Indrajit FernandoUniversity Hospital Birmingham NHS Trust and Cancer Research Clinical Trials Unit, United Kingdom
Title: Is there a role for synchronous chemoradiation in early stage breast cancer
Secrab is the largest trial in the world looking at synchronous versus sequential chemotherapy and radiotherapy in early breast cancer. Recruitment was from 1998-2004. 2297 patients were recruited from 48 centres in the UK. Chemotherapy was either CMF or ECMF. Radiotherapy was 3 weeks or > 3 weeks treatment.
With 10.2 years median follow-up the 10 year local recurrence rates (LRR) were 4.6% and 7.1% in the synchronous and sequential arms respectively (HR) 0.62 (0.43-0.9); p=0.012. In a planned subgroup analysis for patients treated with ECMF 10 year LRR were 3.5% vs 6.7% respectively (HR) 0.48 (0.26-0.88) p=0.018. For CMF alone the difference was not statistically different (HR) 0.79 (0.44-1.13) p=0.149. There was no overall difference in DFS and OS between synchronous and sequential patients. However In an unplanned sub-group analysis, for patients treated by ECMF, a non-statistical trend to benefit in 10 year DFS favouring synchronous treatment 67.7 vs 63.5% (HR=0.86(0.7-1.06 p=0.17)was seen. The same was seen on OS 75.8% vs 72.3% (HR=0.8590.66-1.08 p=0.171) again favouring synchronous treatment. The opposite was seen in those patients treated by CMF where the differences in DFS and OS favoured those treated by sequential treatment. This explains why in the overall study no difference DFS or OS was seen
Acute skin toxicity was worse in patients treated synchronously compared to sequentially (24% vs 14% moderate to severe reactions p< 0.0001). Cosmetic outcome and quality of life was not significantly affected although there was a slight increase in telangiectasia in those treated by synchronous treatment (3% vs 1.7% p=0.03). Other side effects were not significantly different
This trial was never powered for DFS or OS but the differences shown above explain the results of the study and suggest that there is a worthwhile benefit to treatment in patients treated by synchronous chemo radiotherapy if being treated with an ECMF type regimen
Dr Indrajit Fernando is a consultant Clinical Oncologist at University Hospital Birmingham, UK and an honorary senior lecturer in the University Of Birmingham. He is the chief Investigator of the largest trial in the world to date on synchronous chemo radiation in breast cancer. He is a winner of the Frank Ellis Medal 1996 for his paper on acute skin reactions after breast radiotherapy and has sat on the steering committee of several major trials in breast cancer in the UK. He has published over 50 papers in breast and gynaecological cancer but regards chemo radiation as his most important contribution to this field