Table 1.

Selected studies evaluating IMRT versus 2D-RT or 3D-CRT. Patients were further stratified by small, medium or large-sized breasts.

Study	Number of patients	Type of study	Technique	Total dose and Fractionation CF/HF	Breast size (median breast volume)cm3	Scoring system	G1 or G2 (%) (whole group)	G2 or G3 (%) (whole group)	G3 or G4 (%) (whole group)	General comments
Freedman 200627	131	Case-control retrospective study	F-IMRT 2D-RT	46–50 Gy in 23–25 fractions + boost 10–16 Gy	Breast size was grouped as small (34 A, B; 36 A), medium (34 C; 36 B, C; 38A, B, C), or large (any D or size ≥ 40)	CTCAE v. 3.0	30 (IMRT) 28 (2D-RT)	70 (IMRT) 72 (2D-RT)	0 (IMRT) 0 (2D-RT)	IMRT is associated with a decrease in severity of acute desquamation compared with a matched control group treated with conventional radiation therapy.
Harsolia, 200725	172	Retrospective study	F-IMRT 2D-RT	CF median dose 45 Gy + 16 Gy boost	1.326 (IMRT) 1.489 (2D-RT) Breast volume divided into groups: 1.000 cm3 (small), 1.000–1.599 cm3 (medium), 1.600 cm3 (large)	NCI CTC v. 2.0	41 (IMRT) 85 (2D-RT)		1 (IMRT) 6 (2D-RT)	Lower rates of ≥ G2 toxicity with IMRT regardless of breast size. ≥ G2 clinical toxicities associated with larger irradiated breast sizes, on average (<1.000 cm3; vs. >1.600 cm3) No G3 acute toxicity with breast volume (<1.000 cm3) and 3% G3 skin reaction in patients with breast volumes 1.600 cm3.
Freedman 200910	804	Retrospective study	F-IMRT 2D-RT	46–50 Gy in 23–25 fractions + boost 10–18 Gy	Bra size, (at least 63% with small and medium sizes) Small (32; 34A, B; 36A), Medium (34C; 36B, C;38A, B, C); Large (any D or size 40+)	CTCAE v. 3.0	52 (IMRT) 75 (2D-RT)			More large-breasted patients in IMRT group. IMRT reduces the incidence of ≥ G2 dermatitis in women of all breast sizes.
Shah 201223	335	Prospective study	IMRT 2D-RT IMRT: HF -inversely planned IMRT CF - forward planned IMRT	Median dose 45 Gy + boost 16 Gy or 42.56 Gy without a boost	1.378 for the whole group	CTCAE v. 3.0	1 (CF-IMRT) 23 (HF-IMRT) 12 (2D-RT)			IMRT is associated with reduced toxicities compared with 2D radiotherapy.
					Breast volume divided into groups: 1.000 cm3 (small), 1.000-1.599 cm3 (medium), 1.600 cm3 (large)					In large-breasted patients, CF-IMRT was associated with reduced acute toxicities, while HF-IMRT was not.
Hardee 201228	97	Prospective study	H-IMRT 3D-CRT IMRT: hybrid IMRT using a mixture of 3D tangent fields and dynamic multileaf collimator (MLC) IMRT fields in a 2:1 ratio	46 Gy in 23 fractions + 14-Gy boost or 42.72 Gy in 16 fractions; all in prone position	Breast size was classified as small (A cup, <750 cm3), medium (B-C cups, 750–1.499 cm3), and large (D cup or larger,≥ 1,500 cm3)	RTOG	5.1% ≥ G2			Hypofractionated breast radiotherapy is well tolerated when treating patients in the prone position, even among those with large breast volumes. Breast IMRT significantly improves dosimetry but yields only a modest but confirmed benefit in terms of toxicities.
De Langhe 201432	377	Prospective study	Prone or supine position with INV-IMRT or prone with F-IMRT or prone position with DIBH (n = 22) or supine F-IMRT ± DIBH	40.05 Gy in 15 fractions + boost 10 Gy in 4 fractions (90–75% of patients) or 50 Gy in 25 fractions for 65% of patients with bra cup size ≥ D	Breast size was classified A, B, C and ≥ D cup	CTCAE v. 3.0	57.3 (≥ G2)			CF, supine IMRT, concomitant hormone treatment, high BMI, large breast, smoking during treatment, and genetic variation (in MLH1 rs1800734): all were associated with ≥ G2 toxicity.

2D-RT = standard 2D wedged plan; CTCAE v. 3.0 = common terminology criteria for adverse events for acute radiation dermatitis, version 3.0; CF = conventional fractionation; HF = hypofractionation; DIBH = deep inspiration breath hold; F-IMRT = forward planned intensity modulated radiotherapy; H-IMRT = hybrid intensity modulated radiotherapy; NCI CTC v. 2.0 = National Cancer Institute common toxicity criteria; version 2.0; RTOG = Radiation Therapy Oncology Group criteria