||Response to "Comment on 'Objective assessment in digital images of skin erythema
Matsubara, Hiroaki ,
Karasawa, Kumiko ,
Matsufuji, Naruhiro ,
Tsuji, Hiroshi ,
Yamamoto, Naoyoshi ,
Nakajima, Mio ,
Karube, MasatakaTakahashi, Wataru
, p.2689 , 2017-02 , John Wiley and Sons, Inc.
We appreciate the interest of Carrara et al.1 in our recent article on the assessment method in digital images of skin erythema caused by radiotherapy.2 Matsubara et al. presented a linear relationship between skin blood flow and skin dose, while Carrara et al. suggest that their clinical data do not reproduce it even though their sample number of patients treated is ten times larger than that of Matsubara et al. We would like to suggest that the disagreement between the data by Carrara et al. and Matsubara et al. is qualitatively reasonable because it arises from neglecting the recovery process of damaged skin as is explained below. Skin erythema is physiologically caused by expansion of capillaries due to increased blood flow, which is a part of the biological skin repair response. As long as the skin erythema is an acute toxicity, the skin recovers and the symptom usually disappears in several months. This indicates that skin blood flowincreases owing to the repair process just after irradiation, but decreases owing to the recovery process from the damaged skin a few tens of days later. Matsubara et al. treated six patients who had the carbon beam therapy with a total prescription dose of 50 Gy (RBE).2 It should be noted that the prescription dose was delivered by a single fraction from four ports, indicating that the treatment was completed in one day. On the other hand, Carrara et al. treated 61 patients who had the 6/15 MV photon therapy with a total prescription dose of 50 Gy but with a 2 Gy fraction, indicating that the treatment was completed in 25 days. The recovery process for skin erythema is assumed to work during the treatment. This would result in the reduction of skin blood flow per accumulated skin dose, causing nonlinearity between skin blood flow and skin dose. The disagreement between the data by Carrara et al. and Matsubara et al. can be qualitatively understood by taking the recovery process into account. That is why Matsubara et al. selected only the cases of a single fraction in order to avoid the recovery effect. As Carrara et al. suggest, however, we agree that the linearity observed by Matsubara et al. is not based on physical evidence. What Matsubara et al. discussed was just that the gross trend of the obtained data could be expressed by the linear relationship with moderate accuracy, where several variations due to individuality of patient or time dependence of skin erythema were assumed to be negligible as discussed in Ref. 2. There is no known numerical relationship between accumulated skin dose and time dependence of skin erythema. The new data suggested by Carrara et al., therefore, are assumed to be important for further investigation of skin erythema.