The purpose of this study is to build an effective and predictive model for clinicians and patients based on existing studies on ES, as a tool for personalized and accurate medical treatment of patients.Many previous studies have shown that age, tumor volume, metastasis, axial tumor and other factors are risk factors affecting the prognosis of patients, among which tumor metastasis is an important factor affecting the survival of patients [13-16]. However, there is no internationally recognized risk classification scheme for ES patients.For clinicians, prognostic judgment is critical to guide treatment decisions and provide patients with more effective and systematic treatment.At present, the long-term survival rate of patients with non-metastatic disease ES has been increased from 10%~15% to 60%~70% through the application of various treatment methods such as surgery, radiotherapy and chemotherapy[17, 18]. However, as for the invasive behavior of ES, the most common site of first metastasis is lung (70-80%), followed by bone (40-45%). [19] Only 20% of the patients with METASTATIC ES have a good survival time [13, 20, 21]. Successful treatment of ES patients requires systemic chemotherapy combined with surgery or radiation therapy, or both, in order to achieve local tumor control [22]. The prognosis depends on the size and location of the tumor, presence or absence of metastasis, tumor response to treatment, age, and disease recurrence, with patients with distant metastasis having the worst prognosis [22]. Therefore, prognostic tools are urgently needed to accurately predict the risk of ES metastasis and patient survival.Nomogram is a widely used tool today to predict the occurrence of specific events and to estimate the prognosis in medicine. It is able to generate individualized probabilities of clinical events by integrating different predictive variables. The advantages of visualization and quantification are also practical in clinical practice.
The authors of this study used prior studies and data analysis to identify several independent prognostic factors for ES patients, and established two Nomograms to effectively and intuitively predict tumor metastasis risk and survival.The model includes not only systematic demographic data, but also pathological staging, surgical treatment, and other clinical parameters readily available in clinical practice.As a source of data, the SEER database includes 18 different regions, representing 26% of the U.S. population and reflecting the racial, economic, and social diversity of the United States, of great value [13, 23].
In this study, most of the patients were younger than 30 years old, accounting for about 70% in the training and verification set, which was also consistent with the prone age of ES patients in previous studies [20]. Although THE incidence of ES is the highest in the population under 30 years old, the younger the age of onset, the better the prognosis, and the higher the age of onset, the worse the prognosis [21, 24]. This is also consistent with the results of this study (Figure 3). The older the patient is, the worse the prognosis will be.But given that older patients have more diseases, including diabetes, high blood pressure and other cancers, and are less tolerant to treatment, clinicians tend to choose more conservative treatment strategies [25]. Age also has an effect on ES metastasis.One study showed that the sites of primary and metastatic tumors varied significantly with age [26]. Whether the presence of metastases is related to the size of the tumor is a controversial topic, and the results of this study suggest that larger tumors are associated with a higher risk of metastasis.But further research into the mechanism is needed.Table 1 shows that the majority of patients are white, which is the same proportion as the population structure of the United States.When kaplan-Meier survival analysis was performed for RACES (Figure 3, RACE), it showed its P<0.05, and visually showed that the curve of each species had no obvious differentiation degree, so the human species in this study had no significant influence on the prognosis of ES patients.
Both of the most commonly used staging systems for Ewing's osteosarcoma are designed for bone tumors.The first was created by Enneking in 1980 [27]. The second was created by the American Joint Committee on Cancer (AJCC) based on its systematic classification of cancers, which relies on TNM, tumor size, lymph nodes, and metastasis [28]. The biggest advantage of TNM staging lies in its simplicity and speed, but the biggest problem is that the prediction is not accurate enough, which is far from the expectation of clinicians. Combining the TNM staging system with demographic characteristics of patients and treatment and other factors to build a clinical prediction model can improve the accuracy of the prediction to a greater extent. The ES data in THE SEER database from 2004 to 2015 were more complete than the TNM staging data in the pre-2004 data. The TNM staging model included in this study is as easy to use as the TNM staging model, but more accurate than the TNM staging model alone.
The treatment of ES is multidisciplinary, including chemotherapy, surgery and radiation therapy.Surgery and radiation therapy play an important role in improving patients.However, with the increase of systemic chemotherapy, the survival rate has been greatly improved.Before systematic treatment, almost 80-90% of patients develop distant metastases, despite the use of aggressive local control measures and the option of more thorough radical surgery, such as amputation [29]. After chemotherapy for ES patients began in the 1960s, the combination regimen of vincristine, adriamycin, cyclophosphamide and actinomycin increased the survival rate of ES patients [30-32]. Some studies have found that the use of chemotherapy greatly improves the survival rate of patients with localized ES, from about 10% to 70%-80%[33]. ES is special compared to other common primary osteosarcomas because it is very sensitive to radiation [34, 35]. In the process of data analysis, radiotherapy and chemotherapy were considered as important treatment methods to include prognostic factors. However, there are no specific chemotherapy-specific regimens in the SEER database, only chemotherapy with (YES) and without (no/unknown).In the radiotherapy data, the author simplified the data into those who had received radiotherapy and those who had not received radiotherapy, because in the clinical practice, the detailed treatment data are very complex, and it is difficult to include all factors into the prognosis analysis in reality, so the researchers can only analyze these patients as a general population and make adjustments based on the actual situation.
Studies have reported that diameter & GT;The prognosis of 8cm ES is poor, and recurrent ES tumors are more likely to become larger than before no matter how they are measured and treated [21, 36]. Larger tumor volume and axial primary tumors may often be associated with metastatic disease, both of which have been shown to be risk factors for reduced survival [37-39]. In terms of surgical treatment, studies have shown that patients with primary ES undergoing surgical resection may have a higher survival rate [40]. For patients with metastatic ES, surgical treatment is also significant for the survival rate [41]. This is consistent with the results of this study, although the effect of tumor site and size on prognosis is complex. However, this study found that limited resection and radical resection had a limited impact on the survival rate of ES patients (Figure 3, surgery), which may be related to the clinician's choice of a more thorough surgical plan in the case of higher degree of tumor invasion.
The authors of this study, as surgeons, envisage a scenario for the clinical application of the model: the advantage of Nomogram's visual visualization in communicating with ES and explaining treatment options so that patients with no medical knowledge can better understand why doctors choose this treatment. For example, when communicating with a female ES patient over 60 years of age whose tumor is located in the spine and whose tumor is estimated to be larger than 10cm from imaging evidence, Nomogram can calculate that the 3-year survival rate is about 55% without surgical treatment, but more than 80% with surgical treatment. The ultimate goal of the clinical prediction model is to help clinicians make medical decisions and improve patient prognosis and cost.
The limitations of this study are as follows: 1. Even though the author randomly divided it into two data sets, one for modeling and one for validation, both data sets came from the SAME research center, SEER database. If the validation of the model can be further extended to the data set of another research center, the application value of the model will be greatly expanded.2. With the progress of imaging, more and more scholars realize the value of imaging. Using a large number of imaging parameters of color Doppler ultrasound, CT, MR and PET combined with clinical characteristics to construct the prediction model can further improve the accuracy of the prediction model. Unfortunately, imaging data is not included in the SEER database.3. Considering that this study is retrospective, some patient data will inevitably be lost. This may reduce the number of eligible cases and may lead to the risk of potential selection bias. Despite these limitations, Nomogram is an important and effective predictive model for accurate prediction of individual survival outcomes in ES patients.