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Cited by 239Hepatocellular Carcinoma Treatment and PrognosisRadiopharmaceutical Chemistry and ApplicationsAdvanced Radiotherapy Techniques

Efficacy and Toxicity Related to Treatment of Hepatocellular Carcinoma with 90Y-SIR Spheres: Radiobiologic Considerations

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Strigari, Lidia, Sciuto, Rosa, Rea, Sandra, Carpanese, Livio, Pizzi, Giuseppe, Soriani, Antonella, Iaccarino, Giuseppe, Benassi, Marcello +2 more·2010·Journal of Nuclear Medicine
DOI 10.2967/jnumed.110.075861
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Abstract

UNLABELLED: Radioactive (90)Y-selective internal radiation (SIR) sphere therapy is increasingly used for the treatment of nonresectable hepatocellular carcinoma (HCC). However, the maximum delivered dose is limited by severe injury to the nontarget tissue, including liver parenchyma. Our study aimed to implement radiobiologic models for both tumor control probability (TCP) and normal-tissue complication probability (NTCP) to describe more effectively local response and the liver toxicity rate, respectively. METHODS: Patients with documented HCC, adequate bone marrow parameters, and regular hepatic and pulmonary function were eligible for the study. Patients who had pulmonary shunt greater than 20% of (99m)Tc-labeled macroaggregated albumin or any uncorrectable delivery to the gastrointestinal tract, reverse blood flow out of the liver, or complete portal vein thrombosis were excluded. Patients received a planned activity of the (90)Y-SIR spheres, determined using the empiric body surface area method. The dose distribution was determined using posttreatment (3-dimensional) activity distribution and Monte Carlo dose voxel kernel calculations, and the mean doses to healthy liver and tumor were calculated for each patient. Response was defined according to Response Evaluation Criteria in Solid Tumors (RECIST) and recommendations of the European Association for the Study of the Liver (EASL). Criteria were used to assess possible liver toxicities. The parameters of TCP and NTCP models were established by direct maximization of the likelihood. RESULTS: Seventy-three patients were treated. With an average dose of 110 Gy to the tumor, complete or partial response was observed in 74% and 55% of patients according to the EASL guideline and RECIST, respectively, and the predicted TCPs were 73% and 55%, respectively. With a median liver dose of 36 Gy (range, 6-78 Gy), the >or=grade 2 (G2), >or=grade 3 (G3), and >or=grade 4 (G4) liver toxicities were observed in 32% (23/73), 21% (15/73), and 11% (8/73) of patients, respectively. The parameters describing the >or=G2 liver toxicity data using the NTCP model were a tolerance dose of the whole organ leading to a 50% complication probability of 52 Gy (95% confidence interval, 44-61 Gy) and a slope of NTCP versus dose of 0.28 (95% confidence interval, 0.18-0.60), assuming n = 1. CONCLUSION: The radiobiologic approach, based on patient-specific dosimetry, could improve the (90)Y-microsphere therapeutic approach of HCC, maintaining an acceptable liver toxicity.

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  • Data from resin microspheres indicate an approximately 50% rate of toxicity for whole liver mean doses of 44-61 Gy.

    “Data from resin microspheres indicate an approximately 50% rate of toxicity for whole liver mean doses of 44 -61Gy ( 55 ).”

    From Normal-Tissue Tolerance to Radiopharmaceutical Therapies, the Knowns and the Unknowns (2021) · cites this paper as [55]

    The Dosimetry and Radiobiologic Model section reports a modeled 50% probability of grade 2 or higher liver toxicity at a whole-organ tolerance dose of 52 Gy. The 44–61 Gy figures are the 95% confidence interval for that estimated dose, not a range of mean liver doses at which the paper reports an approximately 50% toxicity rate. (LLM, conf=0.87)

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Research works printed but not linked: 6

  1. Di Bisceglie AM, Rustgi VK, Hoofnagle JH, Dusheiko GM, Lotze MT. NIH conference: hepatocellular cancer. Ann Intern Med. 1988;108:390-401.
  2. Strigari L, D'Andrea M, Maini CL, et al. Biological optimization of heterogeneous dose distributions in radionuclide direct therapy. Med Phys. 2006;33:1857-1866.
  3. Jakobs T. Radiologic follow-up of patients treated with SIRT. Paper presented at: Liver-Directed Radiotherapy with Microspheres: A Clinical Symposium; February 11-12, 2006; Barcelona, Spain.
  4. Cremonesi M, Ferrari M, Bartolomei M, et al. Radioembolization with 90 Y- microspheres: dosimetric and radiobiological investigation for multi-cycle treatments. Eur J Nucl Med Mol Imaging. 2008;35:2088-2096.
  5. Ingold J, Reed G, Kaplan H, Bagshaw MA. Radiation hepatitis. AJR. 1965;93:200-208.
  6. Wollner I, Knutsen C, Smith P, et al. Effects of hepatic arterial yttrium-90 glass microspheres in dogs. Cancer. 1988;61:1336-1344.

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Authors
Strigari, L., Sciuto, R., Rea, S., Carpanese, L., Pizzi, G., Soriani, A., Iaccarino, G., Benassi, M., Ettorre, G. M., & Maini, C. L.
Affiliations
  • Instituto Nazionale Tumori Regina Elena (IT)
  • IRCCS San Camillo Hospital (IT)
ORCID
Venue
Journal of Nuclear Medicine
Publisher
Society of Nuclear Medicine
Published
2010-08-18
Volume
51
Issue
9
Pages
1377-1385
ISSN
  • 0161-5505 (ISSN-L)
  • 2159-662X
DOI
10.2967/jnumed.110.075861
OpenAlex
W2103849118
Cited by
239
References
39
Citations by year
2026: 1 · 2025: 8 · 2024: 15 · 2023: 10 · 2022: 31 · 2021: 26 · 2020: 13 · 2019: 15 · 2018: 19 · 2017: 19 · 2016: 18 · 2015: 14 · 2014: 19 · 2013: 20 · 2012: 4
FWCI
6.49
Type
journal article
Language
en
Open access
Locations
  • Journal of Nuclear Medicine (publishedVersion)
  • PubMed (publishedVersion)
  • INFM-OAR (INFN Catania) (submittedVersion, other-oa)
Topics
  • Health Sciences › Medicine › Hepatology › Hepatocellular Carcinoma Treatment and Prognosis
  • Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Radiopharmaceutical Chemistry and Applications
  • Physical Sciences › Physics and Astronomy › Radiation › Advanced Radiotherapy Techniques
Keywords
hepatocellular carcinoma, yttrium-90, radioembolization, tumor control probability, normal tissue complication probability, hepatotoxicity, liver dose, tumor response, treatment toxicity prediction, Monte Carlo dose calculation, likelihood maximization, RECIST
MeSH terms
Adult, Aged, Aged, 80 and over, Female, Carcinoma, Hepatocellular, Humans, Image Processing, Computer-Assisted, Liver Neoplasms, Male, Middle Aged, Radiobiology, Radiometry, Radiotherapy, Retrospective Studies, Yttrium Radioisotopes, Tomography, Emission-Computed, Single-Photon, Treatment Outcome

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