Table 2.
Characteristic of selected studies for systematic review
| Guidolin et. al. [15] | Tiberi et. al. [16] | Liveringhouse et. al. [17] | Meattini et. al. [18] | Horton et. al. [19] | Bondiau et. al. [20] | Vasmel JE et. al. [21], [22] | Guanglei Chen et. al. [23] | De Caluwe et. al. [24] | |
|---|---|---|---|---|---|---|---|---|---|
| Type of study | Phase II SIGNAL trial, prospective, single arm, non randomized | Phase II, prospective, single arm, nonrandomized | Phase II, prospective, single arm, nonrandomized | Phase II ROCK trial, prospective, single arm, non randomized | Phase I, dose escalation, prospective, single arm, nonrandomized | Phase I, dose escalation, prospective, single arm, non randomized | Phase II, prospective, single arm, non randomized | Phase II, prospective, single arm, non randomized | Phase I Neo- Checkray Trial, prospective, single arm, non randomized |
| Number of participants | 27 | 10 | 20 | 22 | 32 | 25 | 36 | 10 | 6 |
| Main endpoints | Feasibility, toxicity, cosmesis | Radiologic and pathologic response, toxicity | Radiologic and pathologic response | Pathologic response, toxicity, cosmesis | Radiologic response, toxicity, cosmesis | Toxicity, cosmetics, pathologic response, establishing maximum tolerable dose in combination with neoadjuvant therapy | Pathologic and radiologic response, toxicity, cosmesis | Pathologic complete resposne, objective resposne rate, residual cancer burden 0-I, safety | Feasibility of delivering SBRT, toxicity, cosmesis |
| Inclusion criteria TNM |
Postmenopausal, unifocal, ≤ 20 mm, unifocal, ER positive, cN0 In initial ultrasound distance ≥ 2 cm between the lesion and the skin and the lesion and the chest wall |
≥ 65 years, ≤ 20 mm, unifocal, ER positive, HER 2 negative, cN0, Grade1-2 | ≥ 50 years, Unifocal, ≤ 20 mm, ER positive, HER 2 negative, cN0 | ≥ 50 years, ER/PR positive, HER 2 negative unifocal, ≤ 25 mm, cN0 | ≥ 55 years, ER/PR positive, HER 2 negative, ≤ 20 mm, low/intermediate grade, no LVSI, DCIS ≤ 2cm, cN0 | ≥ 18 years, cT1-T3, cN0-N1, unifocal, not suitable for BCT | ≥ 50 years, unifocal, ≤ 20 mm, ER positive, HER2 negative, cN0 or ≥ 70 years, unifocal, ≤ 30 mm, ER positive, HER2 negative, cN0 | 18–75 years, TNBC, cT2-T3N0-N2 | ≥ 18 years, Luminal B, Ki67 ≥ 15% or G3, MammaPrint high risk, cT2-3N0 or cT1b-3N1-3, size ≥ 1.5 cm |
| Contouring |
GTV + 5 mm = CTV CTV + 5 mm = PTV |
GTV + 10 mm = CTV CTV + 10 mm = PTV |
GTV + 15 mm = CTV CTV + 3 mm = PTV |
GTV + 15 mm = CTV CTV + 3 mm = PTV |
GTV + 15 mm = CTV CTV + 3 mm = PTV |
GTV + 5 mm = CTV CTV + 2 mm = PTV |
GTV + 20 mm = CTV CTV + 3 mm = PTV |
GTV, margins NR | GTV + margin NR |
| Concurrent systemic therapy | – | – | – | – | – | 3 cycles of docetaxel (100 mg/m [2]), SBRT on 3 consecutive days during the second cycle but not in the chemotherapy days, 3 FEC cycles (fluorouracil 500 mg/m2, epirubicine 100 mg/m [2], and cyclophosphamide 500 mg/m [2]). Cycles q3w | Six patients (17%) -neoadjuvant endocrine started after NA-PBI | 8 cycles of adebrelimab (20 mg/kg every 3 weeks). SBRT at the second cycle every other day, 6 cycles of nab-paclitaksel (125 mg/m [2] on 1st and 8th day) and carboplatin (area uder curve 6 mg/ml per min on 1st day) every 3 weeks since 3rd cycle |
12 cycles of paclitaxel 80 mg/m [2] weekly then 4 cycles q2w dose dense doxorubicin-cyclophosphamide (60 mg/m [2] and 600 mg/m [2] respectively); then 5 administrations of durvalumab 1500 mg Every 5 weeks for five administrations q4w and 4 administrations oleclumab 3000 mg q2w for followed by q4w for 3 administrations SBRT given in week 4–5, followed by the week 5 systemic treatment |
| MRI coregistered to planning CT | + | – | + | + | + | + | + | + | + |
| System and Technique | LINAC/VMAT | LINAC/IMRT | LINAC/VMAT | Cybernife | LINAC/IMRT | Cyberknife | LINAC/VMAT | LINAC/IMRT | LINAC/VMAT |
| Dose fractionation schemas | 21 Gy- 1 fraction | 20 Gy-1 fraction | 28.5 Gy- 3 fractions, 9.5 Gy daily | 21 Gy- 1 fraction | 15 Gy (n = 8), 18 Gy (n = 8), 21 Gy (n = 16) in 1 fraction | 19.5 Gy (n = 3), 22.5 Gy (n = 3), 25.5 Gy, (n = 6), 28.5 Gy (n = 7), 31.5 Gy (n = 6)- 3 fractions q2d | 20 Gy for GTV, 15 Gy for CTV- SIB—1 fraction | 24 Gy- 3 fractions q2d | 24 Gy- 3 fractions n consecutive days |
| Positioning | Surgical clip, cone-beam CT prone | Surgical clip, cone-beam CT supine | Surgical clip, cone-beam CT supine | Supine | Surgical clip, cone-beam CT prone | Supine | Surgical clip, cone-beam CT supine | NR | NR |
| Time from SBRT to surgery | 1 week | 11–13 weeks | 6–8 weeks | 2 weeks | 10 days | 19–23 weeks | 6 months (n = 15), 8 months (n = 21) | 21–23 weeks | 16–20 weeks |
| pCR | NR | pCR—0 (0%), pPR- 80% (n = 8) | 0 (0%) | 2 (9%) | NR | 9 (36%) | 15 (42%), 5 (33%) after 6 months, 10 (48%) after 8 months, 12 (33%) near pCR | 9 (90%) | 2 (33.3%), 2 (33.3%) near pCR |
| Scales used to evaluate toxicity | CTCAE v. 4.03 | CTCAE | CTCAE v. 4.0 | RTOG/EORTC | CTCAE | NR | CTCAE v. 4.03 | CTCAE v. 5.0 | CTCAE v. 5.0 |
| Acute and late toxicity related to SBRT | Acute—3 weeks postop.- 0 ≥ G2, Late—6 month postop.-1 (3.7%) G2 wound infection, 1 year postop.—No ≥ G2 | Acute- 0 ≥ G2, Late- NR | Acute- 4 to 5 weeks after SBRT- G2- toxicity – breast pain – 1 (5%) and erythema – 1 (5%), no G3, Late: patients without postoperative WBRT (n = 16), G2 -3 (19%)-skin induration, breast pain, atrophy), G3—1wound complication. patients after WBRT: skin induration G2- 2 (50%), seroma G2 -1 (25%), atrophy G2 -1 (25%), G3 toxicity in 2: abscess -1 (25%), breast pain -1 (25%) |
Acute (7–30 days after SBRT)—breast oedema- G2—1 (4.55%), Acute (30 days after SBRT) – breast induration G2 -1 (4,5%) Late (6–12 months after SBRT) G2 -1 (4,5%) |
Acute G2: Wound infection – 1 (3%), breast pain 2 (6%), dermatitis 3 (10%) Late: fibrosis G2 -3 (10%), G3 -1 (3%), breast atrophy G2 -2 (6%), G3 – 1 (3%), breast pain G2 -2 (6%), dermatitis G2 1 (3%), infection G2 1 (3%), seroma G2 1 (3%), hyperpigmentation G2 1 (3%) |
Acute—G2 skin erythema- 1 in 22.5 Gy cohort and 1 in 25.5 Gy cohort, G3 dermatologic erythema- 1 on 7 (14%) in 28,5 Gy cohort, Late- 0% |
Before BCS r 6–8 months after SBRT: G2– chest pain- 1 (3%), breast pain- 1 (3%), breast edema- 1 (3%) Late (12 months from SBRT) G2 – breast pain 2 (6%), chest pain -1 (3%), wound infection 5 (15%) Late G3—1 (3%) transient wound infection Late (18 months after BCS): n = 0 |
Related to sbrt Acute- 0 (0%) Late- 0 (0%) |
Acute < G2- 1 (16.7%) breast pain Late- 0 (0%) |
| Cosmesis |
Modified Harvard–Harris Cosmetic Scale-Physician-rated (good or excellent)-100% (baseline), 93% (3 weeks), 96% (6 months), 92% (1 year postoperatively) Patients rated –(good or excellent)-96% (baseline), 93% (3 weeks), 92% (6 months), 96% (1 year postoperatively) No significance difference from the baseline, |
EORTC scale—NR | Overall physician- reported—„good”- 17 (85%), „fair”- 2 (10%), „poor”- 1 (5%) |
NSABP B-39/RTOG 0413 cosmesis evaluation scale After 6 and 12 months: 28 (100%) -good/excellent |
NR | 94% of the patients very satisfied, satisfied, or not unsatisfied | NR | Excellent in 4 (66.6%) and good in 2 (33.3%) | |
| Median Follow-up time | 12 months | 3 months | 14 months | 18 months | 23 months | 30 months | 21 months | 13 months | 25.5 months |
| Adjuvant EBRT | none | none | In 4 patients (20%) with ypN + | In 2 patients | In 3 patients (6%) | All but 2 who refused | none | NR | NR |
e2d—Every 2 days, q2w – Every 2 weeks, BCT- Breast conserving treatment, GTV- Gross tumor volume, CTV- Clinical target volume, PTV- Planning target volume, CTCAE—Common terminology criteria for adverse events, NR- Not reported, EORTC—European organisation for research and treatment of cancer, RTOG—Radiation therapy oncology group, pCR- Pathological complete response, LINAC—Linear accelerator, IMRT—Intensity modulated radiation therapy, VMAT—Volumetric arc therapy