Identification of cutoff values for age
To determine the optimal age stratification for patients with osteosarcoma of the spine, we constructed an X-tile plot to explore the predicted cutoff values. The age of diagnosis was divided into 3 levels: <48 years, 49-62 years, and> 62 years (Figure 2).
Baseline characteristics of patients
Using chi-square test, we studied the demographic and clinicopathological characteristics of patients with osteosarcoma of the spine. The baseline characteristics of the patients are reviewed in Table I. After applying exclusion criteria, a total of 727 patients were included in our cohort from 1973 to 2015. Among them, 370 cases were treated by surgery and 357 cases were not treated.
Chi-square test showed that different treatment patterns was related to age at diagnosis (p<0.001), marital status (p<0.001), SEER historic stage (p<0.001), tumor grade (p<0.001)，radiotherapy (p<0.001) and chemotherapy (p<0.001). Patients younger than 48 years of age choose surgical treatment, while patients older than 62 years old prefer non-surgical treatment. In terms of marital status, married patients accounted for a relatively high proportion (48.0%) of the patients who chose surgery, and divorced or separated patients had poor surgical compliance (4.0%). In SEER tumor staging, patients with regional osteosarcoma of the spine were more likely to receive surgical treatment than patients with distant. As to the chemotherapy, the proportion of patients who received chemotherapy chose surgery treatment was significantly higher than that of patients with no chemotherapy. However, this situation is exactly the opposite in radiotherapy.
Comparison of the survival outcome between different treatment groups
By analyzing the Kaplan-Meier curve with a log-rank test, we found that age at diagnosis (p<0.001), Year of diagnosis (p=0.008)， marital status (p=0.002), SEER historic stage (p<0.001), tumor grade (p<0.001), surgery (p<0.001), radiotherapy (p<0.001) and chemotherapy (p<0.001) were associated with OS (Table II). However, marital status and chemotherapy treatment were not associated with CSS (Table II). The OS median survival time of patients undergoing surgery was 27 months and that of patients without surgery was 8 months (Table II and Figure 3a). For CSS median survival time, patients undergoing surgery was 44 months and patients without surgery was 11 months (Table II and Figure 3b). In both OS and CSS, surgically treated patients had significantly longer survival time than non-surgically treated patients (Figure 3).
Cox regression analysis for the prognostic factors
Cox regression was used to analyze prognostic factors for OS and CSS (Table Ⅲ and Table Ⅳ). Univariate analysis showed that age, marital status, SEER historic stage, surgery and radiotherapy were significant influence factors for OS and CSS. However, chemotherapy had no effect on CSS. Compared with patients received surgery, patients without surgery had a worse OS (HR= 2.69, 95%CI: 2.27-3.19, P < 0.001) and CSS (HR= 2.53, 95%CI: 2.06-3.10, P < 0.001). In terms of radiotherapy, patients who have not received chemotherapy was significantly associated with a better OS (HR= 0.67, 95%CI: 0.56-0.79, P < 0.001) and CSS (HR= 0.62, 95%CI: 0.50-0.77, P < 0.001). For chemotherapy, without chemotherapy had a higher risk in OS (HR= 1.39, 95%CI: 1.18-1.65, P < 0.001).
Objective to explore which variables have significant influence on the prognosis of patients with osteosarcoma of the spine. We further used multivariate analysis to confirm that surgery was an independent prognostic factor for OS and CSS. Compared to patients with surgery treatment, the risk was increased when the patients without surgery in the OS (HR= 1.66, 95%CI: 1.36-2.02, P < 0.001) and CSS (HR= 1.56, 95%CI: 1.24-1.97, P < 0.001). Moreover, for age and SEER historic stage, multivariate analysis also showed statistically significant difference in both OS and CSS.
Factors willing to undergo surgery
We used multivariate logistic regression model to determine the factors that influence whether to undergo surgery. When adjusting for other factors, some variables were proved to be significantly correlated with rejection of surgery (Figure 4). We found that the influencing factors have the following aspects: age, grade, and SEER historic stage. Patients who were 62 years or older (OR, 3.86; 95% CI,2.63-5.56; P < 0.001), at regional stage (OR, 6.05; 95% CI,3.71-9.87; P < 0.001) and at unstaged stage (OR,4.62; 95% CI,2.45-8.72; P < 0.001). Additionally, Patients who were at histological grade Ⅱ (OR, 0.79; 95% CI,0.14-4.62; P =0.797) were more willing to accept surgical therapy.
Trends in survival stratified by the age at diagnosis and SEER historic stage
In order to better demonstrate that surgery as a single factor had a significant impact on the survival of patients with osteosarcoma of the spine. Patients were stratified by the age at diagnosis and SEER historic stage to investigate the trends in survival. For OS and CSS, we found that regardless of the age stage, patients in surgery group had more favorable survival than the other group (Figure 5). Similarly, the outcome in SEER historic stage had the same characteristics (Figure 6).