bluuebunny/crossref_metadata_2025_split huggingface dataset:
Real-world effectiveness and safety of dabrafenib-trametinib as first-line of treatment for BRAF mutated metastatic melanoma: Results of the study GEM1801.
Authors: Berciano-Guerrero Miguel-Ángel , Perez-Ruiz Elisabeth , Muñoz Couselo Eva , Manzano Jose Luis , Cerezuela-Fuentes Pablo , Ayala de Miguel Pablo , Soria Ainara , García Castaño Almudena , Crespo Guillermo , Puértolas Teresa , Aguado De La Rosa Carlos , Gutiérrez Sanz Lourdes , López Castro Rafael , Espinosa Enrique , Lecumberri Maria José , Majem Margarita , Medina Martinez Javier , Bellido Lorena , Fernández-Morales Luis Antonio , Martin-Algarra Salvador 
Published: July 2024

e21515 Background: Dabrafenib-Trametinib (DT) is included in the therapeutic arsenal for BRAFV600-mutant metastatic melanoma. However, detailed effectiveness results for dabrafenib and trametinib depending on patient prognostic profile in the real-world are limited. Methods: GEM1801 is a prospective observational study that analyzes the clinical and pathological disease presentation patterns, the different lines of treatment choices and the health outcomes derived from treatments in patients with melanoma in Spain. Here we focus on patients receiving DT as first-line treatment in the metastatic melanoma. Based on previous studies, we defined 3 subgroups: good prognosis (normal LDH and < 3 metastatic sites), poor prognosis (high LDH and ≥3 metastatic sites), and intermediate prognosis (neither of good or poor prognosis). Results: From August 2018 to December 2022, 140 patients receiving DT were enrolled; 45 (32.1%) with good, 42 (30%) with intermediate and 34 (24.3%) with poor prognosis. Subgroup allocation was not possible for 19 patients due to missing info on LDH or metastatic sites. Overall survival (OS) was longer in patients with good versus poor prognosis (median 26.2 vs 10 months; p = 0.024), while those with intermediate prognosis showed a mixed profile with a median OS of 17.4 months. Response to treatment also showed correlation with OS (3-years OS rate: 57.1% vs 23% vs 46.9% vs 26.8% for CR, PR, SD and PD, respectively; p < 0.001). In patients who had a complete response, the 5-year OS rate was 58.3% (95% CI: 31.3-100) while the median overall survival was not reached. In patients with intermediate prognosis, the ECOG-PS was the main prognostic factor in multivariate analysis (hazard ratio: 4.6; 95% CI: 1.8-1.7; p = 0.002). The reported grade 3-5 toxicity was less than 5%. Treatment-related adverse events were reported in 5 (3.6%) patients, consisting of fever, mucositis, pneumonitis, neutropenia, ocular toxicity and retinal detachment. There were no differences across prognostic subgroups ( p = 0.741). Conclusions: DT in the Real-World has an acceptable effectiveness and safety profile. Prognostic groups could help in the selection of patients who could achieve a complete response, since it is the most important prognostic biomarker. Clinical trial information: NCT03605771 . [Table: see text]
Hyperammonemic encephalopathy: An unaccounted side effect of 5FU and capecitabine.
Authors: Sheikh Taha , Watkins Dean , Hamouda Danae M. 
Published: July 2024

e24108 Background: Metabolic encephalopathy is a serious but reversible condition that is characterized by a diffuse impairment of cognitive function due to the overabundance of various metabolites or toxins. Hyperammonemia ( > 80 μg/dL or > 47 μmol/L) is a well-known cause of metabolic encephalopathy and also a rare side effect of 5-Fluorouracil (5-FU) chemotherapy. Constipation and renal failure are two known risk factors for developing hyperammonemic encephalopathy with 5-FU use. Capecitabine is a 5-FU prodrug that is commonly used as a more tolerated and more convenient alternative chemotherapy agent. Despite being less common than with 5-FU, cases of hyperammonemic encephalopathy related to capecitabine use may be missed clinically due to under-testing. Additionally, diarrhea may be misinterpreted as a side effect of chemotherapy instead of an effective tool for identifying early disease and accelerating disease resolution. Methods: A search using Pubmed was conducted on January 4th, 2024 to identify cases of hyperammonemia and metabolic encephalopathy related to 5-Fluorouracil and capecitabine. The search strategy was ("metabolic encephalopathy 5-fluorouracil" OR “hyperammonemia 5-fluorouracil”) AND (“metabolic encephalopathy capecitabine” OR “hyperammonemia capecitabine”). Cases were then organized into a table where factors of the cases were stratified. Results: A total of 59 total cases were identified. Every case where 5-FU was used reported a serum ammonia level, while only 5 of the 9 cases (55.55%) where capecitabine was used reported a serum ammonia level. Additionally, only 9 cases (15.25%) reported bowel movement status with 1 patient presenting with diarrhea, and 5 with constipation. The most common methods for managing metabolic encephalopathy in these patients included: branched chain amino acids (66.10%), discontinuing/changing the chemotherapeutic agent (62.71%), lactulose (37.29%), intravenous hydration (32.20%), and hemodialysis/hemofiltration (13.56%). For the 52 cases that reported it, the average duration of symptoms post-treatment was 2.15 days. Conclusions: A goal in managing patients receiving 5-FU or capecitabine with hyperammonemic encephalopathy is the excretion of ammonia without causing dehydration. This management is seen with the use of lactulose to increase bowel movements in patients with decompensated liver cirrhosis. Of note, 5FU and capecitabine have been shown to cause diarrhea as a grade 3 and 4 adverse effect in 12.7% and 16.6% of patients, respectively. Thus it can be theorized that the diarrhea from 5FU/capecitabine may offset the development of hyperammonemia. This principle could potentially be expanded to benefit patients with a history of chronic constipation. The oversight of hyperammonemia from 5-FU and capecitabine use is both dangerous and diminishes the quality of life from patients who are not proactively treated to prevent encephalopathy.
Identifying objective risk factors of financial toxicity in patients with cancer.
Authors: Bazhenov Aleksei , Doro Luiza , O'Sullivan David M. , Menendez Alvaro G. 
Published: July 2024

e24116 Background: Current financial toxicity (FT) screening tools rely on patient-reported risk factors (RF)1. Underrepresented populations may not be forthcoming about FT fears due to cultural concerns of treatment withholding or migratory repercussions, if applicable1–4. Identifying objective RF, such as social determinants of health (SDH) and disease-specific factors (DSF), could reduce FT in cancer patients and healthcare systems. Methods: This was a multi-center retrospective study evaluating SDH and DSF associated with FT (defined as ≥$15,000 owed) related to cancer treatment. Inferential statistics were used to evaluate differences between the FT cohort and those who owed < $15,000. Continuous data were compared with a Student’s t or Mann-Whitney U test, depending on distribution. Categorical outcomes were compared with a chi square test. A logistic regression model was used to evaluate multivariate associations with FT, using p < 0.05 to define significant results. Results: The sample comprised 162 records, 81 in each group. Univariate analyses demonstrated differences in age, lack of PCP, non-US country of origin, lack of insurance, lower education levels, need for an English interpreter, stage 4 at diagnosis, recurrent or metastatic disease, use of immune checkpoint inhibitors (ICI), and use of targeted molecular therapy (TMT) (Table 1). Employment status and marital status were not statistically different. The logistic regression model showed that lack of insurance and stage 4 at diagnosis were significantly associated with FT (p = 0.001 and p = 0.0495, resp.). Conclusions: Objective FT screening can minimize response bias and incidence in those at increased risk. Non-US country of origin and lack of English proficiency suggests that first-generation Hispanics may not be appropriately navigated for FT. These findings identify specific subpopulations at risk for FT and will guide prospective interventions looking to minimize FT. Healthcare systems should analyze objective measures of FT while considering loco-regional and subcultural SDH/DSF in order to overcome response bias. Ref. Witte J et al. Methods for measuring financial toxicity after cancer diagnosis and treatment. Annals of Oncology. 2019;30(7) Strasser-Weippl K et al. Progress and remaining challenges for cancer control in Latin America and the Caribbean. Lancet Oncol. 2015;16(14) Zhu Z et al. Cancer survivors’ experiences with financial toxicity. Psychooncology. 2020;29(6) Chebli P et al. Multilevel determinants of financial toxicity in breast cancer care. Supportive Care in Cancer. 2020;28(7). [Table: see text]
LOOP: An observational, prospective, multicenter study of patients with non-small cell lung cancer in the US receiving standard-of-care and initiating an approved therapy with risk of pneumonitis/ILD.
Authors: Piault-Louis Elisabeth C , Marvel Melissa , Newton Michael David , Haddad Vincent , Hutchison Emmette R , Hughes Joseph T , Campbell Alicyn K , Basch Ethan 
Published: July 2024

TPS12157 Background: A wide range of oncology treatments are associated with a risk of pneumonitis or ILD, which is an uncommon but serious side effect with potential for significant morbidity and mortality (Conte et al 2022). The development of pneumonitis/ILD remains unpredictable and relatively uncommon in a single practice or hospital setting. Risk of drug-induced pneumonitis/ILD remains a limiting factor to prescribing life-saving treatments. A non-invasive, patient-centric multimodal solution for remote data capture could support recognition and tracking of pulmonary symptoms in addition to providing insight for the clinical team to personalize the monitoring of patients according to their medical history or specific physiological markers. Methods: LOOP is an observational, prospective, multicenter study conducted in the US. Stage III and IV NSCLC patients receiving SoC and initiating treatment with an FDA-approved ICI (alone or in combination with other agents), ADC, or small molecule EGFR inhibitor are eligible to participate. The primary objective is to enable the development and refinement of an algorithm including documentation of its performance (specificity, sensitivity and odd ratio to inform risk of pulmonary/respiratory/thoracic-related events including ILD). A secondary objective proposes to characterize the risk factors, signs, and symptoms leading to onset, diagnosis, and treatment of pneumonitis/ILD in patients receiving SoC. The study will collect patient-generated data outside of point-of-care for six months, using questionnaires and a medical pulse-oximeter device . Clinical data available per SoC in the medical records will be collected. Approximately 600 patients will be enrolled over 13 months to accrue approximately 100 pneumonitis/ILD events. Events will include all grades of pneumonitis, including ILD and radiation pneumonitis, as determined by the Investigator. Qualitative interviews will be conducted to inform a more granular understanding of the patient specific experience of developing ILD. Logistic regression, area under curve, descriptive statistics and relevant visualizations will map the relationship between pneumonitis/ILD and patient’s health status. The study is currently enrolling; the protocol was approved by a central IRB. Clinical trial information: NCT06192004 .
Advanced renal cell cancer combination immunotherapy clinical trial (ARCITECT; HCRN GU 22-587).
Authors: Serzan Michael Thomas , Jegede Opeyemi , Alter Robert S. , Bilen Mehmet Asim , Braun David A. , Einstein David Johnson , Haas Naomi B. , Herchenhorn Daniel , King Jennifer , Runcie Karie , Sosman Jeffrey A. , Sternberg Cora N. , Yang Yuanquan (Aaron) , Signoretti Sabina , CHOUEIRI Toni K. , Atkins Michael B. 
Published: July 2024

TPS4614 Background: First-line treatment for patients with metastatic clear cell renal cell carcinoma (mccRCC) often includes an anti-PD1 inhibitor in combination with either an anti-CTLA inhibitor (IO/IO) or a VEGF receptor tyrosine kinase inhibitor (TKI) (IO/TKI). Although some patients treated with nivolumab/ipilimumab (Nivo/Ipi) (IO/IO) experience durable responses leading to treatment free intervals, over two-thirds experience disease progression. Resistance to Nivo (anti-PD1) monotherapy has been associated with increased presence of a subpopulation of Tregs in the tumor microenvironment. Botensilimab (Bot) is an IO agent that leverages novel FcyR-associated mechanisms of action to enhance T cell priming, deplete intratumoral Tregs and enhance myeloid activation. Combination botensilimab/balstilimab (Bot/Bal) (anti-CTLA/anti-PD1) has shown impressive anti-tumor activity in diseases where Nivo/Ipi has shown little to no efficacy. Methods: ARCITECT is a phase II, multicenter investigator initiated trial evaluating the efficacy and safety of Bot/Bal relative to Nivo/Ipi. Patients with mccRCC (favorable, intermediate, or poor risk), no prior systemic therapy (including adjuvant or neoadjuvant), and at least one measurable lesion as defined by RECIST 1.1 are eligible for enrollment. 120 patients will be randomized in a 2:1 fashion to Arm A (Bot/Bal induction followed by Bal maintenance) or Arm B (Nivo/Ipi induction followed by Nivo maintenance) each for a maximum of 2 years. Stratification factors include IMDC risk groups and sarcomatoid histology. The primary endpoint is overall response rate (ORR) per RECIST 1.1. We hypothesize that Bot/Bal will lead to a superior ORR (55%) relative to Nivo/Ipi (40%). This trial has > 90% power to detect the alternative hypothesis while maintaining a one-sided significance level of not more than 0.10 using the exact binomial. The study will be monitored for early stopping in favor of the null hypothesis based on a Simon’s two stage design. In the first stage, 69 patients will be enrolled (Arm A:46 and Arm B:23). If at the end of the first stage, Arm A has either at least 18/42 (42.8%) of eligible patients responding or an ORR at least numerically equivalent to that for eligible patients in Arm B, then the trial will progress to the second stage. The primary endpoint will be met if there are 38/80 responders (ORR > 47.5%) in Arm A. Key secondary endpoints include landmark progression-free survival, treatment-free survival and rates of immune-related adverse events. Correlative studies will explore immune and molecular predictors of response and resistance to IO/IO in tumor and blood. Clinical trial information: NCT05928806 .
Midline Low-Grade Gliomas of Early Childhood: Focus on Targeted Therapies
Authors: Papusha Ludmila , Zaytseva Margarita , Panferova Agnesa , Salnikova Ekaterina , Samarin Alexey , Vilesova Irina , Voronin Kirill , Protsvetkina Anastasia , Podlipaeva Svetlana , Zakharov Ilya , Usman Natalia , Hwang Eugene , Karachunskiy Alexander , Packer Roger J. , Novichkova Galina , Druy Alexander 
Published: July 2024

PURPOSE Midline low-grade gliomas (mLGGs) of early childhood have a poorer prognosis compared with tumors of other localizations and in older patients. LGGs are associated with aberrant activation of RAS-RAF-MEK pathway, and pharmacological inhibition of the pathway has therapeutic promise. The aim of this study was clinical and molecular characterization of infantile mLGGs, with emphasis on the efficacy of targeted kinase inhibition. PATIENTS AND METHODS This study enrolled 40 patients with mLGG age <3 years. The majority of the patients (30/40) received first-line chemotherapy (CT) as per International Society of Paediatric Oncology LGG 2004 guidelines. In all patients, molecular genetic investigation of tumor tissue by polymerase chain reaction and RNA sequencing was performed. The median follow-up was 3.5 years. RESULTS First-line CT failed in 24 of 30 recipients. The identified molecular profiles included KIAA1549::BRAF fusions in 26 patients, BRAF V600E in six patients, FGFR1::TACC1 fusions in two patients, and rare fusion transcripts in four patients. At disease progression, targeted therapy (TT) was initiated in 27 patients (22 patients received trametinib) on the basis of molecular findings. TT was administered for a median of 16 months, with partial response achieved in 12 of 26 (46%) patients in which response was evaluated. Severe adverse events were detected only on trametinib monotherapy: acute damage of GI or urinary mucosa complicated by hemorrhage and development of transfusion-dependent anemia in four patients and grade 3 skin toxicity in three patients. CONCLUSION mLGGs of early childhood are often aggressive tumors, resistant to CT, and frequently require alternative treatment. The majority of patients harbor druggable molecular targets and respond to molecular TT.
Clonal Hematopoiesis in Patients With Neuroendocrine Tumor Treated With Lutetium-177 and the Risk of Thrombocytopenia: A Prospective Study
Authors: Kusne Yael , Lasho Terra , Finke Christy , Elsabbagh Zaid , McCue Shaylene , Hobday Timothy , Starr Jason , Bekaii-Saab Tanios , Halfdanarson Thorvardur R. , Patnaik Mrinal M. , Ou Fang-Shu , Sonbol Mohamad Bassam 
Published: July 2024

PURPOSE Thrombocytopenia is a relatively common dose-limiting toxicity during peptide receptor radionuclide therapy (PRRT) in patients with NET. Although uncommon, some patients develop persistent cytopenia and eventually therapy-related myeloid neoplasm (t-MN), which has a dismal prognosis. As the indications for PRRT are expanding, it is important to investigate factors that may predict cytopenias during/after PRRT. We prospectively evaluated the prevalence of clonal hematopoiesis (CH) and cytopenia in patients with NET undergoing PRRT. MATERIALS AND METHODS Patients with metastatic NET with plan to receive four cycles of lutetium-177 were enrolled. CH was evaluated before PRRT using a panel of 220 genes with a targeted depth of ≥1,000×. Patients were followed during PRRT and every 3 months thereafter. RESULTS Of 37 patients enrolled, the median age was 68 years and 51.4% were male. Previous treatment exposures included alkylating agents in 30%, platinum agents in 8%, and external radiation in 13%. CH was detected in 35.1% using a variant allele frequency (VAF) cutoff of ≥2% and 45.9% with a VAF of ≥1%. The most common mutations were in age-related genes ( DNMT3A, TET2). CH was not associated with anemia or neutropenia; however, it was associated with lower platelet count at baseline and more time spent in a thrombocytopenic state during/after PRRT. Five patients had bone marrow biopsies (BMBs) because of sustained hematologic dysfunction post-PRRT, and of those, diagnoses included clonal cytopenia of undetermined significance (CCUS) in three and idiopathic cytopenia of undetermined significance (ICUS) in two. CONCLUSION CH is present in 35.1% of patients with NET and is associated with thrombocytopenia risk during PRRT. Future studies with long-term follow-up will delineate whether CH might be a predictor for higher risk of t-MN after PRRT.
Urachal abnormalities in the adult population. Is physical activity involved in clinical manifestation Literature review
Authors: Męczyńska Joanna , Mazurkiewicz Aleksandra , Mądry Wojciech , Marcicka Justyna , Kołodziej Magdalena , Saiuk Nazarii , Wojciechowska Adriana , Seredyński Tomasz , Kozicz Michał Andrzej , Salasa Weronika 
Published: July 2024

Introduction
The urachal anomaly is a developmental defect, a remnant of fetal life consisting of a patent connection between the dome of the urinary bladder and the umbilicus. It can take various forms. Most commonly it occurs in males, very rarely in adults. The main symptoms associated with this condition are: foul-smelling discharge from the umbilicus, abdominal pain, hematuria, or recurrent urinary tract infections. Imaging plays a crucial role in the diagnosis of the persistent urachus.
Aim of the studyThe aim of the study is to sentize doctors’ attention that patent urachus is the rare but possible diagnosis of acute abdomen pain in adults population and bring the proceedings.Materials and methods: An analysis of papers avaliable on Pubmed and Google Scholar was performed. The following key words: urachal anomalies, adults, abdomen pain, urachal remnants, urachal carcinoma were used.Results:Lately, thanks to modern precise imaging diagnostics, more valuable studies have been conducted, allowing to characterize residual ureteral remnants, which are most often asymptomatic in population of adults. However the manifestation of symptoms is mostly associated with infection of the mentioned area or a tumor transformation. There are at least two case reports which report that infection of urachal remnants could manifestate after intensive physical activity. It is worth in-depth interviewing. Studies indicate the necessity of surgical removal of persistent urachal anomalies, as they carry the risk of rapid growth and unfavorable prognosis of cancerous spread.
The Role of Health Behaviors in the Prevention and Management of Hypertension in Pregnancy: Current Guidelines and Perspectives
Authors: Makuch Rafał , Chrościcka Alicja , Gała Kamil , Czajka Andrzej , Lenard Paweł , Kucharski Adam , Michalska Sara , Pilarski Konrad , Dewicka Martyna , Wawrzyniak Alicja Maria 
Published: July 2024

Introduction and purpose
Hypertensive disorders during pregnancy are related to a greater risk of both maternal, and fetal as well as neonatal morbidity and mortality. This literature review aims to synthesize the health-promoting behaviors in daily life like diet, body mass, exercises in the prevention and management of hypertension and possible complications. Gestational hypertension occurs after 20 weeks' pregnancy and usually resolves after 6 weeks' postpartum. Diagnosis of gestational hypertension appears at values >140/90 mmHg in pregnant women. It has to be confirmed in out-of-office BP measurements, and if it's not possible by two separate medical appointments. According to current European guidelines, pharmacological therapy should be introduced in pregnant women with sustained elevated blood pressure ≥ 150/95 mmHg and at values >140/90 mmHg in pregnant women with gestational hypertension. Summarizing the current understanding of risk factors in hypertensive disorders during pregnancy seeks to enhance implementing positive health behaviors in prevention.
Materials and methods
The following review of studies was based on articles obtained from the PubMed and Google Scholar databases. Key search terms included gestational hypertension, pre-eclampsia, diet, physical activity, pharmacological treatment, obesity, prevention.
Conclusion
The literature review highlights the importance of BP measurements, diet restrictions, exercises of a low to moderate-intensity, pharmacological treatment during pregnancy as key factors in prevention of gestational hypertension. Greater awareness of hypertension in pregnancy encourages optimism for comprehensive research in the future.