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 Mat...

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Main Authors: Daniel F. Polan, PhD, Justin K. Mikell, PhD, Kellen Fitzpatrick, MS, Joseph J. Gemmete, MD, Jared A. Christensen, MD, Hassan Anbari, MD, Molly Roseland, MD, Joseph R. Evans, MD, PhD, Daniel T. Chang, MD, Mamadou Sanogo, MD, Baljendra S. Kapoor, MD, Matthew J. Schipper, PhD, Yue Cao, PhD, Madhava P. Aryal, Theodore S. Lawrence, MD, PhD, Kyle C. Cuneo, MD, Yuni K. Dewaraja, PhD
Format: Article
Language:English
Published: Elsevier 2025-07-01
Series:Advances in Radiation Oncology
Online Access:http://www.sciencedirect.com/science/article/pii/S2452109425000314
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author Daniel F. Polan, PhD
Justin K. Mikell, PhD
Kellen Fitzpatrick, MS
Joseph J. Gemmete, MD
Jared A. Christensen, MD
Hassan Anbari, MD
Molly Roseland, MD
Joseph R. Evans, MD, PhD
Daniel T. Chang, MD
Mamadou Sanogo, MD
Baljendra S. Kapoor, MD
Matthew J. Schipper, PhD
Yue Cao, PhD
Madhava P. Aryal
Theodore S. Lawrence, MD, PhD
Kyle C. Cuneo, MD
Yuni K. Dewaraja, PhD
author_facet Daniel F. Polan, PhD
Justin K. Mikell, PhD
Kellen Fitzpatrick, MS
Joseph J. Gemmete, MD
Jared A. Christensen, MD
Hassan Anbari, MD
Molly Roseland, MD
Joseph R. Evans, MD, PhD
Daniel T. Chang, MD
Mamadou Sanogo, MD
Baljendra S. Kapoor, MD
Matthew J. Schipper, PhD
Yue Cao, PhD
Madhava P. Aryal
Theodore S. Lawrence, MD, PhD
Kyle C. Cuneo, MD
Yuni K. Dewaraja, PhD
author_sort Daniel F. Polan, PhD
collection DOAJ
description 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.
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spelling doaj-art-0fc59eb18b204b28b75f1f0c5d1599fb2025-08-20T03:48:18ZengElsevierAdvances in Radiation Oncology2452-10942025-07-0110710174310.1016/j.adro.2025.101743Sequential 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 StudyDaniel F. Polan, PhD0Justin K. Mikell, PhD1Kellen Fitzpatrick, MS2Joseph J. Gemmete, MD3Jared A. Christensen, MD4Hassan Anbari, MD5Molly Roseland, MD6Joseph R. Evans, MD, PhD7Daniel T. Chang, MD8Mamadou Sanogo, MD9Baljendra S. Kapoor, MD10Matthew J. Schipper, PhD11Yue Cao, PhD12Madhava P. Aryal13Theodore S. Lawrence, MD, PhD14Kyle C. Cuneo, MD15Yuni K. Dewaraja, PhD16Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan; Corresponding author: Daniel F. Polan, PhDDepartment of Radiation Oncology, Washington University in St. Louis, St. Louis, MissouriDepartment of Radiology, University of Michigan, Ann Arbor, MichiganDepartment of Radiology, University of Michigan, Ann Arbor, MichiganDepartment of Radiology, University of Michigan, Ann Arbor, MichiganDepartment of Radiology, University of Michigan, Ann Arbor, MichiganDepartment of Radiology, University of Michigan, Ann Arbor, MichiganDepartment of Radiation Oncology, University of Michigan, Ann Arbor, MichiganDepartment of Radiation Oncology, University of Michigan, Ann Arbor, MichiganDepartment of Radiology, University of Michigan, Ann Arbor, MichiganDepartment of Radiology, University of Michigan, Ann Arbor, MichiganDepartment of Radiation Oncology, University of Michigan, Ann Arbor, MichiganDepartment of Radiation Oncology, University of Michigan, Ann Arbor, Michigan; Department of Radiology, University of Michigan, Ann Arbor, Michigan; Department of Biomedical Engineering, University of Michigan, Ann Arbor, MichiganDepartment of Radiation Oncology, University of Michigan, Ann Arbor, MichiganDepartment of Radiation Oncology, University of Michigan, Ann Arbor, MichiganDepartment of Radiation Oncology, University of Michigan, Ann Arbor, MichiganDepartment of Radiology, University of Michigan, Ann Arbor, MichiganPurpose: 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.http://www.sciencedirect.com/science/article/pii/S2452109425000314
spellingShingle Daniel F. Polan, PhD
Justin K. Mikell, PhD
Kellen Fitzpatrick, MS
Joseph J. Gemmete, MD
Jared A. Christensen, MD
Hassan Anbari, MD
Molly Roseland, MD
Joseph R. Evans, MD, PhD
Daniel T. Chang, MD
Mamadou Sanogo, MD
Baljendra S. Kapoor, MD
Matthew J. Schipper, PhD
Yue Cao, PhD
Madhava P. Aryal
Theodore S. Lawrence, MD, PhD
Kyle C. Cuneo, MD
Yuni K. Dewaraja, PhD
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
Advances in Radiation Oncology
title 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
title_full 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
title_fullStr 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
title_full_unstemmed 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
title_short 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
title_sort 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
url http://www.sciencedirect.com/science/article/pii/S2452109425000314
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