bluuebunny/crossref_metadata_2025_split huggingface dataset:
Efficacy of nivolumab and relatlimab-rmbw in patients with advanced melanoma who were previously treated with PD-1 inhibitor: Real world experience.
Authors: Jang Sekwon , Stahl Chelsea , Al-Mondhiry Jafar , Venna Suraj S 
Published: June 2023

e21533 Background: Nivolumab and relatlimab-rmbw (R/N) combination demonstrated superior efficacy to nivolumab alone in patients with previously untreated metastatic or unresectable melanoma. Sparse data exists on the efficacy of this combination in patients with melanoma that relapsed after,or was resistant to treatment with PD-1 inhibitors. Methods: We conducted a retrospective study of patients with unresectable or metastatic melanoma whose disease recurred or progressed on/after prior PD-1 inhibitor who received R/N at Inova Schar Cancer Institute. Efficacy endpoint was objective response using modified RECIST1.1. Unconfirmed complete response (CR) or partial response (PR) were included in objective response rate (ORR). Patients whose Positron Emission Tomography (PET) scan showing complete metabolic resolution of metastatic sites were also considered CR. Patients who had rapid clinical progression and didn’t have repeat radiologic studies were considered to have progressive disease (PD). Patients who underwent radiation to target lesions were considered non-evaluable (NE). Results: From Sep 2021 through Dec 2022, a total of 32 patients (19 male) received R/N including 8 unresectable stage III melanomas and 24 stage IV melanomas (M1a: 4, M1b: 4, Mc1: 5, M1d: 10). Median age was 67 (39-88), and 12 (38%) had BRAF mutation. Median number of prior therapies was 2 (range: 1-7) including anti-CTLA4 antibody in 22 and BRAF/MEK inhibitor in 8. Nine patients (28%) had ≥ 3 prior therapies. Among 30 patients evaluable for response, ORR was 33% (4 CR, 6 PR). Three had stable disease (SD), and 16 had PD including 2 with rapid clinical progression. Response by subgroup is included in table. Conclusions: R/N shows clinically meaningful antitumor activity in patients who received prior PD-1 inhibitor in real world setting. Additional clinical data of R/N in PD-1 inhibitor relapsed or refractory patients are needed to validate the results of this single-center study. [Table: see text]
Long-term outcomes of melanoma oligoprogressive metastases treated with radiotherapy combined with locoregional hyperthermia.
Authors: Borkowska Aneta , Spalek Mateusz , Teterycz Pawel , Rutkowski Piotr 
Published: June 2023

e21540 Background: Oligoprogression is a limited progression after a prior response to treatment. Oligoprogression remains a major clinical challenge in patients with metastatic melanoma (MM). Local therapy for progressing metastases may enable the continuation of effective systemic therapy. Methods: We identified 77 patients treated with radiotherapy combined with hyperthermia for oligoprogressive MM in a melanoma tertiary center between 2019 and 2022. Patients without any follow-up imaging after irradiation were excluded. We assessed local control (LC), and overall survival (OS). We estimated the correlation between BRAF status, size of the irradiated lesion, radiation dose, and LC. Survival analyses were performed using the Kaplan-Meier estimator, and Log-rank tests and were used for comparison between groups. The data cut-off was 31/Aug/2022. Results: The majority of patients (83%) had one oligoprogressive lesion. At the time of analysis, 59.5% of patients had stable disease, complete or partial response, and 40.5% of patients had progression, in the total response according to RECIST (Table). Most patients (78%) were irradiated during immunotherapy whereas 12% received concomitant BRAF and MEK inhibitors (Table). There were no severe toxicities of radiotherapy nor hyperthermia. The median follow-up was 18 (95%CI: 16-24) months(m). The 12 and 24m LC rates were: 83% (95%CI: 74-94) and 54% (95%CI: 40-73), respectively. The achieved LC rate was 88.3%. The 12 and 24m OS rates were: 87% and 72%, respectively. At the time of analysis, the median of OS and LC were not reached. BRAF status, size of the lesion, or radiation dose were not associated with LC. Conclusions: Preliminary data showed that patients with MM may benefit from radiotherapy combined with hyperthermia for oligoprogressive lesions during systemic treatment. This combination enables good local control of progressive metastases with minimal toxicity. This topic requires further investigation in prospective studies. [Table: see text]
Impact of antibiotics on survival outcomes and risk of gastritis/colitis in patients with advanced-stage melanoma receiving anti-PD-1 therapy.
Authors: Bailey Shannon , Havighurst Thomas , Pozorski Vincent , Mohamoud Yusuf , Tesfamichael Dahlia , Jung Lindsey , Dow-Hillgartner Elizabeth N. , Ma Vincent T. 
Published: June 2023

e21543 Background: Immune checkpoint inhibitors (ICIs), specifically anti-PD-1 therapy, have improved survival in advanced-stage melanoma patients compared to previous treatment options. A healthy gut microbiome has been associated with a positive response to ICIs. Antibiotics are known to disrupt the gut microbiome and may have immune-modulatory effects within the tumor microenvironment. Studies have demonstrated a negative impact on survival with any antibiotic use during ICI treatment. Less information is known regarding the impact of spectrum of activity or antibiotic timing on survival and risk of ICI-associated gastritis/colitis. Methods: We conducted a single-center, retrospective review of advanced-stage melanoma patients treated with anti-PD-1-based therapy (ipilimumab/nivolumab or anti-PD-1 monotherapy) between 2014-2022. Multiple clinicopathologic variables including antibiotic use, survival outcomes, and development of colitis and/or gastritis were assessed. Antibiotic spectrum of activity was divided into two groups: with anaerobic coverage and without anaerobic coverage. Antibiotic timing was assessed as patients who received antibiotics within 30-days prior to starting ICI and/or during treatment. Univariate and multivariate analyses on PFS and OS were performed using Cox proportional hazard models. Logistic regression models were used to assess risk of gastritis and/or colitis. Multivariate analyses accounted for age, gender, melanoma primary type, BRAF mutation status, presence of brain or liver metastases, and pre-treatment LDH levels. Results: A total of 214 patients were analyzed. Multivariate analysis demonstrated any antibiotic exposure during anti-PD-1 therapy was associated with improved OS [HR 0.500, 95% CI 0.303–0.826, p = 0.007]. Although not statistically significant, there was a trend towards worse OS in patients who received antibiotic therapy 30-days prior to ICI therapy [HR 1.726, 95% CI 0.994-2.995, p = 0.052]. Use of antibiotics without anaerobic coverage was associated with improved PFS [HR 0.462, 95% CI 0.273–0.782, p = 0.004] and OS [HR 0.399, 95% CI 0.200–0.789, p = 0.009]. Antibiotic exposure 30-days prior to initiating anti-PD-1 therapy increased the risk of developing gastritis and/or colitis [OR 1.990, 95% CI 0.744–2.651, p = 0.043]. Conclusions: Antibiotic timing and spectrum of activity may be predictive of survival outcomes and risk of gastritis/colitis in anti-PD-1-treated patients with advanced-stage melanoma. Unlike previous studies, we found improved survival in patients receiving antibiotics during treatment and in those receiving antibiotics without anaerobic coverage. Our results demonstrate the need to further investigate specific antibiotic agents as well as antibiotic timing and their clinical impact on patients receiving ICI treatment.
The phase 1 clinical trial of anti–PD-1 (pucotenlimab) plus intrahepatic injection of oncolytic virus (OH2) combined with radiotherapy of liver metastasis in stage IV melanoma.
Authors: Cui Chuanliang , Wang Xuan , Wang Hongzhi , Yin Shanshan , Cong Yue , Lian Bin , Li Caili , Yu Jiayi , Si Lu , Chi Zhihong , Sheng Xinan , Kong Yan , Mao Lili , Zhou Li , Tang Bixia , Yan Xieqiao , Bai Xue , Li Siming , Wang Weihu , Guo Jun 
Published: June 2023

e21545 Background: Melanoma pts with liver metastasis has poor prognosis and reduced response to systemic immunotherapy. Oncolytic herpes simplex virus 2 (OH2) is an oncolytic virus derived from herpes simplex virus type 2. PD-1 antibody combined with intrahepatic oncolytic virus intralesional injection had shown preliminary efficacy in previous clinical trial. The radiation of liver metastasis might exert action on its tumor microenvironment and get benefit from immunotherapy combination. So we perform this phase I study to assess the safety and efficacy of OH2 and pucotenlimab (a humanized immunoglobulin G4 monoclonal antibody) combine with liver metastasis radiation in melanoma pts. Methods: Eligible pts included those over 18 with injectable liver metastasis confirmed by biopsy with or without extra-hepatic metastasis; the ocular melanoma and brain metastasis were excluded. Pts received intravenous Pucotenlimab Q3W combined with ultrasound guided intrahepatic injection (metatstasis lesion) of OH2 Q2W (107CCID50/mL, 8ml per injection) after stereotactic body radiotherapy (24-30Gy/3Fx) of liver metastasis. Liver biopsy performed at baseline and first tumor evaluation (8-12weeks). The primary endpoint was ORR; secondary:toxicity, DCR, PFS and OS. Results: From Dec 2021 to Jan 2023, 10 pts were eligible and enrolled. Baseline characteristics: 70% got previous treatment; LDH＞ULN 50.0%; 90% got extra-hepatic metastasis; median size of ed lesions: 36mm(19-120mm); median number of liver metastasis: 5.5. Among these pts, 5 pts could be evaluated for efficacy (follow-up 10.0 m). The global ORR by investigator was 40.0% (2/5), DCR 80% (4/5). Biopsies of 4 pts for injected lesions at 8 to 12 weeks after first injection were examined to determine the situation of tumor regression and TIL infiltration. Among them, 2 pts ( 1 PR and 1 SD) had no tumor cells residual by immunohistochemistry in biopsies with impressive TIL infiltration, both of them showed PFS more than12.0 months. Most adverse events (AE) were grade 1-2. Only one pts had grade 3-4 thrombocytopenia, with treatment modified. No treatment-related deaths occurred. The median PFS was not reached and now in follow up. Conclusions: Systemic anti-PD-1 plus intralesional injection of Oncolytic virus combined with radiotherapy has shown remarkable ORR and pathological response in melanoma pts with liver metastases with manageable toxicity. Clinical trial information: NCT05068453 . [Table: see text]
Correlation of patient characteristics and tumor histology in patients (pts) with locally advanced cutaneous squamous cell carcinoma (LACSCC) receiving immune checkpoint inhibitor treatment (ICI): A retrospective analysis.
Authors: Ben Haj Frej Khaoula , Kerr Phil , Stewart Campbell , Hegde Upendra P. 
Published: June 2023

e21553 Background: Cutaneous squamous cell carcinoma (CSCC) arising from epidermal keratinocytes is highly curable with surgery. Functional anti-cancer immunity is protective of CSCC and high mortality due to local or systemic dissemination is seen in pts. with immune deficiency. ICI treatment is a logical FDA approved option that result in improved outcomes in affected pts. We report our experience in LACSCC pts. receiving ICI treatment and describe correlation between pt. characteristics, tumor histology and treatment outcome. Methods: Following Institutional Review Board approval, we did a retrospective analysis of LACSCC pts. receiving ICI therapy at the Neag Cancer Center who received at least one dose of ICI between 2018-2023. Analysis includes pt. demographics, relevant comorbidities, medications, and tumor histology and tumor infiltrating lymphocytes (TILs) of tumors reviewed with dermatopathologist. Results: Between 2018-2023, 12 pts. with LACSCC met the criteria for analysis. Median age 77.5 years (yrs.), (range 65-102), 9 males, 3 females, tumors sites - head and neck region 8 pts., torso 2 pts., legs 2 pts. Relevant past medical history included treatment of prostate cancer 3, chronic lymphocytic Leukemia 1, psoriasis 2 (one received anti TNF treatment), and MGUS, Parkinson’s disease and dementia in 1 each. Majority of pts. had significant smoking history (9/12), lymphopenia in 8 out of 12 pts. Tumors were poorly differentiated in 6 out of 12 pts. Brisk TILs was present in 7 and non-brisk TILs in 5 pts. 3 pts. with brisk TILs achieved complete remission (CR), one very good partial response (VGPR), 1 partial response (PR) and 2 not evaluable for response. Out of 5 pts. with non-brisk TILS, one achieved CR, one achieved VGPR, 1 PR, 1 stable disease (SD), and 1 progressive disease (PD) in a pt. who received anti TNF treatment of psoriasis. 9 patients are alive between 1 week and 50 months after initiation of treatment. 3 pts. died, one of PD, one of bacterial sepsis and one of Covid. Conclusions: High risk LACSCC affected males with smoking histories in the majority. Durable responses following ICI treatment occurred irrespective of age, while resistant disease was noted in 1 pt. with previous anti TNF treatment. Brisk TILs predicted high response rate and durable responses although some pts. with non-brisk TILs also showed favorable outcomes. Association with previous cancer and macular degeneration may reflect underlying immune deficiency. Three pts. developed infection within two weeks of ICI treatment (urinary tract infection, wound infection, Covid). More studies will shed light at factors compounding immune deficiency and safety of this treatment in a high-risk population.
Detection of ctDNA in patients with stage III cutaneous melanoma with satellite/in-transit or nodal metastases.
Authors: Al-Mondhiry Jafar , Stahl Chelsea , Venna Suraj S. , Jang Sekwon 
Published: June 2023

e21559 Background: Circulating tumor DNA (ctDNA) has emerged as a biomarker to monitor disease status in cancer patients. Limited data exists on the sensitivity of ctDNA for detection of satellite/in-transit or nodal metastases in melanoma. Methods: We conducted a retrospective study of stage III cutaneous melanomas with clinically detected satellite/in-transit and/or lymph node metastases who underwent ctDNA analysis using an mPCR-NGS-based ctDNA assay ("Signatera") prior to surgery or systemic therapy at Inova Schar Cancer Institute. Results: ctDNA was detected in 4 of 14 patients including 1 of 3 patients with both satellite/in-transit metastases and nodal metastases; 3 of 6 patients with nodal metastases only; none of 5 patients with satellite/in-transit metastases only. Nodal tumor burden (sum of short axis of involved lymph nodes) for ctDNA detected patients was greater than 1.5cm (5.0cm, 3.0cm, 3.0cm, and 1.6cm, respectively), and 1.5cm or less in patients whose ctDNA were not detected. Conclusions: ctDNA may not detect satellite/in-transit metastases or small nodal metastases in melanoma. A larger study is needed to validate this finding. [Table: see text]
Elucidating the connection between pneumonia and melanoma: Risk factors and outcomes for patients with melanoma.
Authors: Hundal Henna , Taneja Kamil , Patel Karan , Zhang Alex , Diaz Michael , Libraro Nicholas , Cohen Jules A. 
Published: June 2023

e21561 Background: Pneumonia is a common cause of morbidity and mortality in patients with melanoma and leads to many ED visits per year in the US. However, there is no national-level study that has assessed factors that increase risk for melanoma patients to present to the ED with a primary diagnosis of pneumonia. Methods: We utilized the 2006-2012 Nationwide Emergency Department Sample to identify melanoma patients that presented to the emergency department (ED) with a primary diagnosis of pneumonia. A multivariate logistic regression was used to identify characteristics that were significantly associated with a higher chance of pneumonia. A p-value less than 0.05 was considered significant. Results: Between 2006 and 2012, 239,956 melanoma patients presented to the ED. Amongst these patients, 3.1% presented to the ED with a primary diagnosis of pneumonia. The majority of patients were at least 80 years old (64.3%), male (61.5%), Medicare beneficiaries (73.1%), of the highest income quartile (28.7%), living in the South (35.7%), presented to non-trauma hospitals (53.1%), and presented to metropolitan non-teaching hospitals (44.9%). Factors associated with the highest risk of pneumonia in melanoma patients are the following: Medicaid patients (odds ratio (OR): 2.5, 95% Confidence Interval (CI): 1.4-4.4, p=0.003), Medicare patients (OR: 2.3, 95% CI: 1.4-3.0, p=0.002), private insurance patients (OR: 2.1, 95% CI: 1.3-3.5, p=0.005), non-metropolitan teaching hospitals (OR: 1.6, 95% CI: 1.3-1.9, p<0.001), living in the Northeast (OR: 1.3, 95% CI: 1.3-3.5, p=0.005), being male (OR: 1.3, 95% CI: 1.1-1.4,p<0.001) a high Charlson Comorbidity Index (OR: 1.3, 95% CI: 1.2-1.3, p<0.001). The majority of patients were either admitted (86.4%) or discharged home the same day (11.1%). Amongst the patients that were admitted, most patients were discharged (59.0%), transferred to a skilled nursing facility or intermediate care facility (19.2%), or given home health care (15.8%). Only 4.0% of admitted patients died in the hospital. Conclusions: A melanoma patient’s risk for developing pneumonia is depending on insurance status, the region of their hospital, their biological sex, and the presence of comorbidities. Clinicians should be aware of these risk factors to minimize the risk of pneumonia occurring in this at-risk population.
An immunogenomic signature for molecular classification in melanoma.
Authors: Liu Yang , Wang Qian , Xiao Shanshan , Wang Tao 
Published: June 2023

e21562 Background: Melanoma is one of the most aggressive tumors in the world, characterized by an increasing incidence and high mortality with half of the patients dying from the advanced tumors. The melanoma tumor is very heterogenous and the appropriate classification of subtypes is the key to guide precision treatment. Previous studies have revealed the important roles of immune cells in melanoma. Therefore, the better classification method and comprehensive analysis of immune cells and immune-related genes can help to better understand the tumor progression and develop effective treatment strategies in melanoma. Methods: Two datasets containing RNA sequencing data and paired patient information with melanoma were collected in this study. The first dataset of skin cutaneous melanoma patients downloaded from The Cancer Genome Atlas database (n = 204) was used as the training set, and the second dataset from a published study was used as internal validation set (n = 102). Single sample gene enrichment analysis (ssGSEA), ESTIMATE, CIBERSORT and k-means analysis were used to classify melanoma patients into two different immune clusters. We then constructed a molecular signature with nine immune related genes that could predict the overall survival (OS) of melanoma patients by LASSO regression and Cox regression analysis. The accuracy of the risk signature was then verified in eight independent cancer types. Results: The melanoma patients were divided into two different immune clusters, the high-immune cell infiltration cluster (Immunity_H) and low-immune cell infiltration cluster (Immunity_L). 1,556 and 1445 differentially expressed genes (DEGs) between the Immunity_H and Immunity_L were detected in the training set and validation set, respectively. Accordingly, 677 and 147 genes associated with overall survival (OS) was further selected by Univariate Cox regression analysis. 59 genes were shared between the 677 and 147 OS related genes. Eventually, 9 DEGs (CST7, CSF2RB, SPARC, SPOCK2, PLA2G2D, MYO1G, NCF1, ICOS and HSH2D) were screened out by LASSO regression analysis and were then subjected to multivariate Cox regression analysis to further construct the prognostic signature. Patients were divided into high-risk and low-risk groups based on the computed risk threshold. Kaplan-Meier analysis indicated that patients in the high-risk group had a significantly worse OS. Finally, 8 independent external pan-cancer cohorts were used to validate the robustness of the model. Conclusions: This study identified two immune-related clusters and a risk signature based on nine immune-related genes was constructed, which could predict the melanoma cancer OS and the constructed model can be used as prognosis predictor in melanoma.
Impact of adjuvant immunotherapy in resected stage II/III/IV melanoma: A single center experience.
Authors: Sevillano Tripero Alberto Rafael , Ortiz Carolina , Lostes Julia , Bodet Domingo , Ferrandiz Carla , Bassas Patricia , Chiquillo Paula , Villacampa Guillermo , Vega-Cano Kreina Sharela , García-Patos Vicente , Recio Juan , Muñoz-Couselo Eva 
Published: June 2023

e21565 Background: The incidence of malignant melanoma (MM) in Mediterranean countries is estimated at 3- 5/100.000 inhabitants/year with a predicted rising trend. MM is responsible for over 90% skin cancer deaths due to its tendency to metastasize early. Surgical excision is the treatment of choice for early-stage melanoma, however, 40-60% of patients with high recurrence risk melanoma, thick ulcerated primary melanomas (Stage IIC) and those with lymph node involvement (Stage III), experience a tumor relapse. Adjuvant therapy in resected high-risk melanomas has shown improved Relapse-Free-Survival (RFS), although no Overall Survival (OS) benefit has been observed to date. This retrospective observational study, conducted in one center, aims to evaluate effectiveness and safety of adjuvant therapies for resected high-risk melanoma. Methods: Single center cross-sectional study that included patients with a resected high-risk melanoma candidate for adjuvant treatment, at 2015-2022 period. Convenience sampling 48 patients recruited. Median follow up 55,4 months. Results: Median age was 54y, 52% were male and 93’6 is cutaneous melanoma. 53% were BRAF WT. Median Breslow (mm) was 3’85, median num/mm2 mitosis are 4 and 62’5% had ulceration. 15% presented satelosis or intransit metastasis and 55% had a lymphadenectomy. Melanoma stage: 9%IIB, 11%IIC, 11%IIIA, 25%IIIB, 38%IIIC, 2% IIID and 2% IV. Adjuvant treatment: 22% nivolumab, 20% ipilimumab+nivolumab, 12% ipilimumab, 16% interferon.75% of patients completed adjuvant treatment, 14% stopped for toxicity and 9% presented disease relapse (21% loca, 64% systemic). Best treatment response in relapse was 12% partial response, 37% progression. Toxicity: 18% presented grad ¾ toxicity. Efficacy: median RFS was 78’8m and median OS was NR. Conclusions: Adjuvant treatment is associated with an increased DFI in resected high risk melanoma patients. Adjuvant therapy was generally well tolerated, with manageable adverse events, consistent in type and incidence to those seen in clinical trials that allowed the approval for these compounds in adjuvant and metastatic scenarios. Prospective studies are needed to determine new biomarkers for the selection of those patients who could benefit to a greater extent from adjuvant therapies in resected high-risk melanoma.