (N2-bulky) and selected stage IIIB (T4 N1-2 M0).

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