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The Holmium Platform

30/10/2020 - Global

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). Publication

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: 

  • Holmium-166 SIRT seems to be a feasible option for the treatment of HCC with a good safety profile

  • Easy to perform Holmium-166 SIRT for physicians familiar with Y90 SIRT 


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:

Publication 

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:

  • Toxicity

  • Local tumor recurrence at 6 months

  • Time to progression

  • Progression-free survival

  • Quality of Life

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

Publication

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: 

  • MTRD was found to be 60 Gy

  • Disease control rate (PR+SD) in target lesions at 12 weeks was reported in 64% patients 



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

Publication

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: 

  • Radioembolization with QuiremSpheres® is technically effective, with an acceptable toxicity profile in the salvage treatment of patients with liver metastases


The Dose-effect relationships6 of 166Holmium radioembolization: 

Publication

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

Publication

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 received 4 cycles of PRRT (peptide receptor radionuclide therapy)

  • Followed by QuiremSpheres® administration to achieve local radiation boost 

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: 

  1.  Radosa et al. Cardiovasc Intervent Radiol. 2019 
  2. https://www.clinicaltrials.gov/ct2/show/NCT03379844?term=HEPAR+Primary&draw=2&rank=1 
  3. https://www.clinicaltrials.gov/ct2/show/NCT03437382?term=HORA+EST&draw=2&rank=1 
  4. Smits MLJ et al., Lancet Oncol, 2012; 13: 1025–34 
  5. Prince JF et al., J Nucl Med., 2018; 59:582-588 
  6. v Roekel. et al. J Nucl Med., June 26 2020 
  7. Braat A. et al Lancet Oncol 2020; 26 
  8. Elschot, M. et al. Eur. J. Nucl. Med. Mol. Imaging 2014 
  9. Braat AJAT et al. Eur Radiol 2017; 28:920-928 
  10. Smits et al. European Journal of Nuclear Medicine and Molecular Imaging - 2019