Offline-adaptive planning of mpMRI- and PSMA-PET- based dose escalation: results of a phase II trial
PD-0581
Abstract
Offline-adaptive planning of mpMRI- and PSMA-PET- based dose escalation: results of a phase II trial
Authors: Simon Spohn1,2,3, Mark Gainey4,2, Michael Mix5, Juri Ruf5, Matthias Benndorf6, Dimos Baltas4,2, Anca Grosu1,2, Constantinos Zamboglou1,2,3,7
1University Medical Center Freiburg, Department of Radiation Oncology, Freiburg, Germany; 2German Cancer Consortium (DKTK), Partner Site Freiburg, Freiburg, Germany; 3Faculty of Medicine - University of Freiburg, Berta-Ottenstein-Programme, Freiburg, Germany; 4University Medical Center Freiburg, Division of Medical Physics - Department of Radiation Oncology, Freiburg, Germany; 5University Medical Center Freiburg, Department of Nuclear Medicine, Freiburg, Germany; 6University Medical Center Freiburg, Department of Radiology, Freiburg, Germany; 7European University of Cyprus, German Oncology Center, Limassol, Cyprus
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Purpose or Objective
The arm A of the HypoFocal phase II trial aims to evaluate the safety of focal dose escalated external beam radiotherapy (EBRT) on combined positron emission tomography targeting prostate specific membrane antigen (PSMA-PET) and multiparametric magnet resonance tomography (mpMRI) defined boost volumes. This approach results in significantly lager boost volumes compared to the usually used mpMRI-only approach. Despite adherence to rectal dose constraints in the initial planning CT, interfractional differences of rectum filling might be particularly relevant for rectal dose metrics in this setting. To prevent increased gastrointestinal (GI) toxicities we developed an offline-adaptive planning strategy to account for various rectum fillings. Here we presents results as part of a planned safety analysis after 6 months.
Material and Methods
Patients treated in arm A of the HypoFocal phase II trial according to the offline-adaptive planning strategy were analyzed. Patients were treated with 60 Gy in 20 fractions to the prostate and up to 75 Gy to mpMRI- and PSMA-PET defined boost volumes. Dose constraints according to the CHHiP trial were applied. The 3D images acquired during the first three fractions were imported into the RT planning software. After manual co-registration with the planning CT, rectum was delineated in each 3D image (CBCTs) and contours were transferred to the planning CT. Based on the average rectum volume and position in CBCTs, a rectum_adapt volume was created. RT plans were re-evaluated considering the additional rectum contours. If ≥ 1 mandatory constraint was not met in more than 1 volume a re-planning with optimization on rectum_adapt was performed. GI toxicities were assessed according to CTCAE v5.0. Dose metrics were evaluated and association with GI toxicities analyzed with univariate binary logistic regression.
Results
23 of 25 patients in arm A were treated according to the adaptive planning strategy. Median boost volume was 10.2 ml (range 4-28). Median mean dose to the boost volume was 70 Gy. In 4 patients re-planning was performed. Median volumes receiving 60 Gy (V60) and V50 were significantly different between rectum and rectum_adapt, but not V40 and V30 (figure 1). Dose metrics were not significantly different between rectum and rectum based on 3D images (CBCT1-3). Cumulative grade 0, 1 and 2 GI toxicity at 6 months FU were 13%, 74% and 13%, respectively. Rectum V60, V50, and V40 but only rectum_adapt V40 were significantly associated with ≥ 2 GI toxicity (p=0.027-0.046).
Figure 1: median volumes and 95% CI of rectum in the initial planning CT, CBCTs of the first three fractions and rectum_adapt receiving 60-30 Gy (V60-30). * indicates p<0.05
Conclusion
Assessment of interfractional rectum filling led to adaptive planning in approx. 17% of patients. Dose distributions between rectum and rectum_adapt vary significantly in higher doses (V50 and 60). The clinical benefit of the proposed offline adaptive-planning strategy should be evaluated in larger cohorts.