Stereotactic Body Radiotherapy for Medically Inoperable Stage I-II Non-Small Cell Lung Cancer: The Mayo Clinic Experience

Abstract

Objective: To examine disease control and survival after stereotactic body radiotherapy (SBRT) for medically inoperable, early-stage non-small cell lung cancer (NSCLC) and determine associations of pretreatment ¹⁸F-fluorodeoxyglucose-positron emission tomography (FDG-PET) maximum standardized uptake values (SUVmax), biologically effective dose, and mediastinal staging with disease control and survival outcomes.

Patients and methods: We retrospectively reviewed the cases of consecutive patients with FDG-PET-staged, medically inoperable NSCLC treated with SBRT at our institution between January 1, 2008, and August 4, 2014. Cumulative incidences of recurrence were estimated, accounting for the competing risk of death. Associations of SUVmax, biologically effective dose, and mediastinal staging with outcomes were evaluated using Cox proportional hazards regression models.

Results: Among 282 patients, 2-year cumulative incidences of recurrence were 4.9% (95% CI, 2.6%-8.3%) for local, 9.8% (95% CI, 6.3%-14.2%) for nodal, 10.8% (95% CI, 7.0%-15.5%) for ipsilateral lung, 6.0% (3.3%-9.8%) for contralateral lung, 9.7% (95% CI, 6.3%-14.0%) for distant recurrence, and 26.1% (95% CI, 20.4%-32.0%) for any recurrence. The 2-year overall survival was 70.4% (95% CI, 64.5%-76.8%), and the 2-year disease-free survival was 51.2% (95% CI, 44.9%-58.5%). Risk of any recurrence was significantly higher for patients with higher SUVmax (hazard ratio [per each doubling], 1.29 [95% CI, 1.05-1.59]; P=.02). A similar association with SUVmax was observed when considering the composite outcome of any recurrence or death (hazard ratio, 1.23 [95% CI, 1.05-1.44]; P=.01). The SUVmax was not significantly associated with other outcomes (P≥0.69). Two-year cumulative incidences of local recurrence for patients receiving 48 Gy in 4 fractions, 54 Gy in 3 fractions, or 50 Gy in 5 fractions were 1.7% (95% CI, 0.3%-5.6%), 3.7% (95% CI, 0.7%-11.4%), and 15.3% (95% CI, 5.9%-28.9%), respectively (P=.02); this difference was independent of lesion size (P=.02).

Conclusion: Disease control was excellent for patients who received SBRT for early-stage NSCLC, and this series represents the largest single-institution experience from the United States on SBRT for early-stage inoperable NSCLC. Higher pretreatment FDG-PET SUVmax was associated with increased risk of any recurrence, and the 50 Gy in 5 fractions dose prescription was associated with increased risk of local recurrence.

Keywords: BED, biologically effective dose; CT, computed tomography; DFS, disease-free survival; EBUS, endobronchial ultrasonography; FDG-PET, 18F-fludeoxyglucose–positron emission tomography; HR, hazard ratio; ITV, internal target volume; LC, local control; NSCLC, non–small cell lung cancer; OS, overall survival; PET, positron emission tomography; RTOG, Radiation Therapy Oncology Group; SBRT, stereotactic body radiotherapy; SUVmax, maximum standardized uptake value.

Figure 1

Kaplan-Meier curves showing cumulative incidence of recurrence according to maximum standardized uptake values (SUVmax). Patients were divided into 3 groups of SUVmax on the basis of sample tertiles: low SUVmax, <4.3 (n=91), moderate SUVmax, 4.3-8.7 (n=98), and high SUVmax, >8.7 (n=93).

Figure 2

Kaplan-Meier curves showing cumulative incidence of local recurrence according to biologically effective dose (n=271). Patients were divided on the basis of Gy fractions: 48 Gy in 4 fractions (n=148), 50 Gy in 5 fractions (n=56), or 54 Gy in 3 fractions (n=67).