Impact of the COVID-19 pandemic on melanoma diagnosis and presentation: a `review.

The ongoing challenges posed by COVID-19 are concerning for their impact on successful detection and recognition of melanoma as total body skin examinations and skin biopsies are critical for identifying early-stage melanoma and intervening before progression to metastatic disease. A comprehensive electronic search of PubMed/MEDLINE was conducted on or before August 1, 2022, using the search terms ("skin" AND "COVID-19"), (["skin cancer" AND "COVID-19"] OR ["skin cancer" AND "coronavirus"]), (["melanoma" AND "COVID-19"] OR ["melanoma" AND "coronavirus"]), ("dermatology" AND "COVID-19"), and ("cutaneous" AND "COVID-19"). Eight articles representing Belgium, Chile, France, Germany, Spain, the United Kingdom, and the United States were included. Four articles analyzed changes in the proportion of in situ melanoma at diagnosis and consistently reported decreases, with an overall decrease ranging from 7.6 to 40.4%. Five studies analyzed changes in the proportion of melanoma diagnoses by staging, but no clear changes in staging patterns were observed. Five studies analyzed changes in the mean Breslow thickness of melanoma diagnoses and consistently reported increases, with an overall increase ranging from 4.0 to 38%. Disruptions to proper diagnosis and treatment of melanoma are creating undue morbidity, mortality, and healthcare costs as the pandemic continues. Continued research with improved, centralized data collection is needed to better address the COVID-19 pandemic's ongoing challenge to appropriate detection and treatment of melanoma.

Apatinib combined with camrelizumab in advanced acral melanoma patients: An open-label, single-arm phase 2 trial.

BACKGROUND: At present, immune monotherapy and combination therapy has not shown satisfactory effects on acral melanoma, and still no standard treatment is available for advanced acral melanoma. Here, a phase II trial was performed to explore the safety and efficacy of apatinib combined with camrelizumab in advanced acral melanoma patients as first-line therapy (NCT03955354). METHODS: Patients with pathologically confirmed, locally unresectable or metastatic treatment native acral melanoma received 250 mg apatinib once daily and camrelizumab 200 mg once every two weeks intravenously every 28-day cycle. The primary end-point was objective response rate and the secondary end-points were disease control rate, overall survival, progression-free survival and safety. RESULTS: Thirty patients were recruited between January 2015 and January 2022. Among them, 21 (70.0%) had stage IV, and a median tumour burden was 50 mm (range: 11-187). Objective response rate was 24.1%, and 7 of 29 patients had an anti-tumour response, including partial response (n = 5) and complete response (n = 2). Disease control rate was 82.8%, median progression-free survival was 7.39 months (confidence interval: 3.65-9.92), and median overall survival was 13.4 months (confidence interval: 1.9-25.0). Grade 3-4 treatment-related toxicity (grade 3 50.5%; grade 4 3.3%) included transaminase elevations, proteinuria, leukocytopenia, vomiting, diarrhea and drug-induced liver injury. No treatment-related mortality occurred. The mutations of TTN, MUC16, VPS13D, ALPK2 and SCUBE1 showed significant alterations with survival outcome. CONCLUSIONS: Apatinib combined with camrelizumab showed manageable safety profile and reasonable anti-tumour activity in advanced acral melanoma patients as first-line therapy.

Neoadjuvant-Adjuvant or Adjuvant-Only Pembrolizumab in Advanced Melanoma.

BACKGROUND: Whether pembrolizumab given both before surgery (neoadjuvant therapy) and after surgery (adjuvant therapy), as compared with pembrolizumab given as adjuvant therapy alone, would increase event-free survival among patients with resectable stage III or IV melanoma is unknown. METHODS: In a phase 2 trial, we randomly assigned patients with clinically detectable, measurable stage IIIB to IVC melanoma that was amenable to surgical resection to three doses of neoadjuvant pembrolizumab, surgery, and 15 doses of adjuvant pembrolizumab (neoadjuvant-adjuvant group) or to surgery followed by pembrolizumab (200 mg intravenously every 3 weeks for a total of 18 doses) for approximately 1 year or until disease recurred or unacceptable toxic effects developed (adjuvant-only group). The primary end point was event-free survival in the intention-to-treat population. Events were defined as disease progression or toxic effects that precluded surgery; the inability to resect all gross disease; disease progression, surgical complications, or toxic effects of treatment that precluded the initiation of adjuvant therapy within 84 days after surgery; recurrence of melanoma after surgery; or death from any cause. Safety was also evaluated. RESULTS: At a median follow-up of 14.7 months, the neoadjuvant-adjuvant group (154 patients) had significantly longer event-free survival than the adjuvant-only group (159 patients) (P = 0.004 by the log-rank test). In a landmark analysis, event-free survival at 2 years was 72% (95% confidence interval [CI], 64 to 80) in the neoadjuvant-adjuvant group and 49% (95% CI, 41 to 59) in the adjuvant-only group. The percentage of patients with treatment-related adverse events of grades 3 or higher during therapy was 12% in the neoadjuvant-adjuvant group and 14% in the adjuvant-only group. CONCLUSIONS: Among patients with resectable stage III or IV melanoma, event-free survival was significantly longer among those who received pembrolizumab both before and after surgery than among those who received adjuvant pembrolizumab alone. No new toxic effects were identified. (Funded by the National Cancer Institute and Merck Sharp and Dohme; S1801 ClinicalTrials.gov number, NCT03698019.).

The impact of the COVID-19 pandemic on the diagnosis of cutaneous melanomas: A retrospective cohort study from five European skin cancer reference centres.

BACKGROUND: The COVID-19 lockdown had a dramatic impact on primary care access and resulted in postponed skin cancer screenings. This raises concerns for a diagnostic delay on primary cutaneous melanomas, which can subsequently increase morbidity and mortality. OBJECTIVES: The aim of the study was to investigate the impact of the COVID-19-related restrictions on the melanoma diagnosis in five European skin cancer reference centres in Switzerland, Germany, Austria and Italy. METHODS: A total of 7865 cutaneous melanoma cases were collected between 01 September 2018 and 31 August 2021. The time period was stratified into pre-COVID (pre-lockdown) and post-COVID (lockdown and post-lockdown) according to the established restrictions in each country. The data collection included demographic, clinical and histopathological data from histologically confirmed cutaneous melanomas. Personal and family history of melanoma, and presence of immunosuppression were used to assess the diagnosis delay in high-risk individuals. RESULTS: There was an overall increase of the Breslow tumour thickness (mean 1.25 mm vs. 1.02 mm) during the post-COVID period, as well as an increase in the proportion of T3-T4 melanomas, rates of ulceration and the number of mitotic rates ≥2 (all, p < 0.001). Patients with immunosuppression and personal history of melanoma showed a decrease in the mean log10-transformed Breslow during lockdown and post-COVID. In the multivariate analysis, age at melanoma diagnosis (p < 0.01) and personal history of melanoma (p < 0.01) showed significant differences in the mean Breslow thickness. CONCLUSIONS: The study confirms the diagnostic delay in cutaneous melanomas due to the COVID-19 lockdown. High-risk individuals, such as patients with personal history of melanoma and elderly individuals, were more hesitant to restart their regular skin cancer screenings post-COVID. Further studies with longer follow-up are required to evaluate the consequences of this diagnostic delay in long-term outcomes.

Development of melanoma clinical quality indicators for the Australian melanoma clinical outcomes registry (MelCOR): A modified Delphi study.

BACKGROUND: Clinical quality registries aim to identify significant variations in care and provide anonymised feedback to institutions to improve patient outcomes. Thirty-six Australian organisations with an interest in melanoma, raised funds through three consecutive Melanoma Marches, organised by Melanoma Institute Australia, to create a national Melanoma Clinical Outcomes Registry (MelCOR). This study aimed to formally develop valid clinical quality indicators for the diagnosis and early management of cutaneous melanoma as an important step in creating the registry. METHODS: Potential clinical quality indicators were identified by examining the literature, including Australian and international melanoma guidelines, and by consulting with key melanoma and registry opinion leaders. A modified two-round Delphi survey method was used, with participants invited from relevant health professions routinely managing melanoma as well as relevant consumer organisations. RESULTS: Nineteen participants completed at least one round of the Delphi process. 12 of 13 proposed clinical quality indictors met the validity criteria. The clinical quality indicators included acceptable biopsy method, appropriate excision margins, standardised pathology reporting, indications for sentinel lymph node biopsy, and involvement of multidisciplinary care and referrals. CONCLUSION: This study provides a multi-stakeholder consensus for important clinical quality indicators that define optimal practice that will now be used in the Australian Melanoma Clinical Outcomes Registry (MelCOR).

Lesion identification and malignancy prediction from clinical dermatological images.

We consider machine-learning-based lesion identification and malignancy prediction from clinical dermatological images, which can be indistinctly acquired via smartphone or dermoscopy capture. Additionally, we do not assume that images contain single lesions, thus the framework supports both focal or wide-field images. Specifically, we propose a two-stage approach in which we first identify all lesions present in the image regardless of sub-type or likelihood of malignancy, then it estimates their likelihood of malignancy, and through aggregation, it also generates an image-level likelihood of malignancy that can be used for high-level screening processes. Further, we consider augmenting the proposed approach with clinical covariates (from electronic health records) and publicly available data (the ISIC dataset). Comprehensive experiments validated on an independent test dataset demonstrate that (1) the proposed approach outperforms alternative model architectures; (2) the model based on images outperforms a pure clinical model by a large margin, and the combination of images and clinical data does not significantly improves over the image-only model; and (3) the proposed framework offers comparable performance in terms of malignancy classification relative to three board certified dermatologists with different levels of experience.

A shallow deep learning approach to classify skin cancer using down-scaling method to minimize time and space complexity.

The complex feature characteristics and low contrast of cancer lesions, a high degree of inter-class resemblance between malignant and benign lesions, and the presence of various artifacts including hairs make automated melanoma recognition in dermoscopy images quite challenging. To date, various computer-aided solutions have been proposed to identify and classify skin cancer. In this paper, a deep learning model with a shallow architecture is proposed to classify the lesions into benign and malignant. To achieve effective training while limiting overfitting problems due to limited training data, image preprocessing and data augmentation processes are introduced. After this, the 'box blur' down-scaling method is employed, which adds efficiency to our study by reducing the overall training time and space complexity significantly. Our proposed shallow convolutional neural network (SCNN_12) model is trained and evaluated on the Kaggle skin cancer data ISIC archive which was augmented to 16485 images by implementing different augmentation techniques. The model was able to achieve an accuracy of 98.87% with optimizer Adam and a learning rate of 0.001. In this regard, parameter and hyper-parameters of the model are determined by performing ablation studies. To assert no occurrence of overfitting, experiments are carried out exploring k-fold cross-validation and different dataset split ratios. Furthermore, to affirm the robustness the model is evaluated on noisy data to examine the performance when the image quality gets corrupted.This research corroborates that effective training for medical image analysis, addressing training time and space complexity, is possible even with a lightweighted network using a limited amount of training data.

Impact of the Covid-19 pandemic on melanoma and non-melanoma skin cancer inpatient treatment in Germany - a nationwide analysis.

BACKGROUND: SARS-CoV-2 has massively changed the care situation in hospitals worldwide. Although tumour care should not be affected, initial reports from European countries were suggestive for a decrease in skin cancer during the first pandemic wave and only limited data are available thereafter. OBJECTIVES: The aim of this study was to investigate skin cancer cases and surgeries in a nationwide inpatient dataset in Germany. METHODS: Comparative analyses were performed in a prepandemic (18 March 2019 until 17 March 2020) and a pandemic cohort (18 March 2020 until 17 March 2021). Cases were identified and analysed using the WHO international classification of diseases codes (ICDs) and process key codes (OPSs). RESULTS: Comparing the first year of the pandemic with the same period 1 year before, a persistent decrease of 14% in skin cancer cases (n = 19 063) was observed. The largest decrease of 24% was seen in non-invasive in situ tumours (n = 1665), followed by non-melanoma skin cancer (NMSC) with a decrease of 16% (n = 15 310) and malignant melanoma (MM) with a reduction of 7% (n = 2088). Subgroup analysis showed significant differences in the distribution of sex, age, hospital carrier type and hospital volume. There was a decrease of 17% in surgical procedures (n = 22 548), which was more pronounced in minor surgical procedures with a decrease of 24.6% compared to extended skin surgery including micrographic surgery with a decrease of 15.9%. CONCLUSIONS: Hospital admissions and surgical procedures decreased persistently since the beginning of the pandemic in Germany for skin cancer patients. The higher decrease in NMSC cases compared to MM might reflect a prioritization effect. Further evidence from tumour registries is needed to investigate the consequences of the therapy delay and identify the upcoming challenges in skin cancer care.

The effect of lockdown on melanoma stage in Devon, UK.

We performed a prospective analysis of Breslow thickness in melanoma before the COVID-19 pandemic and after. It shows that there is a statistically significant increase in melanoma thickness, and ultimately melanoma staging, since the pandemic began.

Necrosis of uveal melanoma post-COVID-19 vaccination.

A 49-year-old Indian male presented with rapidly progressive vision loss 1 day after receiving the second dose of BNT162b2 mRNA coronavirus disease 2019 (COVID-19) vaccine (Pfizer-BioNTech, NY, USA). The eye had secondary angle closure glaucoma, bullous retinal detachment, and massive intraocular hemorrhage. Ultrasound showed an ill-defined subretinal mass with moderate internal reflectivity. Magnetic resonance imaging (MRI) confirmed an enhancing heterogeneous subretinal mass. Histopathology showed a necrotic melanocytic lesion arising from the posterior edge of the ciliary body and choroid. Necrotic uveal melanoma was confirmed after expert histopathology opinion. Uveal melanomas can rarely present with tumor necrosis following mRNA COVID-19 vaccination.

The EORTC protocol for sentinel lymph node biopsy (SLNB) reveals a high number of nodal nevi and a strong association with nevus-associated melanoma.

BACKGROUND: The diagnosis of nodal nevi (NN) is challenging as they mimic melanoma metastases (MM), with a detection rate mostly ranging between 1% and 11% in sentinel lymph node biopsy (SLNB). Herein, we assessed the incidence of NN and the association with the clinical-pathological features of primary melanoma, adopting the updated European Organisation for Research and Treatment of Cancer (EORTC) protocol for SLNB. METHODS: All cases of paired melanoma and SLNB were retrospectively evaluated (April 2019-May 2020). Appropriate statistical tests were adopted, with significant variables included in the logistic regression model. RESULTS: 81 patients and a total of 186 lymph nodes (LNs) were included. Eleven patients had only NN and 4 had both NN and MM (18.5%); 29 LNs (15.6%) showed at least one NN and 12 (6.5%) showed more than one NN (a total amount of 43 NN was detected). All NN and none MM stained for p16. NN were associated with age < 60 years (p: 0.042), no ulceration (p: 0.025) and nevus-associated melanoma (NAM) (p: 0.018), with this latter being the only predictor at the logistic regression model (p: 0.022). CONCLUSIONS: The updated EORTC protocol shows a high number of NN and highlights a strong association with NAM.

The 'number needed to treat' metric: a further marker of the impact of COVID-19 on malignant melanomas.

We comment on a previous article, describing the number needed to treat metric as a further marker on the impact of COVID-19 on treatment of malignant melanomas.

Metastatic melanoma in the breast and axilla: A case report.

Metastatic melanoma of the breast is rare, and demonstrates nonspecific imaging findings which may overlap with both benign and malignant pathology.1-3 Immunohistochemical stains are important to confirm the diagnosis, particularly combining S100, a sensitive marker for melanoma, with more specific tumor markers such as Melan-A and HMB-45, and lack of cytokeratin staining.4-7 We present a case of a 64-year-old female who presented for diagnostic imaging of a palpable abnormality in her right breast, with medical history notable for previously excised cutaneous melanoma, recent COVID-19 vaccination, and significant family history of breast cancer. Diagnostic mammogram of the right breast demonstrated a circumscribed mass in the lower inner quadrant corresponding to the area of palpable concern, as well as an additional non-palpable circumscribed mass in the lower inner quadrant. Targeted right breast ultrasound demonstrated corresponding circumscribed cystic versus solid masses as well as a morphologically abnormal right axillary lymph node. Pathologic results after tissue sampling of the two right breast masses and right axillary lymph node all yielded metastatic melanoma.

Influence of COVID-19 confinement on the size of malignant skin tumours surgically removed at a Spanish hospital.

The COVID-19 pandemic required people to confine themselves to their homes where possible, and disrupted normal hospital activities. We examine whether this lockdown generated changes in the size of the tumours. We compared the dimensions of the surgically removed malignant skin tumours from the first 150 patients treated after the confinement ended in Spain (22 May 2020) with those of the last 150 patients to receive such treatment before the confinement began (13 March 2020). Data on tumour surface area were collected from pathology reports. Overall, no significant difference was seen in the tumour sizes. However, among men, the tumours removed after confinement were significantly larger (P < 0.05). Controversy exists over how the reduction in the number of tumours diagnosed during lockdowns might have influenced the characteristics of tumours. In this study, no overall difference was seen in the size of the tumours removed, although those removed from men after confinement were larger.

COVID-19 vaccination mimicking lymph-node progression in a patient with melanoma: a case report.

COVID-19 vaccination has been rapidly implemented among patients with cancer. We present the case of a patient with high-risk resected cutaneous melanoma, who was a candidate for adjuvant treatment, with postsurgery 18-fluorodeoxyglucose (FDG) PET/computed tomography (CT) scan showing positive axillary lymph nodes after COVID-19 vaccination. This report presents a 50-year-old man with a history of stage IIA cutaneous melanoma. During follow-up, the patient experienced subcutaneous and lymph-node disease progression, documented with 18FDG PET/CT scan. The patient underwent laparoscopic left para-aortic lymphadenectomy and excision of subcutaneous lesion. Histologic examination showed presence of melanoma metastases in 2 lymph nodes out of total 17 excised and neoplastic emboli to the subcutaneous tissue. In view of starting adjuvant nivolumab, the patient underwent CT scan restaging, with evidence of suspect centimetric periaortic and paracaval lymph nodes, which were deemed worthy of 18FDG PET investigation. The 18FDG PET/CT was negative for abdominal hypercaptation, but showed left axillary pathologic lymph nodes. The medical history of the patient revealed that he had received intramuscular Moderna COVID-19 mRNA vaccine in the left deltoid, one week before 18FDG PET examination. Since the patient's clinical examination was negative and suspecting postvaccination false-positive adenopathy, bilateral axillary ultrasound was performed, excluding the presence of pathologic lymph nodes. The patient has started adjuvant treatment with nivolumab, which is currently ongoing. This case demonstrates unexpected findings in response to COVID-19 vaccination in a patient with melanoma. In this specific case, the detection of 18FDG PET hypercaptation could significantly change the patient's management. With growing evidence about the pattern and occurrence of adenopathies after mRNA COVID-19 vaccination, recommendations for scheduling and interpretation of 18FDG PET/CT scans among cancer patients will be implemented, in order to reduce equivocal findings and improve outcomes.