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Our study confirmed the feasibility of an AHF treatment, especially using IMRT technique. Assessing late toxicity by clinical examination, a higher incidence of subcutaneous side effects was recorded in patients undergoing AHF. However, this increase was limited to G1–G2 toxicity. Therefore, the results of our study are not enough to question the safety of hypofractionated regimens in this setting, which have been tested in large randomized controlled trials and have become the clinical standard in many centers. However, we believe that in patients with multiple risk factors for late toxicity (larger PTV volume, diabetes, tobacco smoking), caution should be taken during and after treatment also considering the demonstrated correlation between acute and late effects.19 Further trials on this topic will be useful to identify more precisely the patients who deserve this particular attention. The results from some trials20,21 that completed enrollment some years ago and pending publication could clarify some unanswered questions regarding this issue.


This paper is dedicated to our colleague Cinzia Digesù (1971–2015) who passed away when the study was under development and whose contribution to this trial was invaluable.


The authors report no conflicts of interest in this work.

Cinzia Digesù,1 Francesco Deodato,1 Gabriella Macchia,1Savino Cilla,2 Martina Pieri,3 Alice Zamagni,4 Andrea Farioli,5 Milly Buwenge,4 Gabriella Ferrandina,6,* Alessio G Morganti4,*

1Radiotherapy Unit, General Oncology Unit, Fondazione Giovanni Paolo II, Campobasso, Italy; 2Medical Physics Unit, Fondazione Giovanni Paolo II, Campobasso, Italy;3Radiotherapy Unit, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori, Meldola, Italy; 4Radiation Oncology Center, Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, Bologna, Italy; 5Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy; 6Department of Woman and Child Health, Gynecologic Oncology Unit, Fondazione “Policlinico Universitario A. Gemelli”, IRCSS, Universita’ Cattolica Sacro Cuore, Rome, Italy

*These authors contributed equally to this work.