This study constructed a nomogram to predict the probability of distant metastasis of spinal and pelvic osteosarcoma.We proved that this is a reliable and efficient prediction model by internal and external validation.Our study indicated that there are five risk factor of distant metastasis including sex,race,grade,number of primary tumor and surgery,but only surgery is an independent risk factor.This result will provide an important theoretical basis for the treatment of spinal and pelvic osteosarcoma.
Many studies have shown that metastasis is associated with a poor prognosis for osteosarcoma.Wenhao Chen et al indicated that distant metastatic osteosarcoma has a poor prognosis,and Kyle R. Duchman et al indicated metastatic disease at diagnosis conferred the poorest prognosis in patients with high-grade osteosarcoma.Spinal and pelvic osteosarcoma has a worse prognosis compered with osteosarcoma of other sites.Our study confirmed that the survival time of patients with metastatic spinal and pelvic osteosarcoma was lower than that of patients with non-metastatic spinal and pelvic osteosarcoma used the Kaplan-Meier curve.Therefore,we believe that the prognosis of metastatic spinal and pelvic osteosarcoma is worse than non-metastatic spinal and pelvic osteosarcoma.
Our study showed that the median age of patients with spinal and pelvic osteosarcoma was 45 years and there were fewer adolescents. However, osteosarcoma tends to occur in children and young adults according to previous reports[13, 14].Therefore, we believe that patients with spinal and pelvic osteosarcoma have a older age than patients with osteosarcoma in other sites, and some previous studies have found similar results [15, 16].Our study showed that metastasis occurred in 27.93% of patients with spinal and pelvic osteosarcoma,and previous literature reported 20% of patients with osteosarcoma have metastases at the time of diagnosis, especially lung metastases.We found that 40.50% of all patients with spinal and pelvic osteosarcoma had no surgical treatment,and that could be because of the difficulty of the operation in axial bones. The spine and pelvis contain many important vessels, nerves, and organs, which making the tumor difficult to remove completely. There is literature suggesting that it is almost impossible to remove the tumor in whole when the tumor involves the bilateral pedicle and involves the vertebral artery foramen or lamina,or the odontoid process.
We used LASSO regression analysis to identify five risk factors for metastasis of spinal and pelvic osteosarcoma:sex,race,grade,number of primary tumor and surgery.Our study showed that female patients and black patients with spinal and pelvic osteosarcoma were less likely to metastasis,which may provide some reference for clinical treatment decisions.Tumor grade is the description of a tumor based on how abnormal the tumor cells and the tumor tissue look under a microscope.In our study,the high grade was a risk factor for metastasis of spinal and pelvic osteosarcoma,which should be related to the rapid growth and diffusion of poorly differentiated or undifferentiated tumor cells.In addition,we found that patients with single primary tumors are more likely to metastasize than patients with multiple primary.There are no studies on relationship between number of primary tumor and distant metastasis of spinal and pelvic osteosarcoma,currently.We thought that molecular and biochemical studies of tumors may be needed to explain this.
In our study,surgery was confirmed to be an independent risk factor for distant metastasis of spinal and pelvic osteosarcoma by multivariate logistic regression analysis.Patients who underwent surgery had significantly lower rates of metastasis than those who did not undergo surgery.Therefor,surgery for spinal and pelvic osteosarcoma may be preferred based on this result.The main treatment for the primary osteosarcoma is chemotherapy and surgery,of which complete resection of the primary tumor blocks the progression of osteosarcoma including metastases[21, 22].Due to the specificity of spinal and pelvic anatomy, only intrafocal resection can be achieved in early stage.But these surgical methods lead to incomplete tumor resection and easy to postoperative tumor recurrence and distant metastasis.With the development of surgical techniques,total en bloc spondylectomy(TES) was invented and considered to be an aggressive surgical technique that may be employed in the treatment of spinal neoplasms[24, 25].Several large sample case studies showed extensive resection of osteosarcoma or at least marginal resection based on TES can be performed to minimize tumor cell contamination from surgical procedures and reduce the local recurrence rate and improve the survival rate of patients[26, 27].Pelvic osteosarcoma surgery mainly includes limb salvage surgery and amputation.A number of long-term clinical studies have shown that limb salvage is similar to amputation,and Hindquarter amputation should be considered when limb salvage does not guarantee a satisfactory resection margin.
The nomogram is well known for its predictive accuracy and has made remarkable contributions to modern medical[30, 31].Jiang R et al constructed a nomogram for pelvic and spinal ewing sarcoma patients to facilitate advances in individual treatment by quantitatively analyzing survival predictors.Li W et al constructed a novel nomogram to predict risk factors for chondrosarcoma patients and guided clinicians to optimize personalized treatment and make superior clinical related decisions.To the best of our knowledge, this is the first study constructing a nomogram to predict the probability of metastasis for patients with spinal and pelvic osteosarcoma,and personalized treatment can be developed based on this predictive model.Undoubtedly, compared with general treatment, personalized treatment is more rational and specific.For example,we should pay more attention to check for metastasis when patients who had not undergone surgery were reviewed.In addition,we need to be more targeted in our screening and treatment plans for high-grade spinal and pelvic osteosarcoma patients.Therefor,this predictive model is of great significance to orthopedic surgeons in the clinical management of spinal and pelvic osteosarcoma.
We have validated the reliability and validity of nomogram both internally and externally.C-index can evaluate the probability that the predicted results are consistent with the actual observed results,while assessing calibration is an important component of deriving and validating clinical prediction models.C-index of nomogram in our study is greater than 0.7 and the calibration curves of nomogram in training cohort and validation cohort showed a high degree of agreement between the predicted and actual observed metastasis rates of the training and validation cohorts, indicating that the nomograme are reliable.Receiver operating characteristic (ROC) curve is ofen used to discriminate performance of clinical prediction models.In our study,AUC values were greater than 0.7 in the training and validation cohorts,which indicated a good predictive effect.Decision curve analysis was developed as a method to determine whether use of a prediction model in the clinic to inform clinical decision-making would do more good than harm.The DCA showed that the nomogram has a clinical usefulness and net benefit in most cases.To sum up,the nomogram constructed in our study has good reliability, validity and clinical benefit.
However, there are some limitations to our study.First of all,The sample size of our study was not as large as that of other studies based on SERR databases because patients with spinal and pelvic osteosarcoma are extremely rare.However,our study has been the largest sample size study on distant metastasis of spinal and pelvic osteosarcoma.Secondly, some patients lacking pathological grade were excluded from the study, and some patients included in our study lacked tumor size data,which may lead to inaccurate inferences.Thirdly,the SEER database(18Registries, Nov 2020 Sub(2000-2018)) lacks other important information, such as data about neurological function;specific surgical methods;pivotal serological biomarkers;radiation or chemotherapy;local recurrence,which leaded to some relevant bias.Finally,because of both training and validation cohorts are from the same database, it is necessary to get data from another database for validation.