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

doi:10.1067/mjd.2002.123482

Journal of the American Academy of Dermatology

Volume 47, Issue 3, September 2002, Pages 364-370

https://doi.org/10.1067/mjd.2002.123482 Get rights and content

Abstract

Radiotherapy has been successfully implemented in the treatment of mycosis fungoides (MF) for almost a century. With the development of the modern linear accelerator, it has become possible to treat extended areas of the skin with accelerated electrons. Total skin electron beam radiation (TSEB) has been in use for several decades, and a number of technical modifications have been made with the goals of optimizing dose distribution and improving clinical outcome. Emerging evidence from recent studies suggests an association between TSEB techniques and efficacy in the treatment of MF. Based on this evidence, the European Organization for Research and Treatment of Cancer Cutaneous Lymphoma Project Group, in association with experts from radiotherapy centers in North America, has reached a consensus on acceptable methods and clinical indications for TSEB in the treatment of MF. The aims of this report are to enhance accessibility of this highly efficacious treatment modality to patients with MF and to provide a point of reference for further clinical research. (J Am Acad Dermatol 2002;47:364-70.)

Section snippets

Recommendations regarding TSEB technique

The principal objectives of any method of TSEB are listed in Table I.⁴

. Objectives of any method of total skin electron radiation

• To align the distribution of dose to the target volume

• To be practical, comfortable, and efficient for the patient

• To provide sufficient dose within the target volume

• To reliably attain cutaneous remission

• To minimize toxicity

• To produce beneficial long-term clinical results

• To accommodate repeated administration as required

The primary target volume comprises

Minimizing toxicities, discomfort, and risks

Proper technique limits acute and chronic toxicities in incidence and severity and increases the therapeutic ratio. Tolerance depends on attention to schedule and fractionation,²⁰ cointerventions, and judicious shielding of tissues exposed to relatively high doses.

Clinical indications

Clinical indications for TSEB are listed in Table III.

. Clinical indications for total skin electron radiation

1. Patients with a new diagnosis of mycosis fungoides
“Minimal” stage IA	Not recommended (consider local radiation only)
Stage IA & T1N1	A brief therapy with potential for long-term progression-free survival
Stage IB & T2N1	As in stage IA, consider combination therapy (eg, with psoralen plus UV light)
Stage IIB	Effective palliation, consider combination therapy
Stage III	Potential for long-term

Conclusions

Most patients with MF can benefit from at least one course of TSEB at some time in their clinical course. Some patients experience long-standing remissions. Some appear to experience improved survival. In patients with advanced disease, effective palliation can be achieved with TSEB. The therapeutic ratio for TSEB compares well with ratios for other therapies. TSEB should be considered once a diagnosis of MF is established. It should be an option every time a therapeutic decision is to be made

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Cited by (184)

EORTC consensus recommendations for the treatment of mycosis fungoides/Sézary syndrome – Update 2023
2023, European Journal of Cancer
On behalf of the EORTC Cutaneous Lymphoma Tumours Group (EORTC-CLTG) and following up on earlier versions published in 2006 and 2017 this document provides an updated standard for the treatment of mycosis fungoides and Sézary syndrome (MF/SS). It considers recent relevant publications and treatment options introduced into clinical practice after 2017.
Consensus was established among the authors through a series of consecutive consultations in writing and a round of discussion. Treatment options are assigned to each disease stage and, whenever possible and clinically useful, separated into first- and second line options annotated with levels of evidence.
Major changes to the previous version include the incorporation of chlormethine, brentuximab vedotin, and mogamulizumab, recommendations on the use of pegylated interferon α (after withdrawal of recombinant unpegylated interferons), and the addition of paragraphs on supportive therapy and on the care of older patients.
Still, skin-directed therapies are the most appropriate option for early-stage MF and most patients have a normal life expectancy but may suffer morbidity and impaired quality of life. In advanced disease treatment options have expanded recently. Most patients receive multiple consecutive therapies with treatments often having a relatively short duration of response. For those patients prognosis is still poor and only for a highly selected subset long term remission can be achieved with allogeneic stem cell transplantation. Understanding of the disease, its epidemiology and clinical course, and its most appropriate management are gradually advancing, and there is well-founded hope that this will lead to further improvements in the care of patients with MF/SS.
Computational dose visualization & comparison in total skin electron treatment suggests superior coverage by the rotational versus the Stanford technique
2022, Journal of Medical Imaging and Radiation Sciences
The goal of Total Skin Electron Therapy (TSET) is to achieve a uniform surface dose, although assessment of this is never really done and typically limited points are sampled. A computational treatment simulation approach was developed to estimate dose distributions over the body surface, to compare uniformity of (i) the 6 pose Stanford technique and (ii) the rotational technique.
The relative angular dose distributions from electron beam irradiation was calculated by Monte Carlo simulation for cylinders with a range of diameters, approximating body part curvatures. These were used to project dose onto a 3D body model of the TSET patient's skin surfaces. Computer animation methods were used to accumulate the dose values, for display and analysis of the homogeneity of coverage.
The rotational technique provided more uniform coverage than the Stanford technique. Anomalies of under dose were observed in lateral abdominal regions, above the shoulders and in the perineum. The Stanford technique had larger areas of low dose laterally. In the rotational technique, 90% of the patient's skin was within ±10% of the prescribed dose, while this percentage decreased to 60% or 85% for the Stanford technique, varying with patient body mass. Interestingly, the highest discrepancy was most apparent in high body mass patients, which can be attributed to the loss of tangent dose at low angles of curvature.
This simulation and visualization approach is a practical means to analyze TSET dose, requiring only optical surface body topography scans. Under- and over-exposed body regions can be found, and irradiation could be customized to each patient. Dose Area Histogram (DAH) distribution analysis showed the rotational technique to have better uniformity, with most areas within 10% of the umbilicus value. Future use of this approach to analyze dose coverage is possible as a routine planning tool.
L'objectif de l'électronthérapie cutanée totale (Total Skin Electron Therapy - TSET) est d'obtenir une dose uniforme à la surface du corps, bien que l'évaluation de cet objectif ne soit jamais vraiment effectuée et que des points limités soient généralement échantillonnés. Une approche de simulation de traitement informatique a été développée pour estimer les distributions de dose sur la surface du corps, afin de comparer l'uniformité de (i) la technique de Stanford à 6 poses et (ii) la technique de rotation.
Les distributions angulaires relatives de la dose provenant de l'irradiation par faisceau d'électrons ont été calculées par simulation de Monte Carlo pour des cylindres de différents diamètres, correspondant approximativement aux courbures des parties du corps. Ces cylindres ont été utilisés pour projeter la dose sur un modèle corporel 3D des surfaces de la peau du patient recevant une TSET. Des méthodes d'animation informatique ont été utilisées pour accumuler les valeurs de dose, afin de les afficher et d'analyser l'homogénéité de la couverture.
La technique de rotation a fourni une couverture plus uniforme que la technique de Stanford. Des anomalies de sous-dose ont été observées dans les régions abdominales latérales, au-dessus des épaules et dans le périnée. La technique de Stanford présentait des zones de faible dose plus importantes latéralement. Dans la technique de rotation, 90 % de la peau du patient se situait dans une fourchette de ±10 % de la dose prescrite, tandis que ce pourcentage diminuait à 60 % ou 85 % pour la technique de Stanford, variant selon la masse corporelle du patient. Il est intéressant de noter que l'écart le plus élevé était plus apparent chez les patients ayant une masse corporelle élevée, ce qui peut être attribué à la perte de dose tangente aux faibles angles de courbure.
Cette approche de simulation et de visualisation est un moyen pratique d'analyser la dose de TSET, ne nécessitant que des scans de topographie corporelle de surface optique. Les régions du corps sous-exposées et surexposées peuvent être trouvées et l'irradiation peut être personnalisée pour chaque patient. L'analyse de la distribution de l'histogramme de la zone de dose a montré que la technique de rotation présentait une meilleure uniformité, la plupart des zones se situant à moins de 10 % de la valeur ombilicale. L'utilisation future de cette approche pour analyser la couverture de dose est possible en tant qu'outil de planification de routine
New developments in skin-directed treatments of cutaneous T-cell lymphoma
2022, Presse Medicale
The therapeutic approach for mycosis fungoides, the most common type of primary cutaneous T-cell lymphoma, is based mainly on the stage of the disease, and skin-directed treatment is recommended by all international guidelines as the first-line of treatment for early-stage disease. Skin-directed treatments may be also given in combination with systemic therapies in early-stage mycosis fungoides patients recalcitrant to different types of skin-directed treatments, or in certain patients with high-risk features. Advanced-stage mycosis fungoides is treated mainly with systemic treatments, which may be combined with skin-directed treatments.
Due to the rarity of mycosis fungoides, controlled clinical trials of the different skin-directed treatment modalities are almost non-existent, with a few exceptions, and therefore recommendations are largely based on cohort studies and expert opinion.
This paper reviews the new developments in skin-directed treatments and provides an update on new studies of already well-known therapies, and an update on novel treatments.
Helical Skin Radiation Therapy Including Total Skin Radiation Therapy Using Tomotherapy for Primary Cutaneous Lymphoma With Bone Marrow Suppression as a Related Adverse Event
2021, Practical Radiation Oncology
Total skin electron beam therapy (TSEBT) is useful for primary cutaneous lymphoma. However, helical skin radiation therapy (HSRT) using tomotherapy may avoid the complexity and uncertainty of TSEBT.
All patients with primary cutaneous lymphoma who underwent HSRT at our hospital between June 2015 and July 2019 were investigated, including 7 patients registered in a clinical trial approved by an institutional review board (ID UMIN000022142). HSRT was performed in 3 partitioned skin areas: head and neck, trunk and arms, and legs.
A total of 24 patients with 53 skin areas (including 8 patients with 24 skin areas who had undergone sequential total skin irradiation), with a median follow-up time of 13 months (range, 2-50), were investigated. Twenty patients (83.3%) had mycosis fungoides (MF). For 41 of 53 (77.4%) cases, a dose of 20 Gy in 10 fractions was used. The overall response rate in the treated fields of each HSRT in patients with MF was 100%, including 38 (80.9%) complete response, 4 (8.5%) good partial response, and 5 (10.6%) partial response. Eight patients with MF who underwent sequential total skin irradiation showed a 100% complete response. For patients with MF, the median survival time after a first round of HSRT was 22 months (95% confidence interval [CI], 13.6-30.4 months), the median response duration of each HSRT was 5 months (95% CI, 3.67-6.32 months), and the median time to in-field reirradiation for each HSRT was 15 months (95% CI, 9.76-20.24 months). Bone marrow suppression (grade ≥3) often occurred (94.1%) with HSRT on trunk and arm skin. An early patient died of HSRT-caused grade 5 leukopenia.
HSRT targeting trunk and arm skin induced severe bone marrow suppression that led to a temporary palliative effect. TSEBT should still be considered standard treatment for primary cutaneous lymphoma covering the total body surface area.
Cutaneous Lymphomas — Part I: Mycosis Fungoides, Sézary Syndrome, and CD30<sup>+</sup> Cutaneous Lymphoproliferative Disorders
2021, Actas Dermo-Sifiliograficas
Los linfomas cutáneos primarios son un grupo heterogéneo de procesos linfoproliferativos malignos que se manifiestan inicialmente en la piel sin evidencia de afectación extracutánea en el momento del diagnóstico y que presentan una baja incidencia (7-10 casos × 10⁶ personas/año). Se dividen en linfomas cutáneos derivados de linfocitos T (70-85%) y de células B (15-30%). El reconocimiento de la idiosincrasia de los linfomas cutáneos primarios por parte de hematólogos y oncólogos es cada vez mayor, como queda reflejado en la última actualización de la clasificación de la Organización Mundial de la Salud, si bien todavía quedan matices o peculiaridades a considerar en su manejo que obligan a los dermatólogos a seguir trabajando para una plena integración de las diferentes situaciones clínicas que nos plantean en futuras revisiones de la clasificación de las neoplasias linfoides. El diagnóstico de un linfoma cutáneo primario se establece en base a los hallazgos clínicos, histopatológicos, inmunofenotípicos y genotípicos (demostración de monoclonalidad linfoide T o B) de las lesiones cutáneas y en el resultado de las distintas exploraciones complementarias destinadas a descartar una afectación extracutánea.
CD30⁺ primary cutaneous lymphomas comprise a large group of malignant lymphoproliferative disorders that present in the skin without extracutaneous involvement at the time of diagnosis. The incidence of these lymphomas is low, at 7 to 10 cases per 100 000 population. Two types, derived from T cells (70%–85%) or B cells (15%–30%), have been identified. Hematologists and oncologists have increasingly recognized the idiosyncrasy of primary cutaneous lymphomas, as reflected in the updated classification of the World Health Organization. However, there remain nuances or small differences to consider when managing these conditions, obliging dermatologists to continue to strive to fully reconcile the various clinical pictures in future reviews of the classification of lymphoid neoplasms. A diagnosis of a primary cutaneous lymphoma is based on clinical, histopathologic, immunophenotypic, and genotypic criteria, particularly evidence of T- or B-cell lymphoid monoclonality in lesions. Also relevant are complementary tests to rule out extracutaneous involvement.
In-vivo dosimetry in Total Skin Electron Therapy: Literature review
2021, Journal of Radiotherapy in Practice

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^☆: Funding sources: None.

^☆☆: Conflict of interest: None.

^★: Reprint requests: Robert Knobler, MD, Department of Dermatology, Division of Special and Environmental Dermatology, University of Vienna, Währinger Gürtel 18-20, A-1090 Vienna, Austria.

^★★: Published online May 6, 2002.

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ReportsTotal 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☆,☆☆,★,★★

Abstract

Section snippets

Recommendations regarding TSEB technique

Minimizing toxicities, discomfort, and risks

Clinical indications

Conclusions

Blood

Int J Radiat Oncol Biol Phys

Hematol Oncol Clin North Am

J Am Acad Dermatol

J Am Acad Dermatol

J Am Acad Dermatol

J Am Acad Dermatol

Int J Radiat Oncol Biol Phys

Int J Radiat Oncol Biol Phys

Clin Radiol

Int J Radiat Oncol Biol Phys

J Am Acad Dermatol

Reports
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☆,☆☆,★,★★