Primary Tumor Control in Stereotactic Ablative Radiation Therapy for Large (≥ 5 cm) Non-Small Cell Lung Cancer: Does It Last?

Abstract

<h3>Purpose/Objective(s)</h3> While prospective trials have established stereotactic body radiation therapy (SBRT) as standard of care for inoperable early-stage non-small cell lung cancer (NSCLC), these studies excluded patients with tumors larger than 5 cm. Since these patients have few treatment options and conservative management is associated with significant morbidity, many clinicians utilize SBRT if dosimetric constraints can be met. The purpose of this study is to determine the rate of primary tumor failure (PTF) after SBRT for NSCLC with primaries ≥ 5cm. <h3>Materials/Methods</h3> We performed a retrospective review of all patients with NSCLC and large primary tumors (≥ 5 cm in maximum dimension) treated at our institution using SBRT from 2010 – 2018. Patients with nodal or distant disease were included, but only evaluated for toxicity and PTF. Treatment failures were captured by review of imaging, pathology, and clinical notes. PTF was defined as disease recurrence in or at the margin of the primary tumor volume (PTV) and was measured from end of SBRT to PTF. Patients without PTF were censored at last follow up or death. The Kaplan-Meier method was used to estimate event-time probabilities for PTF. Predictors of PTF were analyzed using log rank tests between groups and a parsimonious multivariate Cox multivariate model. <h3>Results</h3> A total of 145 patients were identified. Median age was 78 years (Interquartile rage [IQR] 72 -84). Evidence of regional disease was present in 5 (3%) patients and metastatic disease in 14 (10%). Median tumor diameter was 5.75 cm (IQR 5.25 – 6.43) and tumor volume was 37.9 cm³ (IQR 25.4 – 53.6). The most common SBRT regimen was 48 Gy in 4 fractions (68 patients). Median BED10 was 105.6 (IQR 105.6-151.2). With a median follow up of 21 months (IQR 9 – 32), PTF at 1, 2, and 3 years was 10.6% (95% Confidence Interval [CI] 5.1 – 16.1), 17.0% (95% CI 9.9 – 24.1), and 22.0% (95% CI 13.4 – 30.6). On univariate analysis, factors associated with PTF included lobe involved (<i>P</i> = 0.01), maximum tumor diameter > 5.75 cm (<i>P</i> < 0.01), four-fraction SBRT (<i>P</i> = 0.01), and BED10 ≤ 105.6 (<i>P</i> = 0.03). On multivariate analysis, tumor diameter > 5.75cm (HR 3.28, 95% CI 1.44 – 7.46) and four-fraction SBRT (HR 3.20, 95% CI 1.38 – 7.41) remained significant. In patients with node negative and non-metastatic disease, 2-year disease free survival and overall survival were 62.1% (95% CI 51.6 – 70.8) and 49.3% (95% CI 41.5 – 59.9). Acute toxicity was absent in 106 (73%) patients and no patients experienced grade 3 or higher acute toxicity. Maximum late toxicity was Grade 1-2 in 96 (66%) patients (predominantly asymptomatic radiation pneumonitis) and Grade 3 or higher in five (3%) patients including one patient with a contralateral pneumonectomy who experienced fatal radiation pneumonitis. <h3>Conclusion</h3> SBRT for medically inoperable NSCLC ≥ 5cm results in acceptable tumor control and toxicity, although the rate of PTF increases with longer follow up. PTF appears to be higher in patients with tumors > 5.75 cm in diameter and those receiving 48 Gy in 4 fractions.