Low-dose Total Skin Electron Beam Therapy Research Articles

Fine-Tuning Low-Dose Total Skin Electron Therapy for Optimal Management of Cutaneous T-Cell Lymphoma: A Comparative Analysis of Regimens

BackgroundLow-dose total skin electron beam therapy (TSEBT) is a proven treatment for managing cutaneous T-cell lymphoma (CTCL) and Sezary syndrome with skin burden. We performed a retrospective comparison of response rates and time to progression for patients receiving low-dose TSEBT based on dose per fractionation, total dose, and stage. MethodsOne hundred and ten patients with CTCL and Sezary syndrome were treated with 135 courses of low-dose (400-1500 cGy) TSEBT or STSEBT (subtotal skin electron therapy) at multiple centers of a single institution between 8/2003 and 6/2023. Patients were stratified according to total dose, dose per fraction, and stage. ResultsThe median follow-up was 301 days [IQR 141, 767]. The median age at treatment was 69.9 years (range 29.7 – 96.5). T-stage distribution was as follows: 3 (2.7%) T1, 74 (67.3%) T2, 16 (14.5%) T3, and 17 (15.5%) T4. AJCC 8th edition Stage distribution was as follows: 3 (2.7%) IA, 53 (48.2%) IB, 3 (2.7%) IIA, 16 (14.5%) IIB, 8 (7.3%) IIIA, 19 (17.3%) IVA, 8 (7.3%) IVB. There was no significant difference in disease distribution between patients treated with different fractionation schemes. The overall response rate was 89.6%. Forty-four courses (32.6%), 34 courses (25.2%), and 43 (31.9%) resulted in a complete, near-complete, and partial response, respectively. Fourteen courses (10.4%) resulted in no clinical response. For all patients, the median time to response was 43.0 days (IQR 23.0 – 70). The median time to skin progression for all patients was 107.5 days [IQR 67.8 – 233.5]. ConclusionsThis analysis demonstrated that CTCL patients treated with low-dose RT delivered over various fractionation schemes had similar overall response rates and median time to progression.

Mycosis fungoides with spongiosis: a case report

BackgroundMycosis fungoides (MF) is the most common form of cutaneous T-cell lymphoma (CTCL). CTCL are an uncommon, heterogeneous group of non-Hodgkin lymphomas (NHLs) of T- and B-cell origin where the skin is the primary organ of involvement. It is characterized by malignant CD4+ T-cells infiltrating the skin and other organs, leading to progressive skin and systemic involvement. Histopathologically, MF is characterized by atypical lymphocytes demonstrating epidermotropism without spongiosis. Spongiosis is the histological hallmark of intercellular epidermal edema, viewed as clear spaces within the epidermis, and is very common in benign inflammatory dermatoses. Very few studies have reported MF in sub-Saharan Africa (SSA). We are reporting a case of MF with a rare presentation of spongiosis treated successfully with a low dose total skin electron beam therapy (TSEBT) followed by maintenance therapy of low dose Methotrexate (MT) at the Ocean Road Cancer Institute (ORCI) in Tanzania. This is the first case of MF to be managed with low-dose TSEBT in Tanzania. The authors wish to create awareness of the disease among physicians and pathologists and expand on the data paucity in SSA.Case descriptionWe are reporting a case of a 31-year-old male of African origin who self-referred to our oncology center with a 4-year history of skin rashes throughout the body, which was unresponsive to topical steroid treatment. The biopsy was taken, and the patient was diagnosed with MF CD 3 positive with spongiosis. The patient was treated with radiotherapy, whereby he received low dose total skin electron beam therapy (TSEBT) 12 Gy in 3 fractions at a daily dose of 4 Gy, followed by maintenance therapy of low dose Methotrexate and attained an excellent therapeutic response.ConclusionSpongiosis is an infrequent presentation of MF. Low-dose TSEBT provides reliable and rapid reduction of disease burden in patients with MF, which could be administered safely multiple times during a patient's disease with an acceptable toxicity profile. Lack of tendency to perform skin biopsies and cost constraints in assessing multiple immunophenotypic markers lead to missing the diagnosis. Diagnosis and treatment of MF in resource-limited countries is challenging.

Short-term efficacy and safety of total skin electron beam therapy in mycosis fungoides: Systematic review and meta-analysis.

Total skin electron beam therapy (TSEBT) is one of the mainstays of treatment for mycosis fungoides. The most common modalities are standard dose (30-36 Gy) and low dose (10-12 Gy). To review the literature on the efficacy and safety profiles of standard dose and low dose TSEBT. We searched electronic databases for studies that enrolled patients with Mycosis Fungoides and treated with TSEBT. We estimated the event rates associated with low dose and standard dose TSEBT. The Preferred Reporting Items for Systematic Reviews and Meta-analyses reporting guideline was followed. Main outcomes were complete response rate, partial response rate, mild and severe adverse events rate low dose TSEBT had a Complete Response Rate of 28% [0.19, 0.37], an Overall Response Rate of 85% [0.76, 0.93], a mild adverse events rate of 93% [0.82, 1.04] and a severe adverse events rate of 5% [-0.04; 0.14] Standard dose TSEBT had a Complete Response Rate of 57% [0.41; 0.73], the Overall Response Rate was 99% [0.97; 1.02], the mild adverse events rate was 100%, the severe adverse events rate was 7% [-0.01; 0.16]. Comparing standard dose TSEBT in the early versus advanced stages, advanced stages patients had a Risk Ratio=0.77 in obtaining a Complete Response [0.64, 0.92](p=0.0158). TSEBT is an associated with an excellent short term safety profile. Both schedules show high ORR, with standard dose TSEBT demonstrating highest CRR. Advanced stage of disease negatively influence the CRR.

Radiotherapy for cutaneous lymphomas

HintergrundPrimär kutane Lymphome (KL) sind sehr strahlenempfindlich. Deshalb ist die Strahlentherapie ein integraler Bestandteil der multimodalen Behandlung.Ziel der ArbeitDie vorliegende Arbeit ermöglicht einen Überblick über Indikationen, Entwicklungen der Techniken und Dosiskonzepte der Ganzhautelektronenbestrahlung (TSEBT), der lokalen Radiatio sowie Erhaltungstherapien und aktuelle Kombinationsstudien kutaner T‑ und B‑Zell-Lymphome.Material und MethodenEs erfolgte eine selektive Literaturrecherche über die Datenbank PubMed zur Radiotherapie der KL, eine Recherche aktueller Studien mittels clinicaltrials.gov, Darstellung interner Behandlungsstrategien sowie Zusammenfassung der nationalen und internationalen Leitlinien.ErgebnisseDie Niedrigdosis-TSEBT wird als Alternative zur konventionellen 36-Gy-TSEBT national und international empfohlen. Die wichtigsten Vorteile sind die bessere Verträglichkeit, die Möglichkeit der Wiederholung, ein verkürzter Verlauf (ca. 3 Wochen) und eine kurze Dauer bis zum Ansprechen. In den aktuellen Studien wird die TSEBT in der Regel mit 12 Gy durchgeführt und mit unterschiedlichen Immuntherapeutika und epigenetischen Regulatoren kombiniert. Die lokale Radiatio ist indiziert bei Tumoren der Mycosis fungoides und ein kuratives Behandlungsschema für andere KL, insbesondere bei primär kutanen B‑Zell-Lymphomen.DiskussionDie TSEBT ist eine sehr effektive Behandlungsoption der Mycosis fungoides (MF) und bietet einen wichtigen palliativen Nutzen, da sie zügig zur Symptomlinderung und Verbesserung der Lebensqualität führt. Sie ist eine wichtige Behandlungsoption, insbesondere bei Patienten mit ausgeprägten generalisierten Plaques oder im Tumorstadium. Die lokale Radiatio wird im Rahmen der TSEBT für Tumoren und Aufsättigung unterversorgter Areale eingesetzt. Andere KL sind primär kurativ mit einer lokalen Radiatio behandelbar.

Changes in total skin electron beam therapy modalities for mycosis fungoides: A single-centre study

BackgroundMycosis fungoides (MF) is a highly radiosensitive disease. Total skin electron beam therapy (TSEBT) is an effective option that may allow prolonged response for several months. Recently, a low-dose regimen (12 Gy) has been reported more frequently, with less complete response than for standard doses (36 Gy) but better safety. Our aim was to compare patients treated with 12-Gy and 36-40-Gy TSEBT regimens at our centre for efficacy and safety. MethodsThis retrospective, monocentric study in Bordeaux University Hospital included all MF patients treated with 12-Gy or 36-40-Gy TSEBT between 2011 and 2020. ResultsPatients presented with MF at the following stages: 15 T2, including 9 folliculotropic MF; 2 T3, including 1 folliculotropic; 8 T4, including 2 Sézary syndromes. The mean follow-up time after TSEBT was 43.5 months [range: 2–128] for the 36-40-Gy group and 25.2 months [range: 4–45] for the 12-Gy group. The 3-month overall response rate (ORR) was similar for both groups (84.6% for 36-40 Gy and 91.7% for 12 Gy), but there was a tendency to more complete response in the 36-40-Gy group (30.8% vs 8.3%, P=0.35). Progression-free survival (PFS) tended to be better in the 36-40-Gy group than in the low-dose group (15.7 months vs 5.3 months; P=0.28). Patients treated with low-dose TSEBT had a lower incidence of radiation dermatitis (16.7% vs 38.4%, P=0.42). ConclusionWe confirm that TSEBT is an effective option, including at lower doses. Differences between low- and standard-dose regimens were not significant in our series. Although a low-dose regimen seemed to result in lower complete response and long-term efficacy rates in comparison with a standard dose, treatment at lower doses presents the advantage of repeatability, with fewer and weaker side effects, in the event of disease recurrence. Second-line treatments were mostly skin-directed in this group.

Low-dose total skin electron beam therapy plus oral bexarotene maintenance therapy for cutaneous T-cell lymphoma.

Total skin electron beam therapy (TSEBT) combined with systemic therapy or maintenance treatment is a reasonable approach to enhance the remission rate and duration in mycosis fungoides (MF) and Sézary syndrome (SS). This study assesses the efficacy of oral bexarotene therapy after low-dose TSEBT for patients with MF and SS. In this prospective observational study, we recruited MF/SS patients for treatment with low-dose total skin electron beam therapy (TSEBT) with or without bexarotene therapy to describe outcomes and toxicities. Forty-six subjects with MF or SS underwent TSEBT between 2016 and 2021 at our institute. Following TSEBT, 27 patients (59%) received oral bexarotene treatment. The median follow-up was 13 months. The overall response rate (ORR) for the cohort was 85%. The response rate was significantly higher with combined modality (CM) than TSEBT alone (96% vs. 68%, p = 0.03). Median progression-free survival (PFS) for the CM was 17 months versus five months following TSEBT alone (p = 0.001). One patient (4%) in the retinoid group discontinued the bexarotene therapy because of adverse events. The administration of bexarotene therapy did not increase radiation-related toxicities. Response rate and progression-free survival might be improved with TSEBT in combination with oral bexarotene compared to TSEBT alone.

Hypofractionated Low-Dose Total Skin Electron Beam Therapy for Primary Cutaneous T-Cell Lymphoma: Analysis of Efficacy and Toxicity

▪IntroductionCutaneous T-cell lymphoma (CTCL) is a rare form of lymphoma that is characterized by the localization of malignant cells to the skin. While considerable advances have been made in both the diagnosis and treatment of this disease, management and long-term disease control continue to be significant challenges. In particular, total skin electron beam therapy (TSEBT)-a technique that allows for homogenous irradiation of the entire skin-has proved to be efficacious for palliatively treating CTCL (Heumann TR et al IJROBP 2015), but a large proportion of patients continue to relapse over time with a limited possibility of retreatment due to skin toxicity (Wilson LD et al J Am Acad Dermatol 1996; Becker M et al IJROBP 1995).Recently, low-dose TSEBT to ~12 Gy has largely replaced traditional TSEBT to ~36 Gy for the palliative treatment of CTCL due to similar high response rate with less toxicity and more room to re-treat as necessary (Hoppe et al J Am Acad Dermatol 2015). However, there is little consensus on the optimal fractionation and dose per fraction (i.e. number of total treatments needed to deliver 12 Gy).At our institution, we have implemented a novel condensed hypofractionated scheme for low-dose TSEBT, where instead of giving ½ cycle (3 positions) per fraction, we give a full cycle (all 6 positions) per fraction, leading to half as many treatments (6 instead of 12) for the same total dose (12 Gy). We hypothesize that condensed low-dose TSEBT given in 6 fractions, compared to 12, will have similar toxicity and efficacy with the additional convenience of half as many treatments.MethodsWe conducted a single-institution retrospective review of patients with primary CTCL who received TSEBT at UT Southwestern between 2012 and 2021. We stratified patients based on whether they received high-dose TSEBT (18 Gy or above) or low-dose TSEBT (12 Gy), and among those with low-dose TSEBT substratified them between standard fractionation (12 fractions) or hypofractionation (6 fractions). We recorded each patient's primary outcomes, which included response to radiation (complete response, near complete response, partial response, stable disease, or progressive disease), time to response, duration of response, and any acute toxicities. Physician-assessed secondary outcomes, demographic information, and any systemic treatments given concurrently or adjuvantly with TSEBT were also included.ResultsOverall, 46 patients received 59 courses of TSEBT, with 39 patients receiving 52 courses of low-dose TSEBT. Of the 52 low-dose courses evaluated, median age at treatment was 62.5 years old (range, 21-91). Most patients had stage IB, IIB, or IVA disease before initiation of TSEBT. The overall response rate was 87%. Nine courses (17%) resulted in a complete response, 5 courses (9.6%) resulted in a near complete response, and 25 courses (48%) resulted in a partial response. The incidence of progression of skin disease was 17% at 6 months and 21% at 1 year.Of the 59 total courses, 40 patients had hypofractionation (full cycle) and 8 patients had standard fractionation (half cycle). There was no significant difference in the response rate between these two groups.The median time to response for the hypofractionation compared to the standard fractionation was 7 weeks versus 8.5 weeks, respectively, while the duration of response was 46 weeks versus 54 weeks, respectively. Concurrent treatments included bexarotene for 2 patients, brentuximab for 2 patients, interferon for 1 patient, and romidepsin for 1 patient. Importantly, no patients experienced significant toxicities including those in the hypofractionation group, with the exception of 1 patient (2.5%) who experienced grade 3 desquamation.ConclusionIn the largest series to date of low-dose TSEBT using a hypofractionation scheme, our results suggest that it is equally safe and effective as traditional fractionation. This novel condensed low-dose TSEBT comes with the added benefits of convenience and cost-effectiveness, as well as decreased patient exposure to the healthcare system during the current pandemic, and should be considered for all CTCL patients needing TSEBT. Moving forward, we look to evaluate the impact of radiation therapy with concurrent or adjuvant treatments for patients with CTCL as alternative options for possibly supplementing the efficacy of radiotherapy and/or reducing the need for recurrent radiation altogether. DisclosuresDesai: Boston Scientific: Consultancy, Research Funding.

Technical report: 3D-printed patient-specific scalp shield for hair preservation in total skin electron beam therapy.

•Techniques for non-lead scalp-shielding in total skin therapy are lacking.•3D-printing is a promising technique for patient-specific conformal shielding.•We present a case of effective scalp shielding with 3D-printing.

Quality of life in patients with mycosis fungoides and Sézary syndrome undergoing low-dose total skin electron beam therapy with or without maintenance therapy

Quality of life in patients with mycosis fungoides and Sézary syndrome undergoing low-dose total skin electron beam therapy with or without maintenance therapy

Ultra-hypofractionated low-dose total skin electron beam followed by maintenance therapy: Preliminary findings from a prospective open-label study

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).1 Prior studies show that LD-TSEBT improves cutaneous manifestations and health-related quality of life (HRQL).2,3 Hypofractionated TSEBT regimens seem to be a feasible alternative to conventional fractionation.4 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.

Low-Dose Total Skin Electron Beam Therapy Combined With Mogamulizumab for Refractory Mycosis Fungoides and Sézary Syndrome

PurposeManagement of patients with refractory mycosis fungoides and Sézary syndrome (SS) is often challenging, as available therapies lack durable response and consistent activity across disease compartments. Combining low-dose total skin electron beam therapy (LD-TSEBT) upfront with mogamulizumab could optimize the clinical outcome of these patients. LD-TSEBT is effective in clearing skin disease, and mogamulizumab is an antitumor immunotherapy with long-term tolerability, suggesting its potential as a maintenance therapy after maximal response. We examine the combination regimen in patients with SS who were previously treated. Methods and MaterialsTwo patients with SS were treated with combination LD-TSEBT and mogamulizumab. Both patients received mogamulizumab 1 mg/kg weekly × 4 and then bi-weekly; LD-TSEBT (12 Gy) was initiated within 2 days of starting mogamulizumab and given over 2-3 weeks. Safety and clinical response were evaluated. ResultsTotal skin electron beam therapy plus mogamulizumab (TSE-Moga) was well-tolerated without any unanticipated adverse events. Patient 1 (T4N2bM0B2) was a 63-year-old woman with 4 prior systemic therapies; time to global response with TSE-Moga was 9 weeks. Patient 2 (T4NxM0B2) was a 75-year-old man with 5 prior systemic therapies; time to global response was 4 weeks. Both patients lacked global response to their prior therapies but achieved global complete response (blood and skin) with TSE-Moga. After a follow-up of 72 weeks and 43 weeks, respectively, global complete response continued. ConclusionsTSE-Moga demonstrated excellent tolerability and promising clinical activity with ongoing global complete responses in 2 patients with refractory SS. This encouraging experience supports our ongoing clinical trial evaluating the efficacy and safety of TSE-Moga in mycosis fungoides and SS.

Acute and sub-acute toxicity profile of ultra-hypofractionated low-dose total skin electron beam with two 4 Gy fractions for cutaneous T cell lymphoma

PurposeLow-dose total skin electron beam therapy (TSEBT) over 3 weeks has proved to be a safe and effective treatment for cutaneous T cell lymphomas (CTCL). In this prospective trial, we examined the feasibility of ultra-hypofractionated low-dose TSEBT regimen in two fractions with 4 Gy combined with systemic therapy to minimize the number of visits to radiation centers.Patients and methodsSix patients with mycosis fungoides (MF) or Sézary syndrome (SS) received TSEBT with a total radiation dose of 8 Gy in two fractions between April 2020 and June 2020. Patient and treatment characteristics, tumor burden, the impact on the quality of life using Skindex-29 questionnaires, and acute toxicities were analyzed.ResultsDuring TSEBT, all patients developed grade 1 toxicities while two patients developed grade 2 toxicities. One patient experienced sepsis. The most common adverse effects were erythema and edema. All grade 2 toxicities regressed after 4 weeks following TSEBT. Based on the reported symptoms measured by Skindex-29, we detected a significant reduction in total Skindex-29 score after 8 weeks of radiation (P = 0.03), particularly in the symptoms (P = 0.01) and emotional domains (P = 0.04).ConclusionUltra-hypofractionated low-dose TSEBT followed by systemic therapy seems to be a safe and feasible alternative to conventional fractionated TSEBT for patients with MF/SS. The skin tumor burden and the health-related quality of life have been significantly improved within 8 weeks following radiotherapy.

Total skin electron beam therapy for primary cutaneous T-cell lymphomas: clinical characteristics and outcomes in a Mexican reference center.

The aim of this study was to assess treatment modalities, treatment response, toxicity profile, disease progression and outcomes in 14 patients with a confirmed diagnosis of primary cutaneous T-cell lymphoma (PCTCL) treated with total skin electron beam therapy (TSEBT). Primary cutaneous lymphomas (PCLs) are extranodal non-Hodgkin lymphomas originating in the skin without evidence of extracutaneous disease at diagnosis. Despite advances in systemic and local therapy options, the management of advanced stages remains mostly palliative. This is a retrospective study of patients with PCTCL, diagnosed and treated in a reference center in Mexico City, analyzing treatment modalities, response to treatment, long-term outcome, and mortality. Eight males (57%) and 6 (43%) females were identified. Most patients were stage IVA (n = 5, 36%) followed by stage IB and IIB (28.5% and 21.4%, respectively). Eleven patients received the low-dose RT scheme (12 Gy), 1 patient, the intermediate-dose RT scheme (24 Gy), and 2 patients, the conventional-dose RT scheme (36 Gy). Mean follow-up time was 4.6 years. At first follow-up examination, 6-8 weeks after radiotherapy, the overall response rate (ORR) for the cohort was 85%. The median PFS for the whole cohort was 6 months. This study reinforces the role of TSEBT when compared with other treatment modalities and novel agents. Low-dose TSEBT is now widely used because of the opportunity for retreatment.

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

Low-dose total skin electron beam therapy (TSEBT) for mycosis fungoides is popular because of reduced toxicity with effective palliation. We condensed TSEBT, reducing visits by half and overall treatment length by one third. To determine the efficacy and safety of a novel condensed low-dose TSEBT for mycosis fungoides. We conducted a cohort study (2014-2018) with a median follow-up of 22.8months. We delivered 12Gy per 6 fractions with the modified Stanford technique, 3 fractions per week, with boosts to shadowed sites at risk between treatments, completing in 2weeks. Primary outcomes included clinical response, duration of and time to response, and toxicity. Secondary outcomes included patient-reported quality of life (pain, pruritus, and Dermatology Life Quality Index) and physician-scored disease burden (body surface area involvement and Modified Skin Weighted Assessment Tool). Of 25 patients, stage IB was most common at the time of TSEBT (36%). The overall response rate was 88%. Most common was a near complete response (36%), and complete response was achieved in 6 (24%) patients. The median duration of response was 17.5months (3.5-44.2), and the median time to response was 2months (range, 0.9-4.1). No patients had toxicity of grade 3 or greater. QOL and disease burden showed significant benefit after TSEBT (P<.001). Cohort study with limited sample size. Condensed, low-dose TSEBT has favorable outcomes and toxicity with logistical convenience.

Quality of Life Improvement Following Low-Dose Total Skin Electron Beam Therapy in Patients with Mycosis Fungoides or Sezary Syndrome

Total skin electron beam therapy (TSEBT) has proved to be a safe and effective treatment for cutaneous T-cell lymphomas. Here, we report our experience applying low-dose TSEBT to patients with mycosis fungoides (MF) or Sezary syndrome (SS). We examined the impact of this treatment on patient quality of life and outcome. Forty-four patients with MF or SS received 48 TSEBT courses with a median dose of 12 Gy (range, 12–24) within the past eight years at our institute. Patient and treatment characteristics for these cases, as well as the impact of TSEBT on quality of life and duration of response, were retrospectively analyzed and compared. The median modified Severity Weighted Assessment Tool score before the start of TSEB was 44 (mean: 57, range: 7–160). The overall response rate was 88%, with a complete response (CR) rate of 33%. Five patients (10%) had near CR (< 1% body surface area). Pruritus improved significantly in 84% of the patients treated (CR rate, 35%). The median follow-up period was 13 months. The median duration of response (DOR), progression-free survival (PFS), and overall survival (OS) for the entire cohort were 10 months, 9 months, and 20 months, respectively. Patients who received maintenance treatments had a longer DOR (13 months vs. 6 months, respectively; P = 0.1), PFS (9 months vs. 3 months, respectively; P = 0.01), and OS (51 months vs. 18 months, respectively; P = 0.15). Meanwhile, patients presenting CR had a noticeably longer PFS (13 months vs. 7 months, respectively; P = 0.05). Patient-reported symptom burden was measured with Dermatological Life Quality Index and Skindex-29 questionnaires. The mean symptom reductions were 6 ± 8 (P = 0.005) and 21 ± 24 (P = 0.002), respectively. In the Functional Assessment of Cancer Therapy-General assessment, significant improvements in both the emotional (P = 0.03) and social (P = 0.08) domains were observed after TSEBT. In univariate analyses, various clinical and hematological parameters were found to be significant. In a multivariate analysis, only CD30+ MF was associated with improved DOR (P = 0.05) and PFS (P = 0.05), while disease stage appears to potentially impact OS (P = 0.06). Taken together, these results indicate that maintenance of TSEBT improves the PFS of patients with MF or SS. In addition, TSEBT improved disease symptoms and significantly improved emotional and social domains of patients’ quality of life.

Total skin electron beam therapy in mycosis fungoides-a shift towards lower dose?

Cutaneous T-cell lymphoma is a rare group of malignancies characterized by the proliferation of CD4+ T-cells, of which mycosis fungoides (MF) is the predominant subtype. The neoplastic lymphocytes of MF are extremely radiosensitive and even low doses of radiation can produce excellent responses. As such, radiotherapy (RT) is considered to be the most efficacious single agent treatment option for MF. Total skin electron beam therapy (TSEBT) is a special RT technique that allows for homogenous irradiation of the entire skin. The effectiveness of conventional-dose (cd) TSEBT (30-36 Gy), particularly at inducing complete cutaneous responses, has been well documented over the years. Nonetheless, most patients eventually relapse. In these cases, cd-TSEBT is limited as RT toxicity is dose-dependent. Consequently, clinicians are moving towards low-dose (ld) TSEBT (10-12 Gy). Institutional studies and prospective trials have shown similar response rates, overall survival and symptomatic relief with this regimen, albeit at the cost of complete response. Advantages of ld-TSEBT include decreased treatment length, improved side effect profile, and the opportunity for multiple applications following disease recurrence. This comprehensive review evaluates TSEBT techniques, clinical outcomes, impact of different dose regimens, and toxicities in the treatment of MF. Future applications of TSEBT with newer systemic agents are also discussed.

Total Skin Electron Beam Therapy for Mycosis Fungoides Revisited With Adjuvant Systemic Therapy

BackgroundAlthough standard-dose total skin electron beam therapy (TSEBT) has been thought to provide the greatest clinical benefit for mycosis fungoides, recent studies have shown that low-dose TSEBT may also provide high rates of disease control. Materials and MethodsA retrospective chart review was conducted for patients receiving TSEBT for mycosis fungoides at a single institution from 2009 to 2017. Patients were evaluated for overall survival, progression-free survival, and duration of clinical benefit. Partial response was defined as any documented clinical regression of lesions, whereas complete response was defined as complete resolution of lesions. ResultsTwenty patients were included in the study. Twelve patients received low-dose radiation (≤ 12 Gy), and 8 received standard-dose radiation (> 12 Gy). Response rate was 100% in both groups. The rate of complete response was 38% in the standard-dose group and 25% in the low-dose group. There was no difference in overall survival between the 2 groups (P = .84). There was also no difference in median progression-free survival (P = .95) or duration of clinical benefit (P = .95) between the 2 groups. Of low-dose patients, 33% received immediate systemic therapy, whereas 92% received adjuvant topical or systemic therapy. In the standard-dose group, only 25% received systemic adjuvant therapy, and 63% received adjuvant topical or systemic therapy. ConclusionLow-dose TSEBT with adjuvant therapy results in adequate symptom palliation, comparable to standard-dose TSEBT. Low-dose TSEBT should be considered a standard treatment option in this population.

Update of Comparison of Low-Dose and Standard-Dose Total Skin Electron Beam Therapy for Mycosis Fungoides

Total skin electron beam therapy (TSEBT) is has been shown to be an effective treatment for mycosis fungoides (MF). Doses of 30-36 Gy have traditionally been used with high response rates, although treatment is associated with toxicity and most patients ultimately progress. Recent studies have proposed 12 Gy as an effective and tolerable dose, and our institution has been utilizing this regimen to treat MF patients since 2015. We compare our experiences using low-dose TSEBT and standard-dose TSEBT. Between 2010 and 2016, 26 patients with Stage IB – IVA MF were treated with TSEBT at our institution. Thirteen patients received a total of 16 courses of low-dose TSEBT to 12 Gy, with 3 of these patients received a repeat course of low-dose TSEBT during this time. As a comparison group, 13 patients received standard-dose TSEBT between 30-36 Gy, all from 2015 and prior. We compare response rates, time to progression and toxicity between these treatment groups. Median follow-up was 15.8 months. Patients who received low-dose TSEBT were more likely to have had prior local radiation treatment (50% versus 8%, p = 0.013). All patients experienced at least a partial response to treatment, with 31% of the low-dose TSEBT courses and 77% of the standard-dose TSEBT courses resulting in initial clinical complete response (p = 0.014). Patients who underwent a repeat course of low-dose TSEBT had a 67% complete response rate as compared to 13% with single course low-dose TSEBT and 77% with standard-dose TSEBT (p = 0.020). Fourteen of 16 courses of low-dose TSEBT and 12 of 13 courses of standard-dose TSEBT resulted in progression. The average time to progression for low-dose TSEBT was 3.2 months versus 8.2 months for standard-dose TSEBT (p = 0.030). Common toxicity to both treatment arms was pain and pruritus. Compared to low-dose TSEBT, standard-dose TSEBT trended toward increased toxicity with hyperpigmentation/erythema (23% versus 6%, p = 0.19) and dry desquamation (46% versus 19%, p = 0.11). Low-dose TSEBT trended towards higher rates of skin dryness compared to standard-dose TSEBT (56% versus 23%, p = 0.071). Rates of dry desquamation increased to 33% with repeat low-dose TSEBT compared to 15% with single course low-dose TSEBT and 46% with standard-dose TSEBT (p = 0.24). Low-dose TSEBT was associated with a significantly lower complete response rate and shorter time to progression compared to standard-dose TSEBT, although rates of complete response improved with a repeat course of low-dose TSEBT. In addition, low-dose TSEBT trended toward lower rates of toxicity compared to standard-dose TSEBT. Given the high rate of progression regardless of treatment regimen, the use of low-dose TSEBT should be considered for the treatment of MF as this approach allows for re-treatment with complete response rates rivaling that of standard-dose TSEBT with a better toxicity profile.

Condensed Low Dose Total Skin Electron Beam Therapy for Mycosis Fungoides: A Single Institution Experience

To determine safety and efficacy of condensed low dose total skin electron beam therapy (TSEBT), 12 Gy over two weeks, for mycosis fungoides (MF). We conducted a retrospective review of patients treated with condensed low dose TSEBT for MF at our institution. Patients were treated with 6-field Stanford technique to a total dose of 12 Gy in 2 Gy fractions, every other day over 2 weeks. A total of 18 patients with minimum 6 months follow up were included. Treatment response rate was defined as complete response (CR), near CR (<5% body surface area [BSA]), and partial response (PR). Duration of response as measured from TSEBT start date to date of progression requiring systemic therapy or death. Pain, pruritus, Dermatology Life Quality Index (DLQI) score , DLQI effect, modified Severity Weighted Assessment Tool (mSWAT), BSA, and TSEBT-related toxicities were also evaluated. Statistical analysis was performed with R (version 3.4.3). Linear mixed models with random effect of patient was used for estimation of pre vs. post comparisons on efficacy endpoints. We evaluated with two-sample t-test, Fisher's exact test, as well as Cox proportional hazards model in addition to summary statistics of baseline characteristics. Of the 18 patients, 14 were male and 4 were female. Median follow-up of 63 weeks. Median age 69 yo (range 37-85). Majority were Stage IB (44%). Three patients had large cell transformation. Overall response rate was 100 percent. Complete response (CR) was seen in 3 patients (17%), and near CR in 7 patients (39%), and PR in 8 patients (44%). Median duration of response was 56 weeks, with seven patients (39%) having progression. Four patients died, of which one had large cell transformation. Treatment response metrics were all significantly reduced after TSEBT. Pruritus had a mean difference of 2.694 (95% CI 1.354, 4.035, p<0.001), pain of 2.694 (95% CI 1.021, 4.368, p=0.003), mSWAT of 57.53 (95% CI 32.08, 82.98, p<0.001), BSA of 32.88 (95% CI 18.86, 46.91, p<0.001), and DLQI of 6.56 (95% CI 3.55, 9.57, p<0.001). Treatment was well tolerated with no toxicity ≥ Grade 3. Most common toxicity was Grade 1 fatigue (33%) and Grade 1 alopecia (22%). Two patients experienced nail loss and three patients had Grade 2 radiation dermatitis that self-resolved. Condensed low dose TSEBT shows excellent initial response with favorable duration of response, and effective palliation of symptoms. Further exploration with a prospective trial is warranted.

A novel approach to low dose total skin electron beam therapy (TSEBT)

Aims: To assess efficacy and toxicity of two low dose TSEBT regimens in the treatment of Cutaneous T-cell Lymphoma (CTCL).