Primary unresectable liver cancer:
Hepatocellular Carcinoma (HCC):
Purpose: The feasibility of Holmium-166 SIRT for the treatment of HCC has been evaluated in a retrospective study in 9 patients1 (BCLC B & C).
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Results:
Response at 2 and 6 months after Holmium-166 SIRT (based on CT/MR)
At 6 months:
Tumor Response (CR + PR) = 60%
Disease control rate (CR + PR + SD) at 6 months: 90%
No death occurred within 2 months after treatment.
The overall toxicity was low with no observed major complications (CTCAE grade 3-5).
Conclusion:
HEPAR PRIMARY2:
Patients: 30 primary HCC patients with liver dominant disease
Inclusion Criteria: Child-Pugh ≤ B7, ECOG ≤ 1, unresectable, no curative surgery before, transplant or RFA possible, BCLC B, but involvement of left or right portal vein branches is acceptable.
Primary objective: To establish the safety and toxicity profile of QuiremSpheres® in patients with HCC
Secondary objectives:
To evaluate mRECIST response to QuiremSpheres®
To evaluate tumour markers, QoL, bio-distribution and dosimetry
Enrolment Status: Completed Expected Completion: 2021 NCT03379844
HORA EST HCC:
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Dr. Mark C. Burgmans, UMC Leiden, Belgium
Sites enrolling: Leiden UMC, Netherlands; Amsterdam Medical Centre
Patients: 20, early stage HCC
This is a dose-finding study, where patients receive Radiofrequency thermal ablation and adjuvant segmental Holmium-166 SIRT (QuiremSpheres®).
Purpose: Combining radiofrequency ablation with adjuvant Ho-166 SIRT in HCC patients (1-3 HCC lesions)
Primary objective: Treatment area dose that will result in delivery of a radiation absorbed dose of ≥ 120Gy to the target area in at least 90% of patients. Holmium-6 SIRT, when
Secondary Objectives:
Enrolment Status: Ongoing
Expected Completion: 2021
Metastatic unresectable liver cancer
The safety and efficacy of
166Holmium-SIRT in the treatment of liver metastases has been evaluated in HEPAR I (phase I) and HEPAR II (phase II) studies and retrospectively analysed to establish dose-response thresholds.
HEPAR I4:
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Phase I -Dose Escalation Study, recruited 15 patients with different liver metastases from various primary tumors (Ocular melanoma, colorectal cancer, cholangiocarcinoma, breast cancer)
Purpose: Primary endpoint: Determination of Maximum Tolerated Radiation Dose (MTRD)
Results:
Conclusion: Holmium-166 SIRT is safe and technically effective for the treatment of patients with unresectable and chemo-refractory liver metastases with an aimed total liver dose of 60Gy.
HEPAR II5:
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Purpose:
Safety & efficacy evaluation of Holmium-166 SIRT
Phase II study in 37 patients with metastases from different primaries
23 of these patients had metastatic CRC
Primary Endpoint: Tumor Response at 3 months (RECIST 1.1)
Results:
Time to liver specific progression was 3 months
Median overall survival was 14.5 months
Median overall survival for mCRC patients was 13.4 months
Conclusion:
The Dose-effect relationships6 of 166Holmium radioembolization:
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Purpose: to explore the relation between dose and effect of
166Holmium radioembolization in mCRC patients, treated in HEPAR II & SIM-Study.
Patients: n= 44, mCRC patients
Results:
Mean tumor-absorbed dose was 84% higher in patients with CR/ PR than in patients with PD.
Survival for patients with a mean tumour-absorbed dose >90 Gy was significantly longer than for patients with mean tumour-absorbed dose < 90 Gy.
Conclusion: Personalized dosimetry for mean tumour-absorbed dose of > 90 Gy and parenchymal dose < 55 Gy
Neuroendocrine metastases (mNET):
HEPAR PLUS7
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Purpose: to evaluated the safety and technical efficacy of 166Holmium-SIRT as adjunct treatment after systemic
177Lu-dotatate in 30 patients with mNET. Prospective, single arm study.
Design:
Patients: 40% of the patients were NET G1 and 60% were NET G2. 80% of these had extra-hepatic disease and 57% received treatment the whole liver in one session.
Results:
The toxicity profile is comparable to literature, mainly grade 1-2 abdominal pain, fatigue and nausea.
The overall toxicity was low: CTCAE v 4.03 grade 3 - 4 with one fatal REILD, while the QoL recovered at 3 months.
Conclusion: Additional embolization with Holmium-166 is effective and safe in the treatment of bulky liver disease after PRRT
Holmium-166 scout dose (QuiremScout® Microspheres):
The safety and performance of the use of
166Holmium as Scout Dose in comparison to 99mTc-MAA has been evaluated in different studies,8,9,10 concluding that:
250 MBq is safe to use prior to SIRT as an alternative to
99mTc-MAA with superior predictive value in estimating the lung shunt in patients with primary and secondary liver tumors8
QuiremScout® showed to be safe in all the patients with extrahepatic depositions9Publication
QuiremScout® could lead to more reliable pre-treatment imaging and subsequently to improved individualized treatment planning due to the identical morphology of the microspheres9
QuiremScout® is more accurate than the commonly used surrogate
99mTc-MAA in predicting lung shunting8 and intrahepatic distribution.9
Qualitative and quantitative analysis of the intrahepatic distribution demonstrated significant better agreement between
166Ho Scout and 166Ho treatment versus 99mTc-MAA.10
99mTc-MAA could lead to unnecessary patient exclusion from SIRT and/ or under-dosing of tumor due to overestimation of lung shunt and other off-target tissue embolization.
10Publication
References:
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Radosa et al. Cardiovasc Intervent Radiol. 2019
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https://www.clinicaltrials.gov/ct2/show/NCT03379844?term=HEPAR+Primary&draw=2&rank=1
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https://www.clinicaltrials.gov/ct2/show/NCT03437382?term=HORA+EST&draw=2&rank=1
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Smits MLJ et al., Lancet Oncol, 2012; 13: 1025–34
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Prince JF et al., J Nucl Med., 2018; 59:582-588
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v Roekel. et al. J Nucl Med., June 26 2020
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Braat A. et al Lancet Oncol 2020; 26
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Elschot, M. et al. Eur. J. Nucl. Med. Mol. Imaging 2014
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Braat AJAT et al. Eur Radiol 2017; 28:920-928
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Smits et al. European Journal of Nuclear Medicine and Molecular Imaging - 2019