Advanced Squamous Cell Carcinoma Of Skin Research Articles

Navigating a Complex Intersection: Immunotherapy and Radiotherapy Synergy in Squamous Cell Carcinoma of the Skin—A Comprehensive Literature Review

Skin squamous cell carcinoma (SCC) represents a major public health concern due to its high incidence and potential for local invasion and metastasis. Compared to local recurrence, metastatic SCC represents an even greater therapeutic challenge. Once distant metastasis occurs, the disease becomes incurable, and treatment focuses on palliation and prolonging survival. The immune microenvironment of SCC is characterized by an infiltration of immune cells, including tumor-infiltrating lymphocytes. In addition to its direct cytotoxic effects, radiotherapy also induces immunomodulatory effects within the tumor microenvironment. Radiation can promote the release of tumor-associated antigens and induce immunogenic cell death, thereby enhancing the recognition of tumor cells by the immune system. Immunotherapy and radiotherapy have emerged as promising therapeutic modalities for metastatic SCC. This literature review aims to evaluate the potential synergy between these treatments and shed light on their combined efficacy. Within the manuscript, we present a compelling case report of a patient with advanced SCC who exhibited resistance to the combined regimen of immunotherapy and radiotherapy, leading to disease progression. Despite the increasing evidence supporting the synergy between these modalities, this case underscores the complex nature of treatment response and the importance of considering individual patient characteristics.

Major Limb Amputation Secondary to Locally Advanced Cutaneous Squamous Cell Carcinoma in Tropical Environments: Determinants

Objective: To identify the determinants of secondary limb amputation in advanced squamous cell carcinoma. Material and Methods: This was a retrospective study carried out in the Orthopedic Traumatology Department of the Bouake University Hospital in Cote d’Ivoire from January 2013 to December 2016. It involved ten patients with locally advanced skin squamous cell carcinoma, confirmed by histology and having amputated limbs. The parameters studied were: demographic data (gender, age), socio-economic conditions (occupation, place of residence), the risk factors involved, the use of topical self-medication and the use of traditional medicine, antecedents and comorbidities factors, lifestyle, clinical aspects (seat, size), extension assessment (X-ray), anatomo-pathological examination data, duration of evolution of squamous cell carcinoma, the function of the affected limb, the treatment performed, the evolutionary modalities and the equipment. Results: Between 2013 and 2016, ten patients underwent either upper or lower limb amputations following locally advanced squamous cell carcinoma. The average age was 34.1 years (19 - 64 years). There were 7 men (70%) and 3 women (30%) and all our patients were black (sub-Saharan Africa). The majority of our patients were farmers (70%). The risk factors for squamous cell carcinoma were neglected chronic wounds. All our patients recognized during the interrogation a large use of the topicals of traditional medicine for the treatment of the initial cutaneous lesions. In terms of lifestyle, five (50%) were smokers and alcoholics. The mean time to progression of squamous cell carcinoma was 5.9 years. Lesions were localized preferentially to the pelvic limbs six (60%) cases and four (40%) to the limbs chest. The lesion was diagnosed late in all our patients. The size of the tumor in all our patients was greater than 5 cm and had a deep invasion (nerves, vessels and bone). The proximal ipsilateral ganglionic invasion was constant. The extension assessment (chest X-ray) showed two cases of pulmonary metastases. Seven patients (70%) had well-differentiated tumors. All patients underwent amputation of the affected limb, sometimes coupled with an accessible lymph node dissection. The evolution was favorable (no recurrence and infection of the amputation stump). The function of the affected limb was limited in all our patients. Seven patients (70%) survive, three of whom have been fitted to the lower limb and are regularly followed on an outpatient basis. We noted three (30%) deaths after the surgical treatment. Conclusion: Limb amputation in patients with locally advanced skin squamous cell carcinoma may be associated with cancer aggressiveness, the socio-economic conditions of patients, the quality of care, and the patient’s relationship to the disease.

Efficacy of neoadjuvant cetuximab alone or with platinum salt for the treatment of unresectable advanced nonmetastatic cutaneous squamous cell carcinomas.

Refractory locally advanced or metastatic nonmelanoma skin cancer (NMSC) is a frequent therapeutic impasse. To address the question of the efficacy of induction therapy with cetuximab as neoadjuvant treatment for locally advanced NMSC. From 2008 to 2013, all patients with a diagnosis of unresectable locally advanced skin squamous cell carcinoma were treated with neoadjuvant cetuximab alone (CM) or combined with a platinum salt and 5-fluorouracil (CC). Resectability, and clinical and pathological response, as well as relapse-free and overall survival were evaluated. Thirty-four patients, with a median age of 74·5years, were evaluated. Twenty-five patients received CC. After three cycles of CC, 23 of 25 patients whose tumours were initially unresectable became amenable to surgery (92%). A complete histological response was observed in 15 (65%) patients. The mean progression-free and mean overall survival in operated patients were 8·5 and 26·0months, respectively. There was a good response in terms of resectability and tumour control in the majority of patients, with few relapses, despite the initially poor prognosis of these tumours in this elderly group of patients. However, this therapeutic strategy needs to be validated in a prospective, randomized study.

Cetuximab in non-melanoma skin cancer

Introduction: Non-melanoma skin cancer (NMSC) has become the most common cancer with squamous cell carcinoma (SCC) as the major cause of morbidity and mortality.Review areas covered: The chimeric human–mouse monoclonal antibody Cetuximab against epidermal growth factor receptor (EGFR) has been approved for advanced head and neck cancer (HNC). Since SCC has been shown to express the EGFR, EGFR-targeted therapy is an option.Methodology:A PUBMED® research 2000 – 2012 have been conducted using the following items: “Non-melanoma skin cancer AND cetuximab,” “cutaneous squamous cell carcinoma AND cetuximab,” and “basal cell carcinoma AND cetuximab.”Results: Current evidence of cetuximab efficacy in NMSC results from a Phase II trial and case reports. Cetuximab can be combined with radiotherapy in analogy to HNC. The total response rate is almost 50% in patients with SCC. The combination with radiotherapy resulted in a complete response rate of 50%. Management of adverse reactions in SCC with particular emphasis on cutaneous toxicities is necessary. Further controlled trials are needed.Expert opinion: EGFR inhibitor cetuximab is an option for recurrent or advanced SCC of skin. The combination with radiotherapy seems to be superior to cetuximab alone.

Cetuximab as first-line monotherapy in patients with skin unresectable squamous cell carcinoma: Final results of a phase II multicenter study.

8510 Background: Patients (pts) with advanced skin squamous cell carcinoma (SSCC) have a poor prognosis. The objective of the study was to evaluate single agent cetuximab (C) as first-line therapy for unresectable SCCS. Methods: Pts with advanced or metastatic EGFR expressing SCCS, ECOG PS ≤ 2 were eligible. No prior chemotherapy was allowed. C was kindly provided by Merck KGaA and administered iv weekly (400 mg/m2 initial dose followed by 250 mg/m2). Disease was evaluated by MRI or CT every 6 wks and independently assessed. Endpoints were disease control rate (DCR) at 6 wks, best objective response rate (ORR) (RECIST criteria) and toxicity, along with determination of KRAS mutations and FcγR genotypes. Statistical analyses were carried out both in the intent to treat (ITT) and per protocol (PP) populations. Results: Between Oct 2005 and Apr 2008, 36 pts were recruited: 58% were males, median age was 79 yrs (range 32-95), median PS was 1 (47%) and 72% of SCCS were AJCC stage 3; 31 pts were evaluable for tumor response and 36 for toxicity. DCR at 6 wks was 69% in the ITT population and 81% in the PP population (21 SD, 3 PR and 1 CR). Best ORR and DCR were 32% and 81% respectively in PP (15 SD, 8PR and 2 CR). Fourteen pts died: 6 due to disease progression; 4 were consideredas NOS and 3 sudden deaths were of unknown causes. Grade ¾ events were noted in 23 pts: infections (22%), nausea/vomiting (3%), anemia (4%), tumor bleeding (8%) and 4 C-related adverse events (2 grade 4 infusion reactions, 1 grade 3 interstitial pneumopathy and 1 grade 3 paronychia). Grade ½ acneiform rash occurred in 78% of pts. No KRAS mutation was identified in the 28 studied pts. In pts with FcγRIIa-131H/H and/or FcγRIIIa-158V/V genotypes, the PFS was similar in 131R and 158F carriers (5.4 vs. 3.5 mths; p = 0.34). Conclusions: Single agent C achieves 69% disease control rate as first-line treatment in pts with unresectable SCCS, therefore representing an interesting therapeutic option, especially in elderly pts. No significant financial relationships to disclose.