Clinicopathologic data. In total, 136 patients who underwent primary surgery for RPS from 2001 to 2016 and underwent preoperative 18F-FDG PET/CT to determine the presence of metastasis were identified. Three patients with Ewing’s sarcoma were excluded. Four patients were excluded due to insufficient pathological data such as mitosis and necrosis. After excluding these patients, data from a total of 129 patients were investigated. The histologic subtypes were dominantly LPS (68.2%) and LMS (15.5%). DDLPS accounted for 68% of the LPS patients, followed by well-differentiated liposarcoma (WDLPS) and pleomorphic liposarcoma (PLS). The distribution of tumor grades was similar for the three grades. Demographic and clinicopathological details are shown in Table 1.
Table 1
Characteristics of patients.
Variable | | Value |
Age, years | | 56.4 ± 12.2 |
Gender (%) | F | 67 (51.9) |
| M | 62 (48.1) |
BMI, kg/㎡ | | 23.5 ± 3.0 |
Underlying disease | | |
DM | Yes | 11 |
| No | 118 |
HTN | Yes | 39 |
| No | 90 |
COPD | Yes | 1 |
| No | 128 |
Chronic renal disease | Yes | 1 |
| No | 128 |
Histologic subtype (%) | Well-differentiated liposarcoma | 24 (18.6) |
| Dedifferentiated liposarcoma | 60 (46.5) |
| Pleomorphic liposarcoma | 4 ( 3.1) |
| Leiomyosarcoma | 20 (15.5) |
| Malignant peripheral nerve sheath tumor | 4 ( 3.1) |
| Perivascular epithelioid cell tumor | 1 ( 0.8) |
| Other | 16 (12.4) |
FNCLCC grade (%) | 1 | 29 (22.5) |
| 2 | 36 (27.9) |
| 3 | 64 (49.6) |
SUVmax (median [range]) | | 4.5 [0.4, 29.0] |
Tumor size, mm | | 166.4 ± 101.3 |
Multifocality (%) | Yes | 23 (17.8) |
| No | 106 (82.2) |
Necrosis (%) | Absent | 60 (46.5) |
| <50% | 60 (46.5) |
| ≥50% | 9 ( 7.0) |
Mitosis (%) | <9/10 HPF | 95 (73.6) |
| 10-19/10 HPF | 24 (18.6) |
| ≥20/10 HPF | 10 ( 7.8) |
Local recurrence (%) | Yes | 54 (41.9) |
| No | 75 (58.1) |
Distant metastasis (%) | Yes | 17 (13.2) |
| No | 112 (86.8) |
Follow up months after primary surgery, mean | | 46.8 ± 34.1 |
Correlation between SUVMmax and pathologic details. The median value of SUVmax was 4.5 (range, 0.4-29). Tumor SUVmax was correlated with higher tumor grade (p < 0.001, Spearman coefficient 0.627) and mitosis (p < 0.001 Spearman coefficient 0.564). The SUVmax value was different depending on histologic subtype. The LPS group showed a lower SUVmax value than did the LMS group. When comparing the SUVmax of the three groups, values were obtained in this order: WDLPS (2.32 ± 0.89), DDLPS (6.32 ± 4.97), and LMS (12.04 ± 6.73). The differences were statistically significant (Fig. 1).
Prognostic factors of RPS and SUVmax. The univariate analysis of prognostic factors associated with OS was performed on all patients with RPS. The factors significantly associated with OS were high-grade tumor (grade III, p = 0.003), SUVmax (p < 0.001), mitosis [≥ 20/10 high power fields (HPF), p < 0.001], and necrosis (≥50%, p < 0.001). On multivariate analysis, SUVmax (p = 0.004) was determined to be the only significant associated factor. When analyzing the prognostic factors of OS by histologic subtype, tumor grade (grade III, p = 0.011) and SUVmax (p < 0.001) were significant prognostic factors in the LPS group, consistent with RPS. However, there was no statistically significant risk factor in the LMS group. The details of analyses are shown in Table 2.
Table 2
Univariate and multivariate analyses of risk factors associated with overall survival.
Variables | Univariate | Multivariate |
HR (95% CI) | p value | HR (95% CI) | p value |
Male | 1.9 (0.98,3.66) | 0.057 | | |
Age | 1.03 (1,1.06) | 0.033 | | |
SUVmax | 1.11 (1.07,1.16) | < 0.001 | 1.09 (1.03,1.15) | 0.004 |
FNCLCC grade : ref.= 1 | | | | |
2 | 0.93 (0.19,4.61) | 0.926 | 0.76 (0.15,4.01) | 0.749 |
3 | 6.06 (1.84,19.98) | 0.003 | 4.4 (0.83,23.45) | 0.083 |
Necrosis : ref.= Absent | | | | |
<50% | 3.26 (1.46,7.28) | 0.004 | 0.81 (0.24,2.74) | 0.74 |
≥50% | 6.49 (2.1,20.02) | 0.001 | 1.37 (0.33,5.73) | 0.666 |
Mitosis : ref.= <9/10 HPF | | | | |
10-19/10 HPF | 2.26 (1.06,4.81) | 0.035 | 0.7 (0.26,1.9) | 0.484 |
≥20/10 HPF | 4.63 (1.83,11.7) | 0.001 | 0.77 (0.21,2.81) | 0.69 |
The univariate analysis of prognostic factors for LR was performed on all RPS patients. The significantly associated factors were SUVmax (p < 0.001), high tumor grade (p < 0.001), mitosis (≥20/10 HPF, p = 0.024), and necrosis (≥ 50%, p < 0.001). On multivariate analysis, the only factors independently associated with LR were high tumor grade (p = 0.013) and necrosis (≥ 50%, p = 0.028). However, in the analysis conducted by histologic subtypes, SUVmax (p < 0.001) and high tumor grade (p = 0.002) were the main factors for LR in LPS groups (Table 3).
Table 3
Univariate and multivariate analyses of risk factors associated with local recurrence.
Variables | Univariate | Multivariate |
HR (95% CI) | p value | HR (95% CI) | p value |
Male | 1.14 (0.67,1.95) | 0.632 | | |
Age | 1.01 (0.99,1.03) | 0.503 | | |
SUVmax | 1.08 (1.04,1.12) | < 0.001 | 1.03 (0.96,1.09) | 0.416 |
FNCLCC grade : ref.= 1 | | | | |
2 | 8.43 (1.9,37.39) | 0.005 | 7.24 (1.56,33.67) | 0.012 |
3 | 15.38 (3.69,64.04) | < 0.001 | 8.16 (1.55,42.96) | 0.013 |
Necrosis : ref.= Absent | | | | |
<50% | 3.35 (1.77,6.33) | < 0.001 | 1.36 (0.59,3.14) | 0.473 |
≥50% | 13.9 (5,38.6) | < 0.001 | 4.01 (1.16,13.87) | 0.028 |
Mitosis : ref.= <9/10 HPF | | | | |
10-19/10 HPF | 3.38 (1.79,6.39) | < 0.001 | 1.57 (0.73,3.41) | 0.25 |
≥20/10 HPF | 2.99 (1.15,7.75) | 0.024 | 1.25 (0.31,4.99) | 0.751 |
Optimal threshold to distinguish high grade sarcoma. The ROC curve analysis demonstrated that the AUC for high tumor grade (Grade III) was maximal when the threshold SUVmax was 4.8. The AUC for high tumor grade at the cut-off SUVmax was 0.820 (p < 0.001). At this threshold, the values of sensitivity and specificity were 0.77 and 0.80, respectively (Fig. 2).
Prediction of outcome with optimal SUVmax threshold. The SUVmax threshold was divided into a high SUVmax group and a low SUVmax group based on a cut off of 4.8; and survival analysis was performed for OS, LR, and DM. In analysis of the entire RPS group, the high SUVmax group showed poor prognosis in OS, LR, and DM (p < 0.001). When analyzed by histologic subtype, the liposarcoma group’s high SUVmax subgroup showed poor prognosis in OS (p < 0.001) and LR (p = 0.004). However, there was no difference in the LMS group (Fig. 3).