Dynamic Hepatic Blood Flow Model Shows Greater Impact of Total Treatment Time Than Integral Dose for Assessing Dose to Circulating Lymphocytes

Abstract

<h3>Purpose/Objective(s)</h3> Radiation-induced lymphocyte depletion has been reported to correlate with survival rate in post-radiotherapy patients with hepatocellular carcinoma. This study aims to assess the impact of integral dose and treatment time on the dose to circulating lymphocytes (CL) with active scanning and passive scattering proton beam therapy (PBS, SOBP), intensity-modulated radiation therapy (IMRT) and volumetric-modulated arc therapy (VMAT). <h3>Materials/Methods</h3> Four plans based on VMAT, IMRT, PBS and SOBP were created for the same hepatocellular carcinoma patient delivering 52.5 Gy in 15 fractions. Six fields, 1 arc, and 2 fields were used for IMRT, VMAT and proton plans, respectively. The dose to CLs after one RT fraction was computed with a novel 4D dynamic blood flow liver model using realistic treatment times (Table 1), which takes into account hepatic vasculature (arterial, portal venous and hepatic venous trees), blood recirculation and time structure of dose delivery. We varied the delivery speed for each modality to achieve total treatment times in the range of 50-250s. The impact of integral dose and treatment time on dose to CLs across different modalities was quantified by the mean dose to CL, the % CL receiving non-zero dose (V_0Gy), the % CL receiving > 0.5 Gy dose (V_0Gy) and the dose received by highest 2% of CLs (D_2%). <h3>Results</h3> Mean liver dose ranges from 19.4 - 22.2 Gy and treatment time from 60 - 3255s depending on the modality. The PBS and SOBP treatments yield 15% and 10% lower mean dose to CLs compare to VMAT, respectively (Table 1). However, the fraction of lymphocytes receiving any dose varies widely from 37.0% for VMAT to 80.8% for PBS, uncorrelated to integral dose. The fraction of lymphocytes receiving a significant dose (V0.5%) also varies considerably with the highest fraction in VMAT (14.6%) and the lowest for PBS (0.6%). Further analysis indicates that V_0Gy depends on both the mean dose and the total treatment time, which explains the large variations observed among various modalities. Every 10s increase in treatment time leads to approximately 3% increase in V_0Gy. The opposite trend was found for V_0.5Gy and D_2%, both decreasing with increasing treatment time. V_0.5Gy and D_2% decrease approximately 0.6% and 0.01Gy for every 10s increase in treatment time, respectively. <h3>Conclusion</h3> We studied dose to CLs across 4 different treatment modalities and found that to minimize the fraction of CL irradiated, it might be more important to shorten the delivery time than to reduce the dose bath. Further investigation is required to find the dose levels most correlated to lymphocyte depletion to optimize delivery time and to design immune-sparing RT regimen.