Clinical Effect Observation of Apatinib Combined with 131I for Radioiodine-Refractory Differentiated Thyroid Cancer and Prognostic Significance Analysis of Macrophage Inflammatory Protein-1α After Treatment: A Cell Regulation Study

SUMMARY: The objective of this study was to observe the clinical efficacy of apatinib (AP) combined with 131I in the treatment of radioiodine-refractory differentiated thyroid cancer (RAIR-DTC) and the prognostic significance of MIP-1α after treatment, and to provide reference and guidance for future treatment and disease assessment of RAIR-DTC. One hundred and six patients with RAIR- DTC admitted to our hospital from January 2019 to October 2020 were selected for the study. All the patients were treated with TC surgery with 131I at our hospital, and 58 of them were subsequently transferred to AP treatment, which was considered as the research group; the other 48 patients were transferred to thyroid stimulating hormone (TSH) suppression treatment, which was considered as the control group. The clinical efficacy of the research group was better than that of the control group (P 0.05). After treatment, Tg, TL, maximum diameter of C/B lymph nodes, number of lymph nodes and number of calcified spots were lower in the research group than in the control group (P < 0.05). ROC analysis revealed that the predictive sensitivity of MIP-1α for prognosis of 3-year RAIR-DTC death in the research group of patients was 84.63 % and the specificity was 72.16 %. AP combined with 131I is effective in the treatment of RAIR-DTC and is worth using in the clinical practice. In addition, elevated levels of MIP-1α predicted a poor prognosis for patients with RAIR-DTC.

El objetivo de este estudio fue observar la eficacia clínica de apatinib (AP) combinado con 131I en el tratamiento del cáncer de tiroides diferenciado refractario al yodo radiactivo (RAIR-DTC) y la importancia pronóstica de MIP-1α después del tratamiento, y proporcionar referencia y orientación para futuros tratamientos y enfermedades. Evaluación de RAIR- DTC. Se seleccionaron para el estudio 106 pacientes con RAIR- DTC ingresados en nuestro hospital desde enero de 2019 hasta octubre de 2020. Todos los pacientes fueron tratados con cirugía CT con 131I, y 58 de ellos fueron trasladados posteriormente a tratamiento AP, los que fueron considerados como grupo de investigación; los otros 48 pacientes fueron transferidos a tratamiento de supresión de la hormona estimulante de la tiroides (TSH), que se consideró como grupo de control. La eficacia clínica del grupo de investigación fue mejor que la del grupo de control (P 0,05). Después del tratamiento, Tg, TL, diámetro máximo de los linfonodos C/B, número linfonodos y número de manchas calcificadas fueron menores en el grupo de investigación que en el grupo de control (P <0,05). El análisis ROC reveló que la sensibilidad predictiva de MIP-1α para el pronóstico de muerte por RAIR-DTC a 3 años en el grupo de pacientes de investigación fue del 84,63 % y la especificidad fue del 72,16 %. AP combinado con 131I es eficaz en el tratamiento del RAIR-DTC y vale la pena utilizarlo en la práctica clínica. Además, los niveles elevados de MIP-1α predijeron un mal pronóstico para los pacientes con RAIR- DTC.

Progress on Targeted Therapy of Radioiodine-refractory Differentiated Thyroid Cancer / 肿瘤防治研究

Targeted therapy has brought revolutionary breakthroughs for radioiodine-refractory differentiated thyroid cancer. New targeted drugs have prolonged the survival of patients with advanced differentiated thyroid cancer. Multiple tyrosine kinase inhibitors, represented by sorafenib and lenvatinib, have remarkably improved the progression-free survival of patients. Novel tyrosine kinase inhibitors targeting BRAF and RET mutation have also achieved remarkable curative effects, greatly enriching the treatment methods for thyroid cancer. This article reviews the latest research progress on targeted therapy in radioiodine-refractory differentiated thyroid cancer.

Progress in Re-differentiating Therapy of Radioiodine-refractory Differentiated Thyroid Cancer / 肿瘤防治研究

The majority patients of differentiated thyroid carcinoma (DTC) with indolent progression have general good prognosis after standard primary treatments including surgery, thyroid stimulating hormone (TSH) suppression and radioactive iodine (RAI) therapy. However, there are still some patients suffered from recurrence or distant metastasis after initial treatment. They may lose the ability of uptaking iodine during their natural course of disease or treatment and could not benefit from subsequent RAI treatment, which will result in radioiodine-refractory differentiated thyroid cancer (RAIR-DTC). Options are very limited for RAIR-DTC patients, which is associated with a poor prognosis. Recently, with the research advances on the molecular mechanism of RAIR-DTC, redifferentiation combined with RAI therapy have been increasingly used to treat RAIR-DTC, and some outcomes are quite encouraging. This paper reviews the progress of signaling pathway inhibitors, histone deacetylase inhibitors, DNA methyltransferase inhibitors, retinoids and peroxisome proliferator-activated receptor agonists in redifferentiating therapy of RAIR-DTC.

Emerging management and its impact on radioiodine refractory differentiated thyroid cancer / 中国实用外科杂志

Differentiated thyroid cancer(DTC) generally carries good prognosis through standard treatment. While,it could dedifferentiate into radioiodine refractory differentiated thyroid cancer(RAIR-DTC),which progresses rapidly with high mortality and limited treatment methods. Recently,along with the increasing of studies on genetic features,signal transduction pathways and immune microenvironment of RAIR-DTC,as well as the development of new radionuclide tracers,more theoretical bases have been provided for the targeted therapy of RAIR-DTC.

Respuesta parcial a lenvatinib como segunda línea de tratamiento en cáncer diferenciado avanzado de tiroides / Partial response to lenvatinib as a second line of treatment in advanced differentiated cancer of thyroid

RESUMEN Las metástasis a distancia ocurren en alrededor del 10% de los pacientes con cáncer diferenciado de tiroides (CDT), y cerca de la mitad de estos casos serán refractarios al radioyodo (RAIR). Sorafenib fue el primer inhibidor multicinasa (IMK) aprobado por la FDA para su uso en cáncer diferenciado de tiroides RAIR avanzado y progresivo, y hasta el momento es el único aprobado por la ANMAT en nuestro país para esta indicación. Lenvatinib es el segundo IMK aprobado por la FDA para este grupo de pacientes, y es una alternativa terapéutica que debe ser considerada, debido a su disponibilidad como fármaco de uso compasivo en nuestro país. Presentamos nuestra experiencia con el uso de lenvatinib como segunda línea de tratamiento en una paciente con CDT progresivo previamente tratado con sorafenib.

ABSTRACT Distant metastases occur in around 10% of patients with differentiated thyroid cancer (DTC), and half of these cases will become refractory to radioiodine therapy (RAIR). Sorafenib was the first multikinase inhibitor (MKI) approved by the FDA for patients with differentiated advanced and progressive RAIR thyroid cancer, and it is the only one approved by ANMAT in our country for this indication. Lenvatinib is the second MKI approved by the FDA for this group of patients, and is a therapeutic alternative that should be considered, due to its availability as a compassive use drug in our country. We present our experience with the use of lenvatinib as a second line of treatment in a patient with DTC with advanced and progressive disease under treatment with sorafenib.

Risk factors for radioiodine-refractoriness and survival analysis of differentiated thyroid cancer with distant metastasis / 中华内分泌代谢杂志

Objective To analyze clinical risk factors for radioiodine(RAI)-refractoriness of DTC with distant metastasis and do survival analysis.Method The clinical data of 77 differentiated thyroid cancer(DTC) patients with distant metastasis admitted to the department of radionuclide therapeutics of Qilu Hospital from Jan 2002 to Sep 2015 were collected to make the retrospective analysis by dividing into radioiodine-refractory(RAI-R) group and radioiodine-efficient(RAI-E) group.Result (1)In DTC patients treated by 131I, there are 77(7.15%) patients with distant metastasis.Among DTC with distant metastasis, 25(32.47%) patients are identified as RAI-R DTC with average age of (56.2±16.0) years old, median age of 57 years old, and male-to female ratio of 1∶2.57.(2)Univariate analysis shows that age of distant metastasis older than 45 years and pathological type of follicular thyroid cancer(FTC) are two risk factors related to RAI-refractoriness.Logistic regression analysis indicates that age of distant metastasis older than 45 years and pathological type of FTC are the independent risk factors for RAI-refractoriness of DTC with distant metastasis.(3)3-year and 5-year survival rates of the 25 RAI-R DTC patients with distant metastasis are 75% and 62%,while RAI-E DTC patients were all alive.The survival of RAI-R DTC with distant metastasis is significantly worse than RAI-E DTC with distant metastasis.Conclusions (1)In the DTC with distant metastasis, the rate of RAI-R DTC is not low, and it is 32.47%.Females of RAI-R DTC are more than males.(2)Age of distant metastasis older than 45 years and pathological type of FTC are independent risk factors for RAI-refractoriness of DTC with distant metastasis.(3)The survival rate of RAI-R DTC with distant metastasis was significantly lower than that of RAI-E DTC with distant metastasis.

18F-FDG PET/CT imaging in the monitoring of response to sorafenib in patients with radioiodine- refractory differentiated thyroid cancer / 中国癌症杂志

Background and purpose:The evaluation of treatment response is one of the most important building blocks in determining the best strategy for the management of malignant tumors. In lymphoma and several solid cancer types, PET/CT-based response evaluation has been shown to be valuable, especially in visualizing the effect of the targeted treatment, which induces tumor activity changes not necessarily followed by tumor shrinkage. This study aimed to evaluate the role of18F-FDG PET/CT in the monitoring of response to sorafenib treatment in radioiodine-refractory differentiated thyroid cancer (RR-DTC) patients; and to compare the Response Evaluation Criteria in Solid Tumors (RECIST 1.1) with the European Organization for Research and Treatment of Cancer (EORTC) criteria.Methods:This was a single-center retrospective analysis of 14 patients with RR-DTC treated with sorafenib in the period from Dec. 2011 to Dec. 2014. A Wilcoxon signed-rank sum test was used to assess the differences in percentage changes between the sum of diameter and ∑SUVmax. These values of responses were statistically compared using the chi-square test (Fisher’s exact test). The differences in PFS between response categories according to either RECIST 1.1 or the EORTC criteria were evaluated using the Wilcoxon signed-rank sum test. The Spearman rank correlation coefficient was estimated between PFS and either morphologic (RECIST 1.1) or metabolic response (EORTC criteria) categories.Results:There was an agreement between the RECIST 1.1 and EORTC criteria in 10 of the 14 patients (χ2=2.345,P=0.424). The remaining 4 patients with SD in-cluded 2 patients with PMR and 2 patients with PMD. Differences in PFS among different response categories according to either RECIST 1.1 (χ2=8.571,P=0.003) or EORTC criteria (χ2=8.781,P=0.003) were statistically significant. Correlations were found between PFS and either morphologic (r=0.741,P=0.002) or metabolic (r=0.816,P=0.0004) response criteria. Conclusion:18F-FDG PET/CT imaging is of value in the monitoring of response to sorafenib in patients with RR-DTC. Although RECIST 1.1 and EORTC criteria agree in 71.4% patients, PET-based metabolic response criteria seems to be more accurate in predicting therapeutic outcome and may be more suitable than morphologic response criteria for the eval-uation of response to targeted therapy.