{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:38:38Z","timestamp":1787027918441,"version":"build-2736575974"},"reference-count":45,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2021,9,13]],"date-time":"2021-09-13T00:00:00Z","timestamp":1631491200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diagnostics"],"abstract":"<jats:p>Background: During radiotherapy (RT), most breast cancer patients experience ionizing radiation (IR)-induced skin injury\u2014acute 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 (RCMcoef) alone and together with dermoscopically determined erythema (RCM-ERYcoef) were significantly associated with ARD severity grade. RCMcoef 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.<\/jats:p>","DOI":"10.3390\/diagnostics11091670","type":"journal-article","created":{"date-parts":[[2021,9,13]],"date-time":"2021-09-13T21:37:12Z","timestamp":1631569032000},"page":"1670","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Acute Radiation Dermatitis Evaluation with Reflectance Confocal Microscopy: A Prospective Study"],"prefix":"10.3390","volume":"11","author":[{"given":"Juras","family":"Ki\u0161onas","sequence":"first","affiliation":[{"name":"Department of Radiation Oncology, National Cancer Institute, LT-08660 Vilnius, Lithuania"},{"name":"Department of Neurobiology and Biophysics, Vilnius University, LT-01513 Vilnius, Lithuania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonas","family":"Venius","sequence":"additional","affiliation":[{"name":"Medical Physics Department, National Cancer Institute, LT-08660 Vilnius, Lithuania"},{"name":"Biomedical Physics Laboratory, National Cancer Institute, LT-08660 Vilnius, Lithuania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mindaugas","family":"Grybauskas","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, National Cancer Institute, LT-08660 Vilnius, Lithuania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daiva","family":"Dabkevi\u010dien\u0117","sequence":"additional","affiliation":[{"name":"Biobank, National Cancer Institute, LT-08660 Vilnius, Lithuania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arvydas","family":"Burneckis","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, National Cancer Institute, LT-08660 Vilnius, Lithuania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0825-4884","authenticated-orcid":false,"given":"Ri\u010dardas","family":"Rotomskis","sequence":"additional","affiliation":[{"name":"Biomedical Physics Laboratory, National Cancer Institute, LT-08660 Vilnius, Lithuania"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,9,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1016\/j.soc.2017.01.013","article-title":"Updates in the Treatment of Breast Cancer with Radiotherapy","volume":"26","author":"Castaneda","year":"2017","journal-title":"Surg. Oncol. Clin. N. Am."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"e825","DOI":"10.1016\/j.clbc.2018.06.015","article-title":"Radiation-induced Skin Toxicity in Breast Cancer Patients: A Systematic Review of Randomized Trials","volume":"18","author":"Yee","year":"2018","journal-title":"Clin. Breast Cancer"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"985","DOI":"10.1038\/jid.2011.411","article-title":"Ionizing Radiation: The Good, the Bad, and the Ugly","volume":"132","author":"Ryan","year":"2012","journal-title":"J. Investig. Dermatol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1007\/s10549-017-4118-7","article-title":"Hypofractionated whole breast radiotherapy in breast conservation for early-stage breast cancer: A systematic review and meta-analysis of randomized trials","volume":"162","author":"Valle","year":"2017","journal-title":"Breast Cancer Res. Treat."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"313","DOI":"10.2147\/BCTT.S109763","article-title":"Acute radiation dermatitis in breast cancer patients: Challenges and solutions","volume":"9","author":"Kole","year":"2017","journal-title":"Breast Cancer Targets Ther."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1159\/000353974","article-title":"Prophylaxis of Acute Radiation Dermatitis with an Innovative FDA-Approved Two-Step Skin Care System in a Patient with Head and Neck Cancer Undergoing a Platin-Based Radiochemotherapy: A Case Report and Review of the Literature","volume":"227","author":"Fetzner","year":"2013","journal-title":"Dermatology"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"564","DOI":"10.1111\/j.1524-4725.1993.tb00390.x","article-title":"Collagen gene expression and wound strength in normal and radiation-impaired wounds. A model of radiation-impaired wound healing","volume":"19","author":"Bernstein","year":"1993","journal-title":"J. Dermatol. Surg. Oncol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1111\/j.1742-4801.2005.00079.x","article-title":"Radiotherapy and wound healing","volume":"2","author":"Dormand","year":"2005","journal-title":"Int. Wound J."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1001\/archsurg.1992.01420030091017","article-title":"Wound-Healing Complications Following Biopsy of the Irradiated Breast","volume":"127","author":"Pezner","year":"1992","journal-title":"Arch. Surg."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"274","DOI":"10.3389\/fmed.2019.00274","article-title":"Skin Imaging Using Ultrasound Imaging, Optical Coherence Tomography, Confocal Microscopy, and Two-Photon Microscopy in Cutaneous Oncology","volume":"6","author":"Oh","year":"2019","journal-title":"Front. Med."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"776","DOI":"10.1002\/lsm.23386","article-title":"Reflectance Confocal Microscopy, Optical Coherence Tomography, and Multiphoton Microscopy in Inflammatory Skin Disease Diagnosis","volume":"53","author":"Csuka","year":"2021","journal-title":"Lasers Surg. Med."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1361","DOI":"10.1038\/nbt892","article-title":"Optical coherence tomography for ultrahigh resolution in vivo imaging","volume":"21","author":"Fujimoto","year":"2003","journal-title":"Nat. Biotechnol."},{"key":"ref_13","first-page":"e33","article-title":"Principles of Multiphoton Microscopy","volume":"103","author":"Dunn","year":"2006","journal-title":"Nephron"},{"key":"ref_14","first-page":"63","article-title":"The role of confocal microscopy in the dermato\u2013oncology practice","volume":"4","author":"Diaconeasa","year":"2011","journal-title":"J. Med. Life"},{"key":"ref_15","first-page":"1004","article-title":"In vivo confocal laser scanning microscopy imaging of skin inflammation: Clinical applications and research directions","volume":"17","author":"Ilie","year":"2019","journal-title":"Exp. Ther. Med."},{"key":"ref_16","first-page":"4102","article-title":"Current and future applications of confocal laser scanning microscopy imaging in skin oncology","volume":"17","author":"Ilie","year":"2019","journal-title":"Oncol. Lett."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Hofmann-Wellenhof, R., Pellacani, G., Malvehy, J., and Soyer, H.P. (2012). Reflectance Confocal Microscopy for Skin Diseases, Springer. [1st ed.].","DOI":"10.1007\/978-3-642-21997-9"},{"key":"ref_18","first-page":"64","article-title":"Role of In Vivo Reflectance Confocal Microscopy in the Analysis of Melanocytic Lesions","volume":"26","author":"Serban","year":"2018","journal-title":"Acta Dermatovenerol. Croat."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1080\/14737140.2019.1593829","article-title":"The use of in vivo reflectance confocal microscopy for the diagnosis of melanoma","volume":"19","author":"Agozzino","year":"2019","journal-title":"Expert Rev. Anticancer Ther."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Lupu, M., Popa, I.M., Voiculescu, V.M., and Caruntu, C. (2019). A Systematic Review and Meta-Analysis of the Accuracy of in Vivo Reflectance Confocal Microscopy for the Diagnosis of Primary Basal Cell Carcinoma. J. Clin. Med., 8.","DOI":"10.3390\/jcm8091462"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"549","DOI":"10.1684\/ejd.2016.2872","article-title":"The current role of in vivo reflectance confocal microscopy within the continuum of actinic keratosis and squamous cell carcinoma: A systematic review","volume":"26","author":"Nguyen","year":"2016","journal-title":"Eur. J. Dermatol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1111\/cup.13598","article-title":"Systematic review and proposal of an in vivo reflectance confocal microscopy assessment tool for cutaneous lymphoma","volume":"47","author":"Gouveia","year":"2020","journal-title":"J. Cutan. Pathol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"631","DOI":"10.1016\/j.ad.2016.01.010","article-title":"Reflectance Confocal Microscopy for Inflammatory Skin Diseases","volume":"107","author":"Agozzino","year":"2016","journal-title":"Actas Dermo-Sifiliogr."},{"key":"ref_24","first-page":"565","article-title":"Reflectance confocal microscopy for inflammatory skin diseases","volume":"150","author":"Prow","year":"2015","journal-title":"G. Ital. Dermatol. Venereol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1111\/j.1524-4725.2009.01421.x","article-title":"Use of Reflectance Confocal Microscopy to Monitor Response of Lentigo Maligna to Nonsurgical Treatment","volume":"36","author":"Nadiminti","year":"2010","journal-title":"Dermatol. Surg."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1159\/000254893","article-title":"Reflectance Confocal Microscopy for Noninvasive Monitoring of Therapy and Detection of Subclinical Actinic Keratoses","volume":"220","author":"Ulrich","year":"2010","journal-title":"Dermatology"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1143","DOI":"10.1111\/j.1468-3083.2012.04680.x","article-title":"Dynamic skin changes of acute radiation dermatitis revealed by in vivo reflectance confocal microscopy","volume":"27","author":"Truchuelo","year":"2013","journal-title":"J. Eur. Acad. Dermatol. Venereol."},{"key":"ref_28","first-page":"93","article-title":"Application of reflectance confocal microscopy for early diagnosis of radiation-induced acute dermatitis in radiosensitive patient: Case study","volume":"182","author":"Venius","year":"2018","journal-title":"Radiat. Prot. Dosim."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"25","DOI":"10.4103\/ejdv.ejdv_32_18","article-title":"Dermoscopy: As a new method for evaluation of radiation dermatitis in patients with breast cancer","volume":"39","author":"Nazik","year":"2019","journal-title":"Egypt. J. Dermatol. Venerol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1111\/bjd.13546","article-title":"Reflectance confocal microscopy correlates of dermoscopic patterns of facial lesions help to discriminate lentigo maligna from pigmented nonmelanocytic macules","volume":"173","author":"Farnetani","year":"2015","journal-title":"Br. J. Dermatol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1111\/jdv.15819","article-title":"Reflectance confocal microscopy and dermoscopy aid in evaluating repigmentation within or adjacent to lentigo maligna melanoma surgical scars","volume":"34","author":"Cordova","year":"2020","journal-title":"J. Eur. Acad. Dermatol. Venereol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1031","DOI":"10.1016\/j.ijrobp.2008.02.053","article-title":"Long-Term Outcomes of IMRT for Breast Cancer: A Single-Institution Cohort Analysis","volume":"72","author":"McDonald","year":"2008","journal-title":"Int. J. Radiat. Oncol."},{"key":"ref_33","unstructured":"Adlien\u0117, D. (2019). Acute Radiodermatitis Clinical Manifestation in Comparison with Reflectance Confocal Microscopy. Medical Physics in The Baltic States 2019, Kaunas University of Technology."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1295","DOI":"10.1111\/jdv.13712","article-title":"A meta-analysis of reflectance confocal microscopy for the diagnosis of malignant skin tumours","volume":"30","author":"Xiong","year":"2016","journal-title":"J. Eur. Acad. Dermatol. Venereol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"2268","DOI":"10.1111\/jdv.16248","article-title":"Reflectance confocal microscopy diagnostic accuracy for malignant melanoma in different clinical settings: Systematic review and meta-analysis","volume":"34","author":"Pezzini","year":"2020","journal-title":"J. Eur. Acad. Dermatol. Venereol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"414","DOI":"10.1111\/exd.12417","article-title":"Distinct melanoma types based on reflectance confocal microscopy","volume":"23","author":"Pellacani","year":"2014","journal-title":"Exp. Dermatol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3310\/hta20940","article-title":"VivaScope\u00ae 1500 and 3000 systems for detecting and monitoring skin lesions: A systematic review and economic evaluation","volume":"20","author":"Edwards","year":"2016","journal-title":"Health Technol. Assess."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"768","DOI":"10.1111\/ddg.14419","article-title":"Monitoring vulvar melanoma response to combined immunotherapy and radiotherapy with in vivo reflectance confocal microscopy","volume":"19","author":"Cordova","year":"2021","journal-title":"J. Dtsch. Dermatol. Ges."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1382","DOI":"10.1111\/ijd.14581","article-title":"The role of reflectance confocal microscopy in the diagnosis and management of squamous cell carcinoma in situ treated with photodynamic therapy","volume":"58","author":"Teoh","year":"2019","journal-title":"Int. J. Dermatol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1222","DOI":"10.1111\/bjd.13499","article-title":"The value of in vivo reflectance confocal microscopy in the diagnosis and monitoring of inflammatory and infectious skin diseases: A systematic review","volume":"172","author":"Hoogedoorn","year":"2015","journal-title":"Br. J. Dermatol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1575","DOI":"10.1016\/j.jaad.2020.07.130","article-title":"In vivo imaging characterization of basal cell carcinoma and cutaneous response to high-dose ionizing radiation therapy: A prospective study of reflectance confocal microscopy, dermoscopy, and ultrasonography","volume":"84","author":"Cordova","year":"2021","journal-title":"J. Am. Acad. Dermatol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1016\/j.det.2016.05.013","article-title":"Telediagnosis with Confocal Microscopy: A Reality or a Dream?","volume":"34","author":"Witkowski","year":"2016","journal-title":"Dermatol. Clin."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1067\/mjd.2003.220","article-title":"Confocal histopathology of irritant contact dermatitis in vivo and the impact of skin color (black vs. white)","volume":"48","author":"Hicks","year":"2003","journal-title":"J. Am. Acad. Dermatol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"19216","DOI":"10.1038\/srep19216","article-title":"In vivo characterization of early-stage radiation skin injury in a mouse model by two-photon microscopy","volume":"6","author":"Jang","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"2652","DOI":"10.1364\/BOE.387400","article-title":"Characterization of early-stage cutaneous radiation injury by using optical coherence tomography angiography","volume":"11","author":"Lee","year":"2020","journal-title":"Biomed. Opt. 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