Proton Radiation Is Associated With Reduced Lymphocyte-Depleting Blood Volume In Glioblastoma Treatment

Abstract

Severe lymphopenia in glioblastoma (GBM) treatment is associated with worse clinical outcomes. Although temozolomide can contribute, lymphopenia is associated with radiotherapy alone potentially due to irradiation of lymphocytes in circulating blood which travel through the treatment volume. Previous data has shown that the D90, D50, and D10 for surviving lymphocyte fraction to be as low as 0.5, 2, and 3 Gy respectively. This suggests that the smaller low-dose volume treated with pencil beam scanning protons (PBS) may provide a significant dosimetric advantage over photon volumetric arc therapy (VMAT) in reducing lymphopenia. No prior studies have compared dosimetric parameters between treatment modalities for these low lymphotoxic doses in this context. We hypothesize that PBS will induce less lymphopenia than VMAT. Here, we calculate and compare the amount of blood volume receiving 0.5, 2, and 3 Gy of radiation for GBM using VMAT and PBS planning. 8 patients with resected WHO Grade IV GBM had comparative plans generated with VMAT and PBS treatment. These 8 tumors were selected to represent the wide range of tumor size and location for GBMs. Treatment planning utilized post-operative MRI, and the PTV was prescribed 60 Gy (RBE) in 2 Gy per fraction using VMAT and PBS. Robust optimization was utilized for PBS planning. The volume of blood receiving 0.5, 2, and 3 Gy were calculated for each plan and compared. The tumor characteristics are listed in table 1. The median brain volumes (cc) receiving 0.5, 2, and 3 Gy for PBS were significantly smaller than those for VMAT, respectively: V0.5Gy: 324.1 vs 1378.6; V2Gy: 263.6 vs 1123.6; and V3Gy: 247.5 vs 1040.9 (p<0.05). The treatment times for PBS and VMAT treatments did not significantly differ (p = 0.92). The median blood volume (cc) receiving 0.5, 2, and 3 Gy for PBS were also significantly smaller than those for VMAT, respectively: V0.5Gy: 260.5 vs 670.5; V2Gy: 212.3 vs 573.7; and V3Gy 200.4vs 528.8 (p<0.05). On average, VMAT therapy irradiated a factor of 3.35, 3.45, and 3.46 times more blood compared with PBS, respectively, at 0.5, 2, and 3 Gy. To our knowledge, this is the first study in GBM that compared VMAT and PBS dosimetry for blood volumes irradiated at known lymphotoxic doses. In our series, which intentionally included a broad range of tumor sizes and locations, an average of ∼3.4-fold greater total blood volume will have received 0.5- 3 Gy with VMAT than with PBS. We hypothesize that PBS may therefore demonstrate a treatment advantage for GBM, and prospective studies are warranted to further investigate these findings.Abstract 3601; TablePatient #Tumor size: Large (L) (>3 cm) vs Small (S) (≤3 cm)Tumor Location: Central (C) (<2 cm from falx) vs Peripheral (P) (≥2 cm from falx)1LC2SP3LP4LP5LP6LC7LC8SP Open table in a new tab