Key question: What is the safety of hypofractionated radiotherapy compared to conventionally fractionated radiotherapy for the treatment of early breast cancer?
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1. Evidence base |
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One level 1 (meta-analysis of RCTs) and six phase II (RCTs) studies with a low risk of bias |
A |
One or more level I studies with a low risk of bias or several level II studies with a low risk of bias |
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B |
One or two Level II studies with a low risk of bias or SR/several Level III studies with a low risk of bias |
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C |
One or two Level III studies with a low risk of bias or Level I or II studies with a moderate risk of bias |
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D |
Level IV studies or Level I to III studies/SRs with a high risk of bias |
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2. Consistency |
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Studies reported different adverse events. Across the adverse events studies reported no difference, a difference that favoured hypofractionated radiotherapy, or a difference that favoured conventionally fractionated radiotherapy. On balance the adverse event profile for hypofractionated versus conventionally fractionated radiotherapy were comparable. |
A |
All studies consistent |
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B |
Most studies consistent and inconsistency can be explained |
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C |
Some inconsistency, reflecting genuine uncertainty around question |
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D |
Evidence is inconsistent |
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NA |
Not applicable (one study only) |
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3. Clinical impact |
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The comparability of the adverse event profiles with the different fractionation methods was considered to be of significance. |
A |
Very large |
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B |
Substantial |
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C |
Moderate |
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D |
Slight/Restricted |
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4. Generalisability |
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Whilst the studies are broadly generalisable, some uncertainty remains regarding the possible cardiac effects of hypofractionated radiotherapy in women with left-sided tumours especially as women with pre-existing heart disease were under-represented in the studies |
A |
Evidence directly generalisable to target population |
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B |
Evidence directly generalisable to target population with some caveats |
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C |
Evidence not directly generalisable to the target population but could be sensibly applied |
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D |
Evidence not directly generalisable to target population and hard to judge whether it is sensible to apply |
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5. Applicability (Is the body of evidence relevant to the Australian healthcare context in terms of health services/delivery of care and cultural factors?) |
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Key studies were conducted in settings considered to be similar to Australia |
A |
Evidence directly applicable to Australian healthcare context |
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B |
Evidence applicable to Australian healthcare context with few caveats |
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C |
Evidence probably applicable to Australian healthcare context with some caveats |
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D |
Evidence not applicable to Australian healthcare context |
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Other Factors
Concerns were raised regarding the possibility of late effects on the heart for women with left-sided tumours. A supplementary review of the literature was undertaken to address these concerns around cardiotoxicity. Whilst it was recognised that late cardiac effects may take up to 20 years to develop, the current evidence base shows no difference in longer term cardiac mortality or morbidity between hypofractionated and conventionally fractioned schedules. It was agreed that whilst a left-sided tumour should not be included as an exclusion criterion for hypofractionated radiotherapy, a Practice Point (c) would be included to highlight the importance of adopting heart sparing protocols, particularly in women with pre-existing heart disease, who are under-represented in the studies in the evidence base.
Evidence Statement Matrix
| Component | Rating | Description |
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A |
One level 1 (meta-analysis of RCTs) and six phase II (RCTs) studies with a low risk of bias |
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B |
On balance the adverse event profile for hypofractionated versus conventionally fractionated radiotherapy were comparable. |
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B |
The comparability of the adverse event profiles was considered to be of substantial clinical impact. |
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B |
Patients broadly generalisable, but with under-representation of women with heart disease |
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A |
Key studies were conducted in settings considered to be similar to Australia |
Recommendation
| When selecting an appropriate radiotherapy schedule, consideration should be given to the possibility of adverse events including acute reactions and late effects. | Grade Of Recommendation |
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B |
Unresolved Issues
The longest duration of follow-up from RCTs is 9.3 and 9.7 years (START A and B), and from prospective cohort studies is 13-14 years. Ideal follow-up for late cardiac effects is thought to be 15-20 years, so additional follow-up for late effects is still required.
Implementation Of Recommendation
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Will this recommendation result in changes in usual care? |
NO |
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Are there any resource implications associated with implementing this recommendation? |
NO |
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Will the implementation of this recommendation require changes in the way care is currently organised? |
NO |
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Are the guideline development group aware of any barriers to the implementation of this recommendation? |
NO |