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 1 Study

Purpose

Selective internal radiation therapy (SIRT) can result in heterogeneous absorbed dose coverage. To address potential underdosing of lesions with SIRT, we designed a phase 1 clinical trial (NCT04518748) to add stereotactic body radiation therapy (SBRT) 6 weeks after ⁹⁰Y SIRT.

Methods and Materials

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 positron emission tomography/computed tomography to calculate mean lesion absorbed doses. Lesions were considered eligible for SBRT treatment if the mean absorbed dose was <290 Gy. In the presence of dose heterogeneity, SBRT gross tumor volumes were optionally limited to subvolumes 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 with the primary endpoint of an increase in Child-Pugh score of ≥2.

Results

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 and 50 Gy. Only 1 patient had a Child-Pugh increase of ≥2 at 6 months following SBRT, and only 1 grade 3 nonlaboratory toxicity was reported after SBRT.

Conclusions

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.