Recommendation 3

Key question: What is the optimal schedule for hypofractionated radiotherapy for the treatment of early breast cancer?

1. Evidence base
Three level II studies (RCTs) 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
	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
	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
	D	Level IV studies or Level I to III studies/SRs with a high risk of bias
2. Consistency
The START B RCT reported better outcomes for hypofractionated radiotherapy compared with standard radiotherapy. The Canadian RCT showed equivalent outcomes for hypofractionated radiotherapy and standard radiotherapy. The Spooner RCT showed comparable rates of tumour control and radiation therapy effects.	A	All studies consistent
	B	Most studies consistent and inconsistency can be explained
	C	Some inconsistency, reflecting genuine uncertainty around question
	D	Evidence is inconsistent
	NA	Not applicable (one study only)
3. Clinical impact
Demonstration of non-inferiority for hypofractionated radiotherapy represents a substantial clinical benefit	A	Very large
	B	Substantial
	C	Moderate
	D	Slight/Restricted
4. Generalisability
Sufficient follow-up from a large number of patients	A	Evidence directly generalisable to target population
	B	Evidence directly generalisable to target population with some caveats
	C	Evidence not directly generalisable to the target population but could be sensibly applied
	D	Evidence not directly generalisable to target population and hard to judge whether it is sensible to apply
5. Applicability
Key studies were conducted in settings considered to be similar to Australia	A	Evidence directly applicable to Australian healthcare context
	B	Evidence applicable to Australian healthcare context with few caveats
	C	Evidence probably applicable to Australian healthcare context with some caveats
	D	Evidence not applicable to Australian healthcare context

Other Factors

It was noted that the proportion of women receiving tumour bed boost was similar among the treatment groups in START B and Spooner, and that a post hoc subgroup analysis demonstrated no statistically significant difference in local-regional relapse rates of cosmetic outcomes between hypofractionated and conventionally fractionated radiotherapy in patients who received tumour bed boost versus those who did not. It was agreed that Practice Point (b) be included to provide guidance on the optimal schedule for a tumour bed boost, based on the schedule used in one of the RCTs included for this Question (START B).

Evidence Statement Matrix

Component	Rating	Description
Evidence base	A	Three level II studies (RCTs) with a low risk of bias
Consistency	B	START B reported better outcomes for hypofractionated radiotherapy compared with standard radiotherapy. The Canadian and Spooner trials showed equivalent outcomes for hypofractionated radiotherapy and standard radiotherapy.
Clinical impact	B	Demonstration of non-inferiority for hypofractionated radiotherapy would represent a substantial clinical benefit
Generalisability	A	Sufficient follow-up from a large number of patients
Applicability	A	Key studies were conducted in settings considered to be similar to Australia

Recommendation

For patients not receiving a tumour bed boost, recommended hypofractionated schedules for whole breast radiotherapy based on current evidence are:

40 Gy in 15 fractions given at the rate of one fraction per day, 5 fractions per week over 21 days,
42.5 Gy in 16 fractions given at the rate of one fraction per day, 5 fractions per week over 22 days

Grade Of Recommendation

Unresolved Issues

None

Implementation Of Recommendation

Will this recommendation result in changes in usual care? Yes, hypofractionated radiotherapy, with or without tumour bed boost, can now be considered as a treatment option	YES
Are there any resource implications associated with implementing this recommendation? Reduced waiting times due to shorter treatment program and increased patient turnover	YES
Will the implementation of this recommendation require changes in the way care is currently organised? No, hypofractionated radiotherapy schedules can already be delivered via current systems	NO
Are the guideline development group aware of any barriers to the implementation of this recommendation?	NO

Recommendation 3