Radiotherapy is a critical partner to surgical resection in the treatment of locally advanced lung cancer. Its primary purpose, when used in combination with surgery, is to downstage tumors to facilitate surgical resection and to sterilize areas of microscopic disease in the mediastinum either before or after surgery. This chapter focuses on the role of adjuvant and neoadjuvant radiotherapy in non-small cell lung cancer (NSCLC).
The first attempts to improve the outcome of resected NSCLC through radiation involved the use of adjuvant (i.e., postoperative) radiotherapy. There are two primary indications for adjuvant radiotherapy for NSCLC. The first is to sterilize the surgical field to minimize microscopic risk in the mediastinum when an N2 lymph node is found at the time of surgery. The second addresses the surgical margin when there is a positive or close margin on bronchial resection.
In 1986, the Lung Cancer Study Group conducted a randomized trial to investigate the role of postoperative (adjuvant) radiotherapy (PORT). In that study, patients were randomized to receive either a 50-Gy dose to the entire mediastinum or no further therapy. The treatment volume included the mediastinum beginning at the sternal notch and extending 5 cm below the carina. The study revealed a significant difference in local control. Local disease control was demonstrated in 97% of patients receiving radiotherapy compared with 59% in the no-therapy control group (p < 0.001). However, because of the high rate of distant failures demonstrated in both groups, neither revealed a significant difference in recurrence-free or overall survival.1 It became clear from this trial that while radiotherapy did have the potential to influence local control in resected NSCLC, overall disease outcome was not affected because of the lack of systemic therapy.
During this same period, multiple randomized trials investigating the role of postoperative radiation therapy were being conducted with varied results. An influential meta-analysis of these trials, called the PORT meta-analysis, attempted to determine the impact of these earlier trials. This study, published in 1998, included nine randomized trials, mostly from Europe. These trials included patients with stage I–III NSCLC after surgical resection. The median survival of all patients was 25 months. The results of this trial, unfortunately, showed a decrement in the overall survival of the group receiving radiotherapy, which raised questions about the safety of this approach.2 The hazard ratio for the PORT group was 1.21, which corresponded to a 7% decrease in overall survival at 2 years. It is noteworthy that the local failure rate in the PORT group actually was lower than in the non-PORT group (195/1056 = 18.5% for PORT versus 276/1072 = 25.7% for no PORT). However, death from other causes was higher in the PORT group, and this factor influenced the overall hazard ratio. In addition, when the data were evaluated in terms of N1 versus N2 positive nodes, the effect on survival appeared to be less severe for patients with positive N2 nodes as opposed to positive N1 nodes. Although the study concluded that radiotherapy should not be used in resected NSCLC, use of ...