Treatment Of Basal Cell Carcinoma Research Articles

Jet-injection assisted photodynamic therapy for superficial and nodular basal cell carcinoma: A pilot study.

Photodynamic therapy (PDT) with topical δ-Aminolevulinic acid (ALA) has efficacy in treating basal cell carcinoma (BCC) but is limited by incomplete penetration of ALA into the deeper dermis. This prospective open-label pilot trial investigated the safety and efficacy of photosensitizer jet injection for PDT (JI-PDT) for BCC treatment. It was performed with 15 patients (n = 15) with histologically confirmed, untreated, low-risk nodular BCCs at a single institution. For the intervention, JI-PDT patients (n = 11) received two sessions of jet-injected ALA with PDT separated by four to 6 weeks. To further understand treatment technique, another group of patients (n = 4) received jet-injected ALA followed by tumor excision and fluorescence microscopy (JI-E). Treatment tolerability was assessed by local skin responses (LSR) score at five distinct time intervals. Fluorescence microscopy assessed protoporphyrin IX penetration depth and biodistribution within the tumor. At the primary endpoint, tumor clearance was evaluated via visual inspection, dermoscopy and reflectance confocal microscopy. Postinjection and postillumination pain levels, and patient satisfaction, were scored on a 0-10 scale. Fifteen participants with mean age of 58.3, who were 15/15 White, non-Hispanic enrolled. The median composite LSR score immediately after JI-PDT was 5(interquartile range [IQR] = 3) which decreased to 0.5 (IQR = 1) at primary endpoint (p < 0.01). Immunofluorescence of excised BCC tumors with jet-injected ALA showed photosensitizer penetration into papillary and reticular dermis. Of the 13 JI-PDT tumors, 11 had tumor clearance confirmed, 1 recurred, and 1 was lost to follow-up. 1/11 patients experienced a serious adverse event of cellulitis. 70% of patients had local scarring at 3 months. Patients reported an average pain level of 5.6 (standard deviation [SD] = 2.3) during jet injection and 3.7 (SD = 1.8) during light illumination. Jet injection of ALA for PDT treatment of nodular low-risk BCC is tolerable and feasible and may represent a novel modality to improve PDT.

Skin Malignancies Due to Anti-Cancer Therapies

Skin cancers involve a significant concern in cancer therapy due to their association with various treatment modalities. This comprehensive review explores the increased risk of skin cancers linked to different anti-cancer treatments, including classic immunosuppressants such as methotrexate (MTX), chemotherapeutic agents such as fludarabine and hydroxyurea (HU), targeted therapies like ibrutinib and Janus Kinase inhibitors (JAKi), mitogen-activated protein kinase pathway (MAPKP) inhibitors, sonic hedgehog pathway (SHHP) inhibitors, and radiotherapy. MTX, a widely used immunosuppressant in different fields, is associated with basal cell carcinoma (BCC), cutaneous squamous cell carcinoma (cSCC), and cutaneous melanoma (CM), particularly at higher dosages. Fludarabine, HU, and other chemotherapeutic agents increase the risk of non-melanoma skin cancers (NMSCs), including cSCC and BCC. Targeted therapies like ibrutinib and JAKi have been linked to an elevated incidence of NMSCs and CM. MAPKP inhibitors, particularly BRAF inhibitors like vemurafenib, are associated with the development of cSCCs and second primary melanomas (SPMs). SHHP inhibitors like vismodegib have been linked to the emergence of cSCCs following treatment for BCC. Additionally, radiotherapy carries carcinogenic risks, especially for BCCs, with increased risks, especially with younger age at the moment of exposure. Understanding these risks and implementing appropriate screening is crucial for effectively managing patients undergoing anti-cancer therapies.

Neoadjuvant Photodynamic Therapy: An Updated Therapeutic Approach for Non-Melanoma Skin Cancers.

Non-melanoma skin cancers (NMSCs) are the most common malignancy and surgical excision is considered treatment of choice for the majority of cases. However, surgery can be very extensive in cases of large, multiple, or cosmetic-sensitive tumors located on areas such as scalp and face or genital region, leading to significant functional and cosmetic deficit. Aminolaevulinic acid photodynamic therapy (ALA-PDT) has emerged as a widely used approach in a variety of skin diseases, demonstrating remarkable efficacy in treatment of actinic keratosis, Bowen disease and basal cell carcinoma. Besides, when employed as a preoperative intervention, ALA-PDT effectively reduces tumor size and minimizes subsequent local surgical morbidity. With its minimally invasive nature and proven effectiveness, ALA-PDT holds significant promise as a neoadjuvant treatment option for NMSCs. In cases where the tumor is large, invasive, multiple, or located in cosmetically and functionally sensitive areas, or when considering patient factors such as age, comorbidity, willingness to undergo surgery, and post-operative quality-of-life, surgical intervention or radiotherapy alone may be impracticable or unacceptable. In such scenarios, neoadjuvant ALA-PDT can offer remarkable outcomes. In order to further ensure the maximum benefit of patients from neoadjuvant PDT, collaboration with multidisciplinary teams and whole-process management may be in need.

Clinical versus Histological Assessment of Basal Cell Carcinoma Subtype and Thickness of Tumours Selected for Photodynamic Therapy.

Photodynamic therapy is an approved treatment for primary, superficial, and small nodular basal cell carcinomas with a thickness of < 2 mm located on low-risk sites. Histologically verified basal cell carcinomas clinically assessed as suited for photodynamic therapy were included. The study aimed to investigate the agreement between clinical and histological assessments of basal cell carcinoma subtypes and thickness of tumours selected for photodynamic therapy with histopathological evaluation as a reference. A total of 343 tumours were included. The agreement between clinical and histological diagnosis of basal cell carcinoma subtype was 72% (p < 0.001). Clinical assessment of subtype had a sensitivity of 93% and specificity of 55% for superficial tumours and a sensitivity of 55% and specificity of 85% for nodular tumours. The mean ± SD thickness values by clinical and histological assessments were 0.95 ± 0.53 and 0.86 ± 0.75. The difference of 0.09 mm was statistically significant (p = 0.017), but not considered to be clinically relevant, although the differences between specific subgroups could be relevant. Among basal cell carcinomas clinically diagnosed as superficial, 91% were histologically consistent with the current photodynamic therapy criteria. The main results suggest that histopathological evaluation should precede photodynamic therapy to ensure selection of suitable basal cell carcinomas. In selected cases, the clinical diagnosis alone may be adequate before proceeding with photodynamic therapy.

Pulse Dosing Vismodegib Therapy as an Effective Treatment of Basal Cell Carcinoma: A Case Report

Basal cell carcinoma (BCC) is a common nonmelanoma skin cancer, frequently present on the face and head. BCC is linked to the Sonic Hedgehog (Shh) signaling pathway. Mutations within the Shh signaling pathway, involving the activation of the ligand-independent pathway by the Smoothened (Smo) protein, can lead to unregulated proliferation of basal cells, resulting in BCC. Vismodegib, a hedgehog pathway inhibitor, is a chemotherapy drug approved for targeting the Shh signaling pathway. We herein report a presentation of nodular BCC in a Caucasian female who was treated with Vismodegib. This case highlights the effectiveness of pulse dosing treatment to minimize side effects.

An Explorative Study on Calcium Electroporation for Low-risk Basal Cell Carcinoma.

In electrochemotherapy, permeabilization of the cell membrane by electric pulses increases the anti-tumour effect of chemotherapeutics. In calcium electroporation, chemotherapy is replaced by calcium chloride with obvious benefits. This study explores the effect and underlying mechanisms of calcium electroporation on basal cell carcinomas using either high- or low-frequency electroporation. Low-risk primary basal cell carcinomas were treated in local anaesthesia with intratumoral calcium chloride followed by electroporation with high (167 kHz) or low (5 kHz) frequencies. Non-complete responders were retreated after 3 months. The primary endpoint was tumour response 3 months after last calcium electroporation. Plasma membrane calcium ATPase was examined in various cell lines as plasma membrane calcium ATPase levels have been associated with calcium electroporation efficacy. Twenty-two out of 25 included patients complete the study and 7 of these (32%) achieved complete response at 3 months with no difference in efficacy between high- and low-frequency pulses. High-frequency calcium electroporation was significantly less painful (p=0.03). Plasma membrane calcium ATPase was increased 16-32-fold in basal cell carcinoma cell lines compared with 4 other cancer cell lines. Calcium electroporation for low-risk basal cell carcinomas does not fulfil the requirements of a new dermatological basal cell carcinoma treatment but may be useful as adjuvant treatment to surgery in more advanced basal cell carcinomas. The elevated PMCA levels in basal cell carcinomas may contribute to low efficacy.

MicroRNA Signatures Associated with Basal Cell Carcinoma Subtypes

Basal cell carcinoma (BCC) is classified histologically into subtypes that determine treatment decisions. Micro RNAs (miRs) are short non-coding RNAs that may serve as diagnostic biomarkers. We investigated if particular miRs could distinguish BCC subtypes. We sequenced miRs from 55 archival BCC and 9 control skin specimens, and then validated these miRs by qRT-PCR assay on a second BCC cohort (18 superficial, 16 nodular, 15 infiltrative) and control skin (n= 12). Expression values for individual miRs were normalized to miR-16-5p, which was least variant among the control skin and BCC samples. We found that 1) miR-383-5p and miR-145-5p are downregulated in all BCC subtypes compared to control skin, 2) miR-181c-5p is downregulated in superficial compared to invasive (nodular/infiltrative) BCC, and 3) miR-22-5p and miR-708-5p are upregulated in infiltrative compared to superficial/nodular BCC and miR-30c-5p is downregulated in infiltrative compared to nodular BCC. Receiver operating characteristic analysis demonstrated excellent capacity of these miRs to discriminate between BCC and control skin (area under curve 0.94-0.98), while capacity to discriminate between superficial and invasive subtypes was less robust (area under curves 0.7-0.8). Future prospective studies may determine the utility of these miRs as diagnostic biomarkers to guide biopsy and treatment of BCC.

Beyond the Label: Real-World Side Effects Experienced With FDA-Approved Drugs for Non-Melanoma Skin Cancers.

With immunotherapy historically focused on cutaneous melanoma, there has been a new wave of systemic medications available for treating non-melanoma skin cancers including basal cell carcinoma (BCC), squamous cell carcinoma (SCC), and Merkel cell carcinoma (MCC). The immune checkpoint inhibitors approved by the FDA target programmed cell death protein 1 (PD-1) and the Hedgehog (Hh) signaling pathway. These medications have expanded treatment options; however, side effects are an important consideration. We used the FDA Adverse Events Reporting System (FAERS) to characterize the most prevalent, real-world side effects experienced by patients on these agents. Muscle spasms (23.45%), alopecia (16.06%), ageusia (12.02%), taste disorder (11.91%), and fatigue (11.67%) were the five most common side effects reported with medications used for BCC treatment. Logistic regression analysis showed males on vismodegib for BCC having greater odds of experiencing muscle spasms (aOR 1.33, P&lt;0.001) and ageusia (aOR 1.34,&nbsp; P&lt;0.001) versus females, who were more likely to exhibit alopecia (aOR 1.82, P&lt;0.001) and nausea (aOR 1.96, P&lt;0.001). With SCC treatment, the 5 most reported adverse events were fatigue (5.58%), rash (3.59%), asthenia (3.59%), pruritus (3.19%), and pyrexia (2.79%). Patients taking cemiplimab-rwlc for BCC compared to SCC were more likely to experience disease progression (aOR 10.98, P=0.02). With medication labels providing an excessively daunting list of side effects, we characterize practical side effects seen in patients receiving systemic treatments for non-melanoma skin cancers.&nbsp; J Drugs Dermatol. 2024;23(5):301-305. doi:10.36849/JDD.7968.

Lasers for the Treatment of Nonmelanoma Skin Cancer: A Systematic Review of the Literature.

Lasers may present an alternative treatment modality for the management of nonmelanoma skin cancer (NMSC). To investigate lasers as a definitive treatment of NMSC. A comprehensive search was performed on MEDLINE, the Cochrane Library, and the National Institutes of Health (www.clinicaltrials.gov). The Preferred Reporting Items for Systematic Reviews and Meta-Analysis was used to finalize a list of relevant literature studies evaluating the role of laser therapy for NMSC. Articles published through May 1, 2023, were included. The authors identified 37 studies investigating nonablative and ablative lasers alone and in combination with other lasers, noninvasive imaging, and additional modalities for the treatment of basal cell carcinomas, 10 focusing on squamous cell carcinoma in situ and 3 focusing on the treatment of both basal and squamous cell carcinomas. Although surgical management continues to be superior to laser therapy for the management of high-risk and cosmetically sensitive tumors, laser therapy may be an acceptable alternative for low-risk lesions on the trunk and extremities. However, further studies are needed to optimize parameters, determine maximal efficacy, and provide long-term follow-up before the adoption of laser therapy for NMSC into daily clinical practice.

Assessment of Mammalian Target of Rapamycin Pathway Activation in Basal Cell Carcinoma as a New Therapeutic Approach.

Targeting the mammalian target of rapamycin (mTOR) pathway represents a potentially novel approach to treat basal cell carcinoma (BCC), but activation of this pathway has not been well described in human BCCs. The purpose of this study was to assess whether mTOR pathway activation occurs in BCCs (both sporadic and syndromic) and report a case of a patient with Gorlin syndrome (GS) whose clinically suspicious BCCs responded to mTOR inhibition through topical sirolimus treatment. After Stanford Institutional Review Board Approval, archived BCCs from patients with GS (n = 25), sporadic BCCs (n = 35), and control tissues were subjected to immunohistochemical analysis for the activation of mTOR pathway, and immunohistochemical staining intensity was evaluated by a dermatopathologist. BCCs (compared with normal skin) had elevated levels of eIF4EBP1 (Padjusted = 0.0336), which is downstream of mTOR. a serine/threonine kinase Phospho-(AKT), which interacts with mTOR, was also significantly elevated (perinuclear: Padjusted < 0.0001; cytoplasmic: Padjusted = 0.0021). When off-label topical 1% sirolimus was used on a pediatric patient with GS, we noted reduction of new BCC development and decreased size of existing neoplasms clinically suspicious for BCCs. This treatment was well tolerated after 2 years of continuous use, with no other treatments needed during this period. Topical sirolimus is a promising therapeutic candidate against both sporadic and GS-associated BCC. Multicenter, prospective studies are needed to understand the efficacy and safety of topical mTOR inhibitors in BCC treatment, and ascertain whether the immunohistochemical markers downstream of mTOR could have predictive value in identifying BCCs most likely to respond to topical mTOR inhibitors, such as sirolimus.

The top 100 most cited articles in the treatment of basal cell carcinoma over the last decade: A bibliometric analysis and review.

Basal cell carcinoma (BCC) represents the most prevalent cancer globally. The past decade has witnessed significant advancements in BCC treatment, primarily through bibliometric studies. Aiming to perform a comprehensive bibliometric analysis of BCC treatments to comprehend the research landscape and identify trends within this domain, a dataset comprising 100 scientific publications from the Web of Science Core Collection was analyzed. Country co-operation, journal co-citation, theme bursts, keyword co-occurrence, author co-operation, literature co-citation, and field-specific references were examined using VOSviewer and CiteSpace visualization tools. These articles, published between 2013 and 2020, originated predominantly from 30 countries/regions and 159 institutions, with the USA and Germany at the forefront, involving a total of 1118 authors. The keyword analysis revealed significant emphasis on the hedgehog pathway, Mohs micrographic surgery, and photodynamic therapy. The research shows developed nations are at the forefront in advancing BCC therapies, with significant focus on drugs targeting the hedgehog pathway. This treatment avenue has emerged as a crucial area, meriting considerable attention in BCC therapeutic strategies.

Long-term follow-up results of a pilot study for nodular basal cell carcinoma with PDT using partial home treatment protocol

SignificanceEvaluate a photodynamic therapy (PDT) protocol with less time at the hospital and less painful for low-risk basal cell carcinoma (BCC) treatment. ApproachEight BCCs were selected, debulked, and received 20% methyl aminolevulinate cream. After 3h, the first irradiation was performed at the hospital (20min, 150J/cm2). Then, the cream was re-applied, a portable irradiation prototype was fixed into the lesion. After 1.5h, the patients turned on the prototype for irradiation (2h, 312J/cm2) at home. Disease-free survival rate and pain score during irradiations were evaluated. ResultsThe clearance at 30 days after PDT was 87.5% by histological analysis. The mean follow-up was 21.5 months and the recurrence-free survival at 22 months was 75%. The pain score was significantly lower at home. ConclusionsA less painful and more comfortable PDT treatment protocol was proved long-term efficient. A randomized clinical trial has been conducted to confirm these results.

Photodynamic therapy for nodular basal cell carcinoma up to 5mm located on high-risk area: effectiveness and long-term follow-up results

SignificanceResponse rates evaluation of photodynamic therapy (PDT) for nodular basal cell carcinoma (BCC) treatment located on high-risk and low-risk areas of the face. ApproachTwo groups of nodular BCC were selected, debulked, and received 20% methyl aminolevulinate cream. After 3h, the first irradiation was performed (20min, 150J/cm2). Then, the cream was re-applied, and a second irradiation was performed after 1.5h (20min, 150J/cm2). Clearance at 30 days and recurrence-free survival rate were evaluated. ResultsThe clearance at 30 days after PDT was 89% for the low-risk area group and 87% for the high-risk group. The recurrence-free survival at 60 months was 82% and 85% for the high-risk and low-risk groups, respectively. ConclusionsNo significant differences were observed between groups, nor for clearance at 30 days, nor recurrence-free follow-up. These results make the PDT an option for nodular BCC less than 5 mm located in high-risk areas.

Abstract 6568: PTCH1 loss-of-function alterations: Mutational landscape and therapeutic outcomes to hedgehog pathway inhibitors in non-canonical histologies

Abstract Background: Loss-of-function (LOF) alterations of the PTCH1 tumor suppressor gene represent canonical events involved in basal cell carcinoma (BCC) oncogenesis. Hedgehog pathway inhibitors (HPIs) are approved for the treatment of advanced BCC, but genomic characterization and therapeutic outcomes remain limited in tumor agnostic cohorts. Methods: Using the MSK Clinical Sequencing Cohort, we performed a mutational landscape analysis of PTCH1 LOF alterations in non-BCC histologies, including Fraction and Allele-Specific Copy Number Estimates from Tumor Sequencing (FACETS) annotation, and analyzed response and progression-free survival (PFS) with HPIs. Results: Out of 115,619 samples, 1972 samples from advanced solid tumors with PTCH1 LOF alterations were identified. Excluding 1306 variants of unknown significance (VUSs) using OncoKB knowledge base as well as 44 BCC samples, a total of 622 samples from 570 patients with oncogenic PTCH1 alterations were identified across histologies. In addition, 124 patients received ≥1 line(s) of HPI at our institution between 2013 and 2023, including 16 patients with non-BCC histologies presenting PTCH1 alterations. At the patient level (n=570), PTCH1 LOF alterations were present across 33 primary sites, including colorectal cancer (CRC; 34%; n=192), endometrial cancer (17%; n=98), gastroesophageal adenocarcinomas (ADC) (8%; n=46), non-small cell lung cancer (NSCLC; 6%; n=34) and soft tissue sarcomas (STS; 4%; n=25). At the sample level (n=622), TMB ≥10 was seen in 83% (n=516), including 324 samples with MSI-high status. PTCH1 alterations most frequently involved frameshift (fs) indels (69%; n=429), followed by nonsense mutations (18%; n=114), splice site mutations (8%; n=47) and fusions (5%; n=32). Recurrent fs events involved S1203Afs*52 (24%; n=150) and R1308Efs*64 (14%; n=89), among others. When comparing monoallelic (monoall) vs biallelic (biall) PTCH1 alterations through FACETS annotation, monoall showed a strong association with higher TMB (p&amp;lt;0.01) whereas biall were associated with higher loss of heterozygosity (LOH; p&amp;lt;0.01). In the 16 non-BCC patients treated with HPIs, histologies included lung squamous cell cancer (SCC; n=4), cutaneous SCC (n=2), medulloblastoma (n=2), carcinosarcoma (n=2), osteosarcoma, chondrosarcoma, chordoma, sebaceous ADC, anal SCC and CRC (each n=1). TMB ≥10 was seen in 31% (n=5), all of which were MSI-low. Tumor regressions on HPI were seen in 50% (n=8), including lung SCC, cutaneous SCC, sebaceous ADC and medulloblastoma, with median time to response of 3.6 months (mo). Median PFS on HPI was 3.9 mo and median OS was 22.7 mo. Median PFS was higher in patients with TMB ≥10 vs TMB &amp;lt;10 (11.8 vs. 1.8 mo, p=0.02). Conclusion: PTCH1 LOF alterations appear actionable in non-BCC cutaneous/adnexal primaries, lung SCC and medulloblastoma, including TMB-high tumors. Citation Format: Antoine Desilets, Matteo Repetto, Soo Ryum Yang, Monica Chen, Dazhi Liu, Nikhil Rizvi, Ezra Rosen, Alan L. Ho, Alexander Drilon, Yonina R. Murciano-Goroff. PTCH1 loss-of-function alterations: Mutational landscape and therapeutic outcomes to hedgehog pathway inhibitors in non-canonical histologies [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6568.

Long-term results after surgical basal cell carcinoma excision in the eyelid region: revisited.

The aim of the study was to readdress basal cell carcinoma (BCC) in the periocular region to prove the efficacy of histologically controlled surgical treatment and to identify high-risk characteristics.Retrospective analysis of 451 microscopically controlled BCC excisions in the periocular region. Tumor location, tumor size, AJCC 7 classification, and histological results were recorded. The same procedure was followed for recurrences.Arecurrence rate of 5.0% was observed after the first microscopically controlled excision. Recurrent BCCs show ashift from nodular to sclerosing BCC as the primary histological type as well as achange in primary location from lower eyelid to medial canthus. The frequency of BCC with deep extension increased from 7.3% to 24.7%, and 57.1% after the second and third operations, respectively. The recurrence rate increased to 9.5% and 42.9%, after the second and third operations, respectively.In conclusion, we are facing the same challenges in surgical BCC treatment as 30years ago. The distribution of periocular BCC location, histologic subtype and recurrence rates mirror the literature und the general consensus. The recurrence rate increases with every operation needed. Sclerosing BCCs with deep extension at the medial canthus bear the greatest risk for recurrence. In such cases, centers of expertise should be consulted and additional treatment options should be considered.

Basal cell carcinoma - the most common form of skin cancer. Methods of treatment

Introduction: Basal cell carcinoma is the most common form of skin cancer. The lifetime risk is estimated as 33% to 39% in white men and 23% to 28% in white women. Because of that it is a very crucial disease for public health. In this article will be described main pathways of treatment which are especially recommended and are the most wide used for different types of basal cell carcinoma. Main division of interventions type used in treatment of basal cell carcinoma are surgical (physical) and non-surgical (medical). Surgical (physical) includes surgical standard excision, Mohs micrographic surgery, curettage and cautery, cryosurgery and laser therapy (ablative lasers, pulsed dye lasers). Non-surgical (medical) includes radiotherapy, topical imiquimod, topical 5- fluorouracil, photodynamic therapy, intralesional interferon. Aim of study: Literature review of the most recommended treatment of basal cell carcinoma. State of knowledge: In this publication will be desribed a current state of knowledge about basic and the most crucial basal cell carcinoma treatment. Conclusion: Because of incidence rate of basal cell carcinoma which is very high- there are many reports about treatment of this disease. Treatment of this disease, especially among low risk patients, is very effective.

Efficacy of photodynamic therapy using ALAHCl in gel with a lipid nanoemulsion and MALHCl in cream in superficial basal cell carcinoma.

Photodynamic therapy (PDT) is a therapeutic option for low-risk basal cell carcinoma (BCC). The aim of the study was to assess the efficacy of topical PDT in the treatment of superficial BCC (sBCC) using two different photosensitizers: aminolevulinic acid hydrochloride (ALA-HCl) in a gel formulation with a lipid nanoemulsion (ALA-HCl in gel) and ALA methyl ester hydrochloride (MAL-HCl) in a cream formulation (MAL-HCl in cream). 21 patients were treated twice with a one week interval between treatments. The formulations were applied onto lesions: 10 patients were treated with MAL-HCl in cream, and 11 with ALA-HCl in gel. After three hours of incubation and removing the preparations, fluorescence was assessed. The skin areas were then irradiated with red light 630 ± 5 nm. At the follow-up visit 12 weeks after the second treatment, complete clinical remission was found in 82% after ALA-HCl in gel and in 80% after MAL-HCl in cream. An excellent cosmetic result was found in 96% of patients after MALHCl in cream and in 100% after ALA-HCl in gel. Faster skin healing and less post-inflammatory hyperpigmentation during follow-up visits was observed after treatment with ALA-HCl in gel. Both formulations - ALA-HCl in gel and MAL-HCl in cream - were highly effective photosensitisers for PDT. The advantage of ALA-HCl in a gel formulation with a lipid nanoemulsion was faster skin healing, resulting in better cosmetic results.

Chinese guildeline on diagnosis and treatment of basal cell carcinoma (2023 edition)

Basal cell carcinoma (BCC) is the most common skin malignancy, with a higher prevalence in Caucasians than in East Asians. Although there is a lack of epidemiological data in China, it is generally believed that the incidence of BCC in China is increasing due to the aging population. A variety of risk factors are related to the occurrence of BCC, among which ultraviolet rays and gene mutations play a major role, especially the abnormal activation of Hedgehog (Hh) signaling pathway, which is considered to be the most important pathogenesis of BCC. The clinical manifestations of BCC are highly specific, and most experienced doctors can make a preliminary diagnosis by clinical manifestations. Dermoscopy and other imaging methods can greatly improve the accuracy of diagnosis, but there are still some atypical or rare types of BCC that need further confirmation through histopathological examination. This guideline is initiated by the National Clinical Research Center for Skin and Immune Diseases (based on Peking University First Hospital). It has invited a panel of experts consisting of 24 senior dermatologists specializing in dermatologic surgery from the Dermatologic Surgery Group of the Chinese Medical Doctor Association of Dermatology, the Dermatologic Surgery Group of the Dermatology & Venereology Committee, Chinese Association of Integration Medicine, and the Dermatologic Surgery and Cosmetic Branch of Clina Leprosy Association. In addition, experts from the Burn and Plastic Surgery (Maxillofacial), Ophthalmology, Otolaryngology, Head and Neck Surgery, Radiation Therapy, and Pathology were also invited to participate. This panel forms the "Chinese Guideline for the Diagnosis and Treatment of Basal Cell Carcinoma" expert group. Based on the latest domestic and international research findings, the guideline was developed through four rounds of discussions by the expert group and revised to provide valuable references for clinical healthcare providers in the diagnosis and treatment of BCC.

Ablative fractional laser treatment reduces hedgehog pathway gene expression in murine basal cell carcinomas

This study aimed to investigate the impact of ablative fractional laser (AFL) on hedgehog pathway gene expression in murine microscopic basal cell carcinomas (BCCs) and compare these results to the effect of topical treatment with vismodegib, an FDA-approved hedgehog inhibitor. In 25 mice, 1 cm2 skin test sites (n = 44) containing microscopic BCCs were exposed to one of three interventions: a single CO2 AFL treatment (1 pulse, 40 mJ/microbeam, wavelength 10.6 μm, 5% density, pulse rate 250 Hz, n = 12), eight topical vismodegib treatments (3.8 mg/mL, n = 8), or combination of AFL and vismodegib treatments (n = 9). Untreated controls were included for comparison (n = 15). After 4 days, skin samples were analyzed for hedgehog gene expression (Gli1, Gli2, and Ptch1) by qPCR and vismodegib concentrations by liquid chromatography mass spectrometry (data analyzed with two-tailed t-tests and linear regression). A single treatment with AFL monotherapy significantly reduced hedgehog gene expression compared to untreated controls (Gli1 72.4% reduction, p = 0.003; Gli2 55.2%, p = 0.010; Ptch1 70.9%, p < 0.001). Vismodegib treatment also reduced hedgehog gene expression (Gli1 91.6%; Gli2 83.3%; Ptch1 83.0%), significantly surpassing AFL monotherapy for two out of three genes (Gli1, p = 0.017; Gli2, p = 0.007; Ptch1, p = 0.15). AFL and vismodegib combination mirrored the effects of vismodegib monotherapy (Gli1, p = 0.424; Gli2, p = 0.289; Ptch1, p = 0.593), possibly due to comparable cutaneous vismodegib concentrations (mean ± SD, vismodegib monotherapy 850 ± 475 µmol/L; combination 1036 ± 824 µmol/L; p = 0.573). In conclusion, a single AFL treatment significantly reduced hedgehog gene expression in murine BCCs mimicking the effects of eight topical applications of vismodegib. Further studies are needed to assess whether AFL can be utilized for BCC treatment, either as monotherapy or in combination with other drugs.

Treatment of Basal Cell Carcinoma of the Lower Eyelid With High-Dose-Rate Brachytherapy.

Objective To report the outcomes with high-dose-rate (HDR) brachytherapy (BT) treatment in patients with lower eyelid basal cell carcinoma (BCC) and to evaluate the relationship between dosimetric parameters and acute and late toxicities. Material and methods A retrospective unicentric study with patients diagnosed with lower eyelid biopsy-proven BCC treated with HDR BT between January 2012 and December 2019. The prescribed dose was 36 Gy to 40 Gy in 9 to 10 fractions, twice daily, over five days. The primary endpoint was local control, and the secondary endpoints were acute and late toxicities, registered according to CTCAE v4.0. The cosmetic result was evaluated on a qualitative scale (the CAIB scale). Local control was calculated according to the Kaplan-Meier test. Two sample T-tests and a Wilcoxon signed-rank test were used to determine the association between dosimetric parameters and side effects. Results Fifty-eight patients with a median age of 76 years were included. Among these patients, 55.2% received adjuvant HDR BT and 44.8% received radical HDR BT. At a median follow-up of 44 months, there were four local relapses, achieving a probability of local control at four years of 95% and 100% in the adjuvant and radical groups, respectively. Acute toxicity occurred in 76% of patients with only one grade 3 event (radiation dermatitis). Late toxicity was present in 56%. Eight patients underwent treatment for grade 3 cataracts during follow-up. Cosmetic results were excellent or very good in 93% of patients. Acute conjunctival hyperemia is strongly associated with the dose received by the ocular globe (volumes of 0.1cc, 1cc, and 2 cc) (p<0.05). Conclusion Lower eyelid BCC treatment with interstitial HDR BT is associated with excellent local control, acceptable long-term side effects, and good cosmetic results.