Tailoring Radiation Therapy for Patients With Limited Cutaneous T Cell Lymphoma: Preliminary Clinical Experience With Subtotal Skin Electron Therapy.

BACKGROUND/AIM: Total skin electron beam therapy (TSEBT) is an effective treatment for managing cutaneous T-cell lymphoma (CTCL), but may result in unnecessary toxicity. With the production of a custom rolling shield holding a configurable stack of plastic slats to block uninvolved skin, we implemented a program for subtotal skin electron beam therapy (STSEBT). We report our preliminary experience with STSEBT vs. TSEBT to manage CTCL. PATIENTS AND METHODS: A retrospective review of 32 CTCL patients who were treated at a single institution between February 28th, 2017, and May 25th, 2022, was completed. Of these cases, seven patients received STSEBT and 25 received TSEBT. RESULTS: Thirty-two patients underwent a course of STSEBT or TSEBT. The median follow-up was 465 days and the median age at diagnosis was 70.8 years. Stage distribution was as follows: one (3%) IA, 16 (50%) IB, 6 (19%) IIB, two (6%) IIIA, five (16%) IVA, and two (6%) IVB. The overall response rate was 96%. For patients receiving TSEBT (n=25), three (12%), 10 (40%), and 11 (44%) had a CR, NCR, and PR, respectively. For the patients receiving STSEBT, four (57.1%), three (42.9%), and zero (0%) had a CR, NCR, and PR, respectively. There was one patient (4%) with no response. Cumulative incidence of progressive skin disease requiring additional electron therapy at three months was 21.1% [IQR=8.6, 51.5%], 36.8% [IQR=20, 68%] at six months, and 57.9% [IQR=38.5, 87.1%] at one year. Low rates of toxicities were recorded. CONCLUSION: This analysis demonstrated that treatment of CTCL patients with low disease burden with STSEBT results in similar overall response and time to progression compared to treatment with TSEBT.

Clinical, histopathological and immunohistochemical evaluation of ultraviolet A1 treatment in early-stage mycosis fungoides.

BACKGROUND/PURPOSE: Mycosis fungoides (MF) is the most common variant of cutaneous T-cell lymphomas primarily involving the skin. Early-stage MF is characterised by non-specific skin lesions and non-diagnostic biopsies. While skin-focused treatments, such as PUVA and narrowband UVB (nbUVB), are the most frequently recommended treatments, the UVA1 efficacy has been researched in recent years. The purpose of this study was to evaluate the clinical, histopathological and immunohistochemical aspects of UVA1 treatment in patients with early-stage MF. METHODS: The modified severity weighted assessment scale (mSWAT) was used for total skin body scoring before and after treatment. Skin punch biopsies were taken from the patients before and after treatment. UVA1 therapy was performed five times each week. RESULTS: This study included 26 patients with early-stage MF. The total number of UVA1 sessions varied between 15 and 34. Complete response was observed in 8 (30.8%) of 26 patients (30.8%). The median mSWAT score decreased statistically significantly from 7.1 to 2.0 after treatment (p < .001). Histopathological complete response was observed in 2 (9.5%) of 21 patients. A statistically significant decrease in dermal interstitial infiltrate was observed on histopathological examination after treatment (p = .039). Epidermal CD4/CD8 levels decreased statistically significantly higher from a median of 2.5-1.2 in the complete clinical response group after treatment (p = .043). CONCLUSION: According to our results, UVA1 treatment has an effect on early-stage MF in terms of clinical, histopathological and immunohistochemistry.

Frequency of skin cancer among psoriasis, vitiligo, and mycosis fungoides patients treated with narrowband ultraviolet B phototherapy.

BACKGROUND: Narrowband ultraviolet B (NB-UVB) phototherapy is a popular and relatively contemporary treatment option. However, only a few studies to date have explored the potential risk of skin cancer following NB-UVB treatment. OBJECTIVE: This study aimed to investigate the potential long-term risk of skin cancer in patients treated with NB-UVB. METHODS: This cohort study included patients with psoriasis, vitiligo, and mycosis fungoides treated with NB-UVB at two university hospitals in Israel in 2000-2005. Patients were followed up for skin cancer for at least 10 years. Data were extracted from the hospital and community medical records. RESULTS: A total of 767 patients were included in this study: 509 with psoriasis, 122 with vitiligo, and 136 with mycosis fungoides. The mean follow-up duration was 13 years. Among these patients, 4.43% developed skin cancer during the follow-up (3.93% had psoriasis, 2.46% had vitiligo, and 8.09% had mycosis fungoides). Old age and fair skin type were the only significant independent risk factors for skin cancer. There was no significant difference in the mean number of NB-UVB treatments among patients who developed skin cancer and those who did not (99.09 vs. 94.79, respectively). CONCLUSION: No association was observed between the number of NB-UVB treatments and carcinogenesis in any study group. Age is a significant risk factor, and older patients treated with NB-UVB should be followed up carefully.

Estimation of serum and tissue level of interleukin-15 (IL-15) and IL-15 receptor alpha (IL-15Rα) in mycosis fungoides before and after phototherapy: An interventional cohort study.

BACKGROUND: Mycosis fungoides (MF) is a chronic, highly recurrent cutaneous T-cell lymphoma, whose pathogenesis has not yet been fully elucidated. Interleukin-15 was previously highlighted as a viability factor for cutaneous T-cell lymphoma with previous studies shedding light on its role in pathogenesis of MF and its plausibility as a potential therapeutic target. OBJECTIVE: This study was conducted to evaluate serum and tissue expression of IL-15 and IL-15Rα in early cases of MF (IA, IB, IIA) at baseline and following phototherapy. MATERIALS AND METHODS: Fourteen early MF cases were recruited. Samples were withdrawn prior to starting phototherapy treatment and following near complete clearance of the biopsied lesion or after a maximum of 36 sessions of phototherapy. Samples were assessed for change in expression of IL-15 and IL-15 Rα levels following treatment, whose levels were compared to healthy controls. RESULTS: Serum and tissue levels of IL-15 and IL-15Rα in early MF cases were significantly higher at baseline than their levels following phototherapy treatment and higher than healthy controls. However, they dropped significantly following treatment with no statistical difference between treated cases and controls, apart from serum IL-15Rα that remained significantly elevated than controls. CONCLUSION: Interleukin-15 and its receptor alpha appear to contribute to the pathogenesis of MF, being significantly elevated than healthy controls, which were normalized following phototherapy treatment, apart from serum IL-15Rα, which remained elevated. Controlling IL-15/IL-15Rα expression is a newly proposed mechanism of action of phototherapy in MF.

Life after total skin electron irradiation; A perspective through the eyes of a radiation oncologist.

Mycosis fungoides (MF) remains a challenge as a disease from its diagnosis through treatment and follow-up. The rarity of the disease and uncharacteristic clinical manifestations pose difficulty in diagnosis, and the lack of treatment facilities adds to the management woes. Though the Stanford technique is the most accepted modality of total skin electron beam therapy (TSEBT), the implementation details are still unstandardized. Different centers adopt different methodologies as per their convenience and suitability. We present a patient of MF with many dimensions of prediagnosis clinical features to the diagnosis, treatment, and follow-up with subsequent developments over a period of 24 years that may help to understand the disease and management in a better manner.

Response and local control in patients treated with low-dose radiotherapy for tumoral mycosis fungoides.

Low-dose radiotherapy (LDRT), defined in this study as 2 fractions of 4 Gy delivered on consecutive days, is an effective option for local palliation of mycosis fungoides (MF), but its efficacy for tumoral lesions (TL) needs investigation. We assessed response and local control (LC) rates for patients treated with LDRT for MF and compared these outcomes between TL and non-TL. A total of 73 lesions in 18 patients treated with LDRT between 2013-2020 were analyzed. Response was defined as complete response (CR), partial response (PR), or no response (NR). In the non-TL versus TL groups, CR was observed in 16.7% v. 4.0%, PR in 81.2% v. 80.0%, NR in 2.1% v. 16.0%, respectively. 2-year LC was 100% for non-TL and 61% for TLs (p < 0.01). LDRT yields excellent response and lesion control for non-TLs and is associated with lower response rates and LC for TLs.

Low-dose radiation therapy yields excellent response and lesion control for non-tumoral lesions.

Single-Fraction Radiation Therapy for Localized Cutaneous T-Cell Lymphoma.

PURPOSE: Mycosis fungoides is the most common type of cutaneous T-cell lymphoma (CTCL). Single-fraction radiation therapy has been used as a skin-targeted therapy to treat localized CTCL lesions. The objective of this study was to investigate the treatment outcomes associated with single-fraction radiation therapy for CTCL. METHODS AND MATERIALS: We retrospectively studied the outcomes among patients with CTCL treated with single-fraction radiation therapy at our institution between October 2013 and August 2022. Clinical response (complete response [CR], partial response [PR], or no response [NR]) and retreatment response were evaluated. RESULTS: A total of 242 lesions from 46 patients were analyzed, for an average of 5.3 lesions treated per patient. The majority of lesions presented with a plaque morphology (n = 145, 60.0%). All lesions were treated to a dose of 8 Gy in 1 fraction. Median follow-up was 24.6 months (range, 1-88 months). Of the 242 lesions, 36 (14.8%) had an initial PR or NR; all were retreated with the same regimen to the same site at a median interval of 8 weeks. Eighteen of the retreated lesions (50.0%) went on to have a CR. Thus, the overall CR rate for CTCL lesions was 92.6%. No recurrences were noted in the treated areas after achieving CR. CONCLUSIONS: Single-fraction radiation therapy to a dose of 8 Gy in 1 fraction to localized areas provided a high rate of complete and durable responses in the affected sites.

Nb-UVB and PUVA therapy in treating early stages of Mycosis Fungoides: A single-center cross-sectional study.

INTRODUCTION: Mycosis fungoides (MF) and Sezary Syndrome are the most common forms of cutaneous T-cell lymphoma. Early-stage MF is known to have an indolent behavior, and the EORTC guidelines recommend treating patients with skin-directed therapies, such as phototherapy, instead of systemic therapies. Phototherapy is a popular therapeutic option, with two commonly used light sources-PUVA and narrow band-nb UVB. PUVA is less commonly used due to its potential carcinogenic role, but it has systemic effects, while nb-UVB has mostly skin-limited effects. There is ongoing debate regarding the role of UVB light, and in 2021, the Cutaneous Lymphoma Italian Study Group reached a consensus on technical schedules for NB-UVB and PUVA for MF. This study aims to analyze and compare the efficacy of the two phototherapy options in treating early-MF patients. MATERIALS AND METHODS: The study included patients diagnosed with stage IA/B MF in the last 10 years, who had at least 12 months of follow-up data and a minimum of 24 phototherapy sessions (PUVA or nb UVB) and treated with topical steroids apart from phototherapy. RESULTS: Results showed that the two phototherapy options were similarly effective in treating early MF, with no significant differences in clinical response, although PUVA was associated with more adverse effects. CONCLUSIONS: The study provides valuable insights into the use of phototherapy in early MF, and the results can be used to guide treatment decisions and improve patient outcomes.

Ultrahypofractionated Low-Dose Total Skin Electron Beam in Advanced-Stage Mycosis Fungoides and Sézary Syndrome.

PURPOSE: The aim of this study was to assess the safety and efficacy of an ultrahypofractionated low-dose total skin electron beam therapy (TSEBT) regimen in patients with advanced mycosis fungoides (MF) or Sézary syndrome (SS). METHODS AND MATERIALS: In this multicenter observational study from 5 German centers, 18 total patients with MF or SS underwent TSEBT with a total dose of 8 Gy in 2 fractions. The primary endpoint was the overall response rate. RESULTS: Fifteen of 18 patients with stage IIB-IV MF or SS were heavily pretreated with a median of 4 prior systemic therapies. The overall response rate was 88.9% (95% confidence interval [CI], 65.3-98.6), with 3 complete responses (16.9%; 95% CI, 3.6-41.4). At a median follow-up period of 13 months, the median time to next treatment (TTNT) was 12 months (95% CI, 8.2-15.8), and the median progression-free survival was 8 months (95% CI, 2-14). A significant reduction in the modified severity-weighted assessment tool, total Skindex-29 score (Bonferroni-corrected P < .005), and all subdomains (Bonferroni-corrected P < .05) was observed after TSEBT. Half of the irradiated patients (n = 9) developed grade 2 acute and subacute toxicities. One patient had confirmed grade 3 acute toxicity. Chronic grade 1 toxicity has been observed in 33% of patients. Patients with erythroderma/SS or prior radiation therapy appear at higher risk of skin toxicities. CONCLUSIONS: TSEBT with 8 Gy in 2 fractions achieves good disease control and symptom palliation with acceptable toxicity, greater convenience, and fewer hospital visits.

Predictors of adherence to Narrowband ultraviolet B first-month treatment dosage plan.

BACKGROUND: The adherence to a narrowband ultraviolet B (NB-UVB) treatment plan is derived, in large part, from the patient's skin tolerance to the phototherapy dose. At present, the initial and first-month incremental phototherapy doses are determined prior to treatment initiation based on the patient's Fitzpatrick skin phototyping. OBJECTIVES: To identify variables that predict adherence to NB-UVB first-month treatment dosage plan. METHODS: Charts of 1000 consecutive patients receiving NB-UVB at a hospital-based phototherapy unit were retrospectively analyzed. We included patients receiving NB-UVB for atopic dermatitis, psoriasis, vitiligo, and mycosis fungoides. The first-month NB-UVB treatment plan was determined based on the patient's Fitzpatrick phototype. Adherence to treatment was defined as receiving at least 80% of the planned first-month cumulative dose. We compared adherent vs. non-adherent patient groups for age, sex, Fitzpatrick phototype, presence of freckles, nevus count category, and type of dermatological disease. RESULTS: The study included 817 eligible patients, mean age 40 (2-95) years; 54% men; 32% had Fitzpatrick phototype I-II. Distribution by diagnosis was atopic dermatitis (29%), psoriasis (27%), vitiligo (23%), and mycosis fungoides (21%). Adherence to NB-UVB treatment plan was observed in 71% of patients. Adherence decreased with age, with 7% decrease per year (P = 0.03) and was higher among mycosis fungoides patients (77.3%) compared to all other diagnoses (69.8%; P = 0.02). CONCLUSIONS: Adherence to NB-UVB treatment may be related to age and diagnosis. Fitzpatrick phototype-based first-month treatment plans should be modified accordingly.

[Radiotherapy for cutaneous lymphomas]. / Radiotherapie kutaner Lymphome.

BACKGROUND: Primary cutaneous lymphomas (CL) are highly radiosensitive. Therefore, radiotherapy is an integral part of multimodality treatment. AIM: The present work provides an overview of indications, technical developments, and dose concepts for total skin electron beam therapy (TSEBT), local radiotherapy as well as maintenance therapy, and current combination studies regarding cutaneous T­ and B­cell lymphomas. MATERIALS AND METHODS: We performed a selective literature search in the PubMed database on the topic of radiotherapy for CL and a search for current studies using clinicaltrials.gov. Furthermore, we describe our own treatment strategies and summarize national and international guidelines. RESULTS: Low-dose TSEBT is nationally and internationally recommended as an alternative to conventional 36 Gy TSEBT. The main advantages are better tolerability, the possibility of retreatment, a shorter treatment course (approximately 3 weeks), and a short time to response. In current studies, TSEBT is usually delivered to a total dose of 12 Gy and combined with immunotherapy and epigenetic therapy. Local radiotherapy is indicated for mycosis fungoides (MF) tumors and is a curative treatment regimen for other CL, particularly primary cutaneous B­cell lymphomas. CONCLUSION: TSEBT is a very effective treatment for MF and is a highly effective palliative treatment, leading to rapid symptom relief and improvement in quality of life. It is an important treatment option, especially in patients with extensive generalized lesions or advanced tumor stage. Local radiation is used as part of TSEBT for tumors and as a boost to undertreated areas. Other CLs are primarily curable with local radiotherapy.

Efficacy of narrowband UVB phototherapy in early-stage mycosis fungoides in Iranian patients.

Narrowband UVB (NB-UVB) has been shown to be effective for the treatment of early mycosis fungoides (MF) in light-skinned patients, but the effect of NB-UVB on patients with darker skin phototypes needs further investigation. The aim of this study was to evaluate the effect of NB-UVB in the treatment of early-stage MF in Iranian patients. In this retrospective study, 24 patients with the diagnosis of early MF (9 stage AI, 15 stage IB) were enrolled. All patients were treated with NB-UVB phototherapy 2-3 times weekly. After achieving complete response, a maintenance treatment was recommended. The response rate, side effects, and recurrence rate in the follow-up period were assessed. The follow-up period was ranged 6 to 24 months. Ten patients (41.7%) had complete remission after a mean number of 42.9 treatment and mean cumulative dose of 58.11 J/cm2. Twelve patients (50%) had partial response, and 2 patients (8.3%) had no response. After discontinuation of maintenance treatment, 4 of 10 patients (40%) with complete remission relapsed within a mean of 5 months. Side effects were limited to erythema (12.5%) and hyperpigmentation (4%). NB-UVB is a safe and effective method for the treatment of early MF, but it seems that more treatment sessions and higher doses of NB-UVB are required for darker skin phototypes.

Prognosis in early stage cutaneous T-cell lymphoma treated with psoralen plus ultraviolet A irradiation and low-dose interferon-α: Long-term efficacy and survival according to conventional and emerging clinical endpoints.

Patients with early stage cutaneous T cell lymphoma (CTCL) usually have a benign and chronic disease course, characterized by temporally response to conventional skin directed therapies and intrinsic possibility to evolve. Using the combination of psoralen plus ultraviolet A irradiation (PUVA) and low-dose interferon-α (INF), the principal treatment goal is to keep confined the disease to the skin, preventing disease progression. Among 87 patients with early stage IA to IIA MF treated with low-dose IFN-α2b and PUVA in our center, complete remission (CR) were reported in 70 patients (80.5%) and the overall response rate (ORR) was 97.8% (n = 85), with a median time to best response to therapy of 5 months (range, 1-30). Among the responders, only the 8% of patients had a relapse with major event. The median follow-up was 207 months (range, 6-295). Survival data showed a median overall survival (OS) not reached (95% CI; 235-NR months), a disease free survival (DFS) of 210 months (95% CI; 200-226 months) and a median time to next treatment (TTNT) of 38.5 months (95% CI, 33-46 months). The long follow up of this study verifies our preliminary results already published in 2006 and confirms the efficacy of INF-PUVA combination therapy in a real world setting, according conventional (OS and DFS) and emerging (TTNT) clinical endpoint of treatment efficacy.

Total skin electron beam therapy (TSEBT) in management of mycosis fungoides: A case series.

A retrospective review was conducted In Aga Khan University from January 2013-December 2020 for patients who received Total Skin Electron Beam Therapy (TSEBT) on the management of Mycosis Fungoides (MF). The clinical response rate and disease-free interval (DFI) was evaluated for three patients. All of the patients received a 3600 cGy dose of radiation. Clinical complete remission (cCR) was observed in two out of three patients, while one patient showed clinical partial response. Following the cCR to TSEBT, the DFI of the first patient with stage 1B lasted 30 months, while the second patient with stage IIB remained disease free for five months. TSEBT is an effective treatment for MF disease. It can thus be expected that patients with limited disease in the early stage can acquire a cCR with a longer DFI. The clinical outcomes of our study show concordance with the literature. The patients who had extensive (T3) skin involvement and had refractory diseases showed lower DFI with radiation.

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

BACKGROUND: Mycosis 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. METHODS: This retrospective, monocentric study in Bordeaux University Hospital included all MF patients treated with 12-Gy or 36-40-Gy TSEBT between 2011 and 2020. RESULTS: Patients 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). CONCLUSION: We 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.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: Response rate and progression-free survival might be improved with TSEBT in combination with oral bexarotene compared to TSEBT alone.