bluuebunny/crossref_metadata_2025_split huggingface dataset:
The current state and future of neoadjuvants in resectable melanoma: Review of phase II/III studies conducted between 2018-2022.
Authors: Lee Chan Mi , Mirsky Matthew M , Wang Margaret , Mangla Ankit 
Published: June 2023

e21568 Background: Adjuvant therapy with single agent anti-PD1 and BRAF/MEK-inhibitors (BRAF/MEKi) is approved for patients diagnosed with high-risk stage III melanoma. The goal of adjuvant therapy is to prevent the growth of the occult metastasis to distant organs. The premise of neoadjuvant therapy in clinical stage III melanoma is to allow for a better antigen exposure when checkpoint inhibitors are administered. We aimed to get an overview of the current state of neoadjuvant therapy in resectable melanoma. Methods: A systematic literature search was conducted in November 2022, using PubMed, American Society of Clinical Oncology (ASCO) Journal of Clinical Oncology and European Society for Medical Oncology (ESMO) abstract databases. Eligible studies included Phase 2 and 3 randomized controlled trials (RCT), single-arm trials, pooled analyses, and planned future trials published between 2018-2022 looking at the efficacy of neoadjuvants in resectable melanoma. Two individuals (CL and MM) screened all the studies, and 3 individuals (CM, MM, MW) went over the list of Abstracts. Primary outcomes and secondary outcomes, as well as median duration of follow up and Grade 3 or above adverse effects (AEs) were recorded. Abstracts with more recent findings or final publications were excluded in the final analysis. Results: A total of 14 published studies (4 RTCs, 5 single-arm, 2 OpACIN-neo and 3 related sub-analysis studies) and 16 abstracts (5 ESMO, 11 ASCO) were identified, representing 34 unique Neoadjuvant arms and a total of 1,496 patients. Thirteen of 27 trials making 71% of patients (n = 1061) tested immune checkpoint inhibitors (ICIs). Four of 27 trials of total n = 112 tested BRAF/MEKi. All ongoing or future studies (7 trials) tested combination of ICI with BRAF/MEKi or other molecules such as MDM2 inhibitors, interferon-α, or oncolytic viruses. Most of studies (54% of ICI studies, 50% of BRAF/MEK inhibitor trials, and 80% of other studies) used pathological response as their primary outcome. Other primary end points included event-free survival (EFS) and relapse-free survival (RFS), and 13/14 published studies and 13/16 abstracts met the primary end point. A pooled analysis of complete pathologic response (pCR) revealed an estimate of 38.3% ± 19.7 (mean ± SD) from 16 unique ICI neoadjuvant arms, 51.9% ± 5.3 for BRAF/MEKi (from 3 data points), and 21.0% ± 7.2 for other agents/combinations (from 3 data points). Rate of ≥ Grade 3 AEs was 28.7% ± 31.0 (from 11 data points) for studies testing ICI, 32.5% ± 14.1 (from 6 data points) for BRAF/MEKi, and 23.6% ± 20.2 (from 3 data points) from studies testing other agents/combinations. Conclusions: Recent studies have shown that neoadjuvant in resectable melanoma can offer increased therapeutic efficacy. While past studies have focused on PD-1 and CTLA-4 inhibitors, ongoing and future studies are beginning to test newer agents and novel molecular targets.
Sun exposure and associated risks: Insight from an international survey with a focus on the population with past medical history of skin cancers.
Authors: Dreno Brigitte , Passeron Thierry , Puig Susana , Goh Cl , Lim Henry , Ly Fatimata , Kang H. , Morita A. , Ocampo Jorge , Schalka Sergio , Wei L. , Lefloch Caroline , Demessant Anne-Laure , Kerob Delphine , Krutmann Jean 
Published: June 2023

e21575 Background: This survey investigates knowledge and behaviors regarding sun exposure among population who have been treated for skin cancer (melanoma/non melanoma) or pre-cancerous lesions in 17 countries. Methods: The survey (N = 17,001) was conducted online in 17 countries (5 continents) from 28 September-18 October 2021. Automated selection from the Ipsos online Panel ensured samples of 1,000 individuals in each country fit the quotas method based on gender, age, employment status, and country regions. Data covered demographics, phototype, exposure habits and practices, knowledge and understanding of risks. The current focus in this abstract was defined as individuals with a history of melanoma/non melanoma skin cancer, pre-cancerous lesions. Results: This sub population represents 8% of the general population (n = 1372), it comprised 54% men, average age was 49.9 years (SD:17.6) and 58% were of phototype 1-2. 90% were aware of sun-related skin-health issues (vs 88% in the general population). 79% did know that sun protection is useful when the weather is overcast, a better knowledge compared to the general population (61%). However, 34% indicated it was safe to expose themselves without protection when already tanned, a larger misconception compared to the general population (23%). 54% did not understand the difference between UVA and UVB vs 70% in the general population. Only 28% systematically/often use all protections measures during exposure; still a higher practice compared to the general population (12%). However, 42% said they protected from the sun all year round, a better habit compared to the general population (23%). During sun exposure, among the 91% who declared using sunscreen, 74% applied sunscreen only once or twice a day, a similar practice among general population (74%). And when already tanned 38% decreased frequency of application and/or used lower protection (44% among general population). 82% regretted not having previously used better protection, a much stronger regret compared to the general population (57%). Conclusions: Although individuals who have been treated for skin cancer or pre-cancerous lesions had better knowledge and behavioral attitudes compared to the general population, this survey shows that even a population at high risk of melanoma and having a regular medical follow-up does not sufficiently perceive the importance of photoprotection in a prevention objective. This leads to discuss the implementation of new information tools with more impact.
Prognostic biomarkers for survival in mucosal melanoma.
Authors: Thierauf Julia Cara , Kaluziak Stefan T. , Codd Elizabeth , Dybel Stacey , Jobaggy Soma , Purohit Rashi , Farahani Alex , Dedeilia Aikaterini , Naranbhai Vivek , Hoang Mai , Fisch Adam , Ritterhouse Lauren , Boland Genevieve Marie , Lennerz Jochen K. , Iafrate A. John 
Published: June 2023

e21576 Background: Mucosal Melanoma is a rare subtype of melanoma with a more aggressive clinical course when compared to cutaneous melanoma. In cutaneous melanoma, the absence of pigmentation and presence of NRAS/KRAS mutations are known as biomarkers indicating an aggressive clinical course with significantly shorter overall survival times. Similar data for mucosal melanoma are currently missing. Here, we present real world outcome data in a large cohort of genotyped mucosal melanoma patients and assessed the prognostic relevance of pigmentation- and NRAS/KRAS mutation status. Methods: We correlated pathological reports and clinical data with overall survival of patients with mucosal melanoma. Furthermore, we performed clinically integrated molecular genotyping and analyzed real world treatment regimens for covariates associated with clinical outcome. For institutional data analysis, we ran a source query and only included patients with the diagnosis of mucosal melanoma, available genotyping data and comprehensive clinical information. As a population-based reference and to directly compare overall survival differences we first queried the National Cancer Institute’s Surveillance, Epidemiology and End Results (SEER) database. Pigmentation status was assessed by pathological review. Treatment regimens were identified by chart review. Results: We identified a cohort of 39 patients with mucosal melanoma where clinical and molecular data was available. Patients with amelanotic mucosal melanoma had a significantly shorter overall survival ( p = 0.003). In addition, the presence of a NRAS or KRAS mutation was significantly associated with poor overall survival (NRAS or KRAS p = 0.024). Therapeutic regimens were heterogeneous with a mean of 5 treatment lines per patient. Patients with low stage tumors who received immunotherapy had a significantly shorter overall survival (p < 0.001), although numbers were small. Conclusions: The absence of pigmentation and the presence of NRAS or KRAS mutations are poor prognostic indicators for survival in CM. Both biomarkers are have been described in MM. Currently, it is unknown if the same prognostic relevance for the lack of pigmentation and RAS mutations exists in MM. Here we analyzed a cohort of MM for outcome measures and determined that two known prognostic biomarkers for CM are in fact novel prognosticators for MM.
Sun exposure and associated risks: Insight from an international survey with a focus on the organ transplant recipient population.
Authors: Kerob Delphine , Dreno Brigitte , Passeron Thierry , Puig Susana , Goh Cl , Lim Henry , Ly Fatimata , Kang H. , Morita A. , Ocampo Jorge , Schalka Sergio , Wei L. , Lefloch Caroline , Demessant Anne-Laure , Krutmann Jean 
Published: June 2023

e21578 Background: This survey investigates knowledge and behaviors regarding sun exposure among population who have been treated with immunosuppressive anti-graft rejection drugs because of an organ transplantation. Methods: The survey (N = 17,001) was conducted online in 17 countries (5 continents) from 28 September-18 October 2021. Automated selection from the Ipsos online Panel ensured samples of 1,000 individuals in each country fit the quotas method based on gender, age, employment status, and country regions. Data covered demographics, phototype, exposure habits and practices, knowledge and understanding of risks. The current focus in this abstract was defined as individuals who have been treated with immunosuppressive anti-graft rejection drugs because of an organ transplantation. Results: This sub population represents 3% of the general population (n = 434), it comprised 65% men, average age was 39.7 years (SD:14.6) and 57% were of phototype 1-2. 85% were aware of sun-related skin-health issues, a similar awareness among general population (88%). 79% did know that sun protection is useful when the weather is overcast, a better knowledge compared to the general population (61%). Furthermore, 75% did understand the difference between UVA and UVB vs 30% in the general population. But, 69% indicated it was safe to expose themselves without protection when already tanned, a much larger misconception compared to the general population (23%). Only 46% systematically/often use all protections measures during exposure; still a higher practice compared to the general population (12%). And, 63% said they protected from the sun all year round, a better habit compared to the general population (23%). However, during sun exposure, among the 93% who declared using sunscreen, 85% applied sunscreen only once or twice a day, a worse practice compared to the general population (74%). And when already tanned 37% decreased frequency of application and/or used lower protection (44% among general population). 89% regretted not having previously used better protection, a much stronger regret compared to the general population (57%). Conclusions: Although individuals who have been treated with immunosuppressive anti-graft rejection drugs because of an organ transplantation had better knowledge and behavioral attitudes compared to the general population, this survey shows that even a population at high risk of skin cancers and having a regular medical follow-up does not sufficiently perceive the importance of photoprotection in a prevention objective. This leads to discuss the implementation of new information tools with more impact.
Tebentafusp (tebe) in a real-world cohort of 72 French metastatic uveal melanoma (UM) patients (pts).
Authors: Piperno-Neumann Sophie , Mailly-Giacchetti Leah , Ramtohul Toulsie , Saint-Ghislain Mathilde , Pracht Marc , Thery Jean Christophe , Combe Pierre , Litrowski Noemie , Martin Hélène , Dutriaux Caroline , Garcia Agathe , de Koning Leanne , Servois Vincent , Rodrigues Manuel 
Published: June 2023

e21583 Background: Up to 50% of UM pts will develop metastases with poor overall survival (OS) and limited treatment options. Tebe, a bispecific T-cell engager binding CD3 and the gp100 protein presented by the HLA A*02-01, recently showed a benefit in overall response rate (ORR), progression-free survival (PFS) and OS in HLA A*02-01pos metastatic UM (mUM) pts in the IMCgp100-202 phase III trial. Prior to the EMA approval, French Health Authorities allowed an early access to tebe in May 2021 to UM metastatic pts. We here report our real-world experience with tebe in metastatic UM pts. Methods: Ongoing ambispective cohort of mUM pts treated with tebe in France. Metastases are evaluated according to RECIST 1.1 with assessments every 12 weeks (liver MRI +/- CT-scan). ORR, PFS, OS and toxicities are retrieved. Results: 72 pts started tebe between May 26th 2021 and December 12th 2022 (29 men and 43 women). Median age was 61 yo (32-78). Thirty, 34 and 7 patients underwent enucleation proton beam therapy or brachytherapy, respectively (one pt did not receive local treatment). The median time to first metastasis was 24 months (0-276). Tebe was prescribed in first-line in 46 patients, in second-line or more in 26 patients. Metastatic sites at tebe initiation were liver, lung, skin, bone and muscle in 71, 4, 2, 3 and 2 patients, respectively. Liver was the sole metastatic site in 63/72 patients (87.5%). With a median follow-up of 44 weeks, patients received a median of 36 weeks of tebe. Thirty patients discontinued tebe because of disease progression, two because of poor health status and none for toxicity. Of 60 assessable pts, 33 (55%) pts showed stable disease and 5 (8%) showed partial response as best response according to RECIST 1.1. Median PFS was 28 weeks (confidence interval 95% [CI95%]: 8-56) in the global cohort. OS at 12 months was 74% ([CI95%] = 0.62-0.89) in the global cohort, 73% ([CI95%] = 0.55-0.99) and 74% ([CI95%] = 0.57-0.97) in 1st and 2nd line and more, respectively. To date, 13 pts died. Circulating tumor DNA analyses and monitoring of peripheral blood leukocytes are ongoing and will be available by June 2023. Conclusions: In this ongoing, real-world, cohort of metastatic UM pts, tebe is associated with similar clinical outcomes as in the IMCgp100-202, phase III trial. Translational studies on blood and tumor samples are ongoing to identify predictive biomarkers of clinical benefit to this drug.
Community outreach in vulnerable populations: Skin cancer screening for firefighters.
Authors: Fay Christopher , Rice Shauna , Krueger Steven , St John Jessica 
Published: June 2023

e21587 Background: Firefighters have both an increased risk (21%) and 20-year younger median age (42) at diagnosis of melanoma compared to the general population. The World Health Organization classifies firefighters’ occupational exposures as "carcinogenic to humans," but there is limited knowledge regarding sun protection habits, skin cancer history, and community outreach in this at-risk population. Methods: Free, full-body skin examinations conducted by board-certified dermatologists using the American Academy of Dermatology’s SPOT Skin CancerTM screening form were offered to firefighters from 26 cities and towns in Massachusetts on two separate days in August 2021 and October 2022. Data from the screening form and subsequent skin biopsy results were obtained and reported. Results: Of 195 firefighters screened, 30 (15.4%) were referred for biopsy. All were white males, mean age was 44.7 years, 26.7% had prior tanning bed exposure, 80% had prior blistering sunburns, 20% used sunscreen regularly, 86.7% did not have a regular dermatologist, and 6.7% had a history of keratinocyte-based skin cancer. Nineteen (63.3%) had biopsies, most frequently on the back or face, which resulted in three nodular basal cell carcinomas and 11 dysplastic nevi (seven moderate-to-severe). Conclusions: Firefighters are an underrecognized vulnerable population for the development of skin cancer. Community outreach in the form of free skin cancer screenings is a successful model for increasing awareness and early diagnosis of skin cancer among this population. In addition to providing access to care, community screenings offer tailored educational opportunities that promote skin cancer prevention in this high-risk group.
Comparing PD-L1 scores for predicting pembrolizumab efficacy in first-line treatment of unresectable cutaneous squamous cell carcinomas.
Authors: Maubec Eve , Boubaya Marouane , Deschamps Lydia , Beylot-Barry Marie , Petrow Peter , Scheer-Senyarich Isabelle , Basset-Seguin Nicole , Grob Jean-Jacques , Dreno Brigitte , Bloch-Queyrat Coralie , Leccia Marie Thérèse , Stefan Andreea Raluca , Saiag Philippe , Grange Florent , Meyer Nicolas , Dalac Sophie , Alloux Céline , Lopez Isabelle , Tibi Annick , Lévy Vincent 
Published: June 2023

e21593 Background: In the CARSKIN study (NCT02883556), 1L pembrolizumab demonstrated promising activity with durable responses and manageable safety in patients (pts) with unresectable locally advanced or metastatic CSCC. Here we report best ORR and survival endpoints of the entire cohort by PD-L1 status. Methods: The imaging assessment per RECIST v1.1 was blinded with independent central review. Best ORR, PFS, DOR OS, in the overall sample and by PD-L1 status was centrally assessed by 2 blinded independent pathologists, one using the anti–PD-L1 E1L3N clone (TPSE1L3N), the other using the 22C3 antibody (TPS22C3 and CPS22C3). Among 57 pts, 6 were excluded from the analysis: 2 untreated pts, 1 early unrelated death and 3 pts tested only with 1 assay). ROC curve analysis was used to compare assays. Results: With a median follow-up of 26 mo, best ORR was 51% with 14 PR (27%) and 12 CR (24%). Relapse occurred in 3 PR and 1 PD-L1 – CR pts. Respective median PFS, DOR, and OS were 13.7, NR, and 25.3 mo; respective 1-year PFS, DOR and OS were 50% [38-66], 80% [65-97] and 73% [61-86]. With a cutoff of 1%, best ORR was higher either for TPSE1L3N + pts vs TPSE1L3N – pts (60% vs 18%, p = 0.02) and for CPS22C3 + pts (59% vs 20%, p = 0.038), but not TPS22C3 + pts (p = 0.76). The optimal cutoff of CPS22C3 for ORR using a ROC curve was estimated to be ≥ 7% with a sensitivity of 0.70 and a specificity of 0.75. For best ORR, area under the ROC curve was higher for CPS22C3 (0.72) than TPSE1L3N (0.62) but the difference was not significant (P = 0.21). Pts with TPSE1L3N ≥ 1% had a higher 1-y PFS (57% vs 27%, p = 0.004) and OS (82% vs 42%, P = 0.01). Pts with CPS22C3 ≥ 1%, had a better 1-y OS (79% vs 50%, p = 0.03), but not 1y-PFS. Conclusions: CPS22C3 ≥ 7% appeared equivalent to TPSE1L3N ≥ 1% for predicting ORR and OS in pts receiving pembrolizumab in 1L treatment of advanced or metastatic CSCCs. Replications are warranted for validation. Pts with low scores might beneficiate from combined treatments. Clinical trial information: NCT02883556 .
Dissecting the relationship between ethnicity and response to checkpoint inhibitors in patients with acral melanoma.
Authors: Kreidieh Firas Y. , Simien Rinata , John Ida , Rodgers Theresa , Abdel-Wahab Noha , Abdel-Wahab Reham , Diab Adi , Ludford Kaysia 
Published: June 2023

e21597 Background: Aral lentiginous melanoma (ALM) constitutes the most common subtype of cutaneous melanoma (CM) among people with pigmented skin, accounting to up to 70% of cases. In a prior study of 44 patients with advanced, unresectable ALM treated with checkpoint inhibitors, we demonstrated differential response to checkpoint inhibitors by ethnicity with Hispanic patients having a higher response to therapy compared to non-Hispanic patients. Accumulating evidence suggests that tumor mutation burden (TMB) can predict the efficacy of immune checkpoint inhibitors (ICI) in solid malignancies, including cutaneous melanoma. ALM however has significantly lower TMB compared to cutaneous melanoma suggesting that there are other mechanisms outside of TMB driving this response. Here, expanding upon our prior work, we will examine outcomes in over 130 patients and report for the first time, the correlation between ethnicity and response to checkpoint inhibitors in the largest dataset to our knowledge of acral melanoma patients. Methods: This was a retrospective analysis of all advanced and metastatic ALM patients treated with anti-CTLA4 (ipilimumab) or anti-PD1 (pembrolizumab or nivolumab) ICI between March 2011 and January 2019 at the University of Texas MD Anderson Cancer Center, Texas. Clinical response, progression free and overall survival outcomes (PFS and OS) and their correlation to ethnicity and TMB will be evaluated. Objective response will be measured using RECIST 1.1. OS and PFS will be estimated using the Kaplan-Meier method, and differences between groups assessed using the log-rank test. Associations between OS and PFS and measures of interest will be determined using Cox proportional hazards regression models. Results: 132 patients with Stages III-IV ALM (III: 27% and IV: 73%) were included in the analysis. Median age was 66.6 years old (15.8-92.5) and 58% were men. 28 (21.2%) self-identified as Hispanic, 101 (76.5%) were non-Hispanic, and 3 (2.3%) did not provide their ethnicity. The best objective response rate (ORR) was 27 (20.4%), with 9 (6.8%) showing complete response (CR) and 18 (13.6%) showing partial response (PR). 48 (36.4%) patients received anti-PD1 based- therapy while 57 (43.2%) received anti-CTLA4 only. We will present immune phenotyping of both adaptive and innate immune arms to investigate further mechanisms of differential response. Conclusions: The data from our prior small retrospective study suggested that non-Hispanic patients with ALM had low response rates to CPI presumably due to low TMB while interestingly, Hispanic patients, despite relatively low TMB have high response rates paralleling those seen in the overall cutaneous melanoma population. This data will provide the rationale to design prospective studies to investigate further how tumor micro-environment varies with ethnicity.