Introduction Objective response rate (ORR), defined as the percentage of patients achieving a complete or partial response to treatment, is a critical endpoint in clinical trials assessing the efficacy of new therapies in solid tumors, including BCC. We performed a post-hoc analysis exploring ORR as a potential primary endpoint for future studies evaluating the efficacy of VP-315, an intratumorally injected, chemotherapeutic oncolytic peptide. Objective To evaluate the effect of various VP-315 8 mg dosing regimens on antitumor response in subjects with BCC. Methods Eighty-two subjects with up to 2 target BCC tumors (total 91 tumors) were treated intratumorally with VP-315 for up to 2 weeks. Cohort 3 was not enrolled based on results from Cohorts 1-2. Each 7-day treatment week was comprised of 2 or 3 consecutive treatment days followed by a no-treatment period of at least 4 days. Dosing scheme: Cohort 1: (n=6) Tumor injected 3 days consecutively (3X/week 4 mg loading dose Day 1 followed by 8 mg dose). Cohort 2: (n=3) Tumor injected 3 days consecutively (3X/week 8 mg dose). Cohort 4: (n=36) Each tumor was injected 2 days consecutively (2X/week 8 mg split dose*). Cohort 5: (n=37) Each tumor was injected 3 days consecutively (3X/week 8 mg split dose*). * Dose split into 2 injections, 30% injected initially; 70% injected 15-30 minutes later. Post-hoc evaluation by ORR was based on response defined a priori as absence of disease progression and ≥30% reduction in lesion size from baseline, or complete resolution of ulceration in all target lesions. Complete response was based upon objective response with no residual BCC on post-treatment excisional biopsy. Partial response was objective response with presence of residual BCC. Results Eighty-two subjects (n=91 tumors) treated with VP-315 had a calculated ORR of 97%. Response rates were: 52% complete response and 45% partial response. No TRSAEs were reported. TRAEs were mostly mild to moderate. Conclusion These results support further investigation of ORR as a reliable endpoint for VP-315 in future BCC studies. Additional research using VP-315 as a potential non-surgical immunotherapy for BCC as a first line therapy in a primary or neoadjuvant setting is warranted.

Background: Basal cell carcinoma (BCC) and squamous cell carcinoma, collectively referred to as nonmelanoma skin cancer (NMSC) are the most common type of skin cancer and can lead to significant morbidity and mortality. There are several treatment options available for NMSC including superficial radiation therapy (SRT), which has improved in recent years with the addition of image guidance (IGSRT). In some cases, patients are not offered IGSRT as a treatment option and additional guidance on its benefits may be beneficial. Objective: For a panel of expert dermatologists to review published studies on IGSRT for the treatment NMSC and create consensus recommendations on its use. Methods: A comprehensive literature search of PubMed, EMBASE, Scopus, and Google Scholar was completed for English-language original research articles on the use of IGSRT to treat NMSC. A panel of six dermatologists with significant expertise in treating NMSC convened to review the articles and create consensus statements based on the available data. A modified Delphi process was used to approve each statement for adoption and a strength of recommendation was assigned using Strength of Recommendation Taxonomy (SORT) criteria. Results: After screening the articles that met the initial search criteria, 12 articles were distributed to the panelists for review prior to the roundtable discussion. The panel unanimously voted to adopt eight statements with an additional two statements receiving five out six votes for adoption. Eight of the statements received a strength of recommendation of “A” while two of the statements were given a strength of recommendation of “B” based on SORT criteria. Conclusion: IGSRT is a safe and effective treatment for NMSC that often results in highly favorable cosmetic outcomes. It can be considered a first-line treatment option for appropriately selected cases of NMSC.

Objective:We evaluated the cosmetic outcome and clearance of actinic keratoses (AKs) using photodynamic therapy (PDT) with microneedling-assisted delivery of 10% aminolevulinic acid (ALA) gel (Ameluz®, Biofrontera, Woburn, MA) with 30-minute incubation followed by 10-minute illumination with a red light (BF-RhodoLED®, 635nm, 37 J/cm2). Methods:Five subjects were treated with red light PDT using microneedling-assisted delivery of 10% ALA gel. ALA gel was applied on the face and incubated for 30 minutes without occlusion, followed by illumination with a red light for 10 minutes (635nm, 37 J/cm2). Follow-up (FU) visits were made at Weeks 1, 2, 4, and 8. The primary endpoints were changes in subject- and investigator-graded Global Aesthetic Improvement Scale (GAIS) scores and assessment of quality in wrinkle, color evenness, texture, spot, and pore analyses with Canfield Visia-CR imaging system. Secondary endpoints were: 1) AK clearance as quantified by the count of AKs at eight-week FU versus baseline and 2) safety as measured by subject-reported pain (10-point VAS scale) during red-light illumination and adverse events. Results:Investigator- and subject-graded GAIS scores showed a sharp increase to "much improved" at two weeks and increased to "very much improved" at eight weeks. There was an average 24.93-percent improvement in texture and an average 10.30-percent improvement in skin tone (color) evenness. AK lesion clearance ranged from 70 to 100 percent, with the mean at 89.2±14.9 percent. Three subjects achieved 100-percent clearance. The mean pain score during red-light illumination was 3.2±1.6. All subjects completed the study. Limitations:The study included a small number of subjects (N=5). Conclusion:Our results indicate that red light PDT using microneedling-assisted delivery of 10% ALA gel and a short 30-minute incubation is a safe and tolerable procedure producing good cosmetic outcomes in several skin quality parameters, such as texture and skin tone evenness, as well as an AK lesion clearance rate of 89.2 percent at Week 8, relatively low pain scores, and a reduced PDT treatment time.

Background: Cutaneous melanoma (CM, is associated with a higher mortality rate than most other skin cancers. The purpose of this expert consensus panel was to review the published literature on new technological advancements for the diagnosis and prognosis for CM and provide updated guidance on their usage, Methods: A comprehensive literature search of PubMed, Scopus, and Google Scholar was completed for English-language original research articles on the topics of non-invasive diagnostic and prognostic testing for CM, including gene expression profiling (GEPI and electrical impedance spectroscopy (Ea A panel of 10 dermatologists with significant expertise in the treatment of CM gathered to review the articles and create consensus statements. A modified Delphi process was used to approve each statement and a strength of recommendation was assigned using widely recognized Strength of Recommendation Taxonomy criteria. Results: The literature search produced 200 articles that met the criteria. A screening of the studies resulted in '19 articles, These were distributed to all panelists for review prior to a roundtable discussion. The panel unanimously voted to adopt 7 consensus statements and recommendations, 5 of which were given a strength of "A: 1 of which was given a strength of "B:' and 1 of which was givers a strength of "C': Conclusion: The 2-GEP test and EIS can aid in the precise diagnosis of clinically indeterminate lesions and the' 3-GEP test can be used when histopathology is equivocal. The 31-GEP test can enhance prognostic assessment beyond AJCC8 staging and improve clinical decision -making.

Background: Drug tolerability is the degree to which a patient can tolerate a drug's adverse effects. VP-102, a drug-device combination product containing cantharidin (0.7%), a vesicant, is approved for treatment of molluscum contagiosum (molluscum) in patients >2. Local skin reactions (LSRs) are expected, including pain. In Phase 3 trials, 97% of LSRs were mild to moderate. The discontinuation rate due to an adverse reaction was 2.3%:0.5% (drug:vehicle) treated subjects, respectively. This post-hoc analysis evaluated VP-102 tolerability based on analgesic usage over the study course. Methods: VP-102 or vehicle was applied to all baseline and new lesions once every 21 days until complete clearance, or up to a maximum of 4 applications. Acetaminophen or ibuprofen were permitted for application site pain and/or other Adverse Reactions. Results: Overall incidence of pain at any time for a VP-102 subject was 62.7% (195/311), with the majority [(60.5%),188/311] as mild to moderate. 18.6% (58/311) of VP-102 and 1.4% (3/216) of vehicle treated subjects received an analgesic, including 15.8% (49/311) for an LSR after the first VP-102 application. Median VP-102 analgesic use for LSR pain (range) was 2 (1-14) days for the entire study, and 2 (1-9) days after the first application. 29% of participants who reported analgesic usage took medication ≤1 day. Analgesic usage for AEs other than LSR pain (≥ 5% of participants) included 6% (19/311) for application site vesicles. There were no treatment-related SAEs reported. Conclusions: In this largely pediatric population, VP-102 was well-tolerated, with a short duration of elective analgesic use.

Introduction: VP-315 is an intratumorally injected, chemotherapeutic oncolytic peptide in development as a non-surgical immunotherapeutic agent to be utilized as first line therapy in a primary or neoadjuvant setting for patients with basal cell carcinoma (BCC). Objective: In Part 2 of this study, the secondary objective was to evaluate the effect of various dosing regimens on the antitumor efficacy of VP-315 in a larger population of adult subjects with biopsy proven BCC. Methods: Eighty-two (82) subjects with up to 2 target BCC tumors (total 91 tumors) were treated intratumorally with VP-315 for up to 2 weeks. Cohort 3 was not enrolled based on results from Cohorts 1-2. Each 7-day treatment week was comprised of 2 or 3 consecutive treatment days followed by a no-treatment period of at least 4 days. Dosing scheme: Cohort 1: (n=6) Tumor injected 3 days consecutively (3X/week 4 mg loading dose Day 1 followed by 8 mg dose). Cohort 2: (n=3) Tumor injected 3 days consecutively (3X/week 8 mg dose). Cohort 4: (n=36) Each tumor was injected 2 days consecutively (2X/week 8 mg split dose*). Cohort 5: (n=37) Each tumor was injected 3 days consecutively (3X/week 8 mg split dose*). * Dose split into 2 injections, 30% injected initially; 70% injected 15-30 minutes later. Efficacy endpoints included histological clearance of target tumor(s) and estimate of remaining tumor volume (tumor size reduction) at excision (Week 12-13). Results: Eighty-two (82) subjects (n=92 lesions) completed treatment for BCC with VP-315 in Part 2. Approximately 51% of tumors achieved complete histologic clearance. All tumors treated had a reduction in tumor size. Overall tumor size reduction was 86%. Tumor size reduction in subjects who still had any residual tumor was 71%. Conclusion: Complete histological clearance in a majority of VP-315 treated tumors could eliminate the need for surgical intervention in those patients in clinical practice. In subjects with residual tumor burden, the substantial reduction in tumor size after VP-315 treatment would markedly reduce the surgical incision area and the amount of potential post-surgical scarring. Based on the favorable results, further research using VP-315 as a potential non-surgical immunotherapy for BCC as a first line therapy in a primary or neoadjuvant setting is warranted.

Introduction VP-315 is an intratumorally injected, chemotherapeutic oncolytic peptide in development as a non-surgical immunotherapeutic agent to be utilized as first line therapy in a primary or neoadjuvant setting for patients with basal cell carcinoma (BCC). Objective In Part 2 of this study, the primary objective was to determine the optimal dosing regimen for VP-315 by exploring the effects of various dosing schemes on the safety and tolerability of VP-315 in a larger population of subjects with biopsy proven BCC. Methods Eighty-two (82) subjects with up to 2 target BCC tumors (total 91 tumors) were treated intratumorally with VP-315 for up to 2 weeks. Cohort 3 was not enrolled based on results from Cohorts 1-2. Each 7-day treatment week was comprised of 2 or 3 consecutive treatment days followed by a no-treatment period of at least 4 days. Dosing scheme: Cohort 1: (n=6) Tumor injected 3 days consecutively (3X/week 4 mg loading dose Day 1 followed by 8 mg dose). Cohort 2: (n=3) Tumor injected 3 days consecutively (3X/week 8 mg dose). Cohort 4: (n=36) Each tumor was injected 2 days consecutively (2X/week 8 mg split dose*). Cohort 5: (n=37) Each tumor was injected 3 days consecutively (3X/week 8 mg split dose*). * Dose split into 2 injections, 30% injected initially; 70% injected 15-30 minutes later. Safety and tolerability were assessed by documenting the occurrence of Treatment Related Adverse Events (TRAEs), including those of special interest, Treatment Related Serious Adverse Events (TRSAEs), discontinuations due to AEs and expected treatment-related cutaneous reactions including tumor necrosis. Results All 82 subjects completed one of the VP-315 treatment regimens for BCC. TRAEs were mostly mild to moderate. AEs included injection site pain (mild 13.4%, moderate 12.2%, severe 1.2%), hypertension (mild 4.9%), hypotension (mild 4.9%), erythema (mild 1.2%, moderate 2.4%), and headache (mild 2.4%). Expected cutaneous reactions were observed. No TRSAEs were reported. Conclusion VP-315 treatment was shown to be safe and well-tolerated when administered once daily 2-3 times per week per tumor for up to 2 weeks using a split dose approach. Given its favorable safety profile, VP-315 warrants continued research as a potential non-surgical immunotherapy for BCC as a first line therapy in a primary or neoadjuvant setting. Sponsored by Verrica Pharmaceuticals Inc.

BACKGROUND: Cutaneous squamous cell carcinoma (cSCC) is a growing health concern with a rapidly increasing incidence. Disease-specific mortality is typically preceded by a metastasis, but current staging systems have significant limitations in predicting this event. The 40-gene expression profile (40-GEP) test is a validated method of further stratifying patients based on the risk of regional or distant metastasis, but limited guidelines exist for incorporating this test into clinical practice. OBJECTIVE: To review the available literature on the use of gene expression profile (GEP) testing to assess prognosis in cSCC and create consensus statements to guide dermatology clinicians on its use. METHODS: A comprehensive literature search of PubMed, EMBASE, and Scopus was completed for English-language original research articles on the use of GEP testing to assess cSCC prognosis. A panel of 8 dermatologists with significant expertise in diagnosing and managing cSCC gathered to review the articles and create consensus statements. A modified Delphi process was used to approve each statement and a strength of recommendation was assigned using the Strength of Recommendation Taxonomy (SORT) criteria. RESULTS: The literature search produced 157 articles that met the search criteria. A thorough screening of the studies for relevance to the research question resulted in 21 articles that were distributed to the panelists for review prior to the roundtable discussion. The panel unanimously voted to adopt 7 consensus statements and recommendations, 6 of which were given a strength of "A" and 1 of which was given a strength of "C". CONCLUSION: The 40-GEP test provides accurate and independent prognostic information beyond standard staging systems that only incorporate pathologic data. Incorporation of GEP testing into national guidelines can help further stratify patients based on risk of metastasis and thus may improve morbidity and mortality. J Drugs Dermatol. 2023;22(12):54-60.   doi:10.36849/JDD.7691.

Background: Cutaneous melanoma (CM) guidelines put forth by the eighth edition of the American Joint Committee on Cancer (AJCC8) and the National Comprehensive Cancer Network (NCCN) do not currently account for lesion genomics when assessing prognosis. Gene Expression Profile (GEP) tests have become a widely adopted tool to help clinicians identify patients at higher risk for metastasis and recurrence. Objective: To review the available literature that has been published since a consensus panel in 2018 on three commercially available GEP tests used in the prognostic assessment of CM and create updated guidelines and consensus statements for their optimal use. Methods: A comprehensive literature search of PubMed and Google Scholar was conducted for relevant English-language original research articles, meta-analyses, and systematic reviews published from 2019 through 2022. A panel of 6 key opinion leaders in dermatology with specialized expertise in diagnosing and managing CM then convened to review the articles and create guidelines. A modified Delphi process was used to approve each statement. The panel assigned each article a level of evidence and each consensus statement a strength of recommendation using Strength of Recommendation Taxonomy (SORT) criteria. Results: The literature search identified 785 articles that met the search criteria. Of these, there were 22 articles that validated the 31-GEP test, 2 that validated the 11-GEP test, and 7 that validated the 8-GEP + CP test. The panel unanimously approved 6 usage guidelines and 5 consensus supporting statements for the appropriate use of these tests. Conclusion: Based on the currently available literature, GEP tests provide valuable information beyond AJCC8 and NCCN guidelines for the prognostic assessment of CM. There are significantly more validation studies supporting the use of the 31-GEP test compared to the 11-GEP test and the 8-GEP + CP test.

Analysis of morphological characteristics for the diagnosis of melanoma remains a challenge. New technologies for the diagnosis and prognosis of melanocytic lesions have been emerging to ensure earlier and more accurate detection. In this article, we review multiple technologies that improve melanoma diagnostic accuracy such as electrical impedance spectroscopy, pigmented lesion assay, reflectance confocal microscopy, and gene expression profile tests.

Background:The current mainstay treatment of perimenstrual acne consists of systemic hormonal therapies, which can be problematic due to their side effects, stigma, or pill burden. Topical treatments are often used as well; however, data on their efficacy in treating this type of hormonal acne are limited.Objective:We sought to evaluate the efficacy and tolerability of clindamycin phosphate and benzoyl peroxide 1.2%/3.75% combination gel in treating perimenstrual acne in adult women.Methods:The single-group interventional pilot study was performed on 22 adult female subjects with perimenstrual acne. The subjects applied the investigational drug daily and were assessed every 14 days for a total of 99 days. Treatment success was evaluated by the investigators using the acne physician global assessment (PGA) scoring system. Drug tolerability assessment was based on the subject-reported adverse events, as well as physician-evaluated erythema, scaling, and dryness.Results:The study demonstrated a significant improvement in PGA score and lesion count, as well as patient-reported outcomes. The medication was well-tolerated in all subjects.Limitations:Limited sample size; lack of concurrent comparison group.Conclusion:Clindamycin phosphate and benzoyl peroxide 1.2%/3.75% combination gel presents an important topical option for perimenstrual acne.

Background Laser-assisted liposuction (LAL) has been used to maximize viable adipocyte yields in lipoaspirates, although optimizing tissue processing methods is still a challenge. A high-quality lipoaspirate has been a key factor for extended graft longevity. Objective To assess the viability and potency of stromal vascular fraction (SVF) cells and adipose-derived stem cells (ASCs) in fat samples from lipoaspirates harvested with a novel 1470-nm diode, radial emitting LAL platform. Two processing methods, enzymatic and nonenzymatic, were compared. Methods Laser-assisted liposuction lipoaspirates harvested from 10 subjects were examined for cell viability after processing by enzymatic or nonenzymatic methods. Isolated SVF cells were cultured with an ASC-permissive medium to assess their viability and proliferation capacity by cell proliferation assay. Flow cytometric analysis with ASC-specific markers, gene expression levels, and immunofluorescence for ASC transcription factors were also conducted. Results Lipoaspirates showed high SVF cell viability of 97% ± 0.02% and 98% ± 0.01%, averaged SVF cell count of 8.7 × 106 ± 3.9 × 106 and 9.4 × 106 ± 4.2 × 106 cells per mL, and averaged ASC count of 1 × 106 ± 2.2 × 105 and 1.2 × 106 ± 5 × 105 cells per mL in nonenzymatic and enzymatic methods, respectively. The ASC-specific markers, gene expression levels, and immunofluorescence for ASC transcription factors confirmed the adipose origin of the cells. Conclusions The laser lipoaspirates provide a high yield of viable and potent SVF cells and ASCs through both nonenzymatic and enzymatic processes. Improved purity of the harvested lipoaspirate and high ASC content are expected to result in extended graft longevity. Furthermore, eliminating enzymatic digestion may provide advantages, such as reducing process time, cost, and regulatory constraints.

Introduction: Psoriasis, an immune-mediated disease that manifests cutaneously with possible arthritic complications, affects millions of people in the United States and worldwide. Depression and suicidal ideation and behavior (SIB) are two prevalent comorbidities associated with psoriasis, due to the chronic nature of the disease, lack of a cure, as well as social stigma, all of which are detrimental to quality of life. Among the options available for management of moderate-severe psoriasis, apremilast and brodalumab represent recent additions to the therapeutic armamentarium for managing psoriasis. It has been suggested that the aforementioned drugs can lead to depression and possibly increase the risk for SIB. Furthermore, a black box warning was issued for brodalumab. This review challenges opinions that the drugs are solely responsible for exacerbating depression and SIB, when in fact it could be psoriasis itself. Methods: An extensive search of available literature linking cytokines to suicidal behavior was performed. After filtering for relevance, 22 articles were reviewed in detail. Results: Brodalumab and apremilast, both molecularly and clinically, do not objectively increase the risk for depression and/or suicidal ideation and behavior. Conclusion: After careful review of the appropriate studies and relevant literature, patients with moderate-severe psoriasis, including those that experience depression resulting from their chronic condition, would likely benefit from early, rather than delayed initiation of effective medications like apremilast and brodalumab. The speed of response and high level of efficacy of brodalumab make it an ideal intervention for patients suffering depression caused by their psoriasis.