The Multidisciplinary Management of Cutaneous Squamous Cell Carcinoma: A Comprehensive Review and Clinical Recommendations by a Panel of Experts

Simple Summary Cutaneous squamous cell carcinoma is one of the most common forms of cancer. Although most cases are cured with surgical excision, a few tumors are associated with a high risk of local or distant relapse; therefore, it is relevant to identify high-risk lesions among all other low-risk CSCCs for the proper diagnostic and therapeutic management. Chemotherapy achieves mostly short-lived responses that do not lead to a curative effect and are associated with severe toxicities. Recently, PD-1 inhibitor cemiplimab was approved by the regulatory authorities for the treatment of advanced cutaneous squamous cell carcinoma; subsequently, the anti-PD-1 agent pembrolizumab received the approval by the FDA only in the same setting. Here, we provide a literature review and clinical recommendations by a panel of experts regarding the diagnosis, treatment, and follow-up of cutaneous squamous cell carcinoma. Cutaneous squamous cell carcinomas (CSCC) account for about 20% of all keratinocyte carcinomas, which are the most common form of cancer. Heterogeneity of treatments and low mortality are a challenge in obtaining accurate incidence data and consistent registration in cancer registries. Indeed, CSCC mostly presents as an indolent, low-risk lesion, with five-year cure rates greater than 90% after surgical excision, and only few tumors are associated with a high-risk of local or distant relapse; therefore, it is particularly relevant to identify high-risk lesions among all other low-risk CSCCs for the proper diagnostic and therapeutic management. Chemotherapy achieves mostly short-lived responses that do not lead to a curative effect and are associated with severe toxicities. Due to an etiopathogenesis largely relying on chronic UV radiation exposure, CSCC is among the tumors with the highest rate of somatic mutations, which are associated with increased response rates to immunotherapy. Thanks to such strong pre-clinical rationale, clinical trials led to the approval of anti-PD-1 cemiplimab by the FDA (Food and Drug Administration) and EMA (European Medicines Agency), and anti-PD-1 pembrolizumab by the FDA only. Here, we provide a literature review and clinical recommendations by a panel of experts regarding the diagnosis, treatment, and follow-up of CSCC

In rheumatoid arthritis soluble CD30 ligand is present at high levels and induces apoptosis of CD30+T cells.

CD30 and CD30 ligand (CD30L) are members of TNF-receptor and TNF superfamilies respectively. CD30+T cells are increased in several diseases and interaction between CD30+ and CD30L+T cells leads either to cell proliferation or apoptosis. In patients with rheumatoid arthritis (RA), soluble CD30 (sCD30) levels seem to reflect the recruitment of CD30+T cells into the inflamed joints and are predictive of a positive response to classical and biological immunosuppressive therapy. We have evaluated the presence of soluble CD30L (sCD30L) in the sera and synovial fluid of patients with RA and defined whether it binds surface CD30 molecule and is functionally active. We found high levels of sCD30L in sera and synovial fluid of RA patients; the molecule is shedded upon direct contact of CD30+/CD30L+T cells. Moreover sCD30L binds surface CD30 constitutively expressed by Jurkat cell line. Finally recombinant sCD30L and sera from patients with high levels of sCD30L are able to inhibit CD30+T cell proliferation by inducing cell apoptosis. Our findings suggest that circulant sCD30L is functionally active and that it may favor persistence of active inflammation by inducing apoptosis of CD30+T cells, known to down-modulate inflammation in rheumatoid synovitis

Heterogeneous Phenotype of Human Melanoma Cells with In Vitro and In Vivo Features of Tumor-Initiating Cells

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Lymph-Node Ratio in Patients with Cutaneous Melanoma: A Multi-Institution Prognostic Study

Lymph node ratio (LNR)-the number of metastatic lymph nodes (LNs) over the number of excised LNs after lymphadenectomy-is a prognostic factor for many solid tumors, but controversies still exist for skin melanoma. We investigated the prognostic relevance of LNR in melanoma patients and formulated a proposal for considering the LNR in the current American Joint Committee on Cancer (AJCC) N staging system. METHODS: Retrospective data of 2,526 melanoma patients with LN metastasis from nine Italian institutions were collected in a multicenter database. The prognostic value of the LNR (categorized as A, ≤0.1; B, 0.11-0.25; and C, >0.25) was assessed by multivariable survival analysis. RESULTS: LNR was a significant independent prognostic factor for melanoma-specific survival (LNR B vs. A: hazard ratio [HR] 1.47, 95 % CI 1.16-1.87, p = 0.002; LNR C vs. A: HR 1.84, 95 % CI 1.29-2.61, p = 0.001). The LNR had prognostic value in patients with AJCC N1a (one positive LN after sentinel LN biopsy [SLNB], HR 2.33, 95 % CI 1.49-3.63, p < 0.001) and N2a (two to three positive LNs after SLNB, HR 1.62, 95 % CI 1.09-2.40, p = 0.016) substages, but not in those with N1b (one clinically positive LN, p = 0.765), N2b (two to three clinically positive LNs, p = 0.165), and N3 (≥ four positive LNs, p = 0.084) substages. CONCLUSION: The LNR is a prognostic factor in melanoma patients with one (AJCC N1a) and two to three (AJCC N2a) positive LNs after SLNB. This easy-to-obtain parameter should be considered for the staging of melanoma patients with LN metastasis, along with the number of positive LNs

Intralesional administration of L19-IL2/L19-TNF in stage III or stage IVM1a melanoma patients: results of a phase II study

ISSN:0340-7004ISSN:1432-085