Table 3. Studies on whole breast irradiation.
| First author, year | Patients (n) | Median age [range], years | Dose to WB/CW | Boost dose | LN dose | RT details | Median FU [range], months | Toxicity evaluation, scale (acute, late) | Acute toxicity (%) | Late toxicity (%) | |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Ortholan, 2005 | 150 | 78 [42–90] | 32.5 Gy (6.5 Gy/fr)* | 1–2 fr (6.5 Gy/fr)* | 27.5 Gy (5.5 Gy/fr)* | Cobalt or 6 MV photon beam, electron beam (for boost and LN); sequential boost: 33.1%; LNI: 31.8% | 65 | RTOG/EORTC, LENT-SOMA | Erythema: G1: 18.7G2: 9.3G3: 0.0 | Subcutaneous fibrosis: G1: 20.7G2: 14.0G3: 4.7 | |
| Courdi, 2006 | 115 | 83 [64–95] | 32.5 Gy (6.5 Gy/fr)* | 1–3 fr (6.5 Gy/fr)* | 27.5 Gy (5.5 Gy/fr)* | Cobalt or 6 MV photon beam, electron beam (for boost and LN); sequential boost: 80%; LNI: 19% | 41 | RTOG/EORTC, LENT-SOMA | Erythema: G1: 20.9G2: 8.7G3: 0.0 | Subcutaneous fibrosis: G1: 16.5G2: 18.3G3: 5.2 | |
| Fiorica, 2012 | 131 | 78 [75–88] | 50 Gy (2.0 Gy/fr)† | 10–16 Gy (2.0 Gy/fr)† | 0 Gy | 3D-CRT; 6–15 MV photon beam; sequential boost: 45.8% | 56 [6–106] | WHO, RTOG-EORTC | Skin toxicity; G1-2: 58.1; G3: 6.1 | Subcutaneous fibrosis: G1-2: 16.0; G3: 0.0 | |
| Méry, 2014 | 44 | 92 | median 40 Gy, median 10 fr; HF: 77% | NR | NR | Curative intent: 73.0%; palliative intent: 27.0% | 9 [1–65] | CTCAE | G1: 34.0; G2: 23.0; G3: 2.0 | G1: 7.0; G2: 2.0; G3: 0.0 | |
| Cante, 2015 | 83 | 70–80: 93%; >80: 7% | 45 Gy (2.25 Gy/fr)† | up to 50 Gy (2.5 Gy/fr)† | 0 Gy | 3D-CRT; 6 MV photon beams | 60 [36–88] | CTCAE | G1: 40.0; G2: 3.0; G3: 0.0 | G1: 21.0; G2: 6.0; G3: 0.0 | |
| Doré, 2015 | 205 | 81 [52–9]; 94%>70 | 45 Gy (3 Gy/fr)‡ | 9 Gy (3 Gy/fr)‡ | Same as WB | 3D-CRT, 4–10 MV photon beam; and 9–12 mev electron beam (for boost and LN); sequential boost: 47.8%; LNI: 32% | 49 | CTCAE | G1: 65.0; G2: 17.0; G3: 4.0 | Fibrosis: 14.6; Telangiectasia: 8.0; hyperpigmentation: 3.9 | |
| Rovea, 2015 | 298 | 80 [57–89] | 80.9%: 32.5 Gy (6.5 Gy/fr)* 19.1%: 30 Gy (6 Gy/fr)* | 0 Gy | 0 Gy | 3D-CRT or IMRT, 5–6 MV photon beam | 46 [12–84] | RTOG/EORTC, CTCAE | G1: 22.6; G2: 4.8; G3: 1.0; G4: 0.3 | Fibrosis: G1: 31.5; G2: 4.2; G3: 3.5; edema: G1: 7.0; G2: 4.2; G3: 1.4 | Telangiectasia: G1: 1.8 G3: 0.7; hyperpigmentation: G1: 4.6; G2: 2.4; atrophy G1: 2.1; pericarditis G1: 0.4 |
| Giugliano, 2016 | 24 | ≥75 | 42.56 Gy (2.66 Gy/fr)* | 0 Gy | 0 Gy | 3D-CRT, 6 MV photon beam | 15 | RTOG/EORTC, CTCAE and LENT-SOMA | G1: 41.7; G2: 29.2; G3: 4.2 | G1: 31.6; G2: 10.5; G3: 0.0 | |
| 36 | < 75 | G1: 66.7; G2: 11.1; G3: 2.8 | G1: 15.6; G2: 0.0; G3: 0.0 | ||||||||
| Monten, 2017 | 95 | 74 | 28.5 Gy (5.7 Gy/fr)‡ | up to 32.5 Gy (6.5 Gy/fr)‡ or 34.5 Gy (6.9 Gy/fr)‡ if R+ | 27 Gy (5.4 Gy/fr)‡ | IMRT-SIB (prone or supine position) or VMAT-SIB (if LNI) | 6 | CTCAE | G1: 52.6; G2: 10.5; G3: 1.1 | NR | |
| Cao, 2018 | 752 | 75 [70–93] | CF: 35%; HF: 57%; HF schemes: −32.5 Gy (6.25 Gy/fr)*; −40.05 Gy (2.67 Gy/fr)†; −41.6 Gy (3.2 Gy/fr)‡ | 16 Gy (2 Gy/fr)† | same as WB | 3D-CRT: 51.7%LD: 42.7% tomotherapy: 0.1%; LNI: 30%; sequential boost: 22.3% | 88 [5–155] | CTCAE, LENT-SOMA | Dermatitis: G1: 35.7; G2: 15.4; G3: 1.6; breast edema: G1: 1.2; G2: 0.1 dysphagia: G1: 0.4 | Breast deformation; G1: 21.3; G2: 2.8; G3: 0.1; fibrosis: G1: 13.8; G2: 2.9; G3: 0.1; acute coronary syndrome G5: 0.1 | Telangiectasia: G1: 8.9; G2: 3.9; G3: 0.4; arm lymphedema: G1: 4.0; G2: 1.0; G3: 0.1; pulmonary fibrosis G1 0.4pneumonitis G2: 0.1 |
| De Santis, 2018 | 752 | 74 [65–92] | 42.4 Gy (2.65 Gy/fr)† | 10 Gy (2.5 Gy/fr)† if high grade; 16 Gy (2 Gy/fr)† if R+ | 0 Gy | 3D-CRT, photon beam for WB, photon or electron beam for boost sequential boost: 25.3% | 46 [8–102] | RTOG/EORTC | G1: 61.8; G2: 21.3; G3: 1.2 | G1: 14.0; G2: 5.0; G3: 0.0 | |
| Fiorentino, 2018 | 40 | 75 [70–83] | 50 Gy (2.0 Gy/fr)† | Up to 60 Gy (2.4 Gy/fr)† | 0 Gy | SIB-IMRT, 6 MV photon beam | 44 [38–66] | RTOG/EORTC | G1: 62.5; G2: 25.0; G3: 0.0 | Skin toxicity: g1: 32.5; g2: 0.0; g3: 0.0 | Fibrosis: G1: 10.0; G2: 0.0; G3: 0.0 |
| 40 | 72 [65–87] | 40.5 Gy (2.7 Gy/fr)† | Up to 48 Gy (3.2 Gy/fr)† | VMAT-SIB, 6 MV photon beam | 45 [34–70] | G1: 52.2; G2: 2.5; G3: 0.0 | Skin toxicity: G1: 5.0; G2: 0.0; G3: 0.0 | Fibrosis: G1: 5.0; G2: 0.0; G3: 0.0 | |||
| Sanz, 2018 | 486 | 79 [58–97] | 90.7%: 37.5 Gy (6.25 Gy/fr)*; 9.3%: 30 Gy; (5 Gy/fr)* | 1–2 fr added (6.25 or 5 Gy)* | Same as WB | Cobalt, 1.25 MV photon: 13.4%; 3D-CRT, photon or electron: 86.6%sequential boost: 17.5%; LNI: 15.0% | 51 [1–163] | RTOG/EORTC | G1: 38.7; G2: 25.3; G3: 10.5 | Subcutaneous fibrosis: G1: 18.5; G2: 6.0; G3: 2.5; G4: 0.2; telangiectasia: 2.7; edema/mastitis: 1.0 | |
*, weekly fractions; †, daily fractions; ‡, alternate days fractions. 3D-CRT, three-dimensional conformal radiotherapy; BCS, breast conservative surgery; CF, conventional fractionation; CTCAE, common terminology criteria for adverse events; CW, chest wall; fr, fraction; FU, follow-up; HF, hypofractionation; IMRT, intensity modulated radiotherapy; LENT-SOMA, Late Effects Normal Tissue Task Force-Subjective, Objective, Management, Analytic; LD, lateral decubitus; LN, lymph nodes; LNI, lymph nodes irradiation; pts, patients; R+, positive margins after BCS; RT, radiotherapy; RTOG-EORTC, radiation therapy oncology group- European Organisation for Research and Treatment of Cancer; SIB, simultaneous integrated boost; VMAT, Volumetric Modulated Arc Therapy; WB, whole breast; WHO, world trade organization; NR, not reported.