Table 1.
Preoperative radiotherapy regimens in soft tissue sarcomas in major published studies.
| References | Evidence | N of patients | Dominant preoperative regimen | EQD2 α/β 4 Gy | Tumors >10 cm | Surgery after RT | R0 | @years local control | All wound complications @severe∧ | Reported late toxicity | @years estimated survival | |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Conventionally fractionated RT regimens | Pollack et al. (9) | Retrospective cohort | 128 (preop) 51 CHT+RT 77 RT | CHT*&50 Gy/25 fr. | 50 Gy | ND median 10 cm |
Delayed | 92% | @5y 82% |
25%@ND | 6% | ND |
| O'Sullivan et al. (3, 10) Davis et al. (4) |
Phase III RCT (preop vs. postop) | 94 (preop) | 50 Gy/25 fr. | 50 Gy | 35% | Delayed (3–6 weeks) |
84% | @5y 93% |
35%@17% | G2+: fibrosis 32% JS 18% edema 15% |
@5y DRFS 67% OS 73% |
|
| Zagars et al. (11) | Retrospective cohort | 271 (preop) 179 CHT+RT 92 RT |
CHT*&
50 Gy/25 fr. |
50 Gy | 42% | Delayed (4–6 weeks) |
86% | @5y 85% @10y 83% |
ND | 5% | @5y DRFS 64% @10y DRFS 61% DSS 64% |
|
| Hui et al. (12) | Retrospective cohort | 67 | 50.4 Gy/28 fr. | 48.7 Gy | ND median 6 cm |
Delayed (3–6 weeks) |
99% | @5y 93% |
41%@18% | 7% | @5y DRFS 68% OS 73% |
|
| Kraybill et al. (13) | Phase II single arm CT | 64 | MAID 22 Gy/11 fr. MAID 22 Gy/11 fr. MAID |
44 Gy | ND median 15 cm |
Delayed | 91% | @3y 90% |
11%@3% | ND | @3y DRFS 65% OS 75% |
|
| Canter et al. (14) | Retrospective cohort | 25 | 50 Gy/25 fr. | 50 Gy | 36% | Delayed (4–6 weeks) |
84% | @3y 100% |
28%@16% | ND | ND | |
| Yoon et al. (15) | Phase II single arm CT | 20 | Bevacizumab 50.4 Gy/28 fr. |
48.7 Gy | ND median 8 cm |
Delayed (6–7 weeks) |
ND | @2y 95% |
20%@ND | ND | @2y DRFS 65% |
|
| Shah et al. (16) | Retrospective cohort | 30 | 50 Gy/25 fr. | 50 Gy | 40% | Delayed (4–6 weeks) |
ND | @5y 100% |
23%@20% | ND | @5y DRFS 61% OS 69% |
|
| O'Sullivan et al. (17) | Phase II single arm CT | 59 | 50 Gy/25 fr. | 50 Gy | ND median 10 cm |
Delayed | 93% | @5y 88% |
31%@10% | Moderate: skin 2% fibrosis 9% JS 7% edema 11% |
@5y DRFS 67% OS 75% |
|
| Lewin et al. (18) | Phase Ib/II single arm CT | 9 | Sunitinib 50.4 Gy/28 fr. |
48.7 Gy | ND median 10 cm |
Delayed (3–6 weeks) |
ND | ND | ND | Any G: 78% | @2y PFS 44% OS 56% |
|
| Canter et al. (19) | Phase I single arm CT | 8 | Sorafenib 50 Gy/25 fr. |
50 Gy | 63% | Delayed (4–6 weeks) |
75% | @3y 100% |
38%@ND | ND | @3y DRFS 42% OS 75% |
|
| Wang et al. (20) | Phase II single arm CT | 79 | 50 Gy/25 fr. with reduced margins |
50 Gy | ND median 11 cm |
Delayed | 76% | @2y 94% |
37%@25% | G2+: fibrosis 5% JS 4% edema 5% |
@2y DRFS 65% OS 81% |
|
| Haas et al. (21) | Phase I single arm CT | 11 | Pazopanib 50 Gy/25 fr. |
50 Gy | 27% | Delayed (5–7 weeks) |
ND | @2y 91% |
20%@0% | ND | @2y DRFS 82% |
|
| Jakob et al. (22) | Phase Ib/II single arm CT | 5 | Sunitinib 50.4 Gy/28 fr. |
48.7 Gy | 40% | Delayed (5–8 weeks) |
100% | @2y 80% |
56%@22% | ND | @2y DRFS 60% |
|
| Hypofractionated RT regimens | Temple et al. (23) | Prospective register | 42 | Doxorubicin 30 Gy/10 fr. |
35 Gy | ND | Delayed (4–6 weeks) |
ND | @5y 97% |
15%@ND | ND | @5y OS 79% |
| Ryan et al. (24) | Retrospective cohort | 25 | EI 28 Gy/8 fr. |
35 Gy | ND median 10 cm |
Delayed (4–5 weeks) |
88% | @2y 88% |
ND@20% | ND | @2y DRFS 78% OS 84% |
|
| MacDermed et al. (25) | Retrospective cohort | 34 included 6 patients with DM |
Ifosfamide 28 Gy/8 fr. |
35 Gy | 32% (>12 cm) | delayed (4–8 weeks) |
100% | @5y 89% |
ND@17% | Fibrosis 14% edema 17% |
@5y (no DM) DRFS 53% OS 45% |
|
| Meyer et al. (26) | Phase I single arm CT | 16 included 2 patients with DM |
Sorafenib EI 28 Gy/8 fr. |
35 Gy | ND | Delayed | 94% | @2y 100% |
38%@ND | ND | @2y PFS 86% |
|
| Koseła-Paterczyk et al. (27) | Prospective register | 272 61 CHT+RT 211 RT |
CHT*&
25 Gy/5 fr. |
37.5 Gy | 42% | Immediate (3–7 days) |
79% | @3y 81% |
all 32% @12% 53% CHT+RT 53% @21% RT 27% @9% |
15% all 23% CHT+RT 12% RT |
@5y OS 60% |
|
| Pennington et al. (28) | Retrospective cohort | 116 | CHT*
28 Gy/8 fr. |
35 Gy | 47% | Delayed (2–3 weeks) |
93% | @3y 89% @6y 83% |
10%@1% | 4% | @3y DRFS 75% OS 82% @6y DRFS 65% OS 67% |
|
| Spalek et al. (29) | Phase II single arm CT | 29 MLPS only |
25 Gy /5 fr. | 37.5 Gy | 66% | Delayed (6–8 weeks) |
93% | @1y 100% |
31%@ND | ND | @1y DRFS 86% |
|
| Spalek et al. (5) | Phase II single arm CT | 30 marginally resectable or unresectable |
1x AI 25 Gy/5 fr. 2x AI |
37.5 Gy | 74% | Delayed (6–8 weeks) |
73% | @1y 97% |
23%@7% | ND | @1y DRFS 74% |
|
| Parsai et al. (30) | Retrospective cohort | 16 3 CHT+RT 13 RT |
CHT*
30 Gy /5 fr. |
50 Gy | 25% | Immediate (0–7 days) |
63% | @1y 100% |
31%@19% | ND | ND | |
| Kalbasi et al. (31) | Phase II single arm CT | 50 | 30 Gy/5 fr. | 50 Gy | 24% | Delayed (2–6 weeks) |
82% | @2y 94% | 32%@24% | G1: fibrosis 24% JS 11% edema 4% G2: fibrosis 11% JS 11% edema 4% |
@2y DRFS 79% |
AI, doxorubicin, ifosfamide; EI, epirubicin, ifosfamide; CHT, chemotherapy; CT, clinical trial; DM, distant metastases; DRFS, distant recurrence-free survival; DSS, disease-specific survival; EQD2, equivalent dose in 2-Gy fractions; G, grade; JS, joint stiffness; MAID, mesna, doxorubicin, ifosfamide, dacarbazine; MLPS, myxoid liposarcomas; ND, no data; OS, overall survival; PFS, progression-free survival; RCT, randomized clinical trial; RT, radiotherapy; STS, soft tissue sarcomas.
*
various regimens were used.
&
only part of a group received chemotherapy.
∧
assessed by authors as grade 3 or higher, or requiring reoperation.