Longer may not be better when it comes to radiation treatment for breast cancer.
For women who underwent radiation treatment after surgery and chemotherapy for breast cancer, a radiation regimen consisting of 15 treatment sessions over 3 weeks appeared to be as effective as an alternate regimen of 25 sessions over 5 weeks after a 10-year follow-up period, according to findings from a large trial released yesterday in The Lancet Oncology. This conclusion was based on the 10-year follow-up results of the UK Standardisation of Breast Radiotherapy (START) trials, 2 randomized controlled trials investigating the optimal regimen of adjuvant radiation therapy for breast cancer.
In the United Kingdom as well as in Canada, the 3-week regimen has been the standard practice in breast cancer treatment for decades. In the United States, however, the long-time standard practice has been the longer 5-week regimen, and until recently no official guidelines on the shorter regimen existed.
The 2 trials (START-A and START-B) began in the United Kingdom in 1998 and randomized more than 4000 women to receive various radiation therapy regimens. START-B looked at longer versus shorter durations of treatment. It compared a radiation regimen of 50 Gy (gray, a standardized measurement of radiation dose) divided into 25 treatment sessions or “fractions” (2 Gy per fraction) over 5 weeks with an alternate regimen of 40 Gy divided into 15 fractions (2.67 Gy per fraction) over 3 weeks. The primary end points of the START trials were local-regional relapse, defined as cancer recurrence in the breast, chest wall, or lymph nodes on the same side of the body, and local radiation-induced toxicity or “tissue effects,” as assessed by clinician examination and photographs.
In 2008, 5-year results of the START trials were published and showed that the 2 regimens were equally effective and that the 3-week regimen had fewer adverse tissue effects. Another randomized (although smaller) Canadian trial published similar results in 2010. These results solidified practice guidelines in the United Kingdom and Canada.
In the United States, the American Society of Radiation Oncology (ASTRO) released new practice guidelines in 2011 to state that the 3-week regimen may be appropriate for a specific subset of patients with early breast cancer. However, this recommendation was not strong and thus has been loosely adopted into clinical practice. The guidelines put greater emphasis on the conventional 5-week regimen, which remains widely used in practice. According to the guidelines, a major rationale for continuing to recommend the 5-week regimen was concern that the higher per-fraction radiation dose in the 3-week regimen (2.67 vs 2 Gy per fraction) may have potential “late” radiation toxicity effects that appear only after 10 or more years, such as late tissue effects, cardiovascular events, and pulmonary toxicity.
The just-released 10-year START trial results may help address these concerns. The new data essentially confirm the 5-year results: the 3-week 40-Gy regimen was just as effective as the 5-week 50-Gy regimen with respect to local-regional relapse, and it also had fewer adverse effects, although the studies focused on local tissue effects and not cardiovascular or pulmonary effects. Nonetheless, these results suggest that the 3-week 40-Gy regimen was less harmful to normal tissue and not less effective in treating cancerous tissue.
There also was an unexpected survival benefit in the group that underwent the 3-week regimen. In other words, it’s possible that the 3-week regimen may be not only equivalent to, but actually somewhat better than, the 5-week regimen. However, because survival was a secondary (and not primary) outcome in these studies, this result needs to be investigated further.
Given the immense cost and convenience benefits of a shorter radiation therapy course in breast cancer, this large follow-up study may have the potential to influence future US clinical practice patterns. On the other hand, it may not be enough to spur immediate change: a US phase 3 clinical trial investigating the same issue is currently recruiting patients, with an estimated completion date of 2020 for final data on primary outcome measures.