Journal of Clinical and Aesthetic Dermatology • Hot Topics in Squamous Cell Carcinoma July 2024 • Journal Watch

☛ In the digital edition, click the PMID after each summary to access the article/abstract.

Integrating the 40-gene expression profile (40-GEP) test improves metastatic risk-stratification within clinically relevant subgroups of highrisk cutaneous squamous cell carcinoma (cSCC) patients

Wysong A, Somani AK, Ibrahim SF, et al. Dermatol Ther (Heidelb). 2024;14(3):593–612.

Summary. Here, Wysong et al assessed risk stratification of the 40-gene expression profile (GEP) test among 897 patients with cutaneous squamous cell carcinoma (cSCC) in clinically relevant subgroups. Patients with a Class 1 (low risk) result had the highest three-year metastasis-free survival (MFS, 94.1%), followed by those with Class 2A (higher risk) and 2B (highest risk) results (81.1% and 56.8%, respectively). Seventy-two percent of metastatic events occurred in patients with Class 2A or 2B results. Multivariate analysis showed that Class 2A and 2B results were significant independent predictors of metastasis. Metastatic risk prediction was significantly more accurate when the 40-GEP test was combined with risk classification systems.

Therapies for cutaneous squamous cell carcinoma in recessive dystrophic epidermolysis bullosa: a systematic review of 157 cases

Summary. In this review of 163 studies, 157 cases of recessive dystrophic epidermolysis bullosa (RDEB) with cSCC were identified. Surgery was the most common treatment option, reported in 131 cases. Eleven patients were treated with immunotherapy, and antiepidermal growth factor receptor therapy was utilized in 13 patients. Undergoing treatments in addition to surgery appeared to prolong survival. Age at first cSCC diagnosis did not impact length of survival.

Lymph node metastasis in cutaneous squamous cell carcinoma of the head and neck

Summary. Among 126 patients with cSCC of the head and neck with parotid lymph node involvement, 79 underwent radical parotidectomy and 47 underwent superficial parotidectomy. Eighty patients had intraparotid lymph node metastasis, and 30 had positive periparotid lymph nodes. There was a significant association between periparotid lymph node metastasis and decreased locoregional control (LRC). Intra- and periparotid lymph node metastasis were linked to decreased overall survival (OS). Extranodal extension of cervical lymph nodes was a predictor of worse LRC and OS.

Low-level expression of p-S6 is associated with nodal metastasis in patients with head and neck cSCC

Gómez-de Castro C, Santos-Juanes R, Nuñez- Gómez B, et al. Int J Mol Sci. 2024;25(8):4304.

Summary. In this study, researchers assessed the impact of ribosomal protein S6 (p-S6) and p21 on head and neck cSCC. Among 116 patients, 61 (52.5%) had p-S6 expression in over 50 percent of tumor cells and 96 (82.8%) had p21 expression in over 10 percent of tumor cells. Expression of both proteins was higher in nonmetastatic disease. According to multivariate analysis, p-S6 negativity was a significant predictor of nodal metastasis, whereas there was no association between p21 and nodal metastasis. Patients with p-S6 positivity had significantly superior nodal MFS, mortality, and OS, compared to those with p-S6 negativity. Patients with p21 negativity had significantly worse nodal MFS, compared to those with p21 positivity.

MiR-34a-5p suppresses cutaneous squamous cell carcinoma progression by targeting SIRT6

Summary. Chen et al found that the microribonucleic acid (miRNA) miR-34a-5p was downregulated in cSCC tissue and cell samples, compared to controls. Sirtuin 6 (SIRT6) messenger RNA (mRNA) expression was increased in cSCC samples, compared to controls. Further analysis highlighted a significant negative correlation between SIRT6 mRNA and miR-34a-5p. Upregulation of miR- 34a-5p resulted in decreased cell proliferation and migration, and miR-34a-5p contributed to cell apoptosis. Overexpression of SIRT6 inhibited the anti-tumor effects of miR-34a-5p.

Multidisciplinary management of cutaneous squamous cell carcinoma of the scalp: an algorithm for reconstruction and treatment

Summary. Among 243 cases of cSCC of the scalp, the most frequent form of reconstruction was skin grafting (n=115), followed by primary closures (n=76) and local flaps (n=33). Primary closures were found to benefit cases with partial-thickness defects up to 3cm in diameter, while local flaps from adjacent scalp skin were often utilized in cases with partial-thickness defects ranging from 1 to 5cm. Cases with partial-thickness medium-to-large defects (up to 10cm) were treated with skin grafting. Patients who were ineligible for surgery underwent radiotherapy or immunotherapy.

Assessment of perineural spread in advanced cutaneous squamous cell carcinomas treated with immunotherapy

Summary. In this study, researchers evaluated perineural spread (PNS) response in 20 patients with advanced cSCC and baseline PNS treated with cemiplimab (n=17) or pembrolizumab (n=3). Partial response, as measured by the Perineural Involvement Response Assessment Criteria (PNI-RAC), was achieved by 14 patients within five months. By the end of the study period, complete resolution of PNS was recorded in seven patients. PNS responses correlated with RECIST 1.1 after 10 months. In a blinded review, five of 14 cases were noted for potential PNS on fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT).

Improved survival over time with immunotherapy in locally advanced and metastatic cutaneous squamous cell carcinomas

Schneider S, Ferte T, Ducharme O, et al. J Cancer Res Clin Oncol. 2024;150(3):133.

Summary. From July 2015 to July 2020, 127 patients initiated systemic therapy for advanced cSCC. Any-grade and Grade 3 or higher adverse events (AEs) occurred in 27 and 17 patients, respectively. Median OS was 20 months in Period 2 (January 1, 2018–July 1, 2020), which was significantly higher than in Period 1 (July 1, 2015–December 31, 2017; median OS: 10 months). There was a 61-percent decreased risk of morality in patients treated with immunotherapy. Immunosuppression was linked to higher risk of death and recurrence or progression, and older age was associated with increased risk of progression. Second-line immunotherapy was associated with a 71- and 67-percent reduced risk of mortality and relapse, respectively, compared to other second-line therapies.

The immune response of cutaneous basosquamous and squamous cell carcinoma associated with sun exposure

Grigore A, Oproiu AM, Iancu I, Florescu IP. Curr Oncol. 2024;31(5):2481–2487.

Summary. Among 132 patients, about 67 percent had cSCC and 33 percent had basosquamous cell carcinoma (BSC). Most patients (80%) had high lifetime sun exposure, which was determined based on self-reported average number of hours spent in the sun without utilizing sun protection. Lymphocyte percentage was significantly higher in the high sun exposure group, whereas neutrophilto-lymphocyte ratio (NLR) was significantly higher in the low sun exposure group. In cSCC, NLR, lymphocyte percentage, and erythrocyte sedimentation rate were increased and lymphocyte-to-monocyte ratio was decreased, compared to BSC.

RESEARCH BITE—Parotid gland metastases of cutaneous SCC of the head: occult metastases occurrence and their late manifestation

In this retrospective study, Horakova et al analyzed the impact of parotid and cervical lymph node metastasis in cutaneous squamous cell carcinoma (cSCC) of the head. Among 39 patients, 32 had Stage cN3b disease, all of whom also had extracapsular extension. Twenty-four patients had parotid lymph node metastasis only, and 15 had simultaneous parotid and cervical lymph node metastasis. Parotidectomy was performed in most patients (n=26) followed by radiotherapy alone (n=9) and symptomatic therapy (n=4). Five-year disease-free interval and overall survival were 55 and 52 percent, respectively. Median survival was significantly prolonged with surgery and postoperative radiotherapy, compared to surgery alone.

Source: Horakova Z, Starek I, Zapletalova J, Salzman R. Parotid gland metastases of cutaneous squamous cell carcinoma of the head: occult metastases occurrence and their late manifestation. Int J Clin Pract. 2024;2024:5525741.

RESEARCH BITE—Impact of cemiplimab treatment duration on clinical outcomes in advanced cutaneous squamous cell carcinoma

Among 95 patients with advanced cutaneous squamous cell carcinoma (cSCC) treated with cemiplimab, 73 received standard treatment (STS group) and 22 discontinued due to causes other than disease progression (DBC group). Median treatment duration was 27.9 months. Median overall survival (OS) and disease-specific survival (DSS) were 28.3 and not reached in the DBC group, respectively. Median OS and DSS were both 25.2 months in the STS group. Median progression-free survival (PFS) was 27.9 months in the DBC group and 8.8 months in the STS group. There were no significant differences in survival outcomes between the two groups.

Source: Mallardo D, Sparano F, Vitale MG, et al. Impact of cemiplimab treatment duration on clinical outcomes in advanced cutaneous squamous cell carcinoma. Cancer Immunol Immunother. 2024;73(8):160.