Acute Radiation Dermatitis Evaluation with Reflectance Confocal Microscopy: A Prospective Study

Abstract

Background: During radiotherapy (RT), most breast cancer patients experience ionizing radiation (IR)-induced skin injury-acute radiation dermatitis (ARD). The severity of ARD is determined by a physician according to CTCAE or RTOG scales, which are subjective. Reflectance confocal microscopy (RCM) is a noninvasive skin imaging technique offering cellular resolution. Digital dermoscopy (DD) performed in conjugation with RCM can provide more information regarding skin toxicity. The purpose of this study is to create an RCM and DD features-based ARD assessment scale, to assess the association with CTCAE scale and possible predictive value.

Methods: One hundred and three breast cancer patients during RT were recruited; every week, clinical symptoms of ARD (CTCAE scale) were evaluated and RCM, together with digital dermoscopy (DD), was performed.

Results: According to RCM; after 2 RT weeks, exocytosis and/or spongiosis were present in 94% of patients; after 3 weeks, mild contrast cells (MMCs) were detected in 45%; disarrayed epidermis (DE) was present in 66% of patients after 4 weeks and in 93% after 5 weeks; abnormal dermal papillae (ADP) were present in 68% of patients after 5 weeks. The coefficients of RCM features (RCM_coef) alone and together with dermoscopically determined erythema (RCM-ERY_coef) were significantly associated with ARD severity grade. RCM_coef is a significant predictive factor for the clinical manifestation of ARD.

Conclusions: RCM features of irradiated skin appear earlier than clinical symptoms, have a characteristic course, and allow the severity of ARD to be predicted.

Keywords: acute radiation dermatitis; breast cancer; reflectance confocal microscopy.

Figure 1

Dermascopic view of a single patient’s skin changes indicating the progression of skin ERY during radiotherapy; fx—radiotherapy fractions.

Figure 2

Dynamics of RCM features during radiotherapy: (a) normal honeycomb-like pattern of epidermis before radiotherapy; (b) normal view of dermal papillae in the dermo-epidermal junction (DEJ) before radiotherapy; (c) white line selection indicating exocytosis (aggregates of round-to-polygonal, mildly refractive cells) in epidermis after 5 radiotherapy fractions (fx); (d) normal view of dermal papillae in the DEJ after 5 fx; (e) white line selection indicating spongiosis (darker area relative to the surrounding epithelium of the stratum spinosum with intercellular spaces between keratinocytes larger than normal) and exocytosis in epidermis after 10 fx; (f) normal view of dermal papillae in the DEJ after 10 fx; (g) white line selection indicating the first signs of disarrayed epidermis (DE) after 15 fx; (h) white arrows indicating mild contrast cells (MMCs) in the DEJ after 15 fx; (i) white ovals indicating DE after 20 fx; (j) white arrows indicating MMCs in the DEJ after 20 fx; (k) white oval indicating large area of DE after 25 fx; (l) white circles indicating abnormal dermal papillae (ADP) after 25 fx.

Figure 2

Dynamics of RCM features during radiotherapy: (a) normal honeycomb-like pattern of epidermis before radiotherapy; (b) normal view of dermal papillae in the dermo-epidermal junction (DEJ) before radiotherapy; (c) white line selection indicating exocytosis (aggregates of round-to-polygonal, mildly refractive cells) in epidermis after 5 radiotherapy fractions (fx); (d) normal view of dermal papillae in the DEJ after 5 fx; (e) white line selection indicating spongiosis (darker area relative to the surrounding epithelium of the stratum spinosum with intercellular spaces between keratinocytes larger than normal) and exocytosis in epidermis after 10 fx; (f) normal view of dermal papillae in the DEJ after 10 fx; (g) white line selection indicating the first signs of disarrayed epidermis (DE) after 15 fx; (h) white arrows indicating mild contrast cells (MMCs) in the DEJ after 15 fx; (i) white ovals indicating DE after 20 fx; (j) white arrows indicating MMCs in the DEJ after 20 fx; (k) white oval indicating large area of DE after 25 fx; (l) white circles indicating abnormal dermal papillae (ADP) after 25 fx.