RESUMEN
BACKGROUND: Bone radiation-induced sarcomas (B-RIS) are secondary neoplasms with reportedly worse overall survival than de novo bone sarcoma. Treatment strategy for these neoplasms remains uncertain. Our systematic review sought to assess overall survival based on histology and surgical intervention. METHODS: A systemic review was conducted following Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines and registered in PROSPERO (438415). Studies describing oncologic outcomes of patients with B-RIS in the appendicular and axial skeleton were included. The Strengthening the Reporting of Observational Studies in Epidemiology checklist was used for quality assessment. Survival analysis by histologic subtype and surgery type was performed in a subset of 234 patients from 11 articles with individualized data. A total of 20 articles with a total of 566 patients were included. The most frequent location was the pelvis (27.7%), and the main histological types were osteosarcoma (69.4%), undifferentiated pleomorphic sarcoma (14.1%), and fibrosarcoma (9.2%). Limb-salvage and amputation were performed in 68.5% and 31.5% of cases, respectively. RESULTS: Local recurrence was 13%, without difference between limb-salvage surgery and amputation (p = 0.51). The metastasis rate was 42.3%. Five-year OS was 43.7% (95% confidence interval [CI], 33.3%-53.5%) for osteosarcoma, 31.5% (95% CI, 11.3%-54.2%) for UPS, and 28.1% (95% CI, 10.6%-48.8%) for fibrosarcoma. Five-year OS was 49.2% (95% CI, 35.3%-61.6%) for limb-salvage and 46.9% (95% CI, 29.1%-62.9%) for amputation. There was no difference in 5-year OS between histologic subtypes (p = 0.18) or treatment type (p = 0.86). CONCLUSION: B-RIS demonstrated poor OS at 5 years after initial management regardless of histology. Limb-salvage surgery was not associated with lower 5-year OS compared with amputation. Future studies should compare both groups while controlling for confounders. LEVEL OF EVIDENCE: Level III. See Instructions for Authors for a complete description of levels of evidence.
Asunto(s)
Neoplasias Óseas , Neoplasias Inducidas por Radiación , Sarcoma , Humanos , Neoplasias Óseas/radioterapia , Neoplasias Óseas/cirugía , Neoplasias Óseas/mortalidad , Neoplasias Óseas/patología , Sarcoma/radioterapia , Sarcoma/patología , Sarcoma/cirugía , Sarcoma/mortalidad , Neoplasias Inducidas por Radiación/patología , Neoplasias Inducidas por Radiación/cirugía , Neoplasias Inducidas por Radiación/etiología , Recuperación del Miembro , Masculino , Femenino , Osteosarcoma/patología , Osteosarcoma/mortalidad , Osteosarcoma/cirugía , Osteosarcoma/radioterapia , Adulto , Resultado del Tratamiento , Persona de Mediana Edad , AdolescenteRESUMEN
INTRODUCTION: different variables have been associated with a worse prognosis of patients with osteosarcoma (OS), highlighting tumor size, location in the axial skeleton and the presence of metastases. The objective of this study is to analyze the prognostic impact of diagnostic delay in osteosarcoma in adults in the Mexican population in a center specialized in sarcomas. MATERIAL AND METHODS: retrospective cohort study from January 1, 2005, to December 31, 2016, 96 patients over 21 years of age with a diagnosis of osteosarcoma were analyzed. RESULTS: the median time to diagnosis from the onset of symptoms was six months (range: 2-36). This variable was dichotomized by applying the operator-dependent curve (ROC) analysis and we determined a cut-off value greater than five months, with an area under the curve (AUC) = 0.93 [95% CI 0.86-0.97], sensitivity 93.2% and specificity 94.6%. CONCLUSION: time until diagnosis is a critical factor in the survival of adult patients with osteosarcoma, highlighting its influence on disease progression and the appearance of metastasis. The correlation between diagnostic delay and an unfavorable prognosis reinforces the need for rapid and efficient evaluation in suspected cases of osteosarcoma.
INTRODUCCIÓN: diferentes variables se han asociado con un peor pronóstico de los pacientes con osteosarcoma, destacando el tamaño tumoral, la localización en esqueleto axial y la presencia de metástasis. El objetivo de este estudio fue analizar el impacto pronóstico del retraso diagnóstico en osteosarcoma en adultos en población mexicana en un centro especializado en sarcomas. MATERIAL Y MÉTODOS: estudio de tipo cohorte retrospectiva del 1 de Enero del 2005 al 31 de Diciembre de 2016, se analizaron 96 pacientes mayores de 21 años con diagnóstico de osteosarcoma. RESULTADOS: la mediana de tiempo al diagnóstico desde el inicio de síntomas fue de seis meses (rango: 2-36). Esta variable se dicotomizó aplicando el análisis de curva dependiente de operador (ROC) y determinamos un valor de corte mayor a cinco meses con un área bajo la curva (AUC) = 0.93 [IC95% 0.86-0.97], sensibilidad 93.2% y especificidad 94.6%. CONCLUSIÓN: el tiempo hasta el diagnóstico es un factor crítico en la supervivencia de los pacientes adultos con osteosarcoma, destacando su influencia en la progresión de la enfermedad y la aparición de metástasis. La correlación entre el retraso diagnóstico y un pronóstico desfavorable refuerza la necesidad de una evaluación rápida y eficiente en casos sospechosos de osteosarcoma.
Asunto(s)
Neoplasias Óseas , Diagnóstico Tardío , Osteosarcoma , Humanos , Osteosarcoma/diagnóstico , Osteosarcoma/patología , Osteosarcoma/mortalidad , Estudios Retrospectivos , Masculino , Adulto , Femenino , Neoplasias Óseas/diagnóstico , Neoplasias Óseas/patología , Pronóstico , Persona de Mediana Edad , Adulto Joven , Anciano , México , Factores de Tiempo , Sensibilidad y Especificidad , Estudios de Cohortes , Progresión de la Enfermedad , Curva ROCRESUMEN
BACKGROUND: Osteosarcoma is the most common primary malignant bone tumor, mainly affecting children, young adults, and the elderly. It is an aggressive cancer with a poor prognosis, exhibiting low survival rates even with standard treatment. Recently, circular RNA molecules capable of influencing gene expression through various functions, with their main role being acting as microRNA sponges and reducing their intracellular expression, have been identified. Recent studies have linked circular RNAs to osteosarcoma development and progression. Therefore, the present study aimed to investigate the alteration in circular RNA expression during osteosarcoma development and progression. METHODS: An integrative literature review was conducted from September 10th to November 12th, 2021, using the following databases: PubMed/MEDLINE, SCOPUS, Web of Science, OVID, and EMBASE. 129 full articles were included in the review. The obtained data were organized using a standardized data collection instrument, which included the following information: altered expression profile of circular RNAs, associated cancer hallmarks, clinical-pathological relationships of circular RNAs, and perspectives on the studied circular RNAs. RESULTS: A total of 94 distinct circular RNAs were identified, predominantly showing an increased expression pattern. Approximately 91% of the studies that aimed to identify the mechanisms of action of circular RNAs highlighted the function of circular RNAs as microRNA sponges. The most associated cancer hallmarks with the identified circular RNAs were proliferative signaling induction, invasion and metastasis, and resistance to cell death. The altered expression of these circular RNAs generally correlated with a worse prognosis for patients, as evidenced by clinical features such as shorter survival, advanced Enneking and/or TNM stage, higher incidence of metastasis, larger tumor size, and increased chemoresistance. CONSLUSION: These findings indicate the significance of circular RNA molecules in osteosarcoma carcinogenesis, suggesting their potential as new prognostic and/or diagnostic biomarkers, as well as alternative therapeutic targets in the fight against osteosarcoma.
Asunto(s)
Neoplasias Óseas , Progresión de la Enfermedad , Osteosarcoma , ARN Circular , Humanos , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Neoplasias Óseas/genética , Neoplasias Óseas/patología , Neoplasias Óseas/metabolismo , Regulación Neoplásica de la Expresión Génica , MicroARNs , Osteosarcoma/genética , Osteosarcoma/patología , Osteosarcoma/metabolismo , Osteosarcoma/mortalidad , Pronóstico , ARN Circular/genéticaRESUMEN
INTRODUCCIÓN: El osteosarcoma (OS) es el tumor óseo primario maligno más frecuente. En 2014 se incorporó en Chile dentro del plan de garantías explícitas en salud (GES), ley que garantiza el tratamiento desde la sospecha hasta su tratamiento y rehabilitación. OBJETIVOS: Describir las características de la población mayor de 15 años, con diagnóstico histopatológico de OS, definir su sobrevida, complicaciones e identificar variables que afectan estos resultados. MATERIAL Y MÉTODOS: Estudio retrospectivo, se incluyó a todos los pacientes con diagnóstico de OS, con confirmación histológica, desde 2014 a 2020. Datos demográficos, sitio anatómico, hallazgos histopatológicos, estadio de ingreso, presencia de metástasis, tratamiento, complicaciones y sobrevida fueron registrados. Se realizó un estudio multivariante para determinar factores pronósticos. RESULTADOS: 133 pacientes fueron incluidos. 58,8% hombres, la edad promedio fue 31 años y la localización más frecuente fue fémur distal (34,9%). El 56,4% de los pacientes ingresó en estadio Enneking IIB, 36,4% presentó metástasis al ingreso. Un 14,3% presentó complicaciones, siendo la más frecuente la infección periprotésica (6 casos). El 16% evolucionó con recidiva local. El modelo multivariante mostró que la edad y presencia de metástasis al ingreso constituyen variables pronósticas independientes, con un cociente de riesgo de 1,017 para edad (p = 0,016) y de 3,13 para presencia de metástasis (p = 0,0000). En el análisis de subgrupos, los pacientes sin metástasis al diagnóstico presentaron sobrevida a 5 años de 54% versus 11% para el grupo con metástasis; al ajustar por edad, la sobrevida a 5 años para el grupo sin metástasis y con metástasis fue de 73% y 22% respectivamente. CONCLUSIÓN: Este es el primer estudio de descripción demográfica de pacientes con OS que se realiza en nuestro país. Los resultados son similares a lo reportado por la literatura internacional, destacando en nuestra serie la edad de presentación y presencia de metástasis al ingreso como factores que afectan el pronóstico de una manera significativa. Al ajustar por edad, los porcentajes de sobrevida son equiparables con lo reportado en otros centros internacionales especializados en sarcomas.
BACKGROUND: Osteosarcoma (OS) is the most frequent malignant primary bone tumor. The explicit health guarantee (GES) plan in Chile, a law that guarantees diagnosis, treatment, and rehabilitation, incorporated OS in 2014. OBJETIVES: To describe the characteristics of the population over 15 years, with a histopathological diagnosis of OS, to define survival rate and complications, and to identify variables that affect these outcomes. METHODS: A retrospective study from 2014 to 2020, including all patients affiliated with the public health system diagnosed with OS, with histological confirmation. From clinical records, we extracted demographic data, anatomical OS location, histopathological findings, admission stage, presence of metastases, treatment, complications, and survival. We determined prognostic factors by multivariate analysis. Results: 133 patients, 58.8% men, the average age was 31 years, and the most frequent location was the distal femur (34.9%). 56.4% of the patients were admitted in Enneking stage IIB, and 36.4% presented metastasis at admission. 14.3% presented complications, the most frequent periprosthetic infection (6 cases). 16% of patients evolved with local recurrence. The multivariate model showed that age and metastases at admission constitute independent prognostic variables, with a hazard ratio of 1.017 for age (p = 0.016) and 3.13 for metastases (p = 0.0000). In the subgroup analysis, patients without metastases at diagnosis had a 5-year survival of 54% versus 11% for the group with metastases. Adjusting for age, the 5-year survival for the non-metastatic and metastatic groups was 73% and 22%, respectively. CONCLUSION: This is our country's first demographic description study of patients with OS. In our series, the age of presentation and the presence of metastases at admission were factors that significantly affect prognosis. When adjusting for age, the survival percentages are comparable to those reported in other international centers specialized in sarcomas.
Asunto(s)
Humanos , Masculino , Femenino , Niño , Adolescente , Adulto , Persona de Mediana Edad , Anciano , Adulto Joven , Neoplasias Óseas/mortalidad , Neoplasias Óseas/patología , Osteosarcoma/mortalidad , Osteosarcoma/patología , Pronóstico , Preescolar , Chile/epidemiología , Tasa de Supervivencia , Estudios Retrospectivos , Estadificación de NeoplasiasRESUMEN
BACKGROUND: Osteosarcoma (OS) is the most frequent malignant primary bone tumor. The explicit health guarantee (GES) plan in Chile, a law that guarantees diagnosis, treatment, and rehabilitation, incorporated OS in 2014. OBJECTIVES: To describe the characteristics of the population over 15 years, with a histopathological diagnosis of OS, to define survival rate and complications, and to identify variables that affect these outcomes. METHODS: A retrospective study from 2014 to 2020, including all patients affiliated with the public health system diagnosed with OS, with histological confirmation. From clinical records, we extracted demographic data, anatomical OS location, histopathological findings, admission stage, presence of metastases, treatment, complications, and survival. We determined prognostic factors by multivariate analysis. RESULTS: 133 patients, 58.8% men, the average age was 31 years, and the most frequent location was the distal femur (34.9%). 56.4% of the patients were admitted in Enneking stage IIB, and 36.4% presented metastasis at admission. 14.3% presented complications, the most frequent periprosthetic infection (6 cases). 16% of patients evolved with local recurrence. The multivariate model showed that age and metastases at admission constitute independent prognostic variables, with a hazard ratio of 1.017 for age (p = 0.016) and 3.13 for metastases (p = 0.0000). In the subgroup analysis, patients without metastases at diagnosis had a 5-year survival of 54% versus 11% for the group with metastases. Adjusting for age, the 5-year survival for the non-metastatic and metastatic groups was 73% and 22%, respectively. CONCLUSION: This is our country's first demographic description study of patients with OS. In our series, the age of presentation and the presence of metastases at admission were factors that significantly affect prognosis. When adjusting for age, the survival percentages are comparable to those reported in other international centers specialized in sarcomas.
Asunto(s)
Neoplasias Óseas , Osteosarcoma , Humanos , Masculino , Femenino , Estudios Retrospectivos , Adulto , Chile/epidemiología , Neoplasias Óseas/patología , Neoplasias Óseas/mortalidad , Persona de Mediana Edad , Adulto Joven , Adolescente , Osteosarcoma/patología , Osteosarcoma/mortalidad , Niño , Pronóstico , Anciano , Tasa de Supervivencia , Preescolar , Estadificación de NeoplasiasRESUMEN
OBJECTIVE: Emerging studies highlight the crucial effects of microRNAs on cancer initiation and malignant progression of various tumors. This study focused on the biological effect of miR-377-3p on CUL1 and epithelial-mesenchymal transition (EMT) and Wnt/ß-catenin pathways in osteosarcoma (OS). METHODS: We performed quantitative real-time polymerase chain reaction (qRT-PCR) to analyze miR-377-3p and CUL1 expression levels in OS tissues and MG-63 cells. Then, cell counting kit (CCK)-8 and Transwell assay were used to examine the functions of miR-377-3p in OS cell growth and metastasis abilities. Meanwhile, luciferase reporter assay was used to validate CUL1 as direct target of miR-377-3p. qRT-PCR and Western blot were then carried out to detect the impact of miR-377-3p on EMT and Wnt/ß-catenin pathways. Tumor xenograft models were established to further examine the effects of miR-377-3p on OS tumorigenesis in vivo. RESULTS: miR-377-3p downregulation was frequently identified in OS tissues and cells, which was associated with worse prognosis of OS patients. Functional experiments showed miR-377-3p restoration could dramatically repress OS cell growth and migration by regulation of EMT and Wnt/ß-catenin pathways. Moreover, luciferase reporter assay revealed that CUL1 acted as a functional target of miR-377-3p. Additionally, the elevated CUL1 expressions in OS tissues also indicated poor prognosis of OS patients. Furthermore, the OS tumor growth was also obviously inhibited by miR-377-3p overexpression in vivo. CONCLUSIONS: Collectively, all the above findings revealed that miR-377-3p exerted anti-OS functions via CUL1 and EMT and Wnt/ß-catenin pathways. These results may contribute to the development of clinical OS treatment.
Asunto(s)
Neoplasias Óseas/metabolismo , Proteínas Cullin/metabolismo , MicroARNs/metabolismo , Osteosarcoma/metabolismo , Vía de Señalización Wnt , Animales , Neoplasias Óseas/mortalidad , Neoplasias Óseas/patología , Línea Celular Tumoral , Progresión de la Enfermedad , Regulación hacia Abajo , Transición Epitelial-Mesenquimal , Genes Reporteros , Xenoinjertos , Humanos , Luciferasas/genética , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Trasplante de Neoplasias , Osteosarcoma/mortalidad , Osteosarcoma/patología , Osteosarcoma/secundario , Pronóstico , Reacción en Cadena de la Polimerasa de Transcriptasa InversaRESUMEN
Purpose: Osteosarcoma is the malignant bone tumor most common in children and adolescents. Many cytochrome P-450 (CYP) members detoxify anticancer drugs used in osteosarcoma treatment, and thus, the aim of the present study was to investigate CYP polymorphisms in osteosarcoma patients. Methods: The present study investigated DNA from peripheral blood from 70 osteosarcoma patients treated with high doses of cisplatin, doxorubicin, and methotrexate. CYP1A2*1F (163C>A; rs762551); CYP2C9*3 (1075A>C; rs1057910); and CYP3A5*3 (6986A>G; rs776746) polymorphisms were investigated through real-time PCR using TaqMan probes. Results: The CYP2C9*3 allele did not present any association with clinical events. The CYP1A2 CC/AC genotypes were associated with ototoxicity occurrence (p = 0.041, odds ratio [OR] = 8.4) and high grades of ototoxicity (p = 0.039, OR = 10.7), when compared with patients carrying the CYP1A2 AA genotype. The CYP1A2 CC genotype was associated with high grades of diarrhea (p = 0.043, OR = 4.6) and fever (p = 0.041, OR = 7.1) in comparison with the CYP1A2 AA/AC genotypes. The CYP3A5 CC genotype was associated with weight loss (p = 0.009, OR = 3.8) and high grades of hepatotoxicity (p = 0.010, OR = 4.3) when compared with the CYP3A5 TT/CT genotypes. The CYP3A5 CC/CT genotypes were associated with high grades of vomit (p = 0.013, OR = 10.8), pulmonary relapse absence (p = 0.029, OR = 9.5), and better overall and event-free survivals (p = 0.017, hazard ratio [HR] = 3.1; p = 0.044, HR = 2.5; respectively) when compared with the CYP3A5 AA genotype. Conclusion:CYP1A2*1A and CYP3A5*3 alleles were associated with toxicity events. CYP3A5*3 allele was associated with better survival. Thus, CYP genotypes might be promising markers to tailoring treatment in osteosarcoma patients.
Asunto(s)
Osteosarcoma/genética , Adolescente , Adulto , Niño , Femenino , Genotipo , Humanos , Masculino , Osteosarcoma/mortalidad , Análisis de Supervivencia , Adulto JovenRESUMEN
BACKGROUND: The aim of this study is to evaluate the relationship between the latency to diagnosis (LD) and the time to completion of chemotherapy (TCC) with clinical outcomes in children with osteosarcoma. METHODS: We performed a retrospective analysis of all patients who received treatment for osteosarcoma in two tertiary centers in Peru from 2008 to 2015. All causes of delayed LD or TCC were evaluated. Overall survival (OS) and event-free-survival (EFS) were estimated and compared according to LD, TCC, and established clinical prognostic factors. RESULTS: One hundred and thirteen patients were included in the study. The median LD was 13.5 weeks (interquartile range, 10-18.5 weeks). No association was observed among clinical stage, tumor size, and LD. Delayed LD was not associated with a worse clinical outcome. Multivariate analysis confirmed that OS and EFS were significantly worse in cases of a delayed TCC (≥4 weeks), with hazard ratios of 2.70 (1.11-6.76, P = 0.003) and 1.13 (1.00-1.26, P = 0.016), respectively. Most delays in TCC (85%) were due to extramedical reasons (e.g., lack of available hospital beds). CONCLUSION: The LD did not seem to influence the EFS and OS in pediatric patients with osteosarcoma. However, a delay in TCC from any cause is independently associated with poor outcome in pediatric patients with osteosarcoma. Based on these results, further efforts may be needed to avoid treatment delays in patients with osteosarcoma in middle-income countries.
Asunto(s)
Neoplasias Óseas , Osteosarcoma , Adolescente , Neoplasias Óseas/diagnóstico , Neoplasias Óseas/mortalidad , Neoplasias Óseas/terapia , Niño , Preescolar , Supervivencia sin Enfermedad , Femenino , Humanos , Masculino , Osteosarcoma/diagnóstico , Osteosarcoma/mortalidad , Osteosarcoma/terapia , Estudios Retrospectivos , Tasa de SupervivenciaRESUMEN
ABSTRACT BACKGROUND: Osteosarcoma is the most prevalent malignant bone tumor in children and adolescents. Lung metastases are associated with poor prognosis. OBJECTIVE: The aim here was to explore the prevalence of and risk and prognostic factors for lung metastases in high-grade osteosarcoma patients. DESIGN AND SETTING: Retrospective cohort study based on the Surveillance, Epidemiology and End Results (SEER) database in the United States. METHODS: Data on 1,408 high-grade osteosarcoma patients registered in the SEER database between 2010 and 2015 were extracted. From these, all patients with high-grade osteosarcoma and initial lung metastasis were selected for analysis on risk and prognostic factors for lung metastases. Overall survival was estimated. RESULTS: There were 238 patients (16.90%) with lung metastases at diagnosis. Axial location, tumor size > 10 cm (odds ratio, OR 3.19; 95% confidence interval, CI: 1.58-6.45), higher N stage (OR 4.84; 95% CI: 1.94-12.13) and presence of bone metastases (OR 8.73; 95% CI: 4.37-17.48) or brain metastases (OR 25.63; 95% CI: 1.55-422.86) were significantly associated with lung metastases. Younger age and surgical treatment (hazard ratio, HR 0.46; 95% CI: 0.30-0.71) favored survival. Median survival was prolonged through primary tumor surgery. CONCLUSIONS: The factors revealed here may guide lung metastasis screening and prophylactic treatment for osteosarcoma patients. A primary tumor in an axial location, greater primary tumor size, higher lymph node stage and presence of bone or brain metastases were significantly correlated with lung metastases. The elderly group (≥ 60 years) showed significant correlation with poor overall survival. For improved survival among high-grade osteosarcoma patients with lung metastases, aggressive surgery on the primary tumor site should be encouraged.
Asunto(s)
Humanos , Masculino , Femenino , Adulto , Persona de Mediana Edad , Adulto Joven , Osteosarcoma/patología , Neoplasias Pulmonares/secundario , Pronóstico , Osteosarcoma/cirugía , Osteosarcoma/diagnóstico , Osteosarcoma/mortalidad , Análisis de Supervivencia , China/epidemiología , Prevalencia , Factores de Riesgo , Estudios de Cohortes , Neoplasias Pulmonares/cirugía , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/mortalidadRESUMEN
OBJECTIVES: Osteosarcoma of the jaw (OSAJ) is fundamentally different in clinical practice from its peripheral counterparts. Studies are difficult to conduct due to low incidence rates. The primary aim of this study was to provide for the first time a comprehensive retrospective analysis of the treatment concepts and outcome data of OSAJ patients treated at the University Hospital Vienna and to compare these with two recently published studies on OSAJ. The clinical study was accompanied by a biomarker study investigating the prognostic relevance of melanoma-associated antigen-A (MAGE-A) in OSAJ specimens. METHOD: Eighteen patients were included, and their outcomes were compared to published data. Immunohistochemistry was performed with mouse monoclonal antibodies against MAGE-A. Survival rates were estimated by the Kaplan-Meyer method. The log-rank test was used to analyze potential prognostic parameters. Fisher's exact test was performed to define the significant differences between the survival rates of the current study and the DOESAK registry. RESULTS: Disease-specific survival was 93.8% after five and 56.3% after ten years. The development of metastases (p=0.033) or relapse (p=0.037) was associated with worsened outcomes in our group as well as in the comparative group. Despite the different treatment concepts of the study groups, survival rates were comparable. MAGE-A failed to show prognostic relevance for OSAJ patients. CONCLUSIONS: Uncertainties about the optimal treatment strategies of OSAJ patients will currently remain. Thus, prospective studies of OSAJ are needed but are only feasible in a multicenter study setting, conducted over a prolonged time period.
Asunto(s)
Neoplasias Óseas/terapia , Osteosarcoma/terapia , Adulto , Anciano , Anciano de 80 o más Años , Anticuerpos Monoclonales/análisis , Antígenos de Neoplasias/análisis , Austria/epidemiología , Biomarcadores/análisis , Neoplasias Óseas/mortalidad , Neoplasias Óseas/patología , Femenino , Humanos , Inmunohistoquímica , Masculino , Persona de Mediana Edad , Osteosarcoma/mortalidad , Osteosarcoma/patología , Pronóstico , Estudios Retrospectivos , Tasa de SupervivenciaRESUMEN
OBJECTIVES: Bone cancers occur frequently in children, adolescents, and young adults aging 15 to 29 years. Osteosarcoma and Ewing sarcoma are the most frequent subtypes in this population. The aim of this study was to describe incidence and mortality trends of bone cancers among Brazilian children, adolescents and young adults. METHODS: Incidence information was obtained from 23 population-based cancer registries. Mortality data were extracted from the Atlas of Cancer Mortality from 1979 to 2013. Specific and adjusted rates per million were analyzed according to gender, morphology and age at diagnosis. Median rates were used as a measure of central tendency. Joinpoint regression was applied to analyze trends. RESULTS: Median incidence rates were 5.74 and 11.25 cases per million in children and young adults respectively. Osteosarcoma in the 15-19 years aged group had the highest incidence rates. Stable incidence rates were observed among five registries in 0-14 year's age group. Four registries had a decreased incidence trend among adolescents and young adults. Median mortality rates were 1.22 and 5.07 deaths per million in children and young adults respectively. Increased mortality was observed on the North and Northeast regions. Decreased mortality trends were seen in the South (children) and Southeast (adolescents and young adults). CONCLUSION: Osteosarcoma and Ewing Sarcoma are the most incident bone cancers in all Brazilian regions. Bone cancers showed incidence and mortality patterns variation within the geographic regions and across age groups, although not significant. Despite limitations, it is crucial to monitor cancer epidemiology trends across geographic Brazilian regions.
Asunto(s)
Neoplasias Óseas/mortalidad , Osteosarcoma/mortalidad , Adolescente , Adulto , Distribución por Edad , Brasil/epidemiología , Niño , Femenino , Humanos , Incidencia , Lactante , Recién Nacido , Masculino , Adulto JovenRESUMEN
OBJECTIVE: to determine the expression of neurotrophins and their tyrosine-kinase receptors in patients with osteosarcoma (OS) and their correlation with clinical outcomes. METHODS: we applied immunohistochemistry to biopsy specimens of patients consecutively treated for primary OS at a single institution between 2002 and 2015, analyzing them for expression receptors of tyrosine kinase A and B (TrKA and TrKB), neural growth factor (NGF) and brain derived neurotrophic factor (BDNF). Independently, two pathologists classified the immunohistochemical markers as negative (negative or weak focal) or positive (moderate focal/diffuse or strong focal/diffuse). RESULTS: we analyzed data from 19 patients (10 females and 9 males), with median age of 12 years (5 to 17.3). Tumors' location were 83.3% in the lower limbs, and 63.2% of patients had metastases at diagnosis. Five-year overall survival was 55.3%. BDNF was positive in 16 patients (84%) and NGF in 14 (73%). TrKA and TrKB presented positive staining in four (21,1%) and eight (42,1%) patients, respectively. Survival analysis showed no significant difference between TrK receptors and neurotrophins. CONCLUSION: primary OS samples express neurotrophins and TrK receptors by immunohistochemistry. Future studies should explore their role in OS pathogenesis and determine their prognostic significance in larger cohorts.
OBJETIVO: determinar a expressão de neurotrofinas e seus receptores tirosina quinases em pacientes com osteossarcoma (OS) e sua correlação com desfechos clínicos. MÉTODOS: biópsias de tumores primários de pacientes com OS tratados em uma única instituição, consecutivamente, entre 2002 e 2015, foram analisados através de imuno-histoquímica para expressão de receptores de tirosina quinase A e B (TrKA e TrKB), fator de crescimento neural (NGF) e fator neurotrófico derivado do cérebro (BDNF). De forma independente, dois patologistas classificaram os marcadores de imuno-histoquímica como negativos (negativos e focais fracos) ou positivos (moderado focal/difuso ou forte focal/difuso). RESULTADOS: foram analisados dados de 19 pacientes (10 do sexo feminino e 9 do masculino) com mediana de idade de 12 anos (5 a 17,3 anos). Dos tumores, 83,3% estavam localizados em membros inferiores e 63,2% dos pacientes eram metastáticos ao diagnóstico. A sobrevida global em cinco anos foi de 55,3%. BDNF foi positivo em 16 pacientes (84%) e NGF em 14 pacientes (73%). TrKA e TrKB apresentaram coloração positiva em quatro (21,1%) e oito (42,1%) pacientes, respectivamente. A análise de sobrevida não demonstrou diferença significativa entre receptores TrK e neurotrofinas. CONCLUSÃO: amostras de OS primário expressam neurotrofinas e receptores TrK através de imuno-histoquímica. Estudos futuros podem auxiliar na identificação do papel das mesmas na patogênese do OS e determinar se há possível correlação prognóstica.
Asunto(s)
Neoplasias Óseas/patología , Factor Neurotrófico Derivado del Encéfalo/análisis , Factores de Crecimiento Nervioso/análisis , Osteosarcoma/patología , Receptor trkA/análisis , Receptor trkB/análisis , Adolescente , Biomarcadores de Tumor , Neoplasias Óseas/mortalidad , Niño , Preescolar , Femenino , Humanos , Inmunohistoquímica , Estimación de Kaplan-Meier , Masculino , Osteosarcoma/mortalidad , Valores de Referencia , Factores de Riesgo , Estadísticas no ParamétricasRESUMEN
BACKGROUND: Osteosarcoma is the most prevalent malignant bone tumor in children and adolescents. Lung metastases are associated with poor prognosis. OBJECTIVE: The aim here was to explore the prevalence of and risk and prognostic factors for lung metastases in high-grade osteosarcoma patients. DESIGN AND SETTING: Retrospective cohort study based on the Surveillance, Epidemiology and End Results (SEER) database in the United States. METHODS: Data on 1,408 high-grade osteosarcoma patients registered in the SEER database between 2010 and 2015 were extracted. From these, all patients with high-grade osteosarcoma and initial lung metastasis were selected for analysis on risk and prognostic factors for lung metastases. Overall survival was estimated. RESULTS: There were 238 patients (16.90%) with lung metastases at diagnosis. Axial location, tumor size > 10 cm (odds ratio, OR 3.19; 95% confidence interval, CI: 1.58-6.45), higher N stage (OR 4.84; 95% CI: 1.94-12.13) and presence of bone metastases (OR 8.73; 95% CI: 4.37-17.48) or brain metastases (OR 25.63; 95% CI: 1.55-422.86) were significantly associated with lung metastases. Younger age and surgical treatment (hazard ratio, HR 0.46; 95% CI: 0.30-0.71) favored survival. Median survival was prolonged through primary tumor surgery. CONCLUSIONS: The factors revealed here may guide lung metastasis screening and prophylactic treatment for osteosarcoma patients. A primary tumor in an axial location, greater primary tumor size, higher lymph node stage and presence of bone or brain metastases were significantly correlated with lung metastases. The elderly group (≥ 60 years) showed significant correlation with poor overall survival. For improved survival among high-grade osteosarcoma patients with lung metastases, aggressive surgery on the primary tumor site should be encouraged.
Asunto(s)
Neoplasias Pulmonares/secundario , Osteosarcoma/patología , Adulto , China/epidemiología , Estudios de Cohortes , Femenino , Humanos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/mortalidad , Neoplasias Pulmonares/cirugía , Masculino , Persona de Mediana Edad , Osteosarcoma/diagnóstico , Osteosarcoma/mortalidad , Osteosarcoma/cirugía , Prevalencia , Pronóstico , Factores de Riesgo , Análisis de Supervivencia , Adulto JovenRESUMEN
RESUMO Objetivo: determinar a expressão de neurotrofinas e seus receptores tirosina quinases em pacientes com osteossarcoma (OS) e sua correlação com desfechos clínicos. Métodos: biópsias de tumores primários de pacientes com OS tratados em uma única instituição, consecutivamente, entre 2002 e 2015, foram analisados através de imuno-histoquímica para expressão de receptores de tirosina quinase A e B (TrKA e TrKB), fator de crescimento neural (NGF) e fator neurotrófico derivado do cérebro (BDNF). De forma independente, dois patologistas classificaram os marcadores de imuno-histoquímica como negativos (negativos e focais fracos) ou positivos (moderado focal/difuso ou forte focal/difuso). Resultados: foram analisados dados de 19 pacientes (10 do sexo feminino e 9 do masculino) com mediana de idade de 12 anos (5 a 17,3 anos). Dos tumores, 83,3% estavam localizados em membros inferiores e 63,2% dos pacientes eram metastáticos ao diagnóstico. A sobrevida global em cinco anos foi de 55,3%. BDNF foi positivo em 16 pacientes (84%) e NGF em 14 pacientes (73%). TrKA e TrKB apresentaram coloração positiva em quatro (21,1%) e oito (42,1%) pacientes, respectivamente. A análise de sobrevida não demonstrou diferença significativa entre receptores TrK e neurotrofinas. Conclusão: amostras de OS primário expressam neurotrofinas e receptores TrK através de imuno-histoquímica. Estudos futuros podem auxiliar na identificação do papel das mesmas na patogênese do OS e determinar se há possível correlação prognóstica.
ABSTRACT Objective: to determine the expression of neurotrophins and their tyrosine-kinase receptors in patients with osteosarcoma (OS) and their correlation with clinical outcomes. Methods: we applied immunohistochemistry to biopsy specimens of patients consecutively treated for primary OS at a single institution between 2002 and 2015, analyzing them for expression receptors of tyrosine kinase A and B (TrKA and TrKB), neural growth factor (NGF) and brain derived neurotrophic factor (BDNF). Independently, two pathologists classified the immunohistochemical markers as negative (negative or weak focal) or positive (moderate focal/diffuse or strong focal/diffuse). Results: we analyzed data from 19 patients (10 females and 9 males), with median age of 12 years (5 to 17.3). Tumors' location were 83.3% in the lower limbs, and 63.2% of patients had metastases at diagnosis. Five-year overall survival was 55.3%. BDNF was positive in 16 patients (84%) and NGF in 14 (73%). TrKA and TrKB presented positive staining in four (21,1%) and eight (42,1%) patients, respectively. Survival analysis showed no significant difference between TrK receptors and neurotrophins. Conclusion: primary OS samples express neurotrophins and TrK receptors by immunohistochemistry. Future studies should explore their role in OS pathogenesis and determine their prognostic significance in larger cohorts.
Asunto(s)
Humanos , Masculino , Femenino , Preescolar , Niño , Adolescente , Neoplasias Óseas/patología , Osteosarcoma/patología , Factor Neurotrófico Derivado del Encéfalo/análisis , Receptor trkA/análisis , Receptor trkB/análisis , Factores de Crecimiento Nervioso/análisis , Valores de Referencia , Neoplasias Óseas/mortalidad , Inmunohistoquímica , Biomarcadores de Tumor , Osteosarcoma/mortalidad , Factores de Riesgo , Estadísticas no Paramétricas , Estimación de Kaplan-MeierRESUMEN
OBJECTIVES: Osteosarcoma of the jaw (OSAJ) is fundamentally different in clinical practice from its peripheral counterparts. Studies are difficult to conduct due to low incidence rates. The primary aim of this study was to provide for the first time a comprehensive retrospective analysis of the treatment concepts and outcome data of OSAJ patients treated at the University Hospital Vienna and to compare these with two recently published studies on OSAJ. The clinical study was accompanied by a biomarker study investigating the prognostic relevance of melanoma-associated antigen-A (MAGE-A) in OSAJ specimens. METHOD: Eighteen patients were included, and their outcomes were compared to published data. Immunohistochemistry was performed with mouse monoclonal antibodies against MAGE-A. Survival rates were estimated by the Kaplan-Meyer method. The log-rank test was used to analyze potential prognostic parameters. Fisher's exact test was performed to define the significant differences between the survival rates of the current study and the DOESAK registry. RESULTS: Disease-specific survival was 93.8% after five and 56.3% after ten years. The development of metastases (p=0.033) or relapse (p=0.037) was associated with worsened outcomes in our group as well as in the comparative group. Despite the different treatment concepts of the study groups, survival rates were comparable. MAGE-A failed to show prognostic relevance for OSAJ patients. CONCLUSIONS: Uncertainties about the optimal treatment strategies of OSAJ patients will currently remain. Thus, prospective studies of OSAJ are needed but are only feasible in a multicenter study setting, conducted over a prolonged time period.
Asunto(s)
Humanos , Masculino , Femenino , Adulto , Persona de Mediana Edad , Anciano , Anciano de 80 o más Años , Neoplasias Óseas/terapia , Osteosarcoma/terapia , Pronóstico , Austria/epidemiología , Neoplasias Óseas/mortalidad , Neoplasias Óseas/patología , Inmunohistoquímica , Biomarcadores/análisis , Osteosarcoma/mortalidad , Osteosarcoma/patología , Tasa de Supervivencia , Estudios Retrospectivos , Anticuerpos Monoclonales/análisis , Antígenos de Neoplasias/análisisRESUMEN
OBJECTIVES: Bone cancers occur frequently in children, adolescents, and young adults aging 15 to 29 years. Osteosarcoma and Ewing sarcoma are the most frequent subtypes in this population. The aim of this study was to describe incidence and mortality trends of bone cancers among Brazilian children, adolescents and young adults. METHODS: Incidence information was obtained from 23 population-based cancer registries. Mortality data were extracted from the Atlas of Cancer Mortality from 1979 to 2013. Specific and adjusted rates per million were analyzed according to gender, morphology and age at diagnosis. Median rates were used as a measure of central tendency. Joinpoint regression was applied to analyze trends. RESULTS: Median incidence rates were 5.74 and 11.25 cases per million in children and young adults respectively. Osteosarcoma in the 15-19 years aged group had the highest incidence rates. Stable incidence rates were observed among five registries in 0-14 year's age group. Four registries had a decreased incidence trend among adolescents and young adults. Median mortality rates were 1.22 and 5.07 deaths per million in children and young adults respectively. Increased mortality was observed on the North and Northeast regions. Decreased mortality trends were seen in the South (children) and Southeast (adolescents and young adults). CONCLUSION: Osteosarcoma and Ewing Sarcoma are the most incident bone cancers in all Brazilian regions. Bone cancers showed incidence and mortality patterns variation within the geographic regions and across age groups, although not significant. Despite limitations, it is crucial to monitor cancer epidemiology trends across geographic Brazilian regions.
Asunto(s)
Humanos , Masculino , Femenino , Recién Nacido , Lactante , Niño , Adolescente , Adulto , Adulto Joven , Neoplasias Óseas/mortalidad , Osteosarcoma/mortalidad , Brasil/epidemiología , Incidencia , Distribución por EdadRESUMEN
PURPOSE: Health-related quality of life (HRQOL) improves throughout treatment of patients with nonmetastatic osteosarcoma. We compared HRQOL for patients in the United States and Chile treated on an international trial (OS99) with polychemotherapy and surgery, and we assessed the relationships among HRQOL measures, event-free survival (EFS), and overall survival (OS). MATERIALS AND METHODS: Patients with newly diagnosed, localized osteosarcoma and their parents completed three HRQOL instruments (PedsQL v.4, PedsQL Cancer v.3, and Symptom Distress Scale [SDS]). Data were collected at four time points throughout therapy. Repeated measures models were used to investigate the effect of treatment site on instrument scores. The log-rank test examined the impact of treatment site on survival outcomes, and Cox proportional hazards regression models evaluated baseline HRQOL measures as predictors of EFS and OS. RESULTS: Of 71 eligible patients, 66 (93%) participated in the HRQOL studies in the United States (n = 44) and Chile (n = 22). The median age was 13.4 years (range, 5 to 23 years). Clinical characteristics were similar between treatment sites. US patients reported better scores for physical ( P = .030), emotional ( P = .027), and school functioning ( P < .001). Chilean patients reported poorer scores for worry ( P < .001) and nausea ( P = .007). Patient and parent nausea scores were similar between patients treated in the United States and Chile by the end of therapy. Differences in symptom distress were not observed between the countries. Neither HRQOL measures nor treatment site were associated with EFS or OS. CONCLUSION: Although significant differences in HRQOL were observed between countries, outcomes were similar, and HRQOL measures were not associated with prognosis.
Asunto(s)
Neoplasias Óseas , Osteosarcoma , Adolescente , Adulto , Neoplasias Óseas/mortalidad , Neoplasias Óseas/psicología , Neoplasias Óseas/terapia , Niño , Preescolar , Chile , Femenino , Recursos en Salud , Humanos , Masculino , Osteosarcoma/mortalidad , Osteosarcoma/psicología , Osteosarcoma/terapia , Calidad de Vida , Resultado del Tratamiento , Estados Unidos , Adulto JovenRESUMEN
Survival rates for osteosarcoma, the most common primary bone cancer, have changed little over the past three decades and are particularly low for patients with metastatic disease. We conducted a multi-institutional genome-wide association study (GWAS) to identify germline genetic variants associated with overall survival in 632 patients with osteosarcoma, including 523 patients of European ancestry and 109 from Brazil. We conducted a time-to-event analysis and estimated hazard ratios (HR) and 95% confidence intervals (CI) using Cox proportional hazards models, with and without adjustment for metastatic disease. The results were combined across the European and Brazilian case sets using a random-effects meta-analysis. The strongest association after meta-analysis was for rs3765555 at 9p24.1, which was inversely associated with overall survival (HR = 1.76; 95% CI 1.41-2.18, p = 4.84 × 10-7 ). After imputation across this region, the combined analysis identified two SNPs that reached genome-wide significance. The strongest single association was with rs55933544 (HR = 1.9; 95% CI 1.5-2.4; p = 1.3 × 10-8 ), which localizes to the GLDC gene, adjacent to the IL33 gene and was consistent across both the European and Brazilian case sets. Using publicly available data, the risk allele was associated with lower expression of IL33 and low expression of IL33 was associated with poor survival in an independent set of patients with osteosarcoma. In conclusion, we have identified the GLDC/IL33 locus on chromosome 9p24.1 as associated with overall survival in patients with osteosarcoma. Further studies are needed to confirm this association and shed light on the biological underpinnings of this susceptibility locus.
Asunto(s)
Neoplasias Óseas/genética , Neoplasias Óseas/mortalidad , Interleucina-33/genética , Osteosarcoma/genética , Osteosarcoma/mortalidad , Adulto , Alelos , Brasil , Femenino , Predisposición Genética a la Enfermedad/genética , Estudio de Asociación del Genoma Completo/métodos , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Polimorfismo de Nucleótido Simple/genética , Modelos de Riesgos Proporcionales , Tasa de Supervivencia , Población Blanca/genéticaRESUMEN
BACKGROUND: Pretreatment neutrophil-to-lymphocyte ratio (NLR) and absolute lymphocyte count (ALC) recovery have been shown to be associated with prognosis in several types of cancer in adults. However, evidence in pediatric cancer is scarce. The aim of our study was to evaluate whether pretreatment NLR and lymphocyte recovery are prognostic factors in pediatric sarcomas. MATERIALS AND METHODS: Study participants were identified from a retrospective cohort of 100 children with osteosarcoma (n=55), rhabdomyosarcoma (n=22), and Ewing sarcoma (n=23). Data for the hematological variables were obtained from medical records and analyzed with other known prognostic factors in univariate and multivariate analyses. RESULTS: In multivariate analysis, NLR>2 was an independent prognostic factor for OS in patients with osteosarcoma (hazard ratio [HR], 2.27, 95% confidence interval [CI], 1.07-5.30; P=0.046) along with metastatic disease and poor histologic response; as well as in patients with rhabdomyosarcoma (HR, 4.76, 95% CI, 1.01-22.24; P=0.0237) along with metastatic disease and risk group. ALC recovery correlated for inferior OS in osteosarcoma (HR, 3.34, 95% CI, 1.37-8.12; P=0.008) and rhabdomyosarcoma (HR, 3.89; 95% CI, 1.01-14.89; P=0.0338). CONCLUSIONS: Our study confirms that NLR and ALC recovery are independent prognostic factors for pediatric sarcomas, implying an important role of immune system in survival. Clinical utility of these prognostic biomarkers should be validated in larger pediatric studies.
Asunto(s)
Linfocitos/patología , Neutrófilos/patología , Pronóstico , Sarcoma/diagnóstico , Biomarcadores , Niño , Estudios de Cohortes , Femenino , Humanos , Recuento de Leucocitos , Masculino , Metástasis de la Neoplasia , Osteosarcoma/tratamiento farmacológico , Osteosarcoma/mortalidad , Estudios Retrospectivos , Rabdomiosarcoma/tratamiento farmacológico , Rabdomiosarcoma/mortalidad , Sarcoma/sangre , Sarcoma/mortalidad , Sarcoma/patología , Sarcoma de Ewing/tratamiento farmacológico , Sarcoma de Ewing/mortalidad , Tasa de SupervivenciaRESUMEN
BACKGROUND: Differences in incidence and survival in osteosarcoma reports are considerable worldwide. PURPOSE: This study describes the incidence and survival of patients with osteosarcoma in Argentina with data from the National Pediatric Cancer Registry (ROHA), and the impact of age, gender, stage, regional, and socioeconomic indicators on outcome. METHODS: Pediatric patients with osteosarcoma reported to ROHA from 2000 through 2013 were analyzed, the annual age-standardized incidence rate (ASR) was calculated using the National Vital Statistics, and survival was estimated. The extended human development index (EHDI) for each reporting region was used as an indicator of socioeconomic status. RESULTS: There were 515 cases of osteosarcoma identified, yielding an ASR of 3.2/1,000,000 children (0-14 years old). The ASR did not vary significantly by year of diagnosis but ranged from 4.0/1,000,000 in the Cuyo/Western Central region to 2.7/1,000,000 in the northeast region (P < 0.000). The estimated 5-year survival rate was 45% (95% confidence interval [CI] 44-51%), with no difference by sex, diagnosis year, region, or EHDI score (P > 0.1 in all cases). Survival rate for localized disease was 52% (95% CI 45-57%) and for metastatic 22% (95% CI 15-30%). CONCLUSIONS: In Argentina, ASR of osteosarcoma is similar to that in high-income countries, but survival is lower in all regions. Future work will focus on identification and reduction of causes of preventable treatment failure.