Hypofractionated Breast Radiotherapy

There are four trials evaluating hypofractionated treatment regimens for early stage breast cancer.

  • The Ontario Trial (42.5 Gy in 16 # vs 50 Gy in 25#)
  • The START-A Trial (41.6 Gy in 13 # vs 39 Gy in 13 # vs 50 Gy in 25#)
  • The START-B Trial (40 Gy in 15 # vs 50 Gy in 25#)
  • The Royal Marsden Hospital Trial (42.9 Gy in 13 # vs 39 Gy in 13 # vs 50 Gy in 25 #)

These have been reviewed in a meta-analysis which concluded that at 5 years, equivalent rates of local control, overall survival and cosmesis are seen for both treatments. This finding is subject to a number of conditions, namely:

  • Patients treated with hypofractionation, on average, had small to medium sized breasts
  • Most patients had tumours < 3 cm and less than 2% had tumours > 5 cm
  • Most patients did not have lymph node involvement (80%)
  • Most patients did not receive systemic cytotoxic therapy
  • Most patients did not receive a boost

American guidelines state that patients should only be considered for hypofractionation if they are older than 50, do not receive chemotherapy, have small tumours (T1 - T2), and have good dose homogeneity in the breast. This excludes a number of patients with lymph node metastases or who receive systemic therapy.
In contrast, nearly all patients in the United Kingdom would receive hypofractionated radiotherapy (40 Gy in 15#) as per START-B. Arguments supporting this approach are that in other studies (eg. the EORTC boost trial), the rates of side effects at 5 years in each arm were similar to the rates of side effects at 10 years and therefore 5 year data should be a reasonable surrogate for late effects.
Further controversy over the use of boost in these patients is present. The EORTC boost study which demonstrated significant reductions in local recurrence, particularly for young women, were not evaluated in any of the hypofractionated studies which demonstrated equivalence to normal fractionated treatment without boost. Most centres would add a boost on for patients who would normally receive a boost with conventional fractionation (eg. 40 Gy in 15 followed by 10 Gy in 5 boost).

Opinion: Most patients in the modern setting should be safely treated with hypofractionated radiotherapy. I would avoid this treatment in patients with large breasts (due to inhomogeneity concerns) and in patients under 50 (due to long term follow up concerns) and in patients with large tumours (> 5 cm) due to limited evidence.

Hypofractionated Post-Mastectomy Radiotherapy

The use of hypofractionated schedules for post mastectomy or regional nodal irradiation is even more controversial. Again, this is done more commonly in the UK where there are constraints on budget. It is not done at any Australian centres in which I have worked.
Given that this is the standard of care in the UK it is hard to be overly critical; the randomised studies which established the use of hypofractionated radiotherapy were however following breast conserving therapy and the results may not be applicable to post-mastectomy patients.

Opinion: These patients should be treated with conventional radiotherapy in most circumstances unless other factors intervene (eg. patient unable to remain in treatment vicinity for 25 days).


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