Обзор актуализирует проблему радиационно-индуцированных кожных реакций (РИКР), выделяет высокую частоту РИКР у пациентов с кожными лимфомами, подвергающихся лучевой терапии, и анализирует многочисленные патологические процессы, формирующиеся в коже при воздействии ионизирующего излучения. Обзор систематизирует внешние и внутренние факторы, влияющие на развитие РИКР, сравнивает методы диагностики, рассматривает меры предупреждения и лечения радиационного дерматита, а также описывает механизм действия препаратов для профилактики и лечения РИКР. РИКР остаются значительной проблемой при лучевой терапии, характеризуясь высокой частотой, разнообразием клинических проявлений и влиянием на качество жизни пациентов. Рассмотрены механизмы, диагностика, профилактика и лечение РИКР.
This review highlights the issue of radiation-induced skin reactions (RISR), emphasizes the high frequency of RISR in patients with cutaneous lymphomas undergoing radiation therapy, and analyzes numerous pathological processes that occur in the skin as a result of ionizing radiation exposure. The review systematically examines external and internal factors influencing the development of RISR, compares diagnostic methods, discusses preventive measures and treatments for radiation dermatitis, and describes the mechanisms of action for drugs used in RISR prophylaxis and treatment. RISR remains a significant problem in radiation therapy, characterized by a high frequency, a wide range of clinical manifestations, and an impact on patients’ quality of life. The mechanisms, diagnosis, prevention, and treatment of RISR are considered.
1. O'Malley JT, de Masson A, Lowry EL, et al. Radiotherapy eradicates malignant T cells and is associated with improved survival in early-stage mycosis fungoides. Clin Cancer Res. 2020;26(2):408-18.
2. Wei J, Meng L, Hou X, et al. Radiation-induced skin reactions: mechanism and treatment. Cancer Manag Res. 2019;11:167-77.
3. Chan RJ, Blades R, Jones L, et al. A single-blind, randomised controlled trial of StrataXRT® – A silicone-based film-forming gel dressing for prophylaxis and management of radiation dermatitis in patients with head and neck cancer. Radiother Oncol. 2019;139:72-8.
4. Hoeller U, Tribius S, Kuhlmey A, et al. Increasing the rate of late toxicity by changing the score? A comparison of RTOG/EORTC and LENT/SOMA scores. Int J Radiation Oncol Biol Physics. 2003;55(4):1013-18.
5. Cancer Institute N. Common terminology criteria for adverse events (CTCAE) common terminology criteria for adverse events (CTCAE) v5. 0. 2017. Available at: https://ctep.cancer.gov/protocoldevelopment/electronic_applications/docs/ctcae_v5_quick_reference_5x.... Accessed: 01.06.2023.
6. Qi Z, Wissman RD. Radiologic Physics: The Essentials. Wolters Kluwer Health, Lippincott Williams & Wilkins, Baltimore and Philadelphia, 2019.
7. Yan W, Lu X, Huang R, et al. Correlated factors of acute oral mucosal and skin reaction induced by radiotherapy in hypopharyngeal carcinoma. Research Square. 2020. DOI:10.21203/rs.3.rs-20081/v1
8. Hegedus F, Mathew LM, Schwartz RA. Radiation dermatitis: an overview. Int J Dermatol. 2017;56(9):909-14.
9. Mapuskar KA, Flippo KH, Schoenfeld JD, et al. Mitochondrial superoxide increases age-associated susceptibility of human dermal fibroblasts to radiation and chemotherapy. Cancer Res. 2017;77(18):5054-67.
10. Fajardo LF. The pathology of ionizing radiation as defined by morphologic patterns. Acta Oncologica. 2005;44(1):13-22.
11. Bray FN, Simmons BJ, Wolfson AH, Nouri K. Acute and chronic cutaneous reactions to ionizing radiation therapy. Dermatol Ther (Heidelb). 2016;6(2):185-206.
12. Yang X, Ren H, Guo X, et al. Radiation-induced skin injury: pathogenesis, treatment, and management. Aging (Albany NY). 2020;12(22):23379-93.
13. Doi H, Matsumoto S, Odawara S, et al. Pravastatin reduces radiation-induced damage in normal tissues. Exp Ther Med. 2017;13(5):1765-72.
14. Jacobson LK, Johnson MB, Dedhia RD, et al. Impaired wound healing after radiation therapy: A systematic review of pathogenesis and treatment. JPRAS Open. 2017;13:92-105.
15. Mahadevan A, Moningi S, Grimm J, et al. Maximizing tumor control and limiting complications with stereotactic body radiation therapy for pancreatic cancer. Int J Radiat Oncol Biol Phys. 2021;110(1):206-16.
16. Fernando IN, Bowden SJ, Herring K, et al. Synchronous versus sequential chemo-radiotherapy in patients with early stage breast cancer (SECRAB): A randomised, phase III, trial. Radiother Oncol. 2020;142:52-61.
17. DiCarlo AL, Bandremer AC, Hollingsworth BA, et al. Cutaneous radiation injuries: models, assessment and treatments. Radiat Res. 2020;194(3):315-44.
18. Quan Y, Sun M, Tan Z, et al. Organ-on-a-chip: the next generation platform for risk assessment of radiobiology. RSC Advances. 2020;10(65):39521-30.
19. Bentzen SM, Overgaard J. Patient-to-patient variability in the expression of radiation-induced normal tissue injury. Seminn Radiat Oncol. 1994;4(2):68-80.
20. Kerns SL, Chuang KH, Hall W, et al. Radiation biology and oncology in the genomic era. Br J Radiol. 2018;91(1091):20170949.
21. Hamilton CS, Denham JW, O’Brien M, et al. Underprediction of human skin erythema at low doses per fraction by the linear quadratic model. Radiother Oncol. 1996;40(1):23-30.
22. Abdlaty R, Hayward J, Farrell T, et al. Skin erythema and pigmentation: a review of optical assessment techniques. Photodiagnosis Photodyn Ther. 2021;33:102127.
23. Huang R, Zhou Y, Hu S, et al. Radiotherapy exposure in cancer patients and subsequent risk of stroke: a systematic review and meta-analysis. Front Neurol. 2019;10:233.
24. Vinnikov VA, Rubleva TV. Predictors of radiation-induced complications in radiation oncology based on cell survival tests after ex vivo exposure: literature review. Ukrainian Journal of Radiology and Oncology. 2021;29(1):89-118.
25. Habash M, Bohorquez LC, Kyriakou E, et al. Clinical and functional assays of radiosensitivity and radiation-induced second cancer. Cancers (Basel). 2017;9(11):147.
26. Kawamura H, Kubo N, Sato H, et al. Quality of life in prostate cancer patients receiving particle radiotherapy: A review of the literature. Int J Urol. 2020;27(1):24-9.
27. Held E, Lorentzen H, Agner T, et al. Comparison between visual score and erythema index (DermaSpectrometer) in evaluation of allergic patch tests. Skin Res Technol.
1998;4(4):188-91.
28. Diffey BL, Farr PM. Quantitative aspects of ultraviolet erythema. Clin Phys Physiol Meas. 1991;12(4):311-25.
29. Treesirichod A, Chansakulporn S, Wattanapan P. Correlation between skin color evaluation by skin color scale chart and narrowband reflectance spectrophotometer. Indian J Dermatol. 2014;59(4):339-42.
30. Lomax ME, Folkes LK, O’neill P. Biological consequences of radiation-induced DNA damage: relevance to radiotherapy. Clin Oncol. 2013;25(10):578-85.
31. Lee JB. Commentary: Instrumentation in dermatology. Clinics in Dermatology. 2021;39(4):553-4.
32. Pazdrowski J, Dańczak-Pazdrowska A, Polańska A, et al. An ultrasonographic monitoring of skin condition in patients receiving radiotherapy for head and neck cancers. Skin Res Technol. 2019;25(6):857-61.
33. Monnier J, Tognetti L, Miyamoto M, et al. In vivo characterization of healthy human skin with a novel, non-invasive imaging technique: line-field confocal optical coherence tomography. J Eur Acad Dermatol Venereol. 2020;34(12):2914-21.
34. Abdlaty R, Doerwald-Munoz L, Madooei A, et al. Hyperspectral imaging and classification for grading skin erythema. Front Phys. 2018;6:72. DOI:10.3389/fphy.2018.00072
35. Gujral MS, Patnaik PM, Kaul R, et al. Efficacy of hydrolytic enzymes in preventing radiation therapy-induced side effects in patients with head and neck cancers. Cancer Chemother Pharmacol. 2001;47 Suppl.:S23-8.
36. Lin LC, Que J, Lin LK, Lin FC. Zinc supplementation to improve mucositis and dermatitis in patients after radiotherapy for head-and-neck cancers: a double-blind, randomized study. Int J Radiat Oncol Biol Phys. 2006;65(3):745-50.
37. Blades R. A cost-effectiveness analysis of a silicone film-forming gel versus 10% glycerine in patients with head and neck cancer. Queensland University of Technology, 2020.
38. Ryan Wolf J, Gewandter JS, Bautista J, et al. Utility of topical agents for radiation dermatitis and pain: a randomized clinical trial. Support Care Cancer. 2020;28(7):3303-11.
39. Menêses AG, Reis PEDD, Guerra ENS, et al. Use of trolamine to prevent and treat acute radiation dermatitis: a systematic review and meta-analysis. Rev Lat Am Enfermagem. 2018;26:e2929.
40. Ferreira EB, Ciol MA, de Meneses AG, et al. Chamomile gel versus urea cream to prevent acute radiation dermatitis in head and neck cancer patients: Results from a preliminary clinical trial. Integr Cancer Ther. 2020;19:1534735420962174.
41. Ahmadloo N, Kadkhodaei B, Omidvari Sh, et al. Lack of prophylactic effects of Aloe Vera gel on radiation induced dermatitis in breast cancer patients. Asian Pac J Cancer Prev. 2017;18(4):1139-43.
42. Miller RC, Schwartz DJ, Sloan JA, et al. Mometasone furoate effect on acute skin toxicity in breast cancer patients receiving radiotherapy: a phase III double-blind, randomized trial from the North Central Cancer Treatment Group N06C4. Int J Radiat Oncol Biol Phys. 2011;79(5):1460-6.
43. Potera ME, Lookingbill DP, Stryker JA. Prophylaxis of radiation dermatitis with a topical cortisone cream. Radiology. 1982;143(3):775-7.
44. Liao Y, Feng G, Dai T, et al. Randomized, self-controlled, prospective assessment of the efficacy of mometasone furoate local application in reducing acute radiation dermatitis in patients with head and neck squamous cell carcinomas. Medicine (Baltimore). 2019;98(52):e18230.
45. Р ФМБА России 2.2.9.84-2015. Организация и проведение психофизиологических обследований работников организаций, эксплуатирующих особо радиационно опасные и ядерно опасные производства и объекты в области использования атомной энергии, при прохождении работниками медицинских осмотров в медицинских организациях ФМБА России. Методические рекомендации (утв. ФМБА России 29.12.2015) [R FMBA Rossii 2.2.9.84-2015. Organizatsiia i provedenie psikhofiziologicheskikh obsledovanii rabotnikov organizatsii, ekspluatiruiushchikh osobo radiatsionno opasnye i iaderno opasnye proizvodstva i ob"ekty v oblasti ispol'zovaniia atomnoi energii, pri prokhozhdenii rabotnikami meditsinskikh osmotrov v meditsinskikh organizatsiiakh FMBA Rossii. Metodicheskie rekomendatsii (utv. FMBA Rossii 29.12.2015) (in Russian)].
________________________________________________
1. O'Malley JT, de Masson A, Lowry EL, et al. Radiotherapy eradicates malignant T cells and is associated with improved survival in early-stage mycosis fungoides. Clin Cancer Res. 2020;26(2):408-18.
2. Wei J, Meng L, Hou X, et al. Radiation-induced skin reactions: mechanism and treatment. Cancer Manag Res. 2019;11:167-77.
3. Chan RJ, Blades R, Jones L, et al. A single-blind, randomised controlled trial of StrataXRT® – A silicone-based film-forming gel dressing for prophylaxis and management of radiation dermatitis in patients with head and neck cancer. Radiother Oncol. 2019;139:72-8.
4. Hoeller U, Tribius S, Kuhlmey A, et al. Increasing the rate of late toxicity by changing the score? A comparison of RTOG/EORTC and LENT/SOMA scores. Int J Radiation Oncol Biol Physics. 2003;55(4):1013-18.
5. Cancer Institute N. Common terminology criteria for adverse events (CTCAE) common terminology criteria for adverse events (CTCAE) v5. 0. 2017. Available at: https://ctep.cancer.gov/protocoldevelopment/electronic_applications/docs/ctcae_v5_quick_reference_5x.... Accessed: 01.06.2023.
6. Qi Z, Wissman RD. Radiologic Physics: The Essentials. Wolters Kluwer Health, Lippincott Williams & Wilkins, Baltimore and Philadelphia, 2019.
7. Yan W, Lu X, Huang R, et al. Correlated factors of acute oral mucosal and skin reaction induced by radiotherapy in hypopharyngeal carcinoma. Research Square. 2020. DOI:10.21203/rs.3.rs-20081/v1
8. Hegedus F, Mathew LM, Schwartz RA. Radiation dermatitis: an overview. Int J Dermatol. 2017;56(9):909-14.
9. Mapuskar KA, Flippo KH, Schoenfeld JD, et al. Mitochondrial superoxide increases age-associated susceptibility of human dermal fibroblasts to radiation and chemotherapy. Cancer Res. 2017;77(18):5054-67.
10. Fajardo LF. The pathology of ionizing radiation as defined by morphologic patterns. Acta Oncologica. 2005;44(1):13-22.
11. Bray FN, Simmons BJ, Wolfson AH, Nouri K. Acute and chronic cutaneous reactions to ionizing radiation therapy. Dermatol Ther (Heidelb). 2016;6(2):185-206.
12. Yang X, Ren H, Guo X, et al. Radiation-induced skin injury: pathogenesis, treatment, and management. Aging (Albany NY). 2020;12(22):23379-93.
13. Doi H, Matsumoto S, Odawara S, et al. Pravastatin reduces radiation-induced damage in normal tissues. Exp Ther Med. 2017;13(5):1765-72.
14. Jacobson LK, Johnson MB, Dedhia RD, et al. Impaired wound healing after radiation therapy: A systematic review of pathogenesis and treatment. JPRAS Open. 2017;13:92-105.
15. Mahadevan A, Moningi S, Grimm J, et al. Maximizing tumor control and limiting complications with stereotactic body radiation therapy for pancreatic cancer. Int J Radiat Oncol Biol Phys. 2021;110(1):206-16.
16. Fernando IN, Bowden SJ, Herring K, et al. Synchronous versus sequential chemo-radiotherapy in patients with early stage breast cancer (SECRAB): A randomised, phase III, trial. Radiother Oncol. 2020;142:52-61.
17. DiCarlo AL, Bandremer AC, Hollingsworth BA, et al. Cutaneous radiation injuries: models, assessment and treatments. Radiat Res. 2020;194(3):315-44.
18. Quan Y, Sun M, Tan Z, et al. Organ-on-a-chip: the next generation platform for risk assessment of radiobiology. RSC Advances. 2020;10(65):39521-30.
19. Bentzen SM, Overgaard J. Patient-to-patient variability in the expression of radiation-induced normal tissue injury. Seminn Radiat Oncol. 1994;4(2):68-80.
20. Kerns SL, Chuang KH, Hall W, et al. Radiation biology and oncology in the genomic era. Br J Radiol. 2018;91(1091):20170949.
21. Hamilton CS, Denham JW, O’Brien M, et al. Underprediction of human skin erythema at low doses per fraction by the linear quadratic model. Radiother Oncol. 1996;40(1):23-30.
22. Abdlaty R, Hayward J, Farrell T, et al. Skin erythema and pigmentation: a review of optical assessment techniques. Photodiagnosis Photodyn Ther. 2021;33:102127.
23. Huang R, Zhou Y, Hu S, et al. Radiotherapy exposure in cancer patients and subsequent risk of stroke: a systematic review and meta-analysis. Front Neurol. 2019;10:233.
24. Vinnikov VA, Rubleva TV. Predictors of radiation-induced complications in radiation oncology based on cell survival tests after ex vivo exposure: literature review. Ukrainian Journal of Radiology and Oncology. 2021;29(1):89-118.
25. Habash M, Bohorquez LC, Kyriakou E, et al. Clinical and functional assays of radiosensitivity and radiation-induced second cancer. Cancers (Basel). 2017;9(11):147.
26. Kawamura H, Kubo N, Sato H, et al. Quality of life in prostate cancer patients receiving particle radiotherapy: A review of the literature. Int J Urol. 2020;27(1):24-9.
27. Held E, Lorentzen H, Agner T, et al. Comparison between visual score and erythema index (DermaSpectrometer) in evaluation of allergic patch tests. Skin Res Technol.
1998;4(4):188-91.
28. Diffey BL, Farr PM. Quantitative aspects of ultraviolet erythema. Clin Phys Physiol Meas. 1991;12(4):311-25.
29. Treesirichod A, Chansakulporn S, Wattanapan P. Correlation between skin color evaluation by skin color scale chart and narrowband reflectance spectrophotometer. Indian J Dermatol. 2014;59(4):339-42.
30. Lomax ME, Folkes LK, O’neill P. Biological consequences of radiation-induced DNA damage: relevance to radiotherapy. Clin Oncol. 2013;25(10):578-85.
31. Lee JB. Commentary: Instrumentation in dermatology. Clinics in Dermatology. 2021;39(4):553-4.
32. Pazdrowski J, Dańczak-Pazdrowska A, Polańska A, et al. An ultrasonographic monitoring of skin condition in patients receiving radiotherapy for head and neck cancers. Skin Res Technol. 2019;25(6):857-61.
33. Monnier J, Tognetti L, Miyamoto M, et al. In vivo characterization of healthy human skin with a novel, non-invasive imaging technique: line-field confocal optical coherence tomography. J Eur Acad Dermatol Venereol. 2020;34(12):2914-21.
34. Abdlaty R, Doerwald-Munoz L, Madooei A, et al. Hyperspectral imaging and classification for grading skin erythema. Front Phys. 2018;6:72. DOI:10.3389/fphy.2018.00072
35. Gujral MS, Patnaik PM, Kaul R, et al. Efficacy of hydrolytic enzymes in preventing radiation therapy-induced side effects in patients with head and neck cancers. Cancer Chemother Pharmacol. 2001;47 Suppl.:S23-8.
36. Lin LC, Que J, Lin LK, Lin FC. Zinc supplementation to improve mucositis and dermatitis in patients after radiotherapy for head-and-neck cancers: a double-blind, randomized study. Int J Radiat Oncol Biol Phys. 2006;65(3):745-50.
37. Blades R. A cost-effectiveness analysis of a silicone film-forming gel versus 10% glycerine in patients with head and neck cancer. Queensland University of Technology, 2020.
38. Ryan Wolf J, Gewandter JS, Bautista J, et al. Utility of topical agents for radiation dermatitis and pain: a randomized clinical trial. Support Care Cancer. 2020;28(7):3303-11.
39. Menêses AG, Reis PEDD, Guerra ENS, et al. Use of trolamine to prevent and treat acute radiation dermatitis: a systematic review and meta-analysis. Rev Lat Am Enfermagem. 2018;26:e2929.
40. Ferreira EB, Ciol MA, de Meneses AG, et al. Chamomile gel versus urea cream to prevent acute radiation dermatitis in head and neck cancer patients: Results from a preliminary clinical trial. Integr Cancer Ther. 2020;19:1534735420962174.
41. Ahmadloo N, Kadkhodaei B, Omidvari Sh, et al. Lack of prophylactic effects of Aloe Vera gel on radiation induced dermatitis in breast cancer patients. Asian Pac J Cancer Prev. 2017;18(4):1139-43.
42. Miller RC, Schwartz DJ, Sloan JA, et al. Mometasone furoate effect on acute skin toxicity in breast cancer patients receiving radiotherapy: a phase III double-blind, randomized trial from the North Central Cancer Treatment Group N06C4. Int J Radiat Oncol Biol Phys. 2011;79(5):1460-6.
43. Potera ME, Lookingbill DP, Stryker JA. Prophylaxis of radiation dermatitis with a topical cortisone cream. Radiology. 1982;143(3):775-7.
44. Liao Y, Feng G, Dai T, et al. Randomized, self-controlled, prospective assessment of the efficacy of mometasone furoate local application in reducing acute radiation dermatitis in patients with head and neck squamous cell carcinomas. Medicine (Baltimore). 2019;98(52):e18230.
45. R FMBA Rossii 2.2.9.84-2015. Organizatsiia i provedenie psikhofiziologicheskikh obsledovanii rabotnikov organizatsii, ekspluatiruiushchikh osobo radiatsionno opasnye i iaderno opasnye proizvodstva i ob"ekty v oblasti ispol'zovaniia atomnoi energii, pri prokhozhdenii rabotnikami meditsinskikh osmotrov v meditsinskikh organizatsiiakh FMBA Rossii. Metodicheskie rekomendatsii (utv. FMBA Rossii 29.12.2015) (in Russian).
1 ФГБУ «Российский научный центр радиологии и хирургических технологий им. акад. A.M. Гранова» Минздрава России, Санкт-Петербург, Россия;
2 ФГБОУ ВО «Санкт-Петербургский государственный педиатрический медицинский университет» Минздрава России, Санкт-Петербург
*m.zelianina@rambler.ru
________________________________________________
Nikolay V. Ilyin1, Yulia N. Vinogradova1, Denis V. Zaslavskiy2, Maria I. Zelianina*1
1 Granov Russian Research Center of Radiology and Surgical Technologies, Saint Petersburg, Russia;
2 Saint Petersburg State Pediatric Medical University, Saint Petersburg, Russia
*m.zelianina@rambler.ru