Scolaris Content Display Scolaris Content Display

Study flow diagram.
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Figure 1

Study flow diagram.

Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
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Figure 2

Risk of bias summary: review authors' judgements about each risk of bias item for each included study.

Forest plot of comparison: 1 Partial breast irradiation (PBI)/accelerated partial breast irradiation (APBI) versus whole breast radiotherapy (WBRT), outcome: 1.1 Local recurrence‐free survival.
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Figure 3

Forest plot of comparison: 1 Partial breast irradiation (PBI)/accelerated partial breast irradiation (APBI) versus whole breast radiotherapy (WBRT), outcome: 1.1 Local recurrence‐free survival.

Forest plot of comparison: 1 Partial breast irradiation (PBI)/accelerated partial breast irradiation (APBI) versus whole breast radiotherapy (WBRT), outcome: 1.3 Overall survival.
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Figure 4

Forest plot of comparison: 1 Partial breast irradiation (PBI)/accelerated partial breast irradiation (APBI) versus whole breast radiotherapy (WBRT), outcome: 1.3 Overall survival.

Forest plot of comparison: 1 Partial breast irradiation (PBI)/accelerated partial breast irradiation (APBI) versus whole breast radiotherapy (WBRT), outcome: 1.8 Cause‐specific survival.
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Figure 5

Forest plot of comparison: 1 Partial breast irradiation (PBI)/accelerated partial breast irradiation (APBI) versus whole breast radiotherapy (WBRT), outcome: 1.8 Cause‐specific survival.

Forest plot of comparison: 1 Partial breast irradiation (PBI)/accelerated partial breast irradiation (APBI) versus whole breast radiotherapy (WBRT), outcome: 1.9 Distant metastasis‐free survival.
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Figure 6

Forest plot of comparison: 1 Partial breast irradiation (PBI)/accelerated partial breast irradiation (APBI) versus whole breast radiotherapy (WBRT), outcome: 1.9 Distant metastasis‐free survival.

Comparison 1 Partial breast irradiation (PBI)/accelerated partial breast irradiation (APBI) versus whole breast radiotherapy (WBRT), Outcome 1 Local recurrence‐free survival.
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Analysis 1.1

Comparison 1 Partial breast irradiation (PBI)/accelerated partial breast irradiation (APBI) versus whole breast radiotherapy (WBRT), Outcome 1 Local recurrence‐free survival.

Comparison 1 Partial breast irradiation (PBI)/accelerated partial breast irradiation (APBI) versus whole breast radiotherapy (WBRT), Outcome 2 Cosmesis, physician‐reported.
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Analysis 1.2

Comparison 1 Partial breast irradiation (PBI)/accelerated partial breast irradiation (APBI) versus whole breast radiotherapy (WBRT), Outcome 2 Cosmesis, physician‐reported.

Comparison 1 Partial breast irradiation (PBI)/accelerated partial breast irradiation (APBI) versus whole breast radiotherapy (WBRT), Outcome 3 Overall survival.
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Analysis 1.3

Comparison 1 Partial breast irradiation (PBI)/accelerated partial breast irradiation (APBI) versus whole breast radiotherapy (WBRT), Outcome 3 Overall survival.

Comparison 1 Partial breast irradiation (PBI)/accelerated partial breast irradiation (APBI) versus whole breast radiotherapy (WBRT), Outcome 4 Acute radiotherapy (RT) skin toxicity.
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Analysis 1.4

Comparison 1 Partial breast irradiation (PBI)/accelerated partial breast irradiation (APBI) versus whole breast radiotherapy (WBRT), Outcome 4 Acute radiotherapy (RT) skin toxicity.

Comparison 1 Partial breast irradiation (PBI)/accelerated partial breast irradiation (APBI) versus whole breast radiotherapy (WBRT), Outcome 5 Late RT skin toxicity.
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Analysis 1.5

Comparison 1 Partial breast irradiation (PBI)/accelerated partial breast irradiation (APBI) versus whole breast radiotherapy (WBRT), Outcome 5 Late RT skin toxicity.

Comparison 1 Partial breast irradiation (PBI)/accelerated partial breast irradiation (APBI) versus whole breast radiotherapy (WBRT), Outcome 6 Fat necrosis.
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Analysis 1.6

Comparison 1 Partial breast irradiation (PBI)/accelerated partial breast irradiation (APBI) versus whole breast radiotherapy (WBRT), Outcome 6 Fat necrosis.

Comparison 1 Partial breast irradiation (PBI)/accelerated partial breast irradiation (APBI) versus whole breast radiotherapy (WBRT), Outcome 7 'Elsewhere primary'.
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Analysis 1.7

Comparison 1 Partial breast irradiation (PBI)/accelerated partial breast irradiation (APBI) versus whole breast radiotherapy (WBRT), Outcome 7 'Elsewhere primary'.

Comparison 1 Partial breast irradiation (PBI)/accelerated partial breast irradiation (APBI) versus whole breast radiotherapy (WBRT), Outcome 8 Cause‐specific survival.
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Analysis 1.8

Comparison 1 Partial breast irradiation (PBI)/accelerated partial breast irradiation (APBI) versus whole breast radiotherapy (WBRT), Outcome 8 Cause‐specific survival.

Comparison 1 Partial breast irradiation (PBI)/accelerated partial breast irradiation (APBI) versus whole breast radiotherapy (WBRT), Outcome 9 Distant metastasis‐free survival.
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Analysis 1.9

Comparison 1 Partial breast irradiation (PBI)/accelerated partial breast irradiation (APBI) versus whole breast radiotherapy (WBRT), Outcome 9 Distant metastasis‐free survival.

Comparison 1 Partial breast irradiation (PBI)/accelerated partial breast irradiation (APBI) versus whole breast radiotherapy (WBRT), Outcome 10 Relapse‐free survival.
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Analysis 1.10

Comparison 1 Partial breast irradiation (PBI)/accelerated partial breast irradiation (APBI) versus whole breast radiotherapy (WBRT), Outcome 10 Relapse‐free survival.

Comparison 1 Partial breast irradiation (PBI)/accelerated partial breast irradiation (APBI) versus whole breast radiotherapy (WBRT), Outcome 11 Loco‐regional recurrence‐free survival.
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Analysis 1.11

Comparison 1 Partial breast irradiation (PBI)/accelerated partial breast irradiation (APBI) versus whole breast radiotherapy (WBRT), Outcome 11 Loco‐regional recurrence‐free survival.

Comparison 1 Partial breast irradiation (PBI)/accelerated partial breast irradiation (APBI) versus whole breast radiotherapy (WBRT), Outcome 12 Mastectomy.
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Analysis 1.12

Comparison 1 Partial breast irradiation (PBI)/accelerated partial breast irradiation (APBI) versus whole breast radiotherapy (WBRT), Outcome 12 Mastectomy.

Summary of findings for the main comparison. Partial breast irradiation (PBI)/accelerated partial breast irradiation (APBI) for early breast cancer

PBI/APBI for women with early breast cancer

Patient or population: women with early breast cancer

Setting: radiotherapy centres

Intervention: PBI/APBI

Comparison: whole breast radiotherapy (WBRT)

Outcomes

Anticipated absolute effects* (95% CI)

Relative effect
(95% CI)

No. of participants
(studies)

Quality of the evidence
(GRADE)

Comments

Risk with WBRT

Risk with PBI/APBI

Local recurrence‐free survival at 5 years

Study population

HR 1.62
(1.11 to 2.35)

6820
(6 RCTs)

⊕⊕⊝⊝
Low 3,4,5,6

10 per 10001

16 per 1000
(11 to 23)

Cosmesis assessed with 4‐point scale

Follow‐up: range 29‐122 months

Study population

OR 1.51
(1.17 to 1.95)

1720
(5 RCTs)

⊕⊕⊝⊝
Low 6,7,8,9

Cosmesis was assessed using a 4‐point scale. We reported those women with poor/fair cosmesis at final review

150 per 1000

218 per 1000
(174 to 272)

Late radiotherapy toxicity (subcutaneous fibrosis)

Follow‐up: median 36 months

Study population

OR 6.58
(3.08 to 14.06)

766
(1 RCT)

⊕⊕⊕⊝
Moderate 5,7,10

Assessed using National Cancer Institute 3‐point scale, events were defined as: Grade II or higher toxicity

Physician assessors, at 3 years' follow‐up

22 per 1000

128 per 1000
(64 to 239)

Cause‐specific survival at 5 years

Study population

HR 1.08
(0.73 to 1.58)

6718
(5 RCTs)

⊕⊕⊕⊝
Moderate 5,11

20 per 10002

22 per 1000
(15 to 32)

Distant metastasis‐free survival at 5 years

Study population

HR 0.94
(0.65 to 1.37)

3267
(4 RCTs)

⊕⊕⊕⊝
Moderate 5,12

33 per 10002

31 per 1000
(21 to 44)

Mastectomy rate

Follow‐up: range 29‐122 months

Study population

OR 1.20
(0.77 to 1.87)

4817
(3 RCTs)

⊕⊕⊝⊝
Low 5,11,13

Mastectomy rate reflected both local recurrence and adverse cosmetic outcome

15 per 1000

18 per 1000
(12 to 28)

Mortality
(follow‐up: 5 years survival)

Study population

HR 0.90
(0.74 to 1.09)

6718
(5 RCTs)

⊕⊕⊕⊕
High

Survival advantage from radiotherapy for breast cancer is not apparent before 15 years' follow‐up (EBCTCG 2011)

51 per 10002

46 per 1000
(38 to 55)

*The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).
CI: confidence interval; HR: hazard ratio; OR: odds ratio; RCT: randomized controlled trial.

GRADE Working Group grades of evidence
High quality: We are very confident that the true effect lies close to that of the estimate of the effect
Moderate quality: We are moderately confident in the effect estimate: The true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different
Low quality: Our confidence in the effect estimate is limited: The true effect may be substantially different from the estimate of the effect
Very low quality: We have very little confidence in the effect estimate: The true effect is likely to be substantially different from the estimate of effect

1 The baseline risk for the control group was calculated at the 5‐year time point from 5 studies.
2 The baseline risks for the control groups were calculated at the 5‐year time point from 4 studies.
3 There was considerable clinical heterogeneity with respect to radiotherapy dose, technique and use of quality assurance procedures. However, the techniques employed delivered a dose that was the same or higher in the accelerated partial breast irradiation arm than the whole breast radiotherapy arm, which should mean the local recurrence‐free survival is better or at least the same.
4 38% of the women contributing to this outcome came from a study deemed at high risk of bias for short follow‐up.
5 There were fewer than 300 events.
6 Confidence intervals did not exclude both clinically important and clinically unimportant harms.
7 Optimum sample size was not met, therefore downgraded.
8 There was evidence of considerable heterogeneity on statistical testing (I2 = 71%; P value < 0.00001).
9 Less than 30% of events came from studies deemed at high risk of bias for subjective outcomes.
10 Testing for heterogeneity was not appropriate, given that there was only one study contributing to this outcome.
11 Confidence intervals did not exclude either clinically significant benefits or harms.
12 Confidence intervals did not exclude the possibility of clinically significant harms.
13 One of the two included studies had median follow‐up of 29 months, which was too short to report this outcome.

Figures and Tables -
Summary of findings for the main comparison. Partial breast irradiation (PBI)/accelerated partial breast irradiation (APBI) for early breast cancer
Table 1. Harvard cosmetic score

Cosmetic score

Excellent

Good

Fair

Poor

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Table 1. Harvard cosmetic score
Table 2. Brachytherapy cosmetic score

Score

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

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Table 2. Brachytherapy cosmetic score
Table 3. RTOG CTC acute skin toxicity

RTOG CTC

Grade I

Grade II

Grade III

Grade IV

Description

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

RTOG CTC: Radiation Therapy Oncology Group Common Toxicity Criteria.

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Table 3. RTOG CTC acute skin toxicity
Table 4. Fat necrosis

Grade

Findings

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

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Table 4. Fat necrosis
Table 5. NCI CTC 3.0

Toxicity

Grade 1

Grade 2

Grade 3

Grade 4

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

ADL: activities of daily living; NCI CTC: National Cancer Institute Common Toxicity Criteria.

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Table 5. NCI CTC 3.0
Table 6. Radiotherapy doses prescribed

Trial

PBI/APBI dose

Fraction size (Gy)

EQD2 PBI/APBI

Control dose

Fraction size (Gy)

EQD2 Control

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

75 Gy

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

2

50 + 10 = 60 Gy

RAPID

38.5 Gy/10 fractions bd (with 6 hour gap)

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

3.85

74.1 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, pre‐specified by centre

2 or 2.65

50 or 47.1 Gy

Rodriguez

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

3.75

71.22 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 not suitable 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

53.6 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 (Dmax), 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

131.2 Gy

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

2.0

50 + 10 Gy

3D‐CRT: 3‐dimensional conformal radiotherapy; APBI: accelerated partial breast irradiation; bd: twice daily; CT: computer tomography; EBRT: external beam radiotherapy; EQD2: equivalent dose in 2 Gy fractions; Gy: Gray; HDR: high‐dose‐rate; IMRT: intensity‐modulated radiotherapy; MeV: mega electron volt; PBI: partial breast irradiation; PDR: pulsed‐dose‐rate; PTV: planning target volume.

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Table 6. Radiotherapy doses prescribed
Table 7. Radiotherapy techniques

Trial

RT technique

Polgár 2007

Interstitial brachytherapy (88/128)

EBRT using photons (40/128)

ELIOT

intra‐operative electrons

Livi 2015

EBRT (IMRT)

TARGIT

intra‐operative kV RT

RAPID

EBRT

Rodriguez

EBRT (3D‐CRT)

3D‐CRT: 3‐dimensional conformal radiotherapy; EBRT: external beam radiotherapy; IMRT: intensity‐modulated radiotherapy; RT: radiotherapy.

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Table 7. Radiotherapy techniques
Comparison 1. Partial breast irradiation (PBI)/accelerated partial breast irradiation (APBI) versus whole breast radiotherapy (WBRT)

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Local recurrence‐free survival Show forest plot

6

6820

Hazard Ratio (95% CI)

1.62 [1.11, 2.35]

1.1 2.4 years' median follow‐up

1

3451

Hazard Ratio (95% CI)

2.05 [1.00, 4.21]

1.2 5 years' follow‐up

4

3111

Hazard Ratio (95% CI)

2.50 [1.21, 5.15]

1.3 10 years' follow‐up

1

258

Hazard Ratio (95% CI)

1.09 [0.63, 1.89]

2 Cosmesis, physician‐reported Show forest plot

5

1720

Odds Ratio (M‐H, Fixed, 95% CI)

1.51 [1.17, 1.95]

3 Overall survival Show forest plot

5

6718

Hazard Ratio (95% CI)

0.90 [0.74, 1.09]

4 Acute radiotherapy (RT) skin toxicity Show forest plot

2

608

Odds Ratio (M‐H, Fixed, 95% CI)

0.04 [0.02, 0.09]

5 Late RT skin toxicity Show forest plot

2

608

Odds Ratio (M‐H, Fixed, 95% CI)

0.21 [0.01, 4.39]

6 Fat necrosis Show forest plot

3

1319

Odds Ratio (M‐H, Fixed, 95% CI)

1.58 [1.02, 2.43]

7 'Elsewhere primary' Show forest plot

3

3009

Odds Ratio (M‐H, Fixed, 95% CI)

3.97 [1.51, 10.41]

8 Cause‐specific survival Show forest plot

5

6718

Hazard Ratio (95% CI)

1.08 [0.73, 1.58]

9 Distant metastasis‐free survival Show forest plot

4

3267

Hazard Ratio (95% CI)

0.94 [0.65, 1.37]

10 Relapse‐free survival Show forest plot

3

3811

Hazard Ratio (95% CI)

1.36 [0.88, 2.09]

11 Loco‐regional recurrence‐free survival Show forest plot

2

3553

Hazard Ratio (95% CI)

1.80 [1.00, 3.25]

12 Mastectomy Show forest plot

3

4817

Odds Ratio (M‐H, Fixed, 95% CI)

1.20 [0.77, 1.87]

Figures and Tables -
Comparison 1. Partial breast irradiation (PBI)/accelerated partial breast irradiation (APBI) versus whole breast radiotherapy (WBRT)