3329 - TWO- vs. Five-fraction Magnetic Resonance-Guided Adaptive Radiotherapy with DOminant-TArgeted Boost in Localized Prostate Cancer (DOTA-2) by MR-Linac: Interim Analysis of Circulating Lymphocyte Change in a Phase II Randomized Trial

Purpose/Objective(s): The “DOTA-2” trial is a single-center, phase II randomized controlled study evaluating two stereotactic body radiotherapy (SBRT) regimens for prostate cancer, comparing a 26 Gy/2F regimen with a dominant intraprostatic lesion (DIL) boost to 32 Gy against a 36.25 Gy/5F regimen with a DIL boost to 40 Gy, both administered without androgen deprivation therapy (ADT). An interim analysis was conducted to assess changes in circulating lymphocytes.

Materials/Methods: Patients with low- to favorable intermediate-risk prostate cancer were randomly assigned in a 1:1 ratio to receive either two fractions over eight days or five fractions over 10–11 days. Each fraction was administered using MR-guided adaptive radiotherapy (MRgART) on the Unity® MR-Linac, utilizing the Adapt-to-Shape (ATS) workflow. An interim analysis was conducted to evaluate changes in circulating lymphocytes, including CD4, CD8, and NK cells, between treatment arms in the first 22 patients out of the planned total of 44. Lymphocyte levels were assessed at Day 0, Day 8, and at months 1, 3, and 6 of follow-up.

Results: A total of 22 patients were randomly assigned to receive either 2-fraction (n=10) or 5-fraction (n=12) SBRT, with stratification based on risk group, prostate volume, and DIL location. The median age was 73.2 years. Among the participants, 82% had NCCN favorable intermediate-risk prostate cancer, while 18% were classified as low-risk. The median follow-up duration was 16 weeks.The mean CD4 levels at Day 0 in the 2-fraction (2F) and 5-fraction (5F) arms were 632.0 cells/µL and 641.3 cells/µL, respectively. During follow-up, CD4 levels decreased until month 6, with a mean reduction of 82.8 cells/µL (13.1%) in the 2F arm and 210.3 cells/µL (32.8%) in the 5F arm, showing statistical significance (p=0.026). For CD8, the levels reached a nadir at month 1 and tended to increase at months 3 and 6, without a significant difference in trends between the two groups (p=0.804). A similar trend was observed for NK cells in the 5F arm, with the nadir at month 1. However, in the 2F arm, NK cell levels showed a continuous decline, with a mean decrease of 148.0 cells/µL (21%). Despite these differences, there was no statistically significant difference in NK cell trends between the two arms (p=0.126).

Conclusion: Two-fraction SBRT with a DIL boost, delivered by MRgART without ADT, showed a trend toward preserving circulating lymphocyte after treatment in this interim analysis. However, mature data with a longer follow-up period and a larger cohort are needed to warrant this finding.