By Stephen Chun, MD, MD Anderson Cancer Center
David Palma, MD, PhD, from Western University in London, Ontario, presented results of the multicenter Canadian SUNSET Trial, which prospectively tests the use of an eight fraction accelerated hypofractionated radiotherapy regimen for ultra-central non-small cell lung cancer (NSCLC). Ultra-central lung tumors overlapping the proximal bronchial tree, esophagus and pulmonary artery/vein have long been known to be at high risk for major toxicity when treated with hypofractionated radiotherapy. Early experiences of stereotactic body radiotherapy (SBRT) for central lung cancers saw high rates of severe pulmonary toxicity, including severe pneumonitis and fatal hemoptysis. While previous trials like NRG Oncology-RTOG 0813 have tested the maximum tolerated dose (MTD) of SBRT for central lung tumors, there were very few ultra-central tumors included. As ultra-central lung cancers are nearly always unresectable, testing the boundaries of radiotherapy is a critical need for patients who have no other curative option. Although various radiation regimens have been reported for ultra-central lung tumors in various retrospective and single-institution analyses, this is particularly robust safety data coming from a prospective multicenter trial.
The SUNSET trial included 30 patients with ultra-centrally-located NSCLC treated to a dose of 60 Gy in 8 fractions. With a median follow-up of over three years, there were two patients with severe pulmonary adverse events (6.7%). The oncologic outcomes and toxicity outcomes seem to mirror what you would expect from SBRT regimens for low-risk peripheral lung tumors seen in trials like RTOG 0236. Notably, the overall survival was 72.5% and local control was 90%. Given these outcomes, this regimen warrants further exploration in the search for the optimal treatment strategy for these high-risk ultra-central lung tumors.
With emerging data demonstrating the efficacy of programmed death-ligand 1 (PD-L1) immunotherapy for early-stage NSCLC treated with SBRT, this fractionation scheme may play a role in trials seeking to integrate immunotherapy with radiation for ultra-central lung tumors, especially as the progression free survival in this study was 66%. From a health services standpoint, this short hypofractionated radiation scheme delivered over 1.5 weeks may also provide opportunities to increase access and reduce inconvenience to patients who live in rural and medically underserved communities. While these initial results are promising, long-term follow-up with be important to evaluate for late radiation adverse effects and long-term safety profile.
