A study of postoperative radiotherapy in patients with non–small-cell lung cancer: a randomized trial

doi:10.1016/S0360-3016(00)00509-5

International Journal of Radiation OncologyBiologyPhysics

Volume 47, Issue 4, 1 July 2000, Pages 925-929

Presented in part at the International Congress of Radiation Oncology, June 5–7, 1997, Beijing, China.

https://doi.org/10.1016/S0360-3016(00)00509-5 Get rights and content

Abstract

Purpose: To study the value of postoperative radiotherapy for non–small-cell lung cancer (NSCLC) with positive regional lymph metastases (NI or N2) after radical surgery.

Materials and Methods: From February 1982 to October 1995, 366 patients with NSCLC and N1 or N2 disease were randomized into postoperative radiotherapy (S + R) (183 patients) and no further treatment (S alone) (182 patients). Postoperative radiotherapy (RT) was administrated 3–4 weeks after radical operation. Irradiated fields covered the bronchial stump, ipsilateral hilum, and most of the mediastinum. The midplane dose was 6000 cGy/30 fractions/6 weeks, with the spinal cord limited to 4000 cGy/20 fractions/4 weeks or less. One hundred thirty-four patients in S + R group and 162 patients in S alone group were evaluated. Clinical data were comparable in both arms, except for the numbers of N2 patients.

Results: The 3-year and 5-year overall survival rates were 51.9% and 42.9% in the S + R group and 50.2% and 40.5% in the S alone Group (p = 0.56). The 3-year and 5-year disease-free survival rates were 50.7% ± 4.7% and 42.9% ± 5.2% in the S + R group vs. 44.4% ± 4.3% and 38.2% ± 4.5% in the S alone group (p = 0.28), respectively. In the patients with NI or T3–4 tumors, there was a trend toward improved survival in the S + R group, especially in the patients with T3–4N1M0. These patients demonstrated 20% improvement in overall survival (p = 0.092) and greater than 20% better disease-free survival (p = 0.057). Postoperative RT reduced local recurrence but had no impact on distant metastases.

Conclusion: Postoperative RT significantly reduced local relapses, but did not improve overall survival, due to a high frequency of distant metastases in this patient group.

Introduction

Lung cancer is one of the main causes of cancer deaths. About 80% of lung cancer is non–small-cell lung cancer. For patients with potentially resectable non–small-cell lung cancer (NSCLC) without distant metastases, the standard treatment is an intended curative resection, but only 30% of patients with cancer confined to the chest are considered surgical candidates. Furthermore survival is greatly reduced if the mediastinal nodes are involved. The 5-year survival rates after a complete surgical resection are over 60% for the patients with T1 tumors and without node involvement (NO). This survival rate drops to less than 30% for those with NI (hilar lymph nodes) and to 10% for the patients with positive mediastinal lymph nodes (N2) (1). Local recurrence following surgery with curative intent has remained a significant problem 1, 2. A number of retrospective surveys claimed to show benefit to patients with mediastinal node metastases from postoperative radiotherapy (RT) 3, 4, 5, 6, 7, but the surveys were in general small and involved unreliable comparison against either historical controls or other series from different centers.

Van Houtte et al. reported the results of a randomized trial showing that the survival of patients with NO disease was better in the nonirradiated group, compared to those receiving postoperative RT (43% vs. 24% at 5 years) (8). In the patients with N1–2 disease, the results of randomized trials showed differences in different center. The Lung Cancer Study Group reported that there was no evidence that postoperative radiotherapy (RT) improves survival, although in this group the local recurrence rate was significantly lower (9). Paterson and Russell reported a similar result in a randomized trial of 202 patients, showing no difference in survival between patients treated with or without the postoperative radiotherapy (10). Mayer et al. reported there were fewer local relapses plus a higher overall survival and disease-free survival (29.7% and 27.1%) in the patients receiving postoperative radiotherapy than in the patients treated with surgery alone (20.4% and 15.7%) (11). Thus, the role of postoperative radiation in the patients with NI or N2 NSCLC remains controversial. Herein, we describe the results of a randomized trial in patients with N1 or N2 NSCLC at the Cancer Hospital, Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical University (PUMU), Beijing, China.

Section snippets

Materials and methods

From Feb. 1982 to December 1995, 365 patients with NSCLC with N1 or N2 lymph node involvement, resected for cure and age of 65 years or less, were randomized to be treated with either postoperative irradiation (S + R) or surgery alone (S alone). There were 183 patients in the S + R group and 182 patients in the S alone group entered into the protocol. Postoperative radiotherapy was administrated with 6- or 8-MV photons, 2–3 weeks after surgery. Irradiated fields covered the bronchial stump,

Characteristics of the patients

There were comparable dates in two groups except there were more patients with N2-stage in S + R group than in S alone group (see Table 1).

Overall survival and disease-free survival

Three-year and 5-year overall survival rates (Fig. 1) were 51.9% ± 4.3% and 43.4% ± 5.1% in S + R group vs. 50.2% ± 4.3% and 40.5% ± 4.6% in S alone group, respectively. The disease-free survival rates were 50.7 % ± 4.7% and 42.9% ± 5.2% at 3 years and 5 years in S + R group vs. 44.4% ± 4.3% and 38.2% ± 4.5% in S alone group (Fig. 1), respectively. These

Discussion

For many years, postoperative radiotherapy has been used to prevent local failure and possibly to increase long-term survival. However, the role of postoperative radiotherapy in non–small-cell lung cancer still remains controversial.

There is no benefit to postoperative radiotherapy in the patients with completely resected stage I NSCLC 8, 12, 13, however, the role of postoperative radiotherapy in the patients with N1, N2 is less clear.

In the present trial, the results show that postoperative

Conclusion

Postoperative RT for NSCLC significantly improves local control, but not overall survival.

Postoperative RT may demonstrate a survival advantage in the subgroup of patients with T3–4N1M0 (Stage III) NSCLC.

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¹: Present address for Dr. Feng: Department of Radiation Oncology, Duke University Medical Center, P.O. Box 3433, Durham, NC 27710, USA. E-mail: [email protected]

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Clinical investigations: LungA study of postoperative radiotherapy in patients with non–small-cell lung cancer: a randomized trial

Abstract

Introduction

Section snippets

Materials and methods

Characteristics of the patients

Overall survival and disease-free survival

Discussion

Conclusion

Int J Radiat Oncol Biol Phys

Int J Radiat Oncol Biol Phys

J Thorac Cardiovasc Surg

Ann Thorac Surg

Lung Cancer

Assessment of the role of surgery for control of lung cancer

Ann Thorac Surg

Sit of recurrence in patients with stage I and stage II carcinoma of the lung resected for cure

Soc Thorac Surg

Postresection irradiation for primary lung cancerA controlled trial after resection of curative design

Int J Radiat Oncol Biol Phys

Mediastinal metastases in bronchogennic carcinomaInfluence of postoperative irradiation, cell type and location

Ann Thorac Surg

Clinical investigations: Lung
A study of postoperative radiotherapy in patients with non–small-cell lung cancer: a randomized trial