Nonresected Non–Small-Cell Lung Cancer in Stages I Through IIIB: Accelerated, Twice-Daily, High-Dose Radiotherapy—A Prospective Phase I/II Trial With Long-Term Follow-Up

Purpose

Our purpose was to investigate the tolerability of accelerated, twice-daily, high-dose radiotherapy. The secondary endpoints were survival and locoregional tumor control.

Methods and Materials

Thirty consecutive patients with histologically/cytologically proven non–small-cell lung cancer were enrolled. Tumor Stage I, II, IIIA, and IIIB was found in 7, 3, 12, and 8 patients, respectively. We applied a median of 84.6 Gy (range, 75.6–90.0 Gy) to the primary tumors, 63.0 Gy (range, 59.4–72.0 Gy) to lymph nodes, and 45 Gy to nodes electively (within a region of about 6 cm cranial to macroscopically involved sites). Fractional doses of 1.8 Gy twice daily, with an interval of 11 hours, were given, resulting in a median treatment time of 35 days. In the majority of patients the conformal target-splitting technique was used. In 19 patients (63%) two cycles of induction chemotherapy were given. The median follow-up time of survivors is 72 months (range, 62–74 months).

Results

We found Grade 1, 2 and 3 acute esophageal toxicity in 11 patients (37%), 2 patients (7%), and 2 patients (7%), respectively. Grade 2 acute pneumonitis was seen in 2 patients (7%). No late toxicity greater than Grade 1 was observed. The actual overall survival rates at 2 and 5 years are 63% and 23%, respectively; the median overall survival, 27.7 months. In 9 patients a local failure occurred, 7 of them presenting initially with an atelectasis without availability of 18-fluorodeoxyglucose–positron emission tomography staging at that time. In 4 patients recurrence occurred regionally.

Conclusions

This Phase I/II trial with long-term follow-up shows low toxicity with promising results for survival and locoregional tumor control.

Non–small-cell lung cancer, Accelerated radiotherapy, Conformal radiotherapy, Target splitting, Phase I/II clinical trials