No abstract

In the last decades, selective internal radiation therapy (SIRT) has become a real alternative in the treatment of unresectable hepatic cancers. In practice, the activity prescription is limited by the irradiation of organs at risk (OAR), such as the lungs and nontumoral liver (NTL). Its clinical implementation is therefore highly dependent on dosimetry. In that context, a 3-dimensional personalized dosimetry technique-personalized Monte Carlo dosimetry (PMCD)-based on patient-specific data and Monte Carlo calculations was developed and evaluated retrospectively on clinical data. Methods: The PMCD method was evaluated with data from technetium human albumin macroaggregates ( 99m Tc-MAA) evaluations of 10 patients treated for hepatic metastases. Region-of-interest outlines were drawn on CT images to create patient-specific voxel phantoms using the OEDIPE software. Normalized 3-dimensional matrices of cumulated activity were generated from 99m Tc-SPECT data. Absorbed doses at the voxel scale were then obtained with the MCNPX Monte Carlo code. The maximum-injectable activity (MIA) for tolerance criteria based on either OAR mean absorbed doses (D mean ) or OAR dose-volume histograms (DVHs) was determined using OEDIPE. Those MIAs were compared with the one recommended by the partition model (PM) with D mean tolerance criteria. Finally, OEDIPE was used to evaluate the absorbed doses delivered if those activities were injected to the patient and to generate the corresponding isodose curves and DVHs. Results: The MIA recommended using D mean tolerance criteria is, in average, 27% higher with the PMCD method than with the PM. If tolerance criteria based on DVHs are used along with the PMCD, an increase of at least 40% of the MIA is conceivable, compared with the PM. For MIAs calculated with the PMCD, D mean delivered to tumoral liver (TL) ranged from 19.5 to 118 Gy for D mean tolerance criteria whereas they ranged from 26.6 to 918 Gy with DVH tolerance criteria. Thus, using the PMCD method, which accounts for fixation heterogeneities, higher doses can be delivered to TL. Finally, absorbed doses to the lungs are not the limiting criterion for activity prescription. However, D mean to the lungs can reach 15.0 Gy. Conclusion: Besides its feasibility and applicability in clinical routine, the interest for treatment optimization of a personalized Monte Carlo dosimetry in the context of SIRT was confirmed in this study.

-For targeted radionuclide therapies, treatment planning usually consists of the administration of standard activities without accounting for the patient-specific activity distribution, pharmacokinetics and dosimetry to organs at risk. The OEDIPE software is a user-friendly interface which has an automation level suitable for performing personalized Monte Carlo 3D dosimetry for diagnostic and therapeutic radionuclide administrations. Mean absorbed doses to regions of interest (ROIs), isodose curves superimposed on a personalized anatomical model of the patient and dosevolume histograms can be extracted from the absorbed dose 3D distribution. Moreover, to account for the differences in radiosensitivity between tumoral and healthy tissues, additional functionalities have been implemented to calculate the 3D distribution of the biologically effective dose (BED), mean BEDs to ROIs, isoBED curves and BED-volume histograms along with the Equivalent Uniform Biologically Effective Dose (EUD) to ROIs. Finally, optimization tools are available for treatment planning optimization using either the absorbed dose or BED distributions. These tools enable one to calculate the maximal injectable activity which meets tolerance criteria to organs at risk for a chosen fractionation protocol. This paper describes the functionalities available in the latest version of the OEDIPE software to perform personalized Monte Carlo dosimetry and treatment planning optimization in targeted radionuclide therapies.

An activity of approximately 185 MBq successfully relieved clinical symptoms of LA. There was good correlation between direct Monte Carlo and voxel based techniques, but OLINDA was shown to overestimate the absorbed dose to the tumor. Accurate dosimetry may help select an activity more tailored to the specific size and location of the LA.

-To go further in the optimization of treatment planning in selective internal radiation therapy (SIRT), radiobiological aspects can be accounted for with the OEDIPE software and used to design fractionation protocols. Dosimetry was performed using data from 99m Tc-MAA evaluations of 10 patients treated for hepatic metastases with SIRT. The maximal injectable activity (MIA) was calculated, using a tolerance criterion on BED mean,healthy liver equal to 54 Gy 2.5 , for different fractionation protocols, varying the number of fractions, the repartition of activity and the time delay between fractions. OEDIPE was also used to calculate BED mean and the EUD to the tumoral liver (TL) that would be delivered with those MIAs. Compared with a single-injection protocol, the MIA is increased on average by 23% ± 3%, 36% ± 5% and 45% ± 7% for fractionation protocols with 2, 3 and 4 equal fractions, respectively, while BED mean,TL is increased by 15% ± 2%, 23% ± 4% and 29% ± 5%. EUD TL , calculated for one evaluation, is increased by 51%, 115% and 159% using 2, 3 and 4 equal fractions, respectively. For this evaluation, the optimal activity repartition for twofraction protocols is (3/4 − 1/4) for time delays of less than 4 days, (2/3 − 1/3) for time delays between 4 and 6 days and (1/2 − 1/2) for time delays superior to 6 days. Finally, this study confirmed that OEDIPE can be regarded as a tool for treatment planning optimization and fractionation protocol design in SIRT.