To our knowledge, this is the first study to establish Nomogram based on the SEER database to analyze the high risk of lung metastases in chondrosarcoma. According to a large population-based study, about 8% of patients with chondrosarcoma develop distant metastases [16]. Because the prognosis of patients with chondrosarcoma associated with PM is poor[17], it is necessary to identify some factors to identify the risk factors for patients with high risk of PM.[9, 18]。The results of this study showed that PM was more likely in patients with larger tumor size, lymphatic metastasis, married, malignant, male, and older age.
The present study found that larger tumors had a higher risk of PM. In univariate and multivariate logistic regression analysis, tumor volume was associated with PM risk, and THE OR value was 1.003, indicating that the risk of PM was 1.003 times higher for each 1 mm increase in tumor volume. The possible reason for this is that larger tumors indicate that the tumor is likely to grow for longer, increasing the likelihood of metastasis [19]. Relevant studies have shown that larger chondrosarcoma may represent a poorer survival expectation[18, 20, 21], and tumor size over 10 cm is an omen of poor prognosis[22], which is also consistent with the conclusion of this study. With regard to age at diagnosis, the study concluded that the older the person is at the time of diagnosis, the greater the risk of metastasis. The results of Logistics analysis in Table 2 show that the risk of transfer is 1.026 times higher for each year of age.先Previous studies have shown that age is an independent risk factor for poor prognosis in patients with chondrosarcoma[23]. A 2018 retrospective analysis identified age over 60 as an independent risk factor for PM, with older patients more likely to develop metastatic disease, and the study explained the poor prognosis in older patients [21]. This is also consistent with the conclusion of this study. But it does not explain exactly why advanced age becomes chondrosarcoma and LM is replaced. Therefore, further research is needed on the cause of age leading to a higher risk of LM.
In addition, it is worth noting that this study found the influence of marital status on LM. This study found that married people had a higher LM detection rate than unmarried people, with a statistical difference. Some studies have proved that marital status is a protective factor for survival, and married cancer patients have a significant survival advantage compared with unmarried patients [24, 25]. This may be due to the fact that married patients may have better financial conditions, or better medical and stable follow-up with the support of their spouse, and thus may be able to detect lung metastases earlier. Unfortunately, the SEER database does not have more detailed data on patients' financial status to further study the effect of financial status on PM. This study showed that male patients with chondrosarcoma had a higher risk of DEVELOPING LM than female patients, and the difference was statistically significant. OR value showed that the risk of LM in female patients was only 0.4 times that in male patients. Some studies have suggested that men are an independent risk factor for survival of patients with chondrosarcoma [19, 26, 27]. Considering that men have a higher LM risk, it may affect survival expectations.
According to the results of Table 2 Logistics regression analysis, the LM risk of patients with lymph node metastasis is about 27 times higher than that of patients without lymph node metastasis (OR = 27.164), and the LM risk of patients with unknown lymph node metastasis is about 8 times higher than that of patients without lymph node metastasis (OR = 8.027). Lymphatic metastasis is rare in bone tumors and may be due to the absence of lymphatic vessels in bone tissue [28]. Studies have suggested that lymphatic vessels are absent in normal bone, benign and malignant intrarenal bone, and this study suggests that lymphatic vessels may be present in the connective tissue covering the periosteum, and that lymphatic vessel diffusion occurs only when the tumor extends through the periosteum to adjacent connective tissue [29]. Thus, the presence of lymphatic metastases may indicate that the patient's tumor is more aggressive .Even though bone tumors have a low percentage of lymphatic metastasis, they are associated with a very high risk of LM, and it is necessary to examine the lymphatic status. Similarly, some studies believe that it is essential to always examine the evidence of regional lymph node metastasis[30], which is consistent with the conclusion of this study. LM - related factors of lymphatic metastasis still need to be further studied.
Nomogram is a quantitative tool for assessing risks and benefits that has been widely used in the medical field for clinical decision-making in a variety of diseases [31, 32]. In previous studies, several Nomogram have been developed and validated to predict specific survival and overall survival for chondrosarcoma [33–35]. However, Nomogram has not been reported for predicting LM.In this study, 944 cases of chondrosarcoma were obtained from the SEER database, and a Nomogram was established to predict LM based on five prognostic factors in logistics regression analysis (i.e., gender, age, tumor size, marital status, and lymphatic metastasis).Moreover, compared with other single variables, LM Nomogram showed better diagnostic efficiency and proved to have better predictive ability after calibration diagram and ROC curve test (Fig. 1.2 and Table 3). DCA curve (Fig. 3B) shows that LM has the maximum benefit when the threshold is about 0.1–0.8.In addition, the clinical impact diagram (Fig. 3C) shows that within the threshold range, there is an acceptable cost-benefit ratio. This demonstrates the value of Nomogram in this study, which can be further applied and improved in clinical practice, enabling clinicians to use Nomogram to select better medical examinations and optimize treatment regiments.
This study still has limitations. First of all, this study is a retrospective analysis, with data bias and certainty, and lack of systematic and prospective data.At the same time, as a single-center study, even if divided into training group and verification group, there is still a lack of external validation by other institutions, which may lead to overfitting of Nomogram to predict LM.