Evidence-based guidelines for hypofractionated radiation in breast cancer: conclusions of the Catalan expert working group

Following breast-conserving surgery for breast cancer, daily, moderate hypofractionation has become standard treatment [1, 2]. Results from randomised trials do not support the use of classic fractionation of 2 Gy in most patients [3, 4], and studies have confirmed the effectiveness of hypofractionated regimens with similar tolerance [5]. Indications for its use have also broadened with the growing body of evidence showing its utility under other circumstances, for example with irradiation of lymph nodes [6] or the chest wall following mastectomy [7], or in patients of all ages [8]. However, there are substantial variations in the use of hypofractionation across different centres and countries [9, 10]. In a previous study, our group assessed its use for breast cancer in Catalonia, Spain [11], finding that it ranged from 8.9 to 74.7% of patients treated with a curative intent. In addition, specific indications for the treatment varied, both between services and among the different professionals that staff fed them.

In light of this heterogeneity and taking as a reference the American Society for Radiation Oncology (ASTRO) consensus guidelines on hypofractionation for breast cancer [12], we decided to launch a consensus-building process to establish recommendations for this breast cancer treatment in our region. Greater knowledge of the real indications and agreement among professionals should lead to an expansion of its use as a standard indication in Catalonia, promote equitable access, reduce differences between public healthcare services, and improve patients’ quality of life by avoiding the need for unnecessary travel and its associated inconveniences. This study describes the methods used to reach a consensus as well as the resulting recommendations as they compare to the ASTRO guidelines [12].

All the invited centres participated in every meeting held, all controversial issues were discussed and finally answered to the corresponding questionnaires submitted.

With regard to the 14 questions considered, these are detailed in Table 2, along with the level of evidence, degree of consensus, and strength of the recommendation.

Our results are comparable to the ASTRO guidelines [12] in terms of the final recommendations and the quality of evidence supporting them. However, there were some differences in the level of consensus achieved, for example in patients under the age of 40 years: compared to ASTRO consensus, the agreement on the use of hypofractionation in these cases was 93%, compared to 63% in our analysis. These differences are probably due to our classification of patient age into three brackets: less than 40 years, 40 to 50 years, and more than 50 years.

Unlike the ASTRO guidelines, we included questions about hypofractionation in patients receiving a mastectomy or who required irradiation of the lymph node chain. For these indications, the degree of consensus was low at 64% and 59%, respectively, in consonance with the low quality of evidence.

Despite the growing evidence of the association between hypofractionated treatment and improved clinical and care quality for patients with breast cancer, the direct translation to clinical practice has been limited. The possible reasons for this lag are numerous and range from missed opportunities following positive results from clinical trials, to knowledge gaps and uncertainty, controversies, irrelevant or conflicting evidence, and vested or conflicting interests [28]. The considerable volume of scientific publications makes it difficult to attain deep knowledge based on the analysis of available evidence; rather, this is often synthesised at an individual level.

Uptake of hypofractionation has been slow for breast cancer in public hospitals in Catalonia, with considerable variability in clinical practice, as reported by Prades et al. [11]. This delay in the translation of evidence to practice has also been observed by other authors, for example Gilbo et al. [29], who observed an improvement in utilisation rates from 49 to 80% in the 4 years following dissemination of the ASTRO guidelines, implementation of clinical practice directives, and follow-up through departmental discussions about clinical indications. As Recht commented in an editorial [30], the use of hypofractionation will only reach recommended levels if specialists are engaged and adherence to guidelines is monitored.

Underpinning this perspective is the assumption that the adoption of healthcare innovations (including process-based innovations like hypofractionation) depends to some extent on how they are communicated and disseminated, not only on the quality of evidence that supports them. To that end, the work described in the present paper followed a consensus-based methodology that incorporates direct knowledge related to clinical practice into the scientific debate. The involvement of 11 clinical departments in an open research and deliberation process converged in a shared vision about the use of hypofractionation, both where a high level of scientific evidence supports its use and where the strength of the evidence is more limited. Following the literature review and the pooling of knowledge among experts with regard to the consensus-based recommendations on the use of hypofractionation in breast cancer, it is significant that 10 of the 14 questions posed yielded full agreement about the intervention. According our results, hypofractionation is appropriate in all patients aged 40 years or more with an indication for adjuvant external beam radiotherapy following breast-conserving surgery for invasive breast carcinoma and without nodal irradiation. The use of hypofractionation schemes in these cases is recommended regardless of other tumour characteristics, like size, histological grade, or molecular subtype; patient characteristics such as size or laterality of the breast; or treatment characteristics, including neoadjuvant or adjuvant chemotherapy, or need for a boost.

The degree of agreement did not meet our 80% cutoff for consensus in cases where available evidence was insufficient at the time of the review, that is, hypofractionation in patients younger than 40 years, receiving mastectomy, requiring irradiation of the lymph nodes, and with ductal carcinoma in situ. However, over half of the experts supported hypofractionation in all these situations.

Overall, our results are quite similar to the consensus reached by ASTRO [12] and reflected on the guidelines, despite the consideration of the age grouping in our survey and the inclusion of questions about the use of hypofractionation in mastectomized patients or in whom node irradiation is indicated.

Future lines of work, following the application of the consensus-based recommendations, will include an analysis of whether these contribute to changing the use of hypofractionation in breast cancer, standardising practice across the network of Catalan public hospitals. We will also analyse the use of hypofractionation where it is more controversial, for example in cases of immediate reconstruction with prosthesis or autologous graft, concomitant hypofractionated boost following intraoperative radiotherapy, or in the presence of autoimmune diseases.