Ultra-central lung tumors: safety and efficacy of protracted stereotactic body radiotherapy

Purpose or Objective
For patients with early stage or medically inoperable lung cancer, stereotactic body radiotherapy (SBRT) is a general accepted and effective treatment option. While most successful data come from peripherally located tumors, the role of SBRT in ultra-central tumors remains controversial. The aim of this single-center cohort study was to evaluate the safety and efficacy of protracted SBRT with 60 Gy in 12 fractions (with a biological effective dose [BED10] of 90Gy) for patients with ultra-central lung tumors.

Materials and Methods
Patients with ultra-central lung tumors treated in our institution with 60 Gy in 12 fractions from January 2012 until April 2020 were included. Ultra-central tumors were defined as planning target volume (PTV) abutting or overlapping the main bronchi, trachea and/or esophagus (Figure). Data regarding patient-, tumor-, and treatment-related characteristics were evaluated.

Results
A total of 72 patients met the criteria for ultra-central tumor location. The PTV abutted the main bronchus, trachea or esophagus in 78%, 21% and 21% of cases, respectively. At a median follow-up of 19 months, 1- and 2-year local failure-free survival rates were 98% and 85%, respectively. Overall survival rates at 1 and 2 years were 77% and 52%, respectively. Grade 3 or higher toxicity was observed in 21%, of which 10 patients (14% of total) died of bronchopulmonary hemorrhage. A significant difference between patients with or without grade ≥3 toxicity was found for the mean dose (Dmean) to the main bronchus (p=0.015), where a Dmean BED3 of ≥90 Gy increased the risk of grade ≥3 toxicity significantly. Age, tumor histology and antithrombotic therapy was not significantly associated with the rate of grade ≥3 toxicity.

Conclusion
A protracted SBRT regimen of 60 Gy in 12 fractions for ultra-central lung tumors leads to high local control rates with acceptable toxicity in most patients, albeit at the risk of serious toxicity and even mortality. Therefore, possible risk factors of lung hemorrhage such as dose to the main bronchus, peri- or endobronchial tumor location and anti–vascular endothelial growth factor (anti-VEGF) or antithrombotic therapy should be taken into account. This study suggests to limit the Dmean BED3 to the main bronchus to 90 Gy.