Background: Human tumour cells can proliferate rapidly, and giving radiotherapy in many small fractions may reduce long-term normal-tissue morbidity. In response to these observations, we developed the CHART (continuous hyperfractionated accelerated radiotherapy) regimen, which uses thirty-six small fractions of 1.5 Gy given three times per day, to give 54 Gy in only 12 consecutive days. We report the long-term follow-up of a trial of CHART versus conventional radiotherapy in patients with locally advanced non-small-cell lung cancer (NSCLC).
Methods: 563 patients were entered by thirteen centres between April, 1990, and March, 1995. We included patients with NSCLC localised to the chest with a performance status of 0 or 1 in whom radical radiotherapy was chosen as the definitive management. Patients were randomly allocated in a 3:2 ratio to CHART or conventional radiotherapy. The latter was thirty fractions of 2 Gy to a total dose of 60 Gy in 6 weeks.
Results: The groups were well matched for possible prognostic factors. Overall there was a 24% reduction in the relative risk of death, which is equivalent to an absolute improvement in 2-year survival of 9% from 20% to 29% (p = 0.004, 95% CI 0.63-0.92). Subgroup analyses (predefined) suggest that the largest benefit occurred in patients with squamous cell carcinomas (82% of the cases), in whom there was a 34% reduction in the relative risk of death (an absolute improvement at 2 years of 14% from 19% to 33%). During the first 3 months, severe dysphagia occurred more often in the CHART group than in the group on conventional radiotherapy (19 vs 3%). Otherwise, there were no important differences in short-term or long-term morbidity.
Interpretation: CHART compared with conventional radiotherapy gave a significant improvement in survival of patients with NSCLC. Further improvement may be achieved with dose escalation in conformal radiotherapy, by the addition of cytotoxic chemotherapy, and by hypoxic cell radiosensitisation.