Prevention, Diagnosis and Treatment of Skin Cancer

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Cancer Therapy".

Deadline for manuscript submissions: closed (30 September 2021) | Viewed by 76865

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First Department of Dermatology, School of Medicine, Faculty of Health Sciences, Aristotle University, Thessaloniki, Greece
Interests: melanoma; skin cancer; basal cell carcinoma; squamous cell carcinoma; dermoscopy; dermatoscopy; diagnosis; nevi
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Dear Colleagues

The landscape of skin cancer is rapidly changing in all aspects. In terms of epidemiology, melanoma incidence and mortality have appeared to stabilize or even decrease for the first time in recent last decades. In diagnosis, dermatoscopy has radically modified the diagnostic capacity of clinicians, enabling them to recognize numerous very early melanomas. This on one hand sounds life-saving, but on the other raises concerns around overdiagnosis and overtreatment of clinically insignificant tumors. At the same time, automated or enhanced image recognition by artificial intelligence appears as a new promising technology for skin cancer diagnosis. In the field of treatment, immunotherapy and targeted therapy have revolutionized the management of metastatic melanoma and now appear to modify even the management of stages II and III. Immunotherapy also changes the management of squamous cell carcinoma and Merkel cell carcinoma, and Hedgehog pathway inhibitors have acquired a considerable place in management of basal cell carcinoma.

This Special Issue will focus on latest updates on prevention, diagnosis, and treatment of skin cancer aiming mainly to investigate how all these new developments are adjusted in clinical practice 

Dr. Aimilios Lallas
Guest Editor

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Keywords

  • skin cancer
  • prevention
  • diagnosis
  • treatment
  • immunotherapy
  • targeted therapy

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Published Papers (17 papers)

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16 pages, 2096 KiB  
Article
Brachytherapy in the Treatment of Non-Melanoma Skin Peri-Auricular Cancers—A Retrospective Analysis of a Single Institution Experience
by Mateusz Bilski, Paweł Cisek, Izabela Baranowska, Izabela Kordzińska-Cisek, Nina Komaniecka, Anna Hymos, Ewelina Grywalska and Paulina Niedźwiedzka-Rystwej
Cancers 2022, 14(22), 5614; https://doi.org/10.3390/cancers14225614 - 15 Nov 2022
Cited by 2 | Viewed by 2221
Abstract
The location of skin neoplasms in the area of the ears qualifies patients to the so-called high-risk group. The location of neoplasms within the auricle and around the ear often causes many problems in surgical treatment. This is due to the presence of [...] Read more.
The location of skin neoplasms in the area of the ears qualifies patients to the so-called high-risk group. The location of neoplasms within the auricle and around the ear often causes many problems in surgical treatment. This is due to the presence of cartilage, the difficulty of performing procedures with obtaining a visually satisfactory cosmetic effect, especially in the presence of extensive lesions and can lead to positive surgical margins which leads to a high risk of recurrence. In such cases, the use of brachytherapy, both as an independent method and as a complementary method after surgery, may be an effective method of local control with an acceptable risk of radiation complications. However, there are no large retrospective studies on the use of brachytherapy in this anatomical region. The aim of the study was to analyse the effectiveness, toxicity profile, and cosmetic effect of two different brachytherapy techniques (contact and interstitial brachytherapy). Methods: This paper presents the results of a retrospective analysis of 33 patients treated with contact or interstitial high-dose-rate (HDR) brachytherapy for skin cancers of the outer ear, involving the auricle and the skin of the adjacent area. Brachytherapy was used both as a definitive treatment (15 patients—43%) and adjuvant treatment after surgery (18 patients—57%). The basic criterion for adjuvant treatment was a positive or narrow (<1 mm) resection margin. Fraction doses from 3 to 7 Gy per fraction were used at intervals from six hours (interstitial brachytherapy) to a maximum of seven days (contact brachytherapy). The treatment time ranged from 1 to 42 days, and the total dose range was 7 to 49 Gy. The follow-up was 29.75 months (range 2–64). Results: In the group of patients treated with adjuvant therapy, in the patients with post-radiation reaction, the mean time from surgery to the start of brachytherapy was 7.72 ± 3.05 weeks, the median was 8 (6–12) weeks, and in the group without post-radiation reaction, the mean time was 11.13 ± 4.41 weeks, the median time was 11 weeks (8–14). The risk of a post-radiation reaction increased significantly more often in patients with more advanced disease. In the case of contact brachytherapy, the post-radiation reaction occurred significantly more often (14/21 patients—43%) than in the case of interstitial brachytherapy (3/11 patients—9.4%). In patients with post-radiation reactions, a significantly larger volume of the skin receiving a dose of 200% was found, and the volume receiving a dose of 150% was close to statistical significance. The mean volume of the skin receiving a 200% dose in the group with post-radiation reactions was 28.05 ± 16.56 cm3, the median was 24.86 (0.5–52.3) cm3, and the mean volume in the group without post-radiation reaction was 17.98 ± 10.96 cm3, median 14.95 (3.9–44.96) cm3. The result was statistically significant (Z = 2.035, p = 0.041). Conclusion: Interstitial HDR (high-dose-rate) brachytherapy for non-melanoma skin cancers around the ear is highly effective, short, and has a relatively low burden on the patient. The toxicity of the treatment was low. In the case of contact brachytherapy, the toxicity profile is slightly higher but acceptable for patients. This method is preferred in patients in whom interstitial brachytherapy is impossible to perform due to anatomical and logistical reasons. The unquestionable advantage of contact brachytherapy is its ability to be performed on an outpatient basis without the need to stay in the hospital. No severe and late CTCAE ≥III and late RTOG ≥III toxicity was observed. In patients after surgery, in order to minimise the risk of radiation reaction, it is optimal to start treatment at least eight weeks after surgery. In the presence of extensive lesions, the use of interstitial brachytherapy seems to be more advantageous, especially when the expected volume of healthy skin in the dose range of 200% and 150% is above 15 cm3 and 50 cm3, respectively. Full article
(This article belongs to the Special Issue Prevention, Diagnosis and Treatment of Skin Cancer)
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11 pages, 272 KiB  
Article
In-Depth Characterisation of Real-World Advanced Melanoma Patients Receiving Immunotherapies and/or Targeted Therapies: A Case Series
by Saira Sanjida, Brigid Betz-Stablein, Victoria Atkinson, Monika Janda, Ramez Barsoum, Harrison Aljian Edwards, Frank Chiu, My Co Tran, H Peter Soyer and Helmut Schaider
Cancers 2022, 14(11), 2801; https://doi.org/10.3390/cancers14112801 - 4 Jun 2022
Viewed by 2529
Abstract
Immunotherapies and targeted therapies have shown significant benefits for melanoma survival in the clinical trial setting. Much less is known about the characteristics and associated outcomes of those receiving such therapies in real-world settings. This study describes the characteristics of patients with advanced [...] Read more.
Immunotherapies and targeted therapies have shown significant benefits for melanoma survival in the clinical trial setting. Much less is known about the characteristics and associated outcomes of those receiving such therapies in real-world settings. This study describes the characteristics of patients with advanced melanoma receiving immuno- and/or targeted therapies in a real-world setting. This prospective cohort study enrolled participants aged >18 years, diagnosed with advanced melanoma and currently undergoing immuno- and/or targeted therapies outside a clinical trial for follow-up with three-dimensional (3D) total-body imaging. Participants (n = 41) had a mean age of 62 years (range 29–86), 26 (63%) were male and the majority (n = 26, 63%) had ≥2 comorbidities. After a median of 39 months (range 1–52) follow-up, 59% (n = 24/41) of participants were alive. Despite multiple co-morbidities, the survival of participants with advanced melanoma treated using immuno- and/or targeted therapies was similar or better in our real-world setting compared to those treated in clinical trials using similar therapies. Larger studies powered to evaluate phenotypic and socio-economic characteristics, as well as specific comorbidities associated with survival in a real-world setting, are required to help determine those who will most benefit from immuno- and/or targeted therapies. Full article
(This article belongs to the Special Issue Prevention, Diagnosis and Treatment of Skin Cancer)
11 pages, 2036 KiB  
Article
Timeline of Adverse Events during Immune Checkpoint Inhibitors for Advanced Melanoma and Their Impacts on Survival
by Lorena Villa-Crespo, Sebastian Podlipnik, Natalia Anglada, Clara Izquierdo, Priscila Giavedoni, Pablo Iglesias, Mireia Dominguez, Francisco Aya, Ana Arance, Josep Malvehy, Susana Puig and Cristina Carrera
Cancers 2022, 14(5), 1237; https://doi.org/10.3390/cancers14051237 - 27 Feb 2022
Cited by 9 | Viewed by 4202
Abstract
Immune-related adverse events (irAEs) are frequent and could be associated with improved response to immune checkpoint inhibitors (ICIs). A prospective cohort of advanced melanoma patients receiving ICI as first-line therapy was retrospectively reviewed (January 2011–February 2019). A total of 116 of 153 patients [...] Read more.
Immune-related adverse events (irAEs) are frequent and could be associated with improved response to immune checkpoint inhibitors (ICIs). A prospective cohort of advanced melanoma patients receiving ICI as first-line therapy was retrospectively reviewed (January 2011–February 2019). A total of 116 of 153 patients presented with at least one irAE (75.8%). The most frequent irAEs were dermatological (derm irAEs, 50%), asthenia (38%), and gastrointestinal (29%). Most irAEs appeared within the first 90 days, while 11.2% appeared after discontinuation of the therapy. Mild grade 1–2 derm irAEs tended to appear within the first 2 months of therapy with a median time of 65.5 days (IQR 26-139.25), while grade 3–4 derm irAEs appeared later (median 114 days; IQR 69-218) and could be detected at any time during therapy. Only derm irAE occurrence was related to improved survival (HR 6.46). Patients presenting derm irAEs showed better 5-year overall survival compared to those with no derm irAEs (53.1% versus 24.9%; p < 0.001). However, the difference was not significant when adjusting for the duration of therapy. In conclusion: the timeline of immune-related-AEs differs according to the organ involved. The (apparent) improved survival of patients who present derm AEs during immunotherapy could be partially explained by longer times under treatment. Full article
(This article belongs to the Special Issue Prevention, Diagnosis and Treatment of Skin Cancer)
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13 pages, 1813 KiB  
Article
Characterizing Malignant Melanoma Clinically Resembling Seborrheic Keratosis Using Deep Knowledge Transfer
by Panagiota Spyridonos, George Gaitanis, Aristidis Likas and Ioannis Bassukas
Cancers 2021, 13(24), 6300; https://doi.org/10.3390/cancers13246300 - 15 Dec 2021
Cited by 5 | Viewed by 6488
Abstract
Malignant melanomas resembling seborrheic keratosis (SK-like MMs) are atypical, challenging to diagnose melanoma cases that carry the risk of delayed diagnosis and inadequate treatment. On the other hand, SK may mimic melanoma, producing a ‘false positive’ with unnecessary lesion excisions. The present study [...] Read more.
Malignant melanomas resembling seborrheic keratosis (SK-like MMs) are atypical, challenging to diagnose melanoma cases that carry the risk of delayed diagnosis and inadequate treatment. On the other hand, SK may mimic melanoma, producing a ‘false positive’ with unnecessary lesion excisions. The present study proposes a computer-based approach using dermoscopy images for the characterization of SΚ-like MMs. Dermoscopic images were retrieved from the International Skin Imaging Collaboration archive. Exploiting image embeddings from pretrained convolutional network VGG16, we trained a support vector machine (SVM) classification model on a data set of 667 images. SVM optimal hyperparameter selection was carried out using the Bayesian optimization method. The classifier was tested on an independent data set of 311 images with atypical appearance: MMs had an absence of pigmented network and had an existence of milia-like cysts. SK lacked milia-like cysts and had a pigmented network. Atypical MMs were characterized with a sensitivity and specificity of 78.6% and 84.5%, respectively. The advent of deep learning in image recognition has attracted the interest of computer science towards improved skin lesion diagnosis. Open-source, public access archives of skin images empower further the implementation and validation of computer-based systems that might contribute significantly to complex clinical diagnostic problems such as the characterization of SK-like MMs. Full article
(This article belongs to the Special Issue Prevention, Diagnosis and Treatment of Skin Cancer)
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16 pages, 728 KiB  
Article
Remote Skin Cancer Diagnosis: Adding Images to Electronic Referrals Is More Efficient Than Wait-Listing for a Nurse-Led Imaging Clinic
by Leah Jones, Michael Jameson and Amanda Oakley
Cancers 2021, 13(22), 5828; https://doi.org/10.3390/cancers13225828 - 20 Nov 2021
Cited by 8 | Viewed by 3103
Abstract
We undertook a retrospective comparison of two teledermatology pathways that provide diagnostic and management advice for suspected skin cancers, to evaluate the time from referral to diagnosis and its concordance with histology. Primary Care doctors could refer patients to either the Virtual Lesion [...] Read more.
We undertook a retrospective comparison of two teledermatology pathways that provide diagnostic and management advice for suspected skin cancers, to evaluate the time from referral to diagnosis and its concordance with histology. Primary Care doctors could refer patients to either the Virtual Lesion Clinic (VLC), a nurse-led community teledermoscopy clinic or, more recently, to the Suspected Skin Cancer (SSC) pathway, which requires them to attach regional, close-up, and dermoscopic images. The primary objective of this study was to determine the comparative time course between the SSC pathway and VLC. Secondary objectives included comparative diagnostic concordance, skin lesion classification, and evaluation of missed skin lesions during subsequent follow-up. VLC referrals from July to December 2016 and 2020 were compared to SSC referrals from July to December 2020. 408 patients with 682 lesions in the VLC cohort were compared with 480 patients with 548 lesions from the 2020 SSC cohort, matched for age, sex, and ethnicity, including histology where available. Median time (SD) from referral to receipt of teledermatology advice was four (2.8) days and 50 (43.0) days for the SSC and VLC cohorts, respectively (p < 0.001). Diagnostic concordance between teledermatologist and histopathologist for benign versus malignant lesions was 70% for 114 lesions in the SSC cohort, comparable to the VLC cohort (71% of 122 lesions). Referrals from primary care, where skin lesions were imaged with variable devices and quality resulted in faster specialist advice with similar diagnostic performance compared to high-quality imaging at nurse-led specialist dermoscopy clinics. Full article
(This article belongs to the Special Issue Prevention, Diagnosis and Treatment of Skin Cancer)
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16 pages, 7736 KiB  
Article
Basal Cell Carcinoma Treated with High Dose Rate (HDR) Brachytherapy—Early Evaluation of Clinical and Dermoscopic Patterns during Irradiation
by Tomasz Krzysztofiak, Grażyna Kamińska-Winciorek, Andrzej Tukiendorf, Magdalena Suchorzepka and Piotr Wojcieszek
Cancers 2021, 13(20), 5188; https://doi.org/10.3390/cancers13205188 - 16 Oct 2021
Cited by 6 | Viewed by 4049
Abstract
Basal cell carcinoma (BCC) is the most frequent malignancy of the Caucasian population. Dermoscopy is an established diagnostic method providing the bridge between clinical and pathological examination. Surface skin high dose rate (HDR) brachytherapy is an organ sparing treatment method used for non-surgical [...] Read more.
Basal cell carcinoma (BCC) is the most frequent malignancy of the Caucasian population. Dermoscopy is an established diagnostic method providing the bridge between clinical and pathological examination. Surface skin high dose rate (HDR) brachytherapy is an organ sparing treatment method used for non-surgical candidates. This prospective study aimed to observe clinical and dermoscopic features and their evolution in 23 patients with pathologically confirmed BCC that have been treated with HDR brachytherapy. In all cases, custom-made surface moulds were used. HDR brachytherapy was performed with 192Ir, dose 45Gy was delivered to the tumour in nine fractions of 5Gy, three times a week. The evolution of clinical and dermoscopic features was followed up at the beginning of treatment, and on the day of every fraction (t1–t9). Dermoscopic evaluation of neoplastic and non-neoplastic structures was based on current diagnostic criteria according to current literature. Univariate logistic regression showed a decreasing number of clinical and pathological features of basal cell carcinoma with every treatment fraction. The effect was more strongly pronounced for cancer-related dermoscopic structures compared with non-neoplastic features. We used multivariate ordinal logistic regression with random effects to prove that the patients’ age corresponds with the tumour’s response to radiation—which may implicate a better response to treatment among older patients. High dose rate brachytherapy decreases the number of clinical and dermoscopic features typical for basal cell carcinoma. The effect is more pronounced among older patients. Full article
(This article belongs to the Special Issue Prevention, Diagnosis and Treatment of Skin Cancer)
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13 pages, 757 KiB  
Article
Results of a Primary Skin-Cancer-Prevention Campaign in Early Childhood on Sun-Related Knowledge and Attitudes in Southern Hungary
by Zsuzsanna Horváth, Csernus A. Evelin, Péter Oláh, Rolland Gyulai and Zsuzsanna Lengyel
Cancers 2021, 13(15), 3873; https://doi.org/10.3390/cancers13153873 - 31 Jul 2021
Cited by 4 | Viewed by 3261
Abstract
Avoidance of ultraviolet (UV) exposure in early childhood is important for reducing the lifetime risk of developing skin cancer. The goal of the present prospective, multicenter pilot study was to assess the sun-protection practices in kindergartens and daycare centers and to evaluate sun [...] Read more.
Avoidance of ultraviolet (UV) exposure in early childhood is important for reducing the lifetime risk of developing skin cancer. The goal of the present prospective, multicenter pilot study was to assess the sun-protection practices in kindergartens and daycare centers and to evaluate sun protection knowledge and behavior among caregivers employed in the surveyed facilities. The study consisted of two parts. A baseline questionnaire was completed by the caregivers in relation to knowledge regarding basic sun protection and sun protection practices of the participating facilities. Afterward, a thirty-minute presentation was hosted in reference to this topic. Six months following the presentation, a follow-up questionnaire was distributed among the caregivers, evaluating the attitude-related and behavioral changes towards children. A total of 153 caregivers from five daycare centers (children between 6 months and 3 years of age) and sixteen kindergartens (children between 3 and 7 years of age) willfully participated in our study. According to our results, the main source of information regarding sun protection originated from different types of media. We found that staying in shaded areas and the use of protective clothing were not frequent in the facilities. Following our presentation regarding skin types and sunscreen use, protective measures improved, but not significantly (p = 0.222). The majority (92.31%) of caregivers distributed the information throughout their environment and also to parents. Sun protection knowledge is necessary; however, motivation among caregivers and parents and involvement of children is also relevant. Hence, a continuous, repetitive educational program regarding sun-smart behavior is deemed essential. Full article
(This article belongs to the Special Issue Prevention, Diagnosis and Treatment of Skin Cancer)
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12 pages, 581 KiB  
Article
Characterization and Clinical Utility of BRAFV600 Mutation Detection Using Cell-Free DNA in Patients with Advanced Melanoma
by Piotr Rutkowski, Patrick Pauwels, Joseph Kerger, Bart Jacobs, Geert Maertens, Valerie Gadeyne, Anne Thielemans, Katrien de Backer and Bart Neyns
Cancers 2021, 13(14), 3591; https://doi.org/10.3390/cancers13143591 - 17 Jul 2021
Cited by 4 | Viewed by 2677
Abstract
Tissue-based tests for BRAFV600 mutation-positive melanoma involve invasive biopsy procedures, and can lead to an erroneous diagnosis when the tumor samples degrade. Herein, we explored a minimally invasive, cell-free deoxyribonucleic acid (cfDNA)-based platform, to retest patients for BRAFV600 mutations. This phase [...] Read more.
Tissue-based tests for BRAFV600 mutation-positive melanoma involve invasive biopsy procedures, and can lead to an erroneous diagnosis when the tumor samples degrade. Herein, we explored a minimally invasive, cell-free deoxyribonucleic acid (cfDNA)-based platform, to retest patients for BRAFV600 mutations. This phase 2 study enrolled adult patients with unresectable/metastatic melanoma. A prescreening testing phase evaluated the concordance between a prior tissue-based BRAFV600 mutation test result and a subsequent plasma cfDNA-based test result. A treatment phase evaluated the patients who were confirmed as BRAFV600 mutation-positive, and were treated with cobimetinib plus vemurafenib. It was found that 35/54 patients (64.8%) with a mutant BRAF status by prior tissue test had a positive BRAFV600 mutation with the cfDNA test. Further, 7/118 patients (5.9%) with a wild-type BRAF status had a positive BRAFV600 mutation cfDNA test; tissue retests on archival samples confirmed BRAFV600 mutation positivity in 5/7 patients (71.4%). One of these patients received BRAF pathway-targeted therapy (cobimetinib plus vemurafenib), and had progression-free survival commensurate with previous experience. In the overall cobimetinib plus vemurafenib-treated population, 29/36 patients (80.6%) had an objective response. The median progression-free survival was 13.6 months (95% confidence interval, 9.5–16.5). Cell-free DNA–based tests may be a fast and convenient option to identify BRAF mutation status in melanoma patients, and help inform treatment decisions. Full article
(This article belongs to the Special Issue Prevention, Diagnosis and Treatment of Skin Cancer)
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11 pages, 1301 KiB  
Article
Novel Insights for Patients with Multiple Basal Cell Carcinomas and Tumors at High-Risk for Recurrence: Risk Factors, Clinical Morphology, and Dermatoscopy
by Dimitrios Sgouros, Dimitrios Rigopoulos, Ioannis Panayiotides, Zoe Apalla, Dimitrios K. Arvanitis, Melpomeni Theofili, Sofia Theotokoglou, Anna Syrmali, Konstantinos Theodoropoulos, Georgia Pappa, Vasileia Damaskou, Alexander Stratigos and Alexander Katoulis
Cancers 2021, 13(13), 3208; https://doi.org/10.3390/cancers13133208 - 27 Jun 2021
Cited by 4 | Viewed by 3522
Abstract
Introduction: Basal cell carcinoma (BCC) quite frequently presents as multiple tumors in individual patients. Neoplasm’s risk factors for local recurrence have a critical impact on therapeutic management. Objective: To detect risk factors for multiple BCCs (mBCC) in individual patients and to describe clinical [...] Read more.
Introduction: Basal cell carcinoma (BCC) quite frequently presents as multiple tumors in individual patients. Neoplasm’s risk factors for local recurrence have a critical impact on therapeutic management. Objective: To detect risk factors for multiple BCCs (mBCC) in individual patients and to describe clinical and dermatoscopic features of low- and high-risk tumors. Materials & Methods: Our study included 225 patients with 304 surgically excised primary BCCs. All patients’ medical history and demographics were recorded. Clinical and dermatoscopic images of BCCs were evaluated for predefined criteria and statistical analyses were performed. Results: Grade II-III sunburns before adulthood (OR 2.146, p = 0.031) and a personal history of BCC (OR 3.403, p < 0.001) were the major predisposing factors for mBCC. Clinically obvious white color (OR 3.168, p < 0.001) and dermatoscopic detection of white shiny lines (OR 2.085, p = 0.025) represented strongly prognostic variables of high-risk BCC. Similarly, extensive clinico-dermatoscopic ulceration (up to 9.2-fold) and nodular morphology (3.6-fold) raise the possibility for high-risk BCC. On the contrary, dermatoscopic evidence of blue-black coloration had a negative prognostic value for high-risk neoplasms (light OR 0.269, p < 0.001/partial OR 0.198, p = 0.001). Conclusions: Profiling of mBCC patients and a thorough knowledge of high-risk tumors’ clinico-dermatoscopic morphology could provide physicians with important information towards prevention of this neoplasm. Full article
(This article belongs to the Special Issue Prevention, Diagnosis and Treatment of Skin Cancer)
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15 pages, 1424 KiB  
Article
Psychological Distress of Metastatic Melanoma Patients during Treatment with Immune Checkpoint Inhibitors: Results of a Prospective Study
by Lisa Wiens, Norbert Schäffeler, Thomas Eigentler, Claus Garbe and Andrea Forschner
Cancers 2021, 13(11), 2642; https://doi.org/10.3390/cancers13112642 - 27 May 2021
Cited by 5 | Viewed by 2467
Abstract
Background: Immune checkpoint inhibitors (ICI) provide effective treatment options for advanced melanoma patients. However, they are associated with high rates of immune-related side effects. There are no data on the distress of melanoma patients during their ICI treatment. We, therefore, conducted a prospective [...] Read more.
Background: Immune checkpoint inhibitors (ICI) provide effective treatment options for advanced melanoma patients. However, they are associated with high rates of immune-related side effects. There are no data on the distress of melanoma patients during their ICI treatment. We, therefore, conducted a prospective longitudinal study to assess distress and the need for psycho-oncological support in these patients. Methods: Questionnaires were completed before initiation of ICI (T0), after 6–8 weeks (T1), and after 12–14 weeks (T2). We furthermore included the Hornheide Screening Instrument (HSI), distress thermometer (DT), and patients’ self-assessment. Binary logistic regression was performed to identify factors indicating a need for psychooncological support. Results: 36.3%/55.8% (HSI / DT) of the patients were above the threshold, indicating a need for psychooncological support at T0, and 7.8% of the patients reported practical problems. In contrast, at T2, the distress values had decreased to 29.0%/40.2% (HSI/DT), respectively. Female gender and occurrence of side effects significantly correlated to values above the threshold. The strongest factor was the patient’s self-assessment. Conclusion: With the beginning of ICI, psychooncological support should be offered. Furthermore, practical problems should be considered, e.g., transport to therapy. Female patients and patients with side effects should be given special attention, as well as the patient self-assessment. Full article
(This article belongs to the Special Issue Prevention, Diagnosis and Treatment of Skin Cancer)
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9 pages, 622 KiB  
Article
Interstitial HDR Brachytherapy in the Treatment of Non-Melanocytic Skin Cancers around the Eye
by Paweł Cisek, Dariusz Kieszko, Mateusz Bilski, Radomir Dębicki, Ewelina Grywalska, Rafał Hrynkiewicz, Dominika Bębnowska, Izabela Kordzińska-Cisek, Agnieszka Rolińska, Paulina Niedźwiedzka-Rystwej and Ludmiła Grzybowska-Szatkowska
Cancers 2021, 13(6), 1425; https://doi.org/10.3390/cancers13061425 - 20 Mar 2021
Cited by 12 | Viewed by 3127
Abstract
Background: Eyelid tumors are rare skin cancers, the most common of which is basal cell carcinoma characterized primarily by local growth. In addition to surgery, radiotherapy is among the basic methods of treatment. External beam radiotherapy is associated with the risk of complications [...] Read more.
Background: Eyelid tumors are rare skin cancers, the most common of which is basal cell carcinoma characterized primarily by local growth. In addition to surgery, radiotherapy is among the basic methods of treatment. External beam radiotherapy is associated with the risk of complications within ocular structures, especially the lens. In the case of interstitial brachytherapy, it is possible to administer a high dose to the clinical target volume (CTV), while reducing it in the most sensitive structures. Methods: This paper presents the results of an analysis of 28 patients treated with interstitial high dose rate (HDR) brachytherapy for skin cancers of the upper and lower eyelid; medial and lateral canthus; and the cheek, nose and temples with the infiltration of ocular structures. The patients were treated according to two irradiation schedules: 49 Gy in 14 fractions of 3.5 Gy twice a day for 7 days of treatment, and 45 Gy in 5 Gy fractions twice a day for 5 days. The mean follow-up was 22 months (3–49 months). Results: two patients (6%) had a relapse: a local recurrence within the irradiated area in one of them, and metastases to lymph nodes in the other. The most common early complication was conjunctivitis (74%), and the most common late complication was dry eye syndrome (59%). Conclusions: Interstitial HDR brachytherapy for skin cancers of the upper and lower eyelid; medial and lateral cants; and the cheek, nose and temples with infiltration of ocular structures is a highly effective, short and relatively low burden type of treatment. Full article
(This article belongs to the Special Issue Prevention, Diagnosis and Treatment of Skin Cancer)
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Review

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19 pages, 1643 KiB  
Review
Update on Management Recommendations for Advanced Cutaneous Squamous Cell Carcinoma
by Jesús García-Foncillas, Antonio Tejera-Vaquerizo, Onofre Sanmartín, Federico Rojo, Javier Mestre, Salvador Martín, Ignacio Azinovic and Ricard Mesía
Cancers 2022, 14(3), 629; https://doi.org/10.3390/cancers14030629 - 27 Jan 2022
Cited by 19 | Viewed by 10527
Abstract
Cutaneous squamous cell carcinoma (cSCC) is the second most common form of skin cancer, the incidence of which has risen over the last years. Although cSCC rarely metastasizes, early detection and treatment of primary tumours are critical to limit progression and local invasion. [...] Read more.
Cutaneous squamous cell carcinoma (cSCC) is the second most common form of skin cancer, the incidence of which has risen over the last years. Although cSCC rarely metastasizes, early detection and treatment of primary tumours are critical to limit progression and local invasion. Several prognostic factors related to patients’ clinicopathologic profile and tumour features have been identified as high-risk markers and included in the stratification scales, but their association with regional control or survival is uncertain. Therefore, decision-making on the diagnosis and management of cSCC should be made based on each individual patient’s characteristics. Recent advances in non-invasive imaging techniques and molecular testing have enhanced clinical diagnostic accuracy. Surgical excision is the mainstay of local treatment, whereas radiotherapy (RT) is recommended for patients with inoperable disease or in specific circumstances. Novel systemic treatments including immunotherapies and targeted therapies have changed the therapeutic landscape for cSCC. The anti-PD-1 agent cemiplimab is currently the only FDA/EMA-approved first-line therapy for patients with locally advanced or metastatic cSCC who are not candidates for curative surgery or RT. Given the likelihood of recurrence and the increased risk of developing multiple cSCC, close follow-up should be performed during the first years of treatment and continued long-term surveillance is warranted. Full article
(This article belongs to the Special Issue Prevention, Diagnosis and Treatment of Skin Cancer)
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12 pages, 545 KiB  
Review
Beyond Nicotinamide Metabolism: Potential Role of Nicotinamide N-Methyltransferase as a Biomarker in Skin Cancers
by Roberto Campagna, Valentina Pozzi, Davide Sartini, Eleonora Salvolini, Valerio Brisigotti, Elisa Molinelli, Anna Campanati, Annamaria Offidani and Monica Emanuelli
Cancers 2021, 13(19), 4943; https://doi.org/10.3390/cancers13194943 - 30 Sep 2021
Cited by 38 | Viewed by 3124
Abstract
Skin cancers (SC) collectively represent the most common type of malignancy in white populations. SC includes two main forms: malignant melanoma and non-melanoma skin cancer (NMSC). NMSC includes different subtypes, namely, basal cell carcinoma (BCC), squamous cell carcinoma (SCC), Merkel cell carcinoma (MCC), [...] Read more.
Skin cancers (SC) collectively represent the most common type of malignancy in white populations. SC includes two main forms: malignant melanoma and non-melanoma skin cancer (NMSC). NMSC includes different subtypes, namely, basal cell carcinoma (BCC), squamous cell carcinoma (SCC), Merkel cell carcinoma (MCC), and keratoacanthoma (KA), together with the two pre-neoplastic conditions Bowen disease (BD) and actinic keratosis (AK). Both malignant melanoma and NMSC are showing an increasing incidence rate worldwide, thus representing an important challenge for health care systems, also because, with some exceptions, SC are generally characterized by an aggressive behavior and are often diagnosed late. Thus, identifying new biomarkers suitable for diagnosis, as well as for prognosis and targeted therapy is mandatory. Nicotinamide N-methyltransferase (NNMT) is an enzyme that is emerging as a crucial player in the progression of several malignancies, while its substrate, nicotinamide, is known to exert chemopreventive effects. Since there is increasing evidence regarding the involvement of this enzyme in the malignant behavior of SC, the current review aims to summarize the state of the art as concerns NNMT role in SC and to support future studies focused on exploring the diagnostic and prognostic potential of NNMT in skin malignancies and its suitability for targeted therapy. Full article
(This article belongs to the Special Issue Prevention, Diagnosis and Treatment of Skin Cancer)
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15 pages, 865 KiB  
Review
Merkel Cell Carcinoma: New Trends
by Ellen M. Zwijnenburg, Satish F.K. Lubeek, Johanna E.M. Werner, Avital L. Amir, Willem L.J. Weijs, Robert P. Takes, Sjoert A.H. Pegge, Carla M.L. van Herpen, Gosse J. Adema and Johannes H. A. M. Kaanders
Cancers 2021, 13(7), 1614; https://doi.org/10.3390/cancers13071614 - 31 Mar 2021
Cited by 28 | Viewed by 8410
Abstract
Merkel cell carcinoma (MCC) is a rare neuroendocrine tumor of the skin mainly seen in the elderly. Its incidence is rising due to ageing of the population, increased sun exposure, and the use of immunosuppressive medication. Additionally, with the availability of specific immunohistochemical [...] Read more.
Merkel cell carcinoma (MCC) is a rare neuroendocrine tumor of the skin mainly seen in the elderly. Its incidence is rising due to ageing of the population, increased sun exposure, and the use of immunosuppressive medication. Additionally, with the availability of specific immunohistochemical markers, MCC is easier to recognize. Typically, these tumors are rapidly progressive and behave aggressively, emphasizing the need for early detection and prompt diagnostic work-up and start of treatment. In this review, the tumor biology and immunology, current diagnostic and treatment modalities, as well as new and combined therapies for MCC, are discussed. MCC is a very immunogenic tumor which offers good prospects for immunotherapy. Given its rarity, the aggressiveness, and the frail patient population it concerns, MCC should be managed in close collaboration with an experienced multidisciplinary team. Full article
(This article belongs to the Special Issue Prevention, Diagnosis and Treatment of Skin Cancer)
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22 pages, 3583 KiB  
Review
Regenerative Wound Dressings for Skin Cancer
by Teodor Iulian Pavel, Cristina Chircov, Marius Rădulescu and Alexandru Mihai Grumezescu
Cancers 2020, 12(10), 2954; https://doi.org/10.3390/cancers12102954 - 13 Oct 2020
Cited by 22 | Viewed by 4891
Abstract
Skin cancer is considered the most prevalent cancer type globally, with a continuously increasing prevalence and mortality growth rate. Additionally, the high risk of recurrence makes skin cancer treatment among the most expensive of all cancers, with average costs estimated to double within [...] Read more.
Skin cancer is considered the most prevalent cancer type globally, with a continuously increasing prevalence and mortality growth rate. Additionally, the high risk of recurrence makes skin cancer treatment among the most expensive of all cancers, with average costs estimated to double within 5 years. Although tumor excision is the most effective approach among the available strategies, surgical interventions could be disfiguring, requiring additional skin grafts for covering the defects. In this context, post-surgery management should involve the application of wound dressings for promoting skin regeneration and preventing tumor recurrence and microbial infections, which still represents a considerable clinical challenge. Therefore, this paper aims to provide an up-to-date overview regarding the current status of regenerative wound dressings for skin cancer therapy. Specifically, the recent discoveries in natural biocompounds as anti-cancer agents for skin cancer treatment and the most intensively studied biomaterials for bioactive wound dressing development will be described. Full article
(This article belongs to the Special Issue Prevention, Diagnosis and Treatment of Skin Cancer)
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10 pages, 18724 KiB  
Commentary
Basosquamous Carcinoma: A Commentary
by Christina Fotiadou, Zoe Apalla and Elizabeth Lazaridou
Cancers 2021, 13(23), 6146; https://doi.org/10.3390/cancers13236146 - 6 Dec 2021
Cited by 12 | Viewed by 5552
Abstract
Basosquamous carcinoma is a rare, aggressive non-melanoma skin cancer with features that lie between those of basal cell carcinoma and squamous cell carcinoma. A lot of controversy has been raised around the classification, pathogenesis, histologic morphology, biologic behavior, prognosis and management of this [...] Read more.
Basosquamous carcinoma is a rare, aggressive non-melanoma skin cancer with features that lie between those of basal cell carcinoma and squamous cell carcinoma. A lot of controversy has been raised around the classification, pathogenesis, histologic morphology, biologic behavior, prognosis and management of this tumor. This is a narrative review based on an electronic search of articles published in PubMed in English language which had in their title the terms “basosquamous carcinoma” and/or “metatypical carcinoma of the skin”. The aim of this review was to summarize and evaluate current data regarding epidemiology, clinical presentation, dermoscopic and histopathologic characteristics, as well as the genetics and management of BSC, in order to shed some more light onto this intriguing entity. As a conclusion, dermoscopy, deep incisional biopsies and immunohistologic techniques (Ber-EP4) should be applied in clinically suspicious lesions in order to achieve an early diagnosis and better prognosis of this tumor. Surgical treatments, including wide excision and Mohs’ micrographic surgery, remain the treatment of choice. Finally, vismodegib, a Hedgehog pathway inhibitor, must be thoroughly investigated, with large controlled trials, since it may offer an alternative solution to irresectable or difficult-to-treat, locally advanced cases of basosquamous carcinoma. Full article
(This article belongs to the Special Issue Prevention, Diagnosis and Treatment of Skin Cancer)
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11 pages, 311 KiB  
Systematic Review
Treatment Options and Post-Treatment Malignant Transformation Rate of Actinic Cheilitis: A Systematic Review
by Katerina Bakirtzi, Ilias Papadimitriou, Dimitrios Andreadis and Elena Sotiriou
Cancers 2021, 13(13), 3354; https://doi.org/10.3390/cancers13133354 - 4 Jul 2021
Cited by 12 | Viewed by 3284
Abstract
Actinic cheilitis is a premalignant condition that may evolve to squamous cell carcinoma. A consensus on its management has not been established, and large clinical trials are lacking. We aimed to review the existing data regarding the treatment of actinic cheilitis with various [...] Read more.
Actinic cheilitis is a premalignant condition that may evolve to squamous cell carcinoma. A consensus on its management has not been established, and large clinical trials are lacking. We aimed to review the existing data regarding the treatment of actinic cheilitis with various modalities regarding safety, efficacy, recursions, and post-treatment malignant transformation. A systematic review was conducted through Pubmed, Ovid and the Cochrane library for studies in English language and the references of included papers from inception to January 2021. Case series were considered if ≥6 patients were included. Of the 698 articles, 36 studies and, overall, 699 patients were eventually reviewed. Laser ablation and vermilionectomy provided the best clinical and aesthetic outcomes with few recurrences, while photodynamic therapy was linked to more relapses. Generally, the adverse events were minor and there was no risk of post-treatment malignant transformation. The limitations of our review include the heterogeneity and the small number of patients across studies. Conclusively, invasive treatments demonstrated superior therapeutic and safety profile. Nevertheless, high-quality head-to-head studies that assess different modalities for actinic cheilitis and report patient preferences are lacking. Full article
(This article belongs to the Special Issue Prevention, Diagnosis and Treatment of Skin Cancer)
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