Tumour regression predicts better response to interferon therapy in melanoma patients: a retrospective single centre study.

We hypothesise that regression may have an impact on the effectiveness of adjuvant IFN therapy, based on its role in the host immune response. Our purpose is to investigate regression and ulceration as prognostic factors in case of interferon-alpha (IFN)-treated melanoma patients. We followed 357 IFN-treated melanoma patients retrospectively, investigating progression-free survival (PFS) and overall survival (OS) depending on the presence of ulceration and regression. A Kaplan-Meier analysis was performed, and we used a Cox regression analysis to relate risk factors. The survival function of the Cox regression was used to measure the effect of regression and ulceration on PFS and OS depending on the Breslow thickness (T1-T4) of the primary tumour. Regression was significantly positively related to PFS ( P  = 0.0018, HR = 0.352) and OS ( P  = 0.0112, HR = 0.380), while ulceration showed a negative effect (PFS: P  = 0.0001, HR = 2.629; OS: P  = 0.0003, HR = 2.388). They influence survival independently. The most favourable outcome was measured in the regressed/non-ulcerated group, whereas the worse was in the non-regressed/ulcerated one. Of risk factors, Breslow thickness is the most significant predictor. The efficacy of regression is regardless of Breslow thickness, though the more favourable the impact of regression was in the thicker primary lesions. Our results indicate that regression is associated with a more favourable outcome for IFN-treated melanoma patients, whereas ulceration shows an inverse relation. Further studies are needed to analyse the survival benefit of regression in relation to innovative immune checkpoint inhibitors.

Survival Benefit of Stereotactic Radiotherapy in the Complex Management of Metastatic Melanoma.

BACKGROUND/AIM: Targeted therapy and immunotherapy, with additional stereotactic radiation therapy (SRT) have revolutionized the management of metastatic malignant melanoma (mMM). We aimed to analyze the effectiveness and safety of SRT and determine its role in the complex management of mMM. PATIENTS AND METHODS: We treated 24 patients with solitary metastasis, 15 with oligometastatic disease and one with multiple metastases. The primary endpoint was to investigate the possible effect of stereotactic radiotherapy for metastatic lesions on patients' survival taking the systemic therapy into consideration. RESULTS: The median overall survival (OS) for the entire group was 30.07 months; 50% of them received immunotherapy, 32% received targeted therapy. Complete remission of the irradiated lesions was observed in six patients, partial tumor response was achieved in 13, while stable disease was detected in 10; tumor progression occurred in four cases. Compartmental recurrence (recurrence in the brain in a not previously irradiated region) developed in seven patients. OS was significantly longer in those with extracranial metastases treated with stereotactic body radiotherapy in comparison to brain SRT. We found a strong correlation between tumor response and mean OS (42.5 months after complete or partial remission versus 11.8 months in those with stable or progressive disease). No OS difference was observed according to the number of irradiated lesions or type of systemic therapy before SRT (no therapy: 43.6 months, with therapy: 25.7 months). Significant OS advantage was shown when immunotherapy was administered post-SRT (mean OS: with immunotherapy: 39.6 months, no immunotherapy: 18.5 months). CONCLUSION: In the case of oligometastatic MM, SRT can be used safely and with good efficiency in addition to targeted therapy/anti-programmed cell death protein 1 therapy. Improved survival warrants including SRT in the complex management of mMM, however, further studies are needed for SRT optimization.

[Electrochemotherapy for multiple cutaneous tumors in immunosuppressed patients]. / Immunszupprimált betegek multiplex bordaganatainak elektrokemoterápiás kezelése.

INTRODUCTION: The risk of cutaneous malignancies is significantly higher in immunosuppressed patients compared to the general population. These high-risk skin tumors tend to be aggressive, multiplex, rapidly growing lesions. It is common to see local recurrence after surgical excision. Multiplex tumors are difficult to treat, especially in the head/neck region. OBJECTIVE: Amongst the standard treatment options, electrochemotherapy can be a suitable option. Our aim was to evaluate the efficacy of electrochemotherapy in immunocompromised patients. METHOD: In 9 immunosuppressed patients, 118 (average: 13, n = 5-27) non-melanoma skin tumors were treated with electrochemotherapy with intravenous administration of bleomycin, according to the ESOPE criteria. RESULTS: The median follow-up was 15 months. 6 months after the treatment, the objective response rate was 96%. We observed complete response in 88%, partial response in 8% and progressive disease in 2% of the treated lesions. In 2%, the response was not evaluable. CONCLUSION: In immunocompromised patients, electrochemotherapy is an effective and safe therapeutic option for non-melanoma skin tumors. In order to provide more ideal management for this special sub-group, prevention, multidisciplinary approach and optimized immunosuppressive therapy is essential. Orv Hetil. 2023; 164(37): 1462-1468.

Challenges in the Complex Management of Neglected Cutaneous Melanomas in the Head and Neck Area: A Single Center Experience.

Familiar controversies in the management of head and neck melanomas are more remarkable in locally advanced cases, and they represent a treatment challenge both surgically and oncologically. In our retrospective study, patients with surgically treated primary malignant melanoma of the head and neck region larger than 3 cm in diameter were included. Five patients met our inclusion criteria. In all cases, wide excision and immediate reconstruction were performed without sentinel lymph node biopsy. The defect on the scalp was covered by a split skin graft, with local flaps chosen for reconstruction on the face on an individual basis. After a 2-6 year follow-up, a good oncological, functional, and esthetic result was achieved. Our results show that in the case of large, locally advanced melanomas, surgical treatment still plays a crucial role that can provide long-term local control and support the effect of systemic treatment.

Innovation in the treatment of non-melanoma skin cancer: daylight photodynamic therapy / Új eljárás a nem melanoma típusú bordaganatok kezelésében: "daylight" fotodinámiás terápia

Introduction: Photodynamic therapy is indicated for the treatment of superficial basal cell carcinoma, Bowen's disease and actinic keratosis. Reactive oxygen radicals are released from the metabolite of the topically applied photosensitizer that is excited by light, which selectively leads to the destruction of tumor cells. The procedure can be performed with an artificial light source or with the use of sunlight. The latter is called daylight photodynamic therapy, which is an effective and painless procedure. Objective: Our aim was to introduce daylight photodynamic therapy in actinic keratoses at our department and to optimize the treatment protocol for the local climatic conditions. Method: Three clinical trials were performed. The difference between the treatment protocols was between the incubation time of the photosensitizer on the skin and in the time patients spent under the sunlight. Results: When using the international treatment protocol, 73% of the actinic keratoses showed complete, while 27% partial remission. By reducing the proportion of time patients spent outdoor, complete remission was achieved in

A Randomized Controlled Trial with a Medical Device Containing Sodium Hyaluronate and Nicotinic Acid to Increase the Efficacy of Ultraviolet Phototherapy in Psoriasis.

INTRODUCTION: The dry and scaly skin of psoriatic patients decreases the efficacy of ultraviolet B (UVB) phototherapy. Different agents are used to facilitate the transmission of light, but most of these preparations are cosmetically unfavorable. We have tested a novel preparation containing sodium hyaluronate and nicotinic acid (UV Fotogel®; Pernix Ltd.) with the double aim to improve the efficacy of UVB phototherapy and assess the cosmetic acceptability of the preparation. METHODS: Ninety patients with plaque psoriasis were enrolled in the study, of whom 44 received narrow-band UVB (NB-UVB) phototherapy. Prior to phototherapy, one side of the patient's body was treated with UV Fotogel while the other side served as a control. The other 46 patients used the preparation at their homes before regular sunbathing. The Local Psoriasis Severity Index (L-PSI), cosmetic acceptability and tolerability were recorded. The median values with the 25th and 75th percentiles (25p and 75p, respectively) were determined for the UV Fotogel-treated and control sites and then compared. RESULTS: The sides of the body to which UV Fotogel was applied prior to NB-UVB phototherapy had a significantly lower median L-PSI score than the non-treated control sides at the end of the treatment (1.0 [25p-75p: 0.0-2.0] vs. 2.0 [1.0-3.0], respectively). The application of UV Fotogel prior to sunbathing also led to a significant decrease in L-PSI score. There was a significant reduction in the median L-PSI score of patients at the final visit compared to baseline (2.5 [25p-75p: 1.5-3.5] vs. 6.0 [6.0-7.0], respectively). Use of the preparation was not accompanied by considerable adverse effects, and the patients found it cosmetically acceptable. Application of UV Fotogel prior to sunbathing was well tolerated by the patients, and the cosmetic acceptability was also good. CONCLUSION: UV Fotogel is potentially a useful device for enhancement of the efficacy of phototherapy in patients with psoriasis.

A comprehensive analysis of coding and non-coding transcriptomic changes in cutaneous squamous cell carcinoma.

Cutaneous Squamous Cell Carcinoma (cSCC) is the most common and fastest-increasing cancer with metastatic potential. Long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs) are novel regulators of gene expression. To identify mRNAs, lncRNAs and circRNAs, which can be involved in cSCC, RNA-seq was performed on nine cSCCs and seven healthy skin samples. Representative transcripts were validated by NanoString nCounter assays using an extended cohort, which also included samples from pre-cancerous skin lesions (actinic keratosis). 5,352 protein-coding genes, 908 lncRNAs and 55 circular RNAs were identified to be differentially expressed in cSCC. Targets of 519 transcription factors were enriched among differentially expressed genes, 105 of which displayed altered level in cSCCs, including fundamental regulators of skin development (MYC, RELA, ETS1, TP63). Pathways related to cell cycle, apoptosis, inflammation and epidermal differentiation were enriched. In addition to known oncogenic lncRNAs (PVT1, LUCAT1, CASC9), a set of skin-specific lncRNAs were were identified to be dysregulated. A global downregulation of circRNAs was observed in cSCC, and novel skin-enriched circRNAs, circ_IFFO2 and circ_POF1B, were identified and validated. In conclusion, a reference set of coding and non-coding transcripts were identified in cSCC, which may become potential therapeutic targets or biomarkers.

Evaluation of Calcium Electroporation for the Treatment of Cutaneous Metastases: A Double Blinded Randomised Controlled Phase II Trial.

Calcium electroporation (Ca-EP) is a new anticancer treatment providing similar features to electrochemotherapy (ECT). The aim of our study is to compare the efficacy of Ca-EP with bleomycin-based ECT. This double-blinded randomized controlled phase II study was conducted at the Medical University of Szeged, Hungary. During this once only treatment up to ten measurable cutaneous metastases per patient were separately block randomized for intratumoral delivery of either calcium or bleomycin, which was followed by reversible electroporation. Tumour response was evaluated clinically and histologically six months after treatment. (ClinicalTrials.gov: NCT03628417, closed). Seven patients with 44 metastases (34 from malignant melanoma, 10 from breast cancer) were included in the study. Eleven metastases were taken for biopsies, and 33 metastases were randomised and treated once. The objective response rates were 33% (6/18) for Ca-EP and 53% (8/15) for bleomycin-based ECT, with 22% (4/18) and 40% (6/15) complete response rates, respectively. The CR was confirmed histologically in both arms. Serious adverse events were not registered. Ulceration and hyperpigmentation, both CTCA criteria grade I side effects, were observed more frequently after bleomycin-based ECT than for Ca-EP. Ca-EP was non-inferior to ECT, therefore, it should be considered as a feasible, effective and safe treatment option.

Electrochemotherapy in the treatment of locally advanced or recurrent eyelid-periocular basal cell carcinomas.

There is increasing evidence about the effectiveness of electrochemotherapy (ECT) in the treatment of basal cell carcinomas in the head and neck region, although its role in the management of eyelid-periocular skin tumors has to be clarified. The aim of the present study is to evaluate the results of ECT in the treatment of locally advanced primary and recurrent eyelid-periocular skin basal cell carcinomas. Twelve patients with basal cell carcinoma involving the eyelid-periocular skin region were treated with ECT. Three patients had locally advanced primary tumors, while 9 patients had recurrent tumors. All treatments were performed according to the ESOPE guidelines, using Cliniporator TM device. All patients received bleomycin based ECT. The route of administration was intratumoral in 3 patients and intravenous in 9 patients. Tumor response was evaluated using the RECIST 1.1. criteria. ECT resulted in complete response of the periocular skin tumors in all patients. Lower eyelid ectropion was developed in 3 patients which had to be corrected surgically. ECT can be used effectively in the treatment of locally advanced or recurrent basal cell carcinomas in the eyelid-periocular skin region. Excellent tumor control can be achieved with good functional and cosmetic results without systemic adverse events with short interval follow-up.

Association of Skin Examination Behaviors and Thinner Nodular vs Superficial Spreading Melanoma at Diagnosis.

Importance: Early melanoma detection strategies include skin self-examination (SSE), physician skin examination (PSE), and promotion of patient knowledge about skin cancer. Objective: To investigate the association of SSE, PSE, and patient attitudes with the detection of thinner superficial spreading melanoma (SSM) and nodular melanoma (NM), the latter of which tends to elude early detection. Design, Setting, and Participants: This cross-sectional, questionnaire-based, multicenter study identified patients with newly diagnosed cutaneous melanoma at 4 referral hospital centers in the United States, Greece, and Hungary. Among 920 patients with a primary invasive melanoma, 685 patients with SSM or NM subtype were included. Interventions: A standardized questionnaire was used to record sociodemographic information, SSE and PSE practices, and patient perceptions in the year prior to diagnosis. Main Outcomes and Measures: Data were analyzed according to histologic thickness, with a 2-mm cutoff for thinner SSM and NM. Results: Of 685 participants (mean [SD] age, 55.6 [15.1] years; 318 [46%] female), thinner melanoma was detected in 437 of 538 SSM (81%) and in 40 of 147 NM (27%). Patients who routinely performed SSE were more likely to be diagnosed with thinner SSM (odds ratio [OR], 2.61; 95% CI, 1.14-5.40) but not thinner NM (OR, 2.39; 95% CI, 0.84-6.80). Self-detected clinical warning signs (eg, elevation and onset of pain) were markers of thicker SSM and NM. Whole-body PSE was associated with a 2-fold increase in detection of thinner SSM (OR, 2.25; 95% CI, 1.16-4.35) and thinner NM (OR, 2.67; 95% CI, 1.05-6.82). Patient attitudes and perceptions focusing on increased interest in skin cancer were associated with the detection of thinner NM. Conclusions and Relevance: Our findings underscore the importance of complementary practices by patients and physicians for the early detection of melanoma, including regular whole-body PSE, SSE, and increased patient awareness.

[Factors influencing early detection of malignant melanoma]. / A melanoma malignum korai felismerését befolyásoló tényezok.

INTRODUCTION AND AIM: Melanoma is a highly aggressive tumour with often unpredictable outcome. Our aim with this study was to determine factors influencing early detection of melanoma. METHOD: We analyzed 139 questionnaires completed by patients diagnosed with melanoma. RESULTS: We found that our patients are health-conscious regarding cardiovascular diseases and attend cancer screenings on recall. However, their knowledge about melanoma is insufficient. Most of them perform skin self-examination, but they do not know what to check. Melanoma is detected mostly by the patients themselves, but it takes more than one year to consult a doctor. Our study confirmed that patients' attitude toward melanoma is an important factor influencing early detection. We found that physical examination and communication about skin cancer prevention is not part of the routine medical care. CONCLUSIONS: It is important to improve knowledge about melanoma among the general population and health care providers and to emphasize that early detection can save lives. Orv. Hetil., 2016, 157(51), 2028-2033.

Successful treatment of multiple basaliomas with bleomycin-based electrochemotherapy: a case series of three patients with Gorlin-Goltz syndrome.

Gorlin-Goltz syndrome is a rare multisystemic disease, characterized by numerous basal cell carcinomas. The ideal approach for patients with the syndrome would be a treatment with a high cure rate, minimal scarring, short healing time and mild side-effects. Electrochemo-therapy is a novel therapeutic option that ablates tumours with electrical current and simultaneously administered anticancer drugs. Three patients with Gorlin-Goltz syndrome were treated with electrochemotherapy using intravenous bleomycin. Clinical response was obtained in 98 (99%) of the lesions, 86 (87%) of them showed complete response. In 2 tumours, regression was confirmed with histological examination. Long-term cosmetic results were excellent. We consider electrochemotherapy to be an additional tool in the therapeutic armamentarium for Gorlin-Goltz syndrome, and suggest using it as early as possible in selected patients to avoid disfiguring scarring.

Electrochemotherapy of cutaneous metastases of melanoma--a case series study and systematic review of the evidence.

OBJECTIVES: Electrochemotherapy (ECT) is a novel therapeutic option for the treatment of cutaneous and subcutaneous metastases of malignant melanoma. During the treatment, electric pulses are applied to tumor nodules to deliver nonpermeant or poorly permeant chemotherapeutic agents into the cells, increasing local cytotoxicity of anticancer drugs. We compared the clinical effectiveness of ECT as an alternative palliative treatment option for unresectable metastatic lesions of malignant melanoma with a systematic review of reported outcomes. METHODS: One hundred fifty-eight cutaneous and subcutaneous metastases of nine patients were treated with ECT. All treatments were performed under general anesthesia using intravenous bleomycin injection. Median follow-up was 195 days. RESULTS: In our case series, complete response rate was 23%, and partial response rate was 39%. We observed no change in 30% and progressive disease in 8% of cases. CONCLUSIONS: ECT is a simple and effective treatment of single or multiple cutaneous and subcutaneous metastases of melanoma with minimal side effects. Our results provide further data for the growing body of evidence in recently published studies that ECT used for palliation has clinical benefit. The authors have indicated no significant interest with commercial supporters.

The Arg160Trp allele of melanocortin-1 receptor gene might protect against vitiligo.

Melanocortin-1 receptor (MC1R) and agouti signaling protein (ASIP) play pivotal roles in the regulation of human pigmentation. We aimed to study whether single nucleotide polymorphisms (SNPs) of the MC1R and ASIP genes contribute to the pathogenesis of the polygenic pigment skin disorder, vitiligo. The PCR-amplified, full-length MC1R gene was studied with sequence analysis, and the 3' untranslated region (3' UTR) SNP of ASIP was detected using restriction fragment length polymorphism. The allele frequency of the ASIP SNP did not show any difference between the skin type, hair color and eye color-matched 97 vitiligo patients and the 59 healthy control individuals. As one of the MC1R polymorphisms showed significantly higher incidence among fair-skinned individuals (Fitzpatrick I+II, n=140) than among dark-skinned individuals (Fitzpatrick III+IV, n=90), both vitiligo patients and controls were divided into two groups and the frequency of the MC1R alleles was studied separately in fair-skinned and dark-skinned subgroups of diseased and healthy groups. C478T, one of the MC1R SNPs studied in 108 fair-skinned vitiligo patients and in 70 fair-skinned healthy control individuals, showed a significant difference (P=0.0262, odds ratio [95% confidence interval]=3.6 [0.0046-0.1003]) in allele frequency between the two groups: the allele frequency was higher in the control group, suggesting protection against vitiligo. Computer prediction of antigenicity has revealed that the Arg160Trp amino acid change caused by this SNP results in a decrease in antigenicity of the affected peptide epitope.

[Photodynamic therapy in dermatooncology]. / Fotodinámiás terápia a dermatoonkológiában.

Non-melanoma skin cancers are the most common skin tumors. Because of their frequent localization on the face and hand, aesthetic aspects of the therapeutic procedures should also be considered. Surgical excision still remains the first choice, but recently several new alternative therapies have emerged, especially for the treatment of superficial skin cancer. Photodynamic therapy has become a widely accepted therapeutic method for certain non-melanoma skin tumors. Photodynamic therapy involves the use of light to activate a photosensitizer, localized in diseased tissues. Photosensitizers are tumor-selective: their accumulation in rapidly proliferating cells and newly formed blood vessels is significantly higher than in the surrounding healthy tissues. During photodynamic therapy, cytotoxic reactive oxygen species are formed from the photosensitizer, leading to changes in subcellular pathways or apoptosis of the cells. Efficacy of the photodynamic therapy has been proven in solar keratosis, superficial basal cell carcinoma and morbus Bowen, with significantly better cosmetic outcome than that of the conventional therapeutic methods. Side effects, like erythema, crusting, serous discharge, or oedema, are usually moderate, and dissolve rapidly. The present article summarizes the authors' experiences with photodynamic treatment (212 non-melanoma skin cancer patients were treated with PDT between December 2003 and January 2006), at the Department of Dermatology and Allergology, University of Szeged, Hungary, and reviews the literature of photodynamic therapy in dermatooncology.