1072 - Sequential ⁹⁰Y Selective Internal Radiation Therapy (SIRT) and Stereotactic Body Radiation Therapy (SBRT) Using ⁹⁰Y PET-Based Absorbed Dose Maps: Interim Analysis of a Phase I St

D. Polan¹, J. Mikell², K. Fitzpatrick³, J. Gemmete³, J. Christensen³, H. Anbari³, M. Roseland³, J. R. Evans¹, D. T. Chang¹, M. Sanogo³, B. S. Kapoor³, M. Schipper¹, Y. Cao^1,4, M. P. Aryal¹, T. S. Lawrence¹, Y. Dewaraja³, and K. C. Cuneo¹; ¹Department of Radiation Oncology, University of Michigan, Ann Arbor, MI, ²Washington University School of Medicine in St. Louis, St. Louis, MO, ³Department of Radiology, University of Michigan, Ann Arbor, MI, ⁴Departments of Radiology and Biomedical Engineering, University of Michigan, Ann Arbor, MI

Purpose/Objective(s): The treatment of hepatic lesions with ⁹⁰Y selective internal radiation therapy (SIRT) can result in heterogeneous absorbed dose coverage due to hemodynamics and irregular tumor perfusion. To address potential underdosing associated with SIRT, we designed a Phase I clinical trial (NCT04518748) to assess the incremental toxicity of delivering stereotactic body radiation therapy (SBRT) 6 weeks after ⁹⁰Y SIRT. Materials/

Methods: In this ongoing, single-center prospective trial, patients received standard-of-care ⁹⁰Y SIRT with glass microspheres for the treatment of unresectable primary or secondary liver cancer. Post-SIRT dosimetry was performed using ⁹⁰Y PET/CT to calculate mean lesion absorbed doses. Lesions were considered eligible for SBRT treatment if the mean absorbed dose was less than 290 Gy. In the presence of dose heterogeneity, SBRT GTVs were optionally limited to subvolumes (voxels) based on a SIRT dose threshold determined from prior modeling. Interim analysis was prespecified after 10 participants received both SIRT and SBRT and completed 6 month follow up. The primary safety endpoint was an increase in Child Pugh (CP) score of 2 or more (early stopping criteria set at 6/10) following SBRT. Secondary safety endpoints included the occurrence of grade 3 or higher toxicity based on CTCAE v5.0 and change in albumin + bilirubin (ALBI) greater than 0.5.

Results: Between September 2020 and June 2023, a total of 31 patients were consented for the trial with 7 not proceeding with treatment. Of the 24 patients who received SIRT as part of the trial, 15 had lesions that were considered dosimetrically eligible for SBRT based on the criteria of 290 Gy mean absorbed dose from ⁹⁰Y. Of those, 10 patients received SBRT with prescription doses between 30–50 Gy. Application of the SIRT absorbed dose subvolume thresholding reduced anatomical SBRT target volumes by a median of 56%. Only one patient had a Child Pugh increase of 2 or more at 6 months following SBRT and only one grade 3 non-laboratory toxicity was reported after SBRT. Four new grade 3 laboratory toxicities were reported across two patients (1 aminotransferase, 1 alanine aminotransferase, 1 alkaline phosphatase, 2 total bilirubin). Four patients had an ALBI increase of greater than 0.5 following SBRT.

Conclusion: Interim analysis found that liver toxicity from ⁹⁰Y SIRT followed by SBRT was below the early stopping threshold and continuation of the study to complete recruitment of 30 evaluable patients was recommended.