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Dose-effect relationships of holmium-166 radioembolization in colorectal cancer.
J Nucl Med. 2020 Jun 26 [Online ahead of print]JN

Abstract

INTRODUCTION:

Radioembolization is a treatment option for colorectal cancer (CRC) patients with inoperable, chemorefractory hepatic metastases. Personalized treatment requires established dose thresholds. Hence, the aim of this study was to explore the relation between dose and effect (i.e. response and toxicity) in CRC patients treated with holmium-166 (166Ho) radioembolization.

MATERIALS AND METHODS:

CRC patients treated in the HEPAR II and SIM studies were analyzed. Absorbed doses were estimated using the activity distribution on post-treatment 166Ho-SPECT/CT. Metabolic response was assessed using the change in total lesion glycolysis on 18FDG-PET/CT between baseline and three-months follow-up. Toxicity between treatment and three months was evaluated according to the Common Terminology Criteria for Adverse Events (CTCAE) version 5, and its relation with parenchymal-absorbed dose was assessed using linear models. The relation between tumor-absorbed dose and patient- and tumor-level response was analyzed using linear mixed-models. Using a threshold of 100% sensitivity for response, the threshold for a minimal mean tumor-absorbed dose was determined and its impact on survival was assessed.

RESULTS:

Forty patients were included. The median parenchymal-absorbed dose was 37 Gy (range 12-55 Gy). New CTCAE grade ≥3 clinical and laboratory toxicity were present in eight and seven patients, respectively. For any clinical toxicity (highest grade per patient), the mean difference in parenchymal dose (Gy) per step increase in CTCAE grade category was 5.75 (95% confidence interval (CI) 1.18-10.32). On a patient level, metabolic response was: complete response (CR) n = 1, partial response (PR) n = 11, stable disease (StD) n = 17 and progressive disease (PD) n = 8. The mean tumor-absorbed dose was 84% higher in patients with CR/PR than in patients with PD (95%CI: 20-180%). Survival for patients with a mean tumor-absorbed dose >90 Gy was significantly better than for patients with a mean tumor-absorbed dose <90 Gy (hazard ratio=0.16, 95%CI 0.06-0.511).

CONCLUSION:

A significant dose-response relationship in CRC patients treated with 166Ho-radioembolization was established and a positive association between toxicity and parenchymal dose was found. For future patients, it is advocated to use 166Ho-scout to select patients and personalize the administered activity targeting a mean tumor-absorbed dose of >90 Gy and a parenchymal dose <55 Gy.

Authors+Show Affiliations

University Medical Center Utrecht, Netherlands.University Medical Center Utrecht, Netherlands.University Medical Center Utrecht, Netherlands.University Medical Center Utrecht, Netherlands.University Medical Center Utrecht, Netherlands.University Medical Center Utrecht, Netherlands.Julius Center for Health Sciences and Primary Care, Netherlands.University Medical Center Utrecht, Netherlands.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

32591491

Citation

van Roekel, Caren, et al. "Dose-effect Relationships of Holmium-166 Radioembolization in Colorectal Cancer." Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine, 2020.
van Roekel C, Bastiaannet R, Smits MLJ, et al. Dose-effect relationships of holmium-166 radioembolization in colorectal cancer. J Nucl Med. 2020.
van Roekel, C., Bastiaannet, R., Smits, M. L. J., Bruijnen, R. C., Braat, A. J. A. T., de Jong, H. W. A. M., Elias, S. G., & Lam, M. G. E. H. (2020). Dose-effect relationships of holmium-166 radioembolization in colorectal cancer. Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine. https://doi.org/10.2967/jnumed.120.243832
van Roekel C, et al. Dose-effect Relationships of Holmium-166 Radioembolization in Colorectal Cancer. J Nucl Med. 2020 Jun 26; PubMed PMID: 32591491.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Dose-effect relationships of holmium-166 radioembolization in colorectal cancer. AU - van Roekel,Caren, AU - Bastiaannet,Remco, AU - Smits,Maarten L J, AU - Bruijnen,Rutger C, AU - Braat,Arthur Johannes Anthonius Theodorus, AU - de Jong,Hugo W A M, AU - Elias,Sjoerd G, AU - Lam,Marnix G E H, Y1 - 2020/06/26/ PY - 2020/02/21/received PY - 2020/05/27/accepted PY - 2020/6/28/entrez KW - Oncology: Liver KW - Radiobiology/Dosimetry KW - Radionuclide Therapy KW - dosimetry KW - holmium KW - radioembolization JF - Journal of nuclear medicine : official publication, Society of Nuclear Medicine JO - J. Nucl. Med. N2 - INTRODUCTION: Radioembolization is a treatment option for colorectal cancer (CRC) patients with inoperable, chemorefractory hepatic metastases. Personalized treatment requires established dose thresholds. Hence, the aim of this study was to explore the relation between dose and effect (i.e. response and toxicity) in CRC patients treated with holmium-166 (166Ho) radioembolization. MATERIALS AND METHODS: CRC patients treated in the HEPAR II and SIM studies were analyzed. Absorbed doses were estimated using the activity distribution on post-treatment 166Ho-SPECT/CT. Metabolic response was assessed using the change in total lesion glycolysis on 18FDG-PET/CT between baseline and three-months follow-up. Toxicity between treatment and three months was evaluated according to the Common Terminology Criteria for Adverse Events (CTCAE) version 5, and its relation with parenchymal-absorbed dose was assessed using linear models. The relation between tumor-absorbed dose and patient- and tumor-level response was analyzed using linear mixed-models. Using a threshold of 100% sensitivity for response, the threshold for a minimal mean tumor-absorbed dose was determined and its impact on survival was assessed. RESULTS: Forty patients were included. The median parenchymal-absorbed dose was 37 Gy (range 12-55 Gy). New CTCAE grade ≥3 clinical and laboratory toxicity were present in eight and seven patients, respectively. For any clinical toxicity (highest grade per patient), the mean difference in parenchymal dose (Gy) per step increase in CTCAE grade category was 5.75 (95% confidence interval (CI) 1.18-10.32). On a patient level, metabolic response was: complete response (CR) n = 1, partial response (PR) n = 11, stable disease (StD) n = 17 and progressive disease (PD) n = 8. The mean tumor-absorbed dose was 84% higher in patients with CR/PR than in patients with PD (95%CI: 20-180%). Survival for patients with a mean tumor-absorbed dose >90 Gy was significantly better than for patients with a mean tumor-absorbed dose <90 Gy (hazard ratio=0.16, 95%CI 0.06-0.511). CONCLUSION: A significant dose-response relationship in CRC patients treated with 166Ho-radioembolization was established and a positive association between toxicity and parenchymal dose was found. For future patients, it is advocated to use 166Ho-scout to select patients and personalize the administered activity targeting a mean tumor-absorbed dose of >90 Gy and a parenchymal dose <55 Gy. SN - 1535-5667 UR - https://www.unboundmedicine.com/medline/citation/32591491/Dose-effect_relationships_of_holmium-166_radioembolization_in_colorectal_cancer L2 - http://jnm.snmjournals.org/cgi/pmidlookup?view=long&amp;pmid=32591491 DB - PRIME DP - Unbound Medicine ER -
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