Three quarters of all cases of lung cancer are due to non–small-cell lung cancer (NSCLC). Conventional radiotherapy usually involves administration of 2 Gy five times a week, to a total dosage of 60 Gy over a six-week period in the hope of balancing tumor treatment and damage to surrounding normal tissue. Saunders and colleagues studied the efficacy and safety of radiotherapy given as three daily treatments of 1.5 Gy for 12 consecutive days in patients with locally advanced NSCLC.
British patients with inoperable NSCLC who met criteria for radical radiotherapy were included in the study. Of 563 patients, 225 were randomized to receive conventional radiotherapy and 338 were randomized to receive accelerated therapy, called continuous hyperfractionated accelerated radiotherapy (CHART). With CHART, the duration of radiotherapy was reduced from 40 days to 12 days with the intent of minimizing the opportunity for cell proliferation.
Patients were followed weekly for six weeks, and then at eight weeks and three months after the first day of radiotherapy. For the next two years, follow-up was every three months, after which a follow-up visit was conducted every six months. Follow-up studies included chest radiographs and computed tomography performed every six months, as well as assessment of symptoms, particularly dysphagia.
In the conventional treatment group, 40 patients (18 percent) did not complete treatment as planned. In the CHART group, 29 (9 percent) did not complete therapy. The 13 participating centers began enrolling patients in 1990, and since that time 444 study participants have died. The one-year survival rate was 63 percent in patients treated with CHART, compared with 55 percent in the group receiving conventional radiotherapy. The survival rate at two years was 29 percent for patients treated with CHART and 20 percent for patients treated with conventional radiotherapy. Analysis of subgroups suggested that CHART may be most effective in patients with squamous cell carcinoma.
CHART patients reported more severe problems with dysphagia during treatment. In the CHART group, 19 percent were able to swallow only fluids, compared with 3 percent of the conventional radiotherapy group. Dysphagia resolved at three months in most patients, although 9 percent of the CHART patients and 7 percent of the conventionally treated patients reported persistent dysphagia. The degree of dysphagia reported usually was slight.
Radiation pneumonitis was slightly more common in the conventional radiotherapy group. In this group, 65 percent had radiologic changes, and 19 percent were symptomatic. In the CHART group, 56 percent had radiologic changes, and 10 percent had symptoms of radiation pneumonitis.
The authors conclude that CHART provided significant improvement in survival in patients with NSCLC, particularly in patients with squamous cell carcinoma. CHART was associated with a higher percentage of patients who completed therapy. Although initial radiation-induced symptoms were more severe in CHART patients, they resolved more rapidly in these patients than in patients treated conventionally.