Partial breast irradiation for early breast cancer

Brigid E Hickey; Margot Lehman; Daniel P Francis; Adrienne M See

doi:10.1002/14651858.CD007077.pub3

Частичное облучение молочной железы на ранней стадии рака

Appendices

Appendix 1. The Cochrane Central Register of Controlled Trials (CENTRAL)

1. MESH DESCRIPTOR Breast Neoplasms EXPLODE ALL TREES

2. breast AND (cancer* OR tumour* OR tumor* OR neoplas*)

3. #1 OR #2

4. brachytherapy:MH

5. brachytherapy

6. partial breast

7. partial breast irradiation

8. whole breast irradiation

9. whole breast radiotherapy

10. less than whole breast rad$

11. high‐dose‐rate brachytherapy

12. acceleration partial breast irradiation

13. acceleration irradiation

14. tumour bed boost

15. sole tumour boost

16. tumour bed boost

17. tumor bed boost

18. sole tumour bed irradiation

19. mammosite

20. MESH DESCRIPTOR Radiotherapy, Conformal EXPLODE ALL TREES WITH QUALIFIERS AE

21. MESH DESCRIPTOR Radiotherapy, Conformal EXPLODE ALL TREES WITH QUALIFIERS MT

22. (balloon dilation):MH

23. MESH DESCRIPTOR Radiotherapy

24. OR/4‐23

25. #3 AND #24

Appendix 2. MEDLINE (Ovid) (1966 to present)

1.RANDOMIZED CONTROLLED TRIAL.pt
2. CONTROLLED CLINICAL TRIAL.pt
3. RANDOMIZED CONTROLLED TRIALS.sh
4. RANDOM ALLOCATION.sh
5. DOUBLE BLIND METHOD.sh
6. SINGLE BLIND METHOD.sh
7. or/1‐6
8. (ANIMALS not HUMANS).sh
9. 7 not 8
10. CLINICAL TRIAL.pt
11. exp CLINICAL TRIALS/
12. (clin$ adj25 trial$).ti,ab
13. ((singl$ or doubl$ or trebl$ or tripl$) adj25 (blind$ or mask$)).ti,ab
14. PLACEBOS.sh
15. placebo$.ti,ab
16. random$.ti,ab
17. RESEARCH DESIGN.sh
18. or/10‐16
19. 18 not 8
20. 19 not 9
21. 9 or 20
22. exp breast neoplasms/
23. exp "neoplasms, ductal, lobular, and medullary"/
24. exp breast/
25. exp neoplasms/
26. 24 AND 25
27 (breast$ adj5 (neoplasm$ or cancer$ or tumo?r$ or carcinoma$ or adenocarcinoma$ or sarcoma$ or dcis or ductal or infiltrat$ or intraductal$ or lobular or medullary)).mp.
28 exp mammary neoplasms/
29 (mammar$ adj5 (neoplasm$ or cancer$ or tumo?r$ or carcinoma$ or adenocarcinoma$ or sarcoma$ or dcis or ductal or infiltrat$ or intraductal$ or lobular or medullary)).mp
30. or/22, 23,26‐29
31. partial breast irradiation.sh,kw,ti,ab
32. partial breast.sh,kw,ti,ab
33. whole breast irradiation.sh,kw,ti,ab
34. whole breast radiotherapy.mp
35. less than whole breast rad$.mp
36. brachytherapy.sh,kw,ti,ab
37. high‐dose‐rate brachytherapy.sh,kw,ti,ab
38. accelerated partial breast irradiation.sh,kw,ti,ab
39. tumour bed boost.sh.kw.ti.ab
40. sole tumour bed irradiation.sh,kw,ti,ab
41. MammoSite.sh.kw.ti.ab
42. Breast Neoplasms/ rt.sh
43. Radiotherapy, Conformal/adverse events.sh
44. Radiotherapy, Conformal/methods.sh
45. Brachytherapy.sh
46. Balloon dilation.sh
47. Radiotherapy/.sh
48. or/31‐47
49. 48 AND 30
50. 49 AND 21

Appendix 3. EMBASE

1. randomised AND controlled AND trial

2. controlled AND clinical AND trial

3. randomi*ed:ab

4. placebo:ab

5. randomly:ab

6. trial:ab

7. groups:ab

8. #1 OR #2 OR #3 OR #4 OR #5 OR #6 OR #7

9. 'breast'/exp AND 'neoplasm'/exp

10. locally AND advance* NEAR/6 breast AND cancer*

11. locally AND advance* NEAR/6 breast AND neoplas*

12. locally AND advance* NEAR/6 breast AND carcinoma*

13. locally AND advance* NEAR/6 breast AND tumour*

14. locally AND advance* NEAR/6 breast AND tumor*

15. early NEAR/6 breast AND cancer*

16. early NEAR/6 breast AND neoplas*

17. early NEAR/6 breast AND carcinoma*

18. early NEAR/6 breast AND tumour*

19. early NEAR/6 breast AND tumor*

20. #10 OR #11 OR #12 OR #13 OR #14 OR #15 OR #16 OR #17 OR $18 OR $19

21. ‘radiotherapy’/exp OR radiotherapy

22. ‘adjuvant’/exp OR adjuvant AND (‘radiotherapy’/exp OR radiotherapy)

23. ‘radiation/exp OR radiation AND (‘therapy’/exp OR therapy)

24. #21 OR #22 OR #23

25. #8 AND #20 AND #24

Appendix 4. CINAHL

1. MH Clinical Trials

2. PT Clinical Trial

3. TX clini* n1 trial*

4. TX ((singl* n1 blind*) or (singl* n1 mask**))

5. TX randomi* control* trial*

6. MH random assignment

7. TX random* allocat*

8. TX placebo*

9. MH "Placebos"

10. MH Quantitative Studies

11. #1 OR #2 OR #3 OR #4 OR #5 OR #6 OR #7 OR #8 OR #9 OR #10

12. MH breast neoplasms

13. TI breast cancer OR SU breast cancer OR AB breast cancer

14. TI breast tumour OR SU breast tumour OR AB breast tumour

15. MM "Carcinoma, Ductal, Breast"

16. #12 OR #13 OR #14 OR #15

17. MM "radiotherapy, Conformal/AE"

18. MM "radiotherapy, Conformal/methods"

19. SU partial breast OR TI partial breast OR AB partial breast

20. SU whole breast irradiation OR TI whole breast irradiation OR AU whole breast irradiation

21. SU whole breast radiotherapy

22. SU whole breast rad$ OR TI whole breast rad$ OR AB whole breast rad$

23. SU brachytherapy OR TI brachytherapy OR AB brachytherapy

24. MH brachytherapy

25. MH radiotherapy

26. SU whole breast radiotherapy OR TI whole breast radiotherapy OR AB whole breast radiotherapy

27. SU high‐dose‐rate brachytherapy OR AB high‐dose‐rate brachytherapy OR TI high‐dose‐rate brachytherapy

28. SU accelerated partial breast irradiation OR TI accelerated partial breast irradiation OR AB accelerated partial breast irradiation

29. SU tumour bed boost OR TI tumour bed boost OR AB tumour bed boost

30. SU MammoSite OR TI MammoSite OR AB MammoSite

31. MH "Breast Neoplasms+/RT"

32. #17 OR #18 OR #19 OR #20 OR #21 OR #22 OR #23 OR #24 OR #25 OR #26 OR #27 OR #28 OR #29 OR #30 OR #31

33. #11 AND #16 AND #32

Appendix 5. Current Contents

1. TS = clinical trial*

2. TS = research design

3. TS = comparative stud*

4. TS = evaluation stud*

5. TS = controlled trial*

6. TS = follow‐up study

7. TS = prospective stud*

8. TS = random*

9. TS = placebo

10. TS = single blind*

11. TS = double blind*

12. #1 OR #2 OR #3 OR #4 OR #5 OR #6 OR #7 OR #8 OR #9 OR #10 OR #11

13. TS = breast cancer

14. TS = breast neoplasms

15. #12 OR #13

16. TS = partial breast irradiation

17. TS = whole breast irradiation

18. TS = less than whole breast

19. TS = brachytherapy

20. TS = tumour bed boost

21. TS = Mammosite

22. #15 OR #16 OR #17 OR #18 OR #19 OR #20

23. TS = radiotherapy

24. TS = radiation therapy

25. #22 OR #23

26. #12 AND #21 AND #24

Appendix 6. WHO ICTRP search portal

Basic search:

Partial irradiation for early breast cancer
Early breast cancer AND partial irradiation
Early breast cancer AND partial breast irradiation
Early breast cancer AND Mammosite
Early breast cancer AND Intracavitary brachytherapy
Early breast cancer AND Interstitial brachytherapy
Early breast cancer AND accelerated partial breast irradiation
Early breast cancer and less than whole breast radiotherapy

Advanced search:

1. Title: Partial irradiation for early breast cancer

Recruitment status: all

2. Condition: early breast cancer

Intervention: partial breast irradiation OR Mammosite OR intracavitary brachytherapy OR interstitial brachytherapy OR accelerated partial breast irradiation OR less than whole breast radiotherapy

Recruitment status: all

Appendix 7. ClinicalTrials.gov

Basic searches:

Partial irradiation for early breast cancer
Early breast cancer AND partial irradiation
Early breast cancer AND partial breast irradiation
Early breast cancer AND Mammosite
Early breast cancer AND Intracavitary brachytherapy
Early breast cancer AND Interstitial brachytherapy
Early breast cancer AND accelerated partial breast irradiation
Early breast cancer and less than whole breast radiotherapy

Advanced searches:

1. Search terms: Partial irradiation for early breast cancer

Recruitment: All studies

Study type: All studies

Gender: All studies

2. Condition: Early breast cancer

Intervention: Partial breast irradiation OR Mammosite OR intracavitary brachytherapy OR interstitial brachytherapy OR accelerated partial breast irradiation OR less than whole breast radiotherapy

Recruitment: All studies

Study type: All studies

Gender: All studies

Appendix 8. OpenGrey

1. (breast cancer OR breast neoplasm* OR breast adenocarcinoma) AND (radiation OR irradiation OR radiotherapy OR radio‐therapy))

Figure 1

Study flow diagram.

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Figure 2

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

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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.

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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.

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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.

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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.

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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.

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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.

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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.

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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.

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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.

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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.

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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'.

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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.

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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.

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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.

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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.

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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.

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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.

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

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Table 1. Harvard cosmetic score

Cosmetic score

Excellent

Good

Fair

Poor

Table 1. Harvard cosmetic score

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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

Table 2. Brachytherapy cosmetic score

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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.

Table 3. RTOG CTC acute skin toxicity

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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

Table 4. Fat necrosis

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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.

Table 5. NCI CTC 3.0

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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 (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	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.

Table 6. Radiotherapy doses prescribed

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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.

Table 7. Radiotherapy techniques

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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]

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

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Частичное облучение молочной железы на ранней стадии рака

Appendices

Appendix 1. The Cochrane Central Register of Controlled Trials (CENTRAL)

Appendix 2. MEDLINE (Ovid) (1966 to present)

Appendix 3. EMBASE

Appendix 4. CINAHL

Appendix 5. Current Contents

Appendix 6. WHO ICTRP search portal

Basic search:

Advanced search:

Appendix 7. ClinicalTrials.gov

Basic searches:

Advanced searches:

Appendix 8. OpenGrey

Scolaris Language Selector Scolaris Language Selector

Scolaris Content Display Scolaris Content Display

Instituciones a las que se accedió previamente

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Appendices

Appendix 1. The Cochrane Central Register of Controlled Trials (CENTRAL)

Appendix 2. MEDLINE (Ovid) (1966 to present)

Appendix 3. EMBASE

Appendix 4. CINAHL

Appendix 5. Current Contents

Appendix 6. WHO ICTRP search portal

Basic search:

Advanced search:

Appendix 7. ClinicalTrials.gov

Basic searches:

Advanced searches:

Appendix 8. OpenGrey

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Instituciones a las que se accedió previamente

Usuarios institucionales

Instituciones a las que se accedió previamente

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