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Background Radiation dermatitis is of common occurrence in patients treated with combined radiotherapy and chemotherapy for head and neck malignancies. Its timely and adequate management is of uttermost importance for both oncological outcomes and patients? global quality of life. In this study, we prospectively evaluated the role of hypericum perforatum and neem oil (Holoil?; RIMOS srl, Mirandola, Italy) in the treat ment of acute skin toxicity for patients undergoing radiotherapy or chemo-radiotherapy for head and neck cancer. Methods A consecutive series of 28 head and neck cancer patients submitted to radiotherapy (RT) was enrolled onto this mono-institutional single-arm prospective observational study between November 2013 and June 2014. Patients undergoing both definitive or post-operative radiotherapy were allowed, either as exclusive modality or combined with (concomitant or induction) chemotherapy. We employed a reactive, rather than a prophylactic approach, starting Holoil treatment whenever bright erythema, moderate oedema or patchy moist desquamation were observed (G2 acute skin toxicity according to the RTOG scoring scale). Holoil? was used during all RT course and during fo llow up time, until acute skin toxicity recovery. Twice a day applications were mostly given. Results The maximum detected acute skin toxicity was Grade 1 in 7% of patients, Grade 2 in 68%, Grade 3 in 25%, while at the end of RT was Grade 0 in 3.5% of patients, Grade 1 in 32%, Grade 2 in 61%, Grade 3 in 3.5%. For patients having G2 acute skin toxicity, it mainly started at weeks 4?5, while for those having G3, it began during weeks 5 and 6. Median times spent with G2 or G3 toxicity during RT were 17.5 and 11 days. Patients having G2 acute skin toxicity had a worsening of their dermatitis in 27% of case, with a median occurrence time of 7 days. G3 events were reconverted to a G2 profile in 100% of patients after a median time of 7 days. Those experiencing a G2 skin event were converted to a G1 score in 23% of cases after a median time of 14 days. Time between maximum acute skin toxicity and complete skin recovery after RT was 27 days. Conclusions Holoil? proved to be a safe and active option in th e management of acute skin toxicity in head and neck cancer patients submitted to RT or chemo-radiotherapy. A prophylactic effect in the prevention of moist desquamation may be hypothesized for hypericum and neem oil and need to be tested within a prospective controlled study. [ABSTRACT FROM AUTHOR]