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1.
Prostate ; 80(11): 850-858, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32501559

RESUMO

BACKGROUND: Oligometastatic cancer has been suggested as an intermediate state between localized disease and wide-ranging metastases. The clinical significance of local treatment in oligometastatic prostate cancer (PCa) has been a recent topic of interest. However, standard definitions of oligometastasis are lacking. Here we studied risk factors among Japanese de novo oligometastatic patients with PCa. METHODS: We retrospectively assessed clinical data from 264 patients, including locally advanced (T3 or T4N0M0) cancer, lymph-node-positive cancer (Tany N1M0), and cancer with ≤10 bone metastases. All patients received androgen deprivation therapy only. The number of bone metastases and clinical factors were evaluated in association with overall survival (OS) and progression-free survival (PFS). The Mann-Whitney U test, Cox proportional hazard models, and Kaplan-Meier methods were used as statistical analyses. RESULTS: Median age, PSA at baseline and OS were 74 years, 55.2 ng/mL, and 129.0 months, respectively. The cutoff for the number of bone metastases having the greatest impact on OS was ≥3 (hazard ratio [HR]: 2.67; P = .0001). In multivariate analysis, non-regional lymph node (LN) metastases (HR: 2.15; P = .0222), ISUP grade group (GG) 5 (HR: 2.04; P = .0186) and ≥3 bone metastases (HR: 1.82; P = .0390) were independent predictors of OS. In risk classification based on these factors, OS and PFS were significantly classifiable into poor (2-3 factors), intermediate (1 factor), and good (no factors) risk groups (P < .0001). CONCLUSION: Not only the number of bone metastases, but also non-regional LN metastases predict OS in patients with de novo oligometastatic PCa.


Assuntos
Neoplasias Ósseas/mortalidade , Neoplasias Ósseas/secundário , Neoplasias da Próstata/mortalidade , Neoplasias da Próstata/patologia , Idoso , Idoso de 80 Anos ou mais , Antagonistas de Androgênios/uso terapêutico , Humanos , Japão/epidemiologia , Estimativa de Kaplan-Meier , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Intervalo Livre de Progressão , Ensaios Clínicos Controlados Aleatórios como Assunto , Estudos Retrospectivos , Taxa de Sobrevida
2.
Bone Joint J ; 102-B(6): 795-803, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32475245

RESUMO

AIMS: To assess the correlation between the histological response to preoperative chemotherapy and event-free survival (EFS) or overall survival (OS) in patients with high-grade localized osteosarcoma. METHODS: Out of 625 patients aged ≤ 40 years treated for primary high-grade osteosarcoma between 1997 and 2016, 232 patients without clinically detectable metastases at the time of diagnosis and treated with preoperative high-dose methotrexate, adriamycin and cisplatin (MAP) chemotherapy and surgery were included. Associations of chemotherapy-induced necrosis in the resected specimen and EFS or OS were assessed using Cox model and the Pearson's correlation coefficients (r). Time-dependent receiver operating characteristic analysis was applied to determine the optimal cut-off value of chemotherapy-induced necrosis for EFS and OS. RESULTS: OS was 74% (95% confidence interval (CI) 67 to 79) at five years. Median chemotherapy-induced necrosis was 85% (interquartile range (IQR) 50% to 97%). In multivariate Cox model, chemotherapy-induced necrosis was significantly associated with EFS and OS (hazard ratio (HR) = 0.99 (95% CI 0.98 to 0.99); p < 0.001 and HR = 0.98 (95% CI 0.97 to 0.99); p < 0.001, respectively). Positive correlation was observed between chemotherapy-induced necrosis and five-year EFS and five-year OS (r = 0.91; p < 0.001, and r = 0.85; p < 0.001, respectively). The optimal cut-off value of chemotherapy-induced necrosis for five-year EFS and five-year OS was 85% and 72%, respectively. CONCLUSION: Chemotherapy-induced necrosis in the resected specimen showed positive correlation with EFS and OS in patients with high-grade localized osteosarcoma after MAP chemotherapy. In our analysis, optimal cut-off values of MAP chemotherapy-induced necrosis in EFS and OS were lower than the commonly used 90%, suggesting the need for re-evaluation of the optimal cut-off value through larger, international collaborative research. Cite this article: Bone Joint J 2020;102-B(6):795-803.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Ósseas/tratamento farmacológico , Neoplasias Ósseas/cirurgia , Cisplatino/administração & dosagem , Doxorrubicina/administração & dosagem , Metotrexato/administração & dosagem , Osteossarcoma/tratamento farmacológico , Osteossarcoma/cirurgia , Adolescente , Neoplasias Ósseas/mortalidade , Neoplasias Ósseas/patologia , Criança , Correlação de Dados , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Necrose/induzido quimicamente , Terapia Neoadjuvante , Osteossarcoma/mortalidade , Osteossarcoma/patologia , Período Pré-Operatório , Estudos Retrospectivos , Taxa de Sobrevida , Adulto Jovem
3.
Medicine (Baltimore) ; 99(24): e20442, 2020 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-32541466

RESUMO

Surgical treatment of malignant bone tumors comprises tumor resection and reconstruction. The most commonly used reconstruction method is prosthesis replacement, which achieves good early function, but has a high long-term incidence of complications. Another reconstruction option is autologous bone replantation, which has the advantages of anatomical matching and no need for large bone bank support. Few studies have evaluated reconstruction with liquid nitrogen-inactivated autogenous bone.The present study aimed to evaluate the oncological results, bone healing results, complications, and indications of reconstruction with liquid nitrogen-inactivated autogenous bone grafts.The study population comprised 21 consecutive patients. The tumor site was the tibia in 9 cases, femur in 8, and humerus in 4. There were 37 osteotomy ends in total. After freezing and rewarming, the medullary cavity of the autogenous bone was filled with antibiotic bone cement. Seventeen patients received bilateral plate fixation, 2 received intramedullary nail and distal plate fixation, and 2 received single plate fixation.The average follow-up was 31 ±â€Š6 months. Eighteen patients survived without tumors, and the 3-year survival rate was 80.4%. All cases had adequate surgical margins, but recurrence developed in 1 patient. Metastasis occurred in 3 patients, who all died of metastasis. Intraoperative inactivated bone fracture occurred in 1 patient, and screw breakage was found in 1 patient. Nonunion occurred at 1 humeral diaphysis osteotomy site, and 1 patient was lost to follow-up; the average healing time of the other 35 ends was 13 ±â€Š6 months, and the bone healing rate was 97.2%. The average bone healing times in the metaphysis and diaphysis were 9 ±â€Š3 months and 15 ±â€Š6 months (P = .003). The average bone healing times in the upper and lower limbs were 16.6 ±â€Š7.4 months and 12.3 ±â€Š5.8 months (P = .020). The average Muscle and Skeletal Tumor Society score was 28 ±â€Š3 (21-30) in the 18 survivors.Liquid nitrogen-inactivated autologous bone replantation for primary malignant limb tumor was safe and effective, as shown by the relatively low complication rate, high bone healing rate, and satisfactory postoperative function. This is a reliable biological reconstruction method for malignant bone tumors with specific site and bone destruction characteristics.


Assuntos
Neoplasias Ósseas/cirurgia , Osso e Ossos/cirurgia , Nitrogênio/uso terapêutico , Osteossarcoma/cirurgia , Reimplante/estatística & dados numéricos , Adolescente , Adulto , Neoplasias Ósseas/mortalidade , Criança , China/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Osteossarcoma/mortalidade , Adulto Jovem
4.
PLoS One ; 15(6): e0232466, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32492019

RESUMO

Malignant fibrous histiocytoma of the bone (MFH-B) is an extremely rare and aggressive malignancy. The clinicopathological characteristics and prognosis of patients with MFH-B have not been defined. We conducted a retrospective study using the data of all MFH-B patients from the Surveillance, Epidemiology and End Results (SEER) database between 1975 and 2016. Initially, the clinicopathological characteristics were described. The difference in prognosis between patients with MFH-B and those with osteosarcoma was compared using propensity score matching analysis. Then, the features affecting the prognosis of patients with MFH-B were further determined using Cox regression analysis. A total of 318 patients with MFH-B were identified. The median overall survival (mOS) of all 318 patients with MFH-B was 29.0 months. The 1-, 3-, 5-, and 10- year survival rates were 67.4%, 53.6%, 38.7%, and 28.7%, respectively. The multivariate Cox regression analysis showed that older age, distant metastases, and flat bone lesion were independent factors for worse prognosis, whereas surgery was an independent factor for favorable survival, and this intervention could decrease risk of death by 61% (HR = 0.39, 95% CI 0.28-0.54). Apart from this, the prognosis of patients with MFH-B was significantly worse than that of patients with osteosarcoma in both unmatched and matched cohorts. In conclusion, MFH-B is a rare malignant bone cancer, with relatively worse prognosis than osteosarcoma. Older age, distant metastases, flat bone lesion, and surgery were independently associated with prognosis. In order to understand this disease more thoroughly and accurately, more cases with adequate information are required in the future.


Assuntos
Neoplasias Ósseas/patologia , Histiocitoma Fibroso Maligno/patologia , Adulto , Fatores Etários , Idoso , Neoplasias Ósseas/mortalidade , Bases de Dados Factuais , Feminino , Histiocitoma Fibroso Maligno/mortalidade , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Metástase Neoplásica , Estadiamento de Neoplasias , Osteossarcoma/mortalidade , Osteossarcoma/patologia , Prognóstico , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Taxa de Sobrevida
5.
J Surg Oncol ; 121(8): 1249-1258, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32232871

RESUMO

BACKGROUND AND OBJECTIVES: Radiation improves limb salvage in extremity sarcomas. Timing of radiation therapy remains under investigation. We sought to evaluate the effects of neoadjuvant radiation (NAR) on surgery and survival of patients with extremity sarcomas. MATERIALS AND METHODS: A multi-institutional database was used to identify patients with extremity sarcomas undergoing surgical resection from 2000-2016. Patients were categorized by treatment strategy: surgery alone, adjuvant radiation (AR), or NAR. Survival, recurrence, limb salvage, and surgical margin status was analyzed. RESULTS: A total of 1483 patients were identified. Most patients receiving radiotherapy had high-grade tumors (82% NAR vs 81% AR vs 60% surgery; P < .001). The radiotherapy groups had more limb-sparing operations (98% AR vs 94% NAR vs 87% surgery; P < .001). NAR resulted in negative margin resections (90% NAR vs 79% surgery vs 75% AR; P < .0001). There were fewer local recurrences in the radiation groups (14% NAR vs 17% AR vs 27% surgery; P = .001). There was no difference in overall or recurrence-free survival between the three groups (OS, P = .132; RFS, P = .227). CONCLUSION: In this large study, radiotherapy improved limb salvage rates and decreased local recurrences. Receipt of NAR achieves more margin-negative resections however this did not improve local recurrence or survival rates over.


Assuntos
Extremidades/efeitos da radiação , Extremidades/cirurgia , Sarcoma/radioterapia , Sarcoma/cirurgia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Ósseas/mortalidade , Neoplasias Ósseas/radioterapia , Neoplasias Ósseas/cirurgia , Bases de Dados Factuais , Extremidades/patologia , Feminino , Humanos , Salvamento de Membro/métodos , Salvamento de Membro/estatística & dados numéricos , Masculino , Margens de Excisão , Pessoa de Meia-Idade , Terapia Neoadjuvante , Recidiva Local de Neoplasia/mortalidade , Recidiva Local de Neoplasia/patologia , Radioterapia Adjuvante , Estudos Retrospectivos , Sarcoma/mortalidade , Sarcoma/patologia , Neoplasias de Tecidos Moles/mortalidade , Neoplasias de Tecidos Moles/radioterapia , Neoplasias de Tecidos Moles/cirurgia , Taxa de Sobrevida , Estados Unidos/epidemiologia , Adulto Jovem
6.
Int J Clin Oncol ; 25(6): 1195-1205, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32215805

RESUMO

OBJECTIVE: The aim of this study was to investigate the efficacy and safety of Apatinib mesylate in the treatment of metastatic osteosarcoma patients who progressed after standard therapy and the VEGFR2 gene polymorphism analysis. METHODS: Designed as a retrospective study, a total of 105 metastatic osteosarcoma patients who progressed after standard therapy were included in this study. The metastatic osteosarcoma patients received 500-750 mg Apatinib mesylate according to body surface area until disease progression or unacceptable toxicity with 28 days one cycle. Overall response was evaluated after two cycles Apatinib treatment, then progression-free survival (PFS) and overall survival (OS) were evaluated, and safety data were recorded. Additionally. peripheral blood and peripheral blood mononuclear cell (PBMC) specimens in the osteosarcoma patients were collected for the genotyping of VEGFR2 genetic variation and mRNA expression, respectively. Analysis on the association between genotype and baseline characteristics and VEGFR2 gene mRNA expression was analyzed. The univariate analysis of genotypes and prognosis was carried out by Kaplan-Meier survival analysis, and multivariate analysis was adjusted by Cox regression analysis. RESULTS: The objective response rate (ORR) of the 105 metastatic osteosarcoma patients was 37.14%, disease control rate (DCR) was 77.14%, median PFS was 4.1 months, and median OS was 9.0 months. Regarding the VEGFR2 gene polymorphisms analysis, only - 906 T > C was of clinical significance. The prevalence of - 906 T > C in VEGFR2 among the study population was as follows: TT genotype 62 cases (59.05%), TC genotype 36 cases (34.29%) and CC genotype 7 cases (6.66%), minor allele frequency of - 906 T > C was 0.24. Compared with patients with TC/CC genotype, patients with TT genotype showed longer median PFS (5.0 versus 3.1 months, P = 0.011) and median OS (9.8 versus 7.6 months, P = 0.032). There was no correlation between the polymorphism and adverse reactions. Additionally, the mRNA expression in 69 randomly selected sample indicated that the mRNA expression of VEGFR2 of the patients with CC/TC genotypes were significantly higher than those of the TT genotype patients (P < 0.001). CONCLUSION: Apatinib was safe and effective in the treatment of metastatic osteosarcoma patients who progressed after standard therapy. The clinical outcomes of Apatinib may be influenced by the polymorphism - 906 T > C of VEGFR2 through mediating the mRNA expression of VEGFR2.


Assuntos
Antineoplásicos/uso terapêutico , Neoplasias Ósseas/tratamento farmacológico , Osteossarcoma/tratamento farmacológico , Polimorfismo Genético , Piridinas/uso terapêutico , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/genética , Adolescente , Adulto , Neoplasias Ósseas/genética , Neoplasias Ósseas/mortalidade , Neoplasias Ósseas/patologia , Feminino , Regulação Neoplásica da Expressão Gênica , Frequência do Gene , Genótipo , Humanos , Estimativa de Kaplan-Meier , Leucócitos Mononucleares/fisiologia , Masculino , Pessoa de Meia-Idade , Osteossarcoma/genética , Osteossarcoma/mortalidade , Osteossarcoma/patologia , Estudos Retrospectivos , Resultado do Tratamento , Adulto Jovem
7.
Eur J Cancer ; 129: 60-70, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32135312

RESUMO

AIM: Real-world data inform the outcome comparisons and help the development of new therapeutic strategies. To this end, we aimed to describe the full characteristics and outcomes in the Epidemiological Strategy and Medical Economics (ESME) cohort, a large national contemporary observational database of patients with metastatic breast cancer (MBC). METHODS: Women aged ≥18 years with newly diagnosed MBC and who initiated MBC treatment between January 2008 and December 2016 in one of the 18 French Comprehensive Cancer Centers (N = 22,109) were included. We assessed the full patients' characteristics, first-line treatments, overall survival (OS) and first-line progression-free survival, as well as updated prognostic factors in the whole cohort and among the 3 major subtypes: hormone receptor positive and HER2-negative (HR+/HER2-, n = 13,656), HER2-positive (HER2+, n = 4017) and triple-negative (n = 2963) tumours. RESULTS: The median OS of the whole cohort was 39.5 months (95% confidence interval [CI], 38.7-40.3). Five-year OS was 33.8%. OS differed significantly between the 3 subtypes (p < 0.0001) with a median OS of 43.3 (95% CI, 42.5-44.5) in HR+/HER2-; 50.1 (95% CI, 47.6-53.1) in HER2+; and 14.8 months (95% CI, 14.1-15.5) in triple-negative subgroups, respectively. Beyond performance status, the following variables had a constant significant negative prognostic impact on OS in the whole cohort and among subtypes: older age at diagnosis of metastases (except for the triple-negative subtype), metastasis-free interval between 6 and 24 months, presence of visceral metastases and number of metastatic sites ≥ 3. CONCLUSIONS: The ESME program represents a unique large-scale real-life cohort on MBC. This study highlights important situations of high medical need within MBC patients. DATABASE REGISTRATION: clinicaltrials.gov Identifier NCT032753.


Assuntos
Neoplasias Abdominais/mortalidade , Neoplasias Ósseas/mortalidade , Neoplasias Encefálicas/mortalidade , Neoplasias da Mama/mortalidade , Metástase Linfática , Neoplasias Cutâneas/mortalidade , Neoplasias Abdominais/prevenção & controle , Neoplasias Abdominais/secundário , Adolescente , Adulto , Fatores Etários , Idoso , Neoplasias Ósseas/prevenção & controle , Neoplasias Ósseas/secundário , Neoplasias Encefálicas/prevenção & controle , Neoplasias Encefálicas/secundário , Mama/patologia , Neoplasias da Mama/patologia , Neoplasias da Mama/terapia , Intervalo Livre de Doença , Feminino , França/epidemiologia , Humanos , Estimativa de Kaplan-Meier , Pessoa de Meia-Idade , Prognóstico , Intervalo Livre de Progressão , Receptor ErbB-2/análise , Receptor ErbB-2/metabolismo , Receptores Estrogênicos/análise , Receptores Estrogênicos/metabolismo , Receptores de Progesterona/análise , Receptores de Progesterona/metabolismo , Estudos Retrospectivos , Neoplasias Cutâneas/prevenção & controle , Neoplasias Cutâneas/secundário , Adulto Jovem
8.
J Surg Oncol ; 121(8): 1241-1248, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32162343

RESUMO

BACKGROUND AND OBJECTIVES: Evidence regarding the impact of sarcopenia on operative outcomes in patients with sarcoma is lacking. We evaluated the relationship between sarcopenia and postoperative complications or mortality among patients undergoing tumor excision and reconstruction. ​ METHODS: We retrospectively reviewed 145 patients treated with tumor excision and limb reconstruction for sarcoma of the extremities. Sarcopenia was defined as psoas index (PI) < 5.45 cm2 /m2 for men and <3.85 cm2 /m2 for women from preoperative axial CT. Regression analyses were used to assess the association between postoperative complications or mortality with PI, age, gender, race, body mass index, tumor histology, grade, depth, location, size, and neoadjuvant/adjuvant therapy. RESULTS: There were 101 soft tissue tumors and 44 primary bone tumors. Sarcopenia was present in 38 patients (26%). Sarcopenic patients were older (median age: 72 vs 59 years, P = .0010) and had larger tumors (86.5%, >5 cm vs 77.7%, P = .023). Seventy-three patients experienced complications (51%) and 18 patients died within 1 year. Sarcopenia and metastatic disease were associated with increased 12-month mortality (hazard ratio [HR] = 6.68, P < .001; HR: 8.51, P < .001, respectively) but not complications (HR 1.45, P = .155, odds ratio, 1.32, P = .426, respectively). CONCLUSIONS: Sarcopenia and metastatic disease were independently associated with postoperative mortality but no complications following surgery.


Assuntos
Extremidades/cirurgia , Sarcoma/mortalidade , Sarcoma/cirurgia , Sarcopenia/mortalidade , Neoplasias de Tecidos Moles/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Ósseas/diagnóstico por imagem , Neoplasias Ósseas/mortalidade , Neoplasias Ósseas/fisiopatologia , Neoplasias Ósseas/cirurgia , Extremidades/diagnóstico por imagem , Extremidades/patologia , Feminino , Humanos , Iowa/epidemiologia , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Prevalência , Procedimentos Cirúrgicos Reconstrutivos/efeitos adversos , Procedimentos Cirúrgicos Reconstrutivos/métodos , Procedimentos Cirúrgicos Reconstrutivos/mortalidade , Estudos Retrospectivos , Sarcoma/diagnóstico por imagem , Sarcoma/fisiopatologia , Sarcopenia/diagnóstico por imagem , Sarcopenia/epidemiologia , Sarcopenia/fisiopatologia , Neoplasias de Tecidos Moles/diagnóstico por imagem , Neoplasias de Tecidos Moles/mortalidade , Neoplasias de Tecidos Moles/fisiopatologia , Adulto Jovem
9.
J Surg Oncol ; 121(7): 1097-1103, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32133661

RESUMO

BACKGROUND AND OBJECTIVES: Malignant fibrous histiocytoma (MFH) of bone, now known as undifferentiated pleomorphic sarcoma of bone, is a rare neoplasm that accounts for less than 2% of all primary malignant bone tumors. The objective of the current study was to evaluate prognosis and survival for MFH of bone. METHODS: The 2004 to 2016 National Cancer Database was queried to identify patients with a primary MFH of bone. Kaplan-Meier survival and Cox regression analyses were used to analyze overall survival and risk factors associated with overall mortality. RESULTS: The overall 5-year and 10-year survival rates were 38.3% and 30.5%, respectively. Increasing stage and metastatic disease at presentation were associated with poor overall survival (P < .001). Patients aged 18 to 50 years (hazard ratio [HR], 0.51), 51 to 75 years (HR, 0.61), and those undergoing surgery (HR, 0.39) had improved survival. Having Medicare insurance (HR, 1.48), residing in a low educated area (HR, 2.56), and positive surgical margins (HR, 1.80) were associated with poor survival. CONCLUSIONS: The overall prognosis of MFH of bone is poor with a reported 5-year survival rate of 38.3%. Undergoing surgery and younger age were associated with a better prognosis. Older age, having Medicare insurance, and positive surgical margins were predictors of mortality.


Assuntos
Neoplasias Ósseas/mortalidade , Histiocitoma Fibroso Maligno/mortalidade , Adolescente , Adulto , Idoso , Neoplasias Ósseas/patologia , Bases de Dados Factuais , Feminino , Histiocitoma Fibroso Maligno/patologia , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Estados Unidos/epidemiologia , Adulto Jovem
10.
J Surg Oncol ; 121(7): 1115-1125, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32141094

RESUMO

BACKGROUND AND OBJECTIVES: Interobserver variability in histological grading of central conventional chondrosarcoma (CCCS) limits the quality of patient information and research progression. We aim to quantify known and new prognostic variables and propose a risk stratification model. METHOD: We selected 149 cases from the Cancer Registry of Norway. Cox proportional hazard models were estimated. Based on these results a dichotomous risk classification was proposed and presented by Kaplan-Meier estimates for rates of local recurrence, metastasis, and disease-specific survival. RESULTS: The influence of axial skeletal location (Hazard ratio [HR] = 19.06), a soft tissue component ≥1 cm (HR = 13.45), and histological grade 3 (HR = 16.46) are all significant in predicting the rate of metastasis. The creation of a variable combining axial skeletal location and a soft tissue component ≥1 cm strongly predicts the risk of metastasis (HR = 14.02; P < .001) and death (HR = 2.74; P = .030) at multivariate analysis, making the histological grade insignificant. Together with metastasis at diagnosis (HR = 285.65; P < .001), this forms the basis of our proposed risk stratification, producing a small high-risk group (39 cases with 33% risk of metastasis) and a large low-risk group (103 cases with 2% risk of metastasis) without a histological grade. CONCLUSION: Axial skeletal location and a soft tissue component ≥1 cm combined divides a CCCS cohort into low- and high-risk groups without a histological grade.


Assuntos
Neoplasias Ósseas/mortalidade , Neoplasias Ósseas/patologia , Condrossarcoma/mortalidade , Condrossarcoma/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Feminino , Seguimentos , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Noruega/epidemiologia , Prognóstico , Modelos de Riscos Proporcionais , Sistema de Registros , Medição de Risco , Análise de Sobrevida , Adulto Jovem
11.
Spine (Phila Pa 1976) ; 45(12): E713-E720, 2020 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-32039945

RESUMO

STUDY DESIGN: Retrospective analysis. OBJECTIVE: Our goal was to provide a predictive model and a risk classification system that predicts cancer-specific survival (CSS) from spinal and pelvic tumors. SUMMARY OF BACKGROUND DATA: Primary bone tumors of the spinal and pelvic are rare, thus limiting the understanding of the manifestations and survival from these tumors. Nomograms are the graphical representation of mathematical relationships or laws that accurately predict individual survival. METHODS: A total of 1033 patients with spinal and pelvic bone tumors between 2004 and 2016 were selected from the Surveillance, Epidemiology, and End Results (SEER) database. Multivariate Cox analysis was used on the training set to select significant predictors to build a nomogram that predicted 3- and 5-year CSS. We validate the precision of the nomogram by discrimination and calibration, and the clinical value of nomogram was assessed by making use of a decision curve analyses (DCA). RESULTS: Data from 1033 patients with initially-diagnosed spinal and pelvic tumors were extracted from the SEER database. Multivariate analysis of the training cohort, predictors included in the nomogram were age, pathological type, tumor stage, and surgery. The value of C-index was 0.711 and 0.743 for the internal and external validation sets, respectively, indicating good agreement with actual CSS. The internal and external calibration curves revealed good correlation of CSS between the actual observation and the nomogram. Then, the DCA showed greater net benefits than that of treat-all or treat-none at all time points. A novel risk grouping system was established for CSS that can readily divide all patients into three distinct risk groups. CONCLUSION: The proposed nomogram obtained more precision prognostic prediction for patients with initially-diagnosed primary spinal and pelvic tumors. LEVEL OF EVIDENCE: 3.


Assuntos
Neoplasias Ósseas/diagnóstico , Neoplasias Ósseas/mortalidade , Estadiamento de Neoplasias/métodos , Nomogramas , Neoplasias Pélvicas/diagnóstico , Neoplasias Pélvicas/mortalidade , Adulto , Estudos de Coortes , Técnicas de Apoio para a Decisão , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Fatores de Risco , Programa de SEER
12.
Pediatr Blood Cancer ; 67(5): e28194, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32077253

RESUMO

BACKGROUND: The survival rate in patients with Ewing sarcoma family of tumors (ESFT) in Japan was reported to be < 50% in the 1990s. The Japan Ewing Sarcoma Study Group was established to improve the prognosis of ESFT in Japan. The aim of this phase II trial was to determine the efficacy and safety of multimodal treatment for nonmetastatic ESFT. PROCEDURE: Patients with ESFT aged < 30 years were eligible for participation. The chemotherapy regimen consisted of vincristine, doxorubicin, and cyclophosphamide (VDC) alternating with ifosfamide and etoposide (IE) repeating every 21 days for 52 weeks. Local treatment included surgery and/or radiation therapy (0-55.8 Gy) based on the margin of resection and histologic response. The primary endpoint was progression-free survival (PFS) at three years. The study was designed to test whether the lower limit of the 90% confidence interval for PFS would exceed the threshold of 60%. The planned sample size was 53 patients, allowing for 10% of patients being ineligible. RESULTS: Of the 53 patients screened for entry, seven were deemed ineligible. Forty-six patients were considered as the per-protocol set and were used for the efficacy analysis. Three-year PFS was 71.7% (0.59-0.81). Estimated five-year PFS and overall survival were both 69.6%. Although no previously unknown adverse event was reported, three patients developed secondary malignancies (acute lymphoblastic leukemia, myelodysplastic syndrome, and osteosarcoma, one patient each). CONCLUSIONS: Multimodal treatment with standard VDC-IE chemotherapy improved the prognosis for patients with ESFT in Japan, although statistical confirmation of efficacy compared to historical control was not achieved.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Neoplasias Ósseas , Sarcoma de Ewing , Adolescente , Adulto , Neoplasias Ósseas/mortalidade , Neoplasias Ósseas/terapia , Criança , Terapia Combinada , Ciclofosfamida/administração & dosagem , Dactinomicina/administração & dosagem , Intervalo Livre de Doença , Feminino , Humanos , Japão/epidemiologia , Masculino , Sarcoma de Ewing/mortalidade , Sarcoma de Ewing/terapia , Taxa de Sobrevida , Vincristina/administração & dosagem
13.
Medicina (B Aires) ; 80(1): 23-30, 2020.
Artigo em Espanhol | MEDLINE | ID: mdl-32044738

RESUMO

Ewing sarcoma of the bone is a rare, highly aggressive tumor that typically affects children and young adults. In Argentina, the lack of Ewing's sarcoma registries reflects in the absence of information regarding prevalence, treatment protocols and patient's outcome. The purpose of this study was to analyze, in a group of patients diagnosed with Ewing sarcoma of the bone, treated with chemotherapy and limb-conserving surgery, their overall survival rate, local recurrence rate, and oncological risk factors. A retrospective research was conducted between 1990 and 2017. Eighty-eight patients with Ewing sarcoma of the bone matched the inclusion criteria. Median age was 14.5 years and median follow-up was 8.8 years. Overall survival rate was 79.5%, 69% and 64% at 2, 5 and 10 years respectively. Negative prognostic factors, associated with less survival rate after univariate analysis, were: bad response to chemotherapy (tumoral necrosis 0-89%), age > 16 years-old, central tumor localization and local recurrence. Gender and tumor size were not significant prognostic factors. After multivariate analysis, response to chemotherapy remained statistical significant. Local recurrence-free survival rate at 2 and 5 years was 87%. Tumor response to chemotherapy (0-89%) was the only significant factor for local recurrence. We consider that limb-salvage surgery, with neoadjuvant and adjuvant chemotherapy, are the mainstays of treatment for Ewing's sarcoma, with an overall survival rate, at 5 years, of 69%. In this population, response to chemotherapy is the most relevant prognostic factor, being associated with both local recurrence and overall survival.


Assuntos
Neoplasias Ósseas/mortalidade , Sarcoma de Ewing/mortalidade , Adolescente , Adulto , Argentina/epidemiologia , Neoplasias Ósseas/terapia , Criança , Pré-Escolar , Intervalo Livre de Doença , Feminino , Humanos , Estimativa de Kaplan-Meier , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Recidiva Local de Neoplasia , Estudos Retrospectivos , Fatores de Risco , Sarcoma de Ewing/terapia , Fatores de Tempo , Adulto Jovem
14.
Cancer Immunol Immunother ; 69(5): 745-758, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32047957

RESUMO

BACKGROUND: Osteosarcoma (OS) is the most common malignant bone tumor and the prognosis of advanced cases is still poor. Recently, there have been several reports suggesting the relationship between innate immunity and OS, but the detailed mechanism is unknown. We demonstrate the relationship between OS and Toll-like receptor 4 (TLR4) which is one of the most important factors in innate immunity. METHODS: We established a syngenic mouse tumor model using C3H/HeN, C3H/HeJ mouse and a highly metastatic OS cell line, LM8. TLR4 activation with lipopolysaccharide (LPS) was performed on both mice and its influence on the progression of OS was evaluated. We also performed CD8 + cells depletion to examine the influence on TLR4 activation effects. RESULTS: Tumor volume of C3H/HeN mice was significantly smaller and overall survival of C3H/HeN mice was significantly longer than C3H/HeJ mice. We found more CD8+ cells infiltrating in lung metastases of C3H/HeN mice and depletion of CD8+ cells canceled the antitumor effects of LPS. CONCLUSION: TLR4 activation by LPS increased CD8+ cells infiltrating into lung metastases and suppressed OS progression in the mouse model. TLR4 activation may suppress the progression of OS via stimulating CD8+ cells and can be expected as a novel treatment for OS.


Assuntos
Neoplasias Ósseas/imunologia , Neoplasias Pulmonares/imunologia , Osteossarcoma/imunologia , Linfócitos T Citotóxicos/imunologia , Receptor 4 Toll-Like/metabolismo , Adjuvantes Imunológicos/administração & dosagem , Adolescente , Animais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Ósseas/mortalidade , Neoplasias Ósseas/patologia , Neoplasias Ósseas/terapia , Linhagem Celular Tumoral/transplante , Quimioterapia Adjuvante , Criança , Pré-Escolar , Modelos Animais de Doenças , Progressão da Doença , Feminino , Humanos , Estimativa de Kaplan-Meier , Lipídeo A/administração & dosagem , Lipídeo A/análogos & derivados , Lipopolissacarídeos/administração & dosagem , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/secundário , Neoplasias Pulmonares/terapia , Depleção Linfocítica , Masculino , Camundongos , Pessoa de Meia-Idade , Osteossarcoma/mortalidade , Osteossarcoma/secundário , Osteossarcoma/terapia , Prognóstico , Intervalo Livre de Progressão , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/imunologia , Linfócitos T Citotóxicos/metabolismo , Receptor 4 Toll-Like/agonistas , Receptor 4 Toll-Like/imunologia , Carga Tumoral/imunologia , Adulto Jovem
15.
Jpn J Clin Oncol ; 50(6): 688-692, 2020 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-32083279

RESUMO

OBJECTIVE: In contrast to acrometastasis, defined as bone metastasis to the hand or foot, the frequency and prognosis of bone metastasis of other limb segments remain unclear. To compare prognosis according to sites of bone metastasis, we defined two new terms in this study: 'mesometastasis' and 'rhizometastasis' as bone metastasis of 'forearm or lower leg' and 'arm or thigh', respectively. METHODS: A total of 539 patients who were registered to the bone metastasis database of The University of Tokyo Hospital from April 2012 to May 2016 were retrospectively surveyed. All patients who were diagnosed to have bone metastases in our hospital are registered to the database. Patients were categorized into four groups according to the most distal site of bone metastases: 'acrometastasis', 'mesometastasis', 'rhizometastasis' and 'body trunk metastasis'. RESULTS: The frequency of rhizometastasis (22.5%) or body trunk metastasis (73.1%) was significantly higher than that of acrometastasis (2.0%) or mesometastasis (2.4%). The median survival time after diagnosis of bone metastases for each group was as follows: 6.5 months in acrometastasis, 4.0 months in mesometastasis, 16 months in rhizometastasis, 17 months in body trunk metastasis and 16 months overall. In survival curve, there was a statistically significant difference between mesometastasis and body trunk metastasis. CONCLUSIONS: Our findings suggest that 'mesometastasis' could be another poor prognostic factor in cancer patients and that patients with mesometastasis should receive appropriate treatments according to their expected prognosis.


Assuntos
Neoplasias Ósseas/secundário , Extremidades , Idoso , Idoso de 80 Anos ou mais , Neoplasias Ósseas/mortalidade , Neoplasias Ósseas/terapia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida
16.
Cancer Lett ; 473: 33-49, 2020 03 31.
Artigo em Inglês | MEDLINE | ID: mdl-31904478

RESUMO

Long non-coding RNAs (lncRNAs) regulates the initiation and progression of osteosarcoma (OS), specifically lncRNA RP11-361F15.2 has been shown to play prominent roles in tumorigenesis. Previously, M2-Like polarization of tumor-associated macrophages (TAMs) has been identified to play a key role in cancer migration/invasion. Hence, it is essential to understand the role of RP11-361F15.2 in tumorigenesis and its association with M2-Like polarization of TAMs. The results indicate that RP11-361F15.2 is significantly increased in OS tissues, and its expression is positively correlated with cytoplasmic polyadenylation element binding protein 4 (CPEB4) expression and negatively associated with miR-30c-5p expression. Further, overexpression of RP11-361F15.2 increased OS cell migration/invasion and M2-Like polarization of TAMs in vitro, as well as promoted xenograft tumor growth in vivo. Mechanistically, luciferase reporter assays indicated that RP11-361F15.2 upregulated CPEB4 expression by competitively binding to miR-30c-5p. Further, we have identified that RP11-361F15.2 promotes CPEB4-mediated tumorigenesis and M2-Like polarization of TAMs through miR-30c-5p in OS. We also identified that RP11-361F15.2 acts as competitive endogenous RNA (ceRNA) against miR-30c-5p thereby binding and activating CPEB4. This RP11-361F15.2/miR-30c-5p/CPEB4 loop could be used as a potential therapeutic strategy for the treatment of OS.


Assuntos
Neoplasias Ósseas/genética , Carcinogênese/genética , Macrófagos/imunologia , MicroRNAs/metabolismo , Osteossarcoma/genética , RNA Longo não Codificante/metabolismo , Proteínas de Ligação a RNA/genética , Adolescente , Animais , Neoplasias Ósseas/imunologia , Neoplasias Ósseas/mortalidade , Neoplasias Ósseas/patologia , Carcinogênese/efeitos dos fármacos , Carcinogênese/imunologia , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Movimento Celular/genética , Feminino , Regulação Neoplásica da Expressão Gênica/imunologia , Técnicas de Silenciamento de Genes , Humanos , Estimativa de Kaplan-Meier , Macrófagos/metabolismo , Masculino , Camundongos , MicroRNAs/agonistas , MicroRNAs/antagonistas & inibidores , Invasividade Neoplásica/genética , Invasividade Neoplásica/imunologia , Invasividade Neoplásica/prevenção & controle , Osteossarcoma/imunologia , Osteossarcoma/mortalidade , Osteossarcoma/patologia , Células RAW 264.7 , RNA Longo não Codificante/genética , RNA Interferente Pequeno/metabolismo , Regulação para Cima , Ensaios Antitumorais Modelo de Xenoenxerto , Adulto Jovem
17.
Oncol Res Treat ; 43(4): 134-139, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31982870

RESUMO

AIMS: The aim of this retrospective study is to evaluate the role of pulmonary metastasectomy (PM) in patients affected by lung metastasis (LM) of grade 2 and 3 chondrosarcoma (CS). PATIENTS AND METHODS: The study included 61 patients affected by LM. Patients unfit for PM were treated with chemotherapy and radiotherapy. RESULTS: The patients' mean age was 51 years, ranging from 17 to 84 years; 44 (66.7%) patients had grade 2 CS, while 17 (25.8%) patients had grade 3 CS. Fifty-one patients presented multiple nodules: 44 of those cases were bilateral LM (72.1%). Twenty-nine (47.5%) patients underwent PM, whereas 32 (52.5%) patients underwent chemotherapy and stereotactic radiotherapy alone. At the final follow-up (average of 83 months, range 13-298), 47 (77.0%) patients had died of the disease. A better post-relapse survival rate was observed in patients who underwent PM (55.1 vs. 13.1% at 5-year follow-up, p < 0.001) and in patients with unilateral LM (60.4 vs. 25.6% at 5-year follow-up, p = 0.016). The number of LM also played a prognostic role. CONCLUSIONS: Until significant improvements in chemotherapy can be made, PM can be a valid option in the attempt to improve post-metastatic survival.


Assuntos
Neoplasias Ósseas/cirurgia , Condrossarcoma/cirurgia , Neoplasias Pulmonares/secundário , Neoplasias Pulmonares/cirurgia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Ósseas/mortalidade , Neoplasias Ósseas/patologia , Condrossarcoma/mortalidade , Condrossarcoma/patologia , Feminino , Seguimentos , Humanos , Neoplasias Pulmonares/mortalidade , Masculino , Metastasectomia/estatística & dados numéricos , Pessoa de Meia-Idade , Gradação de Tumores , Estudos Retrospectivos , Taxa de Sobrevida , Resultado do Tratamento , Adulto Jovem
18.
BMC Cancer ; 20(1): 65, 2020 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-31992246

RESUMO

BACKGROUND: Osteosarcoma is a primary malignant tumor originating from mesenchymal tissue, with a poor distant metastasis prognosis. The molecular mechanisms of osteosarcoma metastasis are extremely complicated. METHODS: A public data series (GSE21257) was used to identify differentially expressed genes (DEGs) in osteosarcoma patients that did, or did not, develop metastases. Functional enrichment analysis, a protein-protein interaction network, and survival analysis of DEGs were performed. DEGs with a prognostic value were considered as candidate genes and their functional predictions, different expression in normal and malignant tissues, and immune infiltration were analyzed. RESULTS: The DEGs were mainly enriched in the immune response. Three candidate genes (ALOX5AP, CD74, and FCGR2A) were found, all of which were expressed at higher levels in lungs and lymph nodes than in matched cancer tissues and were probably expressed in the microenvironment. CONCLUSIONS: Candidate genes can help us understand the molecular mechanisms underlying osteosarcoma metastasis and provide targets for future research.


Assuntos
Proteínas Ativadoras de 5-Lipoxigenase/genética , Antígenos de Diferenciação de Linfócitos B/genética , Neoplasias Ósseas/mortalidade , Perfilação da Expressão Gênica/métodos , Antígenos de Histocompatibilidade Classe II/genética , Osteossarcoma/mortalidade , Receptores de IgG/genética , Neoplasias Ósseas/genética , Bases de Dados Genéticas , Regulação Neoplásica da Expressão Gênica , Redes Reguladoras de Genes , Humanos , Metástase Neoplásica , Osteossarcoma/genética , Prognóstico , Análise de Sobrevida , Microambiente Tumoral
19.
Br J Radiol ; 93(1108): 20190353, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31971828

RESUMO

OBJECTIVE: To evaluate toxicity and clinical outcome in synchronous bone only oligometastatic (≤2 lesions) prostate cancer patients, simultaneously irradiated to prostate/prostatic bed, lymph nodes and bone metastases. METHODS: From 2/2009 to 6/2015, 39 bone only prostate cancer patients underwent radiotherapy (RT) at "radical" doses to bone metastases (median 2 Gy equivalent dose, EQD2>40Gy, α/ß = 1,5), nodes, and prostate/prostatic bed, within the same RT course, in association with androgen deprivation therapy (ADT).Biochemical relapse-free survival, clinical relapse-free survival, freedom from distant metastases and overall survival were evaluated. RESULTS: After a median follow-up of 46.5 (1.2-103.6) months, 5 patients died from disease progression, 10 experienced biochemical relapse, 19, still in ADT, presented undetectable prostate-specific antigen (PSA) at the last follow-up. Five patients who discontinued ADT after a median of 34 months (5.8-41) are free from biochemical relapse.The 4 year Kaplan-Meier estimates of biochemical relapse-free survival, clinical relapse-free survival, freedom from distant metastases and overall survival were 53.3%, 65.7%, 73.4% and 82.4% respectively.No Grade > 2 acute events and only two severe late urinary events were recorded, not due to the concomitant treatment of primary and metastatic disease. CONCLUSION: Our results suggest that "radical" and synchronous irradiation of primitive tumor and metastatic disease may be a valid approach in synchronous bone only prostate cancer patients, showing mild toxicity profile and promising survival results. ADVANCES IN KNOWLEDGE: To the best of our knowledge, this is the first analysis of clinical outcome in synchronous bone-only metastasis (neither nodal nor visceral) patients at diagnosis, treated with radical RT to all disease, associated to ADT.


Assuntos
Neoplasias Ósseas/radioterapia , Irradiação Linfática , Neoplasias da Próstata/radioterapia , Idoso , Antagonistas de Androgênios/uso terapêutico , Neoplasias Ósseas/mortalidade , Neoplasias Ósseas/secundário , Quimioterapia Adjuvante , Progressão da Doença , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/mortalidade , Neoplasias da Próstata/patologia , Neoplasias da Próstata/terapia , Estudos Retrospectivos
20.
J Surg Oncol ; 121(4): 638-644, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31989655

RESUMO

BACKGROUND: Conventional primary pelvic chondrosarcoma often presents as a low- or intermediate-grade tumor in older patients. Although this is the most common variant of pelvic chondrosarcoma, studies examining treatment outcomes are lacking. The purpose of this study was to evaluate patients with these tumors to determine their outcomes of treatment. METHODS: Seventy-three patients (grade I [n = 19, 26%] and grade II [n = 54, 74%]) were reviewed including 55 (75%) males and 18 (25%) females, with a mean age of 51 (range, 17-81) years and follow-up of 9 ± 5 years. RESULTS: The 10-year disease-specific survival was 71%. Grade II disease (hazard ratio [HR], 6.74; P = .04) and age ≥50 years (HR, 3.97; P = .02) was associated with death due to disease. The 10-year local recurrence- and metastatic-free survival were 79% and 72%. Of the patients with a local recurrence (n = 11), 7 (64%) recurred at a higher histological grade. Patient age ≥50 years was associated with local recurrence (HR, 10.03; P = .02) and metastatic disease (HR, 4.20; P = .02). CONCLUSION: Advancing patient age was an independent risk factor for worse survival and disease recurrence. Tumors often recurred locally at a higher grade and as such wide local excision remains the treatment of choice for these tumors.


Assuntos
Neoplasias Ósseas/mortalidade , Neoplasias Ósseas/cirurgia , Condrossarcoma/mortalidade , Condrossarcoma/cirurgia , Ossos Pélvicos/cirurgia , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Neoplasias Ósseas/patologia , Condrossarcoma/patologia , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Ossos Pélvicos/patologia , Modelos de Riscos Proporcionais , Procedimentos Cirúrgicos Reconstrutivos , Resultado do Tratamento , Adulto Jovem
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