Use of tumour bed boost
Tumour bed boost was used in four of the randomised trials; START A, START B, Spooner 2012 and the RMH/GOC trial. Outcomes were reported for START A, START B and their pilot study, RMH/GOC, in a post hoc combined sub-group meta-analysis (n=5,861).10 Between January 1986 and July 1997, patients in the RMH/GOC trial were randomly assigned to receive a boost or not. Subsequently, all patients were offered an elective boost. The proportion of women who received a tumour bed boost was similar among the treatment groups. There was a statistically significant reduced risk of induration (p=0.001) and telangiectasia (p=0.026) in patients randomised to no boost.18
The proportion of women who received a tumour bed boost was similar among the treatment groups in the START A and START B trials. However, sub-group analysis on tumour bed boost was not reported.16,17 In a combined sub-group analysis of START A, START B and their pilot study there was no statistically significant difference in local-regional relapse rates or moderate or marked physician-assessed normal tissue effects in the breast between hypofractionated radiotherapy and conventionally fractionated radiotherapy in patients who received tumour bed boost radiotherapy and those who did not receive tumour bed boost radiotherapy (Haviland 2013). This analysis provides support of equivalence between hypofractionated radiotherapy with boost and conventional radiotherapy without boost for tumour control and improved late tissue effects, with the inclusion of 5,861 patients and lengthy follow-up. While the 2011 ASTRO guidelines state “there were few data to define the indications for and toxicity of a tumour bed boost in patients treated with hypofractionated radiotherapy” this guideline was published in 2011, prior to the 2013 START trial publication of tumour bed boost data.
In the Spooner et al trial (2012), all irradiated patients received a supplementary boost to the local tumour site of a direct 10-14 MeV electron field of 15 Gy in five daily fractions.11
Delivery of radiotherapy
All trials provided information on the radiotherapy techniques used. Patients in all six trials were treated in a supine position. The RMH/GOC and Canadian trials specified that patients were treated with one or both arms raised above the shoulder and Spooner noted patients had arm abducted to 900.
In five trials, 6-megavoltage x-rays were used for most patients but higher energy megavoltage x-rays or cobalt x-rays were also used.6,7,13,16-18,21 Where regional radiotherapy was indicated, the target volume included the supraclavicular nodes with or without the axillary nodes.7,16,17
Four trials reported that the maximum dose to the breast on the central axis was no less than 93% to 95% and no more than 105% to 107% of the prescribed dose.6,7,13,16-18. The Canadian trial excluded patients whose separation along the central axis exceeded 25cm; however the other trials used higher energy x-rays for patients with larger breasts to achieve acceptable dose homogeneity.6,7,13,16,17 RMH/GOC and Canadian trials reported the use of wedge tissue compensators to ensure a uniform dose distribution throughout the target volume.7,13,18
Four trials included women allocated to receive a tumour bed boost. Women allocated to receive a boost in RMH/GOC received a dose of 14 Gy to the 90% isodose (15.5 Gy to 100%) in 7 daily fractions.18 Ten Gy in 5 daily fractions to the 100% isodose was delivered after whole breast radiotherapy to women allocated to receive a boost in the START A and START B trials.16,17 All irradiated patients in the Spooner trial received a supplementary boost to the local tumour site of a direct 10-14 MeV electron field of 15 Gy in five daily fractions.11
Use of adjuvant systemic therapies
Five trials included women who received adjuvant systemic therapies; START A, START B, Spooner 2012, the Canadian trial and RMH/GOC trial. In the Canadian trial, 11% of women received chemotherapy in both the conventional and hypofractionated radiotherapy regimens; and 41% received tamoxifen in both the conventional and hypofractionated radiotherapy regimens.6 Sub-group analysis of the rates of local recurrence showed no statistically significant difference between the conventional and hypofractionated regimens at five years and ten years.6
No sub-group analysis on the use of systemic therapies was reported in the RMH/GOC, START A or START B trials or Spooner trial.7,16-18 In each trial, the proportions of women who received systemic therapies including tamoxifen and/or chemotherapy were similar among the study groups. The START trials required a two week gap between exposure to chemotherapy and radiotherapy.16,17 In the Spooner trial the authors noted that the study was conducted at a time when few patients were given adjuvant chemotherapy and all patients received tamoxifen because hormone receptor status was not routinely available. Patients in the trial received tamoxifen (20mg once daily) for a minimum of 2 years, after which there was a subsequent sub-randomisation to discontinue or continue for at least another 3 years.11
No trials specifically assessed the use of hypofractionated radiotherapy in conjunction with chemotherapy or other biological therapies.