Materials and Methods
Literature Search
Study Selection
Population
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Women with early-stage breast cancer who underwent breast-conserving treatment, including those with stage T1-2N0-3M0;
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Experimental group: IORT boost combined with postoperative WBI;
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Control group: Conventional external beam radiotherapy (EBRT), including WBI using external irradiation with or without tumour bed boost;
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Outcomes: Local recurrence rates (LRRs), survival outcomes, cosmetic outcomes, and toxicity;
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Study design: Randomised, clinical trials (RCTs) and other comparative studies with control groups.
Data Extraction and Quality Assessment
Statistical Analysis
Results
Study Selection
Study Characteristics and Quality Assessment
Study | Item | Total | |||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
(1) | (2) | (3) | (4) | (5) | (6) | (7) | (8) | (9) | (10) | (11) | (12) | ||
Reitsamer 2006 [22] | 2 | 2 | 2 | 2 | 0 | 2 | 2 | 0 | 2 | 2 | 2 | 2 | 20 |
Kraus-Tiefenbacher 2006 [25] | 2 | 2 | 2 | 2 | 0 | 2 | 2 | 0 | 2 | 2 | 1 | 2 | 19 |
Welzel 2010 [24] | 2 | 2 | 2 | 2 | 0 | 2 | 2 | 0 | 2 | 2 | 2 | 2 | 20 |
Sperk 2012 [23] | 2 | 2 | 2 | 2 | 0 | 2 | 2 | 0 | 2 | 2 | 1 | 2 | 19 |
Fastner 2014 [20] | 2 | 2 | 0 | 2 | 0 | 2 | 2 | 0 | 2 | 2 | 2 | 2 | 18 |
Kolberg 2017 [21] | 2 | 2 | 0 | 2 | 0 | 2 | 2 | 0 | 2 | 2 | 2 | 2 | 18 |
Sorrentino 2018 [26] | 2 | 2 | 2 | 2 | 0 | 2 | 2 | 0 | 2 | 2 | 2 | 2 | 20 |
Hashemi 2021 [27] | 2 | 2 | 2 | 2 | 0 | 2 | 2 | 0 | 2 | 2 | 2 | 2 | 20 |
Clinical trials | Dates of accrual | Study design | Age (yr) | Tumour size | Nodal stage | Sample size | Arms | Intervention | Median follow-up | Outcome | Quality assessment |
---|---|---|---|---|---|---|---|---|---|---|---|
Ciabattoni 2021 [19] | 1999 –2004 | RCT | Median IORT: 56.3 EBRT: 56.2 | IORT (n): T1: 96 T2: 28 T3-T4: 1 Missing: 0 EBRT (n): T1: 79 T2: 22 T3-T4: 1 Missing: 8 | IORT: N0: 82 N1: 38 N2: 2 N3: 1 Missing: 2 EBRT: N0: 68 N1: 32 N2: 1 N3: 1 Missing: 8 | 235 | IORT (N = 125) EBRT (N = 110) | IORT: Single dose of 10 Gy to the tumour bed using mobile linear accelerator Novac7+whole breast irradiation (50 Gy). EBRT: Whole breast irradiation (50 Gy) with an external boost (10 Gy). | 12 yr (range 10–16 yr) | Local recurrence; Distant recurrence; Cosmetic outcome; Toxicity; Disease-free survival; Overall survival | 8a |
Fastner 2014 [20] | 2002 –2007 | Non-RCT | Median IORT: 48 EBRT: 53.5 | Median (cm) IORT: 3.40 EBRT: 2.60 | IORT: N0: 47 N1: 29 N2: 5 N3: 0 EBRT: N0: 12 N1: 7 N2: 4 N3: 3 | 107 | IORT (N = 81) EBRT (N = 26) | IORT: Single dose of 9 Gy (10 Gy [Dmax]) to the tumour bed using electrons+whole breast irradiation (51–57 Gy). EBRT: Whole breast irradiation (51–57 Gy) with an external boost (6–16 Gy). | IORT: 59 mo (range, 3–115) EBRT: 67.5 mo (range, 13–120) | Local control; Locoregional control; Metastasis-free survival; Disease-specific survival; Overall survival | 18b |
Sperk 2012 [23] | 2002 –2008 | Non-RCT | Median IORT: 62 EBRT: 69 | IORT (n): yT0: 1 T1: 128 T2: 66 Unknown: 1 EBRT (n): T1: 47 T2: 8 | IORT: N0: 144 N1: 36 N2: 14 Unknown: 2 EBRT: N0: 44 N1: 10 N2: 1 | 251 | IORT (N = 196) EBRT (N = 55) | IORT: Single dose of 20 Gy to the tumour bed using 50 kV x-rays+whole breast irradiation (46–50 Gy). EBRT: Whole breast irradiation (56 Gy/28 fx). | IORT: 52 mo EBRT: 42 mo | Toxicity; Local recurrence; Overall survival | 19b |
Welzel 2010 [24] | 2002 –2006 | Non-RCT | Median IORT: 67 EBRT: 66 | Tumor size <2 cm, n (%) IORT: 14 (61%) EBRT: 17 (74%) | IORT: N0: 20 N1: 3 EBRT: N0: 23 N1: 0 | 46 | IORT (N = 23) EBRT (N = 23) | IORT: Single dose of 20Gy to the tumour bed using 50 kV x-rays+whole breast irradiation (46/50 Gy). EBRT: Whole breast irradiation (56 Gy/28 fx). | IORT: 47 mo EBRT: 44 mo | Quality of life; Toxicity; Disease-free survival | 20b |
Reitsamer 2006 [22] | 1996 –2001 | Non-RCT | Median IORT: 59.03 EBRT: 57.07 | IORT (n): T1a: 3 T1b: 15 T1c: 112 T2: 60 EBRT (n): T1a: 6 T1b: 20 T1c: 102 T2: 60 | IORT: N (-): 117 N1mic: 14 N (+): 59 EBRT: N (-): 126 N1mic: 8 N (+): 54 | 378 | IORT (N = 190) EBRT (N = 188) | IORT: 9 Gy prescribed to the 90% isodose using 4–18 MeV electrons+whole breast irradiation (51/56.1 Gy). EBRT: Whole breast irradiation (51/56 Gy) with an external boost (12 Gy). | IORT: 51.1 mo EBRT: 81 mo | Ipsilateral breast tumour recurrence; Distant recurrence; Disease-free survival | 20b |
Kraus- Tiefenbacher 2006 [25] | 2002 –2005 | Non-RCT | Median IORT: 63 EBRT: 56 | Median (cm) IORT: 1.50 EBRT: 1.70 | IORT: N0: 61 N1: 18 N2: 3 N3: 2 EBRT: N0: 29 N1: 17 N2: 4 N3: 0 | 137 | IORT (N = 84) EBRT (N = 53) | IORT: Single dose of 20 Gy to the tumour bed using 50-kV x-rays+whole breast irradiation (46/23 fx). EBRT: Whole breast irradiation (three patients with ductal carcinoma in situ were treated with a total dose of 50 Gy, and 34 patients were treated with 56 Gy. Additionally, 16 patients younger than age 50 yr were treated with 50 Gy WBRT followed by a 14–16 Gy electron boost) (50–66 Gy). | 4–6 mo | Cosmetic outcome; Toxicity | 19b |
Kolberg 2017 [21] | 2010–2011 | Non-RCT | Mean IORT: 54.9 EBRT: 57.8 | Mean (cm) IORT: 2.16 EBRT: 2.59 | IORT: N (-): 28 N (+): 33 EBRT: N (-): 25 N (+): 30 | 116 | IORT (N = 61) EBRT (N = 55) | IORT: Single dose of 20 Gy to the tumour bed using 50-kV x-rays+whole breast irradiation (50 Gy/25 Fx). EBRT: Whole breast irradiation (50 Gy/25 Fx) with an external boost (10 Gy/16 Gy). | 49 mo | Local recurrence; Local recurrence-free survival; Disease-free survival; Distant disease-free survival; Breast cancer mortality; Non-breast cancer mortality; Overall mortality | 18b |
Hashemi 2021 [27] | 2013–2019 | Non-RCT | Median IORT: 40-50 EBRT: 40-50 | Median (cm) IORT: ≤2.5 cm EBRT: ≤2.5 cm | Negative | 1646 | IORT (N = 989) EBRT (N = 657) | IORT: ①12 Gy as a boost dose by making flaps in breast tissue around the tumour cavity with a maximum thickness of 2 cm, using light intraoperative accelerator (LIAC), a mobile linear accelerator delivering energy levels of 6–12 MeV electrons+whole breast irradiation (45-50 Gy). ②20 Gy intraoperative x-ray radiation therapy of 50 kV was delivered to breast tissue around the tumour cavity+whole breast irradiation (45-50 Gy) EBRT: Whole breast irradiation (45-50 Gy) with an external boost (10 Gy). | IORT: 34.5 mo EBRT: 40.18 mo | Local recurrence; Distant recurrence; Disease-free survival; Overall survival | 20b |
Sorrentino 2018 [26] | 2011–2016 | Non-RCT | Mean IORT: 61.4 (±11.2) EBRT: 65.5 (±8.9) | IORT (n): Tx: 0 Tis: 2 T1a: 3 T1b: 20 T1c: 51 T2: 7 EBRT (n): Tx: 1 Tis: 9 T1a: 24 T1b: 62 T1c: 99 T2: 25 | IORT: N (-): 73 N (+): 10 EBRT: N (-): 185 N (+): 35 | 303 | IORT (N = 83) EBRT (N = 220) | IORT: 12 Gy as a boost using a linear accelerator (LIAC, SIT®)+hypofractionated scheme of 13 daily fractions of 2.85 Gy, up to a total dose of at 37.05 Gy. EBRT: 45 Gy in 20 fractions plus a concomitant 5 Gy boost in four weekly fractions (1.25 Gy per fraction), usually delivered with electrons. | IORT: Mean 37.1 (±13.8) mo EBRT: Mean 33.5 (±17.4) mo | Local recurrence; Distant recurrences; Adverse effects and toxicities; Evaluation of quality of life and self-perception of body image; Changes in working and normal daily activities | 20b |