Leveraging Tissue Engineering for Skin Cancer Models.

Bioengineered in vitro three-dimensional (3D) skin model has emerged as a promising tool for recapitulating different types of skin cancer and performing pre-clinical tests. However, a full-thickness 3D model including the epidermis, dermis, and hypodermis layers is scarce despite its significance in human physiology and diverse biological processes. In this book chapter, an attempt has been made to summarize various skin cancer models, including utilized skin layers, materials, cell lines, specific treatments, and fabrication techniques for three types of skin cancer: melanoma, basal cell carcinoma (BCC), and squamous cell carcinoma (SCC). Subsequently, current limitations and future directions of skin cancer models are discussed. The knowledge of the current status of skin cancer models can provide various potential applications in cancer research and thus a more effective way for cancer treatment.

Heterogeneous Skin Phantoms for Experimental Validation of Microwave-Based Diagnostic Tools.

Considerable exploration has been done in recent years to exploit the reported inherent dielectric contrast between healthy and malignant tissues for a range of medical applications. In particular, microwave technologies have been investigated towards new diagnostic medical tools. To assess the performance and detection capabilities of such systems, tissue-mimicking phantoms are designed for controlled laboratory experiments. We here report phantoms developed to dielectrically represent malign skin lesions such as liposarcoma and nonsyndromic multiple basal cell carcinoma. Further, in order to provide a range of anatomically realistic scenarios, and provide meaningful comparison between different phantoms, cancer-mimicking lesions are inserted into two different types of skin phantoms with varying tumor-skin geometries. These configurations were measured with a microwave dielectric probe (0.5-26.5 GHz), yielding insight into factors that could affect the performance of diagnostic and detection tools.

Techniques and Applications in Skin OCT Analysis.

The skin is the largest organ of our body. Skin disease abnormalities which occur within the skin layers are difficult to examine visually and often require biopsies to make a confirmation on a suspected condition. Such invasive methods are not well-accepted by children and women due to the possibility of scarring. Optical coherence tomography (OCT) is a non-invasive technique enabling in vivo examination of sub-surface skin tissue without the need for excision of tissue. However, one of the challenges in OCT imaging is the interpretation and analysis of OCT images. In this review, we discuss the various methodologies in skin layer segmentation and how it could potentially improve the management of skin diseases. We also present a review of works which use advanced machine learning techniques to achieve layers segmentation and detection of skin diseases. Lastly, current challenges in analysis and applications are also discussed.

Effect of light polarization on the efficiency of photodynamic therapy of basal cell carcinomas: an in vitro cellular study.

In an in vitro study, the effect of light polarization on the efficiency of 5-aminolaevulinic acid (ALA) photodynamic therapy (PDT) of basal cell carcinoma (BCC) was investigated. Three states of light polarization (non-polarized, linearly polarized, and circularly polarized) were considered. Cells were exposed to green (532 pm 20 nm) irradiation from light emitting diodes. Cell survival was measured by the colorimetric assay (WST-1) and Trypan blue staining. The colorimetric assay showed a pronounced decrease in the cell viability (up to 30%) using polarized light compared to the non-polarized one in the wavelength region used. Similar results were obtained by the cell counting method (20-30% increase in cell death). The observed effect was dependent on the concentration of photosensitizer. The effect is more expressed in the case of linearly polarized light compared to the circularly polarized one. Results show that the use of polarized light increases the efficiency of in vitro ALA-PDT of BCC. Utilizing polarized light, it is possible to obtain the same effect from PDT by lower concentrations of photosensitizer. Additionally, the concentration dependency of PDT response and photo-bleaching is also reduced.

Long-term safety and efficacy of vismodegib in patients with advanced basal cell carcinoma: final update of the pivotal ERIVANCE BCC study.

BACKGROUND: In the primary analysis of the ERIVANCE BCC trial, vismodegib, the first US Food and Drug Administration-approved Hedgehog pathway inhibitor, showed objective response rates (ORRs) by independent review facility (IRF) of 30% and 43% in metastatic basal cell carcinoma (mBCC) and locally advanced BCC (laBCC), respectively. ORRs by investigator review were 45% (mBCC) and 60% (laBCC). Herein, we present long-term safety and final investigator-assessed efficacy results in patients with mBCC or laBCC. METHODS: One hundred four patients with measurable advanced BCC received oral vismodegib 150 mg once daily until disease progression or intolerable toxicity. The primary end point was IRF-assessed ORR. Secondary end points included ORR, duration of response (DOR), progression-free survival, overall survival (OS), and safety. RESULTS: At data cutoff (39 months after completion of accrual), 8 patients were receiving the study drug (69 patients in survival follow-up). Investigator-assessed ORR was 48.5% in the mBCC group (all partial responses) and 60.3% in the laBCC group (20 patients had complete response and 18 patients had partial response). ORRs were comparable across patient subgroups, including aggressive histologic subtypes (eg, infiltrative BCC). Median DOR was 14.8 months (mBCC) and 26.2 months (laBCC). Median OS was 33.4 months in the mBCC cohort and not estimable in the laBCC cohort. Adverse events remained consistent with clinical experience. Thirty-three deaths (31.7%) were reported; none were related to vismodegib. CONCLUSIONS: This long-term update of the ERIVANCE BCC trial demonstrated durability of response, efficacy across patient subgroups, and manageable long-term safety of vismodegib in patients with advanced BCC. TRIAL REGISTRATION: This study was registered prospectively with Clinicaltrials.gov , number NCT00833417 on January 30, 2009.

Cohort study of Gorlin syndrome with emphasis on standardised phenotyping and quality of life assessment.

BACKGROUND: Gorlin syndrome (nevoid basal cell carcinoma syndrome) is a rare genetic predisposition to basal cell carcinomas (BCC), keratocysts of the jaw and calcification of the falx cerebri among other clinical features. With the advent of sonic hedgehog inhibitors for the treatment of BCC, it is timely to establish a cohort of individuals with Gorlin syndrome and collect standardised phenotypic information on these individuals. Moreover, the health-related quality of life (QoL) in individuals with Gorlin syndrome is not well studied. AIM: To establish a Victorian cohort of Gorlin syndrome and study the QoL in these individuals. METHODS: Phenotypic data were obtained by reviewing medical records of individuals attending two major tertiary/quaternary genetic referral centres in Victoria, followed by telephone or face-to-face interviews where possible. QoL information was obtained utilising the AQoL-6D quality of life survey form. RESULTS: The median number of BCC in the 19 individuals studied was 17.5 (interquartile range 3-70). The number of patients with ≥100 BCC in this group was similar to a previously described national cohort (22.2 vs 27% respectively). A total of 58% of referrals to the genetics clinics originated from maxillofacial surgeons and 42% from dermatologists. Individuals with ≥100 BCC had worse median QoL scores compared to those with <100 BCC (36 vs 29, P-value of 0.031). CONCLUSION: The clinical features in our cohort were congruent with those previously described in Australia. The QoL is adversely correlated with increased BCC burden.

Lasers and intense pulsed light (IPL) association with cancerous lesions.

The development and use of light and lasers for medical and cosmetic procedures has increased exponentially over the past decade. This review article focuses on the incidence of reported cases of skin cancer post laser or IPL treatment. The existing evidence base of over 25 years of laser and IPL use to date has not raised any concerns regarding its long-term safety with only a few anecdotal cases of melanoma post treatment over two decades of use; therefore, there is no evidence to suggest that there is a credible cancer risk. Although laser and IPL technology has not been known to cause skin cancer, this does not mean that laser and IPL therapies are without long-term risks. Light therapies and lasers to treat existing lesions and CO2 laser resurfacing can be a preventative measure against BCC and SCC tumour formation by removing photo-damaged keratinocytes and encouraged re-epithelisation from stem cells located deeper in the epidermis. A review of the relevant literature has been performed to address the issue of long-term IPL safety, focussing on DNA damage, oxidative stress induction and the impact of adverse events.

The occurrence of non-melanoma malignant skin lesions and non-cutaneous squamous-cell carcinoma among metastatic melanoma patients: an observational cohort study in Denmark.

BACKGROUND: Inhibitors of mutant BRAF are emerging as standard of care in patients with metastatic melanoma who carry relevant oncogenic mutations. However, BRAF inhibitors are found to induce cutaneous squamous cell carcinoma (cuSCC). Population-based background rates of cuSCC and non-cutaneous squamous cell carcinoma (non-cuSCC) in the metastatic melanoma population may contextualize safety signals from randomized clinical trials or the clinics. However, these background rates are lacking. METHODS: We conducted a historical cohort study to evaluate the background rates of new-onset non-melanoma skin lesions and non-cuSCC among 2,814 metastatic malignant melanoma patients diagnosed in 1997-2010, identified through the Danish Cancer Registry and the National Pathology Registry. Patients were excluded if they had a history of cancer before the metastatic melanoma diagnosis, other than skin cancers. We determined the incidence of non-melanoma malignant skin lesions and non-cuSCC that occurred post metastatic melanoma diagnosis, censoring patients at death, emigration, or December 31, 2011 (end of study period), whichever came first. RESULTS: The median age at metastatic melanoma diagnosis was 64 years. Over 40% of patients died within one year of metastatic diagnosis and ~70% died within 5 years. The percentages of patients with prior history or prevalent disease at metastatic melanoma diagnosis included: 8.6% with cuSCC or basal cell carcinoma (BCC), 3.9% with actinic keratosis (AK), and 0.7% with Bowen's disease. No patients had past or current non-cuSCC per study exclusion criterion. The incidence of non-melanoma skin lesions during the 6 months post-metastatic melanoma diagnosis was as follows: BCC, 1.8% (42.5 per 1000 person-years [PY]); AK, 0.8% (18.6 per 1000 PY); cuSCC, 0.1% (1.7 per 1000 PY); Bowen's disease, 0.04% (0.8 per 1000 PY); and keratoacanthoma (KA), 0%. Non-cuSCC was observed in 3 patients (0.1%; 2.5 per 1000 PY) at 3 sites: bronchi, heart and lung. CONCLUSION: CuSCC and non-cuSCC were rare events among metastatic melanoma patients.

Emergence of chemoresistance in a metastatic basal cell carcinoma patient after complete response to hedgehog pathway inhibitor vismodegib (GDC-0449).

Vismodegib (GDC-0449, Genentech, USA), a small molecule inhibitor of the Hedgehog signalling pathway, has potent anti-tumour activity in advanced basal cell carcinoma (BCC). We report a case of a 67-year-old Australian man with metastatic BCC including pulmonary disease with malignant effusion who showed a dramatic complete response to vismodegib but subsequently experienced a recurrence of pulmonary disease, indicative of chemoresistance to vismodegib. This case is the first to illustrate chemoresistance in a patient with metastatic BCC, and demonstrates the need for closely monitoring metastatic BCC patients even after an apparently complete response.

Basal Cell Carcinoma: Comprehensive Review with Emphasis on Scar Tissue Manifestation and Post-Vaccination Incidence.

Basal cell carcinoma (BCC) arising within scar tissue is a rare but clinically significant phenomenon. This comprehensive review aims to provide a succinct overview of the current state of knowledge regarding the etiological factors, pathogenesis, clinical presentation, and management of BCC. This study constitutes a literature review pertaining to BCC, with a particular emphasis on BCC developing within scar tissue. It also provides a clinical case presentation of a patient who had developed BCC in a BCG post-vaccination scar and a review of analogous findings available in the existing literature. Despite the fact that an array of mechanisms play a role in injury-related BCC growth, the main mechanism remains ambiguous and yet to be elucidated. The review also includes a detailed description of the various therapeutic options available for BCC, ranging from surgical interventions to novel pharmacological treatments. By examining these intersections, the review seeks to elucidate the potential mechanisms, identify risk factors, and suggest considerations for clinical practice. The findings underscore the importance of vigilant dermatological assessment in patients with scar tissue and those recently vaccinated, aiming to improve early detection and optimize management strategies for BCC.

Cole-Cole Model for the Dielectric Characterization of Healthy Skin and Basal Cell Carcinoma at THz Frequencies.

THz radiationeffectively probes biological tissue water content due to its high sensibility to polar molecules. Skin and basal cell carcinoma (BCC), both rich in water, have been extensively studied in the THz range. Typically, the Double Debye model is used to study their dielectric permittivity. This work focuses on the viability of the multipole Cole-Cole model as an alternative dielectric model. To determine the best fit parameters, we used a genetic algorithm-based approach, solving a least squares problem. Compared with the Double Debye model, a maximum reduction of the RMSE value up to more than 50% and maximum relative percentage errors of 2.8% have been measured for both second and third order Cole-Cole models. Since the errors of the second and third order Cole-Cole models are similar, a two-poles model is enough to describe the behaviour both tissues from 0.2 THz to 2 THz.

Vismodegib as an adjuvant treatment for periorbital basal cell carcinoma: a case report and review of literature.

Background: Basal cell carcinoma (BCC) is the most common cancer type worldwide. Although there are several treatment options for the treatment of BCC, selecting the best treatment option for periorbital BCC is challenging and it varies case by case. More than half of periocular BCC cases initially occur on the inner angle and lower lid. The treatment options for BCC include radical surgical excision using Mohs micrographic technique, radiotherapy, neoadjuvant vismodegib, imiquimod, and combination therapy followed by reconstruction for functionality and aesthetic outcome. Selection of each treatment varies based on the severity and extension of BCC. Case Description: We report a case of periorbital BCC invading the left lower eyelid in a 50-year-old Caucasian male which was initially excised a few years ago, and, following recurrence, the patient underwent Mohs micrographic surgery. Due to a recurrence after Mohs micrographic surgery, treatment with oral vismodegib was started, which led to near-total tumor shrinkage. To determine the outcome of periorbital BCC treated with vismodegib, we reviewed the literature on the periorbital BCC treated with vismodegib, their follow-up period, outcome, and whether they were metastatic or had recurrence. Conclusions: Neoadjuvant vismodegib, followed by surgery excision, such as Mohs micrographic surgery, has shown a promising clinical and aesthetic outcome in the treatment of periorbital BCC.

Complex Management of Basal Cell Carcinoma in a Frail Patient.

Basal cell carcinoma (BCC) is one of the most common cancers diagnosed in older patients and has low mortality. Surgical versus medical management is considered in patients with multiple comorbidities and limited life expectancy (LLE), where the risk-to-benefit ratio must be carefully assessed. Watchful waiting (WW) is a viable option for some patients with severe LLE when follow-up care can be provided vigilantly and frequently. Special consideration should be given to morbidity factors such as tumor growth, bleeding, pain, and social withdrawal that negatively affect the quality of life. We present the case of a 75-year-old male with a past medical history of multiple system atrophy, who presented with a BCC on the ear and face. We discuss the management of this patient and factors that may have led to the inappropriate use of WW.

Pilot Study on High-Intensity Focused Ultrasound (HIFU) for Basal Cell Carcinoma: Effectiveness and Safety.

Background: The rising incidence of Basal Cell Carcinoma (BCC), especially among individuals with significant sun exposure, underscores the need for effective and minimally invasive treatment alternatives. Traditional surgical approaches, while effective, often result in notable cosmetic and functional limitations, particularly for lesions located on the face. This study explores High-Intensity Focused Ultrasound (HIFU) as a promising, non-invasive treatment option that aims to overcome these challenges, potentially revolutionizing BCC treatment by offering a balance between efficacy and cosmetic outcomes. Methods: Our investigation enrolled 8 patients, presenting a total of 15 BCC lesions, treated with a 20 MHz HIFU device. The selection of treatment parameters was precise, utilizing probe depths from 0.8 mm to 2.3 mm and energy settings ranging from 0.7 to 1.3 Joules (J) per pulse, determined by the lesion's infiltration depth as assessed via pre-procedure ultrasonography. A key component of our methodology included dermatoscopic monitoring, which allowed for detailed observation of the lesions' response to treatment over time. Patient-reported outcomes and satisfaction levels were systematically recorded, providing insights into the comparative advantages of HIFU. Results: Initial responses after HIFU treatment included whitening and edema, indicative of successful lesion ablation. Early post-treatment observations revealed minimal discomfort and quick recovery, with crust formation resolving within two weeks for most lesions. Over a period of three to six months, patients reported significant improvement, with lesions becoming lighter and blending into the surrounding skin, demonstrating effective and aesthetically pleasing outcomes. Patient satisfaction surveys conducted six months post-treatment revealed high levels of satisfaction, with 75% of participants reporting very high satisfaction due to minimal scarring and the non-invasive nature of the procedure. No recurrences of BCC were noted, attesting to the efficacy of HIFU as a treatment option. Conclusions: The findings from this study confirm that based on dermoscopy analysis, HIFU is a highly effective and patient-preferred non-invasive treatment modality for Basal Cell Carcinoma. HIFU offers a promising alternative to traditional surgical and non-surgical treatments, reducing the cosmetic and functional repercussions associated with BCC management. Given its efficacy, safety, and favorable patient satisfaction scores, HIFU warrants further investigation and consideration for broader clinical application in the treatment of BCC, potentially setting a new standard in dermatologic oncology care. This work represents a pilot study that is the first to describe the use of HIFU in the treatment of BCC.

Case report: Sequential treatment strategy for advanced basal cell carcinoma in Gorlin-Goltz syndrome: integration of vismodegib, radiotherapy, surgery, and high-intensity focused ultrasound.

Managing advanced basal cell carcinoma (BCC) in patients with Gorlin-Goltz syndrome presents unique clinical challenges due to the tumor's aggressive nature and potential for widespread metastasis. This case study details a sequential treatment regimen for a 68-year-old female patient with an extensive, inoperable BCC. Employing a multimodal approach that integrates radiotherapy, the Hedgehog pathway inhibitor vismodegib, and High-Intensity Focused Ultrasound (HIFU), we demonstrate the potential for nearly complete remission in a patient with advanced BCC. Initial treatment with radiotherapy and vismodegib reduced tumor size significantly, but the largest mass displayed resistance over time, signifying the need for innovative therapies. Subsequent HIFU treatment targeted individual lesions, showcasing a non-invasive method that provided precise treatment while mitigating systemic side effects. The case emphasizes the necessity of continual adaptation in treatment plans to address the development of resistance and underscores the importance of incorporating new technologies and targeted therapies for complex BCC cases. The successful outcome of this integrated strategy suggests a promising direction for future research and highlights the importance of multidisciplinary approaches that tailor treatment to individual patient needs, tumor characteristics, and evolving therapeutic landscapes.

The Impact of Education Level on Basal Cell Carcinoma Development Risk.

BACKGROUND: Basal cell carcinoma (BCC) stands as the most common skin malignancy, with its high incidence rate and associated costs rising annually. The origin of BCC is related to environmental, genetic, and phenotypic factors. Among these, the most important risk factor is exposure to UV light triggering keratinocyte carcinogenesis, causing cumulative cellular damage that leads to BCC development. Individuals' educational background and awareness of skin cancer risk factors may influence the development of BCC. Lack of knowledge about risk factors (like chronic UV exposure, sunburn, artificial solar beds, and fair skin color), prevention methods, and jobs involving outdoor activities may be associated with BCC formation. AIM: The aim of the study was to analyze recent trends and the risk factors associated with BCC, while also revealing any potential link between BCC and the patient's education level and awareness of skin cancer risk factors. DESIGN AND METHODS: A hospital-based case-control study was conducted, involving a total of 141 individuals. Among them, 47 were clinically and histologically confirmed BCC patients, while the remaining participants served as controls. The control group comprised 94 individuals matched for age and gender. Data on various factors including gender, age, residency, education level, Fitzpatrick skin type, outdoor activities, use of solariums, and UV therapy, as well as awareness of potential BCC triggers, were collected using an adapted questionnaire and subjected to analysis. The collected data underwent statistical evaluation. RESULTS: Most of the BCCs (n = 52; 71.2%) were located in sun-exposed areas (p < 0.001), with a female/male ratio of 1.35 to 1. The nodular type of BCC was the most common form (n = 49; 67.2%). The percentage of patients in the study group with Fitzpatrick phototypes I and II (n = 38; 80.9%) was significantly higher than in controls (n = 50; 53.2%, p = 0.002). The percentage of persons with higher education levels (bachelor's degree, master's degree, and post-diploma) was significantly less prevalent among cases compared to controls (n = 20 (42.6%) vs. n = 58 (61.7%), respectively (p = 0.033)). Notably, BCC patients with low education levels exhibited significantly lesser awareness concerning genetic factors and chronic solar radiation.  Conclusions: Coexistence of factors, such as a medical history of skin cancer, having Fitzpatrick skin types I and II, engaging in outdoor work exposed to the sun, knowledge that genetic factors are risk factors of skin cancer, and knowledge that stress is a risk factor of skin cancer, are significant predictors of the disease. A lower level of education and limited awareness about risk factors can also be a risk factor for BCC. It is essential to raise awareness about potential triggers and preventive measures within the population to reduce the incidence of the disease.

Clinico-epidemiological characteristics and long-term surgical outcome of basal cell carcinoma treated with standard excision in patients of skin of colour: A retrospective study from Northern India.

Background There is scant data on basal cell carcinoma (BCC) in Indian patients. This retrospective study was conducted to explore epidemiology, risk factors, clinical and pathological aspects, and long-term treatment outcomes of BCC in a cohort of North Indian patients. Methods Data about patients registered in the dermatosurgery clinic between 01 January 2017 and 31 December 2022 with a confirmed diagnosis of BCC was collected. Results Among the 83 patients, 56.6% were females, and the median age was 62 years (6-85 years). Most patients (81.9%) had a single BCC lesion, resulting in a total of 126 assessed lesions. The median size of BCC at presentation was 1.90 cm, with nodular BCC being the most common histopathological subtype (39.7%). Head and neck region involvement was observed in 82.5% of patients, with the malar region, nose, and periorbital region being the most commonly affected sites. Pigmentation was clinically evident in 45.2% of cases. Surgical excision was the primary treatment modality (71.1% of patients). The median follow-up duration was 40 months (6-57 months). Recurrence occurred in five patients, with a longer disease-free survival period observed in the surgically treated group (55.58 ± 0.98 months) compared to patients treated with medical or destructive therapies (43.6 ± 3.482 months) (p = 0.003). Conclusion The data from this hospital-based study indicated a slight predilection for females among North Indian patients with BCC, with most cases occurring during their seventh decade of life. The condition commonly occurred on sun-exposed areas such as the malar region and nose, with a high percentage of pigmented lesions. Recurrence following surgical excision was rare, and overall treatment outcomes were favourable.

Comparative Analysis of Slow Mohs Surgery in Melanoma and Mohs Micrographic Surgery in Squamous Cell Carcinoma and Basal Cell Carcinoma.

Skin cancer is one of the most common types of cancer worldwide, and it can affect people of all ages, races, and genders. Mohs micrographic surgery (MMS), a specialized type of skin cancer surgery, boasts the highest cure rates for various types of skin malignancies. Slow Mohs surgery (SMS) is a methodical and meticulous approach to MMS that involves careful and deliberate examination of tissue samples to ensure the complete removal of skin cancer while preserving as much healthy tissue as possible. Both SMS and MMS have been indicated to be effective treatment options for skin cancer, depending on the type and stage of cancer. This case-control study analysis compares the efficacy of SMS for melanoma with that of MMS for squamous cell carcinoma (SCC) and basal cell carcinoma (BCC). We analyzed data from the past two decades to assess recurrence rates and treatment-related complications. Our findings suggest that SMS for melanoma achieves comparable outcomes to MMS in SCC and BCC. Both approaches demonstrated similar cure rates and complication profiles. However, further prospective studies are necessary to solidify these findings and refine the specific role of SMS in melanoma therapy.