Phase I Dose-Escalation Study Combining Irinotecan-Loaded Drug-Eluting Bead Chemoembolization with Yttrium-90 Glass Microspheres Radioembolization in Colorectal Liver Metastases (DEBIR90Y)

Li Shen Ho; Ahmed Alsultan; Maarten L J Smits; Miriam Koopman; Rutger Bruijnen; Arthur J A T Braat; Kirk D Fowers; Matthew R Dreher; Guus M Bol; Marnix G E H Lam

doi:10.1016/j.jvir.2026.108960

Phase I Dose-Escalation Study Combining Irinotecan-Loaded Drug-Eluting Bead Chemoembolization with Yttrium-90 Glass Microspheres Radioembolization in Colorectal Liver Metastases (DEBIR90Y)

Li Shen Ho^*
, Ahmed Alsultan
, Maarten L J Smits
, Miriam Koopman
, Rutger Bruijnen
, Arthur J A T Braat
, Kirk D Fowers
, Matthew R Dreher
, Guus M Bol
, Marnix G E H Lam

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

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Abstract

Purpose: To find the maximum tolerated dose (MTD) of yttrium-90 (⁹⁰Y) glass microspheres, with drug-eluting beads preloaded with irinotecan (DEBIRI) in patients with colorectal liver metastases (CRLMs). Materials and Methods: In this prospective study, participants with bilobar, unresectable, liver-dominant CRLM progressing after first-line systemic therapy received sequential bilobar ⁹⁰Y glass microsphere radioembolization at increasing dose levels (60-Gy, 80-Gy, and 100-Gy perfused normal liver absorbed doses), followed by DEBIRI, using a 3 + 3 dose-escalation design. The primary endpoint was MTD determination. Secondary endpoints included objective response rate (ORR) by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 and Positron Emission Tomography Response Criteria in Solid Tumors (PERCIST), (serious) adverse events ([S]AEs), carcinoembryonic antigen (CEA) response, conversion to resection, and overall survival. Descriptive statistics and independent t-tests were applied. Results: Twelve participants were enrolled. One dose-limiting toxicity (DLT; possible treatment-related fatal liver failure) occurred in the 80-Gy cohort, with no additional DLTs after cohort expansion (n = 6). At 100 Gy, 2 additional DLTs (probable and possible treatment-related fatal liver failure) occurred, establishing 80 Gy as the MTD when combined with full-dose DEBIRI. Eighty treatment-related (S)AEs occurred, most commonly increased gamma-glutamyl transferase (12/12, Grades 1–3) and abdominal pain (10/12, Grades 1–2). ORRs were 9% (RECIST) and 18% (PERCIST). Index lesion response rates were 20% (RECIST) and 35% (PERCIST). CEA response occurred in 42%. Conclusions: In this Phase I study in patients with liver-dominant colorectal metastases, receiving a combination of ⁹⁰Y radioembolization with DEBIRI combined with DEBIRI, the MTD was 80 Gy. Considerable treatment-related toxicity was observed, and ORRs were limited.

Original language	English
Article number	108960
Journal	Journal of Vascular and Interventional Radiology
Volume	37
Issue number	10
Early online date	16 Jul 2026
DOIs	https://doi.org/10.1016/j.jvir.2026.108960
Publication status	Published - Oct 2026

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PIIS1051044326009711Final published version, 1.01 MBLicence: CC BY

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Ho, L. S., Alsultan, A., Smits, M. L. J., Koopman, M., Bruijnen, R., Braat, A. J. A. T., Fowers, K. D., Dreher, M. R., Bol, G. M., & Lam, M. G. E. H. (2026). Phase I Dose-Escalation Study Combining Irinotecan-Loaded Drug-Eluting Bead Chemoembolization with Yttrium-90 Glass Microspheres Radioembolization in Colorectal Liver Metastases (DEBIR90Y). Journal of Vascular and Interventional Radiology, 37(10), Article 108960. https://doi.org/10.1016/j.jvir.2026.108960

@article{d10d5fcd3d9a482cb61707af15e18849,

title = "Phase I Dose-Escalation Study Combining Irinotecan-Loaded Drug-Eluting Bead Chemoembolization with Yttrium-90 Glass Microspheres Radioembolization in Colorectal Liver Metastases (DEBIR90Y)",

abstract = "Purpose: To find the maximum tolerated dose (MTD) of yttrium-90 (90Y) glass microspheres, with drug-eluting beads preloaded with irinotecan (DEBIRI) in patients with colorectal liver metastases (CRLMs). Materials and Methods: In this prospective study, participants with bilobar, unresectable, liver-dominant CRLM progressing after first-line systemic therapy received sequential bilobar 90Y glass microsphere radioembolization at increasing dose levels (60-Gy, 80-Gy, and 100-Gy perfused normal liver absorbed doses), followed by DEBIRI, using a 3 + 3 dose-escalation design. The primary endpoint was MTD determination. Secondary endpoints included objective response rate (ORR) by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 and Positron Emission Tomography Response Criteria in Solid Tumors (PERCIST), (serious) adverse events ([S]AEs), carcinoembryonic antigen (CEA) response, conversion to resection, and overall survival. Descriptive statistics and independent t-tests were applied. Results: Twelve participants were enrolled. One dose-limiting toxicity (DLT; possible treatment-related fatal liver failure) occurred in the 80-Gy cohort, with no additional DLTs after cohort expansion (n = 6). At 100 Gy, 2 additional DLTs (probable and possible treatment-related fatal liver failure) occurred, establishing 80 Gy as the MTD when combined with full-dose DEBIRI. Eighty treatment-related (S)AEs occurred, most commonly increased gamma-glutamyl transferase (12/12, Grades 1{\textendash}3) and abdominal pain (10/12, Grades 1{\textendash}2). ORRs were 9\% (RECIST) and 18\% (PERCIST). Index lesion response rates were 20\% (RECIST) and 35\% (PERCIST). CEA response occurred in 42\%. Conclusions: In this Phase I study in patients with liver-dominant colorectal metastases, receiving a combination of 90Y radioembolization with DEBIRI combined with DEBIRI, the MTD was 80 Gy. Considerable treatment-related toxicity was observed, and ORRs were limited.",

author = "Ho, \{Li Shen\} and Ahmed Alsultan and Smits, \{Maarten L J\} and Miriam Koopman and Rutger Bruijnen and Braat, \{Arthur J A T\} and Fowers, \{Kirk D\} and Dreher, \{Matthew R\} and Bol, \{Guus M\} and Lam, \{Marnix G E H\}",

note = "Publisher Copyright: {\textcopyright} 2026 SIR",

year = "2026",

month = oct,

doi = "10.1016/j.jvir.2026.108960",

language = "English",

volume = "37",

journal = "Journal of Vascular and Interventional Radiology",

issn = "1051-0443",

publisher = "Elsevier",

number = "10",

}

Ho, LS, Alsultan, A, Smits, MLJ , Koopman, M, Bruijnen, R, Braat, AJAT, Fowers, KD, Dreher, MR, Bol, GM & Lam, MGEH 2026, 'Phase I Dose-Escalation Study Combining Irinotecan-Loaded Drug-Eluting Bead Chemoembolization with Yttrium-90 Glass Microspheres Radioembolization in Colorectal Liver Metastases (DEBIR90Y)', Journal of Vascular and Interventional Radiology, vol. 37, no. 10, 108960. https://doi.org/10.1016/j.jvir.2026.108960

Phase I Dose-Escalation Study Combining Irinotecan-Loaded Drug-Eluting Bead Chemoembolization with Yttrium-90 Glass Microspheres Radioembolization in Colorectal Liver Metastases (DEBIR90Y). / Ho, Li Shen; Alsultan, Ahmed; Smits, Maarten L J et al.
In: Journal of Vascular and Interventional Radiology, Vol. 37, No. 10, 108960, 10.2026.

Research output: Contribution to journal › Article › Academic › peer-review

TY - JOUR

T1 - Phase I Dose-Escalation Study Combining Irinotecan-Loaded Drug-Eluting Bead Chemoembolization with Yttrium-90 Glass Microspheres Radioembolization in Colorectal Liver Metastases (DEBIR90Y)

AU - Ho, Li Shen

AU - Alsultan, Ahmed

AU - Smits, Maarten L J

AU - Koopman, Miriam

AU - Bruijnen, Rutger

AU - Braat, Arthur J A T

AU - Fowers, Kirk D

AU - Dreher, Matthew R

AU - Bol, Guus M

AU - Lam, Marnix G E H

PY - 2026/10

Y1 - 2026/10

N2 - Purpose: To find the maximum tolerated dose (MTD) of yttrium-90 (90Y) glass microspheres, with drug-eluting beads preloaded with irinotecan (DEBIRI) in patients with colorectal liver metastases (CRLMs). Materials and Methods: In this prospective study, participants with bilobar, unresectable, liver-dominant CRLM progressing after first-line systemic therapy received sequential bilobar 90Y glass microsphere radioembolization at increasing dose levels (60-Gy, 80-Gy, and 100-Gy perfused normal liver absorbed doses), followed by DEBIRI, using a 3 + 3 dose-escalation design. The primary endpoint was MTD determination. Secondary endpoints included objective response rate (ORR) by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 and Positron Emission Tomography Response Criteria in Solid Tumors (PERCIST), (serious) adverse events ([S]AEs), carcinoembryonic antigen (CEA) response, conversion to resection, and overall survival. Descriptive statistics and independent t-tests were applied. Results: Twelve participants were enrolled. One dose-limiting toxicity (DLT; possible treatment-related fatal liver failure) occurred in the 80-Gy cohort, with no additional DLTs after cohort expansion (n = 6). At 100 Gy, 2 additional DLTs (probable and possible treatment-related fatal liver failure) occurred, establishing 80 Gy as the MTD when combined with full-dose DEBIRI. Eighty treatment-related (S)AEs occurred, most commonly increased gamma-glutamyl transferase (12/12, Grades 1–3) and abdominal pain (10/12, Grades 1–2). ORRs were 9% (RECIST) and 18% (PERCIST). Index lesion response rates were 20% (RECIST) and 35% (PERCIST). CEA response occurred in 42%. Conclusions: In this Phase I study in patients with liver-dominant colorectal metastases, receiving a combination of 90Y radioembolization with DEBIRI combined with DEBIRI, the MTD was 80 Gy. Considerable treatment-related toxicity was observed, and ORRs were limited.

AB - Purpose: To find the maximum tolerated dose (MTD) of yttrium-90 (90Y) glass microspheres, with drug-eluting beads preloaded with irinotecan (DEBIRI) in patients with colorectal liver metastases (CRLMs). Materials and Methods: In this prospective study, participants with bilobar, unresectable, liver-dominant CRLM progressing after first-line systemic therapy received sequential bilobar 90Y glass microsphere radioembolization at increasing dose levels (60-Gy, 80-Gy, and 100-Gy perfused normal liver absorbed doses), followed by DEBIRI, using a 3 + 3 dose-escalation design. The primary endpoint was MTD determination. Secondary endpoints included objective response rate (ORR) by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 and Positron Emission Tomography Response Criteria in Solid Tumors (PERCIST), (serious) adverse events ([S]AEs), carcinoembryonic antigen (CEA) response, conversion to resection, and overall survival. Descriptive statistics and independent t-tests were applied. Results: Twelve participants were enrolled. One dose-limiting toxicity (DLT; possible treatment-related fatal liver failure) occurred in the 80-Gy cohort, with no additional DLTs after cohort expansion (n = 6). At 100 Gy, 2 additional DLTs (probable and possible treatment-related fatal liver failure) occurred, establishing 80 Gy as the MTD when combined with full-dose DEBIRI. Eighty treatment-related (S)AEs occurred, most commonly increased gamma-glutamyl transferase (12/12, Grades 1–3) and abdominal pain (10/12, Grades 1–2). ORRs were 9% (RECIST) and 18% (PERCIST). Index lesion response rates were 20% (RECIST) and 35% (PERCIST). CEA response occurred in 42%. Conclusions: In this Phase I study in patients with liver-dominant colorectal metastases, receiving a combination of 90Y radioembolization with DEBIRI combined with DEBIRI, the MTD was 80 Gy. Considerable treatment-related toxicity was observed, and ORRs were limited.

U2 - 10.1016/j.jvir.2026.108960

DO - 10.1016/j.jvir.2026.108960

M3 - Article

C2 - 42462844

SN - 1051-0443

VL - 37

JO - Journal of Vascular and Interventional Radiology

JF - Journal of Vascular and Interventional Radiology

IS - 10

M1 - 108960

ER -

Ho LS, Alsultan A, Smits MLJ , Koopman M, Bruijnen R, Braat AJAT et al. Phase I Dose-Escalation Study Combining Irinotecan-Loaded Drug-Eluting Bead Chemoembolization with Yttrium-90 Glass Microspheres Radioembolization in Colorectal Liver Metastases (DEBIR90Y). Journal of Vascular and Interventional Radiology. 2026 Oct;37(10):108960. Epub 2026 Jul 16. doi: 10.1016/j.jvir.2026.108960

Phase I Dose-Escalation Study Combining Irinotecan-Loaded Drug-Eluting Bead Chemoembolization with Yttrium-90 Glass Microspheres Radioembolization in Colorectal Liver Metastases (DEBIR90Y)

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