RESUMO
BACKGROUND: The clinical outcomes and implications of radioactive iodine therapy (RAIT) on cancer-specific survival (CSS) in World Health Organization classification of follicular thyroid carcinoma (FTC) are not well established. MATERIAL AND METHODS: The data of eligible patients with minimally invasive FTC (mi-FTC), encapsulated angioinvasive FTC (ea-FTC), or widely invasive FTC (wi-FTC) between 2000 and 2020 were extracted from the Surveillance, Epidemiology, and End Results database. CSS, the primary outcome, was compared among the 3 subtypes of patients with FTC before and after adjusting for differences using propensity score matching (PSM). The patients with FTC in different subtypes were then divided into 2 groups: the RAIT group and the no-RAIT group. Cox proportional hazards regression analyses were applied to discover the relationships of factors associated with CSS in the each PSM cohort. RESULTS: A total of 2433 patients with mi-FTC, 216 patients with ea-FTC, and 554 patients with wi-FTC were enrolled in the original cohorts, respectively. Patients with mi-FTC or ea-FTC had similar CSS (P = .805), which was better than that of patients with wi-FTC (P < .001; P = .021). Cox proportional hazards regression analysis revealed that RAIT was not associated with improved CSS in either the mi-FTC PSM cohort (hazard ratio [HR], 1.21; 95% CI, .46-3.18; P = .705) or the wi-FTC PSM cohort (HR, 0.56; 95% CI, .35-1.08; P = .086). However, subgroup analysis demonstrated that patients with wi-FTC and N1 stage (HR, 0.44; 95% CI, .20-.99; P = .018) or M1 stage (HR, 0.25; 95% CI, .11-.53; P < .001) could gain CSS advantage from RAIT. CONCLUSION: The RAIT can provide a CSS advantage for patients with wi-FTC who with N1-stage or M1-stage disease.
Assuntos
Adenocarcinoma Folicular , Radioisótopos do Iodo , Neoplasias da Glândula Tireoide , Humanos , Radioisótopos do Iodo/uso terapêutico , Feminino , Masculino , Pessoa de Meia-Idade , Neoplasias da Glândula Tireoide/radioterapia , Neoplasias da Glândula Tireoide/mortalidade , Neoplasias da Glândula Tireoide/patologia , Adenocarcinoma Folicular/radioterapia , Adenocarcinoma Folicular/mortalidade , Adenocarcinoma Folicular/patologia , Adulto , Organização Mundial da Saúde , Programa de SEER , Idoso , Resultado do Tratamento , Prognóstico , Taxa de Sobrevida , Estudos RetrospectivosRESUMO
The term noninvasive tumor with a follicular growth pattern and nuclear features of papillary thyroid cancer (NIFTP) is used to describe a tumor currently considered as a pre-malignant lesion for which a conservative therapeutic approach (i.e., lobectomy without radioiodine therapy) is strongly suggested. However, some patients with NIFTP and loco-regional or distant metastases have been already reported. We present an adult male patient with a final histological diagnosis of NIFTP and lymph node metastasis noted at post-therapy whole-body scintigraphy performed some days after radioiodine therapy.
Assuntos
Adenocarcinoma Folicular , Radioisótopos do Iodo , Metástase Linfática , Neoplasias da Glândula Tireoide , Humanos , Masculino , Neoplasias da Glândula Tireoide/patologia , Neoplasias da Glândula Tireoide/diagnóstico por imagem , Neoplasias da Glândula Tireoide/radioterapia , Metástase Linfática/patologia , Metástase Linfática/diagnóstico por imagem , Adenocarcinoma Folicular/patologia , Adenocarcinoma Folicular/secundário , Adenocarcinoma Folicular/diagnóstico por imagem , Adenocarcinoma Folicular/radioterapia , Radioisótopos do Iodo/uso terapêutico , Carcinoma Papilar/patologia , Carcinoma Papilar/diagnóstico por imagem , Câncer Papilífero da Tireoide/patologia , Adulto , Pessoa de Meia-Idade , Carcinoma/patologia , Carcinoma/diagnóstico por imagem , Carcinoma/radioterapiaRESUMO
Objective: Redifferentiation therapy (RDT) can restore radioactive iodine (RAI) uptake in differentiated thyroid cancer (DTC) cells to enable salvage 131I therapy for previously RAI refractory (RAIR) disease. This study evaluated the clinical outcomes of patients who underwent RDT and identified clinicopathologic characteristics predictive of RAI restoration following RDT. Methods: This is a retrospective case series of 33 patients with response evaluation criteria in solid tumors (RECIST)-progressive metastatic RAIR-DTC who underwent RDT between 2017 and 2022 at the Mayo Clinic (Rochester, MN). All patients underwent genomic profiling and received MEK, RET or ALK inhibitors alone, or combination BRAF-MEK inhibitors for 4 weeks. At week 3, those with increased RAI avidity in metastatic foci received high-dose 131I therapy. Baseline and clinicopathologic outcomes were comprehensively reviewed. Results: Of the 33 patients, 57.6% had restored RAI uptake following RDT (Redifferentiated subgroup). 42.1% (8/19) with papillary thyroid cancers (PTC), 100% (4/4) with invasive encapsulated follicular variant PTCs (IEFV-PTCs), and 100% (7/7) with follicular thyroid cancers (FTC) redifferentiated. All (11/11) RAS mutant tumors redifferentiated compared with 38.9% (7/18) with BRAF mutant disease (6 PTC and 1 IEFV-PTC). 76.5% (13/17) of redifferentiated and 66.7% (8/12) of non-redifferentiated patients achieved a best overall RECIST response of stable disease (SD) or non-complete response/non-progressive disease. Both subgroups had a median 12% tumor shrinkage at 3 weeks on drug(s) alone. The redifferentiated subgroup, following high-dose 131I therapy, achieved an additional median 20% tumor reduction at 6 months after RDT. There were no statistically significant differences between both groups in progression free survival (PFS), time to initiation of systemic therapy, and time to any additional therapy. Of the entire cohort, 6.1% (2/33) experienced histologic transformation to anaplastic thyroid cancer, 15.1% (5/33) died, and all had redifferentiated following RDT and received 131I therapy. Conclusion: RDT has the potential to restore RAI avidity and induce RECIST responses following 131I therapy in select patients with RAIR-DTC, particularly those with RAS-driven "follicular" phenotypes. In patients with PTC, none of the evaluated clinical outcomes differed statistically between the redifferentiated and non-redifferentiated subgroups. Further studies are needed to better characterize the long-term survival and/or safety outcomes of high-dose RAI following RDT, particularly whether it could be associated with histologic anaplastic transformation.
Assuntos
Adenocarcinoma Folicular , Iodo , Neoplasias da Glândula Tireoide , Humanos , Neoplasias da Glândula Tireoide/tratamento farmacológico , Neoplasias da Glândula Tireoide/genética , Neoplasias da Glândula Tireoide/radioterapia , Radioisótopos do Iodo/uso terapêutico , Iodo/uso terapêutico , Estudos Retrospectivos , Proteínas Proto-Oncogênicas B-raf/genética , Adenocarcinoma Folicular/tratamento farmacológico , Adenocarcinoma Folicular/genética , Adenocarcinoma Folicular/radioterapia , Inibidores de Proteínas Quinases/uso terapêutico , Quinases de Proteína Quinase Ativadas por Mitógeno/uso terapêuticoRESUMO
OBJECTIVE: Skeletal metastases in differentiated thyroid cancer (DTC) patients are associated with poor prognosis. The objective was to determine the maximum I-131 cumulative activity that could be safely administered without compromising efficacy. The secondary objective was to identify other prognostic factors affecting survival outcomes. MATERIALS AND METHODS: This was a retrospective cohort study done at a tertiary-care institution comprising of data from January 1990-June 2020. 489 DTC patients having skeletal metastases with ≥12 months follow-up were included. Ninety-six percent of patients had thyroidectomy followed by radioiodine therapy for skeletal metastases. All patients were on oral suppressive levothyroxine tablets. External beam radiotherapy (EBRT) and oral tyrosine kinase inhibitors were used whenever indicated. The main outcome measures were overall survival (OS), progression-free survival (PFS), and adverse-events. RESULTS: There were 347 (71%) females and 324 (66%) had follicular carcinoma thyroid. Median follow-up was 78 (interquartile range, IQR: 37-153) months. 333 patients (68%) received ≤37GBq I-131 cumulative activity (group 1) and 156 patients (32%) received >37GBq cumulative RAI activity (group 2). Overall median OS and PFS were 74 (95% confidence interval (CI): 62.2-85.8) and 48 (95%CI: 40.5-55.4) months, respectively. The 5-, 10-, 15- and 20-year estimated overall survival probabilities were 55.7%, 28.4%, 14% and 8.3%, respectively. On multivariate analysis, age(<55years) (p<0.001), female gender(p = 0.01), cumulative I-131 activity >37GBq (p<0.001) and EBRT(p = 0.001) were favourably associated with OS; no factors were significantly associated with PFS. The median OS for groups 1 & 2 were 51 versus 90 months (p<0.001) & median PFS for groups 1 & 2 were 45 versus 53 months respectively (p = 0.9). However, cumulative activity >37GBq resulted in more adverse events (2.4%), particularly bone marrow suppression (3.5%). CONCLUSION: For better survival outcomes, cumulative I-131 activity upto 37GBq could be administered with acceptable toxicity to DTC patients with skeletal metastases.
Assuntos
Adenocarcinoma Folicular , Neoplasias da Glândula Tireoide , Humanos , Feminino , Pessoa de Meia-Idade , Masculino , Estudos Retrospectivos , Radioisótopos do Iodo/uso terapêutico , Neoplasias da Glândula Tireoide/patologia , Adenocarcinoma Folicular/radioterapia , TireoidectomiaRESUMO
Background: The management guidelines of radioactive Iodine (RAI) therapy for distinct types of differentiated thyroid carcinoma (DTC) were the same in clinical practice. However, in distinct types DTC, differences in RAI avidity and response existed and the effect of RAI therapy could not be equated. Methods: DTC patients' data in SEER database were extracted to perform retrospective analysis. The differences between case group and control group were compared by chi-square tests. We used Kaplan-Meier statistics and Cox regression analyses to investigate cancer-specific survival (CSS). Propensity score-matched was performed to make 1:1 case-control matching. Results: 105195 patients who receiving total thyroidectomy were identified in SEER database. Compared to papillary thyroid carcinoma (PTC) (52.3%), follicular thyroid carcinoma (FTC) (63.8%) and oncocytic carcinoma of thyroid (OCA) (64.4%) had higher rates of RAI therapy. In the multivariable Cox regression model, RAI therapy was independent prognosis factor in PTC but not in OCA and FTC. In subgroup analysis, RAI therapy could improve prognosis in PTC when gross extrathyroidal extension or lymph node metastases or early survival when distant metastases (DM) were presented. However, OCA and FTC patients with DM rather than regional lesions only could benefit from RAI therapy. High-risk patients receiving RAI therapy showed a better prognosis in PTC but not in OCA and FTC. Conclusion: RAI therapy was an effective treatment for DTC and should be considered individually in PTC, OCA and FTC patients. Our results provided further guideline for treatment selection in DTC.
Assuntos
Adenocarcinoma Folicular , Neoplasias da Glândula Tireoide , Humanos , Neoplasias da Glândula Tireoide/radioterapia , Neoplasias da Glândula Tireoide/cirurgia , Radioisótopos do Iodo/uso terapêutico , Pontuação de Propensão , Estudos Retrospectivos , Adenocarcinoma Folicular/radioterapia , Adenocarcinoma Folicular/cirurgia , Câncer Papilífero da Tireoide/radioterapiaRESUMO
Objective: Repeat radioiodine (RAI) treatment has been widely implemented for RAI-avid lung metastases and is clinically effective for lung metastatic differentiated thyroid cancer (DTC). We aim to investigate the association between the interval of RAI treatment and short-term response, and the side effects in patients with lung metastases from DTC and to identify predictors for non-effective response to the next RAI treatment. Methods: A total of 282 course pairs from 91 patients were established and categorized into two groups by the interval of neighboring RAI treatment (<12 and ≥12 months), and the characteristics and treatment response between the two groups were compared. Multivariate logistic regression was used to identify predictors associated with treatment response. The side effects in the former course and the latter course were compared while taking into account the interval. Results: No significant difference was found between the two groups in treatment response in the latter course (p > 0.05). In the multivariate analysis, age ≥ 55 years (OR = 7.29, 95% CI = 1.66-33.35, p = 0.008), follicular thyroid cancer (OR = 5.00, 95% CI = 1.23-22.18, p = 0.027), and a second RAI treatment as the former course (OR = 4.77, 95% CI = 1.42-18.61, p = 0.016) were significantly associated with a non-effective response. There was no significant difference in the side effects in the former and latter courses between the two groups (p > 0.05). Conclusion: The interval of RAI treatment does not affect short-term response and side effects of DTC patients with RAI-avid lung metastases. It was feasible to defer repeat evaluation and treatment with an interval of at least 12 months to obtain an effective response and reduce the risk of side effects.
Assuntos
Adenocarcinoma Folicular , Neoplasias Pulmonares , Neoplasias da Glândula Tireoide , Humanos , Pessoa de Meia-Idade , Radioisótopos do Iodo/efeitos adversos , Neoplasias da Glândula Tireoide/tratamento farmacológico , Adenocarcinoma Folicular/radioterapia , Adenocarcinoma Folicular/tratamento farmacológico , Neoplasias Pulmonares/radioterapia , Neoplasias Pulmonares/tratamento farmacológicoRESUMO
Background: Childhood cancer survivors and bone marrow transplant recipients treated with radiation therapy (RT) are at increased risk for subsequent thyroid cancer. However, the genetic landscape of pediatric thyroid cancer, both primary and RT-induced, remains poorly defined, as pediatric papillary thyroid carcinoma (PTC) has been understudied compared with adults and data on pediatric follicular thyroid carcinoma (FTC) are virtually nonexistent. The objective of this study was to characterize and compare the molecular profiles of pediatric RT-induced PTC and FTC cases with primary pediatric thyroid cancers. Methods: A total of 41 differentiated thyroid carcinomas (11 RT cases and 30 primary cases) from 37 patients seen at Phoenix Children's Hospital between January 1, 2010 and December 31, 2019 were evaluated by targeted next-generation sequencing and/or BRAF immunohistochemistry. Results: Eighty-six percent (6/7) of RT-PTC harbored a gene fusion (GF) compared with 56% (14/25) of primary PTC; 14% (1/7) of RT-PTC had a single-nucleotide variant (SNV; specifically, a point mutation in the DICER1 gene) compared with 44% (11/25) of primary PTC (all of the latter had the BRAFV600E mutation). An exceedingly rare ROS1 fusion was identified in a child with RT-PTC. With respect to FTC, copy number alterations (CNAs) were seen in 75% (3/4) of RT cases compared with 40% (2/5) of primary cases. None of the RT-FTC had SNVs compared with 100% (5/5) of primary FTC. Conclusions: In children, the molecular profile of subsequent RT-induced thyroid cancers appears to differ from primary (sporadic and syndromic) cases, with a high prevalence of GFs in RT-PTC (similar to PTC occurring after the Chernobyl nuclear reactor accident) and CNAs in RT-FTC. A better understanding of the molecular mechanisms underlying these cancers may lead to more accurate diagnosis, prognosis, and treatment, as some of the genomic alterations are potentially targetable.
Assuntos
Adenocarcinoma Folicular , Carcinoma Papilar , Neoplasias da Glândula Tireoide , Adenocarcinoma Folicular/genética , Adenocarcinoma Folicular/patologia , Adenocarcinoma Folicular/radioterapia , Adulto , Carcinoma Papilar/patologia , Criança , RNA Helicases DEAD-box/genética , Variações do Número de Cópias de DNA , Fusão Gênica , Humanos , Mutação , Prevalência , Proteínas Tirosina Quinases/genética , Proteínas Proto-Oncogênicas/genética , Proteínas Proto-Oncogênicas B-raf/genética , Ribonuclease III/genética , Câncer Papilífero da Tireoide/genética , Câncer Papilífero da Tireoide/patologia , Neoplasias da Glândula Tireoide/genética , Neoplasias da Glândula Tireoide/patologia , Neoplasias da Glândula Tireoide/radioterapiaRESUMO
BACKGROUND: The term non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) was recently proposed as a non-malignant thyroid lesion with indolent behavior that does not require post-operative radio-iodine treatment. We are reporting a case of NIFTP with bone metastasis that is the second case reported so far. CASE PRESENTATION: We describe a 38-year-old woman who presented with an indeterminate thyroid nodule and underwent total thyroidectomy with the finding of NIFTP on careful pathologic examination. However, her initial follow-up evaluation revealed a serum thyroglobulin level of > 300 ng/ml and a diagnostic whole body 131I scan demonstrated a focus of increased uptake in the left hemipelvis, confirmed on CT scan to be a lytic lesion in the left iliac bone. She was treated with 7.4GBq (200 mCi) of 131I and her follow-up 1 year later revealed an undetectable serum thyroglobulin and a negative whole body 131I scan with no visible uptake in the iliac bone indicating an excellent response. CONCLUSION: This case presentation reminds us to be alert to the rare occurrence of distant metastasis in NIFTP and the need for a case by case analysis and continuing post-operative follow-up for detection of residual or recurrent disease.
Assuntos
Adenocarcinoma Folicular/secundário , Neoplasias Ósseas/secundário , Neoplasias da Glândula Tireoide/patologia , Nódulo da Glândula Tireoide/patologia , Adenocarcinoma Folicular/diagnóstico por imagem , Adenocarcinoma Folicular/radioterapia , Adulto , Neoplasias Ósseas/diagnóstico por imagem , Neoplasias Ósseas/radioterapia , Núcleo Celular/patologia , Feminino , Humanos , Ílio/diagnóstico por imagem , Radioisótopos do Iodo/uso terapêutico , Tomografia Computadorizada com Tomografia Computadorizada de Emissão de Fóton Único , Câncer Papilífero da Tireoide/patologia , Neoplasias da Glândula Tireoide/cirurgia , Nódulo da Glândula Tireoide/cirurgia , Tireoidectomia , Tomografia Computadorizada por Raios XRESUMO
Background: A diagnostic I-131 (Dx) scan is used to detect a thyroid remnant or metastases before treatment of differentiated thyroid cancer (DTC) with I-131. The aim of this study is to specify in which patients with DTC a Dx scan could have an additional value, by studying the effect of the Dx scan on clinical management. Methods: Patients with DTC, treated with I-131 after thyroidectomy were included in this retrospective cohort study. Twenty-four hours after administration of 37 MBq I-131 a whole body Dx scan and an uptake measurement at the original thyroid bed were performed. Outcomes of the Dx scan and the subsequent changes in clinical management, defined as additional surgery or adjustment of I-131 activity, were reported. Risk factors for a change in clinical management were identified with a binary logistic regression. Results: In 11 (4.2%) patients clinical management was changed, including additional surgery (n=5), lowering I-131 activity (n=5) or both (n=1). Risk factors for a change in clinical management were previous neck surgery (OR 5.9, 95% CI: 1.4-24.5), surgery in a non-tertiary center (OR 13.4, 95% CI: 2.8 - 63.8), TSH <53.4 mU/L (OR 19.64, 95% CI: 4.94-78.13), thyroglobulin ≥50.0 ng/L (OR 7.4, 95% CI: 1.6-34.9) and free T4 ≥4.75 pmol/L (OR 156.8, 95% CI: 128.4-864.2). Conclusion: The Dx scan can potentially change clinical management before treatment with I-131, but the yield is low. A Dx-scan should only be considered for patients with a high pre-scan risk of a change in management, based on patient history and prior center-based surgical outcomes.
Assuntos
Adenocarcinoma Folicular/patologia , Carcinoma Papilar/patologia , Radioisótopos do Iodo/uso terapêutico , Neoplasias da Glândula Tireoide/patologia , Imagem Corporal Total/métodos , Adenocarcinoma Folicular/diagnóstico por imagem , Adenocarcinoma Folicular/radioterapia , Carcinoma Papilar/diagnóstico por imagem , Carcinoma Papilar/radioterapia , Gerenciamento Clínico , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Testes de Função Tireóidea , Neoplasias da Glândula Tireoide/diagnóstico por imagem , Neoplasias da Glândula Tireoide/radioterapiaRESUMO
CONTEXT: The recommendations for radioactive-iodine treatment (RAIT) in metastatic differentiated thyroid cancer (DTC) are mostly based in the experience with papillary histotype and do not consider the differences within the distinct types of DTC, in terms of RAIT uptake and response. OBJECTIVE: This work aims to investigate the association between histology and RAIT avidity and response, and to evaluate whether histotype was an independent prognostic factor in progression-free survival (PFS) and disease-specific survival (DSS) after RAIT for distant metastatic disease. METHODS: A retrospective analysis was conducted of all DTC patients who underwent RAIT for distant metastatic disease, from 2001 to 2018, at a thyroid cancer referral center. We included 126 patients: 42 (33.3%) classical variant papillary thyroid cancer (cvPTC), 45 (35.7%) follicular variant PTC (fvPTC), 17 (13.5%) follicular thyroid cancer (FTC) and 22 (17.5%) Hürthle cell carcinoma. Main outcome measures included RAIT avidity and response. RESULTS: RAIT avidity was independently associated with histology (Pâ <â .001) and stimulated thyroglobulin (Tg) at first RAIT for distant lesions (Pâ =â .007). Avidity was lowest in HCC (13.6%), intermediate in cvPTC (21.4%), and highest in fvPTC (75.6%) and FTC (76.5%). Regarding RAIT response, HCC and FTC were not different; both showed significantly more often progression after RAIT than fvPTC and cvPTC. Histology influenced PFS (Pâ =â .014), but tumor type was not a significant prognostic factor in DSS. Instead, age at diagnosis, resection status, and stimulated Tg at the first RAIT were significantly associated with DSS. CONCLUSION: DTC histotype influenced RAIT avidity and PFS. It is crucial to better detect the metastatic patients that may benefit the most from RAIT.
Assuntos
Adenocarcinoma Folicular/patologia , Radioisótopos do Iodo/farmacocinética , Radioisótopos do Iodo/uso terapêutico , Adenocarcinoma Folicular/metabolismo , Adenocarcinoma Folicular/mortalidade , Adenocarcinoma Folicular/radioterapia , Idoso , Disponibilidade Biológica , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/radioterapia , Carcinoma Hepatocelular/secundário , Feminino , Seguimentos , Humanos , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/radioterapia , Neoplasias Hepáticas/secundário , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Portugal/epidemiologia , Prognóstico , Estudos Retrospectivos , Análise de Sobrevida , Resultado do TratamentoRESUMO
AIM: The terminology of "noninvasive follicular thyroid neoplasm with papillary-like nuclear features" (NIFTP) was introduced in 2016; and estimated to cause significant effects in the clinical management of thyroid nodules. The aim of our study is to review our cases that were previously diagnosed as non-invasive encapsulated follicular variant PTC (NI/E-FVPTC) which are compatible with NIFTP and to correlate their follow-up. METHOD: All thyroidectomy cases evaluated in the last 15 years were screened, and possible NIFTP cases were determined among patients with NI/E-FVPTC and they were re-examined microscopically. Revised histopathological criteria were used for the retrospective diagnosis of NIFTP. Histopathological findings were correlated to follow up information. RESULTS: Totally 2138 cases had been previously diagnosed with PTC; 481 (22.5%) of them were FVPTC. After microscopic reevaluation of potential NIFTP cases, 84 cases (3.9%) received final diagnosis of NIFTP. 78.6% of NIFTP patients were female (F/M: 66/18); mean age was 49.0, tumor diameter was 22.7 mm and follow-up time was 66.4 months. 17.9% of NIFTP cases were multifocal and 13.1% were bilateral. No recurrence, lymph node involvement or distant metastasis was detected in any of the patients who were followed up. The mean age of the patients who had total thyroidectomy and received RAI was significantly higher than those who did not. CONCLUSION: Although conservative treatment of NIFTP with lobectomy is recommended, age of the patients has been continuing to be the most important determinant for the clinicians to decide on total thyroidectomy and RAI ablation therapy at our institution.
Assuntos
Adenocarcinoma Folicular/diagnóstico , Núcleo Celular/patologia , Câncer Papilífero da Tireoide/diagnóstico , Neoplasias da Glândula Tireoide/patologia , Adenocarcinoma Folicular/radioterapia , Adenocarcinoma Folicular/cirurgia , Adenocarcinoma Folicular/ultraestrutura , Adulto , Idoso , Idoso de 80 Anos ou mais , Biópsia por Agulha Fina/métodos , Terapia Combinada , Feminino , Seguimentos , Humanos , Incidência , Radioisótopos do Iodo/uso terapêutico , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Câncer Papilífero da Tireoide/radioterapia , Câncer Papilífero da Tireoide/cirurgia , Câncer Papilífero da Tireoide/ultraestrutura , Neoplasias da Glândula Tireoide/epidemiologia , Tireoidectomia/métodos , Turquia/epidemiologiaRESUMO
Management of metastatic radioiodine refractory differentiated thyroid cancer (DTC) can be a therapeutic challenge. Generally, little is known about the paired molecular profile of the primary tumor and the metastases and whether they harbor the same genetic abnormalities. The present study compared the molecular profile of paired tumor specimens (primary tumor/metastatic sites) from patients with radioiodine refractory DTC in order to gain insight into a possible basis for resistance to radioiodine. Twelve patients with radioiodine refractory metastases were studied; median age at diagnosis of 61 years (range, 25-82). Nine patients had papillary TC (PTC), one had follicular TC (FTC), and two had Hürthle cell TC (HTC). Distant metastases were present in the lungs (n = 10), bones (n = 4), and liver (n = 1). The molecular profiling of paired tumors was performed with a panel of 592 genes for Next Generation Sequencing, RNA-sequencing, and immunohistochemistry. Digital microfluidic PCR was used to investigate TERT promoter mutations. The genetic landscape of all paired sites comprised BRAF, NRAS, HRAS, TP53, ATM, MUTYH, POLE, and NTRK genes, including BRAF and NTRK fusions. BRAF V600E was the most common point mutation in the paired specimens (5/12). TERT promoter mutation C228T was detected in one case. PD-L1 expression at metastatic sites was highly positive (95%) for one patient with HTC. All specimens were stable for microsatellite instability testing, and the tumor mutation burden was low to intermediate. Therefore, the molecular profile of DTC primary and metastatic lesions can show heterogeneity, which may help explain some altered responses to therapeutic intervention.
Assuntos
Adenocarcinoma Folicular/genética , Biomarcadores Tumorais/genética , Radioisótopos do Iodo/uso terapêutico , Câncer Papilífero da Tireoide/genética , Neoplasias da Glândula Tireoide/genética , Adenocarcinoma Folicular/patologia , Adenocarcinoma Folicular/radioterapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Feminino , Perfilação da Expressão Gênica , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Masculino , Pessoa de Meia-Idade , Câncer Papilífero da Tireoide/patologia , Câncer Papilífero da Tireoide/radioterapia , Neoplasias da Glândula Tireoide/patologia , Neoplasias da Glândula Tireoide/radioterapiaRESUMO
CONTEXT: Pregnancy-related hormones may stimulate thyroid cancer growth, but whether pregnancy affects the prognoses of patients with lung metastases from differentiated thyroid cancer (DTC-LM) after surgery and radioiodine therapy is unclear. OBJECTIVE: To assess the impact of pregnancy on DTC-LM through the comparison of prognoses between female patients with DTC-LM who did and did not become pregnant after surgery and radioiodine therapy. METHODS: We retrospectively analyzed the records of 124 female patients aged 16 to 35 years who underwent surgery and radioiodine therapy for DTC-LM. These patients were divided into pregnancy group (n = 37) and nonpregnancy group (n = 87) according to whether they became pregnant after surgery and radioiodine therapy, regardless of whether they had a pregnant history before treatment. RESULTS: The 5- and 10-year progression-free survival rates were 94.52% and 63.22% in pregnancy group versus 89.82% and 58.13% in nonpregnancy group. The 5- and 10-year cumulative overall survival rates of pregnancy group were 97.30% and 85.77% versus 93.50% and 81.95% in nonpregnancy group (all P > 0.05). The median time of follow-up in the pregnancy and nonpregnancy groups was 82 months (25-136 months) and 68 months (13-133 months), respectively. Non-radioiodine-avid LM and primary tumors needing repeated resection were independent predictors of poor progression-free survival for patients in pregnancy group. CONCLUSION: Pregnancy does not affect the prognoses of patients with DTC-LM after surgery and radioiodine therapy. Non-radioiodine-avid LM and repeated primary tumor surgeries are independent risk factors for poor prognoses of pregnant patients.
Assuntos
Adenocarcinoma Folicular/secundário , Neoplasias Pulmonares/secundário , Complicações Neoplásicas na Gravidez/patologia , Câncer Papilífero da Tireoide/secundário , Neoplasias da Glândula Tireoide/patologia , Adenocarcinoma Folicular/mortalidade , Adenocarcinoma Folicular/radioterapia , Adolescente , Adulto , Feminino , Humanos , Radioisótopos do Iodo , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/radioterapia , Gravidez , Complicações Neoplásicas na Gravidez/mortalidade , Complicações Neoplásicas na Gravidez/radioterapia , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida , Câncer Papilífero da Tireoide/mortalidade , Câncer Papilífero da Tireoide/radioterapia , Neoplasias da Glândula Tireoide/mortalidade , Neoplasias da Glândula Tireoide/radioterapia , Resultado do Tratamento , Adulto JovemRESUMO
OBJECTIVE: The aim of the study was the quantification of circulating tumour cells (CTCs) in differentiated thyroid cancer (DTC) patients before and 6 weeks after radioiodine therapy (RIT). CONTEXT: Circulating tumour cells (CTCs) were described more recently in cancer patients, mostly correlating with poor outcome and advanced metastases. DESIGN: Peripheral blood for identification and quantification of CTC before RIT or/and 6 weeks after RIT was provided by 55 DTC patients that received RIT for remnant tissue ablation. PATIENTS: 13 follicular thyroid cancer (FTC) patients, 31 papillary thyroid cancer (PTC) patients and 11 patients having the follicular variant PTC (FV-PTC) were included. MEASUREMENTS: Peripheral blood mononuclear cells (PBMCs) were isolated and EpCAM-positive CTCs were counted by immune fluorescent staining. RESULTS: A CTC positivity of 31.8% before RIT could be observed. Six weeks after RIT, the CTC positivity was reduced to 13.6%. Paired data at both time points of blood sampling could be gathered for n = 33 DTC patients. These patients had significantly higher CTC numbers before RIT than 6 weeks afterwards (0.27 ± 0.47 vs 0.05 ± 0.15, P = .0215). Additionally, significantly reduced CTC numbers were also demonstrated in pre-RIT CTC-positive patients (0.88 ± 0.43 vs 0.05 ± 0.16, P = .0039). CONCLUSION: Our results indicate a reducing effect on the number of CTCs by RIT. Therefore, CTC enumeration should be considered as efficient tool for treatment monitoring during RIT.
Assuntos
Adenocarcinoma Folicular , Células Neoplásicas Circulantes , Neoplasias da Glândula Tireoide , Adenocarcinoma Folicular/radioterapia , Humanos , Radioisótopos do Iodo/uso terapêutico , Leucócitos Mononucleares , Neoplasias da Glândula Tireoide/radioterapiaAssuntos
Radioisótopos do Iodo/uso terapêutico , Neoplasias Ovarianas/radioterapia , Neoplasias Ovarianas/cirurgia , Neoplasias Peritoneais/secundário , Estruma Ovariano/radioterapia , Estruma Ovariano/cirurgia , Adenocarcinoma Folicular/patologia , Adenocarcinoma Folicular/radioterapia , Adenocarcinoma Folicular/cirurgia , Anexos Uterinos/cirurgia , Adulto , Apendicectomia , Feminino , Seguimentos , Humanos , Histerectomia , Estadiamento de Neoplasias , Omento/cirurgia , Neoplasias Ovarianas/patologia , Neoplasias Peritoneais/tratamento farmacológico , Neoplasias Peritoneais/radioterapia , Neoplasias Retais/secundário , Estruma Ovariano/patologia , Tireoidectomia , Tomografia Computadorizada por Raios X , UltrassonografiaRESUMO
PURPOSE: We speculated that radioiodine remnant ablation (RRA) could be performed less frequently in differentiated thyroid cancer (DTC) patients, if the recommendations of the 2018 Italian Consensus (ITA) were applied in clinical practice. Therefore, we compared the ITA indications for RRA with the recommendations by the 2015 American Thyroid Association guidelines (ATA). METHODS: We retrospectively evaluated 380 consecutive DTC patients treated with surgery and RRA, followed at the Section of Endocrinology, University of Siena, Italy from January 2006 to December 2019. RESULTS: Using ITA a significant increase of DTC patients classified as low or high risk and a significant decrease of patients defined at intermediate risk were observed (p < 0.0001). Consequently, the percentage of patients without routinary indication for RRA (47.4%, versus 38.2%, p < 0.0001) and those with a definite indication for RRA (8.2 versus 1.8%, p < 0.0001) was significantly higher compared to ATA. Moreover, using ITA the percentage of patients with a selective use of RRA was lower in comparison to ATA (44.7% versus 60%, p < 0.0001). Nevertheless, the prevalence of distant metastases, at post-ablative whole body scan, in patients without indication for RRA, was not different using either ATA or ITA (2.1% and 1.1% respectively, p = 0.37). CONCLUSION: The use of ITA Consensus, in clinical practice, increases significantly the number of patients for whom RRA is not routinely indicated in comparison to ATA guidelines but without differences in delaying the diagnosis of distant metastatic disease.
Assuntos
Adenocarcinoma Folicular/radioterapia , Adenocarcinoma/radioterapia , Carcinoma Papilar/radioterapia , Radioisótopos do Iodo/uso terapêutico , Guias de Prática Clínica como Assunto/normas , Neoplasias da Glândula Tireoide/radioterapia , Adenocarcinoma/patologia , Adenocarcinoma Folicular/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Papilar/patologia , Criança , Feminino , Seguimentos , Humanos , Itália , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Neoplasias da Glândula Tireoide/patologia , Adulto JovemRESUMO
On rare occasions, differentiated thyroid carcinoma causes tumor thrombosis in the great veins. Multimodality treatment with surgery, radioiodine therapy, and targeted therapies is used to manage tumor thrombosis associated with thyroid malignancies, though no established guidelines exist. We present a woman with a tracer-avid tumor thrombus in the right brachiocephalic vein after surgery for follicular thyroid carcinoma. Follow-up revealed an excellent response after treatment with 131I as a single modality for both remnant and tumor thrombus.
Assuntos
Adenocarcinoma Folicular , Trombose , Neoplasias da Glândula Tireoide , Adenocarcinoma Folicular/diagnóstico por imagem , Adenocarcinoma Folicular/radioterapia , Feminino , Humanos , Radioisótopos do Iodo/uso terapêutico , Mediastino , Neoplasias da Glândula Tireoide/radioterapiaRESUMO
Background: Repeated radioiodine (131I) treatment (RT) are commonly performed in patients with 131I-avid distant metastatic differentiated thyroid cancer (DM-DTC), but more precise indications remain indeterminate. This prospective study was conducted to explore predictors for biochemical response (BR) to next RT. Methods: Totally thyroidectomized patients with 131I-avid DM-DTC demonstrated by initial post-therapeutic whole body scan (Rx-WBS) were consecutively recruited. Repeated RTs were performed at a fixed dose and a fixed interval, which was terminated once a decline in thyroid stimulating hormone-suppressed thyroglobulin (Tgon) could not be achieved or Rx-WBS was negative. BR was evaluated by change rate of Tgon level (ΔTgon%). Results: After exclusion of 27 ineligible courses, a total of 166 neighboring course pairs from 77 patients were established and utilized. Univariate and multivariate analyses showed that the maximum target/background ratio (T/Bmax) on the whole body scan and ΔTgon% derived from the former RT were independently associated to the latter one. In predicting biochemical remission, the positive predictive value (PPV) and negative predictive value (NPV) of T/Bmax at the cut-off value of 8.1 were 79.1% and 84.0%, respectively; whereas the PPV and NPV of ΔTgon% at the cut-off value of 25.3% were 70.8% and 77.1%, respectively. Notably, the PPV of combined T/Bmax ≥ 8.1 and ΔTgon% ≥ 25.3% increased to 87.7%; while the NPV of T/Bmax ≥ 8.1 or ΔTgon% ≥ 25.3% reached as high as 97.7%. Conclusions: This study revealed that combined use of the latest RT-derived T/Bmax and ΔTgon% may efficiently identify biochemical responders/non-responders to next RT, warranting management optimization of patients with 131I-avid DM-DTC.
Assuntos
Adenocarcinoma Folicular/sangue , Adenocarcinoma Folicular/radioterapia , Radioisótopos do Iodo/administração & dosagem , Neoplasias Pulmonares/secundário , Compostos Radiofarmacêuticos/administração & dosagem , Tireoglobulina/sangue , Câncer Papilífero da Tireoide/sangue , Câncer Papilífero da Tireoide/radioterapia , Adenocarcinoma Folicular/diagnóstico por imagem , Adenocarcinoma Folicular/patologia , Adulto , Idoso , Feminino , Humanos , Neoplasias Pulmonares/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Indução de Remissão , Câncer Papilífero da Tireoide/diagnóstico por imagem , Câncer Papilífero da Tireoide/patologia , Tireotropina/sangue , Tiroxina/administração & dosagem , Resultado do Tratamento , Imagem Corporal Total/métodos , Adulto JovemRESUMO
Radioiodine therapy with 131I remains the mainstay of standard treatment for well-differentiated thyroid cancer (DTC). Prognosis is good but concern exists that 131I-emitted ionizing radiation may induce double-strand breaks in extra-thyroidal tissues, increasing the risk of secondary malignancies. We, therefore, sought to evaluate the induction and 2-year persistence of micronuclei (MN) in lymphocytes from 26 131I-treated DTC patients and the potential impact of nine homologous recombination (HR), non-homologous end-joining (NHEJ), and mismatch repair (MMR) polymorphisms on MN levels. MN frequency was determined by the cytokinesis-blocked micronucleus assay while genotyping was performed through pre-designed TaqMan® Assays or conventional PCR-restriction fragment length polymorphism (RFLP). MN levels increased significantly one month after therapy and remained persistently higher than baseline for 2 years. A marked reduction in lymphocyte proliferation capacity was also apparent 2 years after therapy. MLH1 rs1799977 was associated with MN frequency (absolute or net variation) one month after therapy, in two independent groups. Significant associations were also observed for MSH3 rs26279, MSH4 rs5745325, NBN rs1805794, and tumor histotype. Overall, our results suggest that 131I therapy may pose a long-term challenge to cells other than thyrocytes and that the individual genetic profile may influence 131I sensitivity, hence its risk-benefit ratio. Further studies are warranted to confirm the potential utility of these single nucleotide polymorphisms (SNPs) as radiogenomic biomarkers in the personalization of radioiodine therapy.
Assuntos
Adenocarcinoma Folicular/patologia , Carcinoma Papilar/patologia , Reparo do DNA , Radioisótopos do Iodo/uso terapêutico , Micronúcleos com Defeito Cromossômico/efeitos da radiação , Polimorfismo de Nucleotídeo Único , Neoplasias da Glândula Tireoide/patologia , Adenocarcinoma Folicular/genética , Adenocarcinoma Folicular/radioterapia , Adulto , Idoso , Carcinoma Papilar/genética , Carcinoma Papilar/radioterapia , Feminino , Seguimentos , Humanos , Linfócitos/patologia , Linfócitos/efeitos da radiação , Masculino , Pessoa de Meia-Idade , Prognóstico , Neoplasias da Glândula Tireoide/genética , Neoplasias da Glândula Tireoide/radioterapiaRESUMO
We retrospectively evaluated the frequency of unexpected accumulation of radioactive iodine on the post-therapy whole-body scan (Rx-WBS) after radioactive iodine (RAI) ablation therapy in patients with differentiated thyroid cancer (DTC). We searched our institutional database for Rx-WBSs of DTC patients who underwent RAI ablation or adjuvant therapy between 2012 and 2019. Patients with distant metastasis diagnosed by CT or PET/CT before therapy, and those had previously received RAI therapy were excluded. In total, 293 patients (201 female and 92 male, median age 54 years) were selected. Two nuclear medicine physicians interpreted the Rx-WBS images by determining the visual intensity of radioiodine uptake by the thyroid bed, cervical and mediastinal lymph nodes, lungs, and bone. Clinical features of the patients with and without the metastatic accumulation were compared by chi-square test and median test. Logistic regression analyses were performed to compare the association between the presence of metastatic accumulation and these clinical factors. Eighty-four of 293 patients (28.7%) showed metastatic accumulation. Patients with metastatic RAI accumulation showed a significantly higher frequency of pathological N1 (pN1) and serum thyroglobulin (Tg) > 1.5 ng/ml under TSH stimulation (p = 0.035 and p = 0.031, respectively). Logistic regression analysis indicated that a serum Tg > 1.5 ng/ml was significantly correlated with the presence of metastatic accumulation (odds ratio = 1.985; p = 0.033). In conclusion, Patients with Tg > 1.5 ng/ml were more likely to show metastatic accumulation. In addition, the presence of lymph node metastasis at the initial thyroid surgery was also associated with this unexpected metastatic accumulation.