RESUMEN
OBJECTIVE: To critically examine the evidence-base for survival benefit of pulmonary metastasectomy (PM) for osteosarcoma (OS) in the pediatric population. BACKGROUND: PM for OS is recommended as the standard of care in both pediatric and adult treatment protocols. Recent results from the "Pulmonary Metastasectomy in Colorectal Cancer" trial demonstrate no survival benefit from PM in colorectal cancer in adults. METHODS: A systematic review was undertaken according to "Preferred Reporting Items for Systematic Reviews and Meta-Analysis" guidelines. Medline, Embase, and 2 clinical trial registers were searched for all studies detailing pediatric patients with OS (<18 years) undergoing PM with a comparison cohort group that did not receive PM. RESULTS: Eleven studies met inclusion criteria dating from 1984 to 2017. All studies were retrospective and none directly compared PM versus no PM in pediatric patients as its main objective(s). Three-year survival rates ranged from 0% to 54% for PM and 0% to 16% for no PM. No patients receiving PM were usually those with unresectable disease and/or considered to have a poor prognosis. All studies were at high risk of bias and there was marked heterogeneity in the patient selection. CONCLUSIONS: There is a weak evidence base (level IV) for a survival benefit of PM for OS in pediatric patients likely due to selection bias of "favorable cases." The included studies many of which detailed outdated treatment protocols were not designed in their reporting to specifically address the questions directly. A randomized controlled trial-while ethically challenging in a pediatric population-incorporating modern OS chemotherapy protocols is needed to crucially address any "survival benefit."
Asunto(s)
Neoplasias Pulmonares , Metastasectomía , Osteosarcoma , Humanos , Osteosarcoma/cirugía , Osteosarcoma/mortalidad , Osteosarcoma/secundario , Neoplasias Pulmonares/secundario , Neoplasias Pulmonares/cirugía , Neoplasias Pulmonares/mortalidad , Metastasectomía/métodos , Niño , Neoplasias Óseas/secundario , Neoplasias Óseas/cirugía , Neoplasias Óseas/mortalidad , Neumonectomía/métodos , Tasa de Supervivencia , Resultado del TratamientoRESUMEN
BACKGROUND: Osteosarcoma is the most common primary malignant bone tumour in children and adolescents. Lungs are the most frequent and often the only site of metastatic disease. The presence of pulmonary metastases is a significant unfavourable prognostic factor. Thoracotomy is strongly recommended in these patients, while computed tomography (CT) remains the gold imaging standard. The purpose of our study was to create tools for the CT-based qualification for thoracotomy in osteosarcoma patients in order to reduce the rate of useless thoracotomies. METHODS: Sixty-four osteosarcoma paediatric patients suspected of lung metastases on CT and their first-time thoracotomies (n = 100) were included in this retrospective analysis. All CT scans were analysed using a compartmental evaluation method based on the number and size of nodules. Calcification and location of lung lesions were also analysed. Inter-observer reliability between two experienced radiologists was assessed. The CT findings were then correlated with the histopathological results of thoracotomies. Various multivariate predictive models (logistic regression, classification tree and random forest) were built and predictors of lung metastases were identified. RESULTS: All applied models proved that calcified nodules on the preoperative CT scan best predict the presence of pulmonary metastases. The rating of the operated lung on the preoperative CT scan, dependent on the number and size of nodules, and the total number of nodules on this scan were also found to be important predictors. All three models achieved a relatively high sensitivity (72-92%), positive predictive value (81-90%) and accuracy (74-79%). The positive predictive value of each model was higher than of the qualification for thoracotomy performed at the time of treatment. Inter-observer reliability was at least substantial for qualitative variables and excellent for quantitative variables. CONCLUSIONS: The multivariate models built and tested in our study may be useful in the qualification of osteosarcoma patients for metastasectomy through thoracotomy and may contribute to reducing the rate of unnecessary invasive procedures in the future.
Asunto(s)
Neoplasias Óseas , Neoplasias Pulmonares , Osteosarcoma , Toracotomía , Tomografía Computarizada por Rayos X , Humanos , Osteosarcoma/diagnóstico por imagen , Osteosarcoma/cirugía , Osteosarcoma/secundario , Osteosarcoma/patología , Neoplasias Pulmonares/diagnóstico por imagen , Neoplasias Pulmonares/cirugía , Neoplasias Pulmonares/secundario , Neoplasias Pulmonares/patología , Adolescente , Niño , Estudios Retrospectivos , Masculino , Femenino , Neoplasias Óseas/secundario , Neoplasias Óseas/diagnóstico por imagen , Neoplasias Óseas/cirugíaRESUMEN
BACKGROUND: Head and neck osteosarcoma (HNOS) is the most common bone malignancy in the head and neck region, accounting for 10% of all osteosarcoma cases. Perineural invasion (PNI) is a notable indication of aggressive tumor behavior, which includes the phenomenon of tumor cells invading any of the 3 layers of the nerve sheath or tumor cells gathering, encircling one-third of the nerve circumference, and infiltrating and metastasizing along the nerve. PNI has been reported in various malignant tumors and is considered to be linked to poor prognosis. PURPOSE: The study's purpose is to measure the association between PNI and survival outcomes in patients with HNOS. STUDY DESIGN, SETTING, SAMPLE: This retrospective cohort study focused on HNOS patients who underwent surgery at the Department of Oral and Maxillofacial Head and Neck Oncology, Shanghai Ninth People's Hospital School of Medicine, Shanghai Jiao Tong University, from January 1, 2019 to December 31, 2021. Patients who did not undergo complete surgical resection of the tumor, did not receive a conventional osteosarcoma diagnosis, and had positive surgical margins were eliminated. PREDICTOR VARIABLE: The predictor variable is PNI status. The pathological section of the tumor was consistent with any of the PNI features, which was considered PNI-positive. MAIN OUTCOME VARIABLE(S): The primary outcome variables were 3-year disease-free survival (DFS) and 3-year overall survival. Secondary outcomes were 3-year tumor local recurrence and 3-year metastasis (MT). COVARIATES: Covariates were categorized into the following categories: demographic variables (age, sex), clinical variables (tumor region, primary tumor), and treatment variables (chemotherapy, radiotherapy). ANALYSES: Analytic statistical methods were used for the data analysis. Pearson χ2 or Fisher's exact test was used to describe the baseline data. Kaplan-Meier is used to calculate survival rates. The Cox regression model was adapted for univariate and multivariate analysis. A P value less than .05 indicated statistical significance. RESULTS: The study sample comprised 70 patients; 33 (47.1%) were male, and the mean age was 42.2 (standard deviation: 16.7) years. There were 15 (21.4%) cases of PNI. The 3-year DSF rate and OS rate were 67.3% and 82.0%, respectively. PNI-positive resulted in higher risk for MT (P ï¼ .01, hazard ratio: 5.95, 95% confidence interval: 1.62-21.86) and negative impact on DFS (P < .01, hazard ratio: 6.35, 95% confidence interval: 2.11-19.17) for HNOS patients. CONCLUSION AND RELEVANCE: Positive PNI status was associated with decreased DFS and increased risk of MT.
Asunto(s)
Neoplasias de Cabeza y Cuello , Invasividad Neoplásica , Osteosarcoma , Humanos , Masculino , Femenino , Estudios Retrospectivos , Osteosarcoma/patología , Osteosarcoma/mortalidad , Osteosarcoma/secundario , Neoplasias de Cabeza y Cuello/patología , Neoplasias de Cabeza y Cuello/cirugía , Adulto , Supervivencia sin Enfermedad , Persona de Mediana Edad , Adolescente , Anciano , Adulto Joven , Niño , Pronóstico , Metástasis de la NeoplasiaRESUMEN
BACKGROUND: Osteosarcoma cells are prone to metastasis, and the mechanism of N6-methyladenosine (m6A) methylation modification in this process is still unclear. Methylation modification of m6A plays an important role in the development of osteosarcoma, which is mainly due to abnormal expression of enzymes related to methylation modification of m6A, which in turn leads to changes in the methylation level of downstream target genes messenger RNA (mRNA) leading to tumor development. METHODS: We analyzed the expression levels of m6A methylation modification-related enzyme genes in GSE12865 whole-genome sequencing data. And we used shRNA (short hairpin RNA) lentiviral interference to interfere with METTL3 (Methyltransferase 3) expression in osteosarcoma cells. We studied the cytological function of METTL3 by Cell Counting Kit-8 (CCK8), flow cytometry, migration and other experiments, and the molecular mechanism of METTL3 by RIP (RNA binding protein immunoprecipitation), Western blot and other experiments. RESULTS: We found that METTL3 is abnormally highly expressed in osteosarcoma and interferes with METTL3 expression in osteosarcoma cells to inhibit metastasis, proliferation, and apoptosis of osteosarcoma cells. We subsequently found that METTL3 binds to the mRNA of CBX4 (chromobox homolog 4), a very important regulatory protein in osteosarcoma metastasis, and METTL3 regulates the mRNA and protein expression of CBX4. Further studies revealed that METTL3 inhibited metastasis of osteosarcoma cells by regulating CBX4. METTL3 has been found to be involved in osteosarcoma cells metastasis by CBX4 affecting the protein expression of matrix metalloproteinase 2 (MMP2), MMP9, E-Cadherin and N-Cadherin associated with osteosarcoma cells metastasis. CONCLUSIONS: These results suggest that the combined action of METTL3 and CBX4 plays an important role in the regulation of metastasis of osteosarcoma, and therefore, the METTL3-CBX4 axis pathway may be a new potential therapeutic target for osteosarcoma.
Asunto(s)
Adenina , Neoplasias Óseas , Metaloproteinasa 2 de la Matriz , Osteosarcoma , Humanos , Adenina/análogos & derivados , Epigénesis Genética , Ligasas/genética , Metaloproteinasa 2 de la Matriz/metabolismo , Metiltransferasas/genética , Metiltransferasas/metabolismo , Osteosarcoma/genética , Osteosarcoma/secundario , Proteínas del Grupo Polycomb/genética , ARN Mensajero/genética , ARN Interferente Pequeño , Neoplasias Óseas/patologíaRESUMEN
Metastasis is the principal factor in poor prognosis for individuals with osteosarcoma (OS). Understanding the events that lead to metastasis is critical to develop better interventions for this disease. Alveolar macrophages are potentially involved in priming the lung microenvironment for OS metastasis, yet the mechanisms involved in this process remain unclear. Since extracellular vesicles (EVs) are a known actor in primary tumor development, their potential role in OS metastagenesis through macrophage modulation is explored here. The interaction of EVs isolated from highly metastatic (K7M2) and less metastatic (K12) osteosarcoma cell lines is compared with a peritoneal macrophage cell line. An EV concentration that reproducibly induced macrophage migration is identified first, then used for later experiments. By confocal microscopy, both EV types associated with M0 or M1 macrophages; however, only K7M2-EVs are associated with M2 macrophages, an interaction that is abrogated by EV pre-treatment with anti-CD47 antibody. Interestingly, all interactions appeared to be surface binding, not internalized. In functional studies, K7M2-EVs polarized fewer macrophages to M1. Together, these data suggest that K7M2-EVs have unique interactions with macrophages that can contribute to the production of a higher proportion of pro-tumor type macrophages, thereby accelerating metastasis.
Asunto(s)
Neoplasias Óseas , Vesículas Extracelulares , Macrófagos , Osteosarcoma , Osteosarcoma/patología , Osteosarcoma/metabolismo , Osteosarcoma/secundario , Vesículas Extracelulares/metabolismo , Humanos , Línea Celular Tumoral , Macrófagos/inmunología , Macrófagos/metabolismo , Neoplasias Óseas/patología , Neoplasias Óseas/metabolismo , Neoplasias Óseas/secundario , Fenotipo , Animales , Microambiente Tumoral , Metástasis de la Neoplasia , Ratones , Movimiento CelularRESUMEN
No disponible
Asunto(s)
Masculino , Adulto , Humanos , Osteosarcoma , Osteosarcoma/secundario , Neoplasias Femorales/patología , Neoplasias PleuralesRESUMEN
El sarcoma osteogénico u osteosarcoma es un tumor maligno de huesos que ocurre en la segunda o tercera década de vida y en muy raras ocasiones ocurre en niños menores de 5 años. Presentamos el caso de un niño de 3 9/12 años de edas, uno de los pacientes más jóvenes descritos en la literatura. En este paciente el tumor fue muy agresivo, con metástasis al pulmón al momento del diagnóstico y una progresión muy rápida a pesar de quimioterapia y cirugía. El diagnóstico de este paciente fue algo tardío por la presentación poco usual a esta edad
Asunto(s)
Preescolar , Niño , Humanos , Masculino , Neoplasias Femorales/diagnóstico , Neoplasias Pulmonares/secundario , Osteosarcoma/diagnóstico , Neoplasias Pulmonares , Imagen por Resonancia Magnética , Osteosarcoma/secundario , Tomografía Computarizada por Rayos XRESUMEN
Se estudia la historia clínica de una niña en quien se practicó la amputación transescápulotorácica izquierda, cuando tenía siete años de edad, por sarcoma osteogénico en húmero izquierdo; y se le prescribió un tratamiento a base de Ciclofosfamida-Methotrexate-Adriamicina, en ciclos mensuales, durante un año; y durante dos ciclos más, con Methotrexate y Ciclofosfamida. La paciente permaneció bien hasta que presentó, ochenta y ocho meses después, una lesión en el tercio distal del muslo derecho; la biopsia reveló que era un Sarcoma osteogénico. Se le amputó el miembro inferior derecho y se prescribió Ciclofosfamida y Decarbacina. Como tres meses después presentara metástasis en los pulmones, se le administró CisPlatinum. La paciente falleció un año después de la segunda operación. Los autores consideran que la niñita sufrió, por las razones que comentan, de un foco primario de sarcoma osteogénico en 1978, del cual aparentemente curó; y de un segundo foco primario de sarcoma osteogénico con metástasis pulmonar, en 1985
Asunto(s)
Niño , Humanos , Femenino , Osteosarcoma/secundario , Neoplasias Femorales/secundario , Neoplasias Primarias Múltiples , Húmero , Osteosarcoma/patología , Osteosarcoma/terapia , Neoplasias Femorales/patología , Amputación Quirúrgica , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Diagnóstico DiferencialRESUMEN
Introducción. Es bien conocido que el osteosarcoma se presenta frecuentemente como segunda neoplasia del retinoblastoma congénito, así como otro tipo de carcinomas, melanomas y tumores neuroepiteliales. Todos los pacientes con retinoblastoma bilateral congéntio presentan una alteración del gen RB1 localizado en el cromosoma 13q14. Caso clínico. Se presenta el caso de una paciente con retinoblastoma bilateral congénito diagnosticado a la edad de 1 año 11 meses, quien recibió tratamiento con ciclofosfamida, epirrubicina y VP 16, entre otros agentes; y que desarrolló osteosarcoma peroneo con metástasis pulmonares tras una latencia de 10 años 6 meses. En esta paciente es conocido el uso de alquilantes, antracíclicos y etopósido, así como los antecedentes familiares de cáncer por ambas ramas. Conclusión. El retinoblastoma bilateral conlleva factores de riesgo para el desarrollo de segundas neoplasias. Los antecedentes familiares constituyen razones suficientes para catalogarlo como un síndrome de cáncer familiar, el uso de agentes alquilantes, antraciclicos y etopósidos, aumentan este riesgo acortando el período de latencia
Asunto(s)
Humanos , Femenino , Adolescente , Genes de Retinoblastoma , Osteosarcoma/diagnóstico , Osteosarcoma/secundario , Retinoblastoma/complicaciones , Retinoblastoma/congénito , Retinoblastoma/tratamiento farmacológico , Retinoblastoma/genética , Enfermedades Genéticas Congénitas/genéticaRESUMEN
Os autores apresentam três casos de pacientes portadores de retinoblastoma, tratados com químio e radioterapia, que desenvolveram segunda neoplasia 4, 10 e 13 anos após o primeiro diagnóstico. Discutem-se efeitos carcinogenéticos da terapêutica antineoplásica (rádio e quimioterapia), e a susceptibilidade genética de mutaçäo que leva os portadores de uma determinada neoplasia a desenvolverem uma segunda (cuja etiologia encontra-se em investigaçäo). Com base em revisäo da literatura e na experiência pessoal, podemos dizer que há evidência clara de que os portadores de retinoblastoma bilateral têm maior probabilidade de manifestar segundo tumor. Nos três casos analisados os tumores secundários foram osteossarcoma em dois casos, e fibrossarcoma em um caso e todos eram portadores de retinoblastoma bilateral. No intuito de alertar para esse fato, propö-se uma menor exposiçäo dos pacientes portadores de retinoblastoma bilateral a tratamentos potencialmente agressivos. O acompanhamento dos pacientes deve ser ser longo, uma vez que os segundos tumores podem ocorrer vários anos após o término do tratamento da primeira neoplasia