bluuebunny/crossref_metadata_2025_split huggingface dataset:
Distant stage melanoma incidence among US adult women.
Authors: Johnson Caitlin Ruth , Liao Cheng-I , Obiakor Bianca , Jiang Ruolin Lorraine , Kapp Daniel Stuart , Chan John K 
Published: June 2023

e21555 Background: To examine trends in distant stage melanoma incidence among U.S. women. Methods: Demographic and clinical data were obtained from the United States Cancer Statistics (USCS) Database from 2001-2019. SEER*Stat 8.3.9.2 and Joinpoint regression program 4.9.0.0 were used to calculate cancer incidences and trends per 100,000. Average annual percentage change (AAPC) was used to describe trends. Age-adjusted incidences were adjusted by the U.S. 2000 standard population. Results: From 2001-2019, 543,051 women were diagnosed with distant stage melanoma. Over this period, incidence rose from 0.37 to 0.59/100,000 with an increasing annual rate of 2.58% per year (p < 0.0001). In 2019, non-Hispanic White women had disproportionately higher incidence rates at 0.76/100,000 compared to Hispanic (0.26/100,000), non-Hispanic Black (0.17/100,000), and non-Hispanic Asian (0.08/100,000) women. Regarding race, the largest increase in distant melanoma incidence was observed in White women with an average annual increase of 2.92% (p < 0.0001). Among age groups, incidence was highest among those aged ≥45 (1.54/100,000) and 40-44 (0.53/100,000) years. However, the largest increases in distant melanoma incidence were found among 30-34-year-olds at a rate of 3.91% per year (p = 0.004) and 40-44-year-olds at 2.78% per year (p = 0.003). When examined by race and age, annual incidence rates were highest among White women aged 40-44 years at 3.68% per year (p < 0.0001). Regarding U.S. state, incidence was highest in Florida (1.34/100,000), West Virginia (1.32/100,000), and Oklahoma (1.20/100,000). The largest annual increases in distant melanoma incidence rates were observed in Nebraska at 8.63% (p = 0.001), Kentucky at 6.18% (p < 0.0001), and West Virginia at 6.06% (p = 0.001). When performing an intersection analysis of race, age, and U.S. stage, White women living in Nebraska aged ≥45 had the largest increase in distant melanoma at a rate of 8.12% annually (p = 0.004). In 2019, White women in Utah had the highest incidence of distant melanoma at 3.45/100,000. Conclusions: Distant stage melanoma is disproportionally increasing among adult women aged 30-44 years, especially among White populations. Further studies are warranted to understand the environmental and socioeconomic implications behind these trends.
Correlation of low B7-H6 expression with efficacy of immunotherapy inpatients with melanoma.
Authors: Chen Jian , Li Deqin , Zhang Weiwei , Song Shujie , Sun Dengjun , Luo Ningning , Yi Huan , Qi Yingxue , Li Mengmeng , Sun Tingting , Qi Chuang 
Published: June 2023

e21556 Background: B7-H6 (NCR3LG1) can bind to NKp30 to trigger antitumor NK cell activation and cytokine secretion. Our previous studies have shown that in gastric cancer, B7-H6 high expression was associated with better prognosis and the low expression of B7-H6 group was correlated with better immune microenvironment. However, the effect of B7-H6 expression on immunotherapy is unknown. Herein, we used the data from a clinically annotated cohort of melanoma patients treated with ICI to analyze the influence of B7-H6 expression on immunotherapy. Methods: The gene expression profile, gene mutation information and clinical data were extracted from the supplementary data in melanoma cohort (PMID: 31792460). Maximally selected rank statistics was used to select the optimum threshold for B7-H6 expression, and the patients was divided into two groups according to the expression of B7-H6, high group and low group. Kaplan-Meier survival analysis was used to evaluate the influence of B7-H6 expression on OS prognosis. Associations between variables and OS survival were tested using univariate and multivariate Cox and displayed by forest (R package). Results: We selected 3.14 as the optimum threshold of B7-H6 expression, and the patients was divided into high group (B7-H6 expression＞3.14) and low group (B7-H6 expression≤3.14). The results showed that low group was significantly associated with longer overall survival (p value = 0.048) in cohort of melanoma patients treated with anti-PD1 ICI, which was consistent with our previous results that low expression of B7-H6 group was correlated with better immune microenvironment. We selected primary lesion type, TMB and the expression of B7-H6 factors for univariate and multivariate analysis. TMB-H (top 25%) (p value = 0.051) and B7-H6 (p value = 0.051) low expression were associated with a better OS. Then the patients were divided into four groups according to the TMB and B7-H6 expression and analyzed the difference in the four groups. The results showed that in patients with TMB-L, B7-H6 low group had significant better OS than the B7-H6 high group (p value = 0.032). Conclusions: The low B7-H6 expression was correlated with better efficacy immunotherapy. The effect of B7-H6 expression on immunotherapy needs to be further prospective trial validation.
Influence of follow-up time on outcome of children and adolescents with atypical Spitz tumor/Spitz melanoma (AST/SM): Results from the MACMEL registry.
Authors: Kacar Marija , Yuan Xiaomeng , Pan Haitao , McPherson Valerie , Pappo Alberto S. 
Published: June 2023

e21558 Background: Pediatric melanoma is a rare and challenging diagnosis, requiring an integrated clinicopathologic and genomic approach to optimize diagnosis and clinical care. The Molecular Analysis of Childhood Melanocytic Tumors (MACMEL) registry (Pappo A Cancer. 2021 Oct 15;127(20):3825-3831) was developed to better characterize pediatric melanocytic lesions by including clinical information, central pathology review, and genomic analysis. The AST/SM subtype of melanocytic lesions often affects younger patients, have a high incidence of nodal involvement, and are genomically characterized by copy number aberrations and kinase fusions. Methods: A review of the MACMEL registry data for patients with AST/SM enrolled from May 2016 to December 2022. Patient data included demographics (age, sex, ethnicity), anatomic location of lesion, sentinel node involvement, AJCC staging, genomic and germline findings, therapy, and disease outcomes. Results: We identified 60 patients with AST (n=17) and SM (n=43). 28 patients had stage III disease and 16 had stage IIIC disease. There were 38 females, and 22 males. The most common primary sites were the extremities and the most common gene rearrangements included MAP3K8 (n= 10) and ALK (n= 12). Other genomic alterations identified included kinase fusions NTRK, ROS1, BRAF, FLOT2-ARAF, RAC1, BRIP1, SDHAF2, ATM, GPNMB-ERBB2, and CDKN2B. None of the 55 patients that underwent TERT promoter analysis had a mutation. Adjuvant treatment was given to 8 patients (interferon 3, pembrolizumab 4, larotrectinib 1). The median follow-up time for the cohort is 3.1 years, with 57 patients alive with no evidence of disease. 1 patient had a local relapse treated with wide local excision and is currently alive with no evidence of disease. 3 patients were lost to follow up. Event free survival (EFS) for the cohort is 98% and overall survival (OS) is 100%. Conclusions: Patients with AST/SM comprise the largest subtype of melanocytic lesions enrolled on the MACMEL registry and have an excellent clinical outcome. This supports our previous observations that patients with AST/SM who lack TERT promoter mutations may be able to be managed conservatively and that an integrated diagnostic approach incorporating genomic information is vital for optimal diagnosis and clinical management. [Table: see text]
Prognostic value of BRAF and RAS mutations in radically resected patients (pts) with stage I-III melanoma: Preliminary results from a retrospective study.
Authors: Brugnara Sonia , Sicher Mariacristina , Girlando Salvatore , Bonandini Maria Elena , Barbareschi Mattia , Frisinghelli Michela , Mangiola Daniela , Caffo Orazio 
Published: June 2023

e21567 Background: Although BRAF and RAS mutations in radically resected pts with stage I- II and III melanoma could have a prognostic value, conflicting evidences are still available. The present retrospective study was aimed to investigate this controversial issue. Methods: We retrospectively evaluated a consecutive series of 201 pts with stage I-III melanoma (AJCC 8th) who have undergone radical surgery from 2005 and 2010. For each pt we retrieved the clinical record and collected data concerning the clinical history. In addition, we evaluated the mutation status of somatic BRAF, KRAS and NRAS on a tissue sample obtained from primary surgery material. We describe the expression rate of such mutations and their relationship with pts’ survival outcomes. Results: To date they are evaluable data on 100 pts (M/F 62/38): the median age was 66 yrs (range 36-91), most of the pts was in stage I-II (66 %). The detected mutations is described in the table. Conclusions: From our preliminary results, it appears that BRAF and RAS mutations did not have prognostic value in the assessed population. The final report of the analyses carried on the whole population will increase the study ability to assess the role of these mutations in predicting the outcomes of radically resected stage I-III melanoma. [Table: see text]
Effect of lymph node dissection and adjuvant therapy in patients with sentinel node+ melanoma: An observational multicenter study.
Authors: Ogata Dai , Iwata Mai , Kato Hiroshi , Fukushima Satoshi , Maekawa Takeo , Nakamura Yasuhiro , Tsutsumida Arata , Suyama Takayuki , Kitagawa Hiroshi , Nakamura Yoshio , Takenouchi Tatsuya , Matsushita Shigeto , Oashi Kohei , Kato Junji , Fujiwara Susumu , Maeda Taku , Nishizawa Aya , Kawahara Yu , Yamazaki Naoya , Namikawa Kenjiro 
Published: June 2023

e21569 Background: Currently, lymph node dissection (LND) is not mandatory for patients with sentinel node (SN)+ melanoma. Anti-programmed cell death receptor-1 (PD-1) monotherapy and dabrafenib/trametinib combination (for BRAF mutations) are standard adjuvant treatments for patients who undergo definitive surgery for melanoma. However, the effects of this approach remain unclear in patients with stage III melanoma in real-world clinical settings. We investigated the effects of the aforementioned therapeutic approaches on the prognosis of stage III melanoma in a Japanese cohort. Methods: We retrospectively analyzed clinical data of patients with SN+ melanoma treated with or without anti-PD-1 monotherapy or combination dabrafenib/trametinib therapy obtained from 39 independent institutions in Japan between 2018 and 2021. Survival outcomes (recurrence-free survival [RFS] and overall survival [OS]) were compared with regard to LND, adjuvant therapy type, and clinical factors. Results: We investigated 357 patients; 35.9% (128/357) of patients underwent LND, of whom 70.3% (90/128) received adjuvant therapy. LND was not performed in 64.1% (229/357) of patients, of whom 74.7% (171/229) received adjuvant therapy. RFS and OS did not differ between patients with and without LND (2-year RFS 54.5% vs. 51.5%, p = 0.98; 2-year OS 84.1% vs. 86.5%, p = 0.39). RFS and OS did not differ between patients with and without adjuvant therapy (2-year RFS 54.5% vs. 50.4%, p = 0.90; 2-year OS 83.4% vs. 89.8%, p = 0.33). Multivariate analysis of RFS after adjustment for adjuvant therapy, clinical subtype, tumor thickness, ulceration, and BRAF status showed significant differences between patients with and without adjuvant therapy (hazard ratio 3.06 [95% confidence interval 1.39–6.76]). Data analysis in 261 patients who received adjuvant therapy showed no difference between patients with and without LND (2-year RFS 55.9% vs. 52.6%, p = 0.74; 2-year OS 83.4% vs. 83.6%, p = 0.73). Regarding adjuvant therapy type, RFS and OS were significantly longer in patients who received BRAF/MEK inhibitors than in those treated with PD-1 monotherapy (2-year RFS 75.0% vs. 42.2%, p < 0.01; 2-year OS 89.3% vs. 79.5%, p = 0.01). Conclusions: Our study revealed that LND did not affect prognosis and adjuvant therapy reduced the recurrence of stage III melanoma in a Japanese cohort. Although the follow-up period was short, with regard to drug selection, RFS and OS were significantly longer in patients treated with BRAF/MEK inhibitors than in those who received PD-1 monotherapy. Factors contributing to the lower effectiveness of PD-1 monotherapy remain unclear and warrant further investigation.
Epidemiology and outcomes of anorectal melanomas: A national database analysis.
Authors: Wang Yating , Yu Qian , Chang Kevin Wei-Lun , Reap Leo Edward , Terebelo Howard R. , Yu Zhiyong , Lyons Susan Elizabeth 
Published: June 2023

e21572 Background: Anorectal melanoma is a rare but aggressive type of melanoma, arising primarily from the mucosal epithelium from the anorectal tract. Knowledge of this rare etiology has been limited given its low incidence. This study aims to characterize the epidemiology and treatment outcomes of anorectal melanoma using a national database. Methods: The Surveillance, Epidemiology and End Results (SEER) Database was queried to identify patients with biopsy-proven anorectal melanoma. The following information was retrieved: tumor site, grade, stage, intervention, lymph node histology, and survival information for oncology codes as per the international classification of diseases. Statistical analysis was performed with Stata 15.1 (STATA Corp., College Station, TX, USA). Results: The age-adjusted anorectal melanoma annual incidence rates have been stable approximately 0.4-0.5 per 1 million from 2000 to 2019. Of the 823 biopsy-proven confirmed cases of anorectal melanoma from 2000 to 2018, 150 (18.2%) received chemotherapy, 182 (22.1%) received radiotherapy, 55 (6.7%) received chemoradiation, while 619 (75.2%) of the population received surgery alone or combined with chemotherapy and/or radiotherapy. Statistically significant improvement in survival was noted in treatment strategies that utilized surgery with and without chemotherapy and/or radiotherapy (median survival time 22 vs 9 months, p < 0.0001). Patients with positive regional lymph nodes on pathology were associated with worse prognosis (median survival time 15 vs 37 months, p < 0.0001). Outcomes did not differ based on sex (p = 0.810) and race (p = 0.372). Conclusions: Incidence of anorectal melanoma in the United States has been stable in the last twenty years. Treatment strategies including surgical resection should be adopted if possible to achieve improved survival outcomes.
Investigating the clinical relevance of RNA editing events and their derived neoantigens in patients with melanoma treated with immunotherapy.
Authors: Zhang Xiaodong , Wang Wei , Zhou Wenhao , Lu Qicheng , Ding Tian , Fan Ligang 
Published: June 2023

e21580 Background: RNA editing (RE) is a post-transcriptional modification occurring in RNA, which promotes transcriptome and proteome diversity. Peptides translated from RE sites may represent a new source of neoantigens in cancer (RE-derived neoantigens, RED-neoantigens) that could be presented on tumor surface by human-leukocyte-antigen (HLA) and recognized by specific T-cells, leading to an improved response to immune checkpoint inhibitors (ICIs). However, the clinical significance of both RE events and RED-neoantigens in melanoma patients with ICIs therapy has not been systematically characterized. Methods: The WES and transcriptome data with immunotherapy response of melanoma were obtained from the GEO and SRA database. Vardict and VEP were used to identify and annotate the somatic mutations. Polysover was applied to identify the HLA genotype. RNA editing events were identified by Reditools2 and filtered by a custom pipeline. miRTar2GO was implemented to predict the RE event whether located in miRNA targets within the 3' UTR region. NetMHCpan and NetCTLpan were used to identify and characterize RED-neoantigens. K-M survival analysis was performed on the training set to investigate the clinical relevance of RNA editing events and RED-neoantigens in melanoma patients treated with immunotherapy. The independent melanoma dataset was used to validate this clinical relevance. Results: In total, 7,116 RE events were identified, most of which were A-to-I events. 34% of RE sites in 3'UTR and 15% in 5' UTR were located in the seed regions of miRNA targets and transcription factor binding sites (TFBS), respectively, suggesting the different functional effects of the RE events. Furthermore, using our custom pipeline, 631 RED-neoantigens were identified that show a significantly greater peptide-MHC affinity, and facilitate epitope processing and presentation than wild-type peptides. Meanwhile, we found that patients exhibiting a high RED-neoantigens burden correlated with an increased OS, and a significantly higher RED-neoantigens burden was observed in responders. The area under the curve (AUC) of the RED-neoantigen was 0.831 of OS and 0.686 of responsiveness. Conclusions: The findings in this study provide a more insightful view and resource for investigating the neoantigens in cancer as well as for novel cancer immunotherapies and biomarker development.
Academic medical center access and outcomes in Kaposi sarcoma.
Authors: Swedek Michelle , Silberstein Peter T. , Vardell Victoria 
Published: June 2023

e21582 Background: Kaposi sarcoma (KS) is a soft tissue tumor commonly affecting the skin. It is seen in patients in immunosuppressed states, such as those with HIV/AIDS or organ transplant history. Treatment may include excision, chemotherapy, or radiotherapy depending on the location and spread of lesions. Prior studies indicate that treatment at academic facilities, which offer higher treatment volume, and access to specialized care, clinical trials, and a greater number of ancillary services, is associated with improved survival in other skin cancers, such as melanoma. In this study we aim to compare the survival and sociodemographic factors for KS patients between academic and non-academic facilities, using the largest dataset of these patients yet examined. Methods: We conducted a retrospective analysis of the National Cancer Database from 2004 to 2019 for subjects with KS, identified by ICD code 9140 (n=5,233). Factors were compared between patients seen at non-academic (NAC) (n=2,278) versus academic centers (AC), (n=2,955). Overall survival (OS) was estimated using Kaplan Meier analysis with pairwise log-rank tests for significance. Multivariate analysis was performed using binary logistic regression. Results: Most individuals in the study were White (70.1%), male (87.1%), not of Spanish or Hispanic origin (82.7%), and had government insurance (54.3%). Treatment at AC was associated with improved survival compared to NAC (median OS 184 vs. 98 months, p<0.001). AC patients were younger compared to NAC patients (mean age 56.1 vs. 60.9 years old, p<0.001). On adjusted logistic regression, AC were more likely to treat minority patients, including Black patients (OR 1.23, 95% CI 1.06-1.43, p=0.005) and Spanish/Hispanic patients (OR 1.26, 95% CI 1.06-1.48, p=0.007). AC were more likely to manage uninsured patients compared to patients with private (OR 0.48, 95% CI 0.39-0.60, p<0.001) or government insurance (OR 0.69, 95% CI 0.55-0.86, p=0.001). Compared to the East Coast, patients in the Central U.S. (OR 0.81, 95% CI 0.71-0.93, p=0.003) and West Coast (OR 0.83, 95% CI 0.71-0.96, p=0.015) were less likely to use AC. Patients residing in high education zip codes were less likely to be treated at academic centers (p<0.001). Patients in the top income quartile were more likely to be treated at AC (OR 1.42, 95% CI 1.15-1.75, p=0.001). Conclusions: Treatment at AC is associated with improved overall survival compared to NAC in KS. AC were more likely to treat younger patients, and those from racial and ethnic minorities, as well as those in the top income quartile. Less academic center use was seen in areas of higher educational attainment and by individuals with government or private insurance. While specialized care and clinical trial access may play a role in this survival benefit, access to AC may also be a surrogate marker of social determinants of health that play a role in KS outcomes. Our study supports the ongoing need for access to comprehensive care in KS.
A retrospective study of Merkel cell carcinoma treated at The Ohio State University (OSU) in the last 20 years.
Authors: Li Chunjie , Kendra Kari Lynn , Contreras Carlo M. , Blakaj Dukagjin , Wu Richard Cheng Han , Verschraegen Claire F. 
Published: June 2023

e21586 Background: Merkel cell carcinoma (MCC) is a rare but aggressive neuroendocrine cutaneous malignancy. The analysis of interventions and benefits of treatments remain limited. In this retrospective study, we analyzed the clinical features and outcomes of MCC patients treated at the OSU Comprehensive Cancer Center (OSUCCC). Methods: Electronic medical records of MCC patients who were treated from 2000 to 2021 at OSUCCC were reviewed. 179 patients were enrolled. 153 patients were analyzed for overall survival (OS) after excluding 26 patients due to loss of follow-up or insufficient data. Clinical features were collected. The first patient was treated with immunotherapy (IO) on 2/24/2015. The period after this date was defined as the IO era (87 patients). Results: Among 179 patients (median age 73, male 64.8%), 41.9% died, 13.4% were lost to follow-up and 44.7% were alive by 12/31/2022. Primary tumor locations were head (50.8%), upper & lower extremities (21.2% & 10.6%), unknown primary (6.1%), trunk (5%) and neck (4.5%). Patients with stage I, II, III and IV were 41.9%, 12.8%, 36.9% and 8.4%, respectively. Sentinel lymph node biopsy (SLNB) was performed in 73.8% of patients; tumor involvement in SNL was confirmed in 38.5% and SLNB attempts failed in 15.1%. Patients who received surgery, local radiation, IO, chemotherapy and targeted medication were 92.7%, 66.5%, 27.4%, 10.1% and 2.8%, respectively. All 75 stage I patients had wide excision, and 50.7% received local radiation. 12% of stage I patients developed tumor recurrence, with IO administered in 55.6% of those patients. Most patients with stage II (52.2%) and stage III (34.8%) received surgery followed by radiation. 20% of patients with stage IV received surgery followed by radiation and IO. The median OS was 95 months (95% CI 67-123), the 3-year survival rate was 70%, and the 5-year survival rate was 61% for the 153 assessable patients. The median OS in stage I, II, III and IV was 149, not reached, 65 and 20 months, respectively ( P< 0.05). Survival in tumors on the head/neck was similar to the upper and lower extremities (median OS 102 vs. 71 vs. 99 months, P> 0.05) but slightly superior to the trunk disease (median OS 102 vs. 15 months, P= 0.072). The outcome of never-smokers was superior to former smokers (median OS 156 vs. 71 months, P< 0.01). The median OS of stage IV patients with IO was superior to those without IO (95 vs. 10 months, P< 0.05). Among dead patients in the IO era, the median OS of patients with IO was longer than those without IO (22 vs. 6 months, P< 0.01). Conclusions: Most MCC occur in the elderly, local or regional disease, and commonly on the head with a good outcome after multidisciplinary therapies. Former smokers and stage IV disease relate to a poorer prognosis. IO shows benefits with prolonged survival, especially in metastatic disease.