Table 2 Results. The table summarizes the current literature on preoperative hypofractionated RT for STS

Koseła-Paterczyk et al. [53]

2021 Poland

Phase II single center trial

Localized G2-G3 STS or G1 if >10cm

311

57

52 : 48

G1-2: 9.7%

G3: 84.1%

Unknown: 6.2%

LE: 72%

UE: 16.7%

Trunk: 11.3%

10 cm

5 x 5 Gy = 25 Gy

CTV = GTV + 2cm transv.; + 4cm long.

PTV = CTV + 0.7-1cm

37.5 Gy/ 56.3 Gy

Spalek et al. [54]

2021 Poland

Phase II single center trial

Localized, marginally resectable G2-G3 STS

46

58

37 : 63

G2: 34.8%

G3: 65.2%

LE: 63%

UE: 15%

Trunk: 22%

17.4 cm

5 x 5 Gy = 25 Gy

CTV = GTV + 2cm transv.; + 4cm long.

PTV = CTV + 0.7-1cm

37.5 Gy/ 56.3 Gy

Leite et al. [55]

2021 Brazil

Phase II single center trial

Localized, extremity G2-G3 STS > 10 cm

25

42

44 : 56

G1-2: 21.7%

G3: 78.3 %

LE: 60%

UE: 40%

14 cm Pre-SBRT

10.5 cm Post-SBRT

5 x 8 Gy = 40 Gy

CTV = GTV + 0.3-0.5 cm radial;

+ 2-3 cm long. PTV = CTV + 0.3cm

80 Gy/120 Gy

Potkrajcic et al. [56]

2021 Germany

Retrosp. Analysis

Age >75 yrs., G2-G3 STS, localized on extremity/trunk

18

83.7

N/A

G2: 33.3%

G3: 55.6%

G2-3: 5.6%

Unknown: 5.6%

LE: 55.6%

UE: 27.8%

Trunk: 16.6%

7.9 cm

5 x 5 Gy = 25 Gy

CTV = GTV + 1.5cm radial; + 3cm long.

PTV = CTV + 0.5-1 cm

37.5 Gy/ 56.3 Gy

Silva et al. [57]

2021 Brazil

Phase II single center trial

Age 18-75, localized STS, not amenable to resection

18

53.5

56 : 44

G2: 11%

G3: 89%

LE: 67%

UE: 33%

8.9 cm

5 x 5 Gy = 25 Gy

CTV = GTV + 1.5cm radial; + 4cm long.

PTV = CTV + 1cm

37.5 Gy/ 56.3 Gy

3D-CRT: 95.8% IMRT: 3.9%

VMAT: 0.3 %

IGRT: 100%

30.2 % pre-OP AI or doxo/DTIC

2-4 days

57.3

63%

5 yrs

13.8%

5 yrs

N/A

N/A

46%

5 yrs.

Major WC: 24%:

Overall: 8.6%

3D-CRT: 6.5%

VMAT: 41.3%

IMRT: 52.2%

IGRT: 100%

AI 3 cycles

6-8 weeks

24.4

53%

3 yrs

3 of 41 resected tumors (7%)

N/A

67%

2 yrs

N/A

Major WC: 34%.

Overall: °1-°4: 44%

pending

SBRT

IMRT

VMAT

IGRT

20% pre-op

8.6 weeks (median)

20.7

≈ 85%

3 yrs

0%

2 yrs

N/A

≈ 85%

3 yrs

N/A

Major WC: 28%

2°: Dermatitis: 48%

Edema: 8%

3° Dermatitis:20%

1°: Fibrosis: 34.7%

Edema: 21.7%

2°: Fibrosis: 4.3%

Edema: 4.3%

Stiffness: 13%

3D-CRT > IMRT/ VMAT

No

4.1 weeks (median)

5.1

100%

2 of 17 followed pts (11.8%)

92%

6 mths

N/A

84% 6 mths

Major WC: 29%

N/A

3D-CRT IMRT

AI 3 cycles

6 weeks (median)

29

95%

N/A

95%

N/A

72%

Major WC: 33%

1°: Fibrosis: 50%

Stiffness: 16%

Edema: 11%

2°: Fibrosis: 6%

Stiffness: 6%

Edema: 11%

Koseła-Paterczyk et al. [58]

2020 Poland

Phase II single center trial

Localized extremity or trunk MLPS, ≥ 5cm

27

43

48 : 52

Myxoid liposarcoma only

G1-G2: 66.6%

G3: 33.3%

LE only

13 cm

5 x 5 Gy = 25 Gy

CTV = GTV + 2cm transv.; +4cm long.

PTV = CTV + 0.7-1cm

37.5 Gy/ 56.3 Gy

Kalbasi et al. [47]

2020 USA

Phase II single center trial

Localized extremity or trunk STS

50

<50: 28% 50-64:

22% 65-79: 40%

>79: 10%

44 : 56

G1: 2 %

G2: 38 %

G3: 60 %

LE: 68%

UE: 18%

Trunk: 14%

26% ≤5 cm 50% >5 -

≤10 cm 24%

>10 cm:

5 x 6 Gy = 30 Gy

CTV = GTV + 1.5cm transv.; + 3cm long.

PTV = CTV + 0.5cm

50 Gy/75 Gy

Parsai et al. [59]

2020 USA

Retrosp. Analysis Localized extremity or trunk STS

16

64

44 : 56

G2: 50%

G3: 18.8%

Unknown: 31.2%

LE: 62.5%

UE: 25%

Trunk: 12.5%

18.8% ≤5 cm 56.2%

>5 - ≤10cm 18.8%

>10 cm - ≤15 cm

6.2% >15 cm

n=1: 5 x 5 Gy = 25 Gy

n=14: 5 x 6 Gy = 30 Gy

n=1 5 x 8 Gy = 40 Gy

Target volumes: according to RTOG-0630 [35]

n=1

37.5 Gy/ 56.3 Gy

n=14

50 Gy/75 Gy

n=1

80 Gy/120 Gy

Pennington et al. [60]

2018 USA

Retrosp. Analysis Localized, non-recurrent STS

116

46

40 : 60

G1: 0.9%

G2: 13%

G3: 79%

Unknown: 7%

LE: 79%

UE: 21%

17% ≤5cm 35%

>5 - ≤10 cm

47% >10 cm

8 x 3.5 Gy = 28 Gy

CTV = GTV + 4-5 cm long.

PTV: N/A

35 Gy/52.5 Gy

3D-CRT > IMRT > VMAT

No

7 weeks (median)

27.1

25 of 27 pts (93%)

0%

N/A

N/A

100% 3 yrs G1-G2 50% 3 yrs G3

Wound dehiscence: 10.3%

Wound infection: 17.2%

Dermatitis: 1°: 34.4%

2°: 3.4%

3°: 3.4%

13.8 %

Edema:

1°: 3.4%

2°: 3.4%

Fibrosis

°1: 3.4%

°2: 3.4%

3D-CRT 20

IMRT 76%

IGRT 96%

Electron 4%

No

4 weeks (median)

29

84%

2 of 35 pts (5.7%)

N/A

N/A

N/A

Major WC: 32%

Most common in LE

°2 dermatitis: 8%

1°: Fibrosis: 24%

Stiffness: 11%

Edema: 4%

2°: Fibrosis: 11%

Stiffness: 11%

Edema: 4%

IMRT

VMAT

IGRT

N = 2 pts^*

1 day (median)

10.7

87.5%

0%

N/A

N/A

N/A

Major WC: 18.8%

Minor WC: 12.5%

≥3°: 0%

3D-CRT

AI

1-2

weeks

5.9 yrs

82% 3 yrs

67% 6 yrs

11% 3 yrs

17% 6 yrs

N/A

N/A

N/A

Toxicity recorded for 17 pts:

Acute WC:

seromas/hematomas: 6

surgical site infection: 5

delayed wound healing: 1

Kubicek et al. [61]

2018 USA

Phase II single center trial

Localized extremity STS

13

N/A, all patients > 18 yrs

N/A

G1-G2: 21.4%

G3: 78.5%

LE: 71.4%

UE: 14.3%

Groin: 14.3%

7.6 cm

Most pts: 5 x 7 Gy = 35 Gy

3 of 13 pts: 5 x 8 Gy = 40 Gy

Median isodose line: 81%

CTV = GTV + 0.5 cm radial; + 3 cm long. PTV= CTV + 0.5 cm

Most pts: 64.17 Gy/96.3 Gy

3 of 13 pts:

80 Gy/120 Gy

Kılıç et al. [62]

2017 Turkey

Retrosp. Analysis

Localized, G2-G3

≥ 4cm or G1 ≥ 8cm extremity STS

67

47

43 : 57

G2: 7.5%

G3: 26.9 %

Unknown: 65.6%

N/A

9.6 cm

8 x 3.5 Gy = 28 Gy

PTV: N/A

35 Gy/52.5 Gy

Koseła-Paterczyk et al. [63]

2016 Poland

Sub-analysis of (64)

32

50

41 : 59

Myxoid liposarcoma only

G1: 15.6 %

G2: 12.5 %

G3: 46.9 %

Unknown: 25%

LE: 97%

UE: 3%

10.5 cm

53%: 5 x 5 Gy = 25 Gy

47%: 5 x 4 Gy = 20 Gy

CTV = GTV + 2cm transv.; + 4cm long.

PTV = CTV + 0.7-1cm

53%: 37.5 Gy/ 56.3 Gy

47%: 26.67 Gy/40 Gy

Koseła-Paterczyk et al. [64]

2014 Poland

Phase II single center trial

Locally advanced trunk wall or extremity G2-G3 STS or G1 if > 10cm diameter

272

55

53 : 47

G1: 11.8 %

G2: 23.6 %

G3: 64.6 %

LE: 70.2%

UE: 16.2%

Trunk: 13.6%

8.5 cm

5 x 5 Gy = 25 Gy

CTV = GTV + 2cm transv.; + 4cm long.

PTV = CTV + 0.7-1cm

37.5 Gy/ 56.3 Gy

SBRT

21.4%; agent N/A

37 days (median)

279 days

N/A

7.7%

93%

N/A

N/A

Major WC: 28.5 %

0%

N/A

50% RT+AI vs. 50% RT alone

2-3 Weeks after pre-op RT

37

3yrs: 74.1% vs. 90.0% p=0.4

14.9%

N/A

3 yrs: 77.1% vs. 76.3%

p=0.86

3 yrs: 50.5% vs. 65.7%

p=0.33

N/A

N/A

3D-CRT

No

3-7 days

60

68% 5 yrs

9.3%

90%^# 5 yrs

N/A^#

N/A

Acute:22 % = 7 patients

3 wound infection

2 wound dehiscence

5 prolonged healing

Late: 9% = 3 patients

1 prolonged edema

2 tissue fibrosis

No differences in RT regimens

3D-CRT IMRT for trunk lesions only (13.6%)

22.4% substance N/A

3-7 days

35

72% 3 yrs

19.1%

81% 3yrs**

N/A**

N/A

Overall: 32.4%: Inflammation requiring antibiotic treatment: 11.8%

Wound dehiscence: 11.8%

Prolonged wound healing: 16.5%

Overall: 14.7% 1°-3°

Fibrosis: 3.7%

Edema: 9.2%