The Italian Association for Radiotherapy and Clinical Oncology (AIRO) position statements for postoperative breast cancer radiation therapy volume, dose, and fractionation

Recent advances in non-metastatic breast cancer radiation therapy significantly reshaped our views on modern dose and fractionation schedules. Especially the advent of hypofractionation and partial breast irradiation defined a new concept of treatment optimization, that should strongly include both patient and tumour characteristics in the physician’s decision-making process. Unfortunately, hypofractionation for breast cancer radiation therapy needed long time to enter the routine practice during the last decades despite the level-1 evidence published over time. Hereby we present the Italian Association for Radiotherapy and Clinical Oncology (AIRO) Breast Cancer Group position statements for postoperative breast cancer radiation therapy volume, dose, and fractionation to harmonically boost routine clinical practice implementation following evidence-based data.


Introduction
Recent advances in non-metastatic breast cancer radiation therapy significantly reshaped our views on modern dose and fractionations schedules. Especially the advent of hypofractionation and partial breast irradiation defined a new concept of treatment optimization, that should strongly consider both patient and tumour features in the decision-making process. In this framework, the European Society for Radiotherapy and Oncology Advisory Committee in Radiation Oncology Practice (ESTRO-ACROP) consensus recommendations on patient selection and dose and fractionation for externalbeam radiotherapy in early breast cancer have been recently released [1].
To facilitate and enhance the breast oncologist's community harmony, the Italian Association for Radiotherapy and Clinical Oncology (AIRO) Breast Cancer Group felt the need for a prompt reaction to integrate this level-1 evidence in the routine clinical practice. Hereby we present the position statements for postoperative breast cancer radiation therapy volume, dose, and fractionation.

Discussion
The AIRO felt the strong needs for sake of clarity to endorse the recently published Consensus statements released in 2022 by the ESTRO-ACROP initiative [1]. Hypofractionation for breast cancer radiation therapy needed too much time to enter the routine clinical practice during the last decades despite the level-1 evidence published over time [1][2][3][4][5][6]. Hypofractionation for breast cancer radiation therapy passed through a long-lasting debate about its safety and efficacy, although there are no economic [19], radiobiologic [20], nor clinic reasons [2, 5, 21] to justify these uncertainties. And this fact was probably caused by several heterogeneous factors, such as shortage of experience in hypofractionation, minimal resources for quality assurance in radiotherapy, inadequate support to change, and reimbursement policies [1]. However, we strongly believe that one of the crucial boosts to harmonically implement evidencebased data in the routine practice of a Country is represented by a clear, transparent, and strong position statement released by the national Society of the leading discipline.
Endorsing the European ESTRO-ACROP initiative [1], in line with the UK Breast Radiotherapy Consensus Working Group [9], we would like to enhance and reinforce the evidence supporting hypofractionation for all the indications of external-beam postoperative radiation therapy for non-metastatic breast cancer, including whole and partial breast, chest wall with or without reconstruction, and regional nodal irradiation. If moderate hypofractionation (40-42.5 Gy in 15-16 fractions) represents the standard of care for all the abovementioned indications, ultra-hypofractionation (26 Gy in 5 fractions) should be considered standard of care for whole breast irradiation and chest wall irradiation without reconstruction. Conversely, further data are awaited to confirm the recommendation in favour of ultra-hypofractionation concerning chest wall with reconstruction and regional nodal irradiation (Table 1). External-beam partial breast irradiation should be preferred over whole breast irradiation in case of clearly identified suitable features (Table 2) [1]. In these selected patients, partial breast irradiation using once-daily, consecutive fractions, schedule (40 Gy in 15 fractions or 26-30 Gy in 5 fractions) warrants equivalent disease control and a favourable safety toxicity profile [11,[14][15][16][17].
Fast implementation of short course radiation therapy schedules will warrant equity of access for all our patients. At the same time, benefits and risks, including uncertainties, of all available cancer treatments should be always discussed and shared with our patients, warranting an adequate counselling on the best evidence-based radiation therapy.
Acknowledgments The Authors thank the Scientific Committee and Board of the AIRO for the critical revision and final approval of the manuscript (Nr. 23/2022).

Author Contributions
All authors contributed to the study conception and design, material preparation, data collection and analysis. The first draft of the manuscript was written by Icro Meattini, and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.
Funding Open access funding provided by Università degli Studi di Firenze within the CRUI-CARE Agreement. The authors declare that no funds, grants, or other support were received during the preparation of this manuscript.

Declarations
Conflict of interest IM received a small fee for occasional attendance at the advisory board supported by Eli Lilly, Novartis, Pfizer, Seagen, Accuray. PP is a medical adviser of Sordina IORT Technologies. All other authors declare no competing interests.

Ethical approval This article does not contain any studies with human participants or animals performed by any of the authors.
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