RESUMO
PURPOSE: To determine efficacy and safety of thermal ablation (TA) for the local treatment of lung metastases of thyroid cancer. METHODS: We retrospectively studied 47 patients from 10 centers treated by TA (radiofrequency, microwaves, and cryoablation) over 10 years. The endpoints were overall survival (OS), local efficacy, complications (CTCAE classification), and factors associated with survival. OS curves after first TA were built using the Kaplan-Meier method and compared with the log-rank test. RESULTS: A total of 107 lung metastases during 75 sessions were treated by radiofrequency (n = 56), microwaves (n = 9), and cryoablation (n = 10). Median follow-up time after TA was 5.2 years (0.2-13.3). OS was 93% at 2 years (95% confidence interval (CI): 86-94) and 79% at 3 years (95% CI: 66-91). On univariate and multivariate analysis with a Cox model, histology was the only significant factor for OS. OS at 3 years was 94% for follicular, oncocytic, or papillary follicular variant carcinomas, compared to 59% for papillary, medullary, insular or anaplastic carcinomas (P = 0.0001). The local control rate was 98.1% at 1 year and 94.8% at 2, 3, 4, and 5 years. Morbidity was low with no major complications (grade 4 and 5 CTCAE) and no complications in 29 of 75 sessions (38.7%). CONCLUSIONS: TA is a useful, safe and effective option for local treatment of lung metastases from thyroid carcinoma. Prolonged OS was obtained, especially for lung metastases from follicular, oncocytic, or papillary follicular variant carcinomas. Achieving disease control with TA delays the need for systemic treatment.
Assuntos
Ablação por Cateter , Neoplasias Pulmonares , Neoplasias da Glândula Tireoide , Humanos , Neoplasias Pulmonares/cirurgia , Micro-Ondas , Estudos Retrospectivos , Taxa de Sobrevida , Neoplasias da Glândula Tireoide/cirurgia , Resultado do TratamentoRESUMO
PURPOSE: Surgical treatment of recalcitrant lateral epicondylitis [LE] remains difficult, with suboptimal results. This prospective study aimed to determine whether percutaneous epicondylar tenotomy combined with PRP injection under ultrasonography control would optimize the surgery results, with an early gain on pain and strength and a rapid return to professional activities at 3 months. The secondary objective was to determine whether clinical or biological risk factors (e.g., composition of the PRP) affected the outcomes. METHODS: A total number of 261 Patients with recalcitrant LE underwent percutaneous epicondylar tenotomy under ultrasonography control, coupled with PRP injection. All patients were clinically assessed using VAS pain scale, the functional scores: QuickDASH [Disabilities of the Arm, Shoulder and Hand], Patient-Rated Tennis Elbow Evaluation [PRTEE] and MEPS [Mayo Elbow Performance Score]; Elbow Self-Assessment Score [ESAS]; grip strength; and return to work. RESULTS: At 3-month follow-up, the VAS score decreased by 3.4 points (SD 2.2; p<0.0001), the QuickDASH decreased by 32.9 points (SD 18.9, range 56.1-23.1; p<0.0001), the PRTEE decreased by 14.8 points (SD 19.1, 49.8-26.4; p=0.017), and the MEPS increased by 19.4 points (SD 13.1, 67.4-86.9; p<0.0001); grip strength increased to 8.3kg (SD 10.7; p<0.0001) and increased by 26% (SD 0.60, 0.7-0.96; p<0.0001) as compared with the opposite side. The ESAS showed 78.3% improvement. CONCLUSION: Treatment of recalcitrant LE by percutaneous tenotomy combined with PRP injection under ultrasonography control provides rapid recovery in terms of pain and strength, with a high level of satisfaction and a high rate of early return to work. STUDY DESIGN: Case series.
Assuntos
Plasma Rico em Plaquetas , Cotovelo de Tenista , Humanos , Estudos Prospectivos , Cotovelo de Tenista/diagnóstico por imagem , Cotovelo de Tenista/cirurgia , Tenotomia , UltrassonografiaRESUMO
An 82-year-old man, who was diagnosed in 2002 with an oncocytic (Hürthle cell) thyroid carcinoma, was initially treated by local surgery and was refractory to radioiodine treatment. The patient had successive secondary recurrences from 2006 onwards. Metastases were suspected due to an elevation of thyroglobulin in serum. Hypermetabolic nodules were targeted using FDG PET as well as CT-guided radiofrequency ablations. Thyroglobulin levels decreased following each procedure. 10 years later, tolerance and efficacy are excellent; 23 lung metastases have been treated during 11 sessions without current relapse. Respiratory function and quality of life are not altered. This report illustrates how radiofrequency ablation can be efficiently integrated into the long-term management of poorly aggressive oligometastatic cancer, in combination with other local and/or systemic therapies.
Assuntos
Ablação por Cateter/métodos , Neoplasias Pulmonares/secundário , Neoplasias Pulmonares/cirurgia , Pulmão/fisiologia , Recidiva Local de Neoplasia/cirurgia , Neoplasias da Glândula Tireoide/patologia , Idoso de 80 Anos ou mais , Humanos , Pulmão/cirurgia , Masculino , Testes de Função RespiratóriaRESUMO
BACKGROUND: The aim of this study was to evaluate the effectiveness of sunitinib in patients with progressive radioiodine refractory (RAIR) thyroid cancer (TC). MATERIALS AND METHODS: A multicentric retrospective analysis was performed of patients treated in six TUmeurs THYroïdiennes REFractaires participating centers. All patients with progressive RAIR TC who were treated with sunitinib outside a clinical trial between August 2007 and March 2015 were retrospectively and consecutively included. The primary endpoint was the overall response rate (ORR) and disease control rate ≥6 months based on RECIST criteria. Secondary endpoints included evaluation of overall survival (OS) and progression-free survival (PFS) from the first dose of sunitinib. Primary and secondary endpoints were also evaluated according to treatment setting: first or second line of tyrosine kinase inhibitor (TKI). RESULTS: Fifty-seven patients (29 men; 50.8%), mean age 62.2 years (range 43-80 years) with progressive RAIR TC were included. Sunitinib was the first-line TKI treatment for 32 (56.1%) patients and the second-line TKI treatment for 25 (43.9%) patients. For all patients, according to RECIST criteria, ORR was 35.1% (20 patients) and disease control rate ≥6 months was 68.4% (39 patients). No complete response was observed. Six (10.5%) patients showed disease progression. When sunitinib was used as first-line TKI therapy, ORR was 46.9% (15/32 patients), and disease control rate ≥6 months was 75% (24/32 patients). When sunitinib was used as second-line TKI therapy, ORR was 20% (5/25 patients), and disease control rate ≥6 months was 60% (15/25 patients). The median OS and PFS were 21.0 (range 15-29) and 10.2 months (range 6-13), respectively, for all patients. With sunitinib as first-line TKI-therapy, median OS and PFS was 30.0 (range 19.0-53.0) and 15 (range 7.0-21.0) months, respectively. As second-line therapy, median OS and PFS were 13 (range 8.0-20.0) and 6 (range 5.0-11.0) months, respectively. Eleven (19.3%) patients experienced grade 3 toxicity, and four patients (7.0%) experienced grade 4 toxicity. CONCLUSION: The efficacy of sunitinib as first- and second-line TKI therapy in a large cohort of patients treated for progressive RAIR TC is herein reported. Further prospective studies are needed to evaluate the effectiveness of sunitinib in RAIR TC.
Assuntos
Adenocarcinoma Folicular/tratamento farmacológico , Antineoplásicos/uso terapêutico , Carcinoma Papilar/tratamento farmacológico , Indóis/uso terapêutico , Pirróis/uso terapêutico , Neoplasias da Glândula Tireoide/tratamento farmacológico , Adenocarcinoma Folicular/mortalidade , Adenocarcinoma Folicular/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/efeitos adversos , Carcinoma Papilar/mortalidade , Carcinoma Papilar/patologia , Intervalo Livre de Doença , Feminino , Humanos , Indóis/efeitos adversos , Masculino , Pessoa de Meia-Idade , Pirróis/efeitos adversos , Estudos Retrospectivos , Sunitinibe , Taxa de Sobrevida , Neoplasias da Glândula Tireoide/mortalidade , Neoplasias da Glândula Tireoide/patologia , Resultado do TratamentoRESUMO
Effective adverse event (AE) management is critical to maintaining patients on anticancer therapies. The DECISION trial was a multicenter, randomized, double-blind, placebo-controlled, Phase 3 trial which investigated sorafenib for treatment of progressive, advanced, or metastatic radioactive iodine-refractory, differentiated thyroid carcinoma. Four hundred and seventeen adult patients were randomized (1:1) to receive oral sorafenib (400âmg, twice daily) or placebo, until progression, unacceptable toxicity, noncompliance, or withdrawal. Progression-free survival, the primary endpoint of DECISION, was reported previously. To elucidate the patterns and management of AEs in sorafenib-treated patients in the DECISION trial, this report describes detailed, by-treatment-cycle analyses of the incidence, prevalence, and severity of hand-foot skin reaction (HFSR), rash/desquamation, hypertension, diarrhea, fatigue, weight loss, increased serum thyroid stimulating hormone, and hypocalcemia, as well as the interventions used to manage these AEs. By-cycle incidence of the above-selected AEs with sorafenib was generally highest in cycle 1 or 2 then decreased. AE prevalence generally increased over cycles 2-6 then stabilized or declined. Among these AEs, only weight loss tended to increase in severity (from grade 1 to 2) over time; severity of HFSR and rash/desquamation declined over time. AEs were mostly grade 1 or 2, and were generally managed with dose interruptions/reductions, and concomitant medications (e.g. antidiarrheals, antihypertensives, dermatologic preparations). Most dose interruptions/reductions occurred in early cycles. In conclusion, AEs with sorafenib in DECISION were typically grade 1 or 2, occurred early during the treatment course, and were manageable over time.
Assuntos
Adenocarcinoma Folicular/tratamento farmacológico , Antineoplásicos/efeitos adversos , Carcinoma Papilar/tratamento farmacológico , Diarreia/induzido quimicamente , Toxidermias/etiologia , Fadiga/induzido quimicamente , Hipertensão/induzido quimicamente , Hipocalcemia/induzido quimicamente , Niacinamida/análogos & derivados , Compostos de Fenilureia/efeitos adversos , Inibidores de Proteínas Quinases/efeitos adversos , Neoplasias da Glândula Tireoide/tratamento farmacológico , Adenocarcinoma Folicular/enzimologia , Adenocarcinoma Folicular/radioterapia , Adenoma Oxífilo/tratamento farmacológico , Adenoma Oxífilo/enzimologia , Adenoma Oxífilo/radioterapia , Idoso , Antineoplásicos/uso terapêutico , Carcinoma Papilar/enzimologia , Carcinoma Papilar/radioterapia , Diarreia/tratamento farmacológico , Diarreia/epidemiologia , Intervalo Livre de Doença , Toxidermias/tratamento farmacológico , Toxidermias/epidemiologia , Resistencia a Medicamentos Antineoplásicos , Dispneia/induzido quimicamente , Dispneia/epidemiologia , Fadiga/epidemiologia , Feminino , Humanos , Hipertensão/tratamento farmacológico , Hipertensão/epidemiologia , Hipocalcemia/epidemiologia , Incidência , Radioisótopos do Iodo/uso terapêutico , Masculino , Pessoa de Meia-Idade , Segunda Neoplasia Primária/induzido quimicamente , Segunda Neoplasia Primária/epidemiologia , Niacinamida/efeitos adversos , Niacinamida/uso terapêutico , Compostos de Fenilureia/uso terapêutico , Prevalência , Inibidores de Proteínas Quinases/uso terapêutico , Compostos Radiofarmacêuticos/uso terapêutico , Sorafenibe , Neoplasias da Glândula Tireoide/enzimologia , Neoplasias da Glândula Tireoide/radioterapia , Redução de Peso/efeitos dos fármacosRESUMO
Thermal ablation (radiofrequency, microwave, cryosurgery, laser interstitial thermal therapy) is being used more frequently as a local treatment of secondary but also primary cancers and benign lesions. It has a low morbidity and is repeatable. The problem is that computed tomographic scan has limits, and RECIST criteria are not applicable. The objective of this article is to summarize the usefulness and pitfalls of PET/computed tomography in detecting a relapse after thermal ablation as soon as possible.
Assuntos
Técnicas de Ablação/métodos , Imagem Multimodal/métodos , Neoplasias/diagnóstico , Neoplasias/cirurgia , Tomografia por Emissão de Pósitrons/métodos , Tomografia Computadorizada por Raios X/métodos , Humanos , Prognóstico , Cirurgia Assistida por Computador/métodos , Resultado do TratamentoRESUMO
PURPOSE: In the ESTIMABL phase III trial, the thyroid ablation rate was equivalent for the two thyroid-stimulating hormone (TSH) stimulation methods (thyroid hormone withdrawal [THW] and recombinant human TSH [rhTSH]) and the two iodine-131 ((131)I) activities (1.1 or 3.7 GBq). The objectives of this article were to present health-related quality-of-life (HRQoL) results and a cost-effectiveness evaluation performed alongside this trial. PATIENTS AND METHODS: HRQoL and utility were longitudinally assessed, from random assignment to the follow-up visit at 8 ± 2 months for the 752 patients with thyroid cancer, using the Short Form-36 and the EuroQoL-5D questionnaires, respectively. A cost-effectiveness analysis was performed from the societal perspective in the French context. Resource use (hospitalization for (131)I administration, rhTSH, sick leaves, and transportation) was collected prospectively. We used the net monetary benefit approach and computed cost-effectiveness acceptability curves for both TSH stimulation methods and (131)I activities. Sensitivity analyses of the costs of rhTSH were performed. RESULTS: At (131)I administration, THW caused a clinically significant deterioration of HRQoL, whereas HRQoL remained stable with rhTSH. This deterioration was transient with no difference 3 months later. rhTSH was more effective than THW in terms of quality-adjusted life-years (QALYs; +0.013 QALY/patient) but more expensive (+474/patient). The probability that rhTSH would be cost effective at a 50,000/QALY threshold was 47% in France. The use of 1.1 GBq of (131)I instead of 3.7 GBq reduced per-patient costs by 955 (US$1,018) but with slightly decreased efficacy (-0.007 QALY/patient). CONCLUSION: rhTSH avoids the transient THW-induced deterioration of HRQoL but is unlikely to be cost effective at its current price.
Assuntos
Análise Custo-Benefício , Radioisótopos do Iodo/uso terapêutico , Qualidade de Vida , Neoplasias da Glândula Tireoide/radioterapia , Recursos em Saúde , Humanos , Anos de Vida Ajustados por Qualidade de Vida , Proteínas Recombinantes/uso terapêutico , Neoplasias da Glândula Tireoide/psicologia , Tireotropina/uso terapêuticoRESUMO
BACKGROUND: A randomized phase III trial demonstrated that vandetanib treatment is effective in patients with metastatic medullary thyroid cancer (MTC), leading to regulatory approval, but its use may be associated with toxicities that require specific monitoring and management. The objective of the present study performed in France was to describe the toxicity profile and efficacy of vandetanib treatment when given outside any trial. METHODS: Sixty-eight patients were treated with vandetanib in the frame of a temporary use authorization (ATU) in France from August 2010 to February 2012, when the drug was available on request for patients with locally advanced or metastatic MTC. Patients were registered by the French health authorities, and characteristics, treatment parameters, toxicity profile, and efficacy were retrospectively reviewed. Eight patients were excluded from the analysis because vandetanib treatment was not administered (n=3), had been given in a trial before ATU (n=3), or was given for a non-MTC cancer (n=2). RESULTS: Data from the 60 MTC patients were analyzed. Mean age was 58 years (range 11-83 years), 39 patients were male, and six had hereditary MTC. Fifty-six (93%) had metastatic disease in the mediastinum (82%), bones (65%), liver (53%), or lung (53%), and four had only locally advanced disease. At the time of study evaluation, with a median follow-up of 20 months and a median duration of treatment of 9.7 months (range 0.3-36 months), 15 patients were continuing vandetanib treatment (range 18-36 months). Median progression-free survival was 16.1 months. Twenty-five patients discontinued treatment for disease progression (range 0.3-29 months). Best tumor response was a complete response in one patient, a partial response in 12 (20%), stable disease in 33 (55%), and progression in seven patients (12%). All patients had at least one adverse event (AE) during treatment. The main AEs were skin toxicity, diarrhea, and asthenia. Sixteen patients (27%) discontinued treatment for toxicity, and one patient died from vandetanib-induced cardiac toxicity. CONCLUSIONS: Vandetanib is an effective option for patients with advanced MTC. AEs should be monitored carefully and should be minimized by educating both patients and care providers and by applying symptomatic treatment and dose reduction.
Assuntos
Antineoplásicos/uso terapêutico , Carcinoma Neuroendócrino/tratamento farmacológico , Piperidinas/uso terapêutico , Inibidores de Proteínas Quinases/uso terapêutico , Quinazolinas/uso terapêutico , Neoplasias da Glândula Tireoide/tratamento farmacológico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/efeitos adversos , Carcinoma Neuroendócrino/mortalidade , Carcinoma Neuroendócrino/patologia , Criança , Feminino , França , Humanos , Masculino , Pessoa de Meia-Idade , Piperidinas/efeitos adversos , Inibidores de Proteínas Quinases/efeitos adversos , Quinazolinas/efeitos adversos , Estudos Retrospectivos , Fatores de Risco , Neoplasias da Glândula Tireoide/mortalidade , Neoplasias da Glândula Tireoide/patologia , Fatores de Tempo , Resultado do Tratamento , Adulto JovemAssuntos
Antineoplásicos/uso terapêutico , Biomarcadores Tumorais/genética , Rearranjo Gênico , Neoplasias Pulmonares/tratamento farmacológico , Inibidores de Proteínas Quinases/uso terapêutico , Pirazóis/uso terapêutico , Piridinas/uso terapêutico , Receptores Proteína Tirosina Quinases/antagonistas & inibidores , Receptores Proteína Tirosina Quinases/genética , Carcinoma Anaplásico da Tireoide/tratamento farmacológico , Neoplasias da Glândula Tireoide/tratamento farmacológico , Idoso , Quinase do Linfoma Anaplásico , Biópsia , Quimioterapia Adjuvante , Crizotinibe , Feminino , Humanos , Imuno-Histoquímica , Hibridização in Situ Fluorescente , Neoplasias Pulmonares/enzimologia , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/secundário , Estadiamento de Neoplasias , Medicina de Precisão , Valor Preditivo dos Testes , Indução de Remissão , Carcinoma Anaplásico da Tireoide/enzimologia , Carcinoma Anaplásico da Tireoide/genética , Carcinoma Anaplásico da Tireoide/secundário , Neoplasias da Glândula Tireoide/enzimologia , Neoplasias da Glândula Tireoide/genética , Neoplasias da Glândula Tireoide/patologia , Tireoidectomia , Fatores de Tempo , Tomografia Computadorizada por Raios X , Resultado do TratamentoRESUMO
BACKGROUND: Spinal metastases (SMs) due to thyroid cancer (TC) are associated with significantly reduced quality of life. The goal of this study is to analyze the clinical manifestations, presentation, and treatments of TC SMs, and to describe specific features of SMs associated with different TC types. PATIENTS AND METHODS: A retrospective analysis of 202 TC SM patients treated at Medstar Washington Hospital Center (37) and collected from the literature (165) was performed. RESULTS: The mean age of patients with SMs was 56.9±14.7 years, and the female-to-male ratio was 2.1:1. Of all patients, 29% (28% of follicular thyroid cancer [FTC] and 37% of papillary thyroid cancer [PTC]) had SMs only. Twenty-nine percent of all patients and 54% of patients with single-site SMs had neither bone non-SMs nor solid organ metastases at the time of presentation. Thirty-five percent of patients had SMs as an initial presentation of TC. TC patients presenting with SMs had a lower rate of other bone and visceral involvement compared with patients whose SMs were diagnosed at the time of thyroid surgery or during follow-up (p<0.05). SMs were more often the initial manifestation of FTC (41% vs. 24%), while PTC SMs were more commonly diagnosed after TC diagnosis (76% vs. 59%; p<0.05). PTC SMs were more frequently diagnosed as synchronous (63% vs. 36% in FTC) versus FTC SMs that developed as metachronous metastases (64% vs. 37% in PTC; p<0.01). All FTC SMs developed within 82 (0-372) months and all PTC SMs within 35 (0-144) months (p<0.01). In FTC SMs as TC manifestation, solid organ metastases involvement was less common than in FTC SMs that were found after TC diagnosis (34% vs. 67%; p<0.01); multisite FTC SMs compared to solitary FTC SMs were associated with the development of other bone nonspinal metastases (82% vs. 30%; p<0.01) and solitary organ metastases (65% vs. 41%; p<0.01). These correlations were not observed in PTC SMs. FTC patients often had neural structure compression (myelopathy/radiculopathy; 72% vs. 36% in PTC), while PTC patients frequently were asymptomatic (38% vs. 5% in FTC; p<0.01). FTC SMs more commonly were (131)I-avid (p<0.01). FTC patients required surgery more frequently (72% vs. 55% in PTC; p<0.05). CONCLUSIONS: Our study reveals that a significant part of TC SMs patients have solitary spinal involvement at the time of presentation and may be considered for aggressive treatment with the intention to improve quality of life and survival. FTC SMs and PTC SMs appear to have distinct presentations, behavior, and treatment modalities, and should be categorized separately for treatment and follow-up planning.
Assuntos
Adenocarcinoma Folicular/secundário , Carcinoma/secundário , Neoplasias da Coluna Vertebral/secundário , Neoplasias da Glândula Tireoide/patologia , Adenocarcinoma Folicular/mortalidade , Adenocarcinoma Folicular/terapia , Adulto , Idoso , Carcinoma/mortalidade , Carcinoma/terapia , Carcinoma Papilar , District of Columbia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Seleção de Pacientes , Estudos Retrospectivos , Fatores de Risco , Neoplasias da Coluna Vertebral/mortalidade , Neoplasias da Coluna Vertebral/terapia , Câncer Papilífero da Tireoide , Neoplasias da Glândula Tireoide/mortalidade , Fatores de Tempo , Resultado do TratamentoRESUMO
OBJECTIVE: Tyrosine kinase inhibitors (TKIs) are used to treat patients with advanced thyroid cancers. We retrospectively investigated the efficacy of TKIs administered outside of clinical trials in metastatic sites or locally advanced thyroid cancer patients from five French oncology centers. DESIGN AND METHODS: THERE WERE 62 PATIENTS (37 MEN, MEAN AGE: 61 years) treated with sorafenib (62%), sunitinib (22%), and vandetanib (16%) outside of clinical trials; 22 had papillary, five had follicular, five had Hürthle cell, 13 had poorly differentiated, and 17 had medullary thyroid carcinoma (MTC). Thirty-three, 25, and four patients were treated with one, two, and three lines of TKIs respectively. Primary endpoints were objective tumor response rate and progression-free survival (PFS). Sequential treatments and tumor response according to metastatic sites were secondary endpoints. RESULTS: Among the 39 sorafenib and 12 sunitinib treatments in differentiated thyroid carcinoma (DTC) patients, partial response (PR) rate was 15 and 8% respectively. In the 11 MTC patients treated with vandetanib, 36% had PR. Median PFS was similar in second-line compared with first-line sorafenib or sunitinib therapy (6.7 vs 7.0 months) in DTC patients, but there was no PR with second- and third-line treatments. Bone and pleural lesions were the most refractory sites to treatment. CONCLUSIONS: This is the largest retrospective study evaluating TKI therapies outside of clinical trials. DTC patients treated with second-line therapy had stable disease as best response, but had a similar median PFS compared with the first-line treatment.
Assuntos
Adenocarcinoma/tratamento farmacológico , Antineoplásicos/uso terapêutico , Indóis/uso terapêutico , Niacinamida/análogos & derivados , Compostos de Fenilureia/uso terapêutico , Piperidinas/uso terapêutico , Proteínas Tirosina Quinases/antagonistas & inibidores , Pirróis/uso terapêutico , Quinazolinas/uso terapêutico , Neoplasias da Glândula Tireoide/tratamento farmacológico , Adenocarcinoma/secundário , Adenocarcinoma Folicular/tratamento farmacológico , Adenocarcinoma Folicular/secundário , Adenoma Oxífilo , Adulto , Idoso , Neoplasias Ósseas/tratamento farmacológico , Neoplasias Ósseas/secundário , Carcinoma/tratamento farmacológico , Carcinoma/secundário , Carcinoma Neuroendócrino , Carcinoma Papilar , Intervalo Livre de Doença , Feminino , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/secundário , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/secundário , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Niacinamida/uso terapêutico , Neoplasias Pleurais/tratamento farmacológico , Neoplasias Pleurais/secundário , Estudos Retrospectivos , Sorafenibe , Sunitinibe , Câncer Papilífero da Tireoide , Neoplasias da Glândula Tireoide/patologia , Neoplasias da Glândula Tireoide/secundário , Resultado do TratamentoRESUMO
Thyroid carcinoma is the most common endocrine malignant tumor and accounts for 1% of all new malignant diseases. Among all types and subtypes of thyroid cancers that have been described so far, papillary thyroid carcinoma is the most frequent. The standard management treatment of these tumors consists of surgery, followed by radioiodine treatment in case of high risk of relapse. The most aggressive forms are commonly treated by chemotherapy, radiotherapy or experimental drug testing. We recently reported the case of a patient presenting an anaplastic thyroid carcinoma with lung metastases. Fluorescence in situ hybridization analysis allowed us to detect a rearrangement of the anaplastic lymphoma kinase (ALK) gene in both tumors. The patient was treated with crizotinib and presented an excellent drug response. We present here the subsequent investigations carried out to further characterize this genetic alteration and to assess the prevalence of ALK rearrangements in thyroid lesions. High resolution array-comparative genomic hybridization data complemented by RT-PCR and sequencing analyses, allowed us to demonstrate the presence of a STRN/ALK fusion. The STRN/ALK transcript consisted of the fusion between exon 3 of STRN and exon 20 of ALK. Subsequent screening of 75 various thyroid tumors by RT-PCR revealed that 2 out of 29 papillary thyroid carcinomas exhibited the same fusion transcript. None was detected in other types of malignant or benign thyroid lesions analyzed. These findings could pave the way for the development of new targeted therapeutic strategies in the treatment of papillary thyroid carcinomas and point to ALK inhibitors as promising agents that merit rapid evaluation.
Assuntos
Proteínas de Ligação a Calmodulina/genética , Fusão Gênica/genética , Rearranjo Gênico/genética , Neoplasias Pulmonares/secundário , Proteínas de Membrana/genética , Proteínas do Tecido Nervoso/genética , Receptores Proteína Tirosina Quinases/genética , Neoplasias da Glândula Tireoide/genética , Quinase do Linfoma Anaplásico , Sequência de Bases , Hibridização Genômica Comparativa , Crizotinibe , Humanos , Imuno-Histoquímica , Hibridização in Situ Fluorescente , Dados de Sequência Molecular , Pirazóis/uso terapêutico , Piridinas/uso terapêutico , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Análise de Sequência de DNA , Carcinoma Anaplásico da Tireoide , Neoplasias da Glândula Tireoide/tratamento farmacológicoRESUMO
BACKGROUND: Brain metastases (BM) from differentiated thyroid carcinoma (DTC) are uncommon, and many questions about their management remain unsolved. The objective of this retrospective study was to analyze the characteristics, treatments, and outcomes of patients with BM from DTC. METHODS: Among the 1523 patients with a DTC prospectively recorded in institutional databases between 1989 and 2012, 21 patients (1.4%) with BM were retrospectively retrieved. Patient characteristics, histological findings on initial thyroidectomy specimen, treatments, and time to death were reviewed. Overall survival (OS) was calculated using the Kaplan-Meier method. Survival curves for various subgroups of patients according to baseline characteristics and treatment received were compared. RESULTS: The mean age at initial and BM diagnosis was, respectively, 52.7 and 63.2 years. World Health Organization performance status (PS) at BM diagnosis was good (<2) for 12 patients and poor (≥2) for 9. The initial carcinoma was papillary for 12 patients, follicular for 5, and poorly differentiated for 4. Eighteen patients had other previous and/or synchronous distant metastases: lung (11), bone (10), and others (2 peritoneum, 1 liver, 1 adrenal gland, and 1 uterine cervix). The average interval between the first metastasis and the BM was 3 years (range 0-35.6 years). The mean number and the mean size of BM were, respectively, 2.8 (range 1-10) and 22.5 mm (range 3-44 mm). Surgery was performed for 10 patients and radiotherapy (RT) for 18, with 2 stereotactic radiosurgery (SRS), 2 conformal RT limited to the metastasis, and 15 whole-brain RT. The median OS after BM was 7.1 months. OS at 1 and 2 years were 41.6% and 35.6%. PS and realization of surgery or SRS had an impact on survival, with OS of 27 months when PS <2 versus 3 months when PS ≥2 (p=0.0009), and OS of 11.9 months after surgery or SRS versus 3.6 months in their absence (p=0.04). CONCLUSIONS: BM from thyroid cancer may have an indolent evolution with survival of one to two years or longer for specific groups of patients. Therefore, aggressive treatment options such as neurosurgery and RT should be strongly considered in patients with good PS.
Assuntos
Neoplasias Encefálicas/secundário , Neoplasias da Glândula Tireoide/patologia , Adolescente , Adulto , Idoso , Neoplasias Encefálicas/mortalidade , Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/terapia , Carcinoma/patologia , Carcinoma/cirurgia , Carcinoma Papilar , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Radiocirurgia , Estudos Retrospectivos , Câncer Papilífero da Tireoide , Neoplasias da Glândula Tireoide/cirurgiaRESUMO
Whole-body (131I) scintigraphy (WBS) is used to detect residual or metastatic tissue during treatment of differentiated thyroid carcinoma in combination with thyroglobulin (Tg) and ultrasonography of the neck. It is a highly sensitive method, but there is a high rate of false positives. We report the case of a 52-year-old woman with false-positive iodine accumulation in a benign cystic mesothelioma discovered during treatment for a oncocytic follicular thyroid carcinoma (stage pT2 pNx Mx). This lesion was detected by WBS and confirmed by surgery and histopathologic analysis.
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Adenocarcinoma Folicular/diagnóstico por imagem , Mesotelioma Cístico/diagnóstico por imagem , Neoplasias Peritoneais/diagnóstico por imagem , Neoplasias da Glândula Tireoide/diagnóstico por imagem , Adenocarcinoma Folicular/secundário , Diagnóstico Diferencial , Reações Falso-Positivas , Feminino , Humanos , Radioisótopos do Iodo , Pessoa de Meia-Idade , Neoplasias Peritoneais/secundário , Cintilografia , Neoplasias da Glândula Tireoide/patologiaRESUMO
PURPOSE: To assess diagnostic accuracy of (18)F-FDG PET/CT at 3 months for the detection of local recurrence after radiofrequency ablation (RFA) of lung metastases. METHODS: The PET/CT scan at 3 months was compared with a baseline PET/CT scan from a maximum of 2 months before RFA, with the reference standard as recurrence diagnosed by CT during a 12-month follow-up. Local recurrence was diagnosed on the PET/CT scan if lesional uptake was greater than the mediastinal background. Maximum standardized uptake values (SUVmax) were recorded. ROC curve analysis for SUVmax was performed. Overall survival (OS) and time to local relapse were computed from the date of RFA using the Kaplan-Meier method (www.clinicaltrials.gov: NCT 00382252). RESULTS: Between 2005 and 2009, 89 patients (mean age 65 years) underwent RFA for 115 lung metastases (mean size 16.2 ± 6.9 mm). The median SUVmax before RFA was 5.8 ± 4. PET/CT at 3 months and the reference standard were available in 77 patients and 100 lesions. Accuracy was 66.00% (95% CI 55.85-75.18%), sensitivity 90.91% (95 % CI 58.72-99.77 %), specificity 62.92% (95% CI 52.03-72.93%), PPV 23.26% (95% CI 11.76-38.63%), and NPV 98.25% (95% CI 90.61-99.96%). One-year OS was 94.2% (95% CI 86.6-97.5%) and the probability of being free of local recurrence 1 year after RFA was 84.6% (95% CI 75.0-90.8%). CONCLUSION: The specificity of PET/CT at 3 months is low because of persistent inflammation, especially when the lesion is close to the pleura. This technique is useful for its negative predictive value, but positive findings need to be confirmed by histology before new treatment is planned.
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Técnicas de Ablação , Fluordesoxiglucose F18 , Neoplasias Pulmonares/radioterapia , Neoplasias Pulmonares/secundário , Tomografia por Emissão de Pósitrons , Terapia por Radiofrequência , Tomografia Computadorizada por Raios X , Técnicas de Ablação/efeitos adversos , Idoso , Feminino , Seguimentos , Humanos , Neoplasias Pulmonares/diagnóstico por imagem , Masculino , Imagem Multimodal , Metástase Neoplásica , Recidiva Local de Neoplasia , Curva ROC , Ondas de Rádio/efeitos adversos , Padrões de Referência , Análise de Sobrevida , Resultado do TratamentoRESUMO
CONTEXT: An increased cancer mortality is reported in transplanted patients. OBJECTIVE: This multicentric study aimed to investigate the rate of thyroid cancer recurrence after transplantation. RESULTS: Sixty-eight patients (35 male/33 female) with a history of both thyroid cancer and organ transplantation were recruited via two nationwide French networks. Histological analysis identified 58 papillary (88%), 5 follicular (7.5%), and 3 poorly differentiated cancer cases (4.5 %). Thirty-one patients (52%) presented high recurrence risk tumors. In the 36 patients with thyroid cancer diagnosed after transplantation, the 5-year disease-free survival (DFS) was 74.7% (SE: 7.3%). One patient died after progression of a poorly differentiated cancer. Persistent disease was observed in six high-risk patients. One of them underwent a second transplantation and disease remained stable after 5 years of follow-up. Thyroid cancer had been diagnosed before transplantation in 32 patients. One patient with cystic fibrosis and thyroid lung metastases at the time of lung transplantation underwent a 4-year remission. For the 31 patients in remission at the time of transplantation, the 5-year DFS was 93.1% (SE: 4.8%). Two patients with local recurrence presented subsequent remission. For the entire study population, the 5-year and 9-year DFS were 81.9% (SE: 5.5%) and 75.6% (SE: 7.9%), respectively. Recurrence or persistent disease occurred in patients with high-risk tumors. CONCLUSIONS: The prognosis of thyroid cancer does not seem to be altered by transplantation. This suggests that a history of thyroid cancer should not be considered a contraindication.
Assuntos
Adenocarcinoma Folicular/epidemiologia , Carcinoma Papilar/epidemiologia , Recidiva Local de Neoplasia/epidemiologia , Transplante de Órgãos/efeitos adversos , Neoplasias da Glândula Tireoide/epidemiologia , Adenocarcinoma Folicular/patologia , Adenocarcinoma Folicular/cirurgia , Adolescente , Adulto , Idoso , Carcinoma Papilar/patologia , Carcinoma Papilar/cirurgia , Criança , Intervalo Livre de Doença , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/etiologia , Recidiva Local de Neoplasia/patologia , Risco , Neoplasias da Glândula Tireoide/patologia , Neoplasias da Glândula Tireoide/cirurgia , Resultado do TratamentoRESUMO
Objectives. Thyroid carcinomas incidence, in particular papillary variants, is increasing. These cancers are generally considered to have excellent prognosis, and papillary microcarcinomas are usually noninvasive. Many prognostic histopathology factors have been described to guide therapeutic decisions. Most patients are treated with total thyroidectomy without radioiodine treatment or partial surgery. Case Summary. A 65-year-old man with no significant medical history presented with pain in the left chest wall that had been present for several months. A computed tomography (CT) found a large tissue mass of 4 cm responsible for lysis of the middle arch of the 4th rib on the left. It was a single lesion, highly hypermetabolic on the 18-FDG PET/CT. The histology analysis of the biopsy and surgical specimen favored an adenocarcinoma with immunostaining positive for TTF1 and thyroglobulin (Tg). The total thyroidectomy carried out subsequently revealed a 4 mm papillary microcarcinoma with vesicular architecture of the right lobe, well delimited and distant from the capsule without vascular embolisms. After two radioiodine treatments, the patient is in complete clinical, biological, and radiological remission. Conclusion. This extremely rare case of a singular bone metastasis revealing a papillary thyroid microcarcinoma illustrates the necessity of further research to better characterize the forms of papillary thyroid microcarcinomas with potentially poor prognosis.
RESUMO
BACKGROUND: No effective standard treatment exists for patients with radioiodine-refractory, advanced differentiated thyroid carcinoma. We aimed to assess efficacy and safety of vandetanib, a tyrosine kinase inhibitor of RET, VEGFR and EGFR signalling, in this setting. METHODS: In this randomised, double-blind, phase 2 trial, we enrolled adults (aged ≥18 years) with locally advanced or metastatic differentiated thyroid carcinoma (papillary, follicular, or poorly differentiated) at 16 European medical centres. Eligible patients were sequentially randomised in a 1:1 ratio with a standard computerised scheme to receive either vandetanib 300 mg per day (vandetanib group) or matched placebo (placebo group), balanced by centre. The primary endpoint was progression-free survival (PFS) in the intention-to-treat population based on investigator assessment. This study is registered with ClinicalTrials.gov, number NCT00537095. FINDINGS: Between Sept 28, 2007, and Oct 16, 2008, we randomly allocated 72 patients to the vandetanib group and 73 patients to the placebo group. By data cutoff (Dec 2, 2009), 113 (78%) patients had progressed (52 [72%] patients in the vandetanib group and 61 [84%] in the placebo group) and 40 (28%) had died (19 [26%] patients in the vandetanib group and 21 [29%] in the placebo group). Patients who received vandetanib had longer PFS than did those who received placebo (hazard ratio [HR] 0·63, 60% CI 0·54-0·74; one-sided p=0·008): median PFS was 11·1 months (95% CI 7·7-14·0) for patients in the vandetanib group and 5·9 months (4·0-8·9) for patients in the placebo group. The most common grade 3 or worse adverse events were QTc prolongation (ten [14%] of 73 patients in the vandetanib group vs none in the placebo group), diarrhoea (seven [10%] vs none), asthenia (five [7%] vs three [4%]), and fatigue (four [5%] vs none). Two patients in the vandetanib group and one in the placebo group died from treatment-related serious adverse events (haemorrhage from skin metastases and pneumonia in the vandetanib group and pneumonia in the placebo group). INTERPRETATION: Vandetanib is the first targeted drug to show evidence of efficacy in a randomised phase 2 trial in patients with locally advanced or metastatic differentiated thyroid carcinoma. Further investigation of tyrosine-kinase inhibitors in this setting is warranted. FUNDING: AstraZeneca.
Assuntos
Antineoplásicos/uso terapêutico , Piperidinas/uso terapêutico , Quinazolinas/uso terapêutico , Neoplasias da Glândula Tireoide/tratamento farmacológico , Neoplasias da Glândula Tireoide/secundário , Adenocarcinoma Folicular , Adolescente , Adulto , Idoso , Neoplasias Ósseas/secundário , Carcinoma , Carcinoma Papilar , Diarreia/induzido quimicamente , Intervalo Livre de Doença , Método Duplo-Cego , Eletrocardiografia/efeitos dos fármacos , Receptores ErbB/antagonistas & inibidores , Feminino , Sistema de Condução Cardíaco/efeitos dos fármacos , Humanos , Estimativa de Kaplan-Meier , Neoplasias Pulmonares/secundário , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Piperidinas/efeitos adversos , Quinazolinas/efeitos adversos , Receptores de Fatores de Crescimento do Endotélio Vascular/antagonistas & inibidores , Neoplasias Cutâneas/secundário , Análise de Sobrevida , Câncer Papilífero da Tireoide , Neoplasias da Glândula Tireoide/mortalidade , Neoplasias da Glândula Tireoide/patologia , Adulto JovemRESUMO
BACKGROUND: It is not clear whether the administration of radioiodine provides any benefit to patients with low-risk thyroid cancer after a complete surgical resection. The administration of the smallest possible amount of radioiodine would improve care. METHODS: In our randomized, phase 3 trial, we compared two thyrotropin-stimulation methods (thyroid hormone withdrawal and use of recombinant human thyrotropin) and two radioiodine ((131)I) doses (i.e., administered activities) (1.1 GBq and 3.7 GBq) in a 2-by-2 design. Inclusion criteria were an age of 18 years or older; total thyroidectomy for differentiated thyroid carcinoma; tumor-node-metastasis (TNM) stage, ascertained on pathological examination (p) of a surgical specimen, of pT1 (with tumor diameter ≤1 cm) and N1 or Nx, pT1 (with tumor diameter >1 to 2 cm) and any N stage, or pT2N0; absence of distant metastasis; and no iodine contamination. Thyroid ablation was assessed 8 months after radioiodine administration by neck ultrasonography and measurement of recombinant human thyrotropin-stimulated thyroglobulin. Comparisons were based on an equivalence framework. RESULTS: There were 752 patients enrolled between 2007 and 2010; 92% had papillary cancer. There were no unexpected serious adverse events. In the 684 patients with data that could be evaluated, ultrasonography of the neck was normal in 652 (95%), and the stimulated thyroglobulin level was 1.0 ng per milliliter or less in 621 of the 652 patients (95%) without detectable thyroglobulin antibodies. Thyroid ablation was complete in 631 of the 684 patients (92%). The ablation rate was equivalent between the (131)I doses and between the thyrotropin-stimulation methods. CONCLUSIONS: The use of recombinant human thyrotropin and low-dose (1.1 GBq) postoperative radioiodine ablation may be sufficient for the management of low-risk thyroid cancer. (Funded by the French National Cancer Institute [INCa] and the French Ministry of Health; ClinicalTrials.gov number, NCT00435851; INCa number, RECF0447.).
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Radioisótopos do Iodo/uso terapêutico , Neoplasias da Glândula Tireoide/radioterapia , Tireotropina/uso terapêutico , Técnicas de Ablação , Adenocarcinoma Folicular/tratamento farmacológico , Adenocarcinoma Folicular/radioterapia , Adenocarcinoma Folicular/cirurgia , Adulto , Carcinoma Papilar/tratamento farmacológico , Carcinoma Papilar/radioterapia , Carcinoma Papilar/cirurgia , Terapia Combinada , Feminino , Seguimentos , Humanos , Hipotireoidismo/etiologia , Radioisótopos do Iodo/efeitos adversos , Masculino , Pessoa de Meia-Idade , Pescoço/diagnóstico por imagem , Qualidade de Vida , Hormônios Tireóideos/sangue , Hormônios Tireóideos/uso terapêutico , Neoplasias da Glândula Tireoide/tratamento farmacológico , Neoplasias da Glândula Tireoide/cirurgia , Tireoidectomia , Tireotropina/efeitos adversos , Resultado do Tratamento , UltrassonografiaRESUMO
BACKGROUND: Distant metastases from differentiated thyroid carcinoma occur in up to 20% of cases and represent the most frequent cause of thyroid cancer-related death. Metastatic disease to the spine has the potential to cause severe morbidity, including pain, neurological deficit, and paraplegia. SUMMARY: We present a case series of eight consecutive patients with symptomatic spinal metastases due to thyroid carcinoma treated by our multidisciplinary team consisting of spinal surgeons, oncologists, and radiologists, with management of each case determined by our surgical algorithm. Four patients underwent surgical decompression and stabilization for spinal metastases causing instability, spinal cord compression, neurological deficit, or intractable pain. Three patients underwent vertebroplasty for focal mechanical pain due to osteolytic metastases in the absence of significant spinal cord compression or spinal instability; one of these patients required subsequent surgical decompression for spinal cord compression. One patient was nonoperatively treated. All patients underwent total thyroidectomy for the primary cancer and adjuvant radioiodine-131 treatment. The only patient with poorly differentiated thyroid cancer, which was refractory to radioiodine-131 died at 6 months after vertebroplasty procedures for symptomatic spinal metastases. One patient with medullary thyroid carcinoma died at 18 months after vertebroplasty. All remaining six patients who had well-differentiated papillary or follicular thyroid carcinoma were alive at an average of 50 months (range: 17-96 months) after diagnosis and treatment of symptomatic spinal metastases and were ambulant, independent, and able to perform activities of daily living and had no significant pain or neurologic symptoms. CONCLUSION: The potential for long-term survival of several years following development of spinal metastases should be considered during the counseling and decision-making process for patients with thyroid cancer.