Excellent

Good

Fair

Poor

Acute skin

Follicular, faint or dull erythema/epilation/dry desquamation/decreased sweating

Tender or bright erythema, patchy moist desquamation/moderate oedema

Confluent, moist desquamation other than skin folds, pitting oedema

Ulceration, haemorrhage, necrosis

Late skin toxicity

Slight atrophy, pigmentation change, some hair loss

Patchy atrophy, moderate telangiectasia, total hair loss

Marked atrophy, gross telangiectasia

Ulceration

Late subcutaneous fibrosis

Slight induration, loss of subcutaneous fat

Moderate fibrosis (asymptomatic)

< 10% linear field contraction

Severe induration, loss of subcutaneous tissue, linear contraction > 10%

Ulceration

Induration (subcutaneous fibrosis)

Increased density on palpation

Moderate increase in density, not interfering with ADL; marked increase in density and firmness on palpation with or without minimal retraction

Dysfunction interfering with ADL; very marked density, retraction or fixation

—

Telangiectasia

Few

Moderate

Many and confluent

—

Pain

Pain mild, not interfering with function

Moderate pain; pain or analgesics interfering with function, but not with ADL

Severe pain; pain or analgesics interfering with ADL

Disability

Pain

Mild, not interfering with function

Moderate/analgesics, interferes with function, but not ADL

Severe or interferes with ADL, or both

—

—

Telangiectasia

Few

Moderate

Many or confluent, or both

—

—

Acute skin toxicity

Faint erythema or dry desquamation

Moderate‐to‐brisk erythema, patchy moist desquamation

Moist desquamation not limited to creases or skin folds, bleeding subsequent to minor trauma or abrasion

Skin necrosis or full dermal thickness ulceration

Death

Induration/fibrosis

Increased density on palpation

Moderate functional impairment, not interfering with ADL, increased density and firmness on palpation with or without minor retraction

Interferes with ADL, very marked increased density, retraction or fixation

—

—

Subcutaneous fibrosis

—

Mild induration, can move skin parallel to the plane (sliding) and perpendicular to the plane (pinching up)

Moderate induration, can slide, cannot pinch up skin

Severe induration cannot slide or pinch skin

Death

Telangiectasia

< 10 % of body surface area

≥ 10% of body surface area, psychosocial impact

—

—

—

Pain

mild

Moderate, not limiting instrumental ADL

Severe, limiting self‐care ADL

—

—

0

No fat necrosis

1

Asymptomatic fat necrosis (only radiological or cytological findings, or both)

2

Symptomatic fat necrosis not requiring medication (palpable mass with or without mild pain)

3

Symptomatic fat necrosis requiring medication (palpable mass with significant pain)

4

Symptomatic fat necrosis requiring surgical intervention

Polgár 2007

After 2000, < 40 years excluded

Unifocal tumour, pT1N0‐1miM0, Grade I or II

Negative

< 2.0 cm

(< 2 mm: 1/258, ≥ 2 mm: 246/258 or had no tumour at ink: 11/258)

—

WLE

ELIOT

48–75 years

"Early breast cancer," "suitable for breast conservation"

Not described

≤ 2.5 cm

AD if SNBx positive

BCS

Livi 2015

> 40 years

—

Negative, ≥ 5 mm

≤ 2.5 cm

—

WLE or quadrantectomy

TARGIT

≥ 45 years

T1 and small T2N0‐1M0 invasive breast cancer, suitable for BCS, available for 10 years' follow‐up

≥ 1 mm

Re‐excision strongly advised for close or positive margins

—

—

BCS

RAPID

≥ 40 years

DCIS^a or invasive breast cancer

Negative

≤ 3 cm

Negative axillary nodal involvement including micrometastasis (> 0.2 mm or positive cells only identified on IHC as determined by sentinel node biopsy; axillary node dissection or clinical examination for DCIS only.

BCS

Rodríguez

≥ 60 years

Invasive ductal carcinoma (pT1‐2cNO MO), unifocal tumour, Grade I or II

< 3 mm

≤ 3 cm

—

—

IMPORT

≥ 50 years

Invasive breast cancer pT1‐2pN0 who have < 1% annual risk of local recurrence

≥ 2 mm

≤ 3 cm

0–3 nodes positive

BCS

GEC‐ESTRO

> 40 years

Stage 0, I or II pN0/pNmi breast cancer (including DCIS) no vascular invasion, unifocal or unicentric disease only, no LVINote: 60/1184 (5%) participants had DCIS

≥ 2 mm in invasive disease, 5 mm in DCIS

Lesions < 3 cm in diameter

Node negative, for DCIS alone: sentinel node biopsy optional

WLE or quadrantectomy, level I–II axillary dissection, removing ≥ 6 (preferably 10 lymph nodes)

NSABP‐B39/RTOG

> 18 years

T0‐2N0‐1M0 DCIS or invasive breast cancer

Note: 531/4216 (12%) participants had DCIS

Negative: "free of cancer, including DCSI"

Lesions < 3 cm

≤ 3 involved nodes permitted

Lumpectomy

Polgár 2007

Postimplant CT scans were performed
for 17/87 (20%) participants to document PTV coverage

Interstitial brachytherapy (88/128)

EBRT using photons (40/128)

2‐dimensional CT‐based
treatment planning was used for all participants

PTV: excision cavity delineated by the surgical clips + 2 cm isotropic margin. For interstitial therapy: if electrons were used, 6–15 MeV were used to treat the cavity with a 2 cm margin

ELIOT

Not stated

Intraoperative electrons 6–9 MeV

CTV: quote: "decided according to the site and size of the tumour. The energy of the electron beams was selected according to the thickness of the gland measured by a graduated needle"

Livi 2015

Not stated

EBRT (IMRT)

CTV = +1 cm isotropic margin around surgical clips

PTV = CTV +10 mm isotropic margin^a

TARGIT

No^b

Intraoperative kV RT

3D‐CRT for WBRT

The target volume was the tumour cavity^c

RAPID

Yes^d

EBRT (3D‐CRT)

APBI: 3–5 non‐coplanar fields

CTV = tumour bed on CT (surgical clips plus a 1‐cm margin inside breast
tissue)

PTV = CTV +1 cm isotropic margin

Rodríguez

Not stated

EBRT (3D‐CRT)

PTV was defined by contouring the same quadrant as the primary tumor site^e

IMPORT

Yes^f

Field‐in‐field IMRT

Tumour bed, surgical clips^g recommended

GEC‐ESTRO

Yes^h

HDR or PDR multicatheter brachytherapy

PBI: tumour bedⁱ +2 cm isotropic margin

NSABP‐B39/RTOG

Quote: "Every institution's RT facilities were quality assessed and each case of APBI was centrally reviewed for RT quality." Benchmarking performed with "dummy run"

HDR brachytherapy^j

APBI EBRT: 3D‐CRT^k (IMRT not permitted).

WBRT: 3D‐CRT (IMRT not permitted)

No RNI permitted

WBRT: entire ipsilateral breast

APBI: CTV = cavity = PTV

Study

RT quality assurance

RT technique

Target volume definition

Excellent

Perfect symmetry, no visible distortion or skin changes and no visible catheter entry/exit sequelae

Good

Slight skin distortion, retraction or oedema, any visible telangiectasia, any visible catheter entry/exit scar or mild hyperpigmentation

Fair

Moderate distortion of the nipple or breast symmetry, moderate hyperpigmentation, or prominent skin retraction, oedema or telangiectasia

Poor

Marked distortion, oedema, fibrosis or severe hyperpigmentation

TARGIT

20 Gy at surface of the applicator (attenuated to 5–7 Gy at 1 cm) (APBI)

80 at cavity surface

12.8 at 1 cm

80 Gy at cavity

surface

12.8 Gy at 1 cm

40–56 Gy/20–28 fractions ± 10–16 Gy boost

2

40–56 Gy ±

10–16 Gy

Livi 2015

30 Gy/5 daily fractions EBRT IMRT. 100% of the PTV was covered by 95% of the prescribed dose

6

50 Gy

50 Gy/25 fractions + 10 Gy/5 fractions boost

2

50 + 10 = 60 Gy

RAPID

38.5 Gy/10 fractions twice daily (with 6‐hour gap)

Dose‐evaluation volume (that part of PTV within the breast) received 95–107% of prescription dose

3.85

49.4 Gy

50 Gy/25 fractions or 42.5 Gy/16 fractions ± boost (10 Gy/4–5 fractions) based on criteria such as young age or close margins, prespecified by centre

2 or 2.65

50 Gy or 47.1 Gy

Rodríguez

37.5 Gy/10 fractions twice daily (with 6‐hour gap) (APBI). PTV covered by ≥ 95% of prescribed dose, with < 105% hot spot

3.75

47.48 Gy

48 Gy/24 fractions ± 10 Gy/5 fractions boost

2

48 ± 10 = 48–58 Gy

Polgár 2007

7 × 5.2 Gy HDR (APBI) or 50 Gy/25 fractions (PBI)
Women unsuitable for HDR had 6–15 MeV beam to tumour bed plus 2 cm margin (field size defined using CT‐planning or simulation films)

5.2 or 2

57.5 Gy or 50 Gy

50 Gy/25 fractions (3D‐CRT was not used)

2

50 Gy

GEC‐ESTRO

30.3 Gy/7 fractions or 32 Gy/8 fractions HDR twice daily or 50 Gy at 0.6–0.8 Gy/hour pulses (1 pulse per hour, 24 hours per day) PDR

7–8

41.64–42.67 Gy

50.0–50.4 Gy to a reference point + 10 Gy/5 fractions boost. Electron dose was prescribed to the point of maximum dose on the beam axis (D_max), ensuring the 85% isodose encompassed the tumour bed

1.8–2.0

48.72–50 + 10 = 58.72–60 Gy

ELIOT

21 Gy/1 fraction at 90% using 6–9 MeV

21

84 Gy

50 Gy/25 fractions + 10 Gy/5 fractions boost (using electrons)

2.0

50 + 10 Gy

IMPORT

40 Gy/15 fractions (EBRT)

2.72

45.23

40 Gy/15 fractions

36 Gy/15 fractions + boost 40 Gy/15 fractions

2.72

2.4

45.23

38.4 + 45.23

Polgár 2007

At 6 months, then annually

Acute: CTCAE^a

Late: EORTC/RTOG^b and LENT‐SOMA^c

Not assessed

Harvard Cosmetic Score^d

ELIOT

Annually

LENT‐SOMA^c

Not assessed

Not assessed

Livi 2015

Annually

Acute and late: EORTC/RTOG^b

EORTC QLQ‐C30^e

QLQ‐BR23 breast cancer module^f

Harvard Cosmetic Score^d

TARGIT

Annually

Acute: nil

Late: EORTC/RTOG,^b LENT‐SOMA,^c CTCAE^a

EORTC QLQ‐C30^e

QLQ‐BR23 breast cancer module

Body‐image scale

Clinician and nurse assessed

RAPID

Annually

Acute and late: NCI version 3.0

EORTC QLQ‐C30^e

QLQ‐BR23 breast cancer module

Body‐image scale

EORTC/RTOG Rating System^g

Rodríguez

Baseline 6 months after RT than annually

Late: EORTC/RTOG^b

Not assessed

Harvard Cosmetic Score^d

IMPORT

Annually 1–5 years,

3 yearly to 10 years

Symptomatic rib fracture

and lung fibrosis

Ischaemic heart disease

recorded at 1, 2, 5 and

10 years' follow‐up

EORTC QLQ‐C30^e

QLQ‐BR23 breast cancer module

Body‐image scale

protocol‐specific questions^h

HADS scale

EuroQol EQ‐5D‐3L health status questionnaire

at baseline; 6 months; 1, 2 and 5 years

Patient‐ and

clinician‐assessedⁱ

Photos^j

GEC‐ESTRO

At 6, 12, 18, 24 months after radiotherapy then annually for 10 years

Fat necrosis measured using Lövey scoring system^k

Physician scored late toxicity

Acute radiotherapy toxicity: CTCAE version 3.0^a

LENT‐SOMA^c

Late RT toxicity: EORTC/RTOG^b

Breast pain and arm lymphoedema measured by CTCAE version 3.0^a

EORTC QLQ‐C30^e and QLQ‐BR23 at baseline and during follow‐up

Harvard Cosmetic Score^d

Physician‐ and patient‐reported

Digital photos^l

NSABP‐B39/RTOG

Annually

Acute radiotherapy toxicity: CTCAE version 4.0

Late RT toxicity: CTCAE version 4.0

Not assessed

Physician reported