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Many study designs are used to provide the answers needed to further the care of orthopedic oncology patients. Underlying these differing study designs, are different data sets. The data sets vary in their size and scope, from single center to population-based, and from provincial to international. They vary in their follow-up time, from years to decades. They vary in the variables included, the fidelity and precision of each variable, and the granularity of detail. This thesis explores the use of population-based studies as a source of data on orthopedic oncology patients, and provides two studies as an example. We make use of the large administrative data collected from every soft tissue sarcoma (STS) patient in Ontario over 23 years by the Institute of Clinical Evaluative Sciences (ICES) to answer two questions only possible with population-based studies. Using this large cohort (n=8,896) we provide for the first-time answers to 1) Given the multidisciplinary treatment of sarcoma patients, how are Ontario sarcoma patients being treated in our universal healthcare system, and, have treatment strategies changed over the past 10 years? 2) What are the long-term survival outcomes of Ontario sarcoma patients? Do these outcomes differ for rural or low-income patients? These studies have engendered international collaborations which are also described. Overall, this thesis explores research questions that are possible to address with population-based data. Through two studies, we aim to provide accurate and clinically useful information that can hopefully be used to better the outcomes of sarcoma patients, both in Ontario and internationally. / Thesis / Master of Science (MSc)

O sarcoma de Ewing é uma neoplasia maligna agressiva que acomete ossos e tecidos moles com maior frequência em crianças e adolescentes. O tratamento consta de quimioterapia de indução, seguida pelo controle local da doença (cirurgia, cirurgia associada à radioterapia, ou apenas radioterapia), e quimioterapia de consolidação. A introdução da quimioterapia possibilitou aumento significativo na sobrevida dos pacientes nas últimas décadas. Por outro lado, o impacto da modalidade de controle local ainda não está bem estabelecido. Estudos observacionais têm demonstrado superioridade do tratamento cirúrgico em relação à radioterapia isolada, no entanto, são limitados os estudos prospectivos que confirmam esta diferença. O objetivo deste estudo é avaliar o impacto da modalidade de tratamento local nos desfechos oncológicos, bem como descrever o perfil clínico-epidemiológico de portadores de sarcoma de Ewing ósseo não-metastático. Os dados foram coletados em 15 instituições no período entre 2003 e 2010 e fazem parte do primeiro estudo do Grupo Colaborativo Brasileiro para Tratamento dos Tumores da Família Ewing (EWING I). Dos 73 pacientes incluídos, 47 foram tratados com cirurgia isolada, 13 receberam cirurgia associada à radioterapia, e 13 apenas radioterapia. O seguimento médio foi de 4,5 anos (2,3 até 6,7 anos) e a sobrevida geral e livre de eventos foi de 63,3 e 62,1 por cento em 5 anos, respectivamente. A falha do tratamento local foi de 0 (zero) por cento para a modalidade de cirurgia associada à radioterapia, 6,5 por cento para cirurgia isolada, e 10 por cento para radioterapia (p=0,5). A sobrevida dos pacientes submetidos à radioterapia isolada foi significativamente inferior à sobrevida dos tratados com cirurgia e com cirurgia associada a radioterapia (30,8 versus 71,7 versus 64,1 por cento, respectivamente). Concluiu-se que não houve diferença em termos de falha local de acordo com a modalidade de tratamento empregada, no entanto houve diferença significativa em termos de sobrevida. Apesar dos resultados cirúrgicos superiores, a radioterapia isolada ainda apresenta papel fundamental no tratamento de casos selecionados. / Ewing sarcoma is a small round cell malignancy of bone and soft tissue that usually occurs in children and adolescents. Current treatment includes induction chemotherapy, local control of the primary tumor (surgery, surgery plus radiotherapy, or radiotherapy) and consolidation chemotherapy. The introduction of chemotherapy has improved significantly the oncologic outcomes in Ewing sarcoma. On the other hand, the impact of the local control modality has not been established. Surgery alone or in combination with radiation has traditionally been considered a good choice for resectable ES, while unresectable tumors have been treated with definitive radiotherapy. Despite the results from a few trials and observational studies, there is no consistent knowledge about the local control modality in ES outcomes. The present study aims to evaluate the impact of the local control modality in the oncologic outcomes, as well as to describe the clinical features of the patients with localized Ewing sarcoma of the bone. The data were collected between 2003 and 2010 in 15 hospitals and were part of the first Brazilian Collaborative Group for the Treatment of the Ewing Sarcoma Family Tumors (EWING 1). From 73 patients (median age 12.8 years old), 47 were treated with surgery, 13 with surgery plus radiotherapy, and 13 with definitive radiotherapy. Median follow up was 4.5 years (2.3 to 6.7 years) and the overall and event-free survival 63.3 and 62.1 percent in 5 years, respectively. The local control failure was 0 percent for surgery plus radiotherapy, 6.5 percent for surgery, and 10 percent for radiotherapy (p=.5). The survival of the patients treated with radiotherapy was significantly worse than those treated with surgery and surgery plus radiotherapy (30.8 versus 71.7 versus 64.1 percent, respectively). In conclusion, there was no significant difference in local failure according to the modality of treatment, but there was significant difference in survival rates. Despite the better outcomes in individuals treated with surgery, the radiotherapy modality has still an important role in selected patients.

O sarcoma de Ewing é uma neoplasia maligna agressiva que acomete ossos e tecidos moles com maior frequência em crianças e adolescentes. O tratamento consta de quimioterapia de indução, seguida pelo controle local da doença (cirurgia, cirurgia associada à radioterapia, ou apenas radioterapia), e quimioterapia de consolidação. A introdução da quimioterapia possibilitou aumento significativo na sobrevida dos pacientes nas últimas décadas. Por outro lado, o impacto da modalidade de controle local ainda não está bem estabelecido. Estudos observacionais têm demonstrado superioridade do tratamento cirúrgico em relação à radioterapia isolada, no entanto, são limitados os estudos prospectivos que confirmam esta diferença. O objetivo deste estudo é avaliar o impacto da modalidade de tratamento local nos desfechos oncológicos, bem como descrever o perfil clínico-epidemiológico de portadores de sarcoma de Ewing ósseo não-metastático. Os dados foram coletados em 15 instituições no período entre 2003 e 2010 e fazem parte do primeiro estudo do Grupo Colaborativo Brasileiro para Tratamento dos Tumores da Família Ewing (EWING I). Dos 73 pacientes incluídos, 47 foram tratados com cirurgia isolada, 13 receberam cirurgia associada à radioterapia, e 13 apenas radioterapia. O seguimento médio foi de 4,5 anos (2,3 até 6,7 anos) e a sobrevida geral e livre de eventos foi de 63,3 e 62,1 por cento em 5 anos, respectivamente. A falha do tratamento local foi de 0 (zero) por cento para a modalidade de cirurgia associada à radioterapia, 6,5 por cento para cirurgia isolada, e 10 por cento para radioterapia (p=0,5). A sobrevida dos pacientes submetidos à radioterapia isolada foi significativamente inferior à sobrevida dos tratados com cirurgia e com cirurgia associada a radioterapia (30,8 versus 71,7 versus 64,1 por cento, respectivamente). Concluiu-se que não houve diferença em termos de falha local de acordo com a modalidade de tratamento empregada, no entanto houve diferença significativa em termos de sobrevida. Apesar dos resultados cirúrgicos superiores, a radioterapia isolada ainda apresenta papel fundamental no tratamento de casos selecionados. / Ewing sarcoma is a small round cell malignancy of bone and soft tissue that usually occurs in children and adolescents. Current treatment includes induction chemotherapy, local control of the primary tumor (surgery, surgery plus radiotherapy, or radiotherapy) and consolidation chemotherapy. The introduction of chemotherapy has improved significantly the oncologic outcomes in Ewing sarcoma. On the other hand, the impact of the local control modality has not been established. Surgery alone or in combination with radiation has traditionally been considered a good choice for resectable ES, while unresectable tumors have been treated with definitive radiotherapy. Despite the results from a few trials and observational studies, there is no consistent knowledge about the local control modality in ES outcomes. The present study aims to evaluate the impact of the local control modality in the oncologic outcomes, as well as to describe the clinical features of the patients with localized Ewing sarcoma of the bone. The data were collected between 2003 and 2010 in 15 hospitals and were part of the first Brazilian Collaborative Group for the Treatment of the Ewing Sarcoma Family Tumors (EWING 1). From 73 patients (median age 12.8 years old), 47 were treated with surgery, 13 with surgery plus radiotherapy, and 13 with definitive radiotherapy. Median follow up was 4.5 years (2.3 to 6.7 years) and the overall and event-free survival 63.3 and 62.1 percent in 5 years, respectively. The local control failure was 0 percent for surgery plus radiotherapy, 6.5 percent for surgery, and 10 percent for radiotherapy (p=.5). The survival of the patients treated with radiotherapy was significantly worse than those treated with surgery and surgery plus radiotherapy (30.8 versus 71.7 versus 64.1 percent, respectively). In conclusion, there was no significant difference in local failure according to the modality of treatment, but there was significant difference in survival rates. Despite the better outcomes in individuals treated with surgery, the radiotherapy modality has still an important role in selected patients.

O sarcoma de Ewing é uma neoplasia maligna agressiva que acomete ossos e tecidos moles com maior frequência em crianças e adolescentes. O tratamento consta de quimioterapia de indução, seguida pelo controle local da doença (cirurgia, cirurgia associada à radioterapia, ou apenas radioterapia), e quimioterapia de consolidação. A introdução da quimioterapia possibilitou aumento significativo na sobrevida dos pacientes nas últimas décadas. Por outro lado, o impacto da modalidade de controle local ainda não está bem estabelecido. Estudos observacionais têm demonstrado superioridade do tratamento cirúrgico em relação à radioterapia isolada, no entanto, são limitados os estudos prospectivos que confirmam esta diferença. O objetivo deste estudo é avaliar o impacto da modalidade de tratamento local nos desfechos oncológicos, bem como descrever o perfil clínico-epidemiológico de portadores de sarcoma de Ewing ósseo não-metastático. Os dados foram coletados em 15 instituições no período entre 2003 e 2010 e fazem parte do primeiro estudo do Grupo Colaborativo Brasileiro para Tratamento dos Tumores da Família Ewing (EWING I). Dos 73 pacientes incluídos, 47 foram tratados com cirurgia isolada, 13 receberam cirurgia associada à radioterapia, e 13 apenas radioterapia. O seguimento médio foi de 4,5 anos (2,3 até 6,7 anos) e a sobrevida geral e livre de eventos foi de 63,3 e 62,1 por cento em 5 anos, respectivamente. A falha do tratamento local foi de 0 (zero) por cento para a modalidade de cirurgia associada à radioterapia, 6,5 por cento para cirurgia isolada, e 10 por cento para radioterapia (p=0,5). A sobrevida dos pacientes submetidos à radioterapia isolada foi significativamente inferior à sobrevida dos tratados com cirurgia e com cirurgia associada a radioterapia (30,8 versus 71,7 versus 64,1 por cento, respectivamente). Concluiu-se que não houve diferença em termos de falha local de acordo com a modalidade de tratamento empregada, no entanto houve diferença significativa em termos de sobrevida. Apesar dos resultados cirúrgicos superiores, a radioterapia isolada ainda apresenta papel fundamental no tratamento de casos selecionados. / Ewing sarcoma is a small round cell malignancy of bone and soft tissue that usually occurs in children and adolescents. Current treatment includes induction chemotherapy, local control of the primary tumor (surgery, surgery plus radiotherapy, or radiotherapy) and consolidation chemotherapy. The introduction of chemotherapy has improved significantly the oncologic outcomes in Ewing sarcoma. On the other hand, the impact of the local control modality has not been established. Surgery alone or in combination with radiation has traditionally been considered a good choice for resectable ES, while unresectable tumors have been treated with definitive radiotherapy. Despite the results from a few trials and observational studies, there is no consistent knowledge about the local control modality in ES outcomes. The present study aims to evaluate the impact of the local control modality in the oncologic outcomes, as well as to describe the clinical features of the patients with localized Ewing sarcoma of the bone. The data were collected between 2003 and 2010 in 15 hospitals and were part of the first Brazilian Collaborative Group for the Treatment of the Ewing Sarcoma Family Tumors (EWING 1). From 73 patients (median age 12.8 years old), 47 were treated with surgery, 13 with surgery plus radiotherapy, and 13 with definitive radiotherapy. Median follow up was 4.5 years (2.3 to 6.7 years) and the overall and event-free survival 63.3 and 62.1 percent in 5 years, respectively. The local control failure was 0 percent for surgery plus radiotherapy, 6.5 percent for surgery, and 10 percent for radiotherapy (p=.5). The survival of the patients treated with radiotherapy was significantly worse than those treated with surgery and surgery plus radiotherapy (30.8 versus 71.7 versus 64.1 percent, respectively). In conclusion, there was no significant difference in local failure according to the modality of treatment, but there was significant difference in survival rates. Despite the better outcomes in individuals treated with surgery, the radiotherapy modality has still an important role in selected patients.

Orientador: Maurício Etchebehere / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas / Made available in DSpace on 2018-08-19T18:46:22Z (GMT). No. of bitstreams: 1 Hanasilo_CarlosEduardoHideo_M.pdf: 2000713 bytes, checksum: 42f9c82aa1621b3b005c51b618a4f40c (MD5) Previous issue date: 2012 / Resumo: Proposta: Em razão de sarcoma de partes moles serem entidades raras e lesões benignas de partes moles serem comuns, a ocorrência de ressecções não planejadas (RNP) de sarcomas de partes moles é extremamente comum. O Objetivo deste estudo é avaliar o impacto desses procedimentos não planejados na sobrevida global, na recidiva local e no surgimento de metástases à distância em pacientes portadores de sarcomas de partes moles de extremidades. Métodos: Em um estudo retrospectivo de maio de 2001 a março de 2011 foram analisados os prontuários de 52 pacientes com diagnóstico de sarcoma de partes moles, sendo 29 (55,8%) desses sem tratamento prévio e os restantes 23 (44,2%) já submetidos à cirurgia prévia de ressecção da neoplasia sem planejamento oncológico. Todos foram submetidos à cirurgia definitiva neste centro de referência em câncer. O tempo de seguimento clínico variou de seis a 122 meses, com média de 39,9 meses. Foram comparados dados entre os grupos com relação à idade, tamanho da lesão, profundidade da lesão, grau histológico, margem cirúrgica, sobrevida global, recidiva local e à distância; foi avaliada a presença de lesão residual nos pacientes submetidos a cirurgias não planejadas. Resultados: Doença residual no espécime ressecado foi encontrada em 91,3% dos reoperados após RNP; O grupo RNP diferiu do grupo de cirurgias planejadas (RP) apresentando maior numero de lesões superficiais (p=0,013), de baixo grau histológico (p=0,033) e com margem comprometida com neoplasia na ampliação de margens (p=0,034); Não se observou diferença entre os grupos com relação à recidiva local (p=0,17) e sobrevida global em cinco anos (p=0,17), mas os pacientes submetidos à RP apresentaram um risco maior para o surgimento de metástase à distância (p=0,03), após ajustes das demais variáveis. Conclusões: A re-ressecção de sarcoma de partes moles previamente submetidos à ressecção não planejada é preconizada e leva a resultados semelhantes daqueles operados com planejamento com relação à recidiva local e sobrevida global de cinco anos. Entretanto, a sobrevida livre de metástase à distância foi pior no grupo RP, provavelmente devido ao viés causado pelo reduzido número de pacientes deste estudo / Abstract: Purpose: The unplanned excision of soft tissue sarcomas is extremely common because, although soft tissue sarcomas are rare entities, benign soft tissue lesions are very frequent. This study evaluated the impact of these unplanned resections on overall survival, local recurrence and distant metastasis in patients with soft tissue sarcomas of the extremities. Methods: Fifty-two patients who were diagnosed with soft tissue sarcoma were analyzed in a retrospective study between May 2001 and March 2011. Twenty-nine (55.8%) of these patients did not undergo previous treatment, and the remaining 23 (44.2%) patients underwent prior resection of the tumor without oncological planning. All patients underwent definitive surgery in the cancer referral center. The follow-up ranged from six to 122 months, with a mean age of 39.89 months. Age, lesion size and depth, histological grade, surgical margin, overall survival, local and distant recurrence and adjuvant therapies were compared. The presence of residual lesions in unplanned excisions was evaluated. Results: Residual disease was observed in 91.3% of the re-resected specimens after definitive surgery on unplanned excision group (Unpex) which exhibited greater numbers of superficial lesions (p=0,013), low histological grade (p=0,033) and contaminated surgical margins on re-resection specimens (p=0,034) compared to the planned excision group (Pex). No differences were observed in local recurrence (p=0,17) and 5-year overall survival (p=0,17) between groups, but distant metastasis were statistically associated with Pex (p=0,03) after adjustments of variables. Conclusions: The re-resection of a soft tissue sarcoma that was previously submitted to unplanned excision is recommended and leads to similar results on local recurrence-free survival and 5-year overall survival rates than sarcomas operated with previous oncological planning, but metastasis-free survival rate was worse on Pex group probably due to bias caused by small number of patients in this study / Mestrado / Fisiopatologia Cirúrgica / Mestre em Ciências

No description available.

A thesis submitted to the Faculty of Medicine, University of the Witwatersrand, Johannesburg, in fulfilment of the requirements for the degree of Master of Medicine in Therapeutic Radiology. / Soft tissue sarcomas of the extremities were previously treated either with wide excision alone, leading to a 30 to 50% local recurrence rate, or amputation, which although lead to a recurrence rate of less than 5%, caused significant physical and psychological morbidity. In addition to the :risk of local recurrence, distant metaatases occur in 30 to 50% of high grade lesions.(Abbreviation abstract) / Andrew Chakane 2018

Paediatric undifferentiated soft tissue sarcomas (USTSs) are a diagnostically challenging group of neoplasms. We hypothesized that USTSs contain distinct subgroups that can be identified based on their morphology, genomic aberrations and expression profiles. We sought to characterize genomic aberrations within primitive round cell (PRC) sarcomas which may underlie aberrant expression patterns. Using molecular and cytogenetic analyses, we identified 5 of 18 CIC-DUX4-positive PRC sarcomas. The consistent involvement of the CIC-DUX4 fusion in a subset of PRC sarcomas suggests a central role for the fusion transcript in such tumours. These analyses also identified a cohort of CIC-DUX4-negative USTSs with no established genetic markers. We performed integrative copy number and expression profiling, and identified significant genomic and transcriptomic changes. We propose that these genes are involved in biological pathways that are important to the initiation and progression of undifferentiated sarcoma, and may provide novel insights into the biological events responsible for sarcomagenesis.

Paediatric undifferentiated soft tissue sarcomas (USTSs) are a diagnostically challenging group of neoplasms. We hypothesized that USTSs contain distinct subgroups that can be identified based on their morphology, genomic aberrations and expression profiles. We sought to characterize genomic aberrations within primitive round cell (PRC) sarcomas which may underlie aberrant expression patterns. Using molecular and cytogenetic analyses, we identified 5 of 18 CIC-DUX4-positive PRC sarcomas. The consistent involvement of the CIC-DUX4 fusion in a subset of PRC sarcomas suggests a central role for the fusion transcript in such tumours. These analyses also identified a cohort of CIC-DUX4-negative USTSs with no established genetic markers. We performed integrative copy number and expression profiling, and identified significant genomic and transcriptomic changes. We propose that these genes are involved in biological pathways that are important to the initiation and progression of undifferentiated sarcoma, and may provide novel insights into the biological events responsible for sarcomagenesis.