RESUMEN
PURPOSE: Chordoma is a rare tumor of the skeletal system that is characterized by a high recurrence rate and treatment resistance. Given the common finding of immune dysregulation in chordoma, immunotherapy has emerged as potential treatment option. As an important immune checkpoint regulator, we evaluated cytotoxic T-lymphocyte antigen-4 (CTLA-4) expression and its prognostic significance for patients with chordoma of the spine. METHODS: CTLA-4 expression was analyzed immunohistochemically in 32 chordoma tissues and 14 nucleus pulposus tissues to examine the specificity of CTLA-4 expression in chordoma. Univariate log-rank analysis was used to evaluate the association of CTLA-4 expression in tumor cells and tumor-infiltrating lymphocytes (TILs) with survival. Cox multivariate analysis was used to identify independent factors of survival. RESULTS: Positive CTLA-4 expression was observed in all of the TILs and tumor cell cytoplasm, and partial in the membrane or in both the membrane and nucleus, with a markedly higher positivity rate than that observed in normal nucleus tissues. Higher CTLA-4 expression in the tumor but not in TILs was significantly associated with shorter continuous disease-free survival (CDFS) and overall survival (OS). CTLA-4 expression in tumor cells and TILs were independent predictors for CDFS, whereas only tumor cell expression was a significant predictor of OS. Furthermore, the combination of CTLA-4 expression in the tumor and TILs had higher prognostic value. CONCLUSIONS: Targeting CTLA-4 may be a potential novel therapeutic strategy for chordoma patients.
Asunto(s)
Antígeno CTLA-4/metabolismo , Cordoma/metabolismo , Linfocitos Infiltrantes de Tumor/metabolismo , Neoplasias de la Columna Vertebral/metabolismo , Adolescente , Adulto , Anciano , Niño , Cordoma/inmunología , Cordoma/mortalidad , Cordoma/terapia , Supervivencia sin Enfermedad , Femenino , Humanos , Inmunoterapia , Masculino , Persona de Mediana Edad , Núcleo Pulposo/metabolismo , Pronóstico , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Neoplasias de la Columna Vertebral/inmunología , Neoplasias de la Columna Vertebral/mortalidad , Neoplasias de la Columna Vertebral/terapia , Adulto JovenRESUMEN
CONTEXT AND OBJECTIVE: Chordoma is a rare tumor with a high risk of locoregional recurrences. The aim of this study was analyze the long-term results from treating this pathological condition. DESIGN AND SETTING: Cohort study in a single hospital in São Paulo, Brazil. METHODS: This was a retrospective cohort study on 42 patients with chordoma who were treated at Hospital A. C. Camargo between 1980 and 2006. The hospital records were reviewed and a descriptive analysis was performed on the clinical-pathological variables. Survival curves were estimated using the Kaplan-Meier method and these were compared using the log-rank test. RESULTS: Nineteen patients were men and 23 were women. Twenty-five tumors (59.5%) were located in the sacrum, eleven (26.2%) in the skull base and six (14.3%) in the mobile spine. Surgery was performed on 28 patients (66.7%). The resection was considered to have negative margins in 14 cases and positive margins in 14 cases. The five-year overall survival (OS) was 45.4%. For surgical patients, the five-year OS was 64.3% (82.2% for negative margins and 51.9% for positive margins). In the inoperable group, OS was 37.7% at 24 months and 0% at five years. CONCLUSION: Complete resection is related to local control and definitively has a positive impact on long-term survival. .
CONTEXTO E OBJETIVO: Cordoma é um tumor raro e com alto risco de recidiva locorregional. O objetivo deste estudo foi analisar os resultados a longo prazo do tratamento dessa doença. TIPO DE ESTUDO E LOCAL: Estudo de coorte realizado em um único hospital em São Paulo, Brasil. MÉTODOS: Estudo de coorte retrospectivo com 42 pacientes com cordoma tratados de 1980 e 2006 no Hospital A. C. Camargo. Os prontuários foram revistos e foi realizada a análise descritiva das variáveis clínicas e patológicas. As curvas de sobrevida foram estimadas pelo método de Kaplan-Meier e a comparação entre elas, pelo teste de log-rank. RESULTADOS: Dezenove pacientes eram homens e 23, mulheres. Vinte e cinco tumores (59,5%) estavam localizados no sacro, 11 (26,2%) na base do crânio e 6 (14,3%), na coluna móvel. A cirurgia foi realizada em 28 pacientes (66,7%). A ressecção foi considerada como tendo margens negativas em 14 casos e margens comprometidas em 14 pacientes. A sobrevida global (SG) em 5 anos foi de 45,4%. Para os pacientes cirúrgicos, a SG em 5 anos foi de 64,3% (82,2% para as margens negativas e 51,9% de margens positivas). No grupo inoperável, a SG em 24 meses foi de 37,7% e 0% em 5 anos. CONCLUSÃO: A ressecção completa está relacionada com o controle local e, definitivamente, tem impacto positivo na sobrevida a longo prazo. .
Asunto(s)
Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Preescolar , Femenino , Humanos , Masculino , Persona de Mediana Edad , Adulto Joven , Cordoma/mortalidad , Sacro , Neoplasias de la Base del Cráneo/mortalidad , Neoplasias de la Columna Vertebral/mortalidad , Brasil/epidemiología , Cordoma/radioterapia , Cordoma/cirugía , Registros Médicos , Recurrencia Local de Neoplasia/mortalidad , Estudios Retrospectivos , Neoplasias de la Base del Cráneo/radioterapia , Neoplasias de la Base del Cráneo/cirugía , Neoplasias de la Columna Vertebral/radioterapia , Neoplasias de la Columna Vertebral/cirugía , Tasa de Supervivencia , Resultado del TratamientoRESUMEN
CONTEXT AND OBJECTIVE: Chordoma is a rare tumor with a high risk of locoregional recurrences. The aim of this study was analyze the long-term results from treating this pathological condition. DESIGN AND SETTING: Cohort study in a single hospital in São Paulo, Brazil. METHODS: This was a retrospective cohort study on 42 patients with chordoma who were treated at Hospital A. C. Camargo between 1980 and 2006. The hospital records were reviewed and a descriptive analysis was performed on the clinical-pathological variables. Survival curves were estimated using the Kaplan-Meier method and these were compared using the log-rank test. RESULTS: Nineteen patients were men and 23 were women. Twenty-five tumors (59.5%) were located in the sacrum, eleven (26.2%) in the skull base and six (14.3%) in the mobile spine. Surgery was performed on 28 patients (66.7%). The resection was considered to have negative margins in 14 cases and positive margins in 14 cases. The five-year overall survival (OS) was 45.4%. For surgical patients, the five-year OS was 64.3% (82.2% for negative margins and 51.9% for positive margins). In the inoperable group, OS was 37.7% at 24 months and 0% at five years. CONCLUSION: Complete resection is related to local control and definitively has a positive impact on long-term survival.
Asunto(s)
Cordoma/mortalidad , Sacro , Neoplasias de la Base del Cráneo/mortalidad , Neoplasias de la Columna Vertebral/mortalidad , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Brasil/epidemiología , Niño , Preescolar , Cordoma/radioterapia , Cordoma/cirugía , Femenino , Humanos , Masculino , Registros Médicos , Persona de Mediana Edad , Recurrencia Local de Neoplasia/mortalidad , Estudios Retrospectivos , Neoplasias de la Base del Cráneo/radioterapia , Neoplasias de la Base del Cráneo/cirugía , Neoplasias de la Columna Vertebral/radioterapia , Neoplasias de la Columna Vertebral/cirugía , Tasa de Supervivencia , Resultado del Tratamiento , Adulto JovenRESUMEN
Chordomas are rare neoplasms arising from notochord remnants. Tyrosine kinase receptors (RTK) are altered in these lesions. We used a tissue microarray containing 58 chordomas to examine the expression of platelet-derived growth factor receptor (PDGFR)-α and PDGFR-ß, epidermal growth factor receptor (EGFR), c-Met, c-Kit, pAKT, mammalian target of rapamycin, and HER2 by immunohistochemistry and fluorescence in situ hybridization. Most tumors were positive for PDGFR-α (92%), PDGFR-ß (85%), c-Kit (77.4%), c-Met (96%), pAKT (82%), mammalian target of rapamycin (56%), HER2 (24%), and EGFR (26%) by immunohistochemistry. Amplifications or deletions could not be identified for HER2 or EGFR in the 13 cases available for fluorescence in situ hybridization analysis; however, chromosome 7 polysomy was detected in 29% of the cases. The only factor directly associated with a poorer survival rate was pAKT positivity (P = .042). The 5-year survival rate for patients with pAKT-negative chordomas was 100%, whereas it was 45% for patients with pAKT-positive chordomas. Our results confirm that RTKs are frequently altered in chordomas. Given the implications of pAKT positivity, RTK inhibitors might be efficacious, and drugs that inhibit AKT, alone or in combination with radiotherapy, could be an effective treatment for patients with refractory chordomas.
Asunto(s)
Cordoma/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Proteínas Tirosina Quinasas Receptoras/metabolismo , Neoplasias de la Columna Vertebral/metabolismo , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Aneuploidia , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Brasil/epidemiología , Niño , Preescolar , Cordoma/genética , Cordoma/mortalidad , Cordoma/patología , Cromosomas Humanos Par 7 , Femenino , Humanos , Hibridación Fluorescente in Situ , Lactante , Masculino , Persona de Mediana Edad , Fosforilación , Proteínas Proto-Oncogénicas c-akt/genética , Proteínas Tirosina Quinasas Receptoras/genética , Estudios Retrospectivos , Neoplasias de la Columna Vertebral/genética , Neoplasias de la Columna Vertebral/mortalidad , Neoplasias de la Columna Vertebral/patología , Tasa de Supervivencia , Análisis de Matrices Tisulares , Adulto JovenRESUMEN
Cordomas são neoplasias raras que se originam dos remanescentes da notocorda primitiva 50% dos casos têm localização sacral, sendo mais frequente ao nível de S4/S5. Nós descrevemos um caso de cordoma sacral ao nível de S1 e discutimos a apresentação clínica, achados de imagem, tratamento cirúrgico e evolução.
Chordomas are rare neoplasias originating from the remaining primitive notochord. 50% of the cases have sacral localization, being more frequent at levels S4/S5. Here we report a case of sacral chordoma at level S1 and discuss its clinical presentation, imaging findings, surgical treatment, and progress.
Asunto(s)
Humanos , Femenino , Anciano , Cordoma/complicaciones , Cordoma/diagnóstico , Cordoma/epidemiología , Cordoma/etiología , Cordoma/mortalidad , Cordoma/patología , Cordoma/terapia , Diagnóstico Diferencial , Tomografía Computarizada de Emisión , Espectroscopía de Resonancia Magnética , Región SacrococcígeaRESUMEN
A clinical study of the TBA was performed in 22 patients harboring tumors of the skull base. The follow-up ranged from 3 to 89 months (average, 30.5 months). The main complications were intracerebral hematoma, ptosis, and infection. One patient died (4.5%) because of an extradural hematoma. Eight patients died during the follow-up because of tumor complications. Among the survivals, the median of the Karnofsky index was 96.4. Based on this study, we propose a classification for the TBA, according to its extension.
Asunto(s)
Procedimientos Neuroquirúrgicos/clasificación , Neoplasias Hipofisarias/cirugía , Neoplasias de la Base del Cráneo/cirugía , Angiofibroma/mortalidad , Angiofibroma/cirugía , Condrosarcoma/mortalidad , Condrosarcoma/cirugía , Cordoma/mortalidad , Cordoma/cirugía , Displasia Fibrosa Ósea/mortalidad , Displasia Fibrosa Ósea/cirugía , Estudios de Seguimiento , Humanos , Neoplasias Meníngeas/mortalidad , Neoplasias Meníngeas/cirugía , Meningioma/mortalidad , Meningioma/cirugía , Neuroblastoma/mortalidad , Neuroblastoma/cirugía , Procedimientos Neuroquirúrgicos/métodos , Osteoma/mortalidad , Osteoma/cirugía , Neoplasias Hipofisarias/mortalidad , Plasmacitoma/mortalidad , Plasmacitoma/cirugía , Complicaciones Posoperatorias , Calidad de Vida , Rabdomioma/mortalidad , Rabdomioma/cirugía , Neoplasias de la Base del Cráneo/mortalidad , Tasa de SupervivenciaRESUMEN
OBJECT: Chordomas are rare tumors that arise from the remnants of the notochord. Because of their deep location, local infiltrative nature, and involvement of surrounding bone, treatment of chordomas is a challenge. In this study the authors analyze the data and prognostic factors obtained during the follow-up period (range 1-150 months, median 38 months) in 53 patients with craniocervical junction chordomas and 10 patients with chondrosarcomas. METHODS: Several surgical approaches were used, and some tumor excisions required staged procedures. Survival was calculated according the Kaplan-Meier method. Statistical analysis was performed using Fisher exact, log rank and Kruskal-Wallis tests. Radical/subtotal resection was achieved in 77.8% of the patients. The mortality rate during the follow-up period was 14.3%. In patients harboring chondrosarcoma better 5-year recurrence-free survival (RFS) rates were demonstrated than in those with chordoma (100% and 50.7%. respectively). Histological patterns (typical or chondroid chordomas) and patient age at onset of symptoms had no effect on the RFS rates. Radical/subtotal resections were associated with better RFS rates than partial resection. Adjuvant proton-beam therapy was shown to increase the RFS rates compared with conventional radiotherapy (90.9% and 19.4%, respectively, at 4 years posttreatment). Karyotypically abnormal tumors were associated with the worst RFS rates compared with karyotypically normal lesions (44.5% and 90.3%, respectively, at 3 years). Cases of cranial nerve palsy followed by those with cerebrospinal fluid leakages were the most frequent postoperative complications. Permanent postoperative neurological deficit was observed in 28.6% of the patients. CONCLUSIONS: A better prognosis was observed in patients with chondrosarcoma compared with those harboring chordoma. Histological pattern and patient age at symptom onset were not factors that influenced prognosis in cases of chordoma. Extensive resection and possibly adjuvant proton-beam therapy provided better prognoses for these patients.
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Cordoma/mortalidad , Cordoma/cirugía , Neoplasias de la Base del Cráneo/mortalidad , Neoplasias de la Base del Cráneo/cirugía , Adolescente , Adulto , Anciano , Niño , Condrosarcoma/mortalidad , Condrosarcoma/radioterapia , Condrosarcoma/cirugía , Cordoma/radioterapia , Fosa Craneal Posterior , Diploidia , Citometría de Flujo , Estudios de Seguimiento , Humanos , Persona de Mediana Edad , Complicaciones Posoperatorias/mortalidad , Pronóstico , Antígeno Nuclear de Célula en Proliferación/análisis , Receptores de Estrógenos/análisis , Receptores de Progesterona/análisis , Recuperación de la Función , Neoplasias de la Base del Cráneo/radioterapia , Tasa de Supervivencia , Resultado del TratamientoRESUMEN
INTRODUCTION: Chordoma is a rare and slow-growing tumor, with local aggressiveness and preferential localization in the vertebral column. OBJECTIVE: The main objective of this study is to evaluate natural history and results of treatment of chordomas. METHODOLOGY: This is a retrospective study from 1953 to 1993. MATERIAL AND METHODS: The age ranged from 2 to 86 years (mean = 34.5). Twelve patients were male and 12 female. The localization of the tumor was: 20 in the sacral region, 3 in head and neck and one out of the spine. RESULTS: The treatment, alone or combined, was surgery, radiation therapy and chemotherapy. The survival rate for patients with lesions in the sacrum ranged from 4 to 119 months, since the date of the symptoms. The 5-year overall survival was 4.2%. CONCLUSION: Chordoma is a rare and slow growing tumor, with a very difficult approach by surgery due to its preferential location in the sacrum and poor therapeutic results with radiation therapy or chemotherapy, mainly in patients with advanced disease.
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Cordoma/terapia , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Preescolar , Cordoma/mortalidad , Cordoma/patología , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Región Sacrococcígea , Tasa de SupervivenciaRESUMEN
The tumors I will discuss in this chapter on chemotherapy will be ethesioneuroblastoma, salivary gland tumors, chordoma and nasopharyngeal carcinoma. Due basically to the rarity of these lesions, with the exception of nasopharyngeal carcinoma, there have been no multi-institutional studies of chemotherapy use reported in the literature. As a result, there is no clear-cut consensus on the standard of care as it relates to chemotherapy for these tumors. As with most authors who have previously reviewed these tumor types, I believe it is important for us to propose protocols of therapy and test these in arenas where we can accumulate enough patients for meaningful results. In this way, we can test the apparently active agents and combinations in relapsed or extensive disease. We might also begin to explore concurrent therapy (i.e., concurrent radiation and chemotherapy after the surgical procedure, for example).