Accelerated Hypofractionated Radiation Therapy with 75 Gy/25 fr/5wks vs. Stereotactic Body Radiation Therapy with 48 Gy/4 fr/1wk for the treatment of Stage I Non-small Cell Lung Cancer — Single Institution Experience with Long-Term Follow-up

Abstract

Although SBRT is one of the standard treatments for stage I NSCLC. it carries the risk of severe adverse events for serial organs concerning central tumors. Accelerated hypofractionated radiotherapy (AHRT; lowering the fraction dose and increasing the total dose) has been considered to be a reasonable alternative to treat central tumors. We have been treating central tumors with AHRT of 75 Gy/25 fr/5wks regimen and we compared the results with those of SBRT’s of 48 Gy/4 fr/1wk. Among SBRT candidates, patients with central tumors, unfit for one-hour fixation, and/or who refused fixation were the candidate for AHRT. Based on the proximity of BED10 of SBRT (48 Gy/4 fr; 105.6 Gy), AHRT of 75 Gy/25 fr (BED10 97.5 Gy) was adopted. The prescription point was isocenter. In both techniques, no elective nodal irradiation was adopted. From October 2003 to December 2010, 187 patients received either AHRT (103 cases) or SBRT (84 cases). In AHRT group (group A), 43 cases (41%) were central tumors whereas in SBRT group (group S) all cases were peripheral tumors (p<0.05). Median age was 78 in both groups (p=0.395). Male to female ratio was 74/29 and 53/31 in groups A and S, respectively (p=0.212). ECOG PS (0-1/2/3) was 94/9/0 and 72/10/2 in groups A and S, respectively (p=0.232). T1/T2 (UICC 6th ed.) ratio was 61/42 and 62/22 in groups A and S, respectively (p<0.05). Histologically, adenocarcinoma/squamous cell carcinoma /others were 67/22/14 and 53/26/5 in groups A and S, respectively (p<0.05). As for operability, operable/high risk operable/inoperable case was 21(20%)/30/52 and 14(17%)/36/34 in groups A and S, respectively (p=0.161). Median follow-up periods of surviving patients were 7.8 years and 8.1 years in groups A and S, respectively (n.s.). Overall 5-year survival rates were 46.5% (95% CI: 36.7 ∼ 56.2%) for group A and 46.4% (95% CI: 35.8 ∼ 57.1%) for group S (n.s.). Overall 5-year local control rates were 81.9% (95% CI: 73.6 ∼ 90.1%) for group A and 78.5% (95% CI: 68.9 ∼ 88.0%) for group S (n.s.). Multivariate analysis revealed that adenocarcinoma histology was better controlled than other histologies (p=0.004) and that women (p<0.001) and smaller tumors (p=0.023) fared better than their counterpart. Hazard ratio of AHRT against SBRT was less than 1 both in local control and overall survival. Concerning pulmonary toxicities, there were 5 grade 3 pulmonary toxicities (5%) for AHRT cases and 4 Grade 3 pulmonary toxicities (5%) for SBRT cases (n.s.). No serial organ toxicity was observed in central tumors. Disease recurrences were observed in 47 cases (45.6%) and 38 cases (45.2%) in groups A and S, respectively (n.s.). Under the long-term follow-up, this AHRT regimen of 75 Gy/25 fr/5wks is promising in that it can obtain similar local control and survival results with SBRT and it can control central tumors as well as peripheral tumors without any serial organ toxicities for central tumors. Based on these results, prospective multicenter trial is worth conducting.