Total Skin Irradiation in the Treatment of Primary Cutaneous Lymphomas: a Literature Review and Clinical Cases

Introduction: Primary cutaneous lymphomas represent a heterogeneous group of diseases, the treatment of advanced stages of which requires a comprehensive approach, including systemic therapy and skin-directed methods. Total skin electron irradiation (TSEB) demonstrates high efficacy due to the radiosensitivity of lymphoid cells. Despite the high overall response rate, the recommended dose ranges and fractionation schemes for TSEB vary, necessitating detailed investigation. Stratification of patients by clinical stage, type of lesions, and the extent of skin involvement is crucial for optimizing TSEB, improving outcomes, and reducing side effects.

Total skin electron beam radiotherapy: A Trend Toward Low Doses: TSEB with cumulative doses of 30ʹ36 Gy has established itself as an effective treatment method; however, there is growing interest in lower doses (10ʹ29 Gy) due to the high radiosensitivity of lymphomas and the need to reduce radiation-related side effects. Studies have confirmed a high overall response to low doses, especially in early stages, with less pronounced radiation reactions and a comparable median duration of response. To optimize the approach, further research is needed, including the development of patient selection criteria and dose individualization with a potential boost to large lesions.

Conclusions: The question of the optimal cumulative dose for TSEB in patients with primary cutaneous lymphomas remains insufficiently studied. Clinical cases confirm the efficacy of both standard doses (30ʹ36 Gy) and low doses (10ʹ20 Gy), demonstrating good clinical responses, symptom reduction, and lower toxicity. Low dose TSEB provides a comparable overall response to standard doses, reduces the number of treatment visits, and enables retreatment in case of disease relapse. The main tasks remain to study the factors influencing dose selection (disease stage, type of lesions, individual patient characteristics) and to develop patient management strategies. TSEB effectively controls disease manifestations even in complex cases. Data analysis highlights the need for unified patient selection criteria and optimization of irradiation techniques to improve outcomes and reduce treatment toxicity.

1. Willemze R, Jaffe ES, Burg G. Primary cutaneous lymphomas: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2018;29(Suppl 4): iv30-iv40. https://doi.org/10.1093/annonc/mdy226. PMID: 30059933.

2. Kubanov AA, Poddubnaya IV, Belousova IE, et al. Clinical guidelines ͞Mycosis fungoides͟. Edited by Kubanov AA, Poddubnaya IV, Belousova IE and co-authors, 2023.

3. Horwitz SM, Ancell S, Ai WZ. Primary Cutaneous Lymphomas. NCCN Clinical Practice Guidelines in Oncology. Version 1.2025. November 11, 2024. https://www.nccn.org/professionals/physician.gls/pdf/primary.cutaneous.pdf.

4. Specht L, Dabaja BS, Illidge T. Modern radiation therapy for primary cutaneous lymphomas: field and dose guidelines from the International Lymphoma Radiation Oncology Group. Int J Radiat Oncol Biol Phys. 2015;92(1):32-9. https://doi.org/10.1016/j.ijrobp.2014.12.034. PMID: 25863701.

5. Vinogradova YN. The role of radiation therapy in chemoradiation treatment of patients with non-Hodgkin lymphomas. Dissertation of Doctor of Medical Sciences. Saint Petersburg, 2015. 168 p. (In Russ.).

6. Jones GW, Kacinski BM, Wilson LD. Prognosis with newly diagnosed mycosis fungoides aŌer total skin electron radiation of 30 or 35 Gy. Int J Radiat Oncol Biol Phys. 1994;28(4):839-45. https://doi.org/10.1016/0360-3016(94)90225-9. PMID: 8037192.

7. Navi D, Riaz N, Hoppe RT. The Stanford University experience with conventional-dose, total skin electron-beam therapy in the treatment of generalized patch or plaque (T2) and tumor (T3) mycosis fungoides. Arch Dermatol. 2011;147(5):561-7. https://doi.org/10.1001/archdermatol.2011.117. PMID: 21482867.

8. Heumann TR, Lingos TI, Hoppe RT. Total skin electron therapy for cutaneous T-cell lymphoma using a modern dual-field rotational technique. Int J Radiat Oncol Biol Phys. 2015;92(1):183-91. PMID: 25529389. https://doi.org/10.1016/j.ijrobp.2014.11.006.

9. Jones GW, Kacinski BM, Wilson LD. Total skin electron radiation in the management of mycosis fungoides: Consensus of the European Organization for Research and Treatment of Cancer (EORTC) Cutaneous Lymphoma Project Group. J Am Acad Dermatol. 2002;47(3):364-70. PMID: 12271315. https://doi.org/10.1067/mjd.2002.124606.

10. Ilyin NV, Korytova LI, Leenman EE, et al. Experience of local radiation therapy and total skin electron beam irradiation in patients with primary cutaneous B- and T-cell lymphomas. Voprosy onkologii. 2013;59(1):109-13. (In Russ.)

11. Nien HH, Pugachev A, Deutschmann H. Total skin treatment with Helical arc radiotherapy. Int J Mol Sci. 2023;24(5):4492. https://doi.org/10.3390/ijms24054492. PMID: 36901048.

12. Karzmark CJ, Tanabe E, Ryu JK. A technique for large-field, superficial electron therapy. Radiology. 1960;74(4):633-44. https://doi.org/10.1148/74.4.633. PMID: 13821554.

13. Kamstrup MR, Gniadecki R, Skov L. A prospective, open-label study of low-dose total skin electron beam therapy in mycosis fungoides. Int J Radiat Oncol Biol Phys. 2008;71(4):1204-7. https://doi.org/10.1016/j.ijrobp.2007.11.060. PMID: 18280064.

14. Harrison C, Prince HM, Cowen EW. Revisiting low-dose total skin electron beam therapy in mycosis fungoides. Int J Radiat Oncol Biol Phys. 2011;81(4):e651-e657. PMID: 21345628. https://doi.org/10.1016/j.ijrobp.2010.12.057.

15. Hoppe RT, Woo S, Harrison C. Low-dose total skin electron beam therapy as an effective modality to reduce disease burden in patients with mycosis fungoides: results of a pooled analysis from 3 phase-II clinical trials. J Am Acad Dermatol. 2015;72(2):286-92. PMID: 25497973. https://doi.org/10.1016/j.jaad.2014.10.028.

16. Morris S, Scarisbrick JJ, Frew J. The results of low-dose total skin electron beam radiation therapy (TSEB) in patients with mycosis fungoides from the UK Cutaneous Lymphoma Group. Int J Radiat Oncol Biol Phys. 2017;99(3):627-33. https://doi.org/10.1016/j.ijrobp.2017.06.003. PMID: 28802488.

17. Taverniers A, Giraldo-Betancur AL, Wolter P. Low-vs. middledose total skin electron beam therapy for mycosis fungoides: an efficiency-based retrospective survey of skin response. Acta Derm Venereol. 2019;99(6):544-50. https://doi.org/10.2340/00015555-3145. PMID: 30981123.

18. Canu D, Escande A, Mirabel X. Changes in total skin electron beam therapy modalities for mycosis fungoides: A singlecentre study. Ann Dermatol Venereol. 2022;149(3):180-4. https://doi.org/10.1016/j.annder.2021.09.015. PMID: 34880300.

19. Georgakopoulos I, Katsenos C, Livaniou E. Low dose total skin electron beam therapy for the management of T cell cutaneous lymphomas. Dermatol Ther. 2020;33(4):e13478. https://doi.org/10.1111/dth.13478. PMID: 32396954.

20. Jeans EB, De la Fuente F, Gibbons G. Low-dose hypofractionated total skin electron beam therapy for adult cutaneous T-cell lymphoma. Pract Radiat Oncol. 2020;10(6):e529-e537. https://doi.org/10.1016/j.prro.2020.04.004. PMID: 32439337.

21. Newman NB, Li W, Fox M. Prospective observational trial of low-dose skin electron beam therapy in mycosis fungoides using a rotational technique. J Am Acad Dermatol. 2021;85(1):121-7. PMID: 33316497. https://doi.org/10.1016/j.jaad.2020.12.003.

22. Smits K, Van Tienhoven G, Zelen CM. Total skin electron beam therapy for cutaneous T-cell lymphomas in the Netherlands: A retrospective analysis of treatment outcomes and selection for high or low dose schedule. Clin Transl Radiat Oncol. 2022;33:77-82. PMID: 35702721. https://doi.org/10.1016/j.ctro.2022.05.001.

23. Grandi V, Muto M, Gaviani C. Short-term efficacy and safety of total skin electron beam therapy in mycosis fungoides: Systematic review and meta-analysis. Dermatol Ther. 2022;35(11):e15840. https://doi.org/10.1111/dth.15840. PMID: 36031510.

24. .Elsayad K, Kriz J, Reinartz G. Ultrahypofractionated Low-Dose Total Skin Electron Beam in Advanced-Stage Mycosis Fungoides and SĠzary Syndrome. Int J Radiat Oncol Biol Phys. 2023. PMID: 36709537. https://doi.org/10.1016/j.ijrobp.2023.01.042.

25. Kamstrup MR, Skov L, Gniadecki R. Low-dose (10-Gy) total skin electron beam therapy for cutaneous T-cell lymphoma: an open clinical study and pooled data analysis. Int J Radiat Oncol Biol Phys. 2015;92(1):138-43. PMID: 25601797. https://doi.org/10.1016/j.ijrobp.2014.12.012.

26. Kroeger K, Greinert R, Heinrich V. Low-dose total skin electron beam therapy for cutaneous lymphoma. Strahlenther Onkol. 2017;193(12):1024-30. PMID: 28861688. https://doi.org/10.1007/s00066-017-1166-7.

27. Piccinno R, Brancaccio G, Stinco G. Radiotherapy of primary cutaneous anaplastic large cell lymphoma: our experience in 30 cases. Int J Dermatol. 2020;59(4):469-73. https://doi.org/10.1111/ijd.14864. PMID: 31686121.