2597 - Does Pulsed Low-Dose Rate Radiotherapy Reduce the Dose to Circulating Lymphocytes in Glioblastoma?

Purpose/Objective(s): Radiation-induced lymphopenia (RIL) has been associated with poor outcomes in radiation therapy for glioblastoma. Predicting the incidence of RIL for glioblastoma patients requires individualized dosimetry of circulating blood/lymphocytes. This study aims to develop a patient-specific dynamic blood dosimetry tool and address a clinical question: Does pulsed low dose rate (PLDR) (<6.7 cGy/minute) radiotherapy reduce the dose to circulating lymphocytes compared to the standard dose rate (600 MU/min) for glioblastoma?

Materials/Methods: Ten glioblastoma patients from the QIN-BRAIN-DSC-MRI dataset in the cancer imaging archive were included. The gross tumor volume ranged from 6.6 to 105.2 cc. Each patient was planned following the RTOG 0825 protocol, with a prescribed dose of 60 Gy in 30 fractions. Intensity-modulated radiation therapy (IMRT) with nine coplanar beams was used for all plans. For PLDR, beam MU rates were reduced to ensure the mean target dose rate was less than 6.7 cGy/minute. Blood motion was modeled for each patient using cerebral blood volume (CBV), cerebral blood flow (CBF), mean transit time (MTT), and time to peak (TTP) derived from dynamic susceptibility contrast MRI perfusion. A total of 20,000 blood particles were simulated and their motion during IMRT treatment was synchronized to dynamic dose delivery. The survival fraction (SF) of the circulating lymphocytes was computed using the dose distribution of blood particles and a linear survival model SF=exp(-alpha x dose) (alpha = 0.58/Gy).

Results: For ten patients, delivery time for standard dose rate and PLDR was 5.5 +/- 0.9 and 38.5 +/-3.0 minutes, respectively. The mean dose to circulating blood was 0.060 +/- 0.017 Gy and 0.061 +/-0.016 Gy in one fraction, and 1.801 +/- 0.496 Gy and 1.822+/-0.489 in 30 fractions for standard dose rate and PLDR, respectively. The mean blood dose was linearly proportional to the volume of PTV (0.005 Gy/cc of PTV volume, R²=0.938). PLDR reduced the variation in blood dose. For ten patients, the standard deviation of blood dose was 0.476 +/- 0.089 for standard dose rate and 0.239 +/- 0.067 Gy for PLDR, respectively. A more uniform blood dose results in a slightly higher lymphocyte kill. After 30 fractions, the survival fraction of lymphocytes was 0.378 +/- 0.102 for the standard dose rate and 0.363 +/- 0.103 for PLDR (p=0.05 for pair t-test). PLDR reduced lymphocyte survival fraction by 0.003-0.037 for the ten patients.

Conclusion: Patient-specific blood dosimetry is feasible with dynamic MRI and blood motion modeling. Pulsed low-dose rate radiotherapy delivers the same mean dose to circulating blood but results in slightly lower lymphocyte survival compared to the standard dose rate.