A phase 1/2 clinical trial reports that stereotactic body radiotherapy (SBRT) is well tolerated by patients with centrally located early-stage non-small cell lung cancer (NSCLC).
A high-dose ablative radiotherapy, SBRT is a standard, generally well-tolerated treatment for patients with inoperable, node-negative NSCLC. It has not previously been studied in patients with centrally located early-stage NSCLC because these patients are at increased risk of experiencing toxicity from high-dose ablative radiation therapy.
The NRG Oncology/RTOG 0813 study, which was designed to determine the maximum tolerated dose, efficacy, and toxicity of SBRT in centrally located NSCLC, enrolled 120 patients with medically inoperable, biopsy-proven, positron emission tomography (PET)-staged T1 to T2 centrally located NSCLC with no spread to lymph nodes or distant sites. The study population consisted of elderly patients, most of whom had a performance status of 0 to 1, with slightly more women than men. The majority of cancers were T1 (65%) and squamous cell (45%). Patients were given a dose-escalating, five-fraction SBRT schedule ranging from 10 to 12 Gy/fraction (fx) delivered over 1.5 to 2 weeks. Patients were followed for a median of 37.9 months.
The researchers defined dose-limiting toxicity as any treatment-related grade 3 or higher predefined toxicity occurring within the first year of treatment. They defined the maximum tolerated dose as the SBRT dose with the probability of dose-limiting toxicities closest to 20% without exceeding that number.
The organs that were most at risk of toxicity were the main bronchus and large vessels. Five of the patients experienced dose-limiting toxicities. The maximum tolerated dose was 12.0 Gy/fx, which carried a 7.2% chance of dose-limiting toxicity. In the 71 patients who were evaluable after two years, the rates for local control of the cancer were 89.4% for the 11.5 Gy/fx cohort and 87.9% for the 12.0 Gy/fx cohort. Overall survival rates were 67.9% (11.5 Gy/fx) and 72.7% (12.0 Gy/fx), and progression-free survival rates were 52.2% and 54.5%, respectively.
"Outcomes in this medically inoperable group of mostly elderly patients with comorbidities were comparable with [those] of patients with peripheral early-stage tumors," state the study authors in their publication in the Journal of Clinical Oncology.
According to lead study author Andrea Bezjak, MD, who is a Professor in the Departments of Radiation Oncology and Health Policy, Management and Evaluation at the University of Toronto, "This trial demonstrated our ability to provide local control and potential for cure in patients with centrally located, node-negative tumors in multiple institutions, while maintaining plan qualities, achieving good patient outcomes, and only allowing modest rates of toxicity."
For More Information
Bezjak A, Paulus R, Gaspar LE, et al (2019). Safety and efficacy of a five-fraction stereotactic body radiotherapy schedule for centrally located non-small-cell lung cancer: NRG Oncology/RTOG 0813 Trial. J Clin Oncol. [Epub ahead of print] DOI:10.1200/JCO.18.00622
Image credit: Yale Rosen. Licensed under CC BY-SA 2.0