Immune checkpoint inhibitors for treatment of periorbital squamous cell carcinoma

2021 ◽  
pp. bjophthalmol-2021-319417
Author(s):  
Jeremy Allan Goldfarb ◽  
Renata Ferrarotto ◽  
Neil Gross ◽  
Ryan Goepfert ◽  
James Matthew Debnam ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Chart Review ◽  
Checkpoint Inhibitors ◽  
Locally Advanced ◽  
Retrospective Chart Review ◽  
Cutaneous Squamous Cell Carcinoma ◽  
Therapeutic Outcomes

PurposeTo report on the outcomes of immunotherapy in patients with locally advanced periorbital squamous cell carcinoma.MethodsWe performed a retrospective chart review of seven consecutive patients with locally advanced periorbital cutaneous squamous cell carcinoma treated with anti-PD-1 immunotherapy. Treatments and therapeutic outcomes were reviewed.ResultsOf the seven patients, six were treated with cemiplimab, and one was treated with pembrolizumab. Five patients were treated with immunotherapy as neoadjuvant therapy before planned surgical resection; two patients received immunotherapy for treatment of advanced recurrent lesions deemed unresectable following multiple previous excisions and radiation therapy. In all seven patients, measurable clinical and/or radiologic response was observed.ConclusionsOur findings support the emerging role of anti-PD-1 immunotherapy in the management of locally advanced periorbital cutaneous squamous cell carcinoma.

scholarly journals Actual treatment options for locally advanced and metastatic cutaneous squamous cell carcinoma

2021 ◽  
Vol 23 (1) ◽  
pp. 94-98
Author(s):  
Anastasia V. Ignatova
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Checkpoint Inhibitors ◽  
Treatment Options ◽  
Locally Advanced ◽  
Cutaneous Squamous Cell Carcinoma ◽  
Molecular Profile ◽  
New Information ◽  
New Treatment

Squamous cell carcinoma of the skin, or cutaneous squamous cell carcinoma (CSCC), is the second most frequent type of skin cancer, and its incidence continues to rise all over the world. Usually has a benign clinical behavior, but it can be presented as locally invasive and metastatic aggressive tumor with 2% mortality rate. Nowadays, new risk factors for have appeared, that form pharmacologically-induced CSCC after immunosuppressant drugs used for organ transplantation, or BRAF inhibitors used for melanoma. In recent years we have got a new information about the role of mutational burden, signaling pathways involved in CSCC development and new possibilities and molecules for targeted therapy. Better understanding of the immune system functioning and benefits of immunotherapy with immune checkpoint inhibitors (PD-1) for CSCC that has changed the therapeutic approach. According to recent clinical trials data, new treatment options with PD-1 inhibitors achieved a response rate of 50% for locally advanced CSCC and 47% for metastatic CSCC, including 16.1% complete remissions. This review focuses on the molecular profile, targeted therapies and immunotherapy for locally advanced and metastatic CSCC.

scholarly journals Cutaneous Squamous Cell Carcinoma: From Pathophysiology to Novel Therapeutic Approaches

Biomedicines ◽  
2021 ◽  
Vol 9 (2) ◽  
pp. 171
Author(s):  
Luca Fania ◽  
Dario Didona ◽  
Francesca Romana Di Pietro ◽  
Sofia Verkhovskaia ◽  
Roberto Morese ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Skin Cancer ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
De Novo ◽  
Checkpoint Inhibitors ◽  
Locally Advanced ◽  
Cutaneous Squamous Cell Carcinoma ◽  
Gradual Process

Cutaneous squamous cell carcinoma (cSCC), a non-melanoma skin cancer, is a keratinocyte carcinoma representing one of the most common cancers with an increasing incidence. cSCC could be in situ (e.g., Bowen’s disease) or an invasive form. A significant cSCC risk factor is advanced age, together with cumulative sun exposure, fair skin, prolonged immunosuppression, and previous skin cancer diagnoses. Although most cSCCs can be treated by surgery, a fraction of them recur and metastasize, leading to death. cSCC could arise de novo or be the result of a progression of the actinic keratosis, an in situ carcinoma. The multistage process of cSCC development and progression is characterized by mutations in the genes involved in epidermal homeostasis and by several alterations, such as epigenetic modifications, viral infections, or microenvironmental changes. Thus, cSCC development is a gradual process with several histological- and pathological-defined stages. Dermoscopy and reflectance confocal microscopy enhanced the diagnostic accuracy of cSCC. Surgical excision is the first-line treatment for invasive cSCC. Moreover, radiotherapy may be considered as a primary treatment in patients not candidates for surgery. Extensive studies of cSCC pathogenic mechanisms identified several pharmaceutical targets and allowed the development of new systemic therapies, including immunotherapy with immune checkpoint inhibitors, such as Cemiplimab, and epidermal growth factor receptor inhibitors for metastatic and locally advanced cSCC. Furthermore, the implementation of prevention measures has been useful in patient management.

scholarly journals Huaier Inhibits Proliferation, Migration, and Invasion of Cutaneous Squamous Cell Carcinoma Cells by Inhibiting the Methylation Levels of CDKN2A and TP53

2021 ◽  
Vol 20 ◽  
pp. 153473542110316
Author(s):  
Liang Wang ◽  
Lei Xu ◽  
Yu Wang
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Dna Methyltransferase ◽  
Cutaneous Squamous Cell Carcinoma ◽  
Migration And Invasion ◽  
Dependent Manner ◽  
Concentration Gradients ◽  
A431 Cells

Cutaneous squamous cell carcinoma (CSCC) is a malignant tumor that originates from keratinocytes in the epidermis or appendage. Traditional Chinese medicine Huaier has anti-tumor activity in various malignancies. Little is known about the role of Huaier in CSCC. Here, we investigated the function of Huaier in CSCC. We treated CSCC cell line (SCL-1 and A431) with a series of concentration gradients of Huaier to examine the half maximal inhibitory concentration (IC50) of Huaier on SCL-1 and A431 cells. The IC50 of Huaier on growth of SCL-1 and A431 cells were 6.96 and 7.57 mg/mL, respectively. Moreover, Huaier reduced the methylation levels of CDKN2A and TP53, and enhanced the expression of CDKN2A and TP53 in SCL-1 and A431 cells in a dosage-dependent manner. The expression of DNA methyltransferase DNMT1 was severely repressed by Huaier treatment in SCL-1 and A431 cells. DNMT1 overexpression enhanced the methylation levels of CDKN2A and TP53, and suppressed the expression of CDKN2A and TP53 in Huaier-treated SCL-1 and A431 cells. Huaier treatment inhibited proliferation, migration, and invasion of SCL-1 and A431 cells. However, inhibition of CDKN2A or TP53 reversed the influence of Huaier treatment on proliferation, migration, and invasion of CSCC cells. In conclusion, our data demonstrate that Huaier inhibits proliferation, migration, and invasion of CSCC cells by regulating DNA methylation of CDKN2A and TP53, thereby attenuating the progression of CSCC. Thus, Huaier extract may act as a drug for treating CSCC.

Cemiplimab in a very frail population of patients with advanced or metastatic cutaneous squamous cell carcinoma: A monocenter real-life experience from Italy.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e21524-e21524
Author(s):  
Michele Guida ◽  
Annarita Fanizzi ◽  
Davide Quaresmini ◽  
Annalisa Nardone ◽  
Andrea Armenio ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Antitumor Activity ◽  
Cell Carcinoma ◽  
Clinical Outcomes ◽  
Squamous Cell ◽  
Life Experience ◽  
Locally Advanced ◽  
Real Life ◽  
Cutaneous Squamous Cell Carcinoma ◽  
High Antitumor Activity

e21524 Background: Cutaneous squamous cell carcinoma (CSCC) is the second most common skin cancer. Although representing less than 5% of all CSCCs, advanced stages are difficult to treat. Cemiplimab, an antiPD-1 monoclonal antibody, is the first approved immunotherapy in the US and EU for patients with locally advanced (laCSCC) or metastatic (mCSCC) CSCC. Phase I-II studies showed high antitumor activity and good tolerability, but few data are still available regarding cemiplimab in real life experience in non-selected patients. Methods: We recruited 30 consecutive patients with laCSCC (25 pts) and mCSCC (5 pts) treated with cemiplimab from August 2019 to November 2020 at our Institution. Median age was 81 years (range 36-95); 24 males; median ECOG PS 1 (range 0-2). Five patients had an immunosuppressive condition including 3 patients with stable hematologic malignancies and two patients on immunosuppressive therapy for kidney transplantation and Crohn’s disease, respectively. The majority of patients had comorbidities (median 3). Cemiplimab was administered at the flat dose of 350 mg i.v. every 21 days until disease progression or unacceptable toxicity. In all patients we evaluated clinical outcomes, toxicity, and associations between clinical outcomes and peripheral blood parameters. Results: We reported 23 responses (ORR 76.7%) with CR in 5 patients (16.7%). One patient had SD for 5 months. The global DCR was 80%. The median duration of response and PFS was not reached at a median follow-up of 6 months. We observed a higher ORR in head and neck primary tumours (87% vs. 42.9% of others, p = 0.016) and in patients with haemoglobin level > 12 g/dL (87.5% vs. 64.3%). No significative difference in ORR was observed with respect to the median age (81.3% in >81 years vs. 71.4% in < 81 years). Among the 5 patients with immunosuppressive status, a response was obtained in 4 patients (80%), including 1 CR. Nine patients died, 7 for PD and 2 for causes unrelated to the disease. Twenty patients (67.7%) still have an ongoing response. The treatment was well tolerated by the majority of patients. The most common adverse events were fatigue in 7 patients (23.3%) and skin toxicity in 10 patients (33.3%) including pruritus in 6 patients, rash in 3 patients, bullous erythema in 1 patient. Only 3 (10%) patients experienced severe (grade 3/4) toxicity. Three responder patients interrupted treatment (2 for toxicity after 7 and 9 cycles, and one for pre-existing dementia) but maintaining their response. Conclusions: In our real-life experience cemiplimab showed high antitumor activity with acceptable safety profile similar to those in selected patients of trials. Moreover, its antitumor activity resulted not impaired in very elderly patients or in those with immunocompromized status.

Cetuximab‐radiotherapy combination in the management of locally advanced cutaneous squamous cell carcinoma

2018 ◽  
Vol 63 (2) ◽  
pp. 257-263 ◽  
Author(s):  
Kurian Joseph ◽  
Khalifa Alkaabi ◽  
Heather Warkentin ◽  
Sunita Ghosh ◽  
Naresh Jha ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Locally Advanced ◽  
Cutaneous Squamous Cell Carcinoma
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