Radioembolization of hepatocarcinoma with 90Y glass microspheres: treatment optimization using the dose-toxicity relationship

Chiesa, Carlo; Mira, M.; Bhoori, Sherrie; Bormolini, G.; Maccauro, Marco; Spreafico, Carlo; Cascella, Tommaso; Cavallo, A.; Nile, M.C. De; Mazzaglia, S.; Capozza, Antonella; Tagliabue, Giovanna; Brusa, A.; Marchianò, Alfonso; Seregni, Ettore; Mazzaferro, V.

doi:10.1007/s00259-020-04845-4

Cited by 49 publications

(59 citation statements)

References 28 publications

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“…This was performed only for the 3- and 6-month follow-ups, as this period has been previously shown to capture procedure-related decompensations, while 12-month follow-up may be influenced by natural progression of liver disease. 14 Following the previously described methodology, ROC curve analysis to determine the relation of treatment parameters with the development of the highest reported grade of albumin or bilirubin toxicities per CTCAE criteria was performed.…”

Section: Methodsmentioning

confidence: 99%

Biochemical Safety of Ablative Yttrium-90 Radioembolization for Hepatocellular Carcinoma as a Function of Percent Liver Treated

Ramos¹,

Overfield²,

Montazeri³

et al. 2021

JHC

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Purpose Transarterial radioembolization can serve as an ablative therapy for early-stage hepatocellular carcinoma (HCC). Given the volumetric variability of liver segments, this study aimed to characterize the safety of ablative radioembolization by determining percent liver treated (%LT) thresholds associated with biochemical toxicity. Patients and Methods Patients with HCC receiving a single ablative radioembolization treatment using glass microspheres from 2017 through 2020 were reviewed. %LT was calculated as treatment angiosome volume divided by whole liver volume. Biochemical toxicities were defined as increases in Albumin-Bilirubin (ALBI) grade or Child-Pugh (CP) class compared to baseline and albumin or bilirubin adverse events (AEs) per the Common Terminology Criteria for Adverse Events. Receiver operating characteristic curves and multivariate logistic regression analyses were performed to assess the impact of %LT on toxicities. Results Of 141 patients analyzed, 53% (n=75) were ALBI 1, 45% (n=64) ALBI 2, 79% (n=111) CP-A, and 21% (n=30) CP-B. A %LT ≥14.5% was associated with grade/class increases in ALBI 2 ( p ≤0.01) and CP-B patients ( p =0.026). In multivariate analysis, a %LT ≥14.5% was an independent predictor of increases in the ALBI 2 and CP-B groups ( p <0.01). No significant %LT threshold was found for ALBI 1 and CP-A patients. No grade 3/4 albumin or bilirubin AEs were reported, while grade 2 AEs were related to an initial whole liver volume <1.3 L ( p ≤0.01). Conclusion Patients with ALBI 2 and CP-B liver function are less likely to have an increase in their respective grade/class when treating <14.5% of the liver using glass microspheres. ALBI 1 and CP-A patients showed no definitive %LT threshold for biochemical toxicity within the range of this study.

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Section: Methodsmentioning

confidence: 99%

Biochemical Safety of Ablative Yttrium-90 Radioembolization for Hepatocellular Carcinoma as a Function of Percent Liver Treated

Ramos¹,

Overfield²,

Montazeri³

et al. 2021

JHC

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“…In external beam radiotherapy (EBRT), this complication occurs with whole liver doses of 30–35 Gy [ 49 ]. The tolerance is higher in RE, 40–50 Gy for resin microspheres and 90 Gy with glass microspheres [ 50 , 51 , 52 ]. A pre-clinical study in pigs with administration of PLLA microspheres demonstrates no toxicity with absorbed doses over 100 Gy.…”

Section: Impact At a Macroscopic Level-clinical Effectsmentioning

confidence: 99%

“…Recent recommendations with resin microsphere also consider performing a personalized dosimetry targeting a tumor dose of at least 100–120 Gy [ 81 ]. Moreover, the toxicity cutoffs doses are well determined, and the treatment plan can be optimized in order to deliver the maximal tolerable absorbed dose to the non-tumoral liver [ 52 ]. With PLLA microspheres, the development of the 166 Ho scout dose may significantly optimize the accuracy of the treatment planning [ 82 ].…”

Section: Future Directionsmentioning

confidence: 99%

Microspheres Used in Liver Radioembolization: From Conception to Clinical Effects

et al. 2021

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Inert microspheres, labeled with several radionuclides, have been developed during the last two decades for the intra-arterial treatment of liver tumors, generally called Selective Intrahepatic radiotherapy (SIRT). The aim is to embolize microspheres into the hepatic capillaries, accessible through the hepatic artery, to deliver high levels of local radiation to primary (such as hepatocarcinoma, HCC) or secondary (metastases from several primary cancers, e.g., colorectal, melanoma, neuro-endocrine tumors) liver tumors. Several types of microspheres were designed as medical devices, using different vehicles (glass, resin, poly-lactic acid) and labeled with different radionuclides, 90Y and 166Ho. The relationship between the microspheres’ properties and the internal dosimetry parameters have been well studied over the last decade. This includes data derived from the clinics, but also computational data with various millimetric dosimetry and radiobiology models. The main purpose of this paper is to define the characteristics of these radiolabeled microspheres and explain their association with the microsphere distribution in the tissues and with the clinical efficacy and toxicity. This review focuses on avenues to follow in the future to optimize such particle therapy and benefit to patients.

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“…The invasive procedure and the use of nonidentical particles may affect the perfect correspondence of pre vs. post-therapeutical activity distribution, depending on patient specific vascularity, type of disease, experience, and shrewdness. However, many authors [6,9,22,23] have shown the good representativity of 99m Tc-MAA activity distribution for treatment planning, which is verified afterwards by post 90 Y-PET or 90 Y-SPECT imaging. 3D approaches based on LDM or convolution of S-voxel values allow to account for the nonuniform activity distribution derived from the SPECT images, whereas they still assume a homogeneous density.…”

Section: Introductionmentioning

confidence: 95%

“…Due to their simplicity, empirical models have been applied for several years, but at present they are not considered as adequate for patient-specific treatments. In fact, the clinical benefit evidence of dosimetry-based approaches [3][4][5][6][7][8][9][10] has led the scientific community to recognize the importance of accurate absorbed dose evaluation and to focus on the absorbed dose-biological effectiveness relationship.…”

Section: Introductionmentioning

confidence: 99%

In Silico Validation of MCID Platform for Monte Carlo-Based Voxel Dosimetry Applied to 90Y-Radioembolization of Liver Malignancies

et al. 2021

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The aim was the validation of a platform for internal dosimetry, named MCID, based on patient-specific images and direct Monte Carlo (MC) simulations, for radioembolization of liver tumors with 90Y-labeled microspheres. CT of real patients were used to create voxelized phantoms with different density and activity maps. SPECT acquisitions were simulated by the SIMIND MC code. Input macros for the GATE/Geant4 code were generated by MCID, loading coregistered morphological and functional images and performing image segmentation. The dosimetric results obtained from the direct MC simulations and from conventional MIRD approach at both organ and voxel level, in condition of homogeneous tissues, were compared, obtaining differences of about 0.3% and within 3%, respectively, whereas differences increased (up to 14%) introducing tissue heterogeneities in phantoms. Mean absorbed dose for spherical regions of different sizes (10 mm ≤ r ≤ 30 mm) from MC code and from OLINDA/EXM were also compared obtaining differences varying in the range 7–69%, which decreased to 2–9% after correcting for partial volume effects (PVEs) from imaging, confirming that differences were mostly due to PVEs, even though a still high difference for the smallest sphere suggested possible source description mismatching. This study validated the MCID platform, which allows the fast implementation of a patient-specific GATE simulation, avoiding complex and time-consuming manual coding. It also points out the relevance of personalized dosimetry, accounting for inhomogeneities, in order to avoid absorbed dose misestimations.

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Radioembolization of hepatocarcinoma with 90Y glass microspheres: treatment optimization using the dose-toxicity relationship

Cited by 49 publications

References 28 publications

Biochemical Safety of Ablative Yttrium-90 Radioembolization for Hepatocellular Carcinoma as a Function of Percent Liver Treated

Biochemical Safety of Ablative Yttrium-90 Radioembolization for Hepatocellular Carcinoma as a Function of Percent Liver Treated

Microspheres Used in Liver Radioembolization: From Conception to Clinical Effects

In Silico Validation of MCID Platform for Monte Carlo-Based Voxel Dosimetry Applied to 90Y-Radioembolization of Liver Malignancies

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