bluuebunny/crossref_metadata_2025_split huggingface dataset:
Malignant blue nevus: Epidemiology, socioeconomic factors, and disease presentation.
Authors: Choe Sharon , Moroz Mark , Puvvadi Suraj , Chin Kat , Silberstein Peter T. , Heise Craig , Hsia Beau 
Published: July 2024

e21565 Background: Malignant blue nevus (MBN) is a rare and aggressive melanoma that arises in a blue nevus and tends to metastasize to the lymph nodes. Metastasis has been described in up to 55% of cases, and the 10-year survival rate is 51%. Current literature on MBN is limited. Data from the National Cancer Database (NCDB) on the demographic and socioeconomic characteristics of patients with MBN could provide insightful information regarding the epidemiology of this rare disease. Methods: The 2004-2020 NCDB was used to perform a retrospective cohort analysis of patients diagnosed with malignant blue nevus (N = 118) using ICD-O-3 code 8780/3. This study used descriptive statistics to analyze factors such as age, sex, income status, insurance status, Charlson-Deyo score, treatments, and survival rates. Results: A total of 118 patients diagnosed with MBN were recorded in the NCDB with an average age at diagnosis of 56.7 ± 17.2 years with a female preponderance (59%). Nearly all patients were insured (99%), mostly by private insurance (59%) or Medicare (27%). Over half of patients (54%) were enrolled in research programs, and 62% of patients comprised the top two income quartiles based on median household income. The vast majority of patients (81%) had no major comorbidities (Charlson-Deyo = 0). The top primary sites were the skin of the scalp and neck (36%) and the trunk (21%). The average tumor size was 21.2 ± 30.3 mm ranging from 2 mm-120 mm. The most frequent treatment performed was surgery, with 92% of patients undergoing surgical procedures of the primary site. Among these, the most common procedures were wide excision or re-excision (52%), excisional biopsy (14%), and shave biopsy followed by gross excision (10%). After resection, 77% of patients showed no residual tumor. In place of surgery, a smaller number of patients received alternate treatments as their main therapy, such as radiation therapy (11%), chemotherapy (6%), or immunotherapy (12%). The 2-year and 5-year survival rates were 88% and 68% respectively. Conclusions: Based on our literature review, this study is the first NCDB analysis on MBN and presents data from the largest cohort of patients to date. Patients with MBN are more likely to be female, and most lack major comorbidities. The most common sites are the scalp, neck, or trunk, in line with current literature. Review of socioeconomic factors revealed that an overwhelming majority of patients are likely to be insured and in the top two income quartiles. These findings could implicate that those who are more socioeconomically advantaged may have more resources for recognition of disease and proper diagnosis, especially considering the challenges of diagnosing MBN due to poorly defined histological criteria. Further research efforts should investigate the impacts of socioeconomic factors on diagnosis, treatments, and prognosis.
Epidemiology and clinical management of primary penile melanoma: A review of the National Cancer Database.
Authors: Choe Sharon , Griffin Julia , Silberstein Peter T. 
Published: July 2024

e21570 Background: Primary penile melanoma (PPM) is an exceedingly rare variant of skin cancer, estimated to account for less than 0.18% of all melanomas. As the incidence of melanoma is projected to increase, it is crucial to further understand subtypes of melanoma like PPM. We sought to use the National Cancer Database (NCDB) to describe the epidemiology, clinical features, and treatment modalities of PPM. Methods: We conducted a retrospective review of adults diagnosed with malignant PPM between 2004 and 2021 using the NCDB. Demographic factors analyzed included age, year of diagnosis, insurance status, and facility type. Clinical features studied included regional lymph node examination and treatments. SPSS was utilized to calculate descriptive statistics and chi-square tests for differences between categorical variables. Results: A total of 137 patients met inclusion criteria. The median age at diagnosis was 73 years. The majority of patients were insured by Medicare (n = 86, 63%) or private insurance (n = 46, 34%). About 50% (n = 69) of patients received care at an academic institution with other popular care centers being comprehensive community cancer centers (n = 33, 24%) and integrated network cancer programs (n = 28, 20%). Of the 91 (66%) patients examined for regional lymph node metastasis, 46% (n = 42/91) tested positive. The treatments of choice were partial amputation (n = 70, 51%), excisional biopsy (n = 30, 22%), total amputation (n = 15, 11%), and local excision (n = 10, 7%). After surgical intervention, 74% of patients (n = 101) showed no residual margins. Immunotherapy treatment, which was typically used as an adjuvant (n = 21,15%), increased from 7% (n = 5) of 68 cases diagnosed between 2004 and 2012 to 32% (n = 22) of 69 cases diagnosed between 2013 and 2021 (p < 0.001). Only 7% (n = 9) of patients underwent chemotherapy. Conclusions: To our knowledge, we present the largest study of PPM. Most patients were of older age, covered by Medicare, and examined for regional lymph node metastasis. In line with existing literature that demonstrates increased adoption of organ-sparing procedures over more aggressive approaches for PPM, partial amputation and excisional biopsy were the most common treatments. We observed a rise in the utilization of immunotherapy in the last decade, which is consistent with the timeline of FDA approval of several immune-based therapies for advanced melanoma. Current literature regarding immunotherapy in penile melanoma is scarce. Further research should investigate patient survival and the impact of different treatment modalities on outcomes.
Immune-related gastritis: An orphan immune-related adverse event.
Authors: Etan Tal , Shachar Shlomit Strulov , Wolf Ido , Leshem Yasmin 
Published: July 2024

e24138 Background: Immune checkpoint inhibitors (ICI) have revolutionized the field of oncology with a significant impact on patients' survival. However, they are not without shortcomings, with 70-90% of patients experiencing immune-related adverse events (irAEs(. Immune-related gastritis is a relatively uncommon irAE, literature publications are scarce and limited to case reports. We aimed to investigate this rare irAE to enhance understanding and improve patient care for oncologists and gastroenterologists. Methods: We performed a retrospective review of medical records of all cancer patients treated with ICI who completed upper gastrointestinal endoscopy during ICI treatment, at a single tertiary center between 2017 and 2023. Results: Of 2553 patients receiving immunotherapy at our medical center, 64 completed upper gastrointestinal endoscopy, and 18 (0.7%) had either endoscopic or microscopic gastritis or both. Overall, 17 (94%) patients with gastritis were symptomatic compared to only 31 of 46 patients (67%) without gastritis (p = 0.025). Epigastric pain was the most common symptom and was experienced by seven (39%) patients with gastritis, and eight (17%) patients without gastritis (P = 0.068). Other symptoms in patients with gastritis were gastrointestinal bleeding (28%), nausea (17%) and vomiting (11%). However, gastrointestinal bleeding (17%), nausea (9%), and vomiting (11%) were also experienced by patients without gastritis at similar rates (P > 0.05 for all comparisons). Two patients had grade 4 and two patients had grade 3 immune-related gastritis. Symptoms resolved in all patients, though most patients continued ICI (77%). Ten patients were treated with high-dose proton pump inhibitors (PPIs), and only four were treated with corticosteroids. Overall survival in patients experiencing gastritis was 40 months and did not differ from that of patients without gastritis (p = 0.929). Conclusions: Immune-related gastritis is an infrequent and non-lethal adverse event. Diagnosis is challenging due to non-specific symptoms, that are common among cancer patients undergoing antineoplastic therapies. Nonetheless, upon diagnosis, treatment with high doses PPIs with or without corticosteroids leads to prompt resolution.
GEMINI-Gastric: A phase 2 study of novel treatment combinations in patients with locally advanced unresectable or metastatic gastric cancers.
Authors: Shen Lin , Shitara Kohei , Chen Jen-Shi , Oh Do-Youn , Jiang Anastasia , Liu Silver , Dong Zhi , Zhu Qian , Kumar Rakesh , Rha Sun Young 
Published: July 2024

TPS4182 Background: A large proportion of patients (pts) with gastric cancer present with locally advanced or metastatic disease, which is linked with poor survival. Platinum- and fluoropyrimidine-based doublet chemotherapy (CTx) remains the standard of care in advanced gastric cancers. Based on recent clinical data, immuno-oncology (IO) agents plus CTx can improve overall survival (OS) in pts with locally advanced unresectable or metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma who have human epidermal growth factor receptor 2 negative/low expression (HER2–) and have not been previously treated for advanced/metastatic disease. GEMINI-Gastric (NCT05702229) is a phase 2, open-label, multidrug, multicenter, master protocol study designed to assess the efficacy, safety, tolerability, pharmacokinetics (PK), and immunogenicity of multiple novel IO + CTx combination therapies in this setting. Methods: Adults (≥18 years) with previously untreated HER2– locally advanced unresectable, or metastatic gastric or GEJ adenocarcinoma are eligible. Pts should have measurable target disease per RECIST v1.1 and an ECOG performance status of 0–1. The GEMINI-Gastric design allows assessment of multiple novel agents plus CTx in different substudies (Table). Novel agents include: volrustomig, an anti-PD-1/CTLA-4 bispecific humanized IgG1 monoclonal antibody (mAb); rilvegostomig, an anti-PD-1/TIGIT bispecific humanized IgG1 mAb; AZD0901, a claudin18.2-targeted antibody-drug conjugate; and AZD7789, an anti-PD-1/TIM-3 bispecific mAb. Co-primary endpoints are objective response rate and progression-free survival (PFS) at 6 months by investigator assessment per RECIST v1.1. Secondary endpoints include safety, duration of response, PFS, OS, PK, and immunogenicity. Sample sizes have been selected to provide adequate precision for the primary endpoints. The study is currently recruiting at sites in the US, Europe, and Asia. Clinical trial information: NCT05702229 . [Table: see text]
TOURMALINE: A phase 3b study of durvalumab with gemcitabine-based chemotherapy regimens in advanced biliary tract cancer.
Authors: Vogel Arndt , He Aiwu Ruth , Oh Do-Youn , Macarulla Teresa , Dane Aaron , Nguyen Binh , Wetherill Graham , Baur Boris , Ikeda Masafumi 
Published: July 2024

TPS4188 Background: In the Phase 3 TOPAZ-1 study (NCT03875235), durvalumab plus gemcitabine + cisplatin (GC) significantly improved overall survival (OS) versus placebo + GC in participants with advanced biliary tract cancer (aBTC) with a manageable safety profile. To expand on TOPAZ-1, there is a need to further assess the safety and efficacy of durvalumab in combination with other gemcitabine (G)-based chemotherapy regimens used in aBTC, and in a more diverse population to reflect real-world clinical practice. Methods: TOURMALINE (NCT05771480) is a Phase 3b, single-arm, multicenter, international study. Approximately 140 adults with aBTC (intra- or extra-hepatic cholangiocarcinoma, gallbladder or ampulla of Vater carcinoma) will be enrolled. Key inclusion criteria include unresectable disease (advanced, metastatic), WHO/ECOG PS of 0–2, and no prior systemic therapy. Key exclusion criteria include any prior immune-mediated therapy and history of another primary malignancy. Participants will receive durvalumab 1500 mg IV plus an investigator-selected, G-based background chemotherapy; durvalumab will be administered Q3W when combined with a G-based chemotherapy Q3W (8 cycles of durvalumab) except for when combined with GC + S-1 Q2W, in which case durvalumab will be administered Q4W (4 cycles of durvalumab/8 cycles of chemotherapy). G-based chemotherapy will consist of G monotherapy, GC (for WHO/ECOG PS 2 participants only), G + oxaliplatin, G + carboplatin, GC + S-1, G + S-1, and GC + albumin-bound paclitaxel. Following the treatment period, durvalumab Q4W +/- chemotherapy (except for paclitaxel) may continue, at the investigator’s discretion, until discontinuation criteria are met. The primary endpoint is the incidence of Grade 3 or 4 adverse events, assessed by the investigator to be possibly related to any study treatment within 6 months after initiation of durvalumab. Secondary endpoints include OS, objective response rate, progression-free survival, and duration of response. Enrollment is ongoing and planned in France, Germany, United States, Spain, Italy, Japan, South Korea, and Singapore. Clinical trial information: NCT05771480 .
A phase 1/2, safety lead-in and dose expansion, open-label, multicenter trial investigating the safety, tolerability, and preliminary activity of ivosidenib in combination with nivolumab and ipilimumab in previously treated subjects with IDH1-mutated nonresectable or metastatic cholangiocarcinoma.
Authors: Kelley Robin Kate , Cleary James M. , Sahai Vaibhav , Baretti Marina , Bridgewater John A , Hua Zhaowei , Gliser Camelia , Bian Ying , Abou-Alfa Ghassan K. 
Published: July 2024

TPS4197 Background: Cholangiocarcinoma (CCA) is a rare cancer with limited therapeutic options, though molecularly targeted therapies have demonstrated anti-tumor activity in certain subsets. Approximately 15% of patients with intrahepatic CCA harbor activating mutations in isocitrate dehydrogenase-1 (mIDH1), and treatment with the mIDH1 inhibitor, ivosidenib (IVO) improved progression-free survival in the phase 3 ClarIDHy trial. mIDH1 is associated with an immune-excluded tumor microenvironment, and anti-CTLA4 immune checkpoint inhibition (ICI) augments anti-tumor activity when combined with IVO in preclinical models. Preliminary anti-tumor activity of dual immune checkpoint inhibitors (IPI, NIVO) has been reported in biliary tract cancers. Methods: This is a phase 1/2, non-comparative, multicenter, open-label study of IVO, IPI, NIVO, in subjects with unresectable or metastatic CCA with mIDH1. Key eligibility criteria include: a histopathological diagnosis; tumor mIDH1 based on local testing; progression on and/or intolerance to 1-2 prior lines of systemic therapy, at least one of which contained either gemcitabine and/or 5-fluorouracil; prior anti-PD-(L)1 therapy is allowed in the safety lead in; Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 or 1; at least 1 measurable lesion as defined by RECIST version 1.1. The study has a safety lead-in phase and an expansion phase with 2 different expansion cohorts: cohort 1, ICI-naive; cohort 2, prior ICI allowed. The primary objective is to evaluate the safety and tolerability of IVO in combination with IPI plus NIVO and determine the recommended combination dose (RCD). This phase will enroll ~6 to 12 dose-limiting toxicity (DLT)–evaluable patients. The first 6 patients enrolled will receive IVO 500 mg orally once daily in combination with IPI 1 mg/kg IV infusion and NIVO 3 mg/kg IV infusion concurrently once every 3 weeks for 4 doses followed by NIVO at 480 mg IV once every 4 weeks until progression or unacceptable toxicity (up to a maximum of 24 months of NIVO). DLTs will be evaluated during the first 2 cycles of treatment. An additional 6 patients may be enrolled to assess an alternative dose of ivosidenib 250 mg once daily. Upon determination of the RCD, the two expansion cohorts will be initiated to assess the clinical activity of the triplet combination in patients with and without prior ICI. First patient in occurred in November 2023. Clinical trial information: NCT05921760 .
REPLACE: A phase III, randomized, open-label trial to evaluate the safety and efficacy of regorafenib and pembrolizumab versus locoregional therapy (LRT) with transarterial chemoembolization (TACE) or transarterial radioembolization (TARE), for the first-line treatment of intermediate-stage hepatocellular carcinoma (HCC) with beyond up-to-7 criteria.
Authors: Galle Peter Robert , Kudo Masatoshi , Llovet Josep M , Cheng Ann-Lii , Lencioni Riccardo , Oviedo Yanina , Desai Kalpna , Monier Amandine , Finn Richard S. 
Published: July 2024

TPS4200 Background: Intermediate-stage HCC represents a heterogeneous population, posing unique challenges for therapeutic management. With the advent of effective systemic therapies for unresectable HCC, the treatment landscape for intermediate-stage extends beyond LRT, particularly in patients with high tumor burden. The growing evidence about the benefit of systemic therapy in intermediate-stage HCC led to the inclusion in some recent guidelines of systemic therapy as the first choice of treatment in TACE-unsuitable patients with intermediate-stage HCC. Despite these recommendations, no randomized clinical trial has been published comparing LRT with TACE/TARE versus systemic therapy in patients with intermediate-stage HCC and high tumor burden. Methods: REPLACE is a phase III, multicenter, randomized, open-label trial that will compare the efficacy and safety of LRT with TACE/TARE versus systemic therapy, for the first-line treatment of intermediate-stage HCC with beyond up-to-7 criteria. Eligible participants will be randomized 1:1 to receive regorafenib (90 mg orally q.d. on days 1 to 21 of a 4-week cycle), and pembrolizumab (400 mg i.v. on day 1 of a 6-week cycle) or LRT with TACE or TARE, and will be stratified according to geographic region (Asia vs. non-Asia), ECOG Performance Status (0 vs 1) and Albumin-Bilirubin (ALBI) grade (1 vs 2). Patients must have intermediate-stage HCC with beyond up-to-seven criteria (Up-to-7 criteria = largest tumor diameter (cm) + number of tumors ≤7), measurable disease per RECIST 1.1, disease not amenable to curative treatment but amenable to LRT with TACE or TARE, no prior systemic or LRT for HCC, except for successful resection and/or ablation completed ≥ 6 months prior to randomization. Patients will be treated until progressive disease, unacceptable toxicity, or other treatment discontinuation criteria is met. The primary endpoint is progression free survival (PFS), assessed locally by the Investigator using mRECIST for HCC. Secondary endpoints include PFS assessed locally by the Investigator using RECIST 1.1; PFS centrally assessed using mRECIST and RECIST 1.1; overall survival; overall response rate according to RECIST v.1.1 and mRECIST based on the Investigator’s and central assessment; time to unTACEable progression; duration of response; safety and tolerability of the trial treatments, and patient reported outcomes for health-related quality of life. The estimated enrollment is 496 patients from approximately 14 countries. Recruitment started in October 2023 and is currently ongoing. Clinical trial information: NCT04777851 .
Repurposing atovaquone as a STAT3 inhibitor for the treatment of platinum resistant ovarian cancer.
Authors: Wood Sarah Jeanne , Frank David , Haas Elizabeth Brannan , Wang Weiyuan , Meisel Jane Lowe , Khanna Namita 
Published: July 2024

TPS5631 Background: Despite advances, ovarian cancer (OC) is the most lethal gynecologic cancer with 5-year survival rates for stage III and IV disease 41% and 21%, respectively. After initial treatment with cytoreductive surgery and chemotherapy, 70% of patients (pts) will relapse. Treatment of relapsed OC is dependent on the amount of time between completion of platinum-based therapy and relapse, known as the platinum-free interval (PFI). Pts with PFI of less than six months are deemed platinum-resistant with low response to further chemotherapy and median progression-free survival (PFS) of 3.6 months. Additional treatment options are needed. Oncogenic signal transduction pathways are a critical component of cancer pathogenesis. In a variety of cancer types, including OC, the transcription factor STAT3 (Signal Transducer and Activator of Transcription 3) has emerged as a key promoter of cellular proliferation and resistance to therapeutic drugs. In OC cells, STAT3 is constitutively activated in over 70% of cells, resulting in enhanced cell survival, angiogenesis, and metastasis. STAT3 also controls innate and adaptive immune response by driving myeloid-derived suppressor cells and regulatory T cells, while hampering CD8+ T cell cytotoxicity. Using the Connectivity Map database to identify drugs that induce gene expression changes contrary to the STAT3 signature, the FDA-approved antimicrobial atovaquone (ATO) was identified as the most active. ATO, a well-tolerated, readily available drug inhibits STAT3 tyrosine phosphorylation by downregulating the cell surface expression of glycoprotein 130, which is necessary for signaling of IL-6 and Janus Kinase, and subsequent phosphorylation of STAT3. Given that the STAT3 pathway is constitutively activated in OC, we hypothesize that ATO, a potent inhibitor of STAT3, could be a repurposed therapeutic agent in OC. Methods: A Phase II, single-arm, investigator-initiated clinical trial is in process at our institution where we are evaluating ATO as targeted therapy in pts with platinum resistant OC whose tumors have progressed despite standard therapies. To date, we have currently enrolled 2 of an anticipated 28 pts. The primary endpoint is PFS, with clinical secondary endpoints to include clinical benefit rate and overall survival. In addition, to confirm the STAT inhibitory effect on OC cells, pre and on-treatment tissue sampling is being obtained to assess changes in STAT3 dependent gene expression via RT-PCR and quantitate changes to the immune profile via flow cytometry. We hypothesize targeting inappropriate activation of STAT3 could be a novel and promising treatment approach in OC. This is the first clinical trial evaluating the clinical efficacy of ATO in OC and could have wide implications on treatment options in the future. Clinical trial information: NCT05998135 .