Discussion
pneumonitis, fatigue, breast cancer, toxicity, pain, insomnia, dyspnoea
RECURRENCES, PNEUMONITIS, RECURRENCE, BREAST CANCER, WEST
The results of the SECRAB trial have been published in details elsewhere [SECRAB was powered only to detect differences in local recurrences rates, the primary outcome. Consequently, the sub-studies were not formally powered, with analyses presented here exploratory in nature. In addition, patients in the QoL and cosmetic sub-studies were from selected centres and were not randomised. As a result, there were differences between those within these analyses and the main study in several factors, which have been discussed. Some of these imbalances may have arisen due to the fact that most of the consultants enrolling patients into the cosmesis study were from the West Midlands and tended to use anthracycline–CMF with 3-weekly radiotherapy. In addition, one hospital, which recruited heavily into the sub-studies, favoured sampling to the axilla if node positive rather than axillary node clearance followed by radiotherapy.The baseline characteristics of the patients within the QoL sub-study were equally balanced between those who received synchronous versus sequential schedules. In addition, although a significant number of patients did not complete all QoL forms, this was equally balanced in the two arms of the study. As noted, significant differences were seen compared to the main study in terms of axillary node dissection performed, radiotherapy boost and endocrine therapy with tamoxifen and/or ovarian ablation.No difference in global well-being between patients receiving synchronous or sequential CRT was observed. Minor differences were seen at the end of treatment in physical and role functioning, and dyspnoea, but these had all resolved by 12 months post-treatment. Of note, there was no additional pain, fatigue or insomnia from synchronous chemotherapy. There was, however, a benefit seen in breast symptoms at the end of all treatment in the synchronous arm, probably as radiotherapy had been given well before the end of chemotherapy. Also, both sexual function and financial difficulties favoured patients treated with synchronous schedules compared to sequential patients. The latter was possibly because patients could return to work after their last chemotherapy cycle in the synchronous group, whereas those in the sequential arm may need to delay a return to work until after the completion of radiotherapy, which may not even start until 4 weeks after chemotherapy.Patients were also equally balanced in the cosmesis sub-study in terms of baseline characteristics, but again there were significant differences to the main study in terms of axillary node dissection performed, chemotherapy and radiotherapy intent, if a radiotherapy boost was given and hormone therapy.No difference in acute toxicity was seen in the cosmesis sub-study. This is at variance to the main study, which had shown a significantly higher rate of moderate/severe toxicity in patients treated using synchronous treatment; this was particularly evident in patients treated with >3 weekly fractionation [There was an apparent improvement in cosmetic outcome in the sequential arm compared to those treated with synchronous treatment at the 5-year follow-up. This may have been due to small numbers of patients at this time point, as at all other time points, and using only the last available assessment for each patient, no differences were detected. It is also noteworthy to mention that clinicians were aware whether patients had been given synchronous or sequential treatment so their assessment was not blinded. This is in contrast to the independent assessments, which were blinded to treatment allocation and no difference was observed. Finally, these data are also in agreement with those received from the patients' responses to specific QoL-related questions within the EORTC QLQ-BR23 questionnaire, which indicated no differences in cosmesis between the two treatment modalities.Significant differences in late toxicity effects were seen in the ARCOSEIN study, which used a concurrent anthracycline (mitoxantrone) regimen [Taxanes were not used as standard treatment when SECRAB was set up and we have discussed previously in our main publication the dangers of using taxanes synchronously with radiotherapy in view of the increased risk of pneumonitis [The median CDDI was high in SECRAB at 88% for synchronous regimens and 90% for sequential regimens (In summary, the results of the SECRAB sub-studies show that there are no long-term QoL or cosmesis effects using synchronous CRT compared with sequential treatment regimens, and that synchronous CRT is deliverable. This supports the main SECRAB trial outcome, which demonstrated the benefit of using synchronous CRT in the management of breast cancer by reducing 10-year local recurrence rates.