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Thyroid Cancer Radiotheragnostics: the case for activity adjusted 131I therapy.

ABSTRACT: Radiotheragnostics represents the systematic integration of diagnostic imaging and therapeutics using radionuclides targeting specific characteristics of tumor biology. Radioiodine (131I) is the classic radiotheragnostic agent used for the diagnosis and treatment of differentiated thyroid cancer (DTC) based on sodium-iodine symporter expression in normal and neoplastic thyroid tissue. Application of radiotheragnostics principles in thyroid cancer involves using pre-ablation diagnostic scans (Dx Scans) for detection of iodine-avid regional and distant metastatic disease and patient-individualized targeted 131I therapy with goal of maximizing the benefits of the first therapeutic 131I administration. Clinically available nuclear medicine imaging technology has significantly evolved over the past 10 years with the introduction of hybrid SPECT/CT and PET/CT systems, as well as advances in iterative image reconstruction with modeling of image degrading physical factors. This progress makes possible the acquisition of accurate diagnostic radioiodine scintigraphy capable of identifying regional and distant metastatic disease, which can be used for 131I treatment planning and delivery of activity adjusted 131I therapy for achieving intended treatment goals (e.g. remnant ablation, adjuvant 131 I treatment and targeted 131-I treatment). The overarching aim of thyroid cancer radiotheragnostics is to optimize the balance between 131I therapeutic efficacy and potential side-effects on non-target tissues.

SUBMITTER: Avram AM

PROVIDER: S-EPMC6430577 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature

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Thyroid Cancer Radiotheragnostics: the case for activity adjusted <sup>131</sup>I therapy.

Avram Anca M AM Dewaraja Yuni K YK

Clinical and translational imaging 20180804 5

Radiotheragnostics represents the systematic integration of diagnostic imaging and therapeutics using radionuclides targeting specific characteristics of tumor biology. Radioiodine (<sup>131</sup>I) is the classic radiotheragnostic agent used for the diagnosis and treatment of differentiated thyroid cancer (DTC) based on sodium-iodine symporter expression in normal and neoplastic thyroid tissue. Application of radiotheragnostics principles in thyroid cancer involves using pre-ablation diagnostic ...[more]

PMID: 30911535

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Project description:Purpose Generally, the prognosis for papillary thyroid cancer (PTC) is favorable. However, the moderate risk involved warrants further evaluation. Hence, we investigated the clinical outcomes in patients with moderate-risk PTC following surgery and the first 131I therapy, as well as the relevant factors that influence the therapeutic efficacy. Methods Retrospective analyses of 175 patients with medium-risk PTC who visited the Second Affiliated Hospital of Chongqing Medical University from September 2017 to April 2019 were conducted. In according with the 2015 American Thyroid Association (ATA) guideline treatment response evaluation system, the patients were categorized into the following groups: excellent response (ER), indeterminate response (IDR), biochemical incomplete response (BIR), and structurally incomplete response (SIR), of which IDR, BIR, and SIR were collectively referred to as the NER group. To compare the general clinical features between the 2 groups of patients, 2 independent samples t-tests, χ2 test, and Mann–Whitney U-test were performed, followed by multivariate logistic regression analyses. With reference to the receiver operating characteristic (ROC) curve, the predicted value of ps-Tg to ER was evaluated, and the best cut-off value was determined. The subgroups with BRAFV600E test results were analyzed by χ2 test only. Results The treatment responses of 123 patients were ER, while those of 52 patients were NER. The differences in the maximum tumor diameter (U = 2495.50), the amount of metastatic lymph nodes (U = 2313.50), the size of metastatic lymph node (U = 2113.50), the metastatic lymph node ratio (U = 2111.50), metastatic lymph node location (χ2 = 9.20), and ps-Tg level (U = 1011.00) were statistically significant. Multivariate regression analysis revealed that ps-Tg (OR = 1.209, 95% CI: 1.120–1.305) was an independent variable affecting ER. The cut-off value of ps-Tg for predicting ER was 6.915 ug/L, while its sensitivity and specificity were 69.2% and 89.4%, respectively. Conclusions Patients with smaller tumor size, fewer lymph nodes, lower metastatic lymph node ratio, metastatic lymph nodes in the central region, smaller lymph node size, and ps-Tg <6.915 ug/L demonstrated better therapeutic effects after the initial treatment.

Project description:High-throughput gene expression analysis is increasingly used in radiation research for discovery of damage-related or absorbed dose-dependent biomarkers. In tissue samples, cell type-specific responses can be masked in expression data due to mixed cell populations which can preclude biomarker discovery. In this study, we deconvolved microarray data from thyroid tissue in order to assess possible bias from mixed cell type data. Transcript expression data [GSE66303] from mouse thyroid that received 5.9 Gy from 131I over 24 h (or 0 Gy from mock treatment) were deconvolved by cell frequency of follicular cells and C-cells using csSAM and R and processed with Nexus Expression. Literature-based signature genes were used to assess the relative impact from ionizing radiation (IR) or thyroid hormones (TH). Regulation of cellular functions was inferred by enriched biological processes according to Gene Ontology terms. We found that deconvolution increased the detection rate of significantly regulated transcripts including the biomarker candidate family of kallikrein transcripts. Detection of IR-associated and TH-responding signature genes was also increased in deconvolved data, while the dominating trend of TH-responding genes was reproduced. Importantly, responses in biological processes for DNA integrity, gene expression integrity, and cellular stress were not detected in convoluted data-which was in disagreement with expected dose-response relationships-but upon deconvolution in follicular cells and C-cells. In conclusion, previously reported trends of 131I-induced transcriptional responses in thyroid were reproduced with deconvolved data and usually with a higher detection rate. Deconvolution also resolved an issue with detecting damage and stress responses in enriched data, and may reduce false negatives in other contexts as well. These findings indicate that deconvolution can optimize microarray data analysis of heterogeneous sample material for biomarker screening or other clinical applications.

Dataset Information

Thyroid Cancer Radiotheragnostics: the case for activity adjusted 131I therapy.

Publications

Thyroid Cancer Radiotheragnostics: the case for activity adjusted <sup>131</sup>I therapy.

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