Even though combining surgery with chemotherapy has significantly improved the prognosis of osteosarcoma patients, advanced, metastatic, or recurrent osteosarcomas are often non-responsive to chemotherapy, making development of novel efficient therapeutic methods an urgent need. Adoptive immunotherapy has the potential to be a useful non-surgical modality for treatment of osteosarcoma. Recently, alternative strategies, including immunotherapies using naturally occurring or genetically modified T cells, have been found to hold promise in the treatment of hematologic malignancies and solid tumors. In this review, we will discuss possible T-cell-based therapies against osteosarcoma with a special emphasis on combination strategies to improve the effectiveness of adoptive T cell transfer and, thus, to provide a rationale for the clinical development of immunotherapies.
Background Metastatic Ewing’s sarcoma (ES) of bone has a poor prognosis. Because there have been few previous studies on the prognostic factors and clinical outcome in patients with ES who have metastases at presentation, the aim of this study was to use the Surveillance, Epidemiology, and End Results (SEER) database to compare the clinical outcome following single and combined radiation treatment and surgery. Material/Methods The SEER database was used to identify patients with ES who presented with bone involvement and metastasis between 1973 to 2015. Prognostic analysis was performed using the Kaplan-Meier method and the Cox proportional hazards regression model. Results There were 643 patients identified from the SEER database. The 5-year overall survival (OS) and cancer-specific survival (CSS) rates were 33.1% and 34.3%, respectively and the median OS and CSS were 29.0±1.9 and 29.0±2.1 months, respectively. Multivariate analysis identified age <20 years and surgical resection of the primary tumor to be significantly associated with improved OS. Radiation therapy was not an independent predictor of OS or CSS. Radiation therapy alone resulted in a significantly reduced the OS and CSS compared with surgical resection alone. Combined surgery and radiation therapy of the primary tumor did not significantly improve the OS or CSS of patients with ES and metastatic disease when compared with surgery alone. Conclusions Age <20 years and surgical resection of the primary tumor were significantly associated with improved OS in patients with primary ES of bone who presented with metastasis.
Patients diagnosed with Ewing sarcoma (ES) usually experience poor outcomes. Accurate prediction of ES patients’ prognosis is essential to improve their survival. Given that ES is a relatively rare tumor with a low incidence, we aim at developing a prognostic nomogram of ES patients based on a large sample analysis. We used the Surveillance, Epidemiology, and End Results (SEER) database to screen eligible patients diagnosed ES of bone. This retrospective study presented the clinicopathological characteristics and prognosis of ES. We randomly assigned all ES patients to 2 sets (training set and validation set) with an equal number of patients. In order to identify independent factors of survival, we performed univariate and multivariate Cox analysis in the training set. Then, we constructed novel nomograms to predict survival of ES patients by integrating significant independent variables from the training set. The prognostic performance of constructed nomograms was examined using concordance index (C-index) and calibration curves in both training and validation set. We included a total of 988 eligible cases diagnosed ES of bone between 2000 and 2015. Age >18 years, distant metastasis, tumor size >10 cm, and no surgery were independent risk factors for poorer survival. Our survival prediction nomograms were established based on those 4 independent risk factors. Good calibration plots were achieved in internal and external validation. The internal validation C-indexes of the nomogram for overall survival (OS) and cancer-specific survival (CSS) were 0.733 and 0.737, respectively. Similar good results were also achieved in external validation setting. The established nomograms show good performance and allow for better evaluating the prognosis of ES patients and recommending appropriate instructions.
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