Author: Smith Apisarnthanarax, Clemens Grassberger, John Kang, Yejin Kim, Justin Leu, Dominic A. Maes, Matthew J. Nyflot, Ramesh Rengan, Annemarie Shepherd, Jing Zeng 👨🔬
Affiliation: Department of Radiation Oncology, University of Washington and Fred Hutchinson Cancer Center, Department of Radiation Oncology, University of Washington, University of Washington, Department of Radiation Oncology, Fred Hutchinson Cancer Center, University of Washington, University of Washington and Fred Hutchinson Cancer Center 🌍
Purpose: Reirradiation (ReRT) is a rapidly growing clinical challenge driven by better systemic therapy and longer survival, though clear guidelines for ReRT are lacking. Fitting traditional normal tissue toxicity models with clinical endpoints to ReRT data is challenging, as patients with symptomatic toxicity are often not re-irradiated. The purpose of this pilot study is to investigate a novel approach to guide re-irradiation using an imaging biomarker of individual lung radiosensitivity.
Methods: We searched our institutional database for lung cancer patients who underwent two courses of thoracic RT and collected planning CTs (pCTs), dose distributions, contours, and follow-up CTs (fuCTs) for each course. FuCTs (median 2.9 months post-RT, IQR 2-3.6) were deformably registered to the pCT to analyze lung density changes as a function of dose, normalized to 2Gy-equivalent. Individual lung radiosensitivity was quantified by fitting dose-response curves to the observed density changes using linear weighted least-squares regression. Non-parametric statistical tests were used to correlations among radiosensitivity, the interval between RTs and other clinical variables.
Results: Seventy-eight RT courses in 39 patients fit our search criteria, with a median interval of 13.9 months (IQR 7.4-25.8) between RTs. Individual lung radiosensitivity at ReRT is significantly correlated to that observed at first-RT (p=0.008). Changes in lung radiosensitivity increase with shorter RT intervals (p=0.004) and increasing tumor-to-lung volume-ratios at ReRT (p=0.006). Notably, RT intervals under 9 months resulted in significantly higher radiosensitivity at ReRT (p=0.009), indicating incomplete normal tissue recovery.
Conclusion: This pilot study demonstrates that patient radiosensitivity quantified by post-treatment lung density changes is conserved between treatment courses and shows increased sensitivity for shorter intervals between treatments. This demonstrates a novel approach for reirradiation planning by assessing individual radiosensitivity from first RT and could enable us to quantify re-irradiation “discount factors” and how they change with time.