Abstract
2017 Background: Severe treatment-related lymphopenia (TRL) occurs in 40% of glioblastoma patients despite minimal radiation (RT) doses to bone marrow or nodal sites. In glioblastoma, TRL is associated with decreased survival. To explain the lymphopenia, we sought to estimate radiation doses received by circulating lymphocytes during partial brain RT. Methods: An in-house computer program linked to treatment planning software was used to calculate the mean radiation dose to circulating blood (DCB) and the fraction of blood receiving >0.5 Gy. The model also studied the impact of different target volumes (PTV), dose rates (DR), and delivery techniques (IMRT, 3D-CRT). Results: The mean DCB for a 60-Gy course (8-cm diameter PTV, dose rate 600 MU/minute) was 2.2 Gy. With this the entire blood pool receives a lymphotoxic dose of >0.5 Gy. DCB is correlated with fraction number, PTV size, and DR. Regardless of dose rate or delivery technique, the percent of circulating blood receiving >0.5 Gy approached 100% as the number of fractions increased. Changing dose rate had minimal effects on mean DCB (3.1Gy for 300 MU/min vs 2.2 Gy for 1200 MU/min). Smaller PTV size reduced the percent of blood receiving >0.5 Gy (15% for 2-cm diameter PTV vs 100% for 8-cm PTV). Conclusions: Standard RT for brain tumors delivers a lymphotoxic radiation dose to circulating blood. Altering dose rate may initially affect DCB, but advantages disappear over the course of 30 fractions. Marked reductions in target size appear to be the best way to avoid radiation injury to normal circulating lymphocytes. Other novel approaches are needed to limit radiation exposure to circulating lymphocytes given evidence associating lymphopenia with poorer outcomes in cancer patients.
Published Version
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