tbuckley/cabot-search huggingface dataset:
Positive baseline thyroid autoantibodies as a predictive biomarker for thyroid immune-related adverse events: A systematic review and meta-analysis.
Authors: Ben Ponvilawan, Chalothorn Wannaphut, Tatiana Tselovalnikova, Dhruv Bansal
Journal: Journal of Clinical Oncology (2024)

e24124 Background: Thyroid dysfunction is one of the most common immune-related adverse events (irAE) by immune checkpoint inhibitors (ICI). Given the known relationship between antithyroid autoantibodies (ATA), including antithyroid peroxidase (TPO Ab) and anti-thyroglobulin (Tg Ab), and autoimmune thyroid disease, they could also play a role as a predictive biomarker for thyroid irAE (T-irAE). We performed this meta-analysis to evaluate the association of positive baseline thyroid autoantibodies and T-irAE. Methods: Eligible studies were screened using Ovid Medline and Embase databases with search terms related to ATA and thyroid irAE. Studies must be case-control or cohort studies with patients who received ICI and report the numbers of patients who have thyroid dysfunction and do not have thyroid dysfunction by the pre-ICI treatment statuses of ATA, TPO Ab, or Tg Ab. The pooled odds ratio (OR) and the associated 95% confidence interval (95% CI) were calculated using the Mantel-Haenszel method. Subgroup analysis by types of ICI (anti-PD1, anti-PD-L1, or combination treatment) and study region were also performed. The presence of publication bias was assessed by direct visualization of funnel plots. Results: After two rounds of screening, 19 case-control and five retrospective cohort studies were included in the meta-analysis. Patients who had positive baseline ATA had increased odds of developing T-irAE, hypothyroidism, and hyperthyroidism (pooled OR 10.95, 95% CI 6.65-18.02, I 2 = 38%; 6.82, 95% CI 2.99-15.56, I 2 = 27%; and 7.59, 95% CI 2.51-22.96, I 2 = 42%; respectively). Positive pre-treatment TPO Ab and Tg Ab were also independently associated with higher odds of hypothyroidism (pooled OR 5.01, 95% CI 2.87-8.75, I 2 = 4%, and 18.73, 95% CI 9.04-38.80, I 2 = 0%, respectively) and hyperthyroidism (pooled OR 2.94, 95% CI 1.57-5.52, I 2 = 25%, and 8.36, 95% CI 1.18-59.31, I 2 = 82%, respectively). The associations did not significantly differ between the types of ICI utilized and the study region. Visualization of funnel plots did not reveal a presence of publication bias. Conclusions: Pre-ICI treatment statuses of ATA, TPO Ab, and Tg Ab are associated with both hypothyroidism and hyperthyroidism. Thyroid autoantibodies as a baseline predictive tool can be helpful for early detection of T-irAE in patients who receive ICI therapy.
Malignant blue nevus: Epidemiology, socioeconomic factors, and disease presentation.
Authors: Sharon Choe, Mark Moroz, Suraj Puvvadi, Kat Chin, Peter T. Silberstein, Craig Heise, Beau Hsia
Journal: Journal of Clinical Oncology (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: Sharon Choe, Julia Griffin, Peter T. Silberstein
Journal: Journal of Clinical Oncology (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 &lt; 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.
Median Breslow thickness during, post and pre-COVID-19 lockdown and correlation with socioeconomic factors.
Authors: Georgiana Marusca, Hunter Dlugas, Seongho Kim, Julie J. Ruterbusch, Diana Duque, Daniel Neill, Darius Mehregan, Steven Daveluy, Steve Kim, Ammar Sukari, Lawrence E. Flaherty, Yusra F. Shao
Journal: Journal of Clinical Oncology (2024)

e21574 Background: Access to routine cancer care during COVID-19 pandemic was greatly affected. The impact of this on melanoma care is unknown. Breslow thickness (BT) was seen to decrease and then increase during and post-COVID-19 lockdown in Italy. Here, we aim to study the impact of COVID-19 lockdown on melanoma care in the United States. Methods: Patients diagnosed with cutaneous melanoma (CM) pre (September 15th 2019-March 14th 2020), during (March 15th-June 14th 2020), and post-lockdown (June 15th-December 14th 2020) were retrospectively studied using Metropolitan Detroit Cancer Surveillance System (MDCSS) database. Patients without an identifiable primary lesion, or with ocular, mucosal, or acral melanoma were excluded. Demographic and clinical characteristics were reviewed. The primary endpoint was median BT during and post vs pre-lockdown. Fisher's exact and Kruskal-Wallis tests were performed for categorical and continuous variables, respectively, to compare groups. Interaction in subgroup analyses was assessed using likelihood ratio tests. Linear regression analyses were performed with Box-Cox transformed BT. Cox proportional hazards regression analyses were performed for overall survival. Covariates for multivariable analysis were selected using LASSO-based penalized regression models. Results: 802 patients were included (pre N = 347, during N = 87, post N = 368). Patients diagnosed with CM post-lockdown were younger (age &lt; 50 years pre = 14%, during = 13%, post = 23%). More patients diagnosed pre-lockdown carried government-issued insurance (pre = 48%, during = 39%, post = 38%). No difference (diff) in median BT was seen between periods (median = 0.6mm for pre, during, and pos). Married status was associated with a lower BT vs unmarried (diff = -0.19, 95% CI -0.36 to -0.014, p = 0.034) and higher census tract poverty level was associated with a higher BT (5%-10% diff = 0.17, 95% CI 0.004 to 0.33, p = 0.045; 10%-100% diff = 0.27, 95% CI 0.093 to 0.45, p = 0.003) vs 0-5% poverty on univariable analysis. Male gender was associated with a lower BT on multivariable analysis (diff = -0.12, 95% CI -0.20 to -0.04, p = 0.005) and lower risk of death on univariable analysis (HR = 0.50, 95% CI 0.31 to 0.82, p = 0.006). Conclusions: We found no difference in median BT during and post- vs pre-lockdown. We also identified at-risk populations (female, unmarried, and living in greater poverty areas) who could benefit from proactive melanoma care. Time to surgery from initial diagnosis during and post vs pre-lockdown would be of interest to study further.
Real world experience of molecular landscape of uveal melanomas: Implications for personalized medicine strategies.
Authors: Tim Crook, Vineet Datta, Eisa Velicaria, Poornima Vijayan, Rahul Ashok Gosavi, Darshana Patil, Ramin Ajami
Journal: Journal of Clinical Oncology (2024)

e21572 Background: In the realm of ocular oncology, Uveal Melanoma (UM) stands out as a rare and formidable malignancy, necessitating a deeper understanding of its molecular landscape to enhance treatment strategies. This abstract delves into the real-world experiences of unraveling the molecular intricacies of UM and explores the implications for personalized medicine strategies. Methods: In this study, we conducted a comprehensive genomic analysis of tissue samples from 7 UM cases to identify key genetic alterations and molecular features, elucidating the heterogeneity of this ocular malignancy. Results: Consistent with other studies, 57% (4/7) of our cohort harbored a driver mutation in either the GNAQ or GNA11 genes. GNAQ Q209 codon mutations (Q209L or Q209P), were the most frequent variants identified. GNAQ/GNA11 mutations are known to activate the MAPK/ERK signaling pathway, contributing to uncontrolled cell proliferation; its presence qualifies for entry into clinical trial testing DYP688 in metastatic UM. Concurrent mutations were identified in EIF1AX (n = 1), SF3B1 genes (n = 1) and BAP1 (n = 1), highlighting the molecular diversity. EIF1AX, SF3B1, and BAP1 inactivating mutations indicate varying risks for distant metastasis, categorized as low, medium, and high risk, respectively. Notably, homologous recombination repair (HRR) pathway gene mutations were identified in 28% (2/7) of cases. Additionally, SF3B1 mutations have been proposed to induce a BRCA-like phenotype, resulting in synthetic lethality to PARP inhibitors (PARPi). These findings provide opportunities to explore additional targeted therapy (off label) options with PARPi. In a case where gene expression profiling (GEP) was performed, an upregulation in PRAME gene expression (PRAME+) was observed. This finding potentially indicates an increased metastatic risk and a shorter time to metastasis, given that PRAME+ status has been established as an independent risk modifier for metastasis, regardless of the GEP-derived UM class (Class 1 or 2). TMB ranged from 2 to 21 muts/mb, with 5 out of 7 specimens showing low TMB ( &lt; 10 mutations/Mb) and two sample with high TMB (15 and 21muts/mb). This case with TMB of 21 muts/mb showed Deficient Mismatch Repair (dMMR) status. All samples evaluated for PD-L1 expression (n = 4) in our cohort showed &lt; 1% PD-L1 expression in tumor cells, including the dMMR tumor. Conclusions: These findings underscore the need for a comprehensive genomic approach in guiding therapeutic decisions, understanding prognostic implications and advancing personalized medicine strategies for UM patients. Our study provides an overview of the molecular landscape of UMs with delineation of key molecular features, thereby enhancing our understanding of UM biology and setting the stage for the development of targeted therapies tailored to the unique genomic profile of each patient.
Immune-related gastritis: An orphan immune-related adverse event.
Authors: Tal Etan, Shlomit Strulov Shachar, Ido Wolf, Yasmin Leshem
Journal: Journal of Clinical Oncology (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 &gt; 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.
Toripalimab (anti-PD-1) plus recombinant human endostatin as adjuvant therapy in patients with resected stage III melanoma: Interim analysis of an open-label phase II trial.
Authors: Xianglin Hu, Yu Xu, Yang-bai Sun, Ling-ge Yang, Bi-qiang Zheng, Zheng-Wang Sun, Yong Chen, Wangjun Yan, Chun-Meng Wang
Journal: Journal of Clinical Oncology (2024)

e21557 Background: Patients with completely resected stage III melanoma are under high risk of disease recurrence. Recurrence-free survival (RFS) remains unsatisfactory despite there is adjuvant anti-PD-1 monotherapy following surgery, with the 1-year RFS about 70% and 2-year RFS about 49% in our country. It's urgent to explore combined regimens with anti-PD-1 to further improve the RFS. Here we report the interim efficacy and safety results of toripalimab (a PD-1 inhibitor) plus recombinant human endostatin (an angiogenesis inhibitor) as combined adjuvant therapy for patients with resected stage III melanoma. Methods: This prospective single-center, single-arm, open-label phase II trial screened adult patients with stage III melanoma who had undergone complete tumor resection within the previous 13 weeks for eligibility. Toripalimab was administrated in intravenous drip to patients at 3 mg/kg every 2 weeks in a 4-week cycle (day 1 and day 15 of each cycle), for up to 13 cycles or until disease recurrence, unacceptable toxicity or decease. Recombinant human endostatin was administrated in a continuous intravenous infusion at a dose of 210 mg from day 1 to day 3 for each 4-week cycle, for up to 6 cycles or until disease recurrence, unacceptable toxicity or decease. The primary endpoints were the 1-year and 2-year RFS. Results: By the data cut-off on Jan 25, 2024, 43 eligible patients with resected stage III melanoma between October 2021 and December 2023 were enrolled. In ITT population (n = 43), patients' median age was 56 (IQR 52~69) years. There were 25 (58%) male and 18 (42%) female; 27 (63%) with acral melanoma and 16 (37%) with cutaneous melanoma. With a median follow-up of 14 months, the 1-year and 2-year RFS rates were 83% and 71%, respectively. For security, 33 (77%) patients experienced at least one adverse event (AE), including 27 grade 1-2 AEs and 6 grade 3~4 AEs. One patient discontinued the combined therapy due to immunotherapy-associated myocarditis. Conclusions: Toripalimab in combination with recombinant human endostatin as adjuvant therapy could further improve disease-free survival in Chinese patients with completely resected stage III melanoma, with a manageable toxicity profile. Clinical trial information: 05907512 .
External validation of a bleeding risk assessment model developed with natural language processing and machine learning (PREDICT-AI study) in patients with anticoagulated cancer with venous thromboembolism in the TESEO international prospective registry.
Authors: Andrés J. Muñoz Martín, María Carmen Viñuela Benéitez, Claudia Iglesias Pérez, Manuel Sánchez-Cánovas, Jaime Rubio, Maria Purificacion Martínez, Marta Garcia de Herreros, Eva Martinez De Castro, Isaura Fernández, Ignacio García Escobar, Rut Porta, Elena Brozos, Maria Teresa Quintanar, Silvia Garcia Adrian, Sara Guirao Sánchez, Marta Covela, José Santiago Crespo, Francisco Pelegrín, Alberto Carmona-Bayonas, Paula Jimenez-Fonseca
Journal: Journal of Clinical Oncology (2024)

e24123 Background: The risk factors for bleeding during anticoagulation in patients with cancer-associated thrombosis (CAT) remain largely unexplored. The recently developed PredictAI model ( Muñoz Martín AJ et al. JCO 40, e18744-e18744(2022) was aimed to predict major bleeding (MB) in anticoagulant-treated cancer patients within the first 6 months following venous thromboembolism (VTE) diagnosis. The goal was to validate the PredictAI model using an independent cohort of patients from the TESEO international, observational, prospective registry. Methods: The performance of the three predictive models developed in PredictAI were assessed in terms of accuracy, precision, recall, F1-score, and the receiver operating characteristic (ROC) area under the curve (AUC): PredictAI decision tree classifier ROC-AUC 0.66 (confidence interval 95% [CI 95%], 0.63-0.69; P &lt; .0001), random forest classifier ROC-AUC 0.61 (CI 95%, 0.58-0.64; P &lt; .0001), and logistic regression ROC-AUC 0.70 (CI 95%, 0.67-0.73; P &lt; .0001). The outcome was MB within 6 months following VTE diagnosis, whereas the analyzed predictors for MB at baseline comprised those from PredictAI, namely patient’s age, presence of metastasis, hemoglobin levels, platelet count, leukocyte count, and serum creatinine levels. Results: The TESEO cohort used for the external validation comprised 2,179 patients (51.9% male, mean age = 64.72 ± 11.34 years) with active cancer and VTE under anticoagulant treatment. The median (Q1, Q3) follow-up duration across patients was 6 (2, 14) months. Considering the ROC-AUC values for the three tested models (table 1), the results confirm a statistically significant validation and best performance of the logistic regression (ROC-AUC = 0.59; 95% CI = 0.53, 0.65; P = .002) approach. Conclusions: Our results support the first external validation of a risk assessment model of bleeding specifically developed for CAT. This model may guide objective decisions regarding the extension and dosing of anticoagulant therapy in this population. Future steps should involve further validation of the present model in other patient cohorts and the generation of a clinical tool to facilitate its use in healthcare settings. [Table: see text]