Patient characteristics
The selection process of the patients is illustrated in Figure 1. According to the inclusion criteria, 334 patients with malignant GCTB seen from 1975 to 2016 were initially selected. After excluding one case that was diagnosed via death certificate and eight patients with extraskeletal GCTB, 325 patients were finally included. Table 1 shows the detailed clinicopathological features of the patients. The median age of the patients was 34 years, and a female predominance (52.3%) was observed. More tumours were located in the long bones and associated joints (64.6%) than in other locations, especially in the lower limbs (48.6%). More than 50% of patients had no clear records of tumour grade, T stage, N stage or M stage. Twenty-two patients showed distant metastasis, including lung metastasis (10/22, 45.45%), bone metastasis (5/22, 22.73%) and other metastasis (7/22, 31.82%). Regarding historic SEER stage, the localized and regional stages were the most frequent, occurring in 61.2% of all the patients, while 13.5% of patients had disease at distant stage. Surgery was performed in 53.85% of the patients.
Eight patients were diagnosed with extraskeletal GCTB. Their data were recorded from 1987 to 2016, and five patients were female. Two of the patients were diagnosed at approximately 20 years old, while the others were older than 50 years. Regarding the primary site, three cases were found in the pancreas, one was found in the kidney, one was found in the thyroid, one was found in the mediastinum, one was found in the lung, and there was one subcutaneous case. There was no clear record of tumour grade in four patients, one of whom had grade I disease, two of whom had grade III disease, and one of whom had grade IV disease. Two patients had long survival (135 and 136 months), one died at 24 months after diagnosis, and five patients died within 7 months.
Survival analysis and prognostic factor identification
The overall survival of the entire cohort is illustrated in Figure 2. The overall 1-, 5-, and 10-year survival rates were 94.3% (95% CI: 91.7-96.8), 82.3% (95% CI: 77.9-86.6), and 80.1% (95% CI: 75.4-84.7), respectively. The detailed OS data for patients with malignant GCTB according to each characteristic are summarized in Table 2. As shown in the Figures 3A and 3B, three knots were applied to the data and stratified the age and diagnosis year into four groups. We observed a potential non-linear J-shaped dose–response relationship between the age or diagnosis year and survival. Elder age had a gradually increased risk for survival.
The results of the univariate and multivariate Cox regression analyses are summarized in Table 3. A lower OS was noted in patients with age from 35 to 60 years (P=0.025) and patients older than 60 years (P<0.001), with grade IV disease (P=0.041), with stage T2/3 disease (P<0.001), with unknown N stage (P=0.019), with stage M1 disease (P<0.001), with a distant historic SEER stage (P<0.001), and who had not undergone surgery for the primary tumour (P=0.05) under univariate analysis. Multivariate Cox regression analysis showed poor survival in patients with age from 35 to 60 years (hazard ratio (HR) =9.99, 95% CI: 1.34-74.80, P=0.025), age older than 60 years (HR=62.03, 95% CI: 7.94-484.38, P<0.001), with stage T2 disease (HR=4.85, 95% CI: 1.52-15.47, P=0.008), with stage T3 disease (HR=6.09, 95% CI: 1.03-36.23, P=0.047), and with distant tumours (HR=2.76, 95% CI: 1.14-6.65, P=0.024). The sensitivity analysis suggested that a primary location of GCTB in extraskeletal sites was associated with poor survival (HR=3.33, 95% CI: 1.02-10.85, P=0.046). Analysis including the extraskeletal cases did not produce significantly different results (supplementary table).