Accelerated partial breast irradiation: Past, present, and future

Table 1 Additional selected, non-randomized clinical experience with interstitial brachytherapy with more than 5 years follow-up

Ref.	No. of patients	Follow-up interval (yr)	Modality	Scheme	Total dose (Gy)	5-yr LR (%)	Good/excellent cosmesis
Strnad et al[57]	274	5.25	PDR/HDR	PDR = 0.6 Gy/h	PDR = 50 Gy	2.9%	90%
				HDR = 4 Gy × 8	HDR = 32 Gy
Rabinovitch et al[32,58]	98	11.3	LDR/HDR	LDR = 3.5-5 d	LDR = 45 Gy	4%	68%
				HDR = 3.4 Gy × 10	HDR = 34 Gy
Shah et al[59,60]	199	12.0	LDR/HDR	LDR 0.52 Gy/h × 96 h	LDR = 50 Gy	5% (12-yr 5%)	99%
				HDR = 4 Gy × 8	HDR = 32 Gy
				HDR = 3.4 Gy × 10	HDR = 34 Gy
King et al[27]	51	6.25	LDR/HDR	LDR = 4 d	LDR = 45 Gy	3.9%	75%
				HDR = 4 Gy × 8	HDR = 32 Gy
Ott et al[61,62]	274	5.33	PDR/HDR	PDR = 0.6 Gy/h	PDR = 49.8 Gy	2.3%	92%
				HDR = 4 Gy × 8	HDR = 32 Gy
Polgár et al[63]	45	11.1	HDR	4.33 Gy × 7	30.3 Gy	4.4% (12-yr 9.3%)	78%
				5.2 Gy × 7	36.4 Gy

HDR: High-dose rate; LDR: Low dose rate; LR: Local recurrence; PDR: Pulsed-dose rate.

Table 2 Accelerated partial breast irradiation patient selection criteria according to American Society for Radiation Oncology consensus statement[52]

Factors	Suitable	Cautionary	Unsuitable
Age (yr)	> 60	50-59	< 50
BRCA1/2 mutation	Not present	NS	Present
Tumor size	< 2 cm	2.1-3.0 cm	> 3 cm
T stage	T1	T0 or T2	T3-4
Margins	Negative (> 2 mm)	Close (< 2 mm)	Positive
Grade	Any	NS	NS
LVSI	No	Limited/focal	Extensive
ER status	Positive	Negative	NS
Multicentricity	Unicentric only	NS	Present
Multifocality	Clinically unifocal with total size < 2 cm	Clinically unifocal with total size 2.1-3.0 cm	Microscopically multifocal > 3 cm in total size or if clinically multifocal
Histology	Invasive ductal or other favorable subtypes	Invasive lobular	NS
Pure DCIS	Not allowed	< 3 cm	> 3 cm
EIC	Not allowed	< 3 cm	> 3 cm
Associated LCIS	Allowed	NS	NS
LN status	pN0 (i-, i+)	NS	pN1, pN2, pN3, or if not evaluated
Neoadjuvant therapy	Not allowed	NS	If used

DCIS: Ductal carcinoma in situ; EIC: Extensive intraductal component; ER: Estrogen receptor; LCIS: Lobular carcinoma in situ; LVSI: Lymphovascular space invasion; LN: Lymph node; NS: Not specified.

Table 3 Accelerated partial breast irradiation patient selection criteria from selected organizations

Organization	Age	Tumor size	Margin	Histology	LN status
American Brachytherapy Society[64]	> 50	< 3 cm	Negative (at inked margin)	Invasive ductal carcinoma	pN0; by SLN or axillary dissection
American Society of Breast Surgeons[36]	> 45	< 2 cm	Negative (> 2 mm)	Invasive ductal carcinoma or DCIS	pN0; by SLN or axillary dissection
ASTRO[52]	> 60	< 2 cm	Negative (> 2 mm)	Invasive ductal or other favorable subtypes (mucinous, tubular, and colloid)	pN0; by SLN or axillary dissection

ASTRO: American Society for Radiation Oncology; DCIS: Ductal carcinoma in situ; SLN: Sentinel lymph node.

Table 4 Phase III prospective randomized trials evaluating the equivalence or non-inferiority of accelerated partial breast irradiation with whole-breast irradiation

Trial	No. of patients	Follow-up interval (yr)	Inclusion criteria	APBI technique	5-yr LR APBI vs WBI (%)
TARGIT-A[45]	3451	2.4	Age ≥ 45 yr; T1, small T2, N0, N1; ductal; non-lobular and no EIC	20 Gy in 1 fraction, IORT low energy X-rays (50 kV)	3.3 vs 1.3
ELIOT[47]	1305	5.8	Age ≥ 48 yr; T ≤ 2.5 cm, N0; invasive carcinoma; quadrantectomy	21 Gy in 1 fraction, IORT, electrons up to 9 MeV	4.4 vs 0.4
RAPID (OCOG)[41]	2135	Pending	Age > 40 yr; T ≤ 3 cm, N0; DCIS or invasive carcinoma; negative margins	38.5 Gy in 10 fractions (5-8 d) using 3D-CRT	Pending
GEC-ESTRO[35]	1184	5.0	Age ≥ 40 yr; T ≤ 3 cm, pN0-Nmi; stage 0, I, II; DCIS, ductal or lobular carcinoma; margin ≥ 2 mm	32 Gy in 8 fractions or 30.3 Gy in 7 fractions MIB HDR or 50 Gy MIB PDR (1 pulse/h, 24 h/d; 0.6-0.8 Gy/h)	1.4 vs 0.9
Florence (NCT02104895)[42]	520	5.0	Age > 40 yr; T < 2.5 cm; clear margins > 5 mm	IMRT 30 Gy in 5 daily fractions	1.5 vs 1.5
IMPORT-LOW	2018	Pending	Age ≥ 50 yr; T ≤ 3 cm, node negative; invasive adenocarcinoma; margin ≥ 2 mm	IMRT; Arm 1: 40 Gy in 15 fractions to primary tumor region + 36 Gy in 15 fractions to low-risk region (EBRT) Arm 2: 40 Gy in 15 fractions to primary tumor region (EBRT)	Pending
IRMA (NCT01803958)	3302 (Currently Enrolling)	Pending	Age ≥ 49 yr; T < 3 cm, N0; invasive carcinoma; margins ≥ 2 mm	38.5 Gy in 10 fractions using 3D-CRT, BID	Pending
SHARE (NCT01247233)	1006	Pending	Age ≥ 50 yr; invasive carcinoma; T ≤ 2 cm; margin≥ 2 mm; pN0 (i+/-)	3D-CRT 40 Gy in 10 fractions, BID	Pending
NSABP B-39/RTOG 0413	4300	Pending	Age ≥ 18 yr; DCIS or invasive adenocarcinoma; stage 0, I, II (T < 3 cm); lumpectomy; margins free of tumor; ≤ 3 positive nodes	34 Gy in 10 fractions using MIB or MammoSite®/MammoSite® ML/SAVI® or 38.5 Gy over 10 fractions using 3D-CRT	Pending

3D-CRT: 3D conformal external-beam radiation; BID: Twice daily; DCIS: Ductal carcinoma in situ; EBRT: External beam radiation therapy; EIC: Extensive intraductal component; HDR: High-dose rate; MIB: Multicatheter interstitial brachytherapy; ML: Multilumen; IMRT: Intensity modulated radiotherapy; IORT: Intraoperative radiotherapy; PDR: Pulsed-dose rate; WBI: Whole-breast irradiation.