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BACKGROUND: Chondrosarcoma (CHS), a bone malignancy, poses a significant challenge due to its heterogeneous nature and resistance to conventional treatments. There is a clear need for advanced prognostic instruments that can integrate multiple prognostic factors to deliver personalized survival predictions for individual patients. This study aimed to develop a novel prediction tool based on recursive partitioning analysis (RPA) to improve the estimation of overall survival for patients with CHS. METHODS: Data from the Surveillance, Epidemiology, and End Results (SEER) database were analyzed, including demographic, clinical, and treatment details of patients diagnosed between 2000 and 2018. Using C5.0 algorithm, decision trees were created to predict survival probabilities at 12, 24, 60, and 120 months. The performance of the models was assessed through confusion scatter plot, accuracy rate, receiver operator characteristic (ROC) curve, and area under ROC curve (AUC). RESULTS: The study identified tumor histology, surgery, age, visceral (brain/liver/lung) metastasis, chemotherapy, tumor grade, and sex as critical predictors. Decision trees revealed distinct patterns for survival prediction at each time point. The models showed high accuracy (82.40%-89.09% in training group, and 82.16%-88.74% in test group) and discriminatory power (AUC: 0.806-0.894 in training group, and 0.808-0.882 in test group) in both training and testing datasets. An interactive web-based shiny APP (URL: https://yangxg1209.shinyapps.io/chondrosarcoma_survival_prediction/) was developed, simplifying the survival prediction process for clinicians. CONCLUSIONS: This study successfully employed RPA to develop a user-friendly tool for personalized survival predictions in CHS. The decision tree models demonstrated robust predictive capabilities, with the interactive application facilitating clinical decision-making. Future prospective studies are recommended to validate these findings and further refine the predictive model.
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Neoplasias Ósseas , Condrossarcoma , Aprendizado de Máquina , Humanos , Condrossarcoma/mortalidade , Condrossarcoma/patologia , Condrossarcoma/terapia , Masculino , Feminino , Neoplasias Ósseas/mortalidade , Neoplasias Ósseas/terapia , Neoplasias Ósseas/patologia , Pessoa de Meia-Idade , Prognóstico , Idoso , Programa de SEER , Árvores de Decisões , Adulto , Curva ROC , Adulto JovemRESUMO
INTRODUCTION: The management of spinal sarcomas is complex, given their widespread involvement and high recurrence rates. Despite consensus on the need for a multidisciplinary approach with surgery at its core, there is a lack of definitive guidelines for clinical decision-making. This study examines a case series of primary spinal sarcomas, focusing on the surgical strategies, clinical results, and survival data to inform and guide therapeutic practices. METHODS: We conducted a retrospective analysis of patients who underwent surgical resection for primary spinal sarcomas between 2005 and 2022. The study focused on gathering data on patient demographics, surgical details, postoperative complications, overall hospital stay, and mortality within 90 days post-surgery. RESULTS: The study included 14 patients with a primary diagnosis of spinal sarcoma, with an average age of 48.6 ± 12.6 years. Chondrosarcoma emerged as the most common tumor type, representing 57.1% of cases, followed by Ewing sarcoma at 35.7%, and synovial sarcoma at 7.1%. Patients with chondrosarcoma were treated with en-bloc resection, while the patient with synovial sarcoma underwent intra-lesional excision and those with Ewing sarcoma received decompression and tumor debulking. Postoperative assessments revealed significant improvements in neurological conditions. Notably, functional status as measured by the Karnofski Performance Index (KPI), improved substantially post-surgery (from 61.4 to 80.0%) The mean follow-up was 34.9 ± 9.2 months. During this time period one patient experienced fatal bleeding after en-bloc resection complications involving the vena cava. None of the patient needed further surgery. CONCLUSIONS: Our 16-year study offers vital insights into managing primary spinal sarcomas, showcasing the effectiveness of surgical intervention, particularly en-bloc resection. Despite their rarity and complexity, our multidisciplinary treatment approach yields improved outcomes and highlights the potential for refined surgical strategies to become standardized care in this challenging domain.
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Sarcoma , Neoplasias da Coluna Vertebral , Humanos , Pessoa de Meia-Idade , Estudos Retrospectivos , Masculino , Feminino , Adulto , Sarcoma/cirurgia , Sarcoma/mortalidade , Neoplasias da Coluna Vertebral/cirurgia , Neoplasias da Coluna Vertebral/mortalidade , Resultado do Tratamento , Procedimentos Neurocirúrgicos/métodos , Idoso , Sarcoma Sinovial/cirurgia , Sarcoma Sinovial/mortalidade , Condrossarcoma/cirurgia , Condrossarcoma/mortalidade , Condrossarcoma/patologia , Sarcoma de Ewing/cirurgia , Sarcoma de Ewing/mortalidade , Complicações Pós-Operatórias/etiologia , Equipe de Assistência ao PacienteRESUMO
BACKGROUND: Peripheral osteochondral tumors are common, and the management of tumors presenting in the pelvis is challenging and a controversial topic. Some have suggested that cartilage cap thickness may indicate malignant potential, but this supposition is not well validated. QUESTIONS/PURPOSES: (1) How accurate is preoperative biopsy in determining whether a peripheral cartilage tumor of the pelvis is benign or malignant? (2) Is the thickness of the cartilage cap as determined by MRI associated with the likelihood that a given peripheral cartilage tumor is malignant? (3) What is local recurrence-free survival (LRFS), metastasis-free survival (MFS), and disease-specific survival (DSS) in peripheral chondrosarcoma of the pelvis and is it associated with surgical margin? METHODS: Between 2005 and 2022, 289 patients had diagnoses of peripheral cartilage tumors of the pelvis (either pedunculated or sessile) and were treated at one tertiary sarcoma center (the Royal Orthopaedic Hospital, Birmingham, UK). These patients were identified retrospectively from a longitudinally maintained institutional database. Those whose tumors were asymptomatic and discovered incidentally and had cartilage caps ≤ 1.5 cm were discharged (95 patients), leaving 194 patients with tumors that were either symptomatic or had cartilage caps > 1.5 cm. Tumors that were asymptomatic and had a cartilage cap > 1.5 cm were followed with MRIs for 2 years and discharged without biopsy if the tumors did not grow or change in appearance (15 patients). Patients with symptomatic tumors that had cartilage caps ≤ 1.5 cm underwent removal without biopsy (63 patients). A total of 82 patients (63 with caps ≤ 1.5 cm and 19 with caps > 1.5 cm, whose treatment deviated from the routine at the time) had their tumors removed without biopsy. This left 97 patients who underwent biopsy before removal of peripheral cartilage tumors of the pelvis, and this was the group we used to answer research question 1. The thickness of the cartilage cap was recorded from MRI and measuring to the nearest millimeter, with measurements taken perpendicular in the plane that best allowed the greatest measurement. Patient survival rates were assessed using the Kaplan-Meier method with 95% confidence intervals as median observation times to estimate MFS, LRFS, and DSS. RESULTS: Of malignant tumors biopsied, in 49% (40 of 82), the biopsy result was recorded as benign (or was considered uncertain regarding malignancy). A malignant diagnosis was correctly reported in biopsy reports in 51% (42 of 82) of patients, and if biopsy samples with uncertainty regarding malignancy were excluded, the biopsy identified a lesion as being malignant in 84% (42 of 50) of patients. The biopsy results correlated with the final histologic grade as recorded from the resected specimen in only 33% (27 of 82) of patients. Among these 82 patients, 15 biopsies underestimated the final histologic grade. The median cartilage cap thickness for all benign osteochondromas was 0.5 cm (range 0.1 to 4.0 cm), and the median cartilage cap thickness for malignant peripheral chondrosarcomas was 8.0 cm (range 3.0 to 19 cm, difference of medians 7.5 cm; p < 0.01). LRFS was 49% (95% CI 35% to 63%) at 3 years for patients with malignant peripheral tumors with < 1-mm margins, and LRFS was 97% (95% CI 92% to 100%) for patients with malignant peripheral tumors with ≥ 1-mm margins (p < 0.01). DSS was 100% at 3 years for Grade 1 chondrosarcomas, 94% (95% CI 86% to 100%) at 3 years for Grade 2 chondrosarcomas, 73% (95% CI 47% to 99%) at 3 and 5 years for Grade 3 chondrosarcomas, and 20% (95% CI 0% to 55%) at 3 and 5 years for dedifferentiated chondrosarcomas (p < 0.01). DSS was 87% (95% CI 78% to 96%) at 3 years for patients with malignant peripheral tumors with < 1-mm margin, and DSS was 100% at 3 years for patients with malignant peripheral tumors with ≥ 1-mm margins (p = 0.01). CONCLUSION: A thin cartilage cap (< 3 cm) is characteristic of benign osteochondroma. The likelihood of a cartilage tumor being malignant increases after the cartilage cap thickness exceeds 3 cm. In our experience, preoperative biopsy results were not reliably associated with the final histologic grade or malignancy, being accurate in only 33% of patients. We therefore recommend observation for 2 years for patients with pelvic osteochondromas in which the cap thickness is < 1.5 cm and there is no associated pain. For patients with tumors in which the cap thickness is 1.5 to 3 cm, we recommend either close observation for 2 years or resection, depending on the treating physician's decision. We recommend excision in patients whose pelvic osteochondromas show an increase in thickness or pain, preferably before the cartilage cap thickness is 3 cm. We propose that surgical resection of peripheral cartilage tumors in which the cartilage cap exceeds 3 cm (aiming for clear margins) is reasonable without preoperative biopsy; the role of preoperative biopsy is less helpful because radiologic measurement of the cartilage cap thickness appears to be accurately associated with malignancy. Biopsy might be helpful in patients in whom there is diagnostic uncertainty or when confirming the necessity of extensive surgical procedures. Future studies should evaluate other preoperative tumor qualities in differentiating malignant peripheral cartilage tumors from benign tumors. LEVEL OF EVIDENCE: Level III, diagnostic study.
Assuntos
Neoplasias Ósseas , Condrossarcoma , Imageamento por Ressonância Magnética , Humanos , Feminino , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto , Neoplasias Ósseas/patologia , Neoplasias Ósseas/diagnóstico por imagem , Neoplasias Ósseas/cirurgia , Condrossarcoma/patologia , Condrossarcoma/cirurgia , Condrossarcoma/diagnóstico por imagem , Condrossarcoma/mortalidade , Biópsia , Idoso , Ossos Pélvicos/diagnóstico por imagem , Ossos Pélvicos/patologia , Ossos Pélvicos/cirurgia , Valor Preditivo dos Testes , Medição de Risco , Adulto Jovem , Fatores de Risco , Margens de Excisão , Adolescente , Cuidados Pré-Operatórios , Intervalo Livre de DoençaRESUMO
BACKGROUND: While distant metastases in primary bone sarcomas have been extensively studied, the impact of isolated regional lymph node (LN) metastasis on survival remains unknown. In patients with primary bone sarcomas, we sought to assess the prevalence of isolated regional LN metastasis and the survival of this population. METHODS: A total of 6651 patients with histologically-confirmed high-grade osteosarcoma, Ewing sarcoma, or chondrosarcoma were retrieved from the SEER database. We defined four subgroups for our analysis: localized disease (N0 M0), isolated regional LN metastasis (N1 M0), isolated distant metastasis (N0 M1), and combined regional LN and distant metastasis (N1 M1). Disease-specific survival (DSS) was assessed using the Kaplan-Meier method. RESULTS: Prevalence of isolated regional LN metastasis (N1 M0) was highest in Ewing sarcoma (27/1097; 3.3 %), followed by chondrosarcoma (18/1702; 1.4 %) and osteosarcoma (26/3740; 0.9 %). In all three histologies, patients with isolated regional LN metastasis had a worse 2-year, 5-year, and 10-year DSS than those with localized disease. Chondrosarcoma patients with isolated regional LN (N1 M0) metastasis had a significantly higher DSS in comparison to those with only distant metastasis (N0 M1) at the 5- and 10-year marks; for osteosarcoma and Ewing sarcoma, only a pattern towards higher survival was seen. Risk factors for presenting isolated regional LN metastasis included tumor location in lower-limb (OR = 2.01) or pelvis (OR = 2.49), diagnosis of Ewing sarcoma (OR = 2.98), and tumor >10 cm (OR = 1.96). CONCLUSIONS: Isolated regional LN metastases in primary bone sarcomas is an infrequent presentation associated with worse survival than localized disease. LEVEL OF EVIDENCE: III.
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Neoplasias Ósseas , Condrossarcoma , Metástase Linfática , Osteossarcoma , Programa de SEER , Sarcoma de Ewing , Humanos , Neoplasias Ósseas/secundário , Neoplasias Ósseas/mortalidade , Neoplasias Ósseas/epidemiologia , Masculino , Feminino , Condrossarcoma/patologia , Condrossarcoma/mortalidade , Condrossarcoma/epidemiologia , Osteossarcoma/mortalidade , Osteossarcoma/patologia , Osteossarcoma/terapia , Sarcoma de Ewing/mortalidade , Sarcoma de Ewing/patologia , Adulto , Estados Unidos/epidemiologia , Incidência , Pessoa de Meia-Idade , Taxa de Sobrevida , Adolescente , Adulto Jovem , Gradação de Tumores , Criança , Estudos de Coortes , Linfonodos/patologia , IdosoRESUMO
OBJECTIVE: To highlight various patient, tumor, diagnostic, and treatment characteristics of laryngeal chondrosarcoma (LC) as well as elucidate factors that may independently affect overall survival (OS) for LCs. STUDY DESIGN: Retrospective cohort study. SETTING: National Cancer Database (NCDB). METHODS: All LC cases from 2004 to 2016 were extracted from the NCDB. Several demographic, diagnostic, and treatment variables were compared between LC subgroups using χ2 and analysis of variance tests. Univariate and multivariate survival analyses were performed for LCs using univariate Kaplan-Meier analysis and Cox proportional hazards regression models. RESULTS: There were 348 LCs included in the main cohort. LCs were predominantly non-Hispanic white males with similar rates of private and government insurance (49.4% vs 45.4%). Most LCs (81.6%) underwent primary surgery, particularly partial and total laryngectomy. The 1-, 5-, and 10-year survivals for LC were 95.7%, 88.2%, and 66.3%, respectively. On multivariate analysis, lack of insurance (P = .019; hazard ratio [HR], 8.21; 95% CI, 1.40-48.03), high grade (P = .001; HR, 13.51; 95% CI, 3.08-59.26), and myxoid/dedifferentiated histological subtypes (P = .0111; HR, 10.74; 95% CI, 1.71-67.33) correlated with worse OS. No difference in OS was found between partial and total laryngectomy. CONCLUSION: This is the first multivariate survival analysis and largest single cohort study of LCs in the literature. Overall, LCs enjoy an excellent prognosis, with insurance status, grade, and histology as the main predictors of survival.
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Condrossarcoma/mortalidade , Neoplasias Laríngeas/mortalidade , Idoso , Condrossarcoma/patologia , Condrossarcoma/terapia , Terapia Combinada , Bases de Dados Factuais , Feminino , Humanos , Neoplasias Laríngeas/patologia , Neoplasias Laríngeas/terapia , Laringectomia , Masculino , Margens de Excisão , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Estudos Retrospectivos , Fatores Socioeconômicos , Análise de Sobrevida , Taxa de Sobrevida , Estados UnidosRESUMO
AIM: This study presents an analysis (efficacy and toxicity) of outcomes in patients with skull-base chordomas or chondrosarcomas treated with a fixed horizontal pencil proton beam. BACKGROUND: Chordomas (CAs) and chondrosarcomas (CSAs) are rare tumours that are usually located near the base of the skull and very close to the brain's most critical structures. Proton therapy (PT) is often considered the best radiation treatment for these diseases, but it is still a limited resource. Active scanning PT delivered via a fixed pencil beamline might be a promising option. METHODS: This is a single-centre experience describing the results of proton therapy for 31 patients with CA (n = 23) or CSA (n = 8) located near the base of the skull. Proton therapy was utilized by a fixed pencil beamline with a chair to position the patient between May 2016 and November 2020. Ten patients underwent resection (32.2%), 15 patients (48.4%) underwent R2 resection, and 6 patients had unresectable tumours (19.4%). In 4 cases, the tumours had been previously irradiated. The median PT dose was 70 GyRBE (relative biological efficacy, 1.1) [range, 60 to 74] with 2.0 GyRBE per fraction. The mean GTV volume was 25.6 cm3 [range, 4.2-115.6]. Patient demographics, pathology, treatment parameters, and toxicity were collected and analysed. Radiation-induced reactions were assessed according to the Common Terminology Criteria for Adverse Events (CTCAE) v 4.0. RESULTS: The median follow-up time was 21 months [range, 4 to 52]. The median overall survival (OS) was 40 months. The 1- and 2-year OS was 100%, and the 3-year OS was 66.3%. Four patients died due to non-cancer-related reasons, 1 patient died due to tumour progression, and 1 patient died due to treatment-related injuries. The 1-year local control (LC) rate was 100%, the 2-year LC rate was 93.7%, and the 3-year LC rate was 85.3%. Two patients with CSA exhibited progression in the neck lymph nodes and lungs. All patients tolerated PT well without any treatment interruptions. We observed 2 cases of ≥ grade 3 toxicity, with 1 case of grade 3 myelitis and 1 case of grade 5 brainstem injury. CONCLUSION: Treatment with a fixed proton beam shows promising disease control and an acceptable toxicity rate, even the difficult-to-treat subpopulation of patients with skull-base chordomas or chondrosarcomas requiring dose escalation.
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Condrossarcoma/radioterapia , Cordoma/radioterapia , Terapia com Prótons/métodos , Neoplasias da Base do Crânio/radioterapia , Adulto , Idoso , Condrossarcoma/mortalidade , Cordoma/mortalidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Órgãos em Risco , Terapia com Prótons/efeitos adversos , Dosagem Radioterapêutica , Radioterapia de Intensidade Modulada , Neoplasias da Base do Crânio/mortalidadeRESUMO
AIMS: Controversy exists as to what should be considered a safe resection margin to minimize local recurrence in high-grade pelvic chondrosarcomas (CS). The aim of this study is to quantify what is a safe margin of resection for high-grade CS of the pelvis. METHODS: We retrospectively identified 105 non-metastatic patients with high-grade pelvic CS of bone who underwent surgery (limb salvage/amputations) between 2000 and 2018. There were 82 (78%) male and 23 (22%) female patients with a mean age of 55 years (26 to 84). The majority of the patients underwent limb salvage surgery (n = 82; 78%) compared to 23 (22%) who had amputation. In total, 66 (64%) patients were grade 2 CS compared to 38 (36%) grade 3 CS. All patients were assessed for stage, pelvic anatomical classification, type of resection and reconstruction, margin status, local recurrence, distant recurrence, and overall survival. Surgical margins were stratified into millimetres: < 1 mm; > 1 mm but < 2 mm; and > 2 mm. RESULTS: The disease--specific survival (DSS) at five years was 69% (95% confidence interval (CI) 56% to 81%) and 51% (95% CI 31% to 70%) for grade 2 and 3 CS, respectively (p = 0.092). The local recurrence-free survival (LRFS) at five years was 59% (95% CI 45% to 72%) for grade 2 CS and 42% (95% CI 21% to 63%) for grade 3 CS (p = 0.318). A margin of more than 2 mm was a significant predictor of increased LRFS (p = 0.001). There was a tendency, but without statistical significance, for a > 2 mm margin to be a predictor of improved DSS. Local recurrence (LR) was a highly significant predictor of DSS, analyzed in a competing risk model (p = 0.001). CONCLUSION: Obtaining wide margins in the pelvis remains challenging for high-grade pelvic CS. On the basis of our study, we conclude that it is necessary to achieve at least a 2 mm margin for optimal oncological outcomes in patients with high-grade CS of the pelvis. Cite this article: Bone Joint J 2021;103-B(6):1150-1154.
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Condrossarcoma/cirurgia , Margens de Excisão , Ossos Pélvicos/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Condrossarcoma/mortalidade , Condrossarcoma/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Recidiva Local de Neoplasia/prevenção & controle , Ossos Pélvicos/patologia , Estudos Retrospectivos , Taxa de SobrevidaRESUMO
INTRODUCTION: IDH1/2 mutations are prevalent in cartilaginous tumors including chondrosarcoma. This meta-analysis using individual patient data (IPD) aimed to investigate the clinical and prognostic association of these mutations in chondrosarcoma patients. METHODS: Two electronic databases including PubMed and Web of Science were searched for relevant data. We included studies providing IPD of chondrosarcoma with available IDH1/2 mutational status for meta-analysis. Chi-square and t-test were performed to compare the groups with and without IDH1/2 mutations. For survival analysis, log-rank test, and Cox proportional hazards model were used to investigate the association of IDH mutations with patient outcomes. RESULTS: Fourteen studies with 488 patients were analyzed. IDH1 and IDH2 mutations were detected in 38.7% and 12.1% of cases, respectively. IDH1/2 mutations were significantly associated with an older age (p = 0.003), tumor origins (p < 0.001), tumor grades (p < 0.001), larger diameter (p = 0.003), relapse (p = 0.014), and patient mortality (p = 0.04). Multivariate Cox regression analysis adjusted for age, gender, tumor grade, and tumor sites confirmed the negative impact of IDH1/2 mutations on patient overall survival (HR = 1.90; 95% CI = 1.06-3.42; p = 0.03). CONCLUSION: Our meta-analysis demonstrated the distinct characteristics of IDH1/2-mutated chondrosarcomas in comparison to those without mutations. These mutations could serve as an independent prognostic biomarker to better prognosticate patient outcomes and design appropriate treatment plans.
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Neoplasias Ósseas/genética , Condrossarcoma/genética , Isocitrato Desidrogenase/genética , Mutação , Fatores Etários , Idoso , Neoplasias Ósseas/mortalidade , Neoplasias Ósseas/patologia , Condrossarcoma/mortalidade , Condrossarcoma/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Fatores Sexuais , Carga Tumoral/genéticaRESUMO
INTRODUCTION: The role of chemotherapy for patients with dedifferentiated chondrosarcoma (DDCS) is still under discussion. Here, we present the outcome in patients with DDCS treated with intensive chemotherapy from the EUROpean Bone Over 40 Sarcoma Study. MATERIALS AND METHODS: The chemotherapy regimen included doxorubicin, ifosfamide and cisplatin. Postoperative methotrexate was added in case of poor histological response. Toxicity was graded based on the National Cancer Institute expanded common toxicity criteria, version 2.0, and survival was analysed using Kaplan-Meier curves, log-rank tests and univariate Cox regression models. RESULTS: Fifty-seven patients with DDCS (localised, 34 [60%]; metastatic, 23 [40%]) aged 42-65 years were included. Surgical complete remission (SCR) was achieved in 36 (63%) patients. The median overall survival (OS) was 24 months (95% confidence interval, 22-25), and the 5-year OS was 39%. Patients with extremity localisation had a 5-year OS of 49% compared with 29% in patients with a central tumour (P = 0.08). Patients with localised disease had a 5-year OS of 46%, whereas patients with metastatic disease had a 5-year OS of 29% (P = 0.12). Patients in SCR had a 5-year OS of 49%, whereas patients not in SCR had a 5-year OS of 23% (P = 0.004). Chemotherapy toxicity was considerable but manageable. There was no treatment-related death, and 39 (70%) patients received ≥6 cycles of the planned nine chemotherapy cycles. CONCLUSIONS: Adding intensive chemotherapy to surgery for treatment of DDCS is feasible and shows favourable survival data compared with previous reports. With the limitations of data from a non-controlled trial, we conclude that chemotherapy could be considered in the management of patients aged >40 years.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Ósseas/terapia , Desdiferenciação Celular , Condrossarcoma/terapia , Terapia Neoadjuvante , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias Ósseas/mortalidade , Neoplasias Ósseas/patologia , Quimioterapia Adjuvante , Condrossarcoma/mortalidade , Condrossarcoma/secundário , Intervalo Livre de Doença , Europa (Continente) , Estudos de Viabilidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante/efeitos adversos , Terapia Neoadjuvante/mortalidade , Estudos Prospectivos , Fatores de TempoRESUMO
INTRODUCTION: We aimed to develop and validate a nomogram for predicting the overall survival of patients with limb chondrosarcomas. METHODS: The Surveillance, Epidemiology, and End Results (SEER) program database was used to identify patients diagnosed with chondrosarcomas, from which data was extracted from 18 registries in the United States between 1973 and 2016. A total of 813 patients were selected from the database. Univariate and multivariate analyses were performed using Cox proportional hazards regression models on the training group to identify independent prognostic factors and construct a nomogram to predict the 3- and 5-year survival probability of patients with limb chondrosarcomas. The predictive values were compared using concordance indexes (C-indexes) and calibration plots. RESULTS: All 813 patients were randomly divided into a training group (n = 572) and a validation group (n = 241). After univariate and multivariate Cox regression, a nomogram was constructed based on a new model containing the predictive variables of age, site, grade, tumor size, histology, stage, and use of surgery, radiotherapy, or chemotherapy. The prediction model provided excellent C-indexes (0.86 and 0.77 in the training and validation groups, respectively). The good discrimination and calibration of the nomograms were demonstrated for both the training and validation groups. CONCLUSIONS: The nomograms precisely and individually predict the overall survival of patients with limb chondrosarcomas and could assist personalized prognostic evaluation and individualized clinical decision-making.
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Neoplasias Ósseas/mortalidade , Condrossarcoma/mortalidade , Extremidades , Nomogramas , Adulto , Condrossarcoma/patologia , Tomada de Decisão Clínica , Extremidades/patologia , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Prognóstico , Análise de Sobrevida , Estados Unidos/epidemiologiaRESUMO
BACKGROUND: This multi-cohort trial explored the efficacy and safety of regorafenib for patients with advanced sarcomas of bone origin; this report details the cohort of patients with metastatic or locally advanced chondrosarcoma (CS), progressing after prior chemotherapy. PATIENTS AND METHODS: Patients with CS, progressing despite prior standard therapy, were randomised (2:1) to receive regorafenib or placebo. Patients on placebo could crossover to receive regorafenib after centrally confirmed progressive disease. The primary endpoint was progression-free rate (PFR) at 12 weeks. With one-sided α of 0.05, and 80% power, at least 16/24 progression-free patients at 12 weeks were needed for success (P0 = 50%, P1 = 75%). RESULTS: From September 2014 to February 2019, 46 patients were included in the CS cohort, and 40 patients were evaluable for efficacy: 16 on placebo and 24 on regorafenib. Thirteen patients (54.2%; 95% CI [35.8%-[) were non-progressive at 12 weeks on regorafenib versus 5 (31.3%; 95% CI [13.2%-[);) on placebo. Median PFS was 19.9 weeks on regorafenib, and 8.0 on placebo. Fourteen placebo patients crossed over to regorafenib after progression. The most common grade ≥3 treatment-related adverse events on regorafenib included hypertension (12%), asthenia (8%), thrombocytopenia (8%) and diarrhoea (8%). One episode of fatal liver dysfunction occurred on regorafenib. CONCLUSION: Although the primary endpoint was not met statistically in this small randomised cohort, there is modest evidence to suggest that regorafenib might slow disease progression in patients with metastatic CS after the failure of prior chemotherapy. CLINICAL TRIAL REGISTRATION: The trial is registered at ClinicalTrials.gov (NCT02389244).
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Antineoplásicos/uso terapêutico , Neoplasias Ósseas/tratamento farmacológico , Condrossarcoma/tratamento farmacológico , Compostos de Fenilureia/uso terapêutico , Piridinas/uso terapêutico , Adulto , Idoso , Antineoplásicos/efeitos adversos , Neoplasias Ósseas/mortalidade , Neoplasias Ósseas/patologia , Condrossarcoma/mortalidade , Condrossarcoma/secundário , Progressão da Doença , Método Duplo-Cego , Feminino , França , Humanos , Masculino , Pessoa de Meia-Idade , Compostos de Fenilureia/efeitos adversos , Intervalo Livre de Progressão , Piridinas/efeitos adversos , Fatores de TempoRESUMO
The purpose of this systematic review was to summarize the available data on TMJ chondrosarcomas and to perform a survival analysis of cases reported to date. This review was conducted in accordance with the PRISMA. Two authors performed an electronic search of case reports of TMJ chondrosarcoma published until August 02, 2020. Forty-seven studies reporting 53 cases were included. Chondrosarcomas of the TMJ were more prevalent in women, with a male:female ratio of 1:1.4. Survival curves were significantly associated with histological diagnosis (p = 0.004), reconstructive surgery (p = 0.024), recurrence (p < 0.001), and distant metastasis (p = 0.001). Only distant metastasis was independently associated with survival (p = 0.017). TMJ chondrosarcomas presented with low recurrence and higher survival rates than other chondrosarcomas. Synovial subtype, absence of reconstructive surgery, and presence of local recurrence or distant metastasis were associated with poorer prognosis.
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Condrossarcoma/mortalidade , Condrossarcoma/patologia , Transtornos da Articulação Temporomandibular/mortalidade , Transtornos da Articulação Temporomandibular/patologia , Adolescente , Adulto , Idoso , Criança , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise de Sobrevida , Adulto JovemRESUMO
Overcoming the radiosensitivity of chondrosarcoma (CS), the second most common primary bone tumor, is needed. Radioresistance is attributed to cancer stem cells (CSCs) in many malignancies. Disulfiram (DSF), an FDA-approved anti-alcoholism drug, complexed with Cu (DSF/Cu) can radiosensitize epithelial CSCs. This prompted us to investigate the radiosensitizing effect of DSF/Cu on CS CSCs (CCSCs). The radiosensitizing effects of DSF/Cu on CCSCs were investigated in vitro using cell lines SW1353 and CS-1. Stemness was identified independently by flow cytometry for CCSCs (ALDH+CD133+), sphere-forming ability, and Western blot analysis of stemness gene protein expression. The radiosensitizing effect of DSF/Cu was studied in an orthotopic CS xenograft mouse model by analyzing xenograft growth and residual xenografts for stemness. CCSCs were found to be resistant to single-dose (IR) and fractionated irradiation (FIR). IR and FIR increased CS stemness. Combined with DSF/Cu in vitro and in vivo, IR and FIR eliminated CS stemness. RT + DSF/Cu was safer and more effective than either RT ± DSF in inhibiting growth of orthotopic CS xenografts. In conclusion, DSF/Cu radiosensitizes CCSCs. These results can be translated into clinical trials for CS patients requiring RT for improved outcomes.
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Neoplasias Ósseas/radioterapia , Condrossarcoma/radioterapia , Cobre/farmacologia , Dissulfiram/farmacologia , Células-Tronco Neoplásicas/efeitos dos fármacos , Radiossensibilizantes/farmacologia , Antígeno AC133/análise , Aldeído Desidrogenase/análise , Animais , Neoplasias Ósseas/mortalidade , Neoplasias Ósseas/patologia , Linhagem Celular Tumoral , Condrossarcoma/mortalidade , Condrossarcoma/patologia , Fracionamento da Dose de Radiação , Feminino , Humanos , Camundongos , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
INTRODUCTION: Primary chest wall sarcoma is a rare entity. It can be classified based on its origin, as bone sarcomas or soft tissue sarcomas. Various prognostic factors have been studied in different case series like age, sex, tumor histology, grade, resection margin status, adjuvant treatment, and others. The present study aimed to analyze common histological types, their management by resection and reconstruction and prognosis, in cases presenting at a regional cancer center in western India. MATERIAL AND METHOD: This was an observational study from a prospectively maintained database. 57 patients with chest wall sarcoma treated with curative intent between January 2016 till January 2019 with a minimum follow-up of 3 months were included in the study. The goals of surgical treatment were to obtain a wide resection margin of 3-4 cm, preserve the function of the chest wall and provide stability and rigidity to protect intrathoracic organs. RESULTS: The median follow-up of the present patient's cohort was for 20.2 months. Overall two-year survival was 74.7%. Two-year OS and DFS of bone sarcoma were 62.3% and 35% and soft tissue sarcomas were 91% and 71.3%. Ewing's sarcoma had the worst two-year overall survival of 50.6% and chondrosarcoma and fibromatosis had 100% two-year overall survival. CONCLUSION: Chest wall sarcoma forms a heterogeneous group of tumors. In the present study, Ewing's sarcoma was the most common histology with the worst survival, since they presented in advanced stages. Management should be multidisciplinary and surgical resection should be aggressive to achieve an R0 resection. Reconstruction of chest wall should aim to provide structural and functional stability with minimal morbidity. Frozen section assessment should be utilized whenever in doubt.
Assuntos
Neoplasias Ósseas/diagnóstico , Condrossarcoma/diagnóstico , Sarcoma de Ewing/diagnóstico , Parede Torácica/patologia , Adolescente , Adulto , Idoso , Neoplasias Ósseas/mortalidade , Neoplasias Ósseas/patologia , Neoplasias Ósseas/cirurgia , Criança , Pré-Escolar , Condrossarcoma/mortalidade , Condrossarcoma/patologia , Condrossarcoma/cirurgia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Estudos Retrospectivos , Sarcoma de Ewing/mortalidade , Sarcoma de Ewing/patologia , Sarcoma de Ewing/cirurgia , Parede Torácica/diagnóstico por imagem , Parede Torácica/cirurgia , Tomografia Computadorizada por Raios X , Adulto JovemRESUMO
Currently, there is no gold standard treatment for Extraskeletal Myxoid Chondrosarcomas (EMC) making wide margin surgical resection the most effective alternative treatment. Nevertheless, in previous preclinical studies our lab demonstrated the potential of the hypoxia-activated prodrug (HAP) ICF05016 on EMC murine model inoculated with the H-EMC-SS human cell line. The aim of this study was to assess, in vivo, the relevance of the combination of this HAP with External Beam Radiotherapy (EBR). Firstly EMC-bearing mice were treated with 6 Gy or 12 Gy of EBR (single 6 MV photon). Then for combination of HAP and EBR, animals received 6 doses of ICF05016 (46.8 µmol/kg, intravenously) at 4-day intervals, with 6 Gy EBR performed 24 h after the 3rd dose of HAP. Animals were monitored throughout the study for clinical observations (tumour growth, side effects) and survival studies were performed. From tumour samples, PCNA, Ki-67 and p21 expressions were used as markers of proliferation and cell cycle arrest. Statistical significances were determined using Kruskall-Wallis and log rank tests. The radiosensitivity of the EMC model was demonstrated at 12 Gy with significant inhibition of tumour growth. Then, the HAP strategy potentiated EBR efficacy at a lower dose (6 Gy) by improving survival without generating side effects. Thus, results of this study showed the potential interest of ICF05016 for the combination with EBR in the management of EMC.
Assuntos
Quimiorradioterapia/métodos , Condrossarcoma/terapia , Imidazóis/administração & dosagem , Neoplasias de Tecido Conjuntivo e de Tecidos Moles/terapia , Pró-Fármacos/administração & dosagem , Animais , Linhagem Celular , Quimiorradioterapia/efeitos adversos , Condrossarcoma/mortalidade , Modelos Animais de Doenças , Feminino , Humanos , Camundongos , Camundongos SCID , Neoplasias de Tecido Conjuntivo e de Tecidos Moles/mortalidade , Doses de Radiação , Carga TumoralRESUMO
OBJECTIVE: The aim of this study was to examine the survival rate of patients with different bone sarcomas and to investigate homogenous and heterogenous prognostic factors for different types of bone sarcomas. METHODS: This is a retrospective analysis of records from the Surveillance, Epidemiology, and End Result (SEER) database. Clear information on the distant metastasis of cancer is provided in the SEER database for patients diagnosed between January 2010 and December 2016. Data for the four types of malignant bone sarcomas were extracted, including osteosarcoma, chondrosarcoma, Ewing sarcoma, and chordoma. Patients with bone sarcomas originated from other sites, diagnosed at autopsy, or indicated in death certification were excluded. The overall survival was calculated for the entire cohort and across different bone sarcomas using the Kaplan-Meier method. A subgroup analysis of the different survival rates of four types of bone sarcomas in various levels of each variable was conducted and the differences were tested with the log-rank test. Cox proportional hazard regression analysis was performed to determine the prognostic factors. Variables with P < 0.05 in the univariate Cox regression analysis were further analyzed using a multivariate Cox regression analysis. The prognostic factors in four groups of bone sarcomas were compared to determine the homogenous and heterogenous factors. RESULTS: A total of 4732 patients were included with a follow up of 25 (0-83) months. The mean age of patients was 39.7 ± 24.1 years. The 1-year, 3-year, and 5-year overall survival rate for the entire cohort was 86.2% (95% confidence interval [CI]: 85.2%-87.2%), 70.5% (95% CI: 68.9%-72.1%), and 63.0% (95% CI: 61.2%-64.8%), respectively. Factors including age older than 40 years, higher grade, regional and distant stage, tumor in the extremities, T2 stage, bone and lung metastases, and non-surgery were significantly associated with the poor survival of the entire cohort. The mean overall survival duration of patients with chordoma, chondrosarcoma, Ewing sarcoma, and osteosarcoma was 66.86 (95% CI: 64.06-69.66), 63.53 (95% CI: 61.81-65.25), 58.06 (95% CI: 55.49-60.62) and 54.91 (95% CI: 53.14-56.69) months, respectively. Compared with chordoma, the hazard ratio (HR) and 95% CI for patients with chondrosarcoma, Ewing sarcoma, and osteosarcoma were 1.30 (95% CI: 1.04-1.62; P = 0.023), 1.69 (95% CI: 1.33-2.14; P < 0.001), and 2.00 (95% CI: 1.61-2.48; P <0.001), respectively. Different bone sarcomas showed homogenous and heterogenous prognostic factors. CONCLUSION: Different clinicopathological characteristics and prognoses were revealed in patients with osteosarcoma, chondrosarcoma, Ewing sarcoma, and chordoma. The risk factors can potentially guide prognostic prediction and sarcoma-specific treatment.
Assuntos
Neoplasias Ósseas/mortalidade , Condrossarcoma/mortalidade , Osteossarcoma/mortalidade , Adolescente , Adulto , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Programa de SEER , Taxa de Sobrevida , Adulto JovemRESUMO
BACKGROUND: Despite combined modality treatment involving surgery and radiotherapy, a relevant proportion of skull-base chordoma and chondrosarcoma patients develop a local recurrence (LR). This study aims to analyze patterns of recurrence and correlate LR with a detailed dosimetric analysis. METHODS: 222 patients were treated with proton radiotherapy for chordoma (n = 151) and chondrosarcoma (n = 71) at the PSI between 1998 and 2012. All patients underwent surgery, followed by pencil-beam scanning proton therapy to a mean dose of 72.5 ± 2.2GyRBE. A retrospective patterns of recurrence analysis was performed: LR were contoured on follow-up MRI, registered with planning-imaging and the overlap with initial target structures (GTV, PTVhigh-dose, PTVlow-dose) was calculated. DVH parameters of planning structures and recurrences were calculated and correlated with LR using univariate and multivariate cox regression. RESULTS: After a median follow-up of 50 months, 35 (16%) LR were observed. Follow-up MRI imaging was available for 27 (77%) of these recurring patients. Only one (3.7%) recurrence was located completely outside the initial PTV (surgical pathway recurrence). The mean proportions of LR covered by the initial target structures were 48% (range 0-86%) for the GTV, 70% (range 0-100%) for PTVhigh and 83% (range 0-100%) for PTVlow. In the univariate analysis, the following DVH parameters were significantly associated with LR: GTV(V < 66GyRBE, p = 0.01), GTV(volume, p = 0.02), PTVhigh(max, p = 0.02), PTVhigh(V < 66GyRBE, p = 0.03), PTVhigh(V < 59GyRBE, p = 0.02), PTVhigh(volume, p = 0.01) and GTV(D95, p = 0.05). In the multivariate analysis, only histology (chordoma vs. chondrosarcoma, p = 0.01), PTVhigh(volume, p = 0.05) and GTV(V < 66GyRBE, p = 0.02) were independent prognostic factors for LR. CONCLUSION: This study identified DVH parameters, which are associated with the risk of local recurrence after proton therapy using pencil-beam scanning for patients with skull-base chordoma and chondrosarcoma.
Assuntos
Condrossarcoma/radioterapia , Cordoma/radioterapia , Terapia com Prótons/métodos , Neoplasias da Base do Crânio/radioterapia , Adulto , Condrossarcoma/mortalidade , Cordoma/mortalidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Terapia com Prótons/efeitos adversos , Dosagem Radioterapêutica , Estudos Retrospectivos , Neoplasias da Base do Crânio/mortalidade , Falha de TratamentoRESUMO
AIMS: Our aim was to develop and validate nomograms that would predict the cumulative incidence of sarcoma-specific death (CISSD) and disease progression (CIDP) in patients with localized high-grade primary central and dedifferentiated chondrosarcoma. METHODS: The study population consisted of 391 patients from two international sarcoma centres (development cohort) who had undergone definitive surgery for a localized high-grade (histological grade II or III) conventional primary central chondrosarcoma or dedifferentiated chondrosarcoma. Disease progression captured the first event of either metastasis or local recurrence. An independent cohort of 221 patients from three additional hospitals was used for external validation. Two nomograms were internally and externally validated for discrimination (c-index) and calibration plot. RESULTS: In the development cohort, the CISSD at ten years was 32.9% (95% confidence interval (CI) 19.8% to 38.4%). Age at diagnosis, grade, and surgical margin were found to have significant effects on CISSD and CIDP in multivariate analyses. Maximum tumour diameter was also significantly associated with CISSD. In the development cohort, the c-indices for CISSD and CIDP at five years were 0.743 (95% CI 0.700 to 0.819) and 0.761 (95% CI 0.713 to 0.800), respectively. When applied to the validation cohort, the c-indices for CISSD and CIDP at five years were 0.839 (95% CI 0.763 to 0.916) and 0.749 (95% CI 0.672 to 0.825), respectively. The calibration plots for these two nomograms demonstrated good fit. CONCLUSION: Our nomograms performed well on internal and external validation and can be used to predict CISSD and CIDP after resection of localized high-grade conventional primary central and dedifferentiated chondrosarcomas. They provide a new tool with which clinicians can assess and advise individual patients about their prognosis. Cite this article: Bone Joint J 2020;102-B(12):1752-1759.
Assuntos
Neoplasias Ósseas/cirurgia , Condrossarcoma/cirurgia , Nomogramas , Adulto , Idoso , Neoplasias Ósseas/mortalidade , Neoplasias Ósseas/patologia , Condrossarcoma/mortalidade , Condrossarcoma/patologia , Progressão da Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Estudos Retrospectivos , Análise de SobrevidaRESUMO
BACKGROUND AND OBJECTIVES: Malignant tumors of the calcaneus are rare but pose a treatment challenge. AIMS: (1) describe the demographics of calcaneal malignancies in a large cohort; (2) describe survival after amputation versus limb-salvage surgery for high-grade tumors. METHODS: Study group: a "pooled" cohort of patients with primary calcaneal malignancies treated at two cancer centers (1984-2015) and systematic literature review. Kaplan-Meier analyses described survival across treatment and diagnostic groups; proportional hazards modeling assessed mortality after amputation versus limb salvage. RESULTS: A total of 131 patients (11 treated at our centers and 120 patients from 53 published studies) with a median 36-month follow-up were included. Diagnoses included Ewing sarcoma (41%), osteosarcoma (30%), and chondrosarcoma (17%); 5-year survival rates were 43%, 73% (70%, high grade only), and 84% (60%, high grade only), respectively. Treatment involved amputation in 52%, limb salvage in 27%, and no surgery in 21%. There was no difference in mortality following limb salvage surgery (vs. amputation) for high-grade tumors (HR 0.38; 95% CI 0.14-1.05), after adjusting for Ewing sarcoma diagnosis (HR 5.15; 95% CI 1.55-17.14), metastatic disease at diagnosis (HR 3.88; 95% CI 1.29-11.64), and age (per-year HR 1.04; 95% CI 1.02-1.07). CONCLUSIONS: Limb salvage is oncologically-feasible for calcaneal malignancies.