Using a mobile Raman system with 785 nm diode laser and handheld probe we studied more than fifty clinical samples ex vivo, including squamous cell carcinoma, basal cell carcinoma, and normal skin, generating almost one thousand Raman spectra in total. We compared preliminary tissue classification results for the new data set using a variety of traditional ML classifiers. PLS-DA gave comparatively few false positives and a good specificity rate of 95.5%. PCA-QDA gave a larger proportion of false positives (Normal/SCC confusion) and a lower specificity rate of 77.7%. Both classifiers exhibited considerable BCC/SCC confusion, resulting in sensitivity rates for PLS-DA and PCA-QDA of 66.5% and 77.8% respectively. The K-nearest neighbors (KNN) and support vector machine (SVM) classifiers displayed the highest overall test accuracy at similar to 84%, whereas a wide shallow feedforward neural network achieved a test accuracy of 80.8% and the highest ROC AUC of 0.910. These three classifiers (especially SVM) performed considerably better than PLA-DA and PCA-QDA at distinguishing BCC and SCC sample spectra. The sensitivity rates for KNN and SVM for the 3-class classification task were 80.0% and 78.7% and the specificity rates were 87.3% and 88.6% respectively. As accuracy, specificity, and sensitivity well above 90% is desired for robust clinical performance, more work is required to tune these classifiers and to explore other potentially better classifiers such as deep neural networks with larger sample numbers.

Patients diagnosed with metastatic basal cell carcinoma (BCC) have a poor prognosis. The current standard of care for adults with locally advanced or metastatic BCC who are not candidates for surgery or radiation therapy is treatment with hedgehog pathway inhibitors (HHIs). For patients who progress while on this therapy, further treatment options are limited. There is also a need for real-world clinical practice data on the clinical characteristics, management, disease progression, and survivorship of these patients. The ongoing CemiplimAb-rwlc Survivorship and Epidemiology (CASE) study is a phase IV, multicenter, prospective, noninterventional survivorship and epidemiology cohort study evaluating the effectiveness and safety of cemiplimab, a fully human immunoglobulin G4 monoclonal antibody that blocks the interaction between the programmed cell death-1 (PD-1) receptor and its ligands. This paper describes one cohort of the CASE study of patients with locally advanced or metastatic BCC who have failed or are intolerant of HHIs or for whom HHI therapy is not appropriate. Outcome measures of the study include response to treatment, quality of life, safety, treatment patterns, patient experience, and survival. This study could provide a more complete characterization of this patient population and fill knowledge gaps related to real-world treatment utilization and patient outcomes.Clinical Trial registration: NCT03836105.

Introduction Cemiplimab 350 mg every 3 weeks intravenously is approved for the treatment of advanced cutaneous squamous cell carcinoma (CSCC) in patients who are not candidates for curative surgery or radiation. For early-stage CSCC, surgery is the standard of care. For patients for whom non-surgical management of early-stage CSCC is preferable, low-dose intralesional (IL) cemiplimab demonstrated promising clinical activity in a pilot study (NCT03889912). The primary objective of this study is to assess the non-inferiority of IL cemiplimab versus primary surgery by event-free survival. Secondary objectives include safety, tolerability, longest diameter of surgical defect after resection in both arms, and composite, complete response in the experimental arm. Trial design In this phase 3 randomized (NCT06585410), open-label, multicenter study, approximately 369 patients with early-stage CSCC will be randomized 2:1 to cemiplimab (5 mg IL every week for 6 weeks) versus primary surgery. Key inclusion criteria are: ≥18 years of age; histologically confirmed invasive CSCC target lesion that is ≥1.0–≤2.0 cm (longest diameter) located in the head and neck, hand, or pre-tibial surface; and adequate performance status and organ function. Key exclusion criteria include autoimmune disease, concurrent or prior solid tumor or hematologic malignancy (except for protocol-allowed exceptions), and a history of solid organ transplant. Patients will be followed for approximately 3 years. Results The study is actively recruiting. Enrollment is planned at study sites across North America and Australia. Conclusions This study will help establish the potential clinical utility and broader applicability of low-dose IL cemiplimab in early-stage CSCC.

BACKGROUND:Surgical procedures remain the gold standard for treating basal cell carcinoma (BCC), although commonly associated with cosmetic defects. The demand for noninvasive alternatives remains high. OBJECTIVE:To determine efficacy and safety of red light photodynamic therapy (PDT) with 10% 5-aminolevulinic acid (ALA) gel vs vehicle for treatment of superficial BCC. METHODS:This randomized, double-blind, vehicle-controlled, pivotal phase III study was conducted at 21 centers in the US. Eligible participants had ≥1 naïve superficial BCC and received 1-2 PDT cycles (2 PDTs each cycle) followed by clinical and histological assessment 12 weeks after start of the last PDT cycle. RESULTS:Of 187 randomized participants, 145 received PDT with 10% ALA gel and 42 with vehicle. Histological clearance was 75.9% with 10% ALA gel vs 19.0% with vehicle (P < .0001). Clinical clearance was 83.4% with 10% ALA gel vs 21.4% with vehicle (P < .0001). A total of 88.1% of participants treated with 10% ALA gel rated the esthetic outcome as very good or good. No previously unknown adverse events occurred. LIMITATIONS:Few participants with lesions on face/scalp; to date, a 60-month follow-up is still ongoing. CONCLUSION:10% ALA gel showed significantly higher clearance rates than vehicle with unproblematic safety and positive esthetic outcome.

OBJECTIVE:To determine the factors that might limit Hispanic patients from participating in dermatological clinical trials.METHODS:From January 2022 to July 2022, we administered a 31-item, in-person questionnaire to patients recruited in the waiting area of the Caridad Center, one of the largest free clinics in the United States with a predominately Hispanic population, and a nearby private primary care clinic.RESULTS:Overall, Hispanic patients agreed significantly more with statements in the domain of attitude and behavioral beliefs compared to non-Hispanic survey respondents. The Hispanic ethnicity was associated with increased odds of agreeing with the following statements: "My community would really benefit from skin cancer clinical trials" (OR=0.52; 95% CI 0.30, 0.92), "My participation in a skin cancer study would be very good" (OR=0.59; 95% CI 0.35, 0.99), and "I like to do good for others" (OR=0.41; 95% CI 0.22, 0.77).CONCLUSION:While the United States population is composed of 18.5% Hispanics, they only account for 1% of patients enrolled in clinical trials. This study helps identify potential motivational factors for Hispanic patients to participate in skin cancer clinical trials.

TPS9614 Background: Basal cell carcinoma (BCC) is the most common form of non-melanoma skin cancer in the United States. Surgical excision is the standard treatment, with < 1% of cases progressing to locally advanced or metastatic disease. Hedgehog pathway inhibitors (HHIs) are the first-line therapy for advanced BCC (aBCC); the US Food and Drug Administration and European Medicines Agency have approved the use of cemiplimab (a programmed cell death-1 inhibitor) in advanced BCC (aBCC) patients previously treated with (or are inappropriate for) HHI. Limited real-world data exist on the clinical characteristics, disease management and progression, and survivorship of patients with aBCC. The ongoing C.A.S.E. study aims to evaluate the efficacy, safety, disease evolution, survivorship, and patient reported outcomes (PRO) in patients treated with cemiplimab in the real-world setting. Methods: This trial in progress (NCT03836105) aims to describe the effectiveness and safety of cemiplimab 350 mg administered every 3 weeks for treatment of patients with aBCC in real-world clinical settings. Up to 100 adult patients with aBCC who are prescribed commercially available cemiplimab from ~65 study sites in the United States will be included. The duration of follow-up will be 24 months. Endpoints for this study relate to real-world efficacy, including overall survival; progression-free survival; objective response rate, (partial or complete response); and disease control rate, defined as the percentage who do not progress for ≥ 6 months; Time to response, duration of response, time to treatment failure, and disease-specific death will also be assessed. Real-world safety outcomes will also be captured, including immune-related adverse events, infusion-related reactions, and serious adverse events. Patient selection criteria and treatment patterns will be analyzed using descriptive statistics. This study also aims to describe the patient experience of real-world treatment with cemiplimab. PROs including global quality of life, functioning, and symptoms will be captured at baseline and follow-up visits via the EORTC QLQ-C30 and the Skin Care Index. Recruitment for this trial is ongoing. Clinical trial information: NCT03836105 .

Cemiplimab is the first programmed cell death-1 inhibitor approved for the treatment of pts with locally advanced or metastatic CSCC who are not candidates for curative surgery or curative radiation. Here, we describe demographics, effectiveness, and safety results of cemiplimab in a general population of pts with advanced CSCC enrolled in the CASE study (NCT03836105). CASE is a real-world study evaluating the effectiveness, safety, disease evolution, survivorship, and quality of life of pts with advanced CSCC treated in 43 US academic and community centres. Pts had received cemiplimab 350 mg intravenously every 3 weeks per standard of care. Prospective data are captured using an electronic case report form and include demographics, disease characteristics, efficacy, and quality-of-life data. Investigator assessment of objective response rate (ORR), survival, and safety was conducted. Data collected between June 2019 and October 2021 are presented. Recruitment is ongoing. As of 1 Oct 2021, 188 pts were enrolled in the CASE study. Median age was 76.0 years (range, 33.0–98.0), 76.9% were male, 90.9% were White, and 36 (19.1%) were considered immunocompromised or immunosuppressed (IC/IS). Median duration of cemiplimab exposure for all pts was 22.1 weeks (quartile [Q] 1–Q3, 9.1–46.4; range, 0–117). Efficacy was evaluated in pts enrolled before Cycle 3 (n=164), when a clear treatment outcome could be established. ORR for the overall population was 42.1% (95% confidence interval [CI], 34.4–50.0) and for the IC/IS population (n=27) was 44.4% (95% CI, 25.5–64.7). Eight (4.3%) pts experienced a treatment-related serious adverse event and 47 (25.3%) experienced a treatment-related immune-related adverse event. Cemiplimab was generally well tolerated in IC/IS pts. In total, 95 (48.2%) pts discontinued treatment. At this timepoint, the safety, tolerability, and effectiveness of cemiplimab in this real-world study of pts with advanced CSCC were consistent with results observed in the registration clinical trial (NCT02383212, NCT02760498).

Cutaneous squamous cell carcinoma (CSCC) is the second most common skin cancer, with an estimated annual incidence of > 700,000 in the United States.1,2 In >95% of patients, CSCC is cured, most commonly with excision or Mohs micrographic surgery. A small percentage of patients develop advanced CSCC (locally advanced CSCC [laCSCC] or metastatic CSCC [mCSCC]), which is associated with a high mortality rate and poor prognosis, with an estimated 3-year survival of 55%.3,4 Traditional treatment options for advanced CSCC include cytotoxic chemotherapy and targeted therapy; eg, epidermal growth factor receptor inhibitors.

BACKGROUND:Dermatologic surgery services are largely absent in Africa and in Afro-Caribbean counties. In the USA, studies of people of African ancestry have demonstrated health care gaps, but there are no data for Africa nor a Afro-Caribbean country. Dermatology surgery has been largely absent from global health because there are few data to demonstrate the need. We sought to determine skin cancer tumor types, and local knowledge and perception in an Afro-Caribbean country.OBJECTIVE:We sought to determine whether there exist knowledge gaps and whether a dermatology surgery medical missions program would improve the health of Afro-Caribbean people.METHODS:First, we conducted a survey of knowledge and behaviors related to skin cancer. Second, we analyzed the number and types of tumors treated during a multi-year surgical dermatology project.RESULTS:In the survey, 62% did not know what melanoma was. Eighty-one percent did not think skin cancer is preventable. Of 163 surgical specimens, 64 were malignancies with 91% related to UV exposure.CONCLUSION:There is a need for a skin cancer treatment and education program in a country of mostly African-ancestry people.

9547 Background: Immunosuppressed and/or immunocompromised patients are at increased risk for solid tumors and cutaneous malignancies. Limited data exist on the safety and effectiveness of immune checkpoint inhibitors (ICIs) in these patients because they are frequently excluded from clinical trials. Here, we describe the safety and effectiveness results from the initial cohort of immunosuppressed and/or immunocompromised patients with advanced CSCC enrolled in the C.A.S.E. study (NCT03836105). Methods: C.A.S.E. is a prospective, real-world, multi-center, longitudinal study evaluating the effectiveness, safety, quality of life, and survivorship in patients with advanced CSCC treated with cemiplimab. Patients received cemiplimab 350 mg intravenously every 3 weeks per routine standard of care. Patient demographics, disease characteristics, immunosuppression, and relevant medical history were collected. Immunosuppressive regimens varied amongst patients. Investigator assessment of objective response rate (ORR), safety, and tolerability was conducted. Data from 26 immunosuppressed and/or immunocompromised patients with advanced CSCC treated with cemiplimab are presented. Recruitment is ongoing. Results: As of November 17, 2020, 121 patients were enrolled in the C.A.S.E. study, of which 26 patients (median age: 74 years [IQR: 71-84]; 85% male; 89% Caucasian) were designated as immunocompromised or immunosuppressed due to a history of solid organ transplant (n = 6), autoimmune disorder (n = 11), or hematologic malignancy (n = 9). Median duration of cemiplimab exposure was 14 months (IQR: 9.1–42, range: 0, 67). Among 19 immunocompromised or immunosuppressed patients who enrolled in C.A.S.E. prior to their third dose of cemiplimab, ORR per investigator assessment was 47% (95% CI: 24–71); 1 (5%) patient had complete response; 8 (42%) had partial response. One patient had a treatment-related serious adverse reaction of organ transplant rejection. One (3.8%) patient discontinued treatment due to increased alanine aminotransferase (not treatment-related). Immune-related AEs (irAEs) occurred in 23% of patients. No treatment-related AEs led to death. Conclusions: The safety, tolerability, and effectiveness of cemiplimab in this initial cohort of immunosuppressed and/or immunocompromised patients with advanced CSCC appear to be consistent with those observed in clinical trials that excluded these patients. Further follow-up and additional data would add to our general understanding of safety and effectiveness of anti-PD1 therapy in immunocompromised and/or immunosuppressed patient populations overall. Clinical trial information: NCT03836105.

Recently, Raman Spectroscopy (RS) was demonstrated to be a non-destructive way of cancer diagnosis, due to the uniqueness of RS measurements in revealing molecular biochemical changes between cancerous vs. normal tissues and cells. In order to design computational approaches for cancer detection, the quality and quantity of tissue samples for RS are important for accurate prediction. In reality, however, obtaining skin cancer samples is difficult and expensive due to privacy and other constraints. With a small number of samples, the training of the classifier is difficult, and often results in overfitting. Therefore, it is important to have more samples to better train classifiers for accurate cancer tissue classification. To overcome these limitations, this paper presents a novel generative adversarial network based skin cancer tissue classification framework. Specifically, we design a data augmentation module that employs a Generative Adversarial Network (GAN) to generate synthetic RS data resembling the training data classes. The original tissue samples and the generated data are concatenated to train classification modules. Experiments on real-world RS data demonstrate that (1) data augmentation can help improve skin cancer tissue classification accuracy, and (2) generative adversarial network can be used to generate reliable synthetic Raman spectroscopic data.

To the Editor: Minority groups are often diagnosed with melanomas at more advanced stages, with few culturally appropriate public health interventions available.1 The positive impacts of community health worker (CHW) programs have been established for the prevention of other cancers, but limited studies examining the effect of CHWs for skin cancer prevention exist.2,3