bluuebunny/crossref_metadata_2025_split huggingface dataset:
Responses to immune checkpoint inhibitor therapy in NF1 mutated cutaneous melanoma.
Authors: Kroll Matthew Robert , Snow Anthony N , Loeffler Bradley T. , Milhem Mohammed M. , Javed Asad 
Published: July 2024

e21535 Background: NF1 mutations occur in 14% of cutaneous melanoma. Less than 20% of advanced melanoma patients on Immune Checkpoint Inhibitor (ICI) therapy achieve radiographic Complete Response (CR). We present data on radiographic responses to ICI therapy in advanced melanoma patients with tumors harboring NF1 (Neurofibromatosis 1) mutations. Methods: Patients with metastatic or unresectable NF1 mutated melanoma were included in the analysis. Mutation status was identified via NGS and mutation pathogenic status was determined using Genome Oncology Software. All patients received ICI therapy. RECIST 1.1 was used to assess treatment responses with CT scans. CR on PET was defined as disappearance of all metabolically active lesions. Results: 26 metastatic or unresectable melanoma patients met criteria for inclusion. Of these, eight (30.8%) had CNS metastasis. ICI therapy included Ipilimumab-Nivolumab, Pembrolizumab, Nivolumab, or Relatlimab-Nivolumab (24/26 in front-line setting). The 12- and 24-month estimated cumulative incidence of CR were 43.9% and 60.6%, respectively. Altogether, 16 patients achieved CR as their best overall response. Four patients that achieved CR subsequently progressed. Four patients progressed without achieving CR. Six patients achieved a partial response by last follow-up without achieving CR or disease progression. Of the 8 patients with CNS metastasis, five (62.5%) had intra-cranial radiographic responses to ICI therapy, including 1 (12.5%) complete response. Five (62.5%) had multifocal ( > 2 sites of intracranial metastasis) intracranial disease. Five (62.5%) of these patients with intracranial disease received radiation, 2/8 (25.0%) received radiation and surgical resection, and one (12.5%) received neither radiation nor surgery. Three (37.5%) patients with CNS metastasis experienced disease progression while on ICI therapy. Conclusions: NF1 mutated melanoma appears to have high rates of radiographic responses to ICI therapy. Prospective validation of this finding, particularly in patients with CNS metastasis, is warranted.
Options for enhancing specific antitumor immunity in patients with melanoma.
Authors: Sultanbaev Alexander Valerievich , Kolyadina Irina Vladimirovna , Sultanbaev Mikhail , Musin Shamil , Menshikov Konstantin , Sultanbaeva Nadezda , Kudlay Dmitry , Tuzankina Irina 
Published: July 2024

e21547 Background: The special interest in oncology is the research of the immune status of patients. Quantification of T-cell receptor excision rings (TREC) and B-cell receptor κ deletion elements (KREC) allows to evaluate a humoral and a cellular immunity. In melanoma, the effectiveness of the use of drugs to control immune points depends on the formation of specific antitumor immunity. Quantitative indicators of excision recombination rings reflect the formation of a different repertoire of T-cell receptors, which are an integral component in the formation of specific immunity. The understanding of changes in TREC levels in patients with melanoma during therapy with various drugs can improve the selection of patients for immunotherapy. The purpose of this study is to assess the dynamics of changes in quantitative indicators of the T-cell receptor during adjuvant therapy for melanoma. Methods: The study included 82 patients with melanoma. Among patients with melanoma, the proportion of male patients was 36.5% (30/82), female - 63.5% (52/82). The median age in the group of patients with cancer was 63 years [Q1-Q3: 52.8-75]. Results: From the results obtained, it follows that in cancer patients, a decrease in the number of TREC in the blood indicates the presence of immunodeficiency. The data obtained indicate significant changes in TREC in melanoma. Targeted therapy (dabrafenib + trametinib) and interferon therapy are accompanied by a significantly significant increase in the level of TREC, which indicates an increase in the formation of specific antitumor immunity. Conclusions: The results obtained demonstrate a significant decrease in TREC content in patients with melanoma compared to healthy individuals. Determination of TREC levels during adjuvant therapy demonstrated the effectiveness of dabrafenib in combination with trametinib and interferon α-2β, which is reflected in a significant increase in the T-cell receptor repertoire. The presented data indicate the possibility of using the method for determining the TREC level to predict the risk of cancer progression and the effectiveness of prescribed therapy.
Analysis of neoadjuvant nivolumab and ipilimumab for clinical stage III melanoma using the SWOG S1801 event-free survival definition.
Authors: De Barros E Silva Milton Jose , Tavares Monique Celeste , Lima Joao Paulo S. N. , Garcia Daniel , Molina Andre , Lobo Matheus , Pinto Clovis Antonio Lopes , De Paula Rafaela Brito , Rinck Jr Jose Augusto , Duprat Neto João Pedreira 
Published: July 2024

e21563 Background: Perioperative pembrolizumab to advanced melanoma, as shown SWOG S1801 trial, was associated with a longer event-free survival (EFS) than those who received adjuvant pembrolizumab (EFS at 2y: 72% vs 49%, respectively). EFS, as defined in this trial, encompasses important factors related to neoadjuvant therapy in clinical practice. So far, there is no data of EFS rate for melanoma patients(pts.) treated with neoadjuvant nivolumab and ipilimumab, which is associated with more response rate but also more toxicity. Methods: We conducted a retrospective analysis of pts. with clinical stage III melanoma treated with neoadjuvant nivolumab 3mg/kg + ipilimumab 1 mg/kg (N3+I1) for two cycles followed by surgery and adjuvant therapy at AC Camargo Cancer Center. We applied the SWOG S1801 EFS definition (which includes inability to receive surgery, to start adjuvant therapy, melanoma recurrence and death) to this cohort. Results: Between Jan 2019 and Jan 2024, 37 pts. with clinical stage III melanoma treated with neoadjuvant N3+I1 were identified. Gender: 25 males (67%), median age (years): 58 (range: 31-78), BRAFV600 mut: 25(67%), Stage AJCC 8th edition: IIIB = 23 (62%), IIIC = 12 (32%), IIID = 2(6%). G3/G4 immune-related adverse events (irAE): 11 patients (30%). Two out 37 pts. did not complete the programmed neoadjuvant cycles due to toxicity (1 = colitis, 1 = myositis). Three pts. (8%) were unable to receive surgery: irAE = 1, metastatic disease = 2. All pts. who underwent surgery (n = 35) achieved R0 resection and started adjuvant therapy within 84-days after the procedure. Major pathological response (MPR) = 23 pts(66%) and non-MPR = 12 pts.(34%). There were 4 melanoma relapses after starting adjuvant therapy (11%). The total number of events was 7 (19%). In a median follow-up of 16.1 months(range:13.9-25), the landmark analysis of EFS at 2 years was 73% (95%CI, 49 to 87). Relapse-free survival(RFS) for MPR at 2 years: 96%. Conclusions: Neoadjuvant N3+I1 seems to have similar EFS compared to SWOG S1801, but numerically more MPR rate and fewer events of progression, relapse and/or death. [Table: see text]
Real world experience of molecular landscape of uveal melanomas: Implications for personalized medicine strategies.
Authors: Crook Tim , Datta Vineet , Velicaria Eisa , Vijayan Poornima , Gosavi Rahul Ashok , Patil Darshana , Ajami Ramin 
Published: July 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 ( < 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 < 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.
Median Breslow thickness during, post and pre-COVID-19 lockdown and correlation with socioeconomic factors.
Authors: Marusca Georgiana , Dlugas Hunter , Kim Seongho , Ruterbusch Julie J. , Duque Diana , Neill Daniel , Mehregan Darius , Daveluy Steven , Kim Steve , Sukari Ammar , Flaherty Lawrence E. , Shao Yusra F. 
Published: July 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 < 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.
Can vitamin D deficiency be considered a risk factor be considered a risk factor in luminal breast cancer?
Authors: Fernández Madrigal Laura , Garcés María Yeray Rodríguez , Castaño López Miguel Angel , Bayo Calero Juan Lucas 
Published: July 2024

e24122 Background: The relationship of vitamin D (VD) with cancer is controversial. Its antiproliferative function by inhibiting the cell cycle has been described, as well as its characteristics as an inhibitor of angiogenesis, inducer of apoptosis and its ability to reduce inflammation, invasion and metastasis. Deficiency of this vitamin is very prevalent, affecting 40% of the population under 65 years of age, and there are some studies that relate it to the increase in the incidence of breast cancer (BC), colon or prostate cancer. VD deficiency is defined as a serum level of 25-hydroxy VD < 20 ng/mL. We analyzed whether VD deficiency can be considered a risk factor for BC, given that it is the most frequent tumor in the world. Methods: A single-center, retrospective, descriptive and analytical study of female patients diagnosed with localized luminal BC (stage I-II and III) in the year 2023 and a control group of healthy women. Baseline VD levels were determined in both groups. Statistical analysis (IBM SPSS Statistics 22) of demographic and clinical characteristics and multivariate analysis using a logistic regression model for the study of VD deficiency, according to the variables age, menopausal status and previous chemotherapy. Results: We analyzed 231 patients (p) with luminal BC and a control group of 324 healthy women. In the BC group the median age was 62 years (range 34 - 88 years), 72% (168 p) in postmenopausal stage. 52% (121 p) had stage I, 37% (86 p) stage II, and 11% stage III. 59.7 % (138 p) had luminal A phenotype and 40.2 % luminal B phenotype. 27.7 % (64 p) had received chemotherapy. In the control group the median age was 65 years (range 45 - 78 years), 90% (287 women) in postmenopausal state. VD deficiency was present in 50.6 % of the BC group with a mean VD value of 21 ng / ml. In the control group the deficit was 33 % with a mean VD value of 24 ng / ml. Therefore, this deficit is significantly higher in breast cancer patients than in healthy patients, with OR of 2.08 with 95% CI (1.4 - 2.7). In the overall multivariate analysis postmenopausal women have 5.1 more risk of presenting VD deficit, with p = 0.04. The variable age did not reach statistical significance. Logistic regression was performed to determine the effects of age, menopausal status, and having received previous chemotherapy, on the probability of BC patients presenting a VD deficit, without reaching statistical significance. Conclusions: VD deficiency is more prevalent in women with BC than the normal population, which is consistent with previous studies. Further well-designed studies are needed to assess the effect of VD supplementation in the female population as prevention of BC.
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: Muñoz Martín Andrés J. , Viñuela Benéitez María Carmen , Iglesias Pérez Claudia , Sánchez-Cánovas Manuel , Rubio Jaime , Martínez Maria Purificacion , Garcia de Herreros Marta , De Castro Eva Martinez , Fernández Isaura , García Escobar Ignacio , Porta Rut , Brozos Elena , Quintanar Maria Teresa , Garcia Adrian Silvia , Guirao Sánchez Sara , Covela Marta , Santiago Crespo José , Pelegrín Francisco , Carmona-Bayonas Alberto , Jimenez-Fonseca Paula ,   Cancer and Thrombosis Section, Spanish Society of Medical Oncology (SEOM)
Published: July 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 < .0001), random forest classifier ROC-AUC 0.61 (CI 95%, 0.58-0.64; P < .0001), and logistic regression ROC-AUC 0.70 (CI 95%, 0.67-0.73; P < .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]
Increase in blood pressure in patients with metastatic kidney cancer treated with combination checkpoint inhibitor and vascular endothelial growth factor receptor tyrosine kinase inhibitor therapy.
Authors: Lin Rick Y. , Patel Neil Jigish , Chatzkel Jonathan Alexander , Benidir Tarik , O'Malley Padraic , Crispen Paul , Ramnaraign Brian Hemendra 
Published: July 2024

e24128 Background: The combination therapy of an immune checkpoint inhibitor (ICI) with a vascular endothelial growth factor receptor tyrosine kinase inhibitor (VEGFR-TKI) is considered a first line treatment option for patients with metastatic clear cell renal cell carcinoma (ccRCC). TKI-induced hypertension is a well-known potential side effect with VEGFR-TKIs however little is known about the real-world increase in systolic blood pressure (SBP) and diastolic blood pressure (DBP) in patients with and without underlying hypertension treated with this combination therapy. Methods: A retrospective study was performed that included patients with metastatic ccRCC who were treated at the University of Florida Health Cancer Center between June 2019 and September 2022 who received treatment with the combination of an ICI and VEGFR-TKI. The data collected included history of hypertension, patients use of anti-hypertensive therapy at baseline, SBP and DBP prior to initiation of therapy and at approximately one month after initiation of treatment. Results: We identified a total of 29 patients who met the inclusion criteria for our study. The median age was 68 years old (IQR 61-72) while 25 patients (86%) were male and 4 (14%) were females. There were 27 patients (93%) who were treated with axitinib with pembrolizumab, while 1 (3%) was treated with cabozantinib with nivolumab, and 1 (3%) was treated with lenvatinib with pembrolizumab. Out of the 29 patients, 11 (38%) did not have hypertension prior to therapy while 18 (62%) did have baseline hypertension and were receiving at least one anti-hypertensive treatment. In those patients without baseline hypertension, the median baseline SBP was 113 and the median SBP after one month of treatment was 144 (p = 0.01). Conversely, those patients with baseline hypertension, the median baseline SBP was 122 and median SBP after one month of treatment was 148 (p = 0.003). In those without hypertension at baseline, the mean SBP increase after one month was 27.3% while in those with baseline hypertension the mean increase in SBP of 17.0%. Conclusions: Our study demonstrates that in a real-world population of patients with metastatic ccRCC there is a statistically significant elevation of both SBP and DBP when treated with the combination of an ICI and VEGFR-TKI and that in those patients without baseline hypertension and not on anti-hypertensive therapy at baseline, there is a more pronounced increase in blood pressure. This data should reinforce the need to have close monitoring of SBP and DBP during therapy, regardless of whether the patient has underlying hypertension or not, and may help guide anti-hypertensive therapy during kidney cancer treatment.