Karaciğer Tümörlerinin Tedavisinde Uygulanacak Y-90 Mikrokürelerin Aktivite Miktarlarının Hastaya Özgü Modelleme İle Belirlenmesi İçin Yöntem Geliştirilmesi ve Yöntemin Standardize Edilmesi

Abstract

Yttrium-90 (Y-90) microsphere treatment is the internal radionuclide treatment through administration of Y-90 loaded microspheres to the tumor microcirculation via the relevant branch of the hepatic artery feeding the tumor. The basic principle of this treatment is based on the supply of tumor cells in the liver via the hepatic artery and the healthy cells via the portal venous system. Since the Y-90 microspheres are selectively directed to tumor cells, tumor cells are exposed to high-dose radiation, while healthy liver tissue and other areas outside the liver are as protected as possible from the possible side-effects of radiation. This technique, which is used in the treatment of primary and metastatic hepatic tumors independent of malignancy type, number of tumors and histopathological behavior characteristics, has gained an important place in clinical practice.

For the Y-90 microsphere treatment, it is aimed to increase cure rates and local regional control and to eliminate the toxic effects on healthy tissues, as in other ionizing radiation therapy applications. However, one of the important limits of this treatment is the infiltration of the radiomicrospheres into undesirable areas by shunting and the negative effects on normal liver tissue and lungs due to the proximity to the treatment area. Another limitation of this treatment is the heterogeneity of intra-tumor radiomicrosphere distribution and the continuing inability to definitely calculate the absorbed dose and the amount of Y-90 microsphere activity in the treatment.

To overcome the above-mentioned limits of the Y-90 microsphere treatment, to eliminate the early and late effects of radiation in the treatment, to determine the treatment parameters of the patient by the patient-specific dosimetry and to obtain maximum benefit from the treatment with the personalized treatment approach, it is planned for the data obtained from this thesis study to be a guide.

90 liver treatment cases in total including with one lobe for 56 patients and two lobes for 17 patients, whose Y-90 glass microsphere treatments have been performed by the Department of Nuclear Medicine of the Faculty of Medicine of Hacettepe University from 2012 to 2018, were re-planned retrospectively in this study as specific for the relevant patient. During planning, a software that provides a voxel-based dosimetric approach through anatomical and functional sequence images of the patient was used. The plan of each patient performed retrospectively was evaluated in terms of targeted effective tumor dose and critical organ doses. The relation of the Y-90 glass microsphere activities, which were calculated by pre-therapeutic classical dosimetric approach, with perfused tissue volume, perfused tissue tumor volume and absorbed doses was investigated. The planning steps of the software used in this study were reviewed in terms of parameters that would affect the dosimetric results, and a standard was specified for these parameters.

Based on the results of the retrospective planning, it was found out that the amounts of Y-90 glass microsphere activity, which were used under current conditions and calculated taking a reference of absorbing a dose of 120 Gy of the lobar volume alone, were lower than normal during some therapies and higher than normal during some therapies when considering the critical organ tolerance doses. This thesis study showed that the patient-specific dosimetric approach, taking into account the anatomic variation of the relevant patient, different tumor size and its localization, is of vital importance for the conscious use of ionized radiation in accordance with the legal regulations. Through the dosimetric approach based on the patient-specific modeling used in this thesis study, it has been possible to reach high doses in the Y-90 microsphere treatment in order to provide higher treatment efficiency in tumor foci in the liver and also to calculate accurately the amount of activity required to keep the dose to be absorbed by the normal tissue at a minimum. We are in the opinion of that, the results of the study will shed light on future clinical studies in this field and will contribute significantly to optimize treatments.