Stereotactic body radiation therapy for stage I non-small-cell lung cancer: a historical overview of clinical studies.

Because of difficulties with stabilization, breathing motion and dosimetry, stereotactic body radiotherapy for lung cancer has only been practiced for the past 15 years. However, a large amount of case data has rapidly been accumulated in recent years. Stereotactic body radiotherapy for Stage I non-small-cell lung cancer has been actively investigated in inoperable patients since around 1995, and a number of clinical trials have been undertaken. Early studies from 2001 presented a 3-year local control rate of 94% and a 3-year overall survival rate of 66% for patients receiving 50-60 Gy in 10 fractions. Another study in 2005, using 48 Gy in four fractions, presented a 3-year local control rate of 98% and 3-year overall survival rates of 83% for Stage IA patients and 72% for Stage IB patients. A multi-institutional study showed favorable local control and survival rates in a group receiving a biologically effective dose of 100 Gy. A dose-escalation study in the USA suggested a maximum tolerated dose of 60 Gy in three fractions. A Phase II clinical trial (RTOG0236) followed, with a reported 3-year local control rate of 98% and a 3-year overall survival rate of 56% for patients who received 60 Gy in three fractions. A Japanese Phase II clinical trial (JCOG0403) investigated a dose of 48 Gy in four fractions among 165 Stage IA patients, showing a 3-year survival rate of 76% and a 3-year locally progression-free survival rate of 69% for the operable group. An overview of past clinical trials in stereotactic body radiotherapy for Stage I non-small-cell lung cancer and current issues is presented and discussed.