Skin-directed Treatment Research Articles

Advances in the treatment of mycoses fungoides and Sézary syndrome: a narrative update in skin-directed therapies and immune-based treatments.

Mycoses fungoides (MF) and Sézary syndrome (SS) are cutaneous T-cell lymphomas that are often challenging to manage given the absence of reliably curative therapies, at times high symptom burden with significant detriment to quality of life, and need for ongoing treatment for disease and symptom control. Recent developments in skin-directed treatments include optimizing the use of existing topical therapies, the introduction of known dermatological agents and treatment modalities for the specific treatment of MF/SS (such as mechlorethamine gel, calcineurin inhibitor creams, and photodynamic therapy), and novel local and topical agents. For advanced disease, dedicated clinical trials have translated to exciting progress, leading to the approval of brentuximab vedotin (2017) and mogamulizumab (2018) for relapsed MF/SS. Additional studies of other active systemic agents, including various cellular therapies, represent further attempts to add to the therapeutic armamentarium in treating MF/SS. In this review, we highlight these recent advancements, ranging from optimization of skin-directed therapies to the introduction of novel systemic agents. We focus on therapies approved in the preceding five years or under investigation in advanced-phase clinical trials.

BI20 Generalized pustular psoriasis in a patient receiving pembrolizumab for metastatic lung adenocarcinoma

Abstract Skin toxicities are the most common immune-related adverse events (irAEs) associated with immune checkpoint inhibitor (ICI) treatment, an emerging field in dermatology. A wide spectrum of skin irAEs, including lichenoid reactions, vitiligo, bullous pemphigoid and other autoimmune skin diseases, have been reported. Psoriasiform irAEs may occur as an exacerbation of pre-existing disease or de novo and often occur later than other skin irAEs. Most cases reported to date are of chronic plaque and palmoplantar psoriasis. Generalized pustular psoriasis has been reported in fewer than 10 cases. We present a patient with mild pre-existing psoriasis who developed plaque psoriasis, evolving into severe pustular psoriasis after 4 months of pembrolizumab therapy for lung cancer. A 67-year-old man with stage 4 lung adenocarcinoma developed a widespread, itchy psoriasiform rash 3 months after starting pembrolizumab. He had a history of rheumatoid arthritis (RA) and pembrolizumab was started when he had progressed through chemotherapy. The RA was controlled on prednisolone, which was increased when methotrexate was discontinued shortly after diagnosis of lung cancer. He had a family history of psoriasis, and although he had previously been noted to have limited plaque and nail psoriasis, this had required minimal treatment. Within 2 months of starting pembrolizumab, he developed scaly, red plaques affecting more than 30% body surface area (BSA). The oncology team diagnosed a grade 3 skin toxicity and increased doses of oral steroids. Upon steroid tapering, the rash flared and was diagnosed in dermatology as consistent with exacerbation of pre-existing plaque psoriasis secondary to pembrolizumab and high-dose steroids. He partially responded to skin-directed treatment, but 2 months later following his sixth cycle of pembrolizumab, he progressed to generalized suberythrodermic pustular psoriasis. He was treated with acitretin and methotrexate. The incidence of ICI-mediated psoriasis and psoriasiform irAEs is approximately 4% of all skin toxicities. A cohort study by the European Network for Cutaneous Adverse Event to Oncologic Drugs group reported that 70% of 115 patients had no history of psoriasis. Ten per cent of psoriasiform irAEs were categorized as severe, involving more than 30% BSA. However, only eight (7%) had pustular involvement and 2% erythroderma. Treatment options include acitretin, methotrexate, apremilast and biologics. Guttate psoriasis and grade 2/3 disease were significant positive predictors for the antitumour response of ICIs. In summary, ICI-related psoriasis is an increasingly common problem with widespread use of immunotherapy. Early diagnosis and adequate management with agents that do not interfere with immunotherapy, or with the underlying malignancy, and close liaison with oncology are crucial.

Clinical Features, Histological Characteristics, and Disease Outcomes of Mycosis Fungoides in Children and Adolescents: A Nationwide Multicentre Cohort of 46 Patients

Background: Our objective was to describe the clinical, histological characteristics, and disease outcome of a cohort of mycosis fungoides (MF) diagnosed during childhood including disease status at adulthood. Methods: This is a retrospective multicentre survey of patients aged under 18 years at diagnosis with histologically confirmed MF. Patients’ clinical and histological characteristics, treatments, and disease outcome (for patients followed for more than 12 months) were analysed. Results: Forty-six patients were included (median age at diagnosis: 11 years; M:F sex ratio: 3:1) with 39 (85%) followed for at least 12 months. Thirty-nine patients (85%) had stage I MF. Hypopigmented patches were observed in 48% and folliculotropism in 43% patients. Immunophenotype of the skin infiltrate was predominantly CD8+ in 17% of patients. Initial management included a wait-and-see strategy in 6/39 (15%), skin-directed treatment in 27 (69%), and systemic treatment in 6 (15%) patients, respectively, with partial or complete clinical response (PR or CR) observed in 28 patients (72%). 14/39 patients (36%) relapsed after initial response. After a median follow-up period of 54 months, disease status at last news was PR or CR in 31/39 (79%), stable disease in 6 (15%), and progression in 2 (5%) patients. Histological transformation was observed in 3/39 (8%). Of the 15 patients followed until adulthood, 13 (87%) had persistent MF. Discussion: This survey confirms the high frequency of hypopigmented and folliculotropic lesions and of CD8+ immunophenotype compared to adult MF patients. The long-term course is usually indolent but transformation may occur sometimes long after disease onset and the disease may persist during adulthood.

Phototherapy and topical treatments for cutaneous graft vs. host disease in haematopoietic stem cell transplantation patients: a scoping review.

Skin is usually the first and most affected organ involved in graft-versus-host disease (GvHD), and treatment is still a clinical challenge. Although the need for skin-directed treatments such as physical treatments and topical medications are generally agreed on, what the gold standard treatment strategy should be remains open to debate. The aim of this scoping review was to synthesize the current knowledge on the topical and physical treatments of cutaneous GvHD in haematopoietic stem cell transplantation patients and to highlight the best evidence available so as to reduce the gap between 'what is known' and 'what is done' in the clinical practice. Twenty-eight studies were included in this qualitative synthesis. Photo-biomodulation with psoralen was not included in this review. Phototherapy (ultraviolet A or B or narrowband B) was the physical treatment most described in the literature in both acute GvHD and chronic GvHD. Topical calcineurin inhibitors such as tacrolimus ointment and pimecrolimus cream as well as corticosteroid creams such as clobetasol and triamcinolone are mainly used in case of chronic GvHD. In all of the studies included in the review, topical treatments were always associated with systemic therapy. None of the topical interventions identified in our review provided strong evidence supporting its use, and the topical approaches seemed to have an adjuvant role in the treatment of cutaneous GvHD.

New developments in skin-directed treatments of cutaneous T-cell lymphoma

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.

An overview of the efficacy of phototherapy in oncodermatology

Cutaneous adverse events (AEs) following cancer immunotherapy, targeted therapy, and chemotherapy have been well-documented in the literature. A number of case reports have identified phototherapy, a form of light therapy that mimics sunlight exposure, as a noninvasive treatment modality for these cutaneous toxicities. By inducing local suppression of the immune system, phototherapy is a skin-directed treatment with minimal effect on tumor response. Phototherapy may therefore be a viable treatment option for cutaneous AEs from cancer therapies. We reviewed the literature for patients treated with phototherapy for cutaneous AEs following cancer immunotherapy, targeted therapy, or chemotherapy. We also included three previously unpublished cases from our own institution. We identified 24 patients (80% male, mean age 67years, range 49-75years). Patients received the following phototherapy types: NB-UVB (n = 17), PUVA (n = 6), or PDT (n = 1). A topical steroid was used in conjunction with phototherapy in seven patients. At phototherapy onset, cancer treatment was either continued, temporarily discontinued, or discontinued (n = 9, 6, 7, respectively; in two cases, the cancer treatment course was unknown). Improvement of cutaneous AEs was observed in 96% of patients. Phototherapy resulted in full or partial improvement in all but one patient. A topical steroid was used in nearly a third of patients, suggesting some oncodermatologists co-administer topicals to further boost response. Continuation of cancer therapy in the majority of patients highlights an additional advantage of phototherapy. We believe phototherapy may be an effective adjunctive treatment to topical steroids when treating these cutaneous toxicities.

Prec-O1-01 - Increased chlormethine induced DNA double stranded breaks in malignant T cells from mycosis fungoides skin lesions

<h3>Background:</h3> Cutaneous T-cell lymphoma (CTCL) is a heterogeneous group of extranodal non-Hodgkin's lymphoma. Mycosis fungoides (MF) is the most common types of CTCL and considered as a malignancy of skin-resident T cells. Chlormethine (CL), also known as mechlorethamine or nitrogen mustard, is a synthetic agent with well-known alkylating capacity. Its topical application has a long tradition in dermatology, as CL-containing products have been used for the treatment of MF since 1940. Recently, a novel CL gel formulation has been approved for the treatment of skin lesions in MF adult patients. <h3>Objective:</h3> Here we aim to study the impact of CL on malignant skin T cells regarding their susceptibility to treatment, proliferation, DNA double strand breaks and the expression of alkylated-nucleotides-excision genes. <h3>Methods:</h3> Tumour blood or skin T cells were isolated by magnetic-activated cell (MACS) sorting. Susceptibility to CL exposure was evaluated by MTT assay. Proliferation and DNA double strand breaks upon CL exposure were detected by BrdU proliferation assay and flowcytometry for γH2AX Ser139. Expression of alkylated-nucleotides-excision genes was measured by reverse transcription quantitative PCR (RT-qPCR). <h3>Results:</h3> While CL exposure in vitro decreased time- and dose-dependently total blood T-cell viability, it did not statistically significantly influence neither blood nor skin T-cell proliferation. Of interest, when acting on skin T cells, CL induce DNA double stranded breaks predominately in the subpopulation of MF clonal malignant skin T cells but not the non-tumoral healthy T cells. Quantitative real-time PCR uncovered that several important genes involved in rescue of alkylated nucleotides were generally decreased in tumor T cells and CL exposure in vitro further significantly decreased the expression of FEN1 and BRCA2, two major alkylated-nucleotides-excision-repair genes. <h3>Conclusion:</h3> This study sheds light on how CL affects malignant skin T cells from patients with MF and provides additional rationale for considering it as an early and valuable skin-directed treatment option for skin lymphoma.

Treatment of mycosis fungoides: results from a large international study

British Journal of DermatologyVolume 184, Issue 4 p. e129-e129 Plain Language Summary Treatment of mycosis fungoides: results from a large international study First published: 09 April 2021 https://doi.org/10.1111/bjd.19840AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat Abstract Mycosis fungoides is a type of blood cancer. The early phases of mycosis fungoides are represented by patches (flat lesions) or plaques (solid lesions) on the skin. Treatment usually consists of topical steroid creams, phototherapy (using ultraviolet light) or radiotherapy (using radiation). Together these methods are called skin-directed treatments. This study enrolled 395 patients with a new diagnosis of mycosis fungoides from 41 centres across 17 countries in Europe, North and South America, and Australia. The results show that the majority of patients (82%) received skin-directed treatment as the first medication, while 11% first received tablets or injections. Patients who were treated first with tablets or injections showed more severe disease, plaques more frequently than patches, thicker skin lesions, and mycosis fungoides involving hair follicles. The presence of plaques was associated with a worse outcome and lower response to therapy. We also showed that half of these patients had significantly reduced quality of life, which improved after treatment. The proportion of patients who achieved a complete or partial clearance of the skin lesions was 67%. Overall, 73% more people receiving skin-directed treatments responded to therapy than those receiving tablets or injections. This means that it is generally preferable to start therapy with skin-directed treatment in most cases. This study suggests that treatment of patients with early-stage mycosis fungoides should focus on patients with high-risk skin features and evaluation of quality of life. Linked Article: Quaglino et al. Br J Dermatol 2021; 184:722–730. Volume184, Issue4April 2021Pages e129-e129 RelatedInformation

Cutaneous T-cell lymphoma: practical recommendations to enhance clinical practice.

Management of cutaneous T-cell lymphoma should provide a holistic approach to a patient's wellbeing. Treatments depend on the stage of lymphoma. Patients with the early stages tend to have a near-normal life expectancy. Management should be aimed at improving the extent of disease and reducing symptoms with minimal therapeutic adverse effects. Skin-directed treatments are preferred and may be used in combination with treatments for symptom relief such as anti-pruritic medication. In advanced stages of disease where the median life expectancy is reduced the aims are also to prevent disease progression and prolong life, and this requires a multidisciplinary approach. Symptom control remains important as patients often have painful, itchy disfiguring lesions which greatly impact on health-related quality of life. National and international guidelines provide stage-related treatment options to be considered with first-line options followed by subsequent second-line therapies. All are listed in no particular order of preference and are chosen according to patients' needs and expertise of the treating centre. Several first-line options may be chosen before moving to the second-line options. Three drugs received European Medicines Agency approval in 2017 and 2018 (chlormethine gel, brentuximab and mogamulizumab) but there still remains an unmet need for more improved treatments or combinations. Most treatments only result in a partial response and there is no cure for early-stage disease; as such, patients live for a long time with their disease. In the advanced stages if a good response is achieved eligible patients will be considered for an allogeneic haematopoietic stem cell transplant.

15469 Retrospective review of 87 patients with classic Kaposi sarcoma: Clinical features, symptomatology, and outcomes

Introduction: Classic Kaposi sarcoma (CKS), an HHV-8–associated lymphoangioproliferative disease, is typically indolent, but can be a progressive condition, causing pain, ulceration, disfigurement, and significantly affecting quality of life. Treatment approach includes observation and skin-directed treatment in limited disease and systemic therapy in symptomatic or multifocal disease. This study summarizes the clinical characteristics and treatments of our CKS patients and identifies any prognostic factors that influence outcome.

Development of a scoring system to predict outcomes of i.v. corticosteroid pulse therapy in rapidly progressive alopecia areata adopting digital image analysis of hair recovery.

Alopecia areata (AA) is a common autoimmune disease manifesting varying degrees of hair loss. Rapidly progressive AA (RP-AA) is a severe subtype of AA and often resistant to skin-directed treatments. i.v. corticosteroid pulse therapy has been applied for RP-AA; however, the treatment outcome can only become evaluable several months after the intervention, discomposing the patients. In this study, we attempted to develop a scoring system to predict treatment outcomes based on statistical correlations between newly identified predictors and the recovery rates calculated by digital image analysis. Thirty RP-AA patients (15 men and 15 women) who underwent pulse therapy and demonstrated total hair loss during the clinical course were included. The percentages of hair regrowth (%HR) at 6months after the treatment were quantitatively calculated by image analysis software. The correlation between %HR and clinicopathological and immunological variables were statistically assessed. The analysis identified four confirmatory contributors including female sex (P=0.015), absence of previous AA history (P=0.02), lower peripheral blood eosinophil count (P=0.02) and mild to moderate cell infiltration around the hair bulb (P=0.034), together with a potential contributor, namely absence of atopic dermatitis in their medical history (P=0.08). The scoring system was developed by double counting confirmatory variables and single counting a potential variable. Importantly, the scores obtained by this system demonstrated significant correlation with %HR (r=0.61, P<0.001). The usefulness of this scoring system was further validated by assessing additional 20 cases of RP-AA. When combined with a recently published algorithm for early detection of self-healing subset, the current scoring system may help strategize the therapeutic approach for RP-AA.

Cutan T-sejtes lymphomák bőrre irányuló kezelése (skin directed treatment) egy eset kapcsán

Cutaneous T-cell lymphomas are rare diseases with significant differences in their clinical course and prognosis. The choice of treatment basically depends on the stage, in the early stages of the disease only skin directed treatment is recommended. With most of the treatment modalities, complete cure is not possible, only long-term remission can be achieved. The authors report the case of a 52-year-old female patient who developed extensive annular, erythematous, infiltrated plaques in the spring of 2019. Histological examination confirmed mycosis fungoides, imaging did not show lymph node or other organ involvement. Given the disease (stage IB), PUVA treatment was initiated. After a total of 21 sessions of phototherapy from September 2019, the patient underwent complete remission. The authors provide a detailed review of skin directed treatment options for mycosis fungoides based on current international recommendations.

Chemical-Associated Vitiligo

An otherwise healthy man in his 40s presented with white macules and patches that appeared on his skin several years ago. Initially, he noticed asymptomatic white discoloration on the ventral aspect of wrists, with subsequent involvement of thehead and neck. He had no relevant medical, drug, or family history, except for thyroid dysfunction in his mother. He worked in a laundry facility, with frequent exposure to detergents. Examination revealed well-demarcated hypopigmented patches without erythema or scaling on the ventral forearms (Figure 1). One patch on the occipital area scalp showed white discoloration of the associated hair (Figure 2). Wood's lamp examination showed no accentuation. Based on the patient’s history of exposure by frequently implicated chemicals, as well as the morphology and distribution of skin lesions, a diagnosis of chemical-associated vitiligo was made.Figure 2Well-defined coalescing hypopigmented patches on ventral forearm.View Large Image Figure ViewerDownload Hi-res image Download (PPT) Chemical-associated vitiligo, an acquired disorder that presents with hypo- or depigmented patches, is thought to be induced by repeated exposure to specific chemicals.1Harris J.E. Chemical-induced vitiligo.Dermatol Clin. 2017; 35: 151-161Abstract Full Text Full Text PDF PubMed Scopus (55) Google Scholar Several chemical compounds have been implicated, most of which contain phenol groups in their chemical structure. Because the phenol group constitutes a part of the amino acid tyrosine, the precursor of melanin, it has been hypothesized that phenol-containing compounds act as tyrosine analogs when applied to the skin, thereby interfering with melanogenesis.1Harris J.E. Chemical-induced vitiligo.Dermatol Clin. 2017; 35: 151-161Abstract Full Text Full Text PDF PubMed Scopus (55) Google Scholar Others have hypothesized that depigmenting chemicals produce metabolites that are toxic to melanocytes or overwhelm the melanocyte ability to withstand oxidative stress.2Boissy R.E. Manga P. On the etiology of contact/occupational vitiligo.Pigment Cell Res. 2004; 17: 208-214Crossref PubMed Scopus (207) Google Scholar In cases of occupational exposure, as in our patient, the hands and forearms are frequently involved. However, some reports demonstrated that lesions could appear in remote areas: that is, those not in direct contact with chemical substances.3Bonamonte D. Vestita M. Romita P. Filoni A. Foti C. Angelini G. Chemical leukoderma. dermatitis: contact, atopic, occupational, drug.Dermatitis. 2016; 27: 90-99Crossref PubMed Scopus (16) Google Scholar This observation has led to invocation of the autoimmune theory, proposing that chemical-induced stress in melanocytes initiates an autoimmune response, leading to their destruction. Subsequently, this immune response can affect other melanocytes in distant regions that are not directly in contact with the chemical.1Harris J.E. Chemical-induced vitiligo.Dermatol Clin. 2017; 35: 151-161Abstract Full Text Full Text PDF PubMed Scopus (55) Google Scholar By contrast, idiopathic vitiligo commonly affects the periorificial areas, nipples, and genitals. Chemical-associated vitiligo represents a diagnostic challenge, as it is often difficult to differentiate it from idiopathic vitiligo based on the clinical as well as the histopathological presentation.1Harris J.E. Chemical-induced vitiligo.Dermatol Clin. 2017; 35: 151-161Abstract Full Text Full Text PDF PubMed Scopus (55) Google Scholar The presence of 3 out of the following 4 criteria are considered sufficient for establishing the diagnosis of chemical-associated vitiligo: acquired vitiligo-like depigmented lesion(s), history of repeated exposure to specific chemical compounds, patterned vitiligo-like macules at site of exposure, and confetti macules.4Ghosh S. Mukhopadhyay S. Chemical leucoderma: a clinico-aetiological study of 864 cases in the perspective of a developing country.Brit J Dermatol. 2009; 160: 40-47Crossref PubMed Scopus (69) Google Scholar Thorough history taking is essential to diagnose chemical-associated vitiligo and identify the possible culprit. Presumably, chemical-associated vitiligo does not confer the same increase in associated autoimmune conditions as does idiopathic vitiligo, although this is not well studied.5Gill L. Zarbo A. Isedeh P. Jacobsen G. Lim H.W. Hamzavi I. Comorbid autoimmune diseases in patients with vitiligo: a cross-sectional study.J Am Acad Dermatol. 2016; 74: 295-302Abstract Full Text Full Text PDF PubMed Scopus (89) Google Scholar In many cases, strict avoidance of the offending chemical agent allows the condition to self-resolve. Moreover, chemical-associated vitiligo tends to respond better to skin-directed treatments than idiopathic vitiligo.1Harris J.E. Chemical-induced vitiligo.Dermatol Clin. 2017; 35: 151-161Abstract Full Text Full Text PDF PubMed Scopus (55) Google Scholar

Romidepsin Plus Liposomal Doxorubicin Is Safe and Effective in Patients with Relapsed or Refractory T-Cell Lymphoma: Results of a Phase I Dose-Escalation Study

The histone deacetylase (HDAC) inhibitor romidepsin and the anthracycline liposomal doxorubicin (LD) have modest single-agent activity in cutaneous T-cell lymphoma (CTCL) and peripheral T-cell lymphoma (PTCL). We investigated the safety and efficacy of the combination of these two agents in CTCL and PTCL. Using CTCL cell lines and primary CTCL tumor cells, we demonstrated synergistic antitumor activity with romidepsin plus doxorubicin. We then conducted a phase I dose-escalation study of the romidepsin/LD combination in relapsed/refractory CTCL and PTCL. The primary objective was to determine the MTD of romidepsin in combination with LD at 20 mg/m2 i.v., once every 28 days. Eleven patients with CTCL and 12 patients with PTCL were treated. The MTD of romidepsin was determined to be 12 mg/m2. Grade 3/4 hematologic toxicities included thrombocytopenia (17%), anemia (13%), and neutropenia (9%). The most frequent treatment-related nonhematologic adverse events were fatigue (48%), nausea (48%), vomiting (35%), and anorexia (30%). Among 21 evaluable patients, the overall response rate was 70% [1 complete response (CR), 6 partial responses (PR)] in CTCL and 27% (3 CR, 0 PR) in PTCL. Of the patients with CTCL, 8 of 10 had skin response, including 6 patients (60%) achieving skin involvement less than 10% of their body surface area at time of best response. Romidepsin plus LD demonstrated an acceptable safety profile and promising clinical efficacy with deep skin responses in relapsed/refractory CTCL. Thus, this combination could be considered as a bridge to skin-directed treatment or allogeneic hematopoietic cell transplantation in patients with aggressive CTCL.

Cost of early-stage mycosis fungoides treatments in Spain.

AimTo identify the most common therapeutic options for the treatment of early-stage mycosis fungoides in Spain, quantify their associated healthcare resource use and costs.MethodsAfter reviewing the literature, a panel of 6 Spanish clinical dermatologists validated the treatments and healthcare resource use through a structured questionnaire. Individual responses were collected, analyzed and presented into a face-to-face meeting in order to reach a consensus. Cost categories considered were: drug acquisition and administration, photo/radiotherapy session and maintenance, clinical follow-up visits and laboratory tests. Costs were expressed in euros from 2018. The Spanish National Health System perspective was considered, taking into account direct health costs and time horizons of 1, 3 and 6 months.ResultsCosts for the skin-directed treatments (SDT) assessed at 1, 3 and 6 months, were: Topical carmustine [€6,593.36, €19,780.09 and €27,592.78]; Phototherapy with psoralens and ultraviolet A light (PUVA) [€1,098.68, €2,999.99 and €3,187.60]; Narrow-band ultraviolet B phototherapy [€1,657.47, €4,842.10 and €4,842.10]; Total skin electron beam therapy (TSEBT) [€6,796.45, €7,913.34 and €7,913.34]. Cost for topical corticosteroids, being considered an adjuvant option, were €17.16, €51.49 and €102.97. Costs for the assessed systemic treatments alone or in combination with SDT at 1, 3 and 6 months, were: Systemic retinoids [€2,026.03, €5,206.63 and €7,426.42]; Systemic retinoids + PUVA phototherapy [€3,066.50, €8,271.26 and €10,046.58]; Interferon alfa + PUVA phototherapy [€1,541.09, €5,167.57 and €6,404.55].ConclusionAccording to the Spanish clinical practice, phototherapies in monotherapy were the treatments with the lowest associated costs regardless of the time horizon considered. TSEBT turned out as the treatment with the highest associated costs when considering 1 month. However, while considering 3 and 6 months the treatment with the highest associated costs was topical carmustine. The results of this analysis may provide critical information to measure the disease burden, to detect unmet medical needs and to advocate towards better treatments for this rare disease.

Radiotherapy Eradicates Malignant T Cells and Is Associated with Improved Survival in Early-Stage Mycosis Fungoides.

Mycosis fungoides is the most common subtype of cutaneous T-cell lymphoma. Skin-directed treatments often improve but do not cure mycosis fungoides skin lesions. The purpose of this study was to (i) assess whether remission was associated with malignant T-cell clone depletion at treated sites using either low-dose radiotherapy (LDRT, 8 Gy) or topical steroids and (ii) assess whether a clone-ablative therapy, like LDRT, is associated with overall survival in patients with high-risk early-stage CTCL. Pre- and posttreatment biopsies from 20 lesional skin samples of 18 patients with mycosis fungoides who received either 8 Gy LDRT (n = 16) or topical steroids (n = 4) underwent high-throughput T-cell receptor sequencing of the TCRB gene to quantify the malignant T-cell clone. For the retrospective chart review, overall survival of 47 high-risk early-stage patients was compared between patients who did or did not receive radiation. LDRT eradicated the clone in 5 of 16 lesions and reduced it >90% in 11 of 16; there were no recurrences in these lesions. Patients treated with topical steroids appeared to clinically improve, but the malignant clone persisted. We found that the number of residual malignant T cells predicted lesion recurrence. A retrospective review showed that early-stage high-risk patients who received radiation as part of their treatment regimen had prolonged overall survival compared with patients who did not. These findings demonstrate that LDRT can eradicate malignant T cells in mycosis fungoides, provides robust disease control, and is associated with improved survival in high-risk early-stage patients.

Cutaneous lymphomas : Clinical presentation- diagnosis- treatment

Cutaneous lymphomas comprise different subgroups with distinct biological behavior. Mycosis fungoides, the most common cutaneous lymphoma, presents with patches, plaques, tumors and erythroderma. Therapeutic options depend on stage and comprise local skin-directed treatment in early stages, while later stages and Sézary syndrome require systemic therapies including bexarotene, interferon or brentuximab vedotin. While the rare CD4-positive lymphoproliferation and acral CD8-positive lymphoma present with an invariably indolent course, cutaneous peripheral T‑cell lymphomas exhibit an aggressive clinical behavior. Among the subgroup of cutaneous B‑cell lymphomas, primary cutaneous marginal zone lymphoma and follicle center cell lymphoma belong to indolent entities with almost unrestricted overall survival, whereas cutaneous large B‑cell lymphoma presents with asignificant risk of systemic dissemination and is associated with high lethality.

Evidence-based, Skin-directed Treatments for Cutaneous Chronic Graft-versus-host Disease.

Chronic graft-versus host disease (cGVHD) occurs in 30% to 70% of patients undergoing allogeneic hematopoietic cell transplantation (HCT). Cutaneous cGVHD affects 75% of cGVHD patients, causing discomfort, limiting the range of movement, and increasing the risk of wound infections. Furthermore, systemic immunosuppression is often needed to treat cGVHD and long-term use can lead to adverse events. Optimal use of skin-directed therapies is integral to the management of cutaneous cGVHD and may decrease the amount of systemic immunosuppression required.This study reviewed English-language articles published from 1990 to 2017 that evaluated the effect of skin-directed treatments for cutaneous cGVHD. A total of 201 papers were identified, 164 articles were screened, 46 were read, and 18 publications were utilized in the review. Skin-directed treatments for cGVHD included topical steroids, topical calcineurin inhibitors, psoralen with ultraviolet A (PUVA) irradiation, ultraviolet A1 (UVA1) irradiation, and ultraviolet B (UVB) irradiation. We report the number of complete remissions, partial remissions, and systemic immunosuppression reduction in each study, as available.Twenty-two out of 30 (73.3%) patients experienced overall improvement with topical calcineurin inhibitors. At least 26 out of 76 patients (34.2%) receiving PUVA experienced complete remission, and 30 out of 76 patients (39.5%) experienced partial remission. In UVA1 studies, 44 out of 52 (84.6%) patients experienced overall improvement. In UVB studies, nine out of 14 patients (64.3%) experienced complete remission and four out of 14 patients (28.6%) experienced partial remission.As more HCTs are performed, more individuals will develop cGVHD. Awareness and optimal use of skin-directed therapies for cutaneous cGVHD may help improve patient outcomes and quality of life.

Lack of Durable Remission with Conventional-Dose Total Skin Electron Therapy for the Management of Sezary Syndrome and Multiply Relapsed Mycosis Fungoides.

Mycosis fungoides (MF) and Sezary syndrome (SS) are multi-relapsing, morbid, cutaneous T-cell lymphomas. Optimal treatment sequencing remains undefined. Total skin electron therapy (TSE) is a highly technical, skin-directed treatment, uniquely producing symptom-free and treatment-free intervals. Recent publications favour low-dose TSE for reduced toxicity, but early data support conventional-dose TSE (cdTSE) for longer disease control. Patient selection requires weighing-up tolerability against response durability. We investigated duration of benefit from cdTSE in patients with poorer prognosis diseases: SS and heavily pre-treated MF. Endpoints were overall survival, and “time to next treatment” (TTNT) as surrogate for clinical benefit duration. Seventy patients (53 MF, 17 SS) were eligible: median prior treatments, 4; median cdTSE dose, 30 Gy; median follow-up, 5.8 years. SS patients had worse prognosis (HR = 5.0, p < 0.001) and shorter TTNT (HR = 4.5, p < 0.001) than MF patients; median TTNT was only 3.7 months. Heavily pre-treated MF patients had inferior prognosis (HR = 1.19 per additional line, p = 0.005), and shorter TTNT (HR = 1.13 per additional line, p = 0.031). Median TTNT for MF patients with ≥3 prior treatments was 7.1 months, versus 23.2 months for 0–2 prior treatments. In conclusion, cdTSE has a limited role in SS. TTNT is reduced in heavily pre-treated MF patients, suggesting greater benefit when utilized earlier in treatment sequencing.

Electrochemotherapy for advanced cutaneous angiosarcoma: A European register-based cohort study from the International Network for Sharing Practices of electrochemotherapy (InspECT).

Cutaneous angiosarcoma (cAS) is a highly aggressive malignancy that challenges the radicality of surgical treatment. Electrochemotherapy (ECT), a skin-directed treatment based on cytotoxic chemotherapy combined with local electric pulses, may be an intraoperative adjunct and a new opportunity in the therapeutic strategy. This cohort study reports the experience with ECT as an option. Data on patients with locally-advanced/metastatic cAS who underwent ECT between October 2013 and October 2018 at eight European centres were prospectively submitted to the InspECT (International network for sharing practices of ECT) register. Patients received therapy according to the European Standard Operating Procedures of ECT (ESOPE). Treatment feasibility was assessed based on tumour coverage with electrodes and recorded tissue current; treatment toxicity and tumour response were graded according to CTCAE v5.0 and RECIST v1.1 criteria, respectively; patient-reported outcomes (PRO) were evaluated using a visual analogue score (VAS) for pain, acceptance of retreatment and the EQ-5D questionnaire. We enrolled 20 patients with advanced cAS in the scalp/face (n = 7), breast/trunk (n = 10) or limbs (n = 3). Target tumours (n = 51) had a median size of 2.3 cm (range, 1-20). We administered 24 ECT courses using 1-4 cm treatment safety margin around tumours. In five patients, ECT was combined/sequenced with surgery. Median tissue current was 3 A (range, 1.5-10), tumour margins coverage rate was 75% (15/20 patients). The objective response rate (ORR) was 80% (complete, 40%). Grade-3 toxicity included skin ulceration (15%) and pain (10%), with no significant change of PRO scores. Bleeding control was achieved in 13/14 patients with ulcerated tumours. With a median overall survival of 12.5 months, the local progression-free survival (LPFS) was 10.9 months. ECT produces sustained response rate with minimal side effects and should be considered an option for advanced cAS. Palliative benefits include patient tolerability, local haemostasis and durable local control. Definition of optimal timing, treatment safety margins and combination with surgery need further investigation.