Hot Spot Not Hot Enough? Differences in Local Control for Non-Small Cell Lung Cancer Treated With Stereotactic Body Radiotherapy Based on Maximum Point Dose within the Planning Target Volume

Abstract

<h3>Purpose/Objective(s)</h3> One of the defining characteristics of stereotactic body radiation therapy (SBRT) is the creation of a steep dose gradient, resulting in a higher dose centrally within the planning target volume (PTV) than at the periphery. However, there is no consensus regarding objectives for the maximum point dose delivered to the PTV. In this study, we investigated whether higher relative maximum doses within the PTV were associated with improved tumor control. <h3>Materials/Methods</h3> We performed a single-institution retrospective review of patients with early-stage, node-negative NSCLC who received curative-intent SBRT between 2005 and 2018. Patients with biopsy-proven NSCLC or presumed NSCLC based on radiographic findings were included. All patients underwent four-dimensional computed tomography (CT) for radiation planning and were treated with a free-breathing technique, utilizing an internal target volume (ITV) to account for tumor motion during the respiratory cycle. The PTV was defined as a 5-mm expansion from the ITV. We calculated the relative maximum dose to the PTV from a ratio of the maximum point dose delivered within the PTV to the prescription dose. We analyzed outcomes using the Kaplan-Meier method and used a log-rank test to assess prognostic impact. <h3>Results</h3> The study population consisted of 175 patients and 186 individual lung nodules with a median follow-up time of 2.6 (range, 0.1 – 12) years for all patients and 3.5 (range, 0.2 – 8.4) years for living patients. The median age was 70.2 (range, 43 – 90) years, and the median maximum tumor diameter was 1.9 (range, 0.7 – 5.6) cm. Most tumors were peripheral with only 9.7% (n=18) centrally located. The median prescription dose was 50 (range, 48 – 62.5) Gy in 5 (range, 4-10) fractions. The median relative maximum dose delivered to the PTV was 110%. Among the entire cohort, the 3-year rates (95% CI) of local control (LC), cause-specific survival, and overall survival were 81.0% (73.8% – 86.5%), 72.4% (64.5 – 79.1%), and 48.3% (40.7% – 55.9%), respectively. The 3-year rate of LC was superior among patients treated with a maximum point dose ≥ 110% vs. < 110% (86% vs. 74%, p=0.03). The difference in 3-year LC was more pronounced between a maximum point dose ≥ 120% vs. < 120% (94% vs. 79%, p = 0.05). The maximum point dose was significant for LC on multivariate analysis (p = 0.03). <h3>Conclusion</h3> Patients with early-stage NSCLC treated with SBRT with a relative maximum dose in the PTV of at least 110% demonstrated improved local control. Thus, more homogeneous SBRT plans may compromise the ablative treatment. Further studies should clarify specific objectives for the maximum point dose delivered to the PTV.