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Illustration of the breast retraction assessment (BRA) measurements as reported by EORTC. BRA = √((a1 ‐ b1)² + (a2 ‐ b2)²); reference length = √(b1² + b2²); percentage breast retraction assessment = (BRA/reference length) x 100.
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Figure 1

Illustration of the breast retraction assessment (BRA) measurements as reported by EORTC. BRA = √((a1 ‐ b1)² + (a2 ‐ b2)²); reference length = √(b1² + b2²); percentage breast retraction assessment = (BRA/reference length) x 100.

Study flow diagram.
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Figure 2

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 3

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

Forest plot of comparison: 1 Tumour bed boost radiotherapy versus no boost, outcome: 1.1 Local control.
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Figure 4

Forest plot of comparison: 1 Tumour bed boost radiotherapy versus no boost, outcome: 1.1 Local control.

Forest plot of comparison: 1 Tumour bed boost radiotherapy versus no boost, outcome: 1.5 Overall survival.
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Figure 5

Forest plot of comparison: 1 Tumour bed boost radiotherapy versus no boost, outcome: 1.5 Overall survival.

Forest plot of comparison: 1 Tumour bed boost radiotherapy versus no boost, outcome: 1.8 Cosmesis, Panel.
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Figure 6

Forest plot of comparison: 1 Tumour bed boost radiotherapy versus no boost, outcome: 1.8 Cosmesis, Panel.

Comparison 1 Tumour bed boost radiotherapy versus no boost, Outcome 1 Local control.
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Analysis 1.1

Comparison 1 Tumour bed boost radiotherapy versus no boost, Outcome 1 Local control.

Comparison 1 Tumour bed boost radiotherapy versus no boost, Outcome 2 Local control ‐ sensitivity analysis.
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Analysis 1.2

Comparison 1 Tumour bed boost radiotherapy versus no boost, Outcome 2 Local control ‐ sensitivity analysis.

Comparison 1 Tumour bed boost radiotherapy versus no boost, Outcome 3 Local control ‐ subgroup +40 years.
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Analysis 1.3

Comparison 1 Tumour bed boost radiotherapy versus no boost, Outcome 3 Local control ‐ subgroup +40 years.

Comparison 1 Tumour bed boost radiotherapy versus no boost, Outcome 4 Local control ‐ subgroup low boost dose.
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Analysis 1.4

Comparison 1 Tumour bed boost radiotherapy versus no boost, Outcome 4 Local control ‐ subgroup low boost dose.

Comparison 1 Tumour bed boost radiotherapy versus no boost, Outcome 5 Overall survival.
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Analysis 1.5

Comparison 1 Tumour bed boost radiotherapy versus no boost, Outcome 5 Overall survival.

Comparison 1 Tumour bed boost radiotherapy versus no boost, Outcome 6 Disease‐free survival.
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Analysis 1.6

Comparison 1 Tumour bed boost radiotherapy versus no boost, Outcome 6 Disease‐free survival.

Comparison 1 Tumour bed boost radiotherapy versus no boost, Outcome 7 Late toxicity, pBRA.
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Analysis 1.7

Comparison 1 Tumour bed boost radiotherapy versus no boost, Outcome 7 Late toxicity, pBRA.

Comparison 1 Tumour bed boost radiotherapy versus no boost, Outcome 8 Cosmesis, Panel.
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Analysis 1.8

Comparison 1 Tumour bed boost radiotherapy versus no boost, Outcome 8 Cosmesis, Panel.

Comparison 1 Tumour bed boost radiotherapy versus no boost, Outcome 9 Cosmesis, Physician.
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Analysis 1.9

Comparison 1 Tumour bed boost radiotherapy versus no boost, Outcome 9 Cosmesis, Physician.

Summary of findings for the main comparison. Boost compared to no boost in breast cancer radiotherapy

Boost compared to no boost in breast cancer radiotherapy

Patient or population: breast‐conserving radiotherapy for breast cancer
Setting: radiotherapy centres
Intervention: boost
Comparison: no boost

Outcomes

Anticipated absolute effects* (95% CI)

Relative effect
(95% CI)

№ of participants
(studies)

Quality of the evidence
(GRADE)

Comments

Risk without boost

Risk with boost

Local control: recurrence at 5 years

Study population

HR 0.64
(0.55 to 0.75)

8315
(5 RCTs)

⊕⊕⊝⊝
LOW 1 2

Nice did not report 5‐year local control.

70 per 1000

45 per 1000
(39 to 53)

Overall survival: mortality at 5 years

Study population

HR 1.04
(0.94 to 1.14)

6342
(2 RCTs)

⊕⊕⊕⊝
MODERATE 3

91 per 1000

94 per 1000
(86 to 103)

Disease‐free survival: disease progression/mortality at 5 years

Study population

HR 0.94
(0.87 to 1.02)

6549
(3 RCTs)

⊕⊕⊝⊝
LOW 4 5

EORTC did not report 5‐year disease‐free survival.

221 per 1000

209 per 1000
(195 to 224)

Late toxicity, pBRA

Mean pBRA 8.17, range 7.55 to 10

Mean pBRA 8.55,
range 8.26 to 9.4

MD 0.38 higher

(0.18 lower to 0.93 higher)

1526
(2 RCTs)

⊕⊝⊝⊝
VERY LOW 2 5

Cosmesis, panel scored: fair or poor

Study population

OR 1.41
(1.07 to 1.85)

1116
(2 RCTs)

⊕⊕⊝⊝
LOW 1 2

202 per 1000

263 per 1000
(213 to 319)

Cosmesis, physician‐scored: fair or poor

Study population

OR 1.58
(0.93 to 2.69)

592
(2 RCTs)

⊕⊝⊝⊝
VERY LOW 1 5 6

85 per 1000

128 per 1000
(80 to 200)

Sensitivity analysis: local control ‐ recurrence at 5 years

Study population

HR 0.62
(0.52 to 0.73)

6963
(3 RCTs)

⊕⊕⊕⊕
HIGH

74 per 1000

47 per 1000
(39 to 55)

Subgroup analysis: local control ‐ > 40 years old, recurrence at 5 years

Study population

HR 0.65
(0.53 to 0.81)

5058
(2 RCTs)

⊕⊕⊕⊕
HIGH

59 per 1000

39 per 1000
(32 to 48)

*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; MD: mean difference; OR: odds ratio; pBRA: percentage breast retraction assessment; RCT: randomised 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 the effect.

1High risk of selective reporting in one study.
2There was considerable clinical heterogeneity with respect to radiotherapy dose and the use of quality assurance procedures.
3One of the two studies has a very wide confidence interval.
4There was considerable clinical heterogeneity on statistical testing, but not on visual inspection.
5Both studies have wide confidence intervals.
6High risk of bias for blinding of outcome assessment in one study.

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Summary of findings for the main comparison. Boost compared to no boost in breast cancer radiotherapy
Table 1. RTOG/EORTC late radiation morbidity scoring scheme

Organ tissue

0

Grade 1

Grade 2

Grade 3

Grade 4

Skin

None

Slight atrophy; pigmentation change; some hair loss

Patchy atrophy; moderate telangiectasia; total hair loss

Marked atrophy; gross telangiectasia

Ulceration

Subcutaneous tissue

None

Slight induration (fibrosis) and loss of subcutaneous fat

Moderate fibrosis but asymptomatic; slight field contracture; < 10% linear reduction

Severe induration and loss of subcutaneous tissue; field contracture > 10% linear measurement

Necrosis

RTOG/EORTC: Radiation Therapy Oncology Group/European Organisation for Research and Treatment of Cancer

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Table 1. RTOG/EORTC late radiation morbidity scoring scheme
Table 2. Harvard cosmetic score

Cosmetic score

Excellent

Good

Fair

Poor

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Table 2. Harvard cosmetic score
Comparison 1. Tumour bed boost radiotherapy versus no boost

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Local control Show forest plot

5

8315

Hazard Ratio (Fixed, 95% CI)

0.64 [0.55, 0.75]

2 Local control ‐ sensitivity analysis Show forest plot

3

6963

Hazard Ratio (Fixed, 95% CI)

0.62 [0.52, 0.73]

3 Local control ‐ subgroup +40 years Show forest plot

2

5058

Hazard Ratio (Fixed, 95% CI)

0.65 [0.53, 0.81]

4 Local control ‐ subgroup low boost dose Show forest plot

2

1352

Hazard Ratio (Fixed, 95% CI)

0.95 [0.55, 1.62]

5 Overall survival Show forest plot

2

6342

Hazard Ratio (Fixed, 95% CI)

1.04 [0.94, 1.14]

6 Disease‐free survival Show forest plot

3

6549

Hazard Ratio (Fixed, 95% CI)

0.94 [0.87, 1.02]

7 Late toxicity, pBRA Show forest plot

2

1526

Mean Difference (IV, Fixed, 95% CI)

0.38 [‐0.18, 0.93]

8 Cosmesis, Panel Show forest plot

2

1116

Odds Ratio (M‐H, Fixed, 95% CI)

1.41 [1.07, 1.86]

9 Cosmesis, Physician Show forest plot

2

592

Odds Ratio (M‐H, Fixed, 95% CI)

1.58 [0.93, 2.69]

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Comparison 1. Tumour bed boost radiotherapy versus no boost