Osteosarcoma como patología GES. Experiencia de 7 años en Centro de Referencia Nacional / Osteosarcoma as a GES-Listed Pathology: 7-Year Experience at a National Reference Center

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.

Lung metastases at the initial diagnosis of high-grade osteosarcoma: prevalence, risk factors and prognostic factors. A large population-based cohort study

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.

Expressão de neurotrofinas e de seus receptores no osteossarcoma primário / Expression of neurotrophins and their receptors in primary osteosarcoma

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.

Osteosarcoma of the jaw - experience at the Medical University Vienna and comparative study with international tumor registries

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.

Incidence and mortality of bone cancer among children, adolescents and young adults of Brazil

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.

Osteosarcoma parostal de bajo grado: Evolución oncológica y clínica / Low grade parosteal osteosaroma. Clinical and oncological outcomes]

El objetivo de este estudio fue analizar una serie de pacientes con osteosarcoma parostal de bajo grado y los resultados de su tratamiento quirúrgico y reconstrucción con un trasplante óseo. Se realizó una búsqueda retrospectiva en nuestra base de datos oncológica entre 1980 y 2010 de todos los pacientes con diagnóstico de osteosarcoma parostal. Se incluyeron para el análisis únicamente los osteosarcomas parostales de bajo grado, tratados quirúrgicamente con cirugía de conservación de miembro y reconstruidos con trasplante óseo cadavérico fresco congelado. Se incluyeron 22 pacientes en el estudio. La edad media de la serie fue de 32 ± 11 años (10-59) y el seguimiento medio de 93 ± 69 meses (8-237). La supervivencia global de los pacientes analizados fue de 91% (IC95%: 79-100) a 10 años. Cuatro pacientes (18%) presentaron una recidiva local de la enfermedad, dos de éstas fueron clasificadas histológicamente como osteosarcoma parostal desdiferenciado. Dos pacientes desarrollaron enfermedad a distancia, siendo el pulmón el único sitio de localización. La tasa de supervivencia de las reconstrucciones de la cirugía de conservación de miembro a 10 años fue de 65% (IC95%: 44-86). La supervivencia a largo plazo de los pacientes con osteosarcoma parostal de bajo grado es superior al 90%. La resección quirúrgica con márgenes amplios debe ser el tratamiento de elección y la reconstrucción biológica es una alternativa válida.

The objective of the study was to analyze a group of patients with low grade parosteal osteosarcoma treated with limb salvage surgery and reconstructed with bone allograft. A retrospective review from our oncologic data base between 1980 and 2010 was done and all patients with diagnosis of low grade parosteal osteosarcoma, treated with limb salvage surgery and reconstructed with allograft were included. Twenty-two patients were included for the analysis. The mean age was 32 ± 11 years (10-59) y the mean follow-up 93 ± 69 months (8-237). Ten year overall survival of the series was 91% (95%CI: 79-100). Four patients developed local recurrence, 2 of them histological classified after the resection dedifferentiated parosteal osteosarcoma. Two patients developed distant recurrence, being the lung the only site of metastasis. Ten year limb salvage reconstruction survival was 65% (95%CI: 44-86). Long term survival rate in low grade parosteal osteosarcoma is over 90%. Surgical resection wide margin should be the elective treatment and biological limb salvage reconstruction is a good alternative.

Osteosarcoma of the Clavicle in an Adolescent Child.

Clavicle is an unusual site for any primary bone tumour, including osteogenic sarcoma. Although a rare site of affection, most clavicular tumours tend to be malignant. We present a case report of osteosarcoma of the clavicle in a twelve-year-old male child who presented with a huge swelling of the left clavicle for the last six months.

Osteosarcoma: a study of 130 cases.

Multidisciplinary treatment of osteosarcoma in the Faculty of Medicine Ramathibodi Hospital, Mahidol University, using preoperative intraarterial and postoperative chemotherapy, with or without local irradiation, combined with surgery and prophylactic lung irradiation provided an excellent 5 years' survival of 55 per cent, the same rate as the 9 years' survival. The survival was stable after 4.4 years. The patients with local irradiation had more tumor destruction apparent on the surgical specimen. The administration of prophylactic whole lung irradiation provided an outcome without any undesirable complication. Sixteen per cent of the cases with PLI developed lung metastasis compared to 48 per cent without PLI. The most important prognostic factor was low level of serum lactic acid dehydrogenase. The unanswered question is what is the optimal treatment for osteosarcoma?

Multidisciplinary "limb salvage" treatment of osteosarcoma.

Intraarterial plus systemic chemotherapy of cis-diamine dichloroplatinum-II and anthracycline together with preoperative radiation and "limb salvage" treatment have increased the chance of local control and facilitated the previous surgically nonresectable to be resectable. Among 30 cases of osteosarcoma from 1986-1989, aged 9-43 years old, 10 of the 17 cases (58.8%) are still alive with the mean disease free survival of 27.8 months. Late pulmonary metastases cause the need for future protocol for prophylactic lung therapy.