Patient‑ and treatment‑related characteristics
Between June 2009 and June 2019,37 patients with 58 lesions were treated in this study. As the table 1 shows, the mean age was 55 years (range, 19-82 years). The number of lesions at the first SBRT less than 3 and equal or more than 3 was 27(73%) and 10(27%). Together, the number of high differentiation ,moderately differentiation and poor differentiation was 19(51%),4(11%) and 14(38%).
Table 1 Patient-related characteristics in STS patients treated by SBRT (per patient)
Patient-related variables (n = 37)
|
Patients, n
|
%
|
Age
|
|
|
<60
|
18
|
49
|
≥60
|
19
|
51
|
Gender
|
|
|
Male
|
25
|
68
|
Female
|
12
|
32
|
Pathological type
|
|
|
leimyosarcoma
|
3
|
8
|
Spindle cell tumor
|
6
|
16
|
Malignant fibroblastoma
|
8
|
22
|
fibrosarcoma
|
3
|
8
|
liposarcoma
|
4
|
11
|
Others
|
13
|
35
|
Grading
|
|
|
high differentiation
|
19
|
51
|
Intermediate differentiation
|
4
|
11
|
low differentiation
|
14
|
38
|
Number of concurrent metastases at the time of first SBRT
|
|
|
<3
|
27
|
73
|
≥3
|
10
|
27
|
Table 2 Treatment-related characteristics in metastases or local recurrences treated by SBRT (per treatment)
Treatment-related variables (n = 58)
|
Treatments, n
|
%
|
Site
|
|
|
Head and neck
|
6
|
10
|
Lung
|
17
|
30
|
Chest
|
5
|
9
|
Abdominal pelvic
|
13
|
22
|
renal region
|
5
|
9
|
Vertebral body bone
|
10
|
17
|
limbs
|
2
|
3
|
Diameter
|
|
|
<50mm
|
26
|
45
|
≥50 mm
|
32
|
55
|
BED
|
|
|
<100Gy
|
29
|
50
|
≥100Gy
|
29
|
50
|
Abbreviations:BED,biologically equivalent dose BED values calculate using α/β = 10.
Table 3 The dosimetry index of the patients during Cyber-knife radiosurgery treatmet
Item
|
CI
|
nCI
|
HI
|
Coverage(%)
|
PTV(cm3)
|
Prescription dose(Gy)
|
fx
|
Isodose(%)
|
Range
|
1.00-2.77
|
1.13-2.93
|
1.10-2.00
|
47.81-99.75
|
2.02-1878.09
|
20-75
|
1-10
|
50-88
|
Mean
|
1.31
|
1.61
|
1.39
|
82.52
|
307.03
|
44.81
|
4.33
|
73.26
|
Median
|
1.13
|
1.42
|
1.33
|
86.12
|
83.25
|
45
|
5
|
75
|
Abbreviations: Coverage: the coverage is volume of the tumor receiving greater than or equal to the prescription dose divided by the total volume of the tumor times 100; CI, conformity index; nCI, new conformity index; HI, homogeneity index.
Local control
Among the 58 lesions in the 37 patients in this study, the median local control time was 25 months and 95%CI was 20-25 months. A Kaplan-Meier plot for overall survival is shown in Fig. 2A.One year local control rate was 75.3% and 55.2% in 2 years. Among them, LC with low differentiation sarcoma was better than high differentiation (P =0.0201), LC with tumor diameter less than or equal 5cm was better (P =0.0081), and was independent of BED (P =0.0891).
Overall survival
In this study, the median time of OS was 24 months, and 95%CI was 12.0-35.0 months. A Kaplan-Meier plot for overall survival is shown in Fig. 2A. 1-year OS was 66.6%, 2-years OS was 45%, and 3-years OS was 26.2%. Among them, OS was related to systemic status, and single lesion was better, P =0.0069. Median OS of single lesion was 28 months, 95%CI was 21-75, 1-year and 3-year survival rates were 100% and 50.5%, respectively. The median OS of multiple lesions was 11 months, 95%CI was 4.00-26.00, and the 1-year and 3-years survival rates were 45.3% and 11.3% respectively.
Progression-free survival
A Kaplan-Meier plot for progression-free survival is shown in Fig. 3. 1-year PFS is 44.9% and 2-years PFS is 26.2%.The median PFS of single lesion was 15 months, 95%CI 8.00-31.00, and the 1-year and 2-years progression-free survival rates were 53.2% and 37.3%, respectively. The median PFS of multiple lesions was August, 95%CI3.00-13.00, and the 1-year and 2-year progression-free survival rates were 26.6% and 0%, respectively. In addition, low-grade lesion PFS was superior to high-grade lesion PFS, p=0.0006, low-grade median PFS was 25 months, 95%CI was 11.00-77.00, 1-year and 2-year progression-free survival rates were 76.9% and 57.7%, 1-year and 2-year progression-free survival rates were 8months(95%CI 4-10), 1-year and 2-year progression-free survival rates were 22.4% and 5.5%, respectively.
Univariate Analysis and A Multi-Logistic Regression Analysis
Univariate and multivariate regression analysis were used to determine which factors were associated with LC, OS and PFS. Multivariate analysis for LC was associated with pathological grade, tumor size, and number of tumors at the time of first SBRT treatment, but not with BED. In univariate analysis, it was only related to pathological grade and tumor size, but not to BED and the number of tumors at the time of first SBRT treatment. Univariate and multivariate analysis of OS and PFS were related to pathological grade and the number of tumors at the time of first SBRT treatment, but not to BED and tumor size.
Table 4 Univariate analysis of PFS and OS
Variable
|
OS
HR and 95%CI
|
p
|
PFS
HR and 95%CI
|
p
|
Grading
|
|
|
|
|
poor differentiation
|
0.205(0.075-0.564)
|
0.002
|
0.234(0.095-0.580)
|
0.002
|
High or moderately differentiation
|
1
|
|
1
|
|
Diameter
|
|
|
|
|
≤50mm
|
0.873(0.386-1.971)
|
0.743
|
0.822(0.362-1.863)
|
0.638
|
>50 mm
|
1
|
|
1
|
|
BED
|
|
|
|
|
≥100Gy
|
0.628(0.284-1.392)
|
0.252
|
0.597(0.269-1.327)
|
0.206
|
<100Gy
|
1
|
|
1
|
|
Number of concurrent metastases at the time of first SBRT
|
|
|
|
|
<3
|
0.349(0.151-0.804)
|
0.013
|
0.372(0.155-0.892)
|
0.027
|
≥3
|
1
|
|
1
|
|
Table 5 A Multi-Logistic Regression Analysis of PFS and OS
|
PFS
|
OS
|
Grading
|
P=0.002
|
P=0.002
|
HR 0.231(0.092-0.578)
|
HR 0.174(0.059-0.512)
|
Number of concurrent metastases at the time of first SBRT
|
P=0.019
|
P=0.008
|
HR 0.303(0.112-0.819)
|
HR 0.261(0.097-0.700)
|
Table 6 Univariate Analysis and A Multi-Logistic Regression Analysis of LC
Local Control
|
|
A Multi-Logistic Regression Analysis
|
Univariate Analysis
|
|
HR and 95%CI
|
p
|
Grading
|
P=0.018
HR:0.225(0.066-0.770)
|
poor differentiation
|
0.282(0.091-0.879)
|
0.029
|
High or moderately differentiation
|
1
|
|
Diameter
|
P=0.040
HR:0.224(0.054-0.932)
|
≤50mm
|
0.170(0.038-0.761)
|
0.021
|
>50 mm
|
1
|
|
BED
|
P=0.056
HR:3.839(0.965-15.269)
|
≥100Gy
|
1
|
0.107
|
<100Gy
|
2.880(0.797-10.409)
|
|
Number of concurrent metastases at the time of first SBRT
|
P=0.013
HR:0.155(0.036-0.671)
|
<3
|
0.538(0.166-1.740)
|
0.301
|
≥3
|
1
|
|
Case presentation
The patient is a 71-year-old male with a mucinous liposarcoma of the medial thigh. The first surgical resection was performed on 2000-08-29, followed by in situ recurrence followed by tumor resection on 2008-12-10, 2011-02-14, 2016-06-20, 2017-08-13, and 2018-11-19, respectively. The postoperative pathology was all mucinous liposarcoma. In May 2019, the patient's repeat MRI suggested a recurrence of Stereotactic radiotherapy for recurrent lesions was performed on 2019-06-06 with a specific plan of 50Gy/5fx. As shown in Figure 4, review after 1 year of treatment suggests disease reduction.
Toxicity
There have been no cases of acute or late grade 4 toxicity or possible treatment-related death. The most common acute toxicity was grades 1–2 fatigue (8/37,21.6%). Acute grades 1–2 radiation pneumonitis occurred in one patients (2.7%),and acute grade 1-2 radiation enteritis was observed in two patients (2.7%). Late grade 3 radiation dermatitis was observed in one patient (2.7%) at 6 months after SBRT.