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 normaltissue 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 $grade 2 (G2), $grade 3 (G3), and $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 $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 5 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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The aim of this study was to investigate the dosimetric characteristics of the electron beams generated by the light intraoperative accelerator, Liac® (SORDINA, Italy), using Monte Carlo (MC) calculations. Moreover we investigated the possibility of characterizing the Liac® dosimetry with a minimal set of dosimetric data. In fact accelerator commissioning requires measurements of both percentage depth doses (PDDs) and off-axis profiles for all the possible combinations of energy, applicator diameter and bevelled angle. The Liac® geometry and water phantom were simulated in a typical measurement setup, using the MC code EGSnrc/BEAMnrc. A simulated annealing optimization algorithm was used in order to find the optimal non-monoenergetic spectrum of the initial electron beam that minimizes the differences between calculated and measured PDDs. We have concluded that, for each investigated nominal energy beam, only the PDDs of applicators with diameters of 30, 70 and 100 mm and the PDD without an applicator were needed to find the optimal spectra. Finally, the output factors of the entire set of applicator diameters/bevelled angles were calculated. The differences between calculated and experimental output factors were better than 2%, with the exception of the smallest applicator which gave differences between 3% and 4% for all energies. The code turned out to be useful for checking the experimental data from various Liac® beams and will be the basis for developing a tool based on MC simulation to support the medical physicist in the commissioning phase.

BackgroundPET/CT has recently been shown to be a viable alternative to traditional post-infusion imaging methods providing good quality images of 90Y-laden microspheres after selective internal radiation therapy (SIRT). In the present paper, first we assessed the quantitative accuracy of 90Y-PET using an anthropomorphic phantom provided with lungs, liver, spine, and a cylindrical homemade lesion located into the hepatic compartment. Then, we explored the accuracy of different computational approaches on dose calculation, including (I) direct Monte Carlo radiation transport using Raydose, (II) Kernel convolution using Philips Stratos, (III) local deposition algorithm, (IV) Monte Carlo technique (MCNP) considering a uniform activity distribution, and (V) MIRD (Medical Internal Radiation Dose) analytical approach. Finally, calculated absorbed doses were compared with those obtained performing measurements with LiF:Mg,Cu,P TLD chips in a liquid environment.ResultsOur results indicate that despite 90Y-PET being likely to provide high-resolution images, the 90Y low branch ratio, along with other image-degrading factors, may produce non-uniform activity maps, even in the presence of uniform activity. A systematic underestimation of the recovered activity, both for the tumor insert and for the liver background, was found. This is particularly true if no partial volume correction is applied through recovery coefficients. All dose algorithms performed well, the worst case scenario providing an agreement between absorbed dose evaluations within 20%. Average absorbed doses determined with the local deposition method are in excellent agreement with those obtained using the MIRD and the kernel-convolution dose calculation approach.Finally, absorbed dose assessed with MC codes are in good agreement with those obtained using TLD in liquid solution, thus confirming the soundness of both calculation approaches. This is especially true for Raydose, which provided an absorbed dose value within 3% of the measured dose, well within the stated uncertainties.ConclusionsPatient-specific dosimetry is possible even in a scenario with low true coincidences and high random fraction, as in 90Y–PET imaging, granted that accurate absolute PET calibration is performed and acquisition times are sufficiently long. Despite Monte Carlo calculations seeming to outperform all dose estimation algorithms, our data provide a strong argument for encouraging the use of the local deposition algorithm for routine 90Y dosimetry based on PET/CT imaging, due to its simplicity of implementation.