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Research Progress of Cutaneous Squamous and Basal Cell Carcinomas
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Research Progress of Cutaneous Squamous and Basal Cell Carcinomas

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Tumor Microenvironment".

Deadline for manuscript submissions: closed (15 May 2023) | Viewed by 29074

Special Issue Editors

Dr. Frederico O. Gleber-Netto

E-Mail Website
Guest Editor
Department of Head and Neck Surgery, Division of Surgery, MD Anderson Cancer Center, Houston, TX 77030, USA
Interests: translational research; cancer genomics; squamous cell carcinoma; biomarkers
Special Issues, Collections and Topics in MDPI journals
Dr. Moran Amit

E-Mail Website
Guest Editor
Department of Head and Neck Surgery, Division of Surgery, MD Anderson Cancer Center, Houston, TX 77030, USA
Interests: cancer; neuroscience; tumor microenvironment; immunotherapy; head and neck
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

We are pleased to invite you to contribute to this Special Issue, which aims to explore the relationship between the TIME(tumor immune microenvironment) and the development, progression and treatment of cuSCC.

More than a million new cases of cutaneous squamous cell carcinomas (cuSCC) are diagnosed yearly in the USA, and their incidence is expected to increase worldwide as the population increases in age. As opposed to other nonmelanoma skin cancers, cuSCC are associated with an increased rate of distant metastasis and elevated morbimortality.

Immunosuppression is directly related to the risk of cuSCC development, and chronically immunosuppressed individuals, such as organ transplant recipients and those with hematological malignancies, represent a significant chunk of cuSCC patients. Unfortunately, since immunodeficiency is a major risk factor for metastatic dissemination, these vulnerable patients are more prone to develop advanced disease.

Chronic ultraviolet exposure (UV) is a major etiological factor for cuSCC and promotes a unique mutation signature in these tumors. It is also an important immunosuppressive agent and may contribute to a reduction in the local immunosurveillance, favoring pro-tumorigenic changes such as skin infection by beta human papillomavirus (HPV), which is considered an important promoter of skin carcinogenesis.

Although the relevance of the tumor immune microenvironment (TIME) in the initiation and progression of cuSCC is widely accepted, our understanding of the intricated relationship between the TIME and the cuSCC is limited. Consequently, development and application of new measures for prevention and treatment of cuSCC, especially those linked to immunomodulation, require further exploration.

Original research articles and reviews are welcome. We look forward to receiving your contributions.

Dr. Frederico O. Gleber-Netto
Dr. Moran Amit
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cancers is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • tumor immune microenvironment
  • cutaneous squamous cell carcinoma
  • immunodeficiency
  • biomarkers
  • therapeutics
  • ultraviolet

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Published Papers (11 papers)

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Research

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12 pages, 888 KiB  
Article
Cetuximab for Immunotherapy-Refractory/Ineligible Cutaneous Squamous Cell Carcinoma
by Julian A. Marin-Acevedo, Bethany M. Withycombe, Youngchul Kim, Andrew S. Brohl, Zeynep Eroglu, Joseph Markowitz, Ahmad A. Tarhini, Kenneth Y. Tsai and Nikhil I. Khushalani
Cancers 2023, 15(12), 3180; https://doi.org/10.3390/cancers15123180 - 14 Jun 2023
Cited by 10 | Viewed by 2191
Abstract
Anti-PD1 therapy demonstrated impressive, prolonged responses in advanced cutaneous squamous cell carcinoma (CSCC). Therapy for ICI-refractory/ineligible disease remains unclear. We performed a retrospective analysis in locally-advanced/metastatic CSCC using cetuximab across three cohorts: immediately after ICI failure (A), not immediately following ICI failure (B), [...] Read more.
Anti-PD1 therapy demonstrated impressive, prolonged responses in advanced cutaneous squamous cell carcinoma (CSCC). Therapy for ICI-refractory/ineligible disease remains unclear. We performed a retrospective analysis in locally-advanced/metastatic CSCC using cetuximab across three cohorts: immediately after ICI failure (A), not immediately following ICI failure (B), or without prior ICI (C). The primary endpoint was the overall response rate (ORR). Secondary endpoints included disease-control rate (DCR), progression-free survival (PFS), overall survival (OS), time-to-response (TTR) and toxicity. Twenty-three patients were included. In cohort A (n = 11), the ORR was 64% and DCR was 91%, with six ongoing responses at data cutoff. In cohort B (n = 2), all patients had progression as the best response. At a median follow-up of 21 months for A and B, TTR and PFS were 2.0 and 17.3 months, respectively. The median OS was not reached. In cohort C (n = 10), the ORR and DCR were 80%, including five ongoing responses at the data cutoff. At a median follow-up of 22.4 months, the TTR, PFS and OS were 2.5, 7.3 and 23.1 months, respectively. Cetuximab was well tolerated in all cohorts. In summary, cetuximab is effective in patients with failure/contraindications to ICI. Cetuximab immediately after ICI failure yielded particularly fast, durable responses. If confirmed, this could be the preferred therapy following ICI failure. Full article
(This article belongs to the Special Issue Research Progress of Cutaneous Squamous and Basal Cell Carcinomas)
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12 pages, 1286 KiB  
Article
Cutaneous Squamous Cell Carcinoma in Immunocompromised Patients—A Comparison between Different Immunomodulating Conditions
by Ofir Zavdy, Tara Coreanu, Dvir Yohai Bar-On, Amit Ritter, Gideon Bachar, Thomas Shpitzer, Noga Kurman, Muhammad Mansour, Dean Ad-El, Uri Rozovski, Gilad Itchaki, Shany Sherman, Limor Azulay-Gitter and Aviram Mizrachi
Cancers 2023, 15(6), 1764; https://doi.org/10.3390/cancers15061764 - 14 Mar 2023
Cited by 10 | Viewed by 2387
Abstract
Background: Immunosuppression is strongly associated with an increased risk of developing cutaneous squamous cell carcinoma (cSCC). Studies on solid organ transplant recipients (SOTR) and chronic lymphocytic leukemia (CLL) patients have already demonstrated higher rates of aggressive cSCC tumors in these populations compared to [...] Read more.
Background: Immunosuppression is strongly associated with an increased risk of developing cutaneous squamous cell carcinoma (cSCC). Studies on solid organ transplant recipients (SOTR) and chronic lymphocytic leukemia (CLL) patients have already demonstrated higher rates of aggressive cSCC tumors in these populations compared to immunocompetent controls. Studies on other immunosuppressed patient groups are scarce. This study was aimed at assessing the effects of different immunomodulating conditions on patients diagnosed with cSCC. We sought to compare the clinical features, treatments, and survival rates among the different study groups, as well as outcomes to those of immunocompetent controls with cSCC. Methods: A retrospective analysis of 465 cSCC patients, both immunosuppressed (IS) and immunocompetent controls. Etiologies for immunosuppression included SOTR, CLL, chronic kidney disease (CKD), psoriasis, rheumatoid arthritis (RA) and systemic lupus erythematous (SLE). Results: Compared to the control group, IS patients demonstrated several significant differences. These include higher rates of positive resection margins, higher recurrence rates, and multiple SCC tumors. Patients in the IS group, who were also given immunomodulating agents, demonstrated even lower survival rates. Cox regression analysis demonstrated statistically significant decreased overall survival (OS) rates for IS patients compared to the controls (OR = 1.9, p = 0.031). SOTR patients tend to have multiple cSCC tumors (35%), with the highest number of primary tumors compared to controls (2.54 tumors per patient on average, p < 0.001), but also compared to all other IS groups. The average SCC lesion size in the SOTR group was the smallest, measuring at 13.5 mm, compared to the control group and all other IS groups. Decreased survival rates were seen on Cox regression analysis compared to controls (HR = 2.4, p = 0.001), but also to all other IS groups. CLL patients also had the highest rates of positive margins compared to controls (36% vs. 9%, p < 0.01) and to all other IS groups. They were also most likely to get adjuvant or definitive oncological treatments, either radiotherapy or chemotherapy, compared to controls (36% vs. 15%, p = 0.02) and to other IS groups. Patients in the CKD group demonstrated the highest rates for multiple cSCC (OR = 4.7, p = 0.001) and the worst rates of survival on Cox regression analysis (HR = 3.2, p = 0.001). Both rheumatoid arthritis and psoriasis patients demonstrated the shortest disease-free survival rates (2.9y ± 1.1, 2.3y ± 0.7, respectively), compared to controls (4.1y ± 2.8) and to all other IS groups. Conclusions: Among cSCC patients, immunosuppression due to SOTR, CLL, CKD, RA, and psoriasis is associated with worse outcomes compared to controls and other IS groups. These patients should be regarded as high-risk for developing aggressive cSCC tumors. This study is the first to assess and compare cSCC outcomes among multiple IS patient groups. Full article
(This article belongs to the Special Issue Research Progress of Cutaneous Squamous and Basal Cell Carcinomas)
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12 pages, 1826 KiB  
Article
Feasibility of Intratumoral Anti-PD1 as Treatment of Human Basal Cell Carcinoma: An Explorative Study with Adjuvant Ablative Fractional Laser
by Silje Haukali Omland, Jacob Secher Ejlertsen, Dorrit Krustrup, Rikke Louise Christensen, Inge Marie Svane, Uffe Hoegh Olesen and Merete Hædersdal
Cancers 2022, 14(23), 5815; https://doi.org/10.3390/cancers14235815 - 25 Nov 2022
Cited by 4 | Viewed by 1687
Abstract
The use of immune checkpoint inhibitors (ICI) is expanding with the approval for advanced/metastatic keratinocyte carcinoma; however, most tumors are non-aggressive. Local administration could broaden ICI, but adequate immune response might require an immune-attractive adjuvant such as ablative fractional laser (AFL). Accordingly, this [...] Read more.
The use of immune checkpoint inhibitors (ICI) is expanding with the approval for advanced/metastatic keratinocyte carcinoma; however, most tumors are non-aggressive. Local administration could broaden ICI, but adequate immune response might require an immune-attractive adjuvant such as ablative fractional laser (AFL). Accordingly, this study aimed to explore intratumoral injection of anti-PD1 with and without AFL in basal cell carcinoma (BCC), exploring anti-PD1 concentration, immune cell infiltration, tumor response, and safety. This open-label, proof-of-concept trial investigated intratumoral anti-PD1 + AFL combination therapy versus anti-PD1 or AFL monotherapy in 28 BCC patients. The primary endpoints were immune cell infiltration evaluated immunohistochemically and clinical tumor response after 3 months. The secondary outcomes were tumoral drug concentration and safety. The most robust response was obtained following intervention with combined anti-PD1+AFL, leading to a ~2.5-fold increase in CD3+ cells (p = 0.027), and tumor reduction ≥25% in 73%, including two tumors with complete remission. Upon anti-PD1 monotherapy, a slight decrease in CD3+ cells was observed while a non-significant increase following AFL was seen. Tumor reduction ≥25% was seen in 45% and 50%, respectively, after anti-PD1 and AFL monotherapy. The CD8/CD3 ratio remained unchanged after anti-PD1+AFL and anti-PD1 monotherapy, while AFL led to a decreased ratio. A non-significant decline in the Foxp3/CD3 ratio was observed for all groups. Side-effects were mild with no systemic drug concentration detected. Intratumoral anti-PD1 injection is feasible, and a single exposure to locally injected anti-PD1 with adjuvant AFL increased immune cell infiltration and reduction in BCC with limited side-effects. Full article
(This article belongs to the Special Issue Research Progress of Cutaneous Squamous and Basal Cell Carcinomas)
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11 pages, 1229 KiB  
Article
Risk Factors and Clinicopathological Features for Developing a Subsequent Primary Cutaneous Squamous and Basal Cell Carcinomas
by Magdalena Ciążyńska, Marta Pabianek, Martyna Sławińska, Adam Reich, Bogumił Lewandowski, Katarzyna Szczepaniak, Małgorzata Ułańska, Dariusz Nejc, Robert Brodowski, Michał Sobjanek, Witold Owczarek, Grażyna Kamińska-Winciorek, Dariusz Lange, Monika Słowińska, Katarzyna Wróbel, Andrzej Bieniek, Anna Woźniacka, Anika Pękala, Łukasz Kuncman, Magdalena Salińska, Marcin Noweta, Małgorzata Skibińska, Joanna Narbutt, Karol Ciążyński, Marta Lewandowska, Elżbieta Dziankowska-Zaborszczyk and Aleksandra Lesiakadd Show full author list remove Hide full author list
Cancers 2022, 14(13), 3069; https://doi.org/10.3390/cancers14133069 - 23 Jun 2022
Cited by 9 | Viewed by 2463
Abstract
Background: Patients with diagnosed keratinocyte carcinomas (KCs) have an increased risk of subsequent skin cancers development. Current studies indicate that patients with subsequent tumors should be followed up regularly. However, none of the studies indicate the connection between the specific subtypes and an [...] Read more.
Background: Patients with diagnosed keratinocyte carcinomas (KCs) have an increased risk of subsequent skin cancers development. Current studies indicate that patients with subsequent tumors should be followed up regularly. However, none of the studies indicate the connection between the specific subtypes and an increased risk for further KCs development. The study assesses the differences in the risk of developing a subsequent skin cancer after a previous diagnosis of KC, especially considering individual types of skin malignances, and identifies potential factors associated with an increased risk of new cutaneous tumor describing non-invasive diagnosis and monitoring. Methods: Pathology and medical records were examined to identify the characteristics of patients with multiple KCs diagnosed between 1999 and 2019. Results: The study group comprised 13,913 KCs occurring in 10,083 patients. Multiple KCs were observed in 2300 patients (22.8%). The analysis showed aggressive subtypes, multiple tumors, and male sex as significant prognostic factors. Conclusions: The most crucial risk factors for developing subsequent KC are being of a male gender, an aggressive tumor subtype, and previous history of multiple skin cancers. Basal cell carcinoma subtypes, such as infiltrative basosquamous, with aggressive growth patterns predispose not only to increased risk for the recurrence but are also expected to be at higher risk of subsequent KCs. Full article
(This article belongs to the Special Issue Research Progress of Cutaneous Squamous and Basal Cell Carcinomas)
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Review

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18 pages, 738 KiB  
Review
Management of Cutaneous Head and Neck Squamous and Basal Cell Carcinomas for Immunocompromised Patients
by Krishna K. Bommakanti, Nikitha Kosaraju, Kenric Tam, Wanxing Chai-Ho and Maie St. John
Cancers 2023, 15(13), 3348; https://doi.org/10.3390/cancers15133348 - 26 Jun 2023
Viewed by 1635
Abstract
The incidence of non-melanoma skin cancer (NMSC) continues to rise, and more than one million cases are diagnosed in the United States each year. The increase in prevalence has been attributed to increased lifespan and improvements in survival for conditions that increase the [...] Read more.
The incidence of non-melanoma skin cancer (NMSC) continues to rise, and more than one million cases are diagnosed in the United States each year. The increase in prevalence has been attributed to increased lifespan and improvements in survival for conditions that increase the risk of these malignancies. Patients who are immunocompromised have a higher risk of developing NMSC compared to the general population. In immunosuppressed patients, a combination of prevention, frequent surveillance, and early intervention are necessary to reduce morbidity and mortality. In this review, we collate and summarize current knowledge regarding pathogenesis of head and neck cutaneous SCC and BCC within immunocompromised patients, examine the potential role of the immune response in disease progression, and detail the role of novel immunotherapies in this subset of patients. Full article
(This article belongs to the Special Issue Research Progress of Cutaneous Squamous and Basal Cell Carcinomas)
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11 pages, 932 KiB  
Review
Non-Melanoma Skin Cancer Detection in the Age of Advanced Technology: A Review
by Haleigh Stafford, Jane Buell, Elizabeth Chiang, Uma Ramesh, Michael Migden, Priyadharsini Nagarajan, Moran Amit and Dan Yaniv
Cancers 2023, 15(12), 3094; https://doi.org/10.3390/cancers15123094 - 7 Jun 2023
Cited by 7 | Viewed by 2630
Abstract
Skin cancer is the most common cancer diagnosis in the United States, with approximately one in five Americans expected to be diagnosed within their lifetime. Non-melanoma skin cancer is the most prevalent type of skin cancer, and as cases rise globally, physicians need [...] Read more.
Skin cancer is the most common cancer diagnosis in the United States, with approximately one in five Americans expected to be diagnosed within their lifetime. Non-melanoma skin cancer is the most prevalent type of skin cancer, and as cases rise globally, physicians need reliable tools for early detection. Artificial intelligence has gained substantial interest as a decision support tool in medicine, particularly in image analysis, where deep learning has proven to be an effective tool. Because specialties such as dermatology rely primarily on visual diagnoses, deep learning could have many diagnostic applications, including the diagnosis of skin cancer. Furthermore, with the advancement of mobile smartphones and their increasingly powerful cameras, deep learning technology could also be utilized in remote skin cancer screening applications. Ultimately, the available data for the detection and diagnosis of skin cancer using deep learning technology are promising, revealing sensitivity and specificity that are not inferior to those of trained dermatologists. Work is still needed to increase the clinical use of AI-based tools, but based on the current data and the attitudes of patients and physicians, deep learning technology could be used effectively as a clinical decision-making tool in collaboration with physicians to improve diagnostic efficiency and accuracy. Full article
(This article belongs to the Special Issue Research Progress of Cutaneous Squamous and Basal Cell Carcinomas)
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12 pages, 1609 KiB  
Review
Review of the Tumor Microenvironment in Basal and Squamous Cell Carcinoma
by Elizabeth Chiang, Haleigh Stafford, Jane Buell, Uma Ramesh, Moran Amit, Priyadharsini Nagarajan, Michael Migden and Dan Yaniv
Cancers 2023, 15(9), 2453; https://doi.org/10.3390/cancers15092453 - 25 Apr 2023
Cited by 10 | Viewed by 2174
Abstract
It is widely known that tumor cells of basal and squamous cell carcinoma interact with the cellular and acellular components of the tumor microenvironment to promote tumor growth and progression. While this environment differs for basal and squamous cell carcinoma, the cellular players [...] Read more.
It is widely known that tumor cells of basal and squamous cell carcinoma interact with the cellular and acellular components of the tumor microenvironment to promote tumor growth and progression. While this environment differs for basal and squamous cell carcinoma, the cellular players within both create an immunosuppressed environment by downregulating effector CD4+ and CD8+ T cells and promoting the release of pro-oncogenic Th2 cytokines. Understanding the crosstalk that occurs within the tumor microenvironment has led to the development of immunotherapeutic agents, including vismodegib and cemiplimab to treat BCC and SCC, respectively. However, further investigation of the TME will provide the opportunity to discover novel treatment options. Full article
(This article belongs to the Special Issue Research Progress of Cutaneous Squamous and Basal Cell Carcinomas)
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19 pages, 2215 KiB  
Review
The Role of Radiation Therapy in the Treatment of Non-Melanoma Skin Cancer
by Eyal Yosefof, Noga Kurman and Dan Yaniv
Cancers 2023, 15(9), 2408; https://doi.org/10.3390/cancers15092408 - 22 Apr 2023
Cited by 6 | Viewed by 3267
Abstract
Non-melanoma skin cancer (NMSC) is the most common malignancy in the United States. While surgery is considered as the main treatment modality for both cutaneous basal cell carcinoma (cBCC) and cutaneous squamous cell carcinoma (cSCC), radiotherapy plays an important role in the treatment [...] Read more.
Non-melanoma skin cancer (NMSC) is the most common malignancy in the United States. While surgery is considered as the main treatment modality for both cutaneous basal cell carcinoma (cBCC) and cutaneous squamous cell carcinoma (cSCC), radiotherapy plays an important role in the treatment of NMSC, both in the adjuvant setting for cases considered high-risk for recurrence, and in the definitive setting, when surgery is not feasible or desired by the patient. The last years have seen the emergence of immunotherapy treatment for cases of advanced cSCC in the palliative, and possibly neoadjuvant settings, making the treatment paradigm more complex. In this review, we attempt to describe the different radiation modalities available for the treatment of NMSC, the indications for adjuvant post-operative treatment with radiotherapy for cSCC, the role of radiotherapy in elective neck treatment, and the efficacy, safety, and toxicity profile of this treatment in these different settings. Furthermore, we aim to describe the efficacy of radiotherapy combined with immunotherapy as a promising horizon for treating advanced cSCC. We also aim to describe the ongoing clinical studies that attempt to examine future directions for the role of radiation treatment in NMSC. Full article
(This article belongs to the Special Issue Research Progress of Cutaneous Squamous and Basal Cell Carcinomas)
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19 pages, 505 KiB  
Review
Advances in Management and Therapeutics of Cutaneous Basal Cell Carcinoma
by Olivia M. Chen, Keemberly Kim, Chelsea Steele, Kelly M. Wilmas, Nader Aboul-Fettouh, Carrick Burns, Hung Quoc Doan, Sirunya Silapunt and Michael R. Migden
Cancers 2022, 14(15), 3720; https://doi.org/10.3390/cancers14153720 - 30 Jul 2022
Cited by 8 | Viewed by 4104
Abstract
Basal cell carcinoma (BCC), the most common cancer in humans, is a malignant neoplasm of cells derived from the basal layer of the epidermis. Tumor characteristics such as histologic subtype, primary versus recurrent tumor, anatomic location, size, and patient attributes determine the risk [...] Read more.
Basal cell carcinoma (BCC), the most common cancer in humans, is a malignant neoplasm of cells derived from the basal layer of the epidermis. Tumor characteristics such as histologic subtype, primary versus recurrent tumor, anatomic location, size, and patient attributes determine the risk level and acceptable treatment options. Surgical options offer histologic confirmation of tumor clearance. Standard excision provides post-treatment histologic assessment, while Mohs micrographic surgery (MMS) provides complete margin assessment intraoperatively. Additional treatment options may be employed in the correct clinical context. Small and low-risk BCCs, broad field cancerization, locally-advanced disease, metastatic disease, cosmetic concerns, or morbidity with surgical approaches raise consideration of other treatment modalities. We review herein a range of treatment approaches and advances in treatments for BCC, including standard excision, MMS, electrodesiccation and curettage, ablative laser treatment, radiation therapy, targeted molecular therapies, topical therapies, field therapies, immunotherapy, and experimental therapies. Full article
(This article belongs to the Special Issue Research Progress of Cutaneous Squamous and Basal Cell Carcinomas)
21 pages, 399 KiB  
Review
Advances in Cutaneous Squamous Cell Carcinoma Management
by Carrick Burns, Shelby Kubicki, Quoc-Bao Nguyen, Nader Aboul-Fettouh, Kelly M. Wilmas, Olivia M. Chen, Hung Quoc Doan, Sirunya Silapunt and Michael R. Migden
Cancers 2022, 14(15), 3653; https://doi.org/10.3390/cancers14153653 - 27 Jul 2022
Cited by 24 | Viewed by 3333
Abstract
cSCC is increasing in prevalence due to increased lifespans and improvements in survival for conditions that increase the risk of cSCC. The absolute mortality of cSCC exceeds melanoma in the United States and approaches that of melanoma worldwide. This review presents significant changes [...] Read more.
cSCC is increasing in prevalence due to increased lifespans and improvements in survival for conditions that increase the risk of cSCC. The absolute mortality of cSCC exceeds melanoma in the United States and approaches that of melanoma worldwide. This review presents significant changes in the management of cSCC, focusing on improvements in risk stratification, new treatment options, optimization of existing treatments, and prevention strategies. One major breakthrough in cSCC treatment is the advent of immune checkpoint inhibitors (ICIs) targeting programmed cell death protein 1 (PD-1) and programmed death-ligand 1 (PD-L1), which have ushered in a renaissance in the treatment of patients with locally advanced and metastatic disease. These agents have offered patients with advanced disease decreased therapeutic toxicity compared to traditional chemotherapy agents, a more durable response after discontinuation, and improved survival. cSCC is an active field of research, and this review will highlight some of the novel and more developed clinical trials that are likely to impact cSCC management in the near future. Full article
(This article belongs to the Special Issue Research Progress of Cutaneous Squamous and Basal Cell Carcinomas)

Other

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15 pages, 2455 KiB  
Systematic Review
The Prognostic Value and Clinical Utility of the 40-Gene Expression Profile (40-GEP) Test in Cutaneous Squamous Cell Carcinoma: Systematic Review and Meta-Analysis
by Razan Masarwy, Shahaf Shilo, Narin Nard Carmel Neiderman, Liyona Kampel, Gilad Horowitz, Nidal Muhanna and Jobran Mansour
Cancers 2023, 15(9), 2456; https://doi.org/10.3390/cancers15092456 - 25 Apr 2023
Cited by 1 | Viewed by 1732
Abstract
Background: The current tumor staging systems for cutaneous squamous cell carcinoma (cSCC) are considered inadequate and insufficient for evaluating the risk of metastasis and for identifying patients at high risk of cSCC. This meta-analysis aimed to assess the prognostic significance of a 40-gene [...] Read more.
Background: The current tumor staging systems for cutaneous squamous cell carcinoma (cSCC) are considered inadequate and insufficient for evaluating the risk of metastasis and for identifying patients at high risk of cSCC. This meta-analysis aimed to assess the prognostic significance of a 40-gene expression profile (40-GEP) both independently and integrated with clinicopathologic risk factors and established staging systems (American Joint Committee on Cancer, eighth edition (AJCC8) and Brigham and Women’s Hospital (BWH)). Methods: Electronic databases, including PubMed (MEDLINE), Embase, the Cochrane Library, and Google Scholar, were systematically searched to identify cohort studies and randomized controlled trials on evaluations of the prediction value of 40-GEP in cSCC patients up to January 2023. The metastatic risk analysis of a given 40-GEP class combined with tumor stage and/or other clinicopathologic risk factors was based upon log hazard ratios (HRs) and their standard error (SE). Heterogeneity and subgroup analyses were performed, and data quality was assessed. Results: A total of 1019 patients from three cohort studies were included in this meta-analysis. The overall three-year metastatic-free survival rates were 92.4%, 78.9%, and 45.4% for class 1 (low risk), class 2A (Intermediate risk), and class 2B (high risk) 40-GEP, respectively, indicating a significant variation in survival rates between the risk classification groups. The pooled positive predictive value was significantly higher in class 2B when compared to AJCC8 or BWH. The subgroup analyses demonstrated significant superiority of integrating 40-GEP with clinicopathologic risk factors or AJCC8/BWH, especially for class 2B patients. Conclusions: The integration of 40-GEP with staging systems can improve the identification of cSCC patients at high risk of metastasis, potentially leading to improved care and outcomes, especially in the high-risk class 2B group. Full article
(This article belongs to the Special Issue Research Progress of Cutaneous Squamous and Basal Cell Carcinomas)
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