Sunan Cui, PhD, et al.1 presents findings from a phase II trial evaluating functional lung avoidance and response-adaptive escalation radiotherapy (FLARE-RT) in unresectable non-small cell lung cancer. The study includes 49 patients planned to 60 Gy in 30 fractions. Fluorodeoxyglucose-positron emission tomography (FDG-PET) imaging is performed during the course of treatment with non-responders at week three receiving a simultaneous integrated boost of 14 Gy in 15 fractions as a form of treatment intensification based on metabolic activity. Two-year locoregional progression and distant metastasis rates were 18.5% and 43.1% respectively, with comparable survival rates as compared to historic controls. Interestingly, the authors report that pre-radiation PET total lesion glycolysis (TLG) correlated with an increased rate of locoregional progression whereas mid-RT TLG corresponded to distant progression, which were the majority of the treatment failures in the study.
The authors conclude that the approach of using biologically guided imaging for potential dose-escalation is feasible and may have predictive properties for both local and distant progression. Safety data was not provided in the abstract.
Presently, there are a number of studies that have attempted to incorporate radiographic imaging to dose adapt or escalate the disease and avoid the more functional sections of the lung. Vinogadskiy et al2 published results from their phase II multi-institutional study incorporating four-dimensional computerized tomography ventilation to avoid functional regions of the lung with the primary endpoint of reducing rates of grade 2 or higher pneumonitis. Additional work since the infamous publication of the NRG-RTOG 0617 trial failing to show a benefit of dose-escalation in lung cancer, has attempted to dose-escalate based on inter-fraction PET imaging as demonstrated above. Vera et al3 performed a multicenter phase 2 randomized trial comparing standard radiation (66 Gy in 33 fractions) to dose-escalated radiotherapy with a boost to residual FDG avid disease at 42 Gy going up to 74 Gy in 33 fractions.
Precision oncology as it relates to radiation treatment has been somewhat behind in comparison to our medical oncology colleagues. Our newer technologies including both CT and MRI adaptive radiotherapy provide one opportunity to adjust our treatments based on tumor response and anatomical changes during treatment. Additionally, potential technologies including SCINTIX and similar concepts utilizing the metabolic activity of the disease to target in real time may provide further opportunity to adapt delivery based on the biology of the tumor and its response during treatment.
I commend the authors for their great work opening the door for additional work in adaptive planning based on functional imaging during treatment. “The FLARE-RT trial represents an important step toward next-generation precision oncology concepts that individualize combinations of adaptive local and systemic therapies based on imaging, tissue, and blood biomarkers,” said senior author Stephen Bowen, PhD, and colleagues.
Abstract 191, Phase II Trial of Risk-Adaptive Chemoradiation for Unresectable Non-Small Cell Lung Cancer: FLARE-RT Mature Outcomes and Patterns of Failure, was presented during the SS 16 - Lung 3: Clinical Trials of Chemoradioimmunotherapy and Risk Adapted Radiotherapy for Advanced Lung Cancer session of the 66th ASTRO Annual Meeting.
