Stereotactic Body Radiation Therapy for Stage I Non-small-cell Lung Cancer: A Historical Overview of Clinical Studies

Abstract

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.

Surgical and nonsurgical approaches to small-size nonsmall cell lung cancer

“…Considering the robustness of these findings within many studies worldwide, it is fair to state that SBRT has been proven to be comparable to outcome of lobectomy and lymph node dissection [69,70]. Indeed, in the International Association for the Study of Lung Cancer database, which also comprises a large, relatively non-selected group of patients, the 2-year overall survival was 68% (66-70%) [56].…”

“…45 studies concerning SABR in early stage NSCLC have been reported [56]. 13 studies including 996 patients were prospective, and 32 studies including 2645 patients were retrospective.…”

“…The 2-year overall survival was 65.2%, with a 2-year local tumour control rate of 90.4%. When all 45 studies on SABR, totalling 3641 patients, were considered, the 2-year overall survival was 70% (95% CI 67-92%) and the average local tumour control rate after 2 years was 91% (95% CI 90-93%) [56]. Even though the patient selection may have been different between studies and older reports used inevitably simpler techniques, neither the 2-year overall survival nor the 2-year local tumour control rate different significantly [56].…”

“…When all 45 studies on SABR, totalling 3641 patients, were considered, the 2-year overall survival was 70% (95% CI 67-92%) and the average local tumour control rate after 2 years was 91% (95% CI 90-93%) [56]. Even though the patient selection may have been different between studies and older reports used inevitably simpler techniques, neither the 2-year overall survival nor the 2-year local tumour control rate different significantly [56]. The 2-year local tumour control rate was 91% (95% CI 89-93%) for linear accelerator-based techniques, 88% (95% CI 78-94%) for Cyberknife (Accuracy Inc., Sunnyvale, CA, USA), and 80% (95% CI 68-91%) for other technologies.…”

High-dose-rate Three-dimensional Conformal Radiotherapy Combined with Active Breathing Control for Stereotactic Body Radiotherapy of Early-stage Non-small-cell Lung Cancer

“…Stereotactic body radiotherapy (SBRT) allows improved local control and overall survival for patients with inoperable early-stage non-small cell lung cancer (NSCLC) (1)(2)(3)(4). The two most important factors for SBRT of NSCLC are accurate positioning for tumor targeting and minimizing side effects (3,5).…”