Identifying candidates for immunotherapy with cemiplimab to treat advanced cutaneous squamous cell carcinoma: an expert opinion

Cutaneous squamous cell carcinoma (CSCC) is the second most common skin malignancy in white-skinned populations. Only a minority of patients (<5%) develop advanced disease, but this is often difficult to treat and characterised by a poor prognosis. Cemiplimab, a fully human IgG4 monoclonal antibody against programmed cell death-1 receptor, is indicated for advanced (i.e. locally advanced or metastatic) CSCC. Although the definition of metastatic CSCC is clear, there is currently no agreed definition of locally advanced CSCC. In recent guidelines, locally advanced CSCC was described as non-metastatic CSCC that is unlikely to be cured with surgery, radiotherapy or combination treatment. A multi-disciplinary advisory group of Italian CSCC experts was convened to develop criteria to assist in identifying appropriate candidates for cemiplimab therapy in advanced CSCC, based on the literature and clinical experience. In locally advanced CSCC, absolute, or mandatory, criteria for the use of cemiplimab are deep invasion, multiple lesions without defined margins, inadequate surgical excision margins and multiple recurrences, whereas relative criteria include large lesions, in critical or functionally significant areas and that are surgically complex. In addition, physicians should consider patient willingness/preferences (an absolute criterion), and their age and health status/comorbidities (relative criteria). It is hoped that these proposed absolute and relative criteria will help guide rational identification of patients who will receive maximum benefit from immunotherapy, while more clinical data accumulate.

Nanoparticle-Based Drug Delivery Systems for Photodynamic Therapy of Metastatic Melanoma: A Review

Metastatic melanoma (MM) is a skin malignancy arising from melanocytes, the incidence of which has been rising in recent years. It poses therapeutic challenges due to its resistance to chemotherapeutic drugs and radiation therapy. Photodynamic therapy (PDT) is an alternative non-invasive modality that requires a photosensitizer (PS), specific wavelength of light, and molecular oxygen. Several studies using conventional PSs have highlighted the need for improved PSs for PDT applications to achieve desired therapeutic outcomes. The incorporation of nanoparticles (NPs) and targeting moieties in PDT have appeared as a promising strategy to circumvent various drawbacks associated with non-specific toxicity, poor water solubility, and low bioavailability of the PSs at targeted tissues. Currently, most studies investigating new developments rely on two-dimensional (2-D) monocultures, which fail to accurately mimic tissue complexity. Therefore, three-dimensional (3-D) cell cultures are ideal models to resemble tumor tissue in terms of architectural and functional properties. This review examines various PS drugs, as well as passive and active targeted PS nanoparticle-mediated platforms for PDT treatment of MM on 2-D and 3-D models. The overall findings of this review concluded that very few PDT studies have been conducted within 3-D models using active PS nanoparticle-mediated platforms, and so require further investigation.

Phototherapy in Dermatology

Phototherapy is a therapeutic procedure in dermatology. Phototherapy uses certain ultraviolet wavelengths classified into 3 types,broadband UVB (BBUVB), narrowband UVB (NBUVB), and psoralen UVA (PUVA). The most widely used is NBUVB for treating psoriasis, atopic dermatitis and vitiligo. The mechanism of action of phototherapy is to reduce epidermal proliferation, suppress the immune system, reduce the inflammatory process, and induce repigmentation. Before starting phototherapy, the dose adjustment depends on skin type and minimal erythema dose (MED). Frequency of use is recommended based on the severity of the disease, continuously administered needed. Besides of this therapeutic effect, some contraindications and side effects that need to be considered in the use of phototherapy such as drug interactions, photoallergic and risk of skin malignancy.

Innate Lymphoid Cells in Skin Homeostasis and Malignancy

Innate lymphoid cells (ILCs) are mostly tissue resident lymphocytes that are preferentially enriched in barrier tissues such as the skin. Although they lack the expression of somatically rearranged antigen receptors present on T and B cells, ILCs partake in multiple immune pathways by regulating tissue inflammation and potentiating adaptive immunity. Emerging evidence indicates that ILCs play a critical role in the control of melanoma, a type of skin malignancy thought to trigger immunity mediated mainly by adaptive immune responses. Here, we compile our current understanding of ILCs with regard to their role as the first line of defence against melanoma development and progression. We also discuss areas that merit further investigation. We envisage that the possibility to harness therapeutic potential of ILCs might benefit patients suffering from skin malignancies such as melanoma.

704 An Audit of Marking of Cutaneous Lesions in A Two-Week Wait Skin Malignancy Service

Aim Clinical photography enhances a medical record and facilitates communication with other professionals involved in care. It is utilised frequently in the management of skin malignancy. The essence of good photography lies in accurate identification of the cutaneous lesion in question. National guidelines and local policy advise the use of circumferential marking to delineate a lesion of interest, and an alphabetical system for marking of multiple lesions. We audited compliance to standards for medical illustrations of cutaneous lesions in the two-week wait skin cancer clinic at University Hospital North Durham. Method Prospective audit of patients attending the clinic over a 7-day period (07/09/20-15/09/20). Data was collated from electronic records on a number of variables. Results 175 patients met inclusion criteria. The majority (n = 160, 89.9%) were referred for a single lesion, the rest for multiple lesions. Hospital clinical photography was obtained in 148 patients (83.2%). Marking was deemed inappropriate in 44.6% of those in which clinical photography was obtained. Of these 66 cases, 12 cases were multiple lesions marked without letters, 52 had an incorrect indicator for the lesion (such as arrows or dots, allowing more ambiguous interpretation), and 8 had no indicator at all. Incidentally, one patient was photographed with dressings covering the lesions. Conclusions Compliance with standards for demarcation of skin lesions for clinical photography was found to be poor. This permits the wrong identification of lesions in future treatment episodes and could potentially have a significant impact on care. We propose the introduction of a referral document illustrating correct marking guidelines.