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Objective:To investigate the significance of B-Raf proto-oncogene, serine/threonine kinase (BRAF) V600E mutation in the prediction of response to apatinib treatment in advanced radioactive iodine-refractory differentiated thyroid cancer (RAIR-DTC). Methods:Twenty patients (10 males, 10 females, age: 51.5(46.3, 65.0) years) with advanced RAIR-DTC from Peking Union Medical College Hospital between March 2016 and March 2023 were retrospectively enrolled, and all patients were treated with apatinib and underwent genetic sequencing (including BRAF V600E and telomerase reverse transcriptase (TERT) promoter). The serological and imaging data, progression-free survival (PFS) and overall survival (OS) data were collected during apatinib treatment. The Kaplan-Meier survival analysis (log-rank test) was performed, and Mann-Whitney U test were used to analyze the differences of duration of response (DOR) between mutation group and wild-type group. Then univariate and multivariate Cox regression analyses were conducted. Results:The PFS (35.3 vs 9.2 months, χ2=7.53, P=0.006) and DOR (25.8(7.4, 35.2) vs 8.2(2.5, 13.4) months, U=23.00, P=0.046) of the BRAF V600E mutation group were longer than those of the wild-type group. Univariate Cox regression analysis showed that the BRAF V600E mutation group had better PFS benefit (hazard ratio ( HR)=0.22 (95% CI: 0.06-0.72), P=0.013), and the risk of disease progression or death in patients with lung metastasis and bone or brain metastasis was 3.06(95% CI: 1.10-8.54, P=0.033) times higher than that in patients with lung metastasis alone. Further, multivariate cox regression analysis showed that only BRAF V600E mutation was an independent predictor of PFS ( HR=0.23 (95% CI: 0.07-0.80), P=0.021), suggesting that RAIR-DTC patients with BRAF V600E mutation might have better efficacy of apatinib. There was no significant difference in PFS ( χ2=1.34, P=0.247) and OS ( χ2=0.19, P=0.664) between TERT promoter mutation group and wild-type group. Conclusion:RAIR-DTC patients with BRAF V600E mutation have longer PFS and DOR after apatinib treatment than those with BRAF V600E wild-type, suggesting that BRAF V600E may be a potential biomarker to guide tyrosine kinase inhibitor (TKI) therapy and help to refine TKI treatment indications.
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Objective · To investigate the curative efficacy and influential factors of 131I treatment for pulmonary metastases from differentiated thyroid carcinoma (DTC). Methods · A total of 95 DTC patients (33 males and 62 females) with pulmonary metastasis who underwent 131I treatment in Department of Nuclear Medicine, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, from April 2012 to May 2016 were retrospectively analyzed. The efficacy of 131I treatment was assessed using determination of serum thyroglobulin level and 18F-fluorodeoxyglucose positron-emission tomography/computed tomography (～ (18) F-FDG PET/CT). The possible factors affecting efficacy included gender, age, pathological classification, wheteer pulmonary metastasis diagnosed before treatment, the iodine and 18F-FDG uptake of pulmonary lesions, the size and number of lung lesions, extrapulmonary distant metastasis.Univariate analysis was performed using Rank test and χ2 test, the critical value was obtained through receiver operating characteristic (ROC) curve and Logistic regression was also performed. Results · The rates of efficacy and inefficacy of 131I treatment were 53.68％ and 46.32％, respectively. Univariate analyses showed that maximum standardized uptake value (SUVmax) evaluated by 18F-FDG PET/CT (P=0.004), the size of lung metastases (P=0.000), age＜45 years (P=0.004), 131I uptake (P=0.022), whether pulmonary metastasis diagnosed before treatment (P=0.000), extrapulmonary distant metastasis (P=0.014) were the factors influencing outcome of 131I treatment. The critical value of 18F-FDG uptake for patients obtained by ROC curve was 1.45 (sensitivity of 56.8％ and specificity of 76.5％) and the critical value of lung lesion diameter was 9.63 mm (sensitivity of 43.2％ and specificity of 88.2％). Multivariate Logistic regression analysis showed that the influential factors included the age of patients, the size and 18F-FDG SUVmax of lung metastases and whether pulmonary metastasis diagnosed before treatment. Conclusion · 131I treatment is an effective method for pulmonary metastases from DTC. The patients aged less than 45 years, with the lung lesion size less than 9.63 cm, low 18F-FDG SUVmax and diagnosed before treatment may have good response to 131I treatment.
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Objective • To investigate the curative efficacy and influential factors of 131I treatment for pulmonary metastases from differentiated thyroid carcinoma (DTC). Methods • A total of 95 DTC patients (33 males and 62 females) with pulmonary metastasis who underwent 131I treatment in Department of Nuclear Medicine, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, from April 2012 to May 2016 were retrospectively analyzed. The efficacy of 131I treatment was assessed using determination of serum thyroglobulin level and 18F-fluorodeoxyglucose positron-emission tomography/computed tomography (18F-FDG PET/CT). The possible factors affecting efficacy included gender, age, pathological classification, wheteer pulmonary metastasis diagnosed before treatment, the iodine and 18F-FDG uptake of pulmonary lesions, the size and number of lung lesions, extrapulmonary distant metastasis. Univariate analysis was performed using Rank test and χ2 test, the critical value was obtained through receiver operating characteristic (ROC) curve and Logistic regression was also performed. Results • The rates of efficacy and inefficacy of 131I treatment were 53.68% and 46.32%, respectively. Univariate analyses showed that maximum standardized uptake value (SUVmax) evaluated by 18F-FDG PET/CT (P=0.004), the size of lung metastases (P=0.000), age<45 years (P=0.004), 131I uptake (P=0.022), whether pulmonary metastasis diagnosed before treatment (P=0.000), extrapulmonary distant metastasis (P=0.014) were the factors influencing outcome of 131I treatment. The critical value of 18F-FDG uptake for patients obtained by ROC curve was 1.45 (sensitivity of 56.8% and specificity of 76.5%) and the critical value of lung lesion diameter was 9.63 mm (sensitivity of 43.2% and specificity of 88.2%). Multivariate Logistic regression analysis showed that the influential factors included the age of patients, the size and 18F-FDG SUVmax of lung metastases and whether pulmonary metastasis diagnosed before treatment. Conclusion • 131I treatment is an effective method for pulmonary metastases from DTC. The patients aged less than 45 years, with the lung lesion size less than 9.63 cm, low 18F-FDG SUVmax and diagnosed before treatment may have good response to 131I treatment.
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Objective Some drugs can effectively improve the uptake of 131 I in dedifferentiated thyroid cancer .This study was to investigate the effect of all-trans retinoic acid (ATRA) combined with interferon-α2a (IFN-α2a) on the iodine uptake and re-tention rate of FTC-133 follicular thyroid carcinoma cells . Methods FTC-133 cells were cultured in the presence of 2 μmol/L AT-RA and/or 1500 IU/mL IFN-α2a for 72 hours.The the cells were collected for measurement of the uptake and retention rate of Na 125 I. Results The Na125 I uptake of the FTC-133 cells was significantly increased after 72-hour incubation with 2μmol/L ATRA and 1500 IU/mL IFN-α2a (2423.1 ±237.5) as compared with those of the control (1279.5 ±102.8), ATRA (1438.2 ±149.6), and IFN-α2a groups (1355.3 ±198.4) (P<0.05).Statistically significant differences were observed in the retention rate of Na 125I in the FTC-133 cells at different time points in the each of the blank control , 2μmol/L ATRA, 1500 IU/mL IFN-α2a, and combination groups (P<0.01), but not in that of Na125I among these groups (P<0.05). Conclusion ATRA in combination with IFN-α2a can promote the Na125 I uptake but cannot improve the Na 125 I retention rate in FTC-133 cells.
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During 131Ⅰ therapy or the natural course of DTC,2％ to 5％ of them will gradually no longer be sensitive to 131Ⅰ therapy and lead to radioactive iodine-refractory DTC (RAIR-DTC).Recent studies found that alterations of critical molecular targets in main signal transduction pathways could decrease the iodine-trapping function of thyroid carcinoma,such as BRAFV600E mutation,followed by negative 131 Ⅰ-whole body scan (WBS) and discounted efficacy.This article reviews novel diagnostic and therapeutic modalities for RAIR-DTC.
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Objective To observe the influence of recombinant human thyrotropin(rhTSH)on serum concentration of endogenous thyrotropin(TSH), free triiodothyronine(FT3), free thyroxine(FT4), thyroglobulin antibody(TGAb), and thyroglobulin(Tg). To evaluate the efficacy of rhTSH-aided radioiodine treatment in patients with differentiated thyroid carcinoma(DTC). Methods The study recruitment took place between November 2007 and March 2009. 62 patients(including 45 females)with biopsy confirmed DTC had undergone total or nearly total thyroidectomy, and received 131I treatment. 31 patients(including 22 females), median age of 45 years(23-72), received radioiodine treatment 4 weeks after L-thyroxine(T4)withdrawal. The other 31 patients(including 23 females), median age of 44 years(14-70), underwent rhTSH-aided radioiodine treatment. Before and after rhTSH injection, serum TSH, FT3, FT4, TGAb, and thyroglobulin were tested. Post-radiotherapy whole body scan was performed 5 to 7 days after radioiodine treatment and qualitatively and blindly evaluated by two nuclear medicine physicians. Follow-up took place 6 to 12 months after radioiodine treatment. The efficacy of rhTSH-aided radioiodine treatment was evaluated by whole body scan with diagnostic dose radioiodine. SPSS 13.0 statistical software was applied. Results (1)Before and after rhTSH-aided radioiodine treatment, the serum TSH was(1.08±4.01)vs(140.26±27.20)mIU/L(P＜0.05), thyroglobulin(23.75±132.92)vs(169.58±178.49)μg/L(P＜0.05), FT3(4.52±1.16)vs(4.42±1.11)pmol/L(P＞0.05), and FT4(15.09±5.83)vs(13.66±5.85)pmol/L(P＞0.05),respectively.(2)rhTSH-aided radioiodine ablation treatment had the same effect as L-T4withdrawal aided. The complete response ratio was 77.4% vs 71.0%(P＞0.05)by radioiodine whole body scan of diagnostic dose. Conclusion rhTSH-aided radioiodine treatment of DTC was effective and safe, and did at least at equivalent degree as did L-T4withdrawal. Furthermore, Serum thyroglobulin level could be effectively stimulated by rhTSH with tumor relapse or metastasis.
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Objective To semiquantify salivary gland damage after 131I treatment in patients post thyroidectomy using salivary gland scintigraphy. Methods Fifty-six patients underwent salivary gland scintigraphy 6 months after 131I ablation therapy following thyroidectomy, including 21 with both baseline (before 131I treatment) and follow-up (6 months after the 1st 131I treatment) imaging. Salivary gland function was quantified by uptake ratios at 4 minutes (UR4) and 15 minutes (UR15), and excretory index at maximum secretion (MS), time duration from stimulation to minimum count (Tmin ). Paired t test was used for the 21 patients with both baseline and follow-up imaging. All the studies were divided into four groups: before 131I therapy, after 1st therapy, after 2nd therapy, and after 3rd or more times of therapy. Group differences were evaluated by the one-way analysis of variance (ANOVA)/Kruskal-Wallis test. Spearman test was used to analyze the correlation between the parameters and times of therapy. Results After the 1st 131I therapy, UR15 for the left and right parotid glands were 16% and 14% lower than the baseline, respectively (t=2.188, 3.322, both P0.05). Among the four groups, significantly different parameters for both parotid glands were found: UR4, UR15, MS for the left parotid of the four groups were 1.76±0.29, 2.60±0.38, (72.8±24.2)%; 1.55±0.34, 2.15±0.51, (64.4±21.6)%; 1.55±0.40, 2.02±0.68, (57.2±34.2)%; 1.45±0.33, 1.69±0.46, (30.6±36.9)%; respectively (F values for UR4 and UR15 were 7.018, 3.112 and H value for MS was 12.240, all P0.05). According to pair-pair comparison, only the degree of reduction of UR15 for parotid glands was significantly different between the 1st and 2nd therapy (P<0.05). UR4, UR15, MS for bilateral parotid glands reduced significantly after 3 or more times of therapy (all P<0.05).The parametres UR4, UR15, MS were correlated with times of 131I therapy (r:-0.296 to -0.566, all P<0.05). Conclusions Salivary uptake function is impaired slightly after the 1st radioiodine therapy. After several times of therapy, both parotid uptake and excretion functions are impaired. Submandibular functions are not affected even after repeated 131I therapy.
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Objective To assess the feasibility, safety and curative effect of permanent implantation of ~(125)I seeds combined with GP scheme chemotherapy for the treatment of non-small cell lung carcinoma (NSCLC) in aged patients. Methods CT-guided permanent implantation of ~(125)I seeds combined with GP scheme chemotherapy was performed in 46 patients with NSCLC, of whom 26 received primary treatment and 20 underwent renewed treatment. During the procedure, ~(125)I seeds were embedded into the tumor in all the patients. Three to five days after the implantation, GP scheme chemotherapy started. GEM (1 000 mg/m~2) was given (intravenously dripping for 30 min.) on the 1st, 8th and 15th day; DDP (30 mg/m~2) was employed on the 1st, 2nd and 3rd day, and recombinant human endostatin (Endostar, 7.5 mg/m~2) was administered (intravenously dripping for 3-4 hours) from the 1st to the 14th day. Every 28 days completed one treatment course. Two months after ~(125)I seed implantation, at this time the patient had received two courses of treatment, the short-term effect and the toxic side-effect were evaluated. Results Two months after the ~(125)I particles were embedded in the tumor, all the 46 cases were able to be evaluate for the curative effect. Of 46 patients, complete relief (CR) was seen in 12, partial relief (PR) in 24, stable (SD) in 6 and progression (PD) in 4, with an effective rate of 78.26%. Of 26 patients in the primary treatment group, CR was obtained in 7, PR in 15, SD in 3 and PD in 1, with an effective rate of 84.6%. Of 20 patients in the renewed treatment group, CR was seen in 5, PR in 9, SD in 3 and PD in 3, with an effective rate of 70.0%. Conclusion Permanent implantation of ~(125)I seeds combined with GP scheme chemotherapy is an effective, safe and feasible treatment for NSCLC in aged patients.
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PURPOSE: Localizing and differentiating a metastatic lesion of differentiated thyroid cancer (DTC) by using radio?iodine whole body scan could be difficult because a whole body scan (WBS) lacks anatomic information. This study was performed to evaluate the usefulness of radio-iodine SPECT/CT for differentiating equivocal lesions. MATERIALS AND METHODS: Among 253 patients with DTC who had undergone radio-iodine scan between February and July 2006, 26 patients were enrolled (M:F = 8:18, Age 50.7 +/- 12.5 years) in this study. The patients had abnormal uptakes in the WBSs that necessitated precise anatomical localization for differentiating between a metastatic lesion and a false-positive lesion. SPECT/CT was performed for the region with abnormal uptake in the WBS. WBS and SPECT/CT were evaluated visually. Metastases were diagnosed based on the results of the radio-iodine scan along with the results of other radiological examinations and serological tests. RESULTS: Based on the WBS images, 13 were suspected with cervical lymph node (LN) metastases in 16 patients with abnormal neck uptake, and in the 11 patients with abnormal extra-cervical uptakes, extra-cervical metastases were doubtful in all. After SPECT/CT was performed, the diagnostic results were altered for 16 patients (62%). SPECT/CT revealed that only 5 patients had cervical LN metastases, while 3 patients had extra-cervical (mediastinal) LN metastases. Overall, there was a 58% (15/26) change in diagnoses and plans for treatment due to SPECT/CT. Among 8 patients suspected with metastases on SPECT/CT, 6 patients underwent another radio-iodine therapy. In 96% (24/25) of the patients, the results of SPECT/CT corresponded with those of further radiological examinations and with other clinical information. CONCLUSION: Radio-iodine SPECT/CT images permitted the differentiation of abnormal radio-iodine uptake and improved anatomical interpretation in DTC.
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Humanos , Diagnóstico , Linfonodos , Pescoço , Metástase Neoplásica , Testes Sorológicos , Glândula Tireoide , Neoplasias da Glândula Tireoide , Imagem Corporal TotalRESUMO
During the last decade the issue of therapy-related myelodysplasia (t-MDS) and acute myeloid leukemia (t-AML) following high-dose chemotherapy (HD-CT) and autologous stem cell transplantation (ASCT) or conventional chemotherapy, radiotherapy for malignant diseases has become increasingly important. The number of patients with hematologic malignancies and chemosensitive or radiosensitive solid tumors undergoing this new type of treatment has expanded dramatically. Recently, we experienced a case of 35-year-old female patient with therapy-related acute lymphoblastic leukemia (t-ALL) after 131I treatment for thyroid papillary carcinoma. Total 131I dose the patient received was 900mCi and patient was diagnosed as having ALL 11 months after last 131I treatment. Although the prognosis of therapy-related acute leukemia/myelodysplastic syndrome is poor, the patient is alive in complete remission after allogeneic bone marrow transplantation from HLA-matched sibling donor. Given the rarity of this case, we report the case with literature reviews.
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Adulto , Feminino , Humanos , Transplante de Medula Óssea , Carcinoma Papilar , Tratamento Farmacológico , Neoplasias Hematológicas , Leucemia Mieloide Aguda , Segunda Neoplasia Primária , Leucemia-Linfoma Linfoblástico de Células Precursoras , Prognóstico , Radioterapia , Irmãos , Transplante de Células-Tronco , Glândula Tireoide , Neoplasias da Glândula Tireoide , Doadores de TecidosRESUMO
To evaluate the utility of I-131, T1-201 scintigraphy, and serum thyroglobulin(Tg) in the follow-up of differentiated thyroid cancer, we compared retrospectively the data from 33 patients who underwent total or subtotal thyroidectomy. I-131 scintigraphy was performed after optimal endogenous TSH stimulation (TSH>50microgram/ml). Total 41 cases of I-l3l and T1-201 scintigraphy pairs were examined. Concomitant serum thyroglobulin levels were measured for 41 pairs of scan. Tg-off levels(that measured after discontinuation of the thyroid hormone) higher than 40ng/ml were considered positive, and Tg-on levels(that measured during the thyroid hormone replacement) higher than 5ng/ml were considered positive. The concordance rates between I-131 therapeutic scintigraphy and T1-201 scintigraphy was 48% in the 38 case of total scan pairs(59% in the 17 cases of postoperative preablation group, and 38% in the 21 cases of postoperative postablation group), Of 17 studies before the I-131 ablation therapy (preablation group), 7 showed positive I-131 therapeutic scintigraphy despite of negative T1-201 scintigraphy. Among patients with negative I-131 therapeutic scintigraphy, no patients had abnormal T1-201 uptake. However, of 21 studies which were done after radioiodine therapy(postablation group) 6 had abnormal uptake on T1-201 scintigraphy which were not seen on I-131 therapeutic scintigraphy, and Tg-off levels also elevated in this 4 of 6 cases. As a result, I-131 therapeutic scintigraphy showed highest positive rate at postoperative preablation follow-up study in differentiated thyroid cancer patients. T1-201 scintigraphy may be useful in postablation studies, and the use of the combined modalities(T1-201 and Tg levels) provides a higher diagnostic yield.