Analysis of side effect in thyroid cancer patients received combined treatment with radioiodine and external beam radiotherapy

I. Khvostunov, V. Krylov, A. Rodichev, N. Shepel, O. Korovchuk, T. Kochetova, T.I. Khvostunova, A.S. Zhironkina
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Abstract

Radical surgery is the mainstay for differentiated thyroid cancer, radioiodine therapy followed by the surgery is the “gold standard” treatment modality indicated after the surgery. Radioiodine therapy becomes practically non-alternative treatment for patients with distant metastases. How-ever, orally administered radioiodine may be also absorbed into the bloodstream and can dam-age surrounding normal organs and tissues and cause side effect. To test radioiodine therapy safety side effects of the radionuclide on somatic cells should be accurately assessed. In addi-tion, external beam radiotherapy can also damage adjacent normal organs and tissues and thereby increases radioiodine therapy side effect. It is possible to evaluate patient-specific total radiation dose with the use of cytogenetic assay of chromosome aberrations level in peripheral blood lymphocytes because some types of chromosome aberrations are specific radiation mark-ers clearly indicating that the cells have been exposed to radiation. Radiation absorbed dose can be estimated by the number of the aberrations occurrence frequency, and the value of side radia-tion dose greatly depends on a patient personality. In this case peripheral blood lymphocytes are thought of as a model of somatic and bone marrow cells. The paper present results of application of cytogenetic assay for estimating side effects caused by exposure of adjacent organs and tis-sues to external beam radiotherapy and surrounding somatic cells to radioiodine therapy. Results of statistical analysis of external beam radiotherapy related side effect contribution to the total side effect are present in the paper. The joint group of 43 patients was involved in the study, all patients received radioiodine therapy and 5 of them received also external beam radiotherapy in addition to radioiodine therapy. All patents received radioiodine therapy in the Radionuclide Therapy Department, A. Tsyb MRRC in Obninsk. Cytogenetic assay was carried out in the Radia-tion Cytogenetics Laboratory, A. Tsyb MRRC. Results of the study and examination of regularities of radioiodine therapy and external beam radiotherapy related side effects development make it evident that patients received combining radioiodine therapy and external beam radiotherapy should present special group with the treatment plan different from that for the radioiodine thera-py exposed group. Exposure to external radiation may cause not only significant overestimation but also a false-positive underestimation of the number of radiation-specific markers because of lymphocytes inhibition following exposure to high total radiation dose. Inhibition effect may be a result of overestimating multiple radioiodine therapy administrations to achieve total I-131 activity (Σact) exceeds 1200 mCi. The absolute value of the total focal radiotherapy dose is probably ir-relevant. In general, patients assigned to both radioiodine therapy and external beam radiothera-py require personalized approach to treatment.
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放射性碘与外束放疗联合治疗甲状腺癌的副反应分析
根治性手术是分化型甲状腺癌的主要治疗手段,放射碘治疗配合手术治疗是术后的“金标准”治疗方式。放射性碘治疗实际上已成为远处转移患者的不可替代的治疗方法。然而,口服放射性碘也可能被血液吸收,损害周围的正常器官和组织,并产生副作用。为了检验放射性碘治疗的安全性,必须准确评估放射性核素对体细胞的副作用。此外,外部放射治疗还会损害邻近的正常器官和组织,从而增加放射性碘治疗的副作用。利用外周血淋巴细胞染色体畸变水平的细胞遗传学测定来评估患者特异性总辐射剂量是可能的,因为某些类型的染色体畸变是特异性辐射标记,清楚地表明细胞已暴露于辐射。辐射吸收剂量可由畸变发生频率的多少来估计,而侧辐射剂量的大小在很大程度上取决于患者的个性。在这种情况下,外周血淋巴细胞被认为是体细胞和骨髓细胞的模型。本文介绍了应用细胞遗传学测定法估计外束放射治疗引起的邻近器官和组织以及周围体细胞放射碘治疗的副作用。本文统计分析了外束流放疗相关副作用对总副作用的贡献。联合组43例患者均接受放射碘治疗,其中5例患者除接受放射碘治疗外还接受外束放疗。所有患者在奥布宁斯克的A. Tsyb MRRC放射性核素治疗部门接受放射性碘治疗。细胞遗传学检测在A. Tsyb MRRC辐射细胞遗传学实验室进行。放射性碘治疗和外束放疗相关副作用发生规律的研究和检查结果表明,接受放射性碘治疗和外束放疗联合治疗的患者应分为特殊组,治疗方案与放射性碘治疗照射组不同。由于暴露于高总辐射剂量后淋巴细胞抑制,暴露于外部辐射不仅可能导致显著高估,而且可能导致对辐射特异性标记物数量的假阳性低估。抑制作用可能是为了使总I-131活性(Σact)超过1200 mCi而高估多次放射性碘治疗的结果。局灶放疗总剂量的绝对值可能是无关的。一般来说,同时接受放射性碘治疗和外束放射治疗的患者需要个性化的治疗方法。
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