RESUMEN
PURPOSE: Poorly differentiated thyroid carcinoma (PDTC) and anaplastic thyroid carcinoma (ATC) are rare, aggressive thyroid cancers with poor prognosis. At present, there are a limited number of research reports on PDTC and ATC. The study aimed to analysis the predictive value of hematologic parameters and clinicopathological features of PDTC and ATC. METHODS: This study retrospectively analyzed 67 patients at Tianjin Medical University Cancer Hospital from 2007 to 2019. We analyzed the clinicopathological features and survival outcomes of PDTC and ATC. RESULTS: This study showed that positive D-dimer, a high NLR, and a high PLR were more common in death patients. At the end of follow-up, 22 (32.8%) patients were alive at the time of study and 45 (67.2%) patients died from thyroid carcinoma. Disease-related death rates were 93.8% in ATC and 42.9% in the PDTC group. The median overall survival (OS) was 2.5 (0.3-84) months for patients with ATC, and 56 (3-113) months of PDTC patients. Univariate analysis showed that age at diagnosis and surgery were associations with OS in ATC patients, what's more, age at diagnosis, a high NLR, a high PLR, and positive D-dimer were associations with OS in PDTC patients. Multivariate analysis revealed that age at diagnosis was an independent association with OS in ATC patients. CONCLUSIONS: The hematologic parameters and clinicopathological features may provide predictive value of prognosis for patients with PTDC and ATC.
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Valor Predictivo de las Pruebas , Carcinoma Anaplásico de Tiroides , Neoplasias de la Tiroides , Humanos , Masculino , Femenino , Neoplasias de la Tiroides/patología , Neoplasias de la Tiroides/mortalidad , Neoplasias de la Tiroides/sangre , Neoplasias de la Tiroides/cirugía , Persona de Mediana Edad , Carcinoma Anaplásico de Tiroides/patología , Carcinoma Anaplásico de Tiroides/mortalidad , Carcinoma Anaplásico de Tiroides/sangre , Estudios Retrospectivos , Anciano , Adulto , Pronóstico , Tasa de Supervivencia , Anciano de 80 o más AñosRESUMEN
Background: Anaplastic thyroid cancer (ATC) is highly invasive, prone to distant metastasis (DM), and has a very poor prognosis. This study aims to construct an accurate survival prediction model for ATC patients with DM, providing reference for comprehensive assessment and treatment planning. Methods: We extracted data of ATC patients with DM diagnosed between 2004 and 2019 from the SEER database, randomly dividing them into a training set and a validation set in a ratio of 7:3. Univariate and multivariate Cox regression analyses were sequentially performed on the training set to identify independent prognostic factors for overall survival (OS) and construct nomograms for 3-month, 6-month, and 8-month OS for ATC patients with DM based on all identified independent prognostic factors. Receiver operating characteristic (ROC) curve analysis, decision curve analysis (DCA) curve analysis, and calibration curves were separately plotted on the training and validation sets to demonstrate the model's performance. Furthermore, patients were stratified into high- and low-risk groups based on their risk scores, and the Kaplan-Meier (KM) survival curves were used to illustrate the survival differences between the two groups. Results: A total of 322 patients were included in this study. Univariate and multivariate Cox regression analyses identified five independent prognostic factors for OS in ATC patients with DM: surgery, tumor size, age, chemotherapy, and radiotherapy. Nomograms for 3-month, 6-month, and 8-month OS were established based on these factors. The training set AUC values (3-month AUC: 0.767, 6-month AUC: 0.789, 8-month AUC: 0.795) and validation set AUC values (3-month AUC: 0.753, 6-month AUC: 0.798, 8-month AUC: 0.806) as well as the calibration curves demonstrated excellent applicability and accuracy of the model. Additionally, the DCA curves indicated substantial clinical net benefit of the model. The KM curves also confirmed the model's excellent stratification ability for patient OS. Conclusion: The nomogram developed in this study accurately predicts OS for ATC patients with DM. It can assist clinicians in formulating appropriate treatment strategies for these patients.
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Nomogramas , Programa de VERF , Carcinoma Anaplásico de Tiroides , Neoplasias de la Tiroides , Humanos , Masculino , Femenino , Persona de Mediana Edad , Carcinoma Anaplásico de Tiroides/mortalidad , Carcinoma Anaplásico de Tiroides/patología , Carcinoma Anaplásico de Tiroides/terapia , Neoplasias de la Tiroides/mortalidad , Neoplasias de la Tiroides/patología , Neoplasias de la Tiroides/terapia , Anciano , Pronóstico , Metástasis de la Neoplasia , Adulto , Tasa de Supervivencia , Curva ROCRESUMEN
BACKGROUND: According to the latest classification of thyroid tumors released by the WHO in 2022, primary squamous cell carcinoma of the thyroid (PSCCTh) is classified as anaplastic thyroid carcinoma (ATC). The objective of this study was to determine the differences in characteristics between ATC and PSCCTh and develop a nomogram to predict overall survival patients with the redefined anaplastic thyroid carcinoma (rATC). METHODS: Patients diagnosed with ATC and PSCCTh between 2000 and 2018 from the Surveillance, Epidemiology, and End Results (SEER) database were enrolled and randomly divided into a training cohort and a validation cohort with a ratio of 7:3. Overall survival (OS) and cancer-specific survival (CSS) was estimated using the Kaplan-Meier method and compared using log-rank tests. The univariate and multivariate Cox proportional hazards regression analyses were used to determine independent prognostic factors of rATC patients. We then developed and validated nomograms to predict the 3-, 6- and 12-month OS of rATC and the results were evaluated by C-index and calibration curves. RESULTS: After application of the inclusion and exclusion criteria, a total of 1338 ATC and 127 PSCCTh patients were included in the study. Further, OS and CSS of patients with PSCCTh were better than that of patients with ATC. Prognostic factors were not identical for the two cancers. Multivariate Cox model analysis indicated that age, tumor size, metastasis, surgery, radiotherapy, chemotherapy are independent prognostic factors for CSS in patients with ATC; while for patients with PSCCTh, the corresponding factors are age, and surgery. We selected six survival predictors (age, tumor size, metastasis, surgery, radiation, and, chemotherapy) for nomogram construction. The C-indexes in the training and validation cohort were 0.740 and 0.778, respectively, reflecting the good discrimination ability of the model. The calibration curves also showed good consistency in the probability of 3-, 6-, and 12-month OS between the actual observation and the nomogram prediction. CONCLUSION: We constructed a nomogram to provide a convenient and reliable tool for predicting OS in rATC patients. Prognostic factors influencing CSS were not identical in patients with ATC and PSCCTh. These findings indicate that different clinical treatment and management plans are required for patients with these two types of thyroid cancer.
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Nomogramas , Programa de VERF , Carcinoma Anaplásico de Tiroides , Neoplasias de la Tiroides , Humanos , Carcinoma Anaplásico de Tiroides/patología , Carcinoma Anaplásico de Tiroides/mortalidad , Carcinoma Anaplásico de Tiroides/terapia , Masculino , Femenino , Persona de Mediana Edad , Neoplasias de la Tiroides/mortalidad , Neoplasias de la Tiroides/patología , Neoplasias de la Tiroides/terapia , Anciano , Pronóstico , Adulto , Estimación de Kaplan-Meier , Carcinoma de Células Escamosas/mortalidad , Carcinoma de Células Escamosas/patología , Carcinoma de Células Escamosas/terapia , Modelos de Riesgos ProporcionalesRESUMEN
Background: Tyrosine kinase inhibitors (TKIs) contribute to the treatment of patients with anaplastic thyroid cancer (ATC). Although prospective clinical studies of TKIs exhibit limited efficacy, whether ATC patients benefit from TKI treatment in real-world clinical practice may enlighten future explorations. Therefore, we conducted this effective analysis based on real-world retrospective studies to illustrate the efficacy of TKI treatment in ATC patients. Methods: We systematically searched the online databases on September 03, 2023. Survival curves were collected and reconstructed to summarize the pooled curves. Responses were analyzed by using the "meta" package. The primary endpoints were progression-free survival (PFS), overall survival (OS), objective response rate (ORR), and disease control rate (DCR). Results: 12 studies involving 227 patients were enrolled in the study. Therapeutic strategies included: anlotinib, lenvatinib, dabrafenib plus trametinib, vemurafenib, pembrolizumab plus dabrafenib and trametinib, pembrolizumab plus lenvatinib, pembrolizumab plus trametinib, and sorafenib. The pooled median OS and PFS were 6.37 months (95% CI 4.19-10.33) and 5.50 months (95% CI 2.17-12.03). The integrated ORR and DCR were 32% (95% CI 23%-41%) and 40% (95% CI 12%-74%). Conclusion: In real-world clinical practice, ATC patients could benefit from TKI therapy. In future studies, more basic experiments and clinical explorations are needed to enhance the effects of TKIs in the treatment of patients with ATC.
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Carcinoma Anaplásico de Tiroides , Neoplasias de la Tiroides , Humanos , Supervivencia sin Progresión , Estudios Retrospectivos , Carcinoma Anaplásico de Tiroides/tratamiento farmacológico , Carcinoma Anaplásico de Tiroides/mortalidad , Carcinoma Anaplásico de Tiroides/patología , Neoplasias de la Tiroides/tratamiento farmacológico , Neoplasias de la Tiroides/patología , Neoplasias de la Tiroides/mortalidad , /uso terapéuticoRESUMEN
BACKGROUND: Anaplastic thyroid carcinoma (ATC) is a rare but aggressive malignancy, which accounts for only 1-2% of all thyroid cancers. The median overall survival (OS) time for all stages patients is at about 5 months. The benefit of surgery combined with adjuvant radiation and chemotherapy in stage IVC anaplastic thyroid cancer is still controversial. The aim of this study is to investigating surgery combined with adjuvant radiation and chemotherapy and survival outcomes in stage IVC ATC patients. METHOD: Anaplastic thyroid carcinoma patients from the Surveillance, Epidemiology, and End Results database from 2004 to 2016 were used to conduct a cross-sectional study in the analysis. The endpoint of this study was overall survival. RESULTS: The median OS of the overall population was 2.0 months. Multivariate analysis showed that age (<67 vs. ≥67 years old, P = 0.017, HR = 1.355, 95% CI: 1.057-1.738), tumor size (<7 cm vs. ≥7 cm, P = 0.001, HR = 1.579, 95% CI: 1.202-2.073), Surgery (thyroidectomy vs. non-surgery, P < 0.001, HR = 0.554, 95% CI: 0.401-0.766), radiation therapy (P < 0.001, HR = 0.571, 95% CI: 0.445-0.733) and chemotherapy (P = 0.003, HR = 0.684, 95% CI: 0.531-0.881) were independent prognostic factor for worse OS in stage IVC ATC patients. Surgery combined with adjuvant radiation and chemotherapy exhibited the better overall survival time for 4 months. CONCLUSIONS: Surgery combined with adjuvant radiation and chemotherapy can improve overall survival in stage IVC ATC patients. We recommend surgical approach with fully evaluation combined with radiation therapy and chemotherapy for selected stage IVC ATC patients.
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Programa de VERF , Carcinoma Anaplásico de Tiroides , Neoplasias de la Tiroides , Tiroidectomía , Humanos , Carcinoma Anaplásico de Tiroides/mortalidad , Carcinoma Anaplásico de Tiroides/terapia , Carcinoma Anaplásico de Tiroides/patología , Carcinoma Anaplásico de Tiroides/tratamiento farmacológico , Carcinoma Anaplásico de Tiroides/radioterapia , Carcinoma Anaplásico de Tiroides/cirugía , Masculino , Femenino , Persona de Mediana Edad , Anciano , Neoplasias de la Tiroides/mortalidad , Neoplasias de la Tiroides/terapia , Neoplasias de la Tiroides/patología , Neoplasias de la Tiroides/radioterapia , Neoplasias de la Tiroides/cirugía , Radioterapia Adyuvante , Estudios Transversales , Estadificación de Neoplasias , Adulto , Terapia Combinada , Quimioterapia Adyuvante , Anciano de 80 o más Años , Resultado del TratamientoRESUMEN
BACKGROUND: Anaplastic thyroid carcinoma (ATC) is a highly invasive malignant tumor with a poor prognosis. Traditional treatment methods have not been effective. However, advancements in targeted therapy and immunotherapy in recent years have shed new light on the management of ATC. The aim of this study was to examine the treatment plan and prognostic factors of ATC. METHODS: This study conducted a retrospective analysis of ATC patients who received treatment at our institution between 2000 and 2023 to evaluate the clinical characteristics, treatment methods, and factors influencing survival. Survival analysis was performed by the KaplanâMeier method and log-rank test, and multivariate analysis was performed using the Cox proportional hazard model. RESULTS: The 6-month and 1-year disease-specific OS rates were 49% and 29%, respectively. The presence of clinical symptoms and the timing of treatment significantly impacted patient prognosis (P < 0.05). Compared with surgery + radiotherapy/chemotherapy and only surgery, targeted therapy and targeted + immunotherapy represented an improved overall survival, The 6-month/1-year survival rates of which were 81%/61% and 91%/73% (P < 0.05), respectively. Multivariate analysis indicated that the symptoms at initial diagnosis, year of presentation, performance status and treatment plan were independent factors affecting the prognosis. The year of presentation (P = 0.048) and the treatment plan (P = 0.038) were significantly meaningful in predicting prognosis. CONCLUSION: Targeted therapy and targeted+immune therapy can effectively prolong the survival period of ATC patients. Symptoms at initial diagnosis and treatment plan have a significant impact on the prognosis.
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Inmunoterapia , Terapia Molecular Dirigida , Carcinoma Anaplásico de Tiroides , Neoplasias de la Tiroides , Humanos , Carcinoma Anaplásico de Tiroides/terapia , Carcinoma Anaplásico de Tiroides/patología , Carcinoma Anaplásico de Tiroides/mortalidad , Masculino , Femenino , Estudios Retrospectivos , Inmunoterapia/métodos , Persona de Mediana Edad , Anciano , Neoplasias de la Tiroides/terapia , Neoplasias de la Tiroides/mortalidad , Terapia Molecular Dirigida/métodos , Pronóstico , Adulto , Anciano de 80 o más Años , Terapia Combinada , Tasa de SupervivenciaRESUMEN
Importance: Survival outcomes for anaplastic thyroid cancer (ATC), the most aggressive subtype of thyroid cancers, have remained poor. However, targeted therapies and immunotherapies present new opportunities for treatment of this disease. Evaluations of survival outcomes over time with new multimodal therapies are needed for optimizing treatment plans. Objective: To evaluate the association of treatment strategies and tumor characteristics with overall survival (OS) among patients with ATC. Design, Setting, and Participants: This retrospective case series study evaluated the survival outcomes stratified by treatment strategies and tumor characteristics among patients with ATC treated at a tertiary level academic institution from January 1, 2000, to December 31, 2021. Demographic, tumor, treatment, and outcome characteristics were analyzed. Kaplan-Meier method and log rank test modeled OS by treatment type and tumor characteristics. Data were analyzed in May 2022. Main Outcomes and Measures: Overall survival (OS). Results: The study cohort comprised 97 patients with biopsy-proven ATC (median [range] age at diagnosis, 70 [38-93] years; 60 (62%) female and 85 [88%] White individuals; 59 [61%] never smokers). At ATC diagnosis, 18 (19%) patients had stage IVA, 19 (20%) had stage IVB, and 53 (55%) had stage IVC disease. BRAF status was assessed in 38 patients; 18 (47%) had BRAF-V600E variations and 20 (53%), BRAF wild type. Treatment during clinical course included surgery for 44 (45%) patients; chemotherapy, 41 (43%); definitive or adjuvant radiation therapy, 34 (RT; 35%); and targeted therapy, 28 (29%). Median OS for the total cohort was 6.5 (95% CI, 4.3-10.0) months. Inferior OS was found in patients who did not receive surgery (hazard ratio [HR], 2.12; 95% CI, 1.35-3.34; reference, received surgery), chemotherapy (HR, 3.28; 95% CI, 1.99-5.39; reference, received chemotherapy), and definitive or adjuvant RT (HR, 2.47; 95% CI, 1.52-4.02; reference, received definitive/adjuvant RT). On multivariable analysis, age at diagnosis (HR, 1.03; 95% CI, 1.01-1.06), tumor stage IVC (HR, 2.65; 95% CI, 1.35-5.18), and absence of definitive or adjuvant RT (HR, 1.90; 95% CI, 1.01-3.59) were associated with worse OS. Conclusions and Relevance: This retrospective single-institution study found that lower tumor stage, younger age, and the ability to receive definitive or adjuvant RT were associated with improved OS in patients with ATC.
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Carcinoma Anaplásico de Tiroides , Neoplasias de la Tiroides , Carcinoma Anaplásico de Tiroides/mortalidad , Carcinoma Anaplásico de Tiroides/patología , Carcinoma Anaplásico de Tiroides/terapia , Neoplasias de la Tiroides/mortalidad , Neoplasias de la Tiroides/patología , Neoplasias de la Tiroides/terapia , Humanos , Masculino , Femenino , Tasa de Supervivencia , Terapia Combinada , Adulto , Persona de Mediana Edad , Anciano , Anciano de 80 o más Años , Estudios Retrospectivos , Radioterapia Adyuvante , Antineoplásicos/uso terapéutico , Tiroidectomía , Resultado del TratamientoRESUMEN
AIMS: We aimed to study the clinicopathological and molecular features of high-grade non-anaplastic thyroid carcinomas (HGTCs), a carcinoma with a prognosis intermediate between those of well-differentiated carcinoma and anaplastic carcinoma. METHODS AND RESULTS: This study included 364 HGTC patients: 200 patients (54.9%) were diagnosed with poorly differentiated thyroid carcinoma (PDTC), based on the Turin consensus (HGTC-PDTC), and 164 were diagnosed with high-grade features that did not meet the Turin criteria (HGTC-nonPDTC). HGTCs are aggressive: the 3-year, 5-year, 10-year and 20-year disease-specific survival (DSS) rates were 89%, 76%, 60%, and 35%, respectively. Although DSS was similar between HGTC-PDTC and HGTC-nonPDTC patients, HGTC-PDTC was associated with higher rate of radioactive iodine avidity, a higher frequency of RAS mutations, a lower frequency of BRAF V600E mutations and a higher propensity for distant metastasis (DM) than HGTC-nonPDTC. Independent clinicopathological markers of worse outcome were: older age, male sex, extensive necrosis and lack of encapsulation for DSS; older age, male sex and vascular invasion for DM-free survival; and older age, necrosis, positive margins and lymph node metastasis for locoregional recurrence-free survival. The frequencies of BRAF, RAS, TERT, TP53 and PTEN alterations were 28%, 40%, 55%, 11%, and 10%, respectively. TP53, PTEN and TERT were independent molecular markers associated with an unfavourable outcome, independently of clinicopathological parameters. The coexistence of BRAF V600E and TERT promoter mutation increased the risk of DM. CONCLUSIONS: The above data support the classification of HGTC as a single group with two distinct subtypes based on tumour differentiation: HGTC-PDTC and HGTC-nonPDTC.
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Carcinoma Anaplásico de Tiroides/patología , Neoplasias de la Tiroides/patología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores de Tumor/genética , Niño , Preescolar , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos , Tasa de Supervivencia , Carcinoma Anaplásico de Tiroides/genética , Carcinoma Anaplásico de Tiroides/mortalidad , Neoplasias de la Tiroides/genética , Neoplasias de la Tiroides/mortalidad , Adulto JovenRESUMEN
Background: Whether anaplastic thyroid cancer (ATC) patients benefit more from radiotherapy plus chemotherapy (RCT) than from radiotherapy alone (RT) was controversial. We aimed to investigate the effectiveness of RCT versus RT on ATC overall and within subgroups by surgical resection and distant metastasis in a large real-world cohort. Methods: Patients with ATC diagnosed between 2004 and 2015 were identified from the Surveillance, Epidemiology, and End Results Program database. Inverse probability weighting (IPW) was performed to balance variables between the two groups. Multivariate Cox proportional hazard model and Fine-Gray compete-risk model were carried out to investigate prognostic factors relating to overall survival (OS) and cancer-specific survival (CSS). Subgroup analysis was carried out, and a forest plot was graphed. Results: Of the 491 ATC patients, 321 (65.4%) were in the RCT group and 170 (34.6%) were in the RT group. The median OS was 4 months [interquartile range (IQR) 2-7] and 2 months (IQR 1-4) for patients in the RCT and RT groups, respectively. As indicated by the inverse probability weighting multivariate regression, RCT was associated with significantly improved OS (adjusted HR = 0.69, 95% CI = 0.56-0.85, p < 0.001) and CSS (adjusted subdistribution HR = 0.77, 95% CI = 0.61-0.96, p = 0.018). The prominent effect of RCT versus RT alone remains significant within each subgroup stratified by surgical resection and distant metastasis. Older age, single marital status, surgical resection, distant metastasis, and tumor extension were significant prognostic factors of survival. Conclusions: RCT contributes to prolonged OS and CSS compared with RT alone in ATC patients, regardless of surgical resection and distant metastasis. RCT should be preferentially applied to ATC patients.
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Carcinoma Anaplásico de Tiroides/terapia , Neoplasias de la Tiroides/terapia , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Tasa de Supervivencia , Carcinoma Anaplásico de Tiroides/tratamiento farmacológico , Carcinoma Anaplásico de Tiroides/mortalidad , Carcinoma Anaplásico de Tiroides/radioterapia , Neoplasias de la Tiroides/tratamiento farmacológico , Neoplasias de la Tiroides/mortalidad , Neoplasias de la Tiroides/radioterapia , Tiroidectomía , Resultado del TratamientoRESUMEN
BACKGROUND: The management of anaplastic thyroid cancer (ATC) is controversial; thus, proper treatment and prognostic factors should be investigated. OBJECTIVES: To compare the survival outcomes of the intervention and palliative treatment in ATC patients. METHODS: A hospital-based retrospective study was conducted at a single tertiary university hospital. The medical record charts were retrieved from November 20, 1987, to December 31, 2016. The final follow-up ended by December 31, 2017. The patients' demographic data, laboratory data, clinical presentation, and treatment modality results were analyzed. RESULTS: One hundred twenty-one records were analyzed with a one-year overall survival rate of 3.5% (median survival time: 77 days); however, 16 cases had insufficient data to classify staging and treatment modalities. Therefore, 105 ATC patients (37 with stage IVa, 39 with stage IVb, and 29 with stage IVc disease) were included with a one-year overall survival rate of 4.0% (median survival time of 82 days). Intervention treatment allowed longer median survival times (p < 0.05) and a better survival rate (p < 0.05). Among the interventional treatment groups, postoperative chemoradiation yielded the longest median survival time (187 days) and the highest survival rate (20%) (p < 0.05). The intervention modality allowed a better median survival time at all stages, particularly in stage IVa (p < 0.05). Unfavorable prognostic factors were adjusted for in a multiple Cox regression model showing that significant factors included age ≥65 years (hazard ratio HR: 2.57), palliative treatment (HR: 1.85), and leukocytosis ≥10,000 cells/mm3 (HR: 2.76). CONCLUSIONS: Intervention treatment provided a better survival outcome in all stages, particularly in stage IVa, with a significantly better median survival time. Among interventional treatments, postoperative chemoradiation led to the longest survival rate, suggesting that this treatment should be considered in ATC patients with resectable tumors and no poor prognostic factors, such as older age and leukocytosis.
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Carcinoma Anaplásico de Tiroides/cirugía , Neoplasias de la Tiroides/cirugía , Adulto , Factores de Edad , Anciano , Hospitales , Humanos , Leucocitosis , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos , Tasa de Supervivencia , Carcinoma Anaplásico de Tiroides/mortalidad , Neoplasias de la Tiroides/mortalidad , Resultado del TratamientoRESUMEN
BACKGROUND/AIM: Anaplastic thyroid carcinoma (ATC) is the least common but most lethal of thyroid cancer, despite various therapeutic options, with limited efficacy. In order to help therapeutic decision-making, the purpose of this study was to develop a new prognostic score providing survival estimates in patients with ATC. PATIENTS AND METHODS: Based on a multivariate analysis of 149 retrospectively analyzed patients diagnosed with ATC from 1968 to 2017 at a referral center, a propensity score was developed. A model was generated providing survival probability at 6 months and median overall survival estimates. RESULTS: The median survival was 96 days. The overall survival rate was 35% at 6 months, 20% at 1 year and 13% at 2 years. Stepwise Cox regression revealed that the most appropriate death prediction model included metastatic spread, tumor size and age class as explanatory variables. This model made it possible to define three categories of patients with different survival profiles. CONCLUSION: Distant metastasis, age and primary tumor size are strong independent factors that affect prognosis in patients with ATC. Using these significant pretreatment factors, we developed a score to predict survival in these patients with poor prognosis.
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Carcinoma Anaplásico de Tiroides/mortalidad , Neoplasias de la Tiroides/mortalidad , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Metástasis de la Neoplasia , Pronóstico , Puntaje de Propensión , Modelos de Riesgos Proporcionales , Sistema de Registros , Estudios Retrospectivos , Carcinoma Anaplásico de Tiroides/tratamiento farmacológico , Carcinoma Anaplásico de Tiroides/patología , Neoplasias de la Tiroides/tratamiento farmacológico , Neoplasias de la Tiroides/patología , Adulto JovenRESUMEN
Background: Anaplastic thyroid carcinoma (ATC) and metastatic poorly differentiated thyroid carcinomas (PDTCs) are rare aggressive malignancies with poor overall survival (OS) despite extensive multimodal therapy. These tumors are highly proliferative, with frequently increased tumor mutational burden (TMB) compared with differentiated thyroid carcinomas, and elevated programmed death ligand 1 (PD-L1) levels. These tumor properties implicate responsiveness to antiangiogenic and antiproliferative multikinase inhibitors such as lenvatinib, and immune checkpoint inhibitors such as pembrolizumab. Patients and Methods: In a retrospective study, we analyzed six patients with metastatic ATC and two patients with PDTC, who received a combination therapy of lenvatinib and pembrolizumab. Lenvatinib was started at 14-24 mg daily and combined with pembrolizumab at a fixed dose of 200 mg every three weeks. Maximum treatment duration with this combination was 40 months, and 3 of 6 ATC patients are still on therapy. Patient tumors were characterized by whole-exome sequencing and PD-L1 expression levels (tumor proportion score [TPS] 1-90%). Results: Best overall response (BOR) within ATCs was 66% complete remissions (4/6 CR), 16% stable disease (1/6 SD), and 16% progressive disease (1/6 PD). BOR within PDTCs was partial remission (PR 2/2). The median progression-free survival was 17.75 months for all patients, and 16.5 months for ATCs, with treatment durations ranging from 1 to 40 months (1, 4, 11, 15, 19, 25, 27, and 40 months). Grade III/IV toxicities developed in 4 of 8 patients, requiring dose reduction/discontinuation of lenvatinib. The median OS was 18.5 months, with three ATC patients being still alive without relapse (40, 27, and 19 months) despite metastatic disease at the time of treatment initiation (UICC and stage IVC). All patients with long-term (>2 years) or complete responses (CRs) had either increased TMB or a PD-L1 TPS >50%. Conclusions: Our results implicate that the combination of lenvatinib and pembrolizumab might be safe and effective in patients with ATC/PDTC and can result in complete and long-term remissions. The combination treatment is now being systematically examined in a phase II clinical trial (Anaplastic Thyroid Carcinoma Lenvatinib Pembrolizumab [ATLEP]) in ATC/PDTC patients.
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Anticuerpos Monoclonales Humanizados/uso terapéutico , Antineoplásicos/uso terapéutico , Compuestos de Fenilurea/uso terapéutico , Quinolinas/uso terapéutico , Carcinoma Anaplásico de Tiroides/tratamiento farmacológico , Neoplasias de la Tiroides/tratamiento farmacológico , Anciano , Anciano de 80 o más Años , Protocolos de Quimioterapia Combinada Antineoplásica , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Tasa de Supervivencia , Carcinoma Anaplásico de Tiroides/mortalidad , Carcinoma Anaplásico de Tiroides/patología , Neoplasias de la Tiroides/mortalidad , Neoplasias de la Tiroides/patología , Resultado del TratamientoRESUMEN
BACKGROUND/AIM: This study aimed to examine survival and surgical complications in patients with anaplastic thyroid cancer (ATC) after multimodal treatment. PATIENTS AND METHODS: Since 2002, the recommended treatment strategy for ATC at our centre has been hyperfractionated accelerated radiotherapy (HART) with high doses to the neck (64 Gy), combined with weekly doxorubicin, and surgery after 4-8 weeks, if feasible. RESULTS: Between 2002 and 2014, 14 patients completed HART and thyroid surgery. Eight patients had preoperative HART, and six postoperative HART. Median survival was 20 months (range=4-110 months) in all patients, 51 months (range=4-110 months) and 18.5 months (range=9-56 months) in the preoperative and postoperative HART groups, respectively. Six patients survived for more than two years, and four patients survived for more than five years. Seven patients had postoperative complications. CONCLUSION: In this series of selected patients, an improved survival after aggressive, multimodal treatment was observed. Preoperative HART may promote survival although complications may be more frequent.
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Terapia Combinada/métodos , Carcinoma Anaplásico de Tiroides/cirugía , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Análisis de Supervivencia , Carcinoma Anaplásico de Tiroides/mortalidadRESUMEN
Anaplastic thyroid cancer (ATC) is a rapidly growing, highly metastatic cancer with limited therapeutic alternatives, thus targeted therapies need to be developed. This study aimed to examine desmoglein 2 (Dsg2) expression in ATC and its biological role and potential as a therapeutic target in ATC. Consequently, Dsg2 was downregulated or aberrantly expressed in ATC tissues. ATC patients with low Dsg2 expression levels also presented with distant metastasis. Dsg2 depletion significantly increased cell migration and invasion, with a relatively limited effect on ATC cell proliferation in vitro and increased distant metastasis in vivo. Dsg2 knockdown induced cell motility through the hepatocyte growth factor receptor (HGFR, c-Met)/Src/Rac1 signaling axis, with no alterations in the expression of EMT-related molecules. Further, specific targeting of c-Met significantly inhibited the motility of shDsg2-depleted ATC cells. Decreased membrane Dsg2 expression increased the metastatic potential of ATC cells. These results indicate that Dsg2 plays an important role in ATC cell migration and invasiveness. Therapies targeting c-Met might be effective among ATC patients with low membrane Dsg2 expression levels, indicating that the analysis of Dsg2 expression potentially provides novel insights into treatment strategies for ATC.
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Desmogleína 2/genética , Proteínas Proto-Oncogénicas c-met/metabolismo , Carcinoma Anaplásico de Tiroides/genética , Adulto , Anciano , Anciano de 80 o más Años , Animales , Línea Celular Tumoral , Movimiento Celular , Femenino , Humanos , Masculino , Ratones , Persona de Mediana Edad , Invasividad Neoplásica , Estudios Retrospectivos , Análisis de Supervivencia , Carcinoma Anaplásico de Tiroides/mortalidad , TransfecciónRESUMEN
Background: Survival rates for anaplastic thyroid cancer (ATC) have not improved in the past four decades; however, preliminary clinical data indicate that lenvatinib may provide efficacy benefits for patients with ATC. This real-world study aimed to define the potential role of lenvatinib in ATC by examining the impact of treatment administered alongside existing therapies. Methods: This was a retrospective, single-center analysis of Korean patients with confirmed ATC who received lenvatinib between October 2015 and February 2018. Eighteen patients were included (mean ± standard deviation age, 64.9 ± 11.1 years; 61.1% female). Six [33.3%] had resectable disease that progressed after a combination of surgery, radiotherapy, and chemotherapy, and 12 [66.7%] had unresectable disease that progressed after radiation treatment and chemotherapy. Study endpoints were overall survival (OS) and change in volume of the largest tumor assessed via imaging. Results: Median OS for the 18 lenvatinib-treated patients was 230 days (range 64-839 days). Survival rates at 6 months and 1 year were 61.1 and 22.2%, respectively. Three patients (16.7%) survived beyond 1 year; 15 patients died, of whom four (26.7%) had local disease and 11 (73.3%) had distant metastasis. Two patients (11.1%) had tumor volume increases of 9-10%. The other 16 patients (88.9%) had tumor volume reductions of 2-69%. Six patients (33.3%) had tumor volume reductions ≥50%. Conclusions: In patients with ATC who had progressed on prior therapy, addition of lenvatinib could improve survival duration and reduce tumor volume. Further studies of lenvatinib in ATC are warranted.
Asunto(s)
Compuestos de Fenilurea/uso terapéutico , Quinolinas/uso terapéutico , Carcinoma Anaplásico de Tiroides/tratamiento farmacológico , Neoplasias de la Tiroides/tratamiento farmacológico , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Tasa de Supervivencia , Carcinoma Anaplásico de Tiroides/mortalidad , Neoplasias de la Tiroides/mortalidad , Resultado del TratamientoRESUMEN
Genomic profiling shows that many solid tumors are characterized by specific driver aberrations, and this has expanded the therapeutic options for many patients. The mitogen-activated protein kinase (MAPK) pathway is a key cell signaling pathway involved in regulating cellular growth, proliferation, and survival. Driver mutations in the BRAF gene, a key player in the MAPK pathway, are described in multiple tumor types, including subsets of melanoma, non-small cell lung cancer (NSCLC), and anaplastic thyroid cancer (ATC), making BRAF a desirable target for inhibition. BRAF inhibitors have shown efficacy in several cancers; however, most patients eventually develop resistance. To delay or prevent resistance, combination therapy targeting BRAF and MEK, a downstream signaling target of BRAF in the MAPK pathway, was evaluated and demonstrated synergistic benefit. BRAF and MEK inhibitor combinations have been approved for use in various cancers by the US FDA. We review the clinical data for various BRAF plus MEK combination regimens in three cancer types with underlying BRAF driver mutations: melanoma, NSCLC, and ATC. We also discuss practical treatment considerations and management of selected combination therapy toxicities.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/farmacología , Quinasas de Proteína Quinasa Activadas por Mitógenos/antagonistas & inhibidores , Inhibidores de Proteínas Quinasas/farmacología , Proteínas Proto-Oncogénicas B-raf/antagonistas & inhibidores , Animales , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Carcinoma de Pulmón de Células no Pequeñas/patología , Diferenciación Celular/genética , Línea Celular Tumoral , Proliferación Celular/genética , Ensayos Clínicos como Asunto/estadística & datos numéricos , Resistencia a Antineoplásicos/efectos de los fármacos , Resistencia a Antineoplásicos/genética , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/epidemiología , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/etiología , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/prevención & control , Humanos , Incidencia , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/mortalidad , Neoplasias Pulmonares/patología , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Melanoma/tratamiento farmacológico , Melanoma/genética , Melanoma/mortalidad , Melanoma/patología , Ratones , Quinasas de Proteína Quinasa Activadas por Mitógenos/metabolismo , Mutación , Supervivencia sin Progresión , Inhibidores de Proteínas Quinasas/uso terapéutico , Proteínas Proto-Oncogénicas B-raf/genética , Proteínas Proto-Oncogénicas B-raf/metabolismo , Neoplasias Cutáneas/tratamiento farmacológico , Neoplasias Cutáneas/genética , Neoplasias Cutáneas/mortalidad , Neoplasias Cutáneas/patología , Carcinoma Anaplásico de Tiroides/tratamiento farmacológico , Carcinoma Anaplásico de Tiroides/genética , Carcinoma Anaplásico de Tiroides/mortalidad , Carcinoma Anaplásico de Tiroides/patología , Neoplasias de la Tiroides/tratamiento farmacológico , Neoplasias de la Tiroides/genética , Neoplasias de la Tiroides/mortalidad , Neoplasias de la Tiroides/patología , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
Background Anaplastic thyroid cancer (ATC) is one of the most aggressive tumors. The aim of the study was to determine the correlation between a higher dietary intake of iodine, frequency of ATC and the characteristics of ATC, and to find out how often patients with ATC had a history of radioiodine (RAI) therapy. Patients and methods This retrospective study included 220 patients (152 females, 68 males; mean age 68 years) with ATC who were treated in our country from 1972 to 2017. The salt was iodinated with 10 mg of potassium iodide/ kg before 1999, and with 25 mg of potassium iodide/kg thereafter. The patients were assorted into 15-year periods: 1972-1986, 1987-2001, and 2002-2017. Results The incidence of ATC decreased after a higher iodination of salt (p = 0.04). Patients are nowadays older (p = 0.013) and have less frequent lymph node metastases (p = 0.012). The frequency of distant metastases did not change over time. The median survival of patients in the first, second, and third periods was 3, 4, and 3 months, respectively (p < 0.05). The history of RAI therapy was present in 7.7% of patients. Conclusions The number of patients with a history of RAI therapy did not change statistically over time. The incidence of ATC in Slovenia decreased probably because of higher salt iodination.
Asunto(s)
Radioisótopos de Yodo/uso terapéutico , Yodo/administración & dosificación , Yoduro de Potasio/administración & dosificación , Cloruro de Sodio Dietético/administración & dosificación , Carcinoma Anaplásico de Tiroides/epidemiología , Neoplasias de la Tiroides/epidemiología , Anciano , Femenino , Humanos , Incidencia , Metástasis Linfática , Masculino , Estudios Retrospectivos , Eslovenia/epidemiología , Carcinoma Anaplásico de Tiroides/mortalidad , Carcinoma Anaplásico de Tiroides/prevención & control , Carcinoma Anaplásico de Tiroides/secundario , Neoplasias de la Tiroides/mortalidad , Neoplasias de la Tiroides/patología , Neoplasias de la Tiroides/prevención & control , Factores de TiempoRESUMEN
Although prior studies have reported that patients with anaplastic thyroid carcinoma (ATC) with a focal anaplastic component may have a prolonged survival compared to other ATC patients, the outcome data are limited. We evaluated a cohort of ATC resected between 2003 and 2018. Tumor slides were reviewed to confirm the diagnosis and to identify cases with a minor ATC component (defined as comprising < 10% of the tumor). We evaluated the clinical outcome of these patients compared to that of all other cohort patients (characterized as having conventional ATC). Our cohort was composed of 24 cases of ATC that underwent resection, including 8 (33%) with a minor ATC component. Tumors with a minor ATC component were predominantly associated with papillary thyroid carcinoma. For patients with tumors with a minor ATC component, the 1-year and 2-year survival rates and median survival for patients who died of disease were 88%, 43%, and 17 months (range 6-73 months), respectively. In comparison, for patients with conventional ATC, the 1-year and 2-year survival rates and median survival for patients who died of disease were 56%, 44%, and 7 months (range 2-26 months), respectively. There was no difference in 1- and 2-year survival or overall survival by Kaplan-Meier analysis for patients with tumors with a minor ATC component and those with conventional ATC. In conclusion, the difference in overall survival between ATC groups in our cohort was not significant; however, this could be due to the small cohort size or due to characteristics of our group with a minor ATC component; that is, no tumors in this group were limited to the thyroid (stage IVA), resectability with negative margins was infrequent, and 38% of this group had distant metastases at diagnosis (stage IVC).
Asunto(s)
Carcinoma Anaplásico de Tiroides/diagnóstico , Neoplasias de la Tiroides/diagnóstico , Anciano , Anciano de 80 o más Años , Estudios de Cohortes , Femenino , Humanos , Masculino , Márgenes de Escisión , Persona de Mediana Edad , Metástasis de la Neoplasia , Estadificación de Neoplasias , Fenotipo , Pronóstico , Estudios Retrospectivos , Carcinoma Anaplásico de Tiroides/mortalidad , Carcinoma Anaplásico de Tiroides/patología , Carcinoma Anaplásico de Tiroides/cirugía , Neoplasias de la Tiroides/mortalidad , Neoplasias de la Tiroides/patología , Neoplasias de la Tiroides/cirugía , Tiroidectomía , Resultado del TratamientoRESUMEN
OBJECTIVE: To perform a nationwide population based study in ATC on incidence, treatment and survival. DESIGN: Retrospective cohort study. METHODS: All patients with primary ATC between 1989 and 2016 were identified in the Netherlands Cancer Registry (NCR). Of all these patients excerpts from the pathology reports from PALGA: Dutch Pathology registry were linked to the data of the NCR. Standardized incidences were calculated, survival was estimated using Kaplan-Meier method and univariable statistically significant factors were included in a multivariable regression model. RESULTS: In total, 812 patients were included. Mean standardized incidence rates were 0.18/100 000 (range 0.11-0.27/100 000) with a significant trend over the years with an estimated annual percentage change of 1.3% per year (95% CI 0.4-2.1%). Median overall survival was 2.2 months, and estimated 1-year survival was 12%. Patients without distant metastases at diagnosis had an estimated 1-year survival of 21.6%. Prognostic factors for prolonged survival were double or triple therapy, age below 65 years, M0-status and absence of bilateral lymph node metastases. CONCLUSIONS: ATC is rare, but often lethal, form of thyroid cancer, with a median survival of 2 months and 1-year survival of approximately 10%. The incidence is slightly rising in the Netherlands over the past 3 decades. There appears to be a subgroup of patients that survive longer, mainly those with relatively limited disease who underwent double or triple therapy. Further research is needed to define these patients more distinctively.
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Carcinoma Anaplásico de Tiroides/epidemiología , Carcinoma Anaplásico de Tiroides/terapia , Neoplasias de la Tiroides/epidemiología , Neoplasias de la Tiroides/terapia , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Estudios de Cohortes , Femenino , Humanos , Incidencia , Estimación de Kaplan-Meier , Metástasis Linfática , Masculino , Persona de Mediana Edad , Metástasis de la Neoplasia , Países Bajos/epidemiología , Sistema de Registros , Estudios Retrospectivos , Análisis de Supervivencia , Carcinoma Anaplásico de Tiroides/mortalidad , Neoplasias de la Tiroides/mortalidadRESUMEN
BACKGROUND: The role of radiotherapy (RT) in the treatment of patients with anaplastic thyroid cancer (ATC) for local tumor control is critical because mortality often is secondary to complications of tumor volume rather than metastatic disease. Herein, the authors report the long-term outcomes of RT for patients with ATC. METHODS: A total of 104 patients with histologically confirmed ATC were identified who presented to the study institution between 1984 and 2017 and who received curative-intent or postoperative RT. Locoregional progression-free survival (LPFS), overall survival (OS), and distant metastasis-free survival were assessed. RESULTS: The median age of the patients was 63.5 years. The median follow-up was 5.9 months (interquartile range, 2.7-17.0 months) for the entire cohort and 10.6 months (interquartile range, 5.3-40.0 months) for surviving patients. Thirty-one patients (29.8%) had metastatic disease prior to the initiation of RT. Concurrent chemoradiation was administered in 99 patients (95.2%) and 53 patients (51.0%) received trimodal therapy. Systemic therapy included doxorubicin (73.7%), paclitaxel with or without pazopanib (24.3%), and other systemic agents (2.0%). The 1-year OS and LPFS rates were 34.4% and 74.4%, respectively. On multivariate analysis, RT ≥60 Gy was associated with improved LPFS (hazard ratio [HR], 0.135; P = .001) and improved OS (HR, 0.487; P = .004), and trimodal therapy was associated with improved LPFS (HR, 0.060; P = .017). The most commonly observed acute grade 3 adverse events included dermatitis (20%) and mucositis (13%), with no grade 4 subacute or late adverse events noted (adverse events were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events [version 4.0]). CONCLUSIONS: RT appears to demonstrate a dose-dependent, persistent LPFS and OS benefit in patients with locally advanced ATC with an acceptable toxicity profile. Aggressive RT should be strongly considered for the treatment of patients with ATC as part of a trimodal treatment approach.