Ultra-hypofractionated low-dose total skin electron beam followed by maintenance therapy: Preliminary findings from a prospective open-label study
Authors: Daniel Rolf, Khaled Elsayad, Hans Theodor Eich
Journal: Journal of the American Academy of Dermatology (2020)

To the Editor: low-dose total skin electron beam therapy (LD-TSEBT) with 12 Gy in 8 fractions is a reasonable approach for mycosis fungoides (MF) and Sezary syndrome (SS).1Hoppe R.T. Harrison C. Tavallaee M. et al.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: 286-292Abstract Full Text Full Text PDF PubMed Scopus (136) Google Scholar Prior studies show that LD-TSEBT improves cutaneous manifestations and health-related quality of life (HRQL).2Elsayad K. Stadler R. Steinbrink K. Eich H.T. Combined total skin radiotherapy and immune checkpoint inhibitors: a promising potential treatment for mycosis fungoides and Sezary syndrome.J Dtsch Dermatol Ges. 2020; 18: 193-197Google Scholar,3Song A. Gochoco A. Zhan T. et al.A prospective cohort study of condensed low-dose total skin electron beam therapy for mycosis fungoides: reduction of disease burden and improvement in quality of life.J Am Acad Dermatol. 2020; 83: 78-85Abstract Full Text Full Text PDF PubMed Scopus (15) Google Scholar Hypofractionated TSEBT regimens seem to be a feasible alternative to conventional fractionation.4Jeans E.B. Hu Y.-H. Stish B.J. et al.Low-dose hypofractionated total skin electron beam therapy for adult cutaneous T-cell lymphoma.Pract Radiat Oncol. 2020; 10: e529-e537Abstract Full Text Full Text PDF PubMed Scopus (10) Google Scholar Accordingly, the International Lymphoma Radiation Oncology Group recommends ultra-hypofractionated LD-TSEBT as a compelling option during the COVID-19 pandemic to decrease therapy duration and any possible exposure to COVID-19.5Yahalom J. Dabaja B.S. Ricardi U. et al.ILROG Emergency guidelines for radiation therapy of hematological malignancies during the COVID-19 pandemic.Blood. 2020; 135: 1829-1832Crossref PubMed Scopus (14) Google Scholar In this prospective study, we present the feasibility of ultra-hypofractionated LD-TSEBT. Seven radiation courses were administered to 7 patients with MF/SS at our radiation oncology department at the university hospital Münster during the initial phase of COVID-19 pandemic from April to July 2020 (Table I). Patients underwent TSEBT with two 4 Gy fractions. Patients with thicker tumors or pathologically enlarged lymph nodes at the treatment time received additional focal radiotherapy. Treatment characteristics, modified skin-weighted severity (mSWAT), Skindex-29 questionnaire, and toxicity profiles were analyzed.Table IPatient characteristicsPatientGender/age (y)Type/stageTSEBT doseAdditional focal radiotherapyPrior therapiesConcurrent therapyMaintenance therapiesAcute toxicities D1-W6Subacute toxicities W8-W12ResponsemSWAT D1/W8PFS (W)Follow-up1M/69SS2 × 4 GyNonePUVA, INF, ECP, MTX, CST, 12 Gy TSEBTNoneBexaroteneEdema, erythema, and nail atrophy grade 2Edema and alopecia grade 1PR112/1336ANEP2M/66MF/IIB2 × 4 GyTumors and lymph nodesbrentuximab, 2 x 12 Gy TSEBTNoneMogamulizumabSepsis, alopecia grade 1, and nausea grade 1Nail changes and alopecia grade 1PR31/426Dead (due to COVID-19)3M/78MF/IIB2 × 4 GyTumorsPUVABexaroteneBexaroteneEdema, erythema grade, alopecia, and blistering grade 1Alopecia grade 1PR59/1626ANEP4F/77SS2 × 4 GyLymph nodesMTX, acitretin, bexarotene, ECPNoneBexarotene, ECPErythema grade 2, edema grade 2, alopecia grade 1Fatigue, nail changes, and alopecia grade 1PR100/3731ANEP5M/60MF/IIB2 × 4 GyNonePUVA, MTX, SCT, INF, brentuximab, bexaroteneBexaroteneBexaroteneErythema and fatigue grade 1Fatigue, and edema grade 1PR46/528ANEP6F/55MF/IIB2 × 4 GyNoneIFN, bexarotene, PUVA, gemcitabinAcitretinAcitretinFatigue, Erythema, and blistering grade 1NoneCR9/028ANEP7M/57MF/IIB2 × 4 GyTumorsMTX, 12 Gy TSEBT, PUVANoneMethotrexateErythema grade 2Fatigue, alopecia, and blistering grade 1PR28/1415Progressed after 15 weeksANEP, Alive with no evidence of progression; CR, complete response; CST, corticosteroids; D, day; ECP, extracorporeal photophoresis; INF, interferon; MF, mycosis fungoides; MTX, methotrexate; PFS, progression-free survival; PR, partial remission; PUVA, psoralen plus ultraviolet A; SCT, stem cell transplantation; SS, Sézary syndrome; TSEBT, total skin electron beam therapy; W, week. Open table in a new tab ANEP, Alive with no evidence of progression; CR, complete response; CST, corticosteroids; D, day; ECP, extracorporeal photophoresis; INF, interferon; MF, mycosis fungoides; MTX, methotrexate; PFS, progression-free survival; PR, partial remission; PUVA, psoralen plus ultraviolet A; SCT, stem cell transplantation; SS, Sézary syndrome; TSEBT, total skin electron beam therapy; W, week. In this cohort study, the median mSWAT score before the LD-TSEBT was 46. Three patients received concomitant oral retinoid therapy. Moreover, all patients received maintenance treatment after irradiation. The median follow-up duration was 28 weeks. All patients experienced a clinical response with a median mSWAT reduction to 13. Among 5 patients with pruritus (median, 7), a substantial benefit was seen 8 weeks after LD-TSEBT, with a median score of 0. A marked decline in the global Skindex-29 score has been observed regarding patients' quality of life after 8 weeks of therapy with a clinically meaningful difference in the symptoms and emotional subscales. During ultra-hypofractionated LD-TSEBT, all of the patients encountered mild toxicities (Table I). Four patients had grade 1 toxicities, whereas three patients exhibited grade 2 toxicities. The most common adverse effects were erythema, followed by edema. One patient, who had a thick ulcerated lesion, had sepsis during the treatment course and was successfully treated with antibiotics. After 8 weeks, all grade 2 adverse events were resolved. No patients had grade 4 to 5 adverse events. In this research letter, we report the acute and subacute toxicities after LD-TSEBT with two 4-Gy fractions. Long-term outcome and toxicities need to be investigated in a subsequent report. Our preliminary results showed that ultra-hypofractionated LD-TSEBT is a safe and feasible alternative to conventionally fractionated TSEBT for patients with MF/SS to reduce the overall therapy duration and possible COVID-19 exposure. The mSWAT scores and the HRQL recovered after ultra-hypofractionated LD-TSEBT. A detailed HRQL analysis using several instruments and the possible role of oral retinoids as a maintenance treatment after TSEBT are under development by our cutaneous lymphoma group and is supposed to help clinicians find the suitable fractionation regimen and maintenance therapies for MF/SS patients. None disclosed.