One-year follow-up after fractionated ultra-high-dose-rate FLASH radiotherapy in patient with extramammary Paget disease of the scrotum

Hui Luo; Chengliang Yang; Ronghu Mao; Leijie Ma; Hongchang Lei; Peng Chen; Yanping Zhang; Meng Xu; Chao Wang; Yiwu Wang; Mingxia Wu; Chanjun Sun; Han Liu; Hui Liu; Hong Ge

doi:10.1002/pro6.70045

Precision Radiation Oncology ›› 2026, Vol. 10 ›› Issue (2) :120 -126. DOI: 10.1002/pro6.70045

ORIGINAL ARTICLE

One-year follow-up after fractionated ultra-high-dose-rate FLASH radiotherapy in patient with extramammary Paget disease of the scrotum

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Abstract

Objective: Ultrahigh-dose-rate radiotherapy (FLASH-RT) has been shown to reduce radiation-induced normal tissue injury in preclinical studies. Here, we describe the first patient worldwide to receive fractionated FLASH-RT.

Methods: An elderly male patient was diagnosed with extramammary Paget disease of the scrotum along with multiple lymph node and bone metastases. After 6 cycles of chemotherapy, the disease progressed in the scrotum. The scrotal lesions were evaluated for FLASH-RT. 9 MeV electron FLASH-RT was performed at a dose rate of 120 Gy/s. The field size was 5 cm × 5 cm, and the prescribed dose was 40 Gy in five fractions. Dosimetric verification was performed daily. Treatment response was evaluated at 3-month post FLASH-RT, and normal tissue toxicity was assessed from the beginning of FLASH-RT to 12-month post-irradiation.

Results: A 1-year follow-up was achieved for scrotal lesions treated with electron FLASH-RT in patients with extramammary Paget disease. Electron FLASH-RT was safe, and treatment-related adverse events were mild. Transient skin toxicity occurred 2–5 weeks post FLASH-RT, and exudation and burning pain were significantly alleviated. A complete response was achieved 2–3 months post FLASH-RT, and the tumor lesions were covered by the normal epithelium of the scrotum. At the end of the one-year follow-up, the tumor lesions continued to respond, and one-year survival was achieved without additional injury to the irradiated areas after FLASH-RT.

Conclusion: Fractionated electron FLASH-RT is feasible and safe for the treatment of extramammary Paget disease of the scrotum. Our findings support further exploration of electron FLASH-RT in patients with skin tumors.

Keywords

adverse effect / Electron FLASH / scrotal lesions / extramammary Paget disease / FLASH radiotherapy / ultra-high dose rate

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Hui Luo, Chengliang Yang, Ronghu Mao, Leijie Ma, Hongchang Lei, Peng Chen, Yanping Zhang, Meng Xu, Chao Wang, Yiwu Wang, Mingxia Wu, Chanjun Sun, Han Liu, Hui Liu, Hong Ge. One-year follow-up after fractionated ultra-high-dose-rate FLASH radiotherapy in patient with extramammary Paget disease of the scrotum. Precision Radiation Oncology, 2026, 10 (2) : 120-126 DOI:10.1002/pro6.70045

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References

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[1]	Shabihkhani M, Patil P, Murati Amador B, et al. Extramammary Paget Disease of the Scrotum: A Contemporary Clinicopathologic Analysis of 20 Cases in the United States. Appl Immunohistochem Mol Morphol. 2020; 28(7): 524-531.

[2]	Hashimoto H, Ito T. Current Management and Treatment of Extramammary Paget's Disease. Curr Treat Options Oncol. 2022; 23(6): 818-830.

[3]	Kibbi N, Owen JL, Worley B, et al. Evidence-Based Clinical Practice Guidelines for Extramammary Paget Disease. JAMA Oncol. 2022; 8(4): 618-628.

[4]	Tagliaferri L, Casà C, Macchia G, et al. The Role of Radiotherapy in Extramammary Paget Disease: A Systematic Review. Int J Gynecol Cancer. 2018; 28(4): 829-839.

[5]	Majeed H, Gupta V. Adverse Effects of Radiation Therapy. In: StatPearls. edn. Treasure Island (FL) ineligible companies. Disclosure: Vikas Gupta declares no relevant financial relationships with ineligible companies.: StatPearls Publishing Copyright © 2023, StatPearls Publishing LLC.; 2023.

[6]	McLaren DB, Aitman TJ. Redefining precision radiotherapy through liquid biopsy. Br J Cancer. 2023; 129(6): 900-903.

[7]	Fiorino C, Guckemberger M, Schwarz M, van der Heide UA, Heijmen B. Technology-driven research for radiotherapy innovation. Mol Oncol. 2020; 14(7): 1500-1513.

[8]	Fendler W, Tomasik B, Atkins K, Stawiski K, Chałubińska-Fendler J, Kozono D. The clinician's guide to radiotherapy complications. Pol Arch Intern Med. 2022; 132(1):16190.

[9]	Vozenin MC, Bourhis J, Durante M. Towards clinical translation of FLASH radiotherapy. Nat Rev Clin Oncol. 2022; 19(12): 791-803.

[10]	Vozenin MC, De Fornel P, Petersson K, et al. The Advantage of FLASH Radiotherapy Confirmed in Mini-pig and Cat-cancer Patients. Clin Cancer Res. 2019; 25(1): 35-42.

[11]	Gao F, Yang Y, Zhu H, et al. First demonstration of the FLASH effect with ultrahigh dose rate high-energy X-rays. Radiother Oncol. 2022; 166: 44-50.

[12]	Velalopoulou A, Karagounis IV, Cramer GM, et al. FLASH Proton Radiotherapy Spares Normal Epithelial and Mesenchymal Tissues While Preserving Sarcoma Response. Cancer Res. 2021; 81(18): 4808-4821.

[13]	Bourhis J, Sozzi WJ, Jorge PG, et al. Treatment of a first patient with FLASH-radiotherapy. Radiother Oncol. 2019; 139: 18-22.

[14]	Gaide O, Herrera F, Jeanneret Sozzi W, et al. Comparison of ultra-high versus conventional dose rate radiotherapy in a patient with cutaneous lymphoma. Radiother Oncol. 2022; 174: 87-91.

[15]	Mascia AE, Daugherty EC, Zhang Y, et al. Proton FLASH Radiotherapy for the Treatment of Symptomatic Bone Metastases: The FAST-01 Nonrandomized Trial. JAMA Oncol. 2023; 9(1): 62-69.

[16]	Luo H, Yang C, Yue J, Ge H. Consensus statement on the exploration of clinical translation and application of electron ultra-high dose rate FLASH radiotherapy. Precis Radiat Oncol. 2025; 9(1): 4-12.

[17]	Yang CL, Luo H, Marie-Catherine V, et al. Efficacy of electron ultra-high dose rate radiotherapy for scrotal Paget' s disease. Journal of Zhengzhou University(Medical Sciences). 2025; 60(6): 822-825.

[18]	Brouwer CL, Wiesendanger EM, van der Hulst PC, van Imhoff GW, Langendijk JA, Beijert M. Scrotal irradiation in primary testicular lymphoma: review of the literature and in silico planning comparative study. Int J Radiat Oncol Biol Phys. 2013; 85(2): 298-308.

[19]	Dahbi Z, Sr., Elmejjabar R, Alami R, Kouhen F. Testicular Radiotherapy. A Challenging Irradiation Site. Cureus. 2023; 15(4):e37638.

[20]	Ma LJ, Mao RH, Lei HC, et al. Transform routine medical accelerators to achieve Flash-RT and physical performance measurements. Chin J Radiat Oncol. 2022; 31(11): 1022-1027.

[21]	Schwartz LH, Litière S, de Vries E, et al. RECIST 1.1-Update and clarification: From the RECIST committee. Eur J Cancer. 2016; 62: 132-137.

[22]	Yang C, Luo H, Leijie M, et al. A safety study of ultra-high dose rate FLASH radiotherapy in the treatment of superficial skin tumors: study protocol of a phase I trial (ChiCTR2400080935). Precis Radiat Oncol. 2025; 9(2): 72-76.

[23]	Jain S. Radiation in medical practice & health effects of radiation: Rationale, risks, and rewards. J Family Med Prim Care. 2021; 10(4): 1520-1524.

[24]	Majeed H, Gupta V. Adverse Effects of Radiation Therapy. In: StatPearls. edn. Treasure Island (FL) ineligible companies. Disclosure: Vikas Gupta declares no relevant financial relationships with ineligible companies.: StatPearls Publishing Copyright © 2024, StatPearls Publishing LLC. 2024.

[25]	Held KD, McNamara AL, Daartz J, Bhagwat MS, Rothwell B, Schuemann J. Dose Rate Effects from the 1950s through to the Era of FLASH. Radiat Res. 2024; 202(2): 161-176.

[26]	Böhlen TT, Germond JF, Bourhis J, et al. Normal Tissue Sparing by FLASH as a Function of Single-Fraction Dose: A Quantitative Analysis. Int J Radiat Oncol Biol Phys. 2022; 114(5): 1032-1044.

[27]	Rohrer Bley C, Wolf F, Gonçalves Jorge P, et al. Dose- and Volume-Limiting Late Toxicity of FLASH Radiotherapy in Cats with Squamous Cell Carcinoma of the Nasal Planum and in Mini Pigs. Clin Cancer Res. 2022; 28(17): 3814-3823.

[28]	Maity A, Koumenis C. Shining a FLASHlight on Ultrahigh Dose-Rate Radiation and Possible Late Toxicity. Clin Cancer Res. 2022; 28(17): 3636-3638.

[29]	Kacem H, Almeida A, Cherbuin N, Vozenin MC. Understanding the FLASH effect to unravel the potential of ultra-high dose rate irradiation. Int J Radiat Biol. 2022; 98(3): 506-516.

[30]	Luo H, Yang C, Vozenin MC, et al. FLASH irradiation-induced acute lung injury promotes metastatic colonization via neutrophil extracellular trap formation. Med Phys. 2025; 52(10):e70054.

[31]	Zou W, Zhang R, Schüler E, et al. Framework for Quality Assurance of Ultrahigh Dose Rate Clinical Trials Investigating FLASH Effects and Current Technology Gaps. Int J Radiat Oncol Biol Phys. 2023; 116(5): 1202-1217.

[32]	Siddique S, Ruda HE, Chow JCL. FLASH Radiotherapy and the Use of Radiation Dosimeters. Cancers (Basel). 2023; 15(15): 3883. https://doi.org/10.3390/cancers15153883

[33]	McManus M, Romano F, Lee ND, et al. The challenge of ionisation chamber dosimetry in ultra-short pulsed high dose-rate Very High Energy Electron beams. Sci Rep. 2020; 10(1): 9089. https://doi.org/10.1038/s41598-020-65819-y

[34]	Subiel A, Romano F. Recent developments in absolute dosimetry for FLASH radiotherapy. Br J Radiol. 2023; 96(1148):20220560.

[35]	Romano F, Bailat C, Jorge PG, Lerch MLF, Darafsheh A. Ultra-high dose rate dosimetry: Challenges and opportunities for FLASH radiation therapy. Med Phys. 2022; 49(7): 4912-4932.

[36]	Marinelli M, Felici G, Galante F, et al. Design, realization, and characterization of a novel diamond detector prototype for FLASH radiotherapy dosimetry. Med Phys. 2022; 49(3): 1902-1910.

[37]	Chabi S, To THV, Leavitt R, et al. Ultra-high-dose-rate FLASH and Conventional-Dose-Rate Irradiation Differentially Affect Human Acute Lymphoblastic Leukemia and Normal Hematopoiesis. Int J Radiat Oncol Biol Phys. 2021; 109(3): 819-829.