Impact of Age on Inflammation-Based Scores among Patients Diagnosed with Stage III Non-Small Cell Lung Cancer

[EN] Background: Inflammatory and nutritional indexes are prognostic factors in non-small cell lung cancer (NSCLC). Furthermore, a low grade of chronic inflammation has been described in the older population (inflammaging). We aimed to evaluate the neutrophil-to-lymphocyte ratio (NLR), the Prognostic Nutritional Index (PNI), the advanced lung cancer inflammation index (ALI), the platelet-to-lymphocyte ratio (PLR), and the Glasgow Prognostic Score (GPS) in young and older patients diagnosed with locally advanced NSCLC to determine if significant differences between these groups exist.Methods:We conducted a retrospective study analyzing the impact of age on the NLR, PNI, ALI, PLR, and GPS among patients diagnosed with stage III NSCLC at Hospital Universitario Doctor Peset between 2010 and 2015.Results:We included 124 patients (84 young, 40 older patients). The median hemoglobin level and leukocyte count were lower in the older patients (p= 0.0158 andp= 0.001, respectively). A higher median C-reactive protein level was also found in this group (p= 0.0095). Regarding specific inflammatory indexes, the PNI, comprising inflammatory and nutritional parameters, was lower among the older patients (p= 0.0463). The median NLR, ALI, and PLR were similar in both age groups. Moreover, no differences between the age groups were found in the percentage of patients showing high versus low NLR (cutoff point, 5) or ALI (cutoff point, 18) or in the different GPS groups.Conclusions:The baseline PNI, hemoglobin level, and lymphocyte count were lower among the older patients; furthermore, CRP was higher, possibly, because of a more prominent inflammatory status in older patients with lung cancer. No other immunological or nutritional analytical variables were different between the age groups.Palomar-Abril, V.; Soria-Comes, T.; Tarazona Campos, S.; Martín Ureste, M.; Giner-Bosch, V.; Maestu-Maiques, IC. (2020). Impact of Age on Inflammation-Based Scores among Patients Diagnosed with Stage III Non-Small Cell Lung Cancer. Oncology. 98(8):528-533. https://doi.org/10.1159/000506204S52853398

Validation of Cell-Free DNA Collection Tubes for Determination of EGFR Mutation Status in Liquid Biopsy from NSCLC Patients

Altres ajuts: Roche Farma S.A., Spain.Precision medicine has revolutionized the understanding and treatment of cancer by identifying subsets of patients who are amenable to specific treatments according to their molecular characteristics, as exemplified by epidermal growth factor receptor (EGFR) mutations in non-small cell lung cancer (NSCLC). Although tissue biopsy is the gold standard for determining molecular alterations in tumors, its limitations have prompted the development of new techniques for studying tumor biomarkers in liquid biopsies, such as mutation analysis in cell-free DNA (cfDNA). cfDNA analysis can accurately determine tumor progression and prognosis and more effectively identify appropriate targeted therapies. However, cfDNA is vulnerable, particularly during plasma sample shipping. We compared the cell- and DNA-stabilizing properties of cell-free DNA blood collection tubes (BCTs) with those of the traditional shipping method (frozen plasma) for EGFR mutation testing using the cobas ® EGFR Mutation Test v2 in a prospective cohort of 49 patients from three different Spanish hospitals. In total, 98 NSCLC samples, two from each patient, were studied; five of the 49 cases were considered invalid by cobas ® with one of the two shipping methods analyzed. After excluding these samples, we analyzed 88 samples from 44 patients. Considering the current methodology (frozen plasma) for sending samples as the gold standard, we evaluated the sensitivity and specificity of cfDNA BCT shipment. The global agreement between the two methods was 95.4%, with 100% sensitivity and 94.6% specificity for the cfDNA BCTs. cfDNA BCTs had a positive predictive value of 81.8% and negative predictive value of 100%. cfDNA BCTs have the same sensitivity for EGFR mutation analysis in liquid biopsy as the current methodology and very high specificity. They also have some additional advantages in terms of collection and further shipment. Therefore, cfDNA BCTs can be perfectly incorporated into the routine practice for EGFR mutation determination. Roche Farma S.A., Spain. The online version of this article (10.1007/s40487-019-00099-9) contains supplementary material, which is available to authorized users

Individualización de Carboplatino en el anciano con cáncer de pulmón no microcítico avanzado

Non small cell lung cancer (NSCLC) is frequently diagnosed in patients older than age 65 years. Elderly patients often have comorbidities associated with the antineoplasic treatment that request individualization of the chemotherapy. Treatment options are numerous and carboplatin (CbPt) is in the first line of treatment. Conventional doses of CbPt are individually adjusted applying the Calvert formulae (standar) that demands the accurate measure of renal function. The aim of this study is to develop a pharmacokinetic model in order to individualise the dose of CbPt in elderly patients in advanced NSCLC, and to characterize its bias and precision respect to the standard. The pharmacokinetic models for the unbound fraction of CpPt were obtained from concentration-time data of ultrafiltrate plasma samples of twenty-four advanced NSCLC men patients enrolled in the study. Age was significantly related to the carboplatin clearance, although is a confusion factor. The mean dose error, in percentage, was 5% (1-9%) in adult patients (Age< 65 years) and 25% (19-30%) in elderly patients. Consequently, CbPt the dose regimen in enderly patients, established by means of Calvert’s formula is overestimated and the exposure to the antineoplastic is higher than desired. The clinical relevance of these results requires the validation of the model with a new population group.El cáncer de pulmón no microcítico (CPNM) se diagnostica mayoritariamente en pacientes mayores de 65 años. Los pacientes ancianos presentan una elevada comorbilidad asociada al tratamiento antineoplásico que demanda la individualización de las pautas posológicas. Las opciones de tratamiento son abundantes y el carboplatino (CbPt) se encuentra entre los fármacos de primera línea. La dosis de CbPt se establece con la fórmula de Calvert (estándar) que requiere la medida exacta de la función renal. El objetivo de este trabajo es aportar un modelo farmacocinético que permita individualizar las dosis de CbPt en ancianos con CPNM avanzado y evaluar su exactitud y precisión respecto al estándar. Los modelos farmacocinéticos para el CbPt no unido a las proteínas plasmáticas, obtenidos con las concentraciones plasmáticas de una población de 24 pacientes varones con CPNM, indican que la edad es la covariable biométrica más estrechamente relacionada con el aclaramiento plasmático de CbPt, sin dejar por ello de ser un factor de confusión. El error relativo medio (ERM) de la dosis ha sido para los pacientes adultos (edad < 65 años) del 5% (1-9%) y para los pacientes ancianos del 25% (19-30%). Por consiguiente, la dosificación de CbPt con la fórmula de Calvert conduce a una sobredosificación en los pacientes ancianos, produciendo mayor exposición al fármaco de la deseada. El alcance clínico de estos hallazgos requiere su validación en una nueva población de pacientes

Prospective Exploratory Analysis of Angiogenic Biomarkers in Peripheral Blood in Advanced NSCLC Patients Treated With Bevacizumab Plus Chemotherapy: The ANGIOMET Study

[EN] Finding angiogenic prognostic markers in advanced non-small-cell lung cancer is still an unmet medical need. We explored a set of genetic variants in the VEGF-pathway as potential biomarkers to predict clinical outcomes of patients with non-small-cell lung cancer treated with chemotherapy plus bevacizumab. We prospectively analyzed the relationship between VEGF-pathway components with both pathological and prognostic variables in response to chemotherapy plus bevacizumab in 168 patients with non-squamous non-small-cell lung cancer. Circulating levels of VEGF and VEGFR2 and expression of specific endothelial surface markers and single-nucleotide polymorphisms in VEGF-pathway genes were analyzed. The primary clinical endpoint was progression-free survival. Secondary endpoints included overall survival and objective tumor response. VEGFR-1 rs9582036 variants AA/AC were associated with increased progression-free survival (p = 0.012 and p = 0.035, respectively), and with improved overall survival (p = 0.019) with respect to CC allele. Patients with VEGF-A rs3025039 harboring allele TT had also reduced mortality risk (p = 0.049) compared with the CC allele. The VEGF-A rs833061 variant was found to be related with response to treatment, with 61.1% of patients harboring the CC allele achieving partial treatment response. High pre-treatment circulating levels of VEGF-A were associated with shorter progression-free survival (p = 0.036). In conclusion, in this prospective study, genetic variants in VEGFR-1 and VEGF-A and plasma levels of VEGF-A were associated with clinical benefit, progression-free survival, or overall survival in a cohort of advanced non-squamous non-small-cell lung cancer patients receiving chemotherapy plus antiangiogenic therapy.The authors thank Drs. Blanca Piedrafita and Vanessa Marfil at Medical Statistics Consulting for medial writing services. RR also wish to acknowledge the support by the Asociacion Espanola Contra el Cancer (AECC).Jantus-Lewintre, E.; Massuti Sureda, B.; Gonzalez Larriba, JL.; Rodríguez-Abreu, D.; Juan, O.; Blasco, A.; Domine, M.... (2021). Prospective Exploratory Analysis of Angiogenic Biomarkers in Peripheral Blood in Advanced NSCLC Patients Treated With Bevacizumab Plus Chemotherapy: The ANGIOMET Study. Frontiers in Oncology. 11:1-11. https://doi.org/10.3389/fonc.2021.695038S1111

Prospective Exploratory Analysis of Angiogenic Biomarkers in Peripheral Blood in Advanced NSCLC Patients Treated With Bevacizumab Plus Chemotherapy: The ANGIOMET Study

Finding angiogenic prognostic markers in advanced non-small-cell lung cancer is still an unmet medical need. We explored a set of genetic variants in the VEGF-pathway as potential biomarkers to predict clinical outcomes of patients with non-small-cell lung cancer treated with chemotherapy plus bevacizumab. We prospectively analyzed the relationship between VEGF-pathway components with both pathological and prognostic variables in response to chemotherapy plus bevacizumab in 168 patients with non-squamous non-small-cell lung cancer. Circulating levels of VEGF and VEGFR2 and expression of specific endothelial surface markers and single-nucleotide polymorphisms in VEGF-pathway genes were analyzed. The primary clinical endpoint was progression-free survival. Secondary endpoints included overall survival and objective tumor response. VEGFR-1 rs9582036 variants AA/AC were associated with increased progression-free survival (p = 0.012 and p = 0.035, respectively), and with improved overall survival (p = 0.019) with respect to CC allele. Patients with VEGF-A rs3025039 harboring allele TT had also reduced mortality risk (p = 0.049) compared with the CC allele. The VEGF-A rs833061 variant was found to be related with response to treatment, with 61.1% of patients harboring the CC allele achieving partial treatment response. High pre-treatment circulating levels of VEGF-A were associated with shorter progression-free survival (p = 0.036). In conclusion, in this prospective study, genetic variants in VEGFR-1 and VEGF-A and plasma levels of VEGF-A were associated with clinical benefit, progression-free survival, or overall survival in a cohort of advanced non-squamous non-small-cell lung cancer patients receiving chemotherapy plus antiangiogenic therapy

Reorganization of Functional Networks in Mild Cognitive Impairment

Whether the balance between integration and segregation of information in the brain is damaged in Mild Cognitive Impairment (MCI) subjects is still a matter of debate. Here we characterize the functional network architecture of MCI subjects by means of complex networks analysis. Magnetoencephalograms (MEG) time series obtained during a memory task were evaluated by synchronization likelihood (SL), to quantify the statistical dependence between MEG signals and to obtain the functional networks. Graphs from MCI subjects show an enhancement of the strength of connections, together with an increase in the outreach parameter, suggesting that memory processing in MCI subjects is associated with higher energy expenditure and a tendency toward random structure, which breaks the balance between integration and segregation. All features are reproduced by an evolutionary network model that simulates the degenerative process of a healthy functional network to that associated with MCI. Due to the high rate of conversion from MCI to Alzheimer Disease (AD), these results show that the analysis of functional networks could be an appropriate tool for the early detection of both MCI and AD

Testing Lung Cancer Patients' and Oncologists' Experience with the Lalaby App for Monitoring the Quality of Life through Mobile Sensors and Integrated Questionnaires

[EN] As there is now a growing interest in mHealth apps for cancer patients, we here present and test the Lalaby App to monitor lung cancer patients' Quality of life (QoL) through mobile sensors and integrated questionnaires. The app was used in a 2-week study to register two lung cancer patients' activity without problems or interruptions. The patients frequently reported activities, symptoms, and questionnaires, indicating their engagement with the app. They registered their experience through the UEQ-S integrated into the app. Patient 1 mainly reported a neutral experience, while Patient 2 found it highly positive. They considered the app leading-edge and helpful and would recommend it to others, while both patients valued it positively (3.72 and 4.64 on a scale of 1-5). The app's aesthetics and its notifications helped their engagement. We found correlations between sensors' data and patients' QoL. We also detected QoL and functional status variations after treatment for both patients. After a "Tasks Test," two oncologists assessed the app's dashboard usability as excellent (SUS scores 85 and 87.5 on a 0-100 scale), easy-to-use and helpful. Their experience was positive (UEQ-S overall scale 2.81 (mean), -3 to +3 scale). The app allows monitoring the QoL of lung cancer patients remotely and in real-time while controlling patients' experience to stop the use if necessary, avoiding overwhelm.The authors acknowledge the support for this study provided by the Instituto de Tecnologias de la Informacion y Comunicaciones (ITACA) and the Hospital Universitario Dr. Peset de Valencia.Asensio-Cuesta, S.; Sánchez-García, Á.; Teresa Soria Comes; Maestu-Maiques, I.; Martín Ureste, M.; Conejero, JA.; Garcia-Gomez, JM. (2024). Testing Lung Cancer Patients' and Oncologists' Experience with the Lalaby App for Monitoring the Quality of Life through Mobile Sensors and Integrated Questionnaires. International Journal of Human-Computer Interaction. 40(3):1-12. https://doi.org/10.1080/10447318.2022.212156111240