br ACCEPTED MANUSCRIPT br and validate the nomograms
and validate the nomograms. Statistical significance was defined as two-sided P<0.05.
Patient baseline characteristics
A total of 558 patients with chordoma of the skull base, vertebral column, and JQ-1 between 1973 and 2014 were identified from the SEER database according to inclusion and exclusion criteria. The patients were randomly divided into the training cohort (n = 372) and the validation cohort (n=186). The training cohort was assigned for construction and internal validation of the nomograms. And, the validation cohort was assigned for the external validation of the nomograms.
The patient characteristics are summarized in Table 1. There were 327 (58.6%) male patients and 231 (41.4%) female patients in the current study. The primary site of 245 (43.9%) patients were the bones of the skull and face and associated joints; 90 (16.1%) patients’ primary site was the vertebral column; and 261 (40.0%) patients’ primary site was the pelvic bones, sacrum, coccyx, and associated joints. Among all the patients, 224 patients (40.1%) had localized disease, 283 patients (50.7%) had regional disease, and the remaining 51 patients (9.1%) had distant disease. In the entire cohort, 117 (20.9%) patients had death attributed to chordoma and 52 (9.3%) patients had death attributed to other causes. No significant differences regarding patient age, gender, primary site, tumor size, histology, surgical stage, use of surgery, use of chemotherapy, and use of radiation were found between the training and validation cohorts.
Univariate and multivariate Cox proportional hazards regression analyses of the training cohort
The data of the training cohort, including patient age, gender, primary site, tumor size, histology, surgical stage, use of surgery, use of chemotherapy, and use of radiation, were selected to conduct the univariate Cox analysis. The results of the analysis (Table 2) showed that there were six variables involving patient age, primary site, histology, tumor stage, use of surgery, and tumor size that were related to OS (P<0.05), and the other variables lost significance. Further, six variables including patient age, histology, tumor stage, tumor size, use of surgery, and chemotherapy were related to CSS (P<0.05), and the other variables lost significance (Table 3). Multivariate Cox analyses (Table 2 and 3) were further performed to control for confounding variables. From multivariate analysis results, age, primary site, histology,
surgical stage, use of surgery, and tumor size were identified as independent prognostic factors for both OS and CSS (P<0.05), and the other variables lost significance.
Construction and validation of the nomograms for OS and CSS
After selection, patient age, primary site, histology, surgical stage, use of surgery, and tumor size were used to construct the prognostic nomograms that predict 3- and 5-year OS and CSS of patients with chordoma (Figure 2 and Table 4). Internal and external validations of prognostic nomograms were performed. The predictive accuracy of the final prognostic nomogram models was evaluated by C-index. For the internal validation of the nomogram in the training cohort, the C-indices were 0.775 (95%CI, 0.770 to 0.779) and 0.756 (95%CI, 0.749 to 0.762) for internal validation of the OS and CSS nomograms, respectively. And, the external validation C-indices were 0.673 (95%CI, 0.660 to 0.685) and 0.603 (95%CI, 0.586 to 0.619) for the OS and CSS nomograms, respectively. A good agreement between nomogram prediction and actual survival was shown in calibration plots (Figure 3). These prognostic nomograms can easily be used by surgeons to estimate the prognosis of patients with chordoma with the following data: age at diagnosis, primary site, histology, surgical stage, whether surgery was performed, and tumor size.
Chordomas are specific tumors that originate from remnants of the embryonic notochord. The location of this bone tumor involves the sacral area in most (55%), followed by the skull base region (35%) and the vertebral column region (10%) . Understanding the natural history of chordoma can help surgeons evaluate prognostic information. Various prognostic factors can influence patient survival; however, a single prognostic factor has only limited utility in predicting individual survival. The nomogram, a tool commonly used for estimating individual patient survival, is capable of calculating the accumulated effect by integrating all prognostic factors predict 3- and 5-year survival probabilities[20-22]. Nevertheless, no prognostic nomogram for patients with chordoma had been constructed. In the present study, we established comprehensive prognostic nomograms to predict 3- and 5-year OS and CSS rates for patients with chordoma of the skull base, mobile spine, and pelvis according to the SEER database, which covers approximately 28% of the US population. We hypothesized that these validated nomograms could be used in the