Abstract
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Introduction: Targeted hepatic radiotherapy using Yttrium-90 (90Y) microsphere radioembolization has become a viable option for patients with hepatic malignancies. The goal of therapy is to deliver high radiation dose to tumor while sparing normal tissue. Radiation to normal tissues is a dose-limiting factor due to potential toxicity to normal hepatic and lung tissues. The current method for estimating absorbed dose in lung uses the fraction of activity shunted to the lungs and an assumed 1kg lung mass for every patient. We investigated whether using a personalized lung mass derived individually for each patient would significantly affect the estimation of the absorbed dose.
Methods: We performed a retrospective analysis of 68 patients who underwent a 99mTc-macroaggregated albumin (MAA) planning study and subsequent 90Y radiotherapy at University Hospitals Cleveland Medical Center between 1/2/2019 and 10/29/2020 and had a usable chest CT performed within 6 months of treatment. Lung shunt fraction was determined from the MAA planning study. Lung volumes for each patient were measured from CT scans manually. Volumes were converted to lung mass using a lung density of 0.181 g/mL, determined from the data. Differences between lung absorbed dose calculated using an assumed 1kg mass vs personalized lung masses were compared using Wilcoxon signed-rank test. Differences between males vs females were compared using Wilcoxon Rank Sum Test.
Results: The study included 40 males age 64.0 ± 8.24 (mean ± SD) years and 28 females age 64.54 ± 11.09 years (p=0.57). Patient height was 177.85 ± 7.10 cm for males and 161.10 ± 6.86 cm for females (p < 0.0001). Median personalized lung mass was 0.71 (IQR: 0.59, 1.02) kg. The difference between an assumed 1kg lung mass and personalized lung masses was statistically significant (P < 0.0001). Lung mass was higher for males, 0.99 (0.71, 1.14) kg, than females, 0.59 (0.50, 0.68) kg, (p < 0.0001). Median estimated lung absorbed dose was 3.45 (1.81, 6.68) Gy using an assumed 1kg lung mass vs 4.48 (2.38, 11.71) Gy using a personalized lung mass, (p < 0.0001). In 11 patients, the dose difference was ≥5 Gy. In 6 patients, the estimated lung absorbed dose increased to >25 Gy using the personalized method. In 3 patients, the lung absorbed dose increased to >30 Gy.
Conclusions: In patients undergoing 90Y radiotherapy, absorbed dose to the lungs is a potential treatment-limiting toxicity and should be ≤30 Gy for any single treatment and ≤50 Gy lifetime. When compared to using individual patient-specific lung masses, using an assumed 1kg lung mass for all patients results in a significant underestimation of lung absorbed dose. In 4% of patients, lung absorbed dose increased to above the single-therapy limit of 30 Gy with the personalized method, requiring a reduction in total administered dose in these patients. In 9% of patients, lung absorbed dose increased to >25 Gy using the personalized method, making lifetime total lung absorbed dose limit a potentially treatment-limiting toxicity factor with respect to the maximum administered dose in future 90Y radiotherapy. Personalized dose planning, including personalized lung absorbed dose calculation, is needed to avoid unintended toxicities and maximize potential treatment benefits. Additional studies investigating the importance of personalized methodology in 90Y radiotherapy dose planning are warranted.
Table 1. Lung Mass and Absorbed Dose: Personalized vs Assumed.