Long-Term Outcomes of Salvage Stereotactic Ablative Radiotherapy for Isolated Lung Recurrence of Non-Small Cell Lung Cancer: A Phase II Clinical Trial

Abstract

Objectives: Our goal was to evaluate stereotactic ablative radiotherapy (SABR) as a salvage option for isolated recurrence of NSCLC in the lung parenchyma after definitive treatment of stage I to III disease.

Methods: Patients who had histologically confirmed, positron emission tomography-staged, isolated NSCLC recurring locally or metastasis in the lung parenchyma (≤3 cm, suitable for SABR) after previous definitive treatment were prospectively enrolled in this trial and treated with volumetric, image-guided SABR to 50 Gy in four fractions. Patients were then followed with computed tomography or positron emission tomography/computed tomography. Primary end points included the pattern of failure after salvage SABR, overall survival (OS), and progression-free survival (PFS).

Results: Fifty-nine patients with recurrent disease were treated with salvage SABR. The median age was 70 years (range 45-86 years), and the median follow-up time after salvage SABR was 58.3 months. Re-recurrence after salvage SABR developed in 19 patients (32%). Measuring from the date of salvage SABR, the estimated 5-year rates of local, regional, and distant failure were 5.2%, 10.3%, and 22.4%, respectively; the estimated PFS was 46.2% at 3 years and 41.1% at 5 years; and the OS rates were 63.5% at 3 years and 56.5% at 5 years. A high post-SABR neutrophil-to-lymphocyte ratio was found to predict poor survival. Grade 3 treatment-related adverse events developed in three patients (5%). No patient had a grade 4 or 5 event.

Conclusion: Our study showed that salvage SABR provides excellent 5-year OS, local control, and PFS rates with minimal toxicity for patients with isolated NSCLC recurrence in the lung parenchyma. These results are striking and comparable to historically reported outcomes of patients with primary early-stage NSCLC treated with definitive SABR. SABR appears to be a very effective and safe salvage option for patients with isolated lung parenchyma recurrent disease after definitive treatment and should be considered along with surgery as a potential first-line option for patients with local lung parenchymal recurrent disease.

Trial registration: ClinicalTrials.gov NCT00489008.

Keywords: Non–small cell lung cancer; Pattern of failure; Recurrent lung cancer; Stereotactic ablative radiotherapy; Toxicity.

Figure 1

(A) Freedom from any recurrence and estimated cumulative incidence of any recurrence after salvage stereotactic ablation radiotherapy as determined by competing risk analysis. (B) Kaplan-Meier curves and estimated cumulative incidences of overall survival (OS), progression-free survival (PFS), and lung cancer-specific survival after SABR. CI, confidence interval. † Simultaneous RR and DM occurred in 3 patients. * Estimation of 95% CI is limited.

Figure 1

(A) Freedom from any recurrence and estimated cumulative incidence of any recurrence after salvage stereotactic ablation radiotherapy as determined by competing risk analysis. (B) Kaplan-Meier curves and estimated cumulative incidences of overall survival (OS), progression-free survival (PFS), and lung cancer-specific survival after SABR. CI, confidence interval. † Simultaneous RR and DM occurred in 3 patients. * Estimation of 95% CI is limited.

Figure 2

Kaplan-Meier curves of progression-free survival (A) and overall survival (B) after salvage stereotactic ablation radiotherapy by prior disease stage, and (C) overall survival by recurrence event after salvage SABR. LRR, local or regional recurrence only; DM, distant metastasis.