Characteristics of Lung Cancer Patients With Asymptomatic or Undiagnosed SARS-CoV-2 Infections.

INTRODUCTION: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may be spread by individuals unaware they are infected. Such dissemination has heightened ramifications in cancer patients, who may need to visit healthcare facilities frequently, be exposed to immune-compromising therapies, and face greater morbidity from coronavirus disease 2019 (COVID-19). We determined characteristics of (1) asymptomatic, clinically diagnosed, and (2) serologically documented but clinically undiagnosed SARS-CoV-2 infection among individuals with lung cancer. PATIENTS AND METHODS: In a multicenter registry, individuals with lung cancer (regardless of prior SARS-CoV-2 vaccination or documented infection) underwent collection of clinical data and serial blood samples, which were tested for antinucleocapsid protein antibody (anti-N Ab) or IgG (N) levels. We used multivariable logistic regression models to investigate clinical characteristics associated with the presence or absence of symptoms and the presence or absence of a clinical diagnosis among patients with their first SARS-CoV-2 infection. RESULTS: Among patients with serologic evidence or clinically documented SARS-CoV-2 infection, 80/142 (56%) had no reported symptoms at their first infection, and 61/149 (40%) were never diagnosed. Asymptomatic infection was more common among older individuals and earlier-stage lung cancer. In multivariable analysis, non-white individuals with SARS-CoV-2 serologic positivity were 70% less likely ever to be clinically diagnosed (P = .002). CONCLUSIONS: In a multicenter lung cancer population, a substantial proportion of SARS-CoV-2 infections had no associated symptoms or were never clinically diagnosed. Because such cases appear to occur more frequently in populations that may face greater COVID-19-associated morbidity, measures to limit disease spread and severity remain critical.

Time-Dependent Effects of Clinical Interventions on SARS-CoV-2 Immunity in Patients with Lung Cancer.

In patients with lung cancer (LC), understanding factors that impact the dynamics of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) anti-spike antibody (SAb) titers over time is critical, but challenging, due to evolving treatments, infections, vaccinations, and health status. The objective was to develop a time-dependent regression model elucidating individual contributions of factors influencing SAb levels in LC patients using a prospective, longitudinal, multi-institutional cohort study initiated in January 2021. The study evaluated 296 LC patients-median age 69; 55% female; 50% stage IV. Blood samples were collected every three months to measure SAb levels using FDA-approved ELISA. Asymptomatic and unreported infections were documented through measurement of anti-nucleocapsid Ab levels (Meso Scale Discovery). Associations between clinical characteristics and titers were evaluated using a time-dependent linear regression model with a generalized estimating equation (GEE), considering time-independent variables (age, sex, ethnicity, smoking history, histology, and stage) and time-dependent variables (booster vaccinations, SARS-CoV-2 infections, cancer treatment, steroid use, and influenza vaccination). Significant time-dependent effects increasing titer levels were observed for prior SARS-CoV-2 infection (p < 0.001) and vaccination/boosters (p < 0.001). Steroid use (p = 0.043) and chemotherapy (p = 0.033) reduced titer levels. Influenza vaccination was associated with increased SAb levels (p < 0.001), independent of SARS-CoV-2 vaccine boosters. Prior smoking significantly decreased titers in females (p = 0.001). Age showed no association with titers. This GEE-based linear regression model unveiled the nuanced impact of multiple variables on patient anti-spike Ab levels over time. After controlling for the major influences of vaccine and SARS-CoV-2 infections, chemotherapy and steroid use were found to have negatively affected titers. Smoking in females significantly decreased titers. Surprisingly, influenza vaccinations were also significantly associated, likely indirectly, with improved SARS-CoV-2 titers.

An IL-4 signalling axis in bone marrow drives pro-tumorigenic myelopoiesis.

Myeloid cells are known to suppress antitumour immunity1. However, the molecular drivers of immunosuppressive myeloid cell states are not well defined. Here we used single-cell RNA sequencing of human and mouse non-small cell lung cancer (NSCLC) lesions, and found that in both species the type 2 cytokine interleukin-4 (IL-4) was predicted to be the primary driver of the tumour-infiltrating monocyte-derived macrophage phenotype. Using a panel of conditional knockout mice, we found that only deletion of the IL-4 receptor IL-4Rα in early myeloid progenitors in bone marrow reduced tumour burden, whereas deletion of IL-4Rα in downstream mature myeloid cells had no effect. Mechanistically, IL-4 derived from bone marrow basophils and eosinophils acted on granulocyte-monocyte progenitors to transcriptionally programme the development of immunosuppressive tumour-promoting myeloid cells. Consequentially, depletion of basophils profoundly reduced tumour burden and normalized myelopoiesis. We subsequently initiated a clinical trial of the IL-4Rα blocking antibody dupilumab2-5 given in conjunction with PD-1/PD-L1 checkpoint blockade in patients with relapsed or refractory NSCLC who had progressed on PD-1/PD-L1 blockade alone (ClinicalTrials.gov identifier NCT05013450 ). Dupilumab supplementation reduced circulating monocytes, expanded tumour-infiltrating CD8 T cells, and in one out of six patients, drove a near-complete clinical response two months after treatment. Our study defines a central role for IL-4 in controlling immunosuppressive myelopoiesis in cancer, identifies a novel combination therapy for immune checkpoint blockade in humans, and highlights cancer as a systemic malady that requires therapeutic strategies beyond the primary disease site.

Longitudinal nucleocapsid antibody testing reveals undocumented SARS-CoV-2 infections in patients with lung cancer.

Patients diagnosed with lung cancer (LC) exhibit increased susceptibility to SARS-CoV-2 infection. Rodilla et al. monitor the levels of plasma anti-nucleocapsid antibodies within a cohort of fully vaccinated LC patients and reveal that the actual infection rate is nearly twice the documented rate, indicating a significant prevalence of unreported cases.

Amivantamab plus lazertinib in osimertinib-relapsed EGFR-mutant advanced non-small cell lung cancer: a phase 1 trial.

Patients with epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC) often develop resistance to current standard third-generation EGFR tyrosine kinase inhibitors (TKIs); no targeted treatments are approved in the osimertinib-relapsed setting. In this open-label, dose-escalation and dose-expansion phase 1 trial, the potential for improved anti-tumor activity by combining amivantamab, an EGFR-MET bispecific antibody, with lazertinib, a third-generation EGFR TKI, was evaluated in patients with EGFR-mutant NSCLC whose disease progressed on third-generation TKI monotherapy but were chemotherapy naive (CHRYSALIS cohort E). In the dose-escalation phase, the recommended phase 2 combination dose was established; in the dose-expansion phase, the primary endpoints were safety and overall response rate, and key secondary endpoints included progression-free survival and overall survival. The safety profile of amivantamab and lazertinib was generally consistent with previous experience of each agent alone, with 4% experiencing grade ≥3 events; no new safety signals were identified. In an exploratory cohort of 45 patients who were enrolled without biomarker selection, the primary endpoint of investigator-assessed overall response rate was 36% (95% confidence interval, 22-51). The median duration of response was 9.6 months, and the median progression-free survival was 4.9 months. Next-generation sequencing and immunohistochemistry analyses identified high EGFR and/or MET expression as potential predictive biomarkers of response, which will need to be validated with prospective assessment. ClinicalTrials.gov identifier: NCT02609776 .

Modulation of chemoimmunotherapy efficacy in non-small cell lung cancer by sex and histology: a real-world, patient-level analysis.

BACKGROUND: It has been postulated that patient's sex impacts response to immunotherapy. Sex modulation of immunotherapy benefit, however, has not yet been explored using patient-level data, where potential confounders, as well as histologic type, can be accounted for. Here we investigated the association between sex and chemoimmunotherapy efficacy for non-small cell lung cancer (NSCLC) using a large, nation-wide dataset. PATIENTS & METHODS: Stage IV NSCLC patients diagnosed in 2015 were identified in the National Cancer Database (NCDB). Patients were treated with either chemoimmunotherapy or chemotherapy alone. The efficacy of the addition of immunotherapy treatment by sex was investigated using both an adjusted Cox proportional hazards model and propensity-score matching, in both the overall cohort and stratified by histological subtype. RESULTS: 2064 (16%) patients received chemoimmunotherapy and10,733 (84%) received chemotherapy alone. Adjusted survival analysis in the overall cohort showed that both males (hazards ratio (HR)adj: 0.80, 95% CI: 0.74-0.87) and females (HRadj: 0.83, 95% CI: 0.76-0.90) had better OS when treated with chemoimmunotherapy than chemotherapy alone, with no statistically significant interaction between sex and receipt of immunotherapy (p = 0.63). Propensity matching confirmed these results. However, for those with squamous cell histology, male patients derived more benefit from chemoimmunotherapy treatment than females (HRadj: 0.73, 95% CI: 0.58-0.91 vs HRadj: 1.03, 95% CI: 0.76-1.38; p for interaction = 0.07). CONCLUSION: Male patients with squamous cell carcinoma may derive more benefit from chemoimmunotherapy treatment. Histology likely plays an important role in how sex modulates immunotherapy efficacy.

Lung Cancer and Severe Acute Respiratory Syndrome Coronavirus 2 Infection: Identifying Important Knowledge Gaps for Investigation.

Patients with lung cancer are especially vulnerable to coronavirus disease 2019 (COVID-19) with a greater than sevenfold higher rate of becoming infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) COVID-19, a greater than threefold higher hospitalization rate with high complication rates, and an estimated case fatality rate of more than 30%. The reasons for the increased vulnerability are not known. In addition, beyond the direct impact of the pandemic on morbidity and mortality among patients with lung cancer, COVID-19, with its disruption of patient care, has also resulted in substantial impact on lung cancer screening and treatment/management.COVID-19 vaccines are safe and effective in people with lung cancer. On the basis of the available data, patients with lung cancer should continue their course of cancer treatment and get vaccinated against the SARS-CoV-2 virus. For unknown reasons, some patients with lung cancer mount poor antibody responses to vaccination. Thus, boosting vaccination seems urgently indicated in this subgroup of vulnerable patients with lung cancer. Nevertheless, many unanswered questions regarding vaccination in this population remain, including the magnitude, quality, and duration of antibody response and the role of innate and acquired cellular immunities for clinical protection. Additional important knowledge gaps also remain, including the following: how can we best protect patients with lung cancer from developing COVID-19, including managing care in patient with lung cancer and the home environment of patients with lung cancer; are there clinical/treatment demographics and tumor molecular demographics that affect severity of COVID-19 disease in patients with lung cancer; does anticancer treatment affect antibody production and protection; does SARS-CoV-2 infection affect the development/progression of lung cancer; and are special measures and vaccine strategies needed for patients with lung cancer as viral variants of concern emerge.

Predictors of chemoradiotherapy versus single modality therapy and overall survival among patients with unresectable, stage III non-small cell lung cancer.

INTRODUCTION: Concurrent chemoradiotherapy (cCRT) was the standard of care for patients with unresectable stage III non-small cell lung cancer (NSCLC) prior to the PACIFIC trial, however, patients also received single modality therapy. This study identified predictors of therapy and differences in overall survival (OS). METHODS: This retrospective study included stage III NSCLC patients aged ≥65 years, with ≥1 claim for systemic therapy (ST) or radiotherapy (RT) within 90 days of diagnosis, identified in SEER-Medicare data (2009-2014). Patients who had overlapping claims for chemotherapy and RT ≤90 days from start of therapy were classified as having received cCRT. Patients who received sequential CRT or surgical resection of tumor were excluded. Predictors of cCRT were analyzed using logistic regression. OS was compared between therapies using adjusted Cox proportional hazards models. RESULTS: Of 3,799 patients identified, 21.7% received ST; 26.3% received RT; and 52.0% received cCRT. cCRT patients tended to be younger (p <0.001), White (p = 0.002), and have a good predicted performance status (p<0.001). Patients who saw all three specialist types (medical oncologist, radiation oncologist, and surgeon) had increased odds of receiving cCRT (p<0.001). ST and RT patients had higher mortality risk versus cCRT patients (hazard ratio [95% CI]: ST: 1.38 [1.26-1.51]; RT: 1.75 [1.61, 1.91]); p<0.001). CONCLUSIONS: Several factors contributed to treatment selection, including patient age and health status, and whether the patient received multidisciplinary care. Given the survival benefit of receiving cCRT over single-modality therapy, physicians should discuss treatment within a multidisciplinary team, and be encouraged to pursue cCRT for patients with unresectable stage III NSCLC.

Treatment patterns and overall survival among patients with unresectable, stage III non-small-cell lung cancer.

Aim: To analyze treatment patterns and overall survival (OS) across time (2009-2014) among patients with unresected, stage III non-small-cell lung cancer (NSCLC). Patients & methods: Stage III NSCLC patients aged ≥65 years who initiated therapy were identified using SEER-Medicare data. Results: Among 4564 patients, 84% received chemotherapy (with or without radiotherapy), and 59% received chemoradiotherapy (CRT). Carboplatin + paclitaxel was the most frequent regimen. Median (interquartile range) OS among chemotherapy patients was 13.2 (6.0-28.9) months, and 14.8 (6.7-33.4) months among CRT patients. Among CRT patients, there was no difference in OS across years of CRT initiation. Conclusion: OS remained static across 2009-2014, indicating stagnancy in clinical outcomes for stage III NSCLC patients and a need for more effective therapeutic options.

Biomasa microbiana y respiración basal del suelo bajo sistemas agroforestales con cultivos de café / Microbial biomass and basal soil respiration under agroforestry systems with coffee crops

RESUMEN La actividad microbiológica es esencial para mantener la calidad de los suelos y los sistemas agroforestales surgen como alternativa, para el manejo agroecológico y sostenible del suelo. Este estudio evaluó el efecto de las variedades de café (Caturra y Catuaí) y de las fluctuaciones por épocas climáticas, sobre algunas propiedades microbiológicas del suelo, como indicadores de calidad, en un sistema agroforestal. Las muestras de suelo, se tomaron en la capa superior, a 5cm de profundidad, durante un año en épocas seca y lluviosa. Las mayores emisiones de CO2, se observaron en los suelos con la variedad Catuaí, en época seca. Los niveles de carbono de la biomasa microbiana (Cmic) no mostraron diferencias entre las variables estudiadas. Los valores obtenidos para el cociente metabólico (qCO2) fueron mayores en los suelos con la variedad Catuaí, mientras que el cociente microbiano (qMic) presentó los mayores valores en los suelos con la variedad Caturra. El cociente de eficiencia metabólica (qCO2.Corg -1) no mostró diferencias entre los suelos estudiados; sin embargo, sus niveles fueron más altos para las muestras tomadas durante la época seca. La microbiota del suelo denotó sensibilidad a los cambios por época climática de muestreo y tipo de variedad cultivada, mientras que las constantes ecofisiológicas resultaron sensiblemente apropiadas, para evaluar la calidad del suelo.

ABSTRACT The microbiological activity is essential to maintain soil quality, and agroforestry systems emerge as an alternative to the agro-ecological and sustainable land management. This work evaluated the effect of the Caturra and Catuaí coffee varieties, and the weather fluctuation on some microbiological properties of the soil, as indicators of quality in an agroforestry system. The soil samples were taken from the top layer with a depth of 5cm, during a year in dry and rainy seasons. The highest CO2 emissions were observed in soils with the Catuaí variety, in the dry season. On the other hand, Carbon levels of the microbial biomass (Cmic) did not show differences between the variables studied. The values obtained for the metabolic quotient (qCO2) were higher in soils with the Catuaí variety; while the microbial quotient (qMic) presented the highest values in soils with the Caturra variety. The metabolic efficiency ratio (qCO2.Corg-1) showed no differences between the studied soils, however, their levels were higher for the samples taken during the dry season. Soil microbiota showed sensitivity to changes by climatic period and by the type of variety, while the constant eco-physiological were substantially appropriate to evaluate soil quality and sensitive to changes by climatic period and variety of coffee grown in these agroecosystems.

Neoadjuvant Tyrosine Kinase Inhibition in Locally-advanced Non-small Cell Lung Cancer: Two Cases and a Brief Literature Review.

BACKGROUND: Despite their remarkable efficacy in metastatic non-small cell lung cancer (NSCLC), EGFR- and ALK-targeted therapies have not been shown to confer any survival benefit in stage III disease, even in subsets of patients with driver mutations. CASE STUDIES: Here, two patients with unresectable stage III NSCLC carrying mutations in the ALK (case 1) and EGFR (case 2) genes are presented. Treatment of the patient carrying an ALK mutation with an ALK inhibitor and the patient carrying an EGFR mutation with an EGFR inhibitor resulted in dramatic and durable responses. CONCLUSION: These cases demonstrated that ALK or EGFR mutation-positive stage III NSCLC patients can be treated with the corresponding inhibitors. They also highlight the urgent need for prospective data to assess their potential efficacy in order to improve patient outcomes.

Concurrent Chemotherapy and Radiation Therapy for Inoperable Locally Advanced Non-Small-Cell Lung Cancer.

The Oncology Grand Rounds series is designed to place original reports published in the Journal into clinical context. A case presentation is followed by a description of diagnostic and management challenges, a review of the relevant literature, and a summary of the authors' suggested management approaches. The goal of this series is to help readers better understand how to apply the results of key studies, including those published in Journal of Clinical Oncology, to patients seen in their own clinical practice. A 72-year-old man with a 40-pack-year tobacco history developed a cough and decreased exercise tolerance. A chest x-ray demonstrated a right-upper-lobe opacity. Chest computed tomography (CT) scan revealed a 2.5-cm mass in the right upper lobe with multiple mediastinal lymph node disease ( Fig 1 ). A positron emission tomography (PET) scan confirmed the lung lesion and the mediastinal lymphadenopathy without distant metastases. Brain magnetic resonance imaging results were negative. The biopsy specimen revealed adenocarcinoma with no actionable mutations present. Cervical mediastinoscopy was positive for carcinoma in level 2, 3, 4R, and 7 lymph nodes; level 4L was negative. The patient's stage was T1bN2M0, stage IIIA. His medical history was significant for hyperlipidemia and hypothyroidism. He had smoked one pack a day for 40 years and had quit 15 years earlier. Physical examination was unrevealing, and the patient had an Eastern Cooperative Oncology Group performance status of 0. Because of the extent of lung cancer in the mediastinum, the patient's cancer was deemed inoperable, and he was referred for consideration of concurrent chemotherapy and radiation.

Treatment Toxicity in Elderly Patients With Advanced Non-Small Cell Lung Cancer.

OBJECTIVES: Toxicity is a main concern limiting the use of chemotherapy and radiotherapy (RT) for elderly patients with non-small cell lung cancer (NSCLC). The objective of this study was to assess the rates of treatment-related toxicity among elderly stage IIIB and IV NSCLC patients. MATERIALS AND METHODS: We used the Surveillance, Epidemiology, and End Results registry linked to Medicare records to identify 2596 stage IIIB and 14,803 stage IV NSCLC patients aged 70 years and above, diagnosed in 2000 or later. We compared rates of toxicity requiring hospitalization according to treatment (chemotherapy, RT, or chemoradiation [CRT]) in unadjusted and adjusted models controlling for selection bias using propensity scores. RESULTS: Among stage IIIB patients, rates of any severe toxicity were 10.1%, 23.8%, 30.4%, and 39.2% for patients who received no treatment, RT, chemotherapy alone, and CRT, respectively. In stage IV patients, rates of any severe toxicity were 31.5% versus 13.5% among those treated with and without chemotherapy, respectively. In stage IIIB patients treated with CRT, the most common toxicities was esophagitis (odds ratio, 48.5; 95% confidence interval, 6.7-350.5). Among stage IV patients treated with chemotherapy, the risk of toxicity was highest for neutropenia (odds ratio, 8.4; 95% confidence interval, 6.1-11.5). CONCLUSIONS: Toxicity was relatively common among stage IIIB patients with up to a 6-fold increase in elderly individuals treated with CRT and a 4-fold increase in toxicities among stage IV patients. This information should be helpful to guide discussions about the risk-benefit ratio of chemotherapy and RT in elderly patients with advanced NSCLC.

The non-small cell lung cancer immune contexture. A major determinant of tumor characteristics and patient outcome.

Solid tumors, beyond mere accumulation of cancer cells, form a complex ecosystem consisting of normal epithelial cells, fibroblasts, blood and lymphatic vessels, structural components, and infiltrating hematopoietic cells including myeloid and lymphoid elements that impact tumor growth, tumor spreading, and clinical outcome. The composition of the immune microenvironment is diverse, including various populations of T cells, B cells, dendritic cells, natural killer cells, myeloid-derived suppressor cells, neutrophils, or macrophages. The immune contexture describes the density, location, and organization of these immune cells within solid tumors. In lung cancer, which is the deadliest type of cancer, and particularly in non-small cell lung cancer, its most prevalent form, reports have described some of the interactions between the tumor and the host. These data, in addition to articles on various types of tumors, provide a greater understanding of the tumor-host microenvironment interaction and stimulate the development of prognostic and predictive biomarkers, the identification of novel target antigens for therapeutic intervention, and the implementation of tools for long-term management of patients with cancer.

Dyadic psychosocial intervention for advanced lung cancer patients and their family caregivers: results of a randomized pilot trial.

BACKGROUND: Advanced lung cancer (LC) patients and their families have reported low self-efficacy for self-care/caregiving and high rates of distress, yet few programs exist to address their supportive care needs during treatment. This pilot study examined the feasibility, acceptability, and preliminary efficacy of a 6-session, telephone-based dyadic psychosocial intervention that was developed for advanced LC patients and their caregivers. The program was grounded in self-determination theory (SDT), which emphasizes the importance of competence (self-efficacy), autonomy (sense of choice/volition), and relatedness (sense of belonging/connection) for psychological functioning. The primary outcomes were patient and caregiver psychological functioning (depression/anxiety) and caregiver burden. The secondary outcomes were the SDT constructs of competence, autonomy, and relatedness. METHODS: Thirty-nine advanced LC patients who were within 1 month of treatment initiation (baseline) and their caregivers (51% spouses/partners) completed surveys and were randomized to the intervention or usual medical care. Eight weeks after baseline, they completed follow-up surveys. RESULTS: Solid recruitment (60%) and low attrition rates demonstrated feasibility. Strong program evaluations (mean, 8.6/10) and homework completion rates (88%) supported acceptability. Participants receiving the intervention evidenced significant improvements (P < .0001) in depression, anxiety, and caregiver burden in comparison with usual medical care. Large effect sizes (d ≥ 1.2) favoring the intervention were also found for patient and caregiver competence and relatedness and for caregiver autonomous motivation for providing care. CONCLUSION: These findings support intervention feasibility, acceptability, and preliminary efficacy. By empowering families with the skills to coordinate care and meet the challenges of LC together, this intervention holds great promise for improving palliative/supportive care services in cancer.

Prognostic significance of visceral pleural involvement in early-stage lung cancer.

BACKGROUND: Visceral pleural invasion (VPI) may impact non-small cell lung cancer (NSCLC) survival. However, previous studies are mixed as to whether VPI is an independent prognostic factor in early-stage cancers and whether its effect is size dependent. In the current American Joint Committee on Cancer (AJCC) staging system, VPI leads to upstaging of cancers < 3 cm but not of those 3 to 7 cm in size. METHODS: Using the Surveillance, Epidemiology, and End Results (SEER) registry, we identified 16,315 patients with stage I-II NSCLC treated with lobectomy. We used the Kaplan-Meier method and Cox regression to assess the association of VPI with lung cancer-specific (primary outcome) and overall survival. Based on these results, we created a revised VPI staging classification. RESULTS: Overall, 3,389 patients (21%) had VPI. Kaplan-Meier analysis stratified by tumor size showed worse cancer-specific survival in patients with VPI (P < .0001). VPI was independently associated with decreased lung cancer-specific survival (hazard ratio, 1.38; 95% CI, 1.29-1.47) after controlling for tumor size and other confounders; this effect was not size dependent. In our revised classification, tumors < 7 cm with VPI were upstaged to the next T category. CONCLUSIONS: VPI is a prevalent finding associated with worse prognosis in early-stage lung cancer, even among patients with tumors > 3 cm, a factor not captured in the current staging system. Patients with VPI may be considered candidates for more aggressive treatment.

Targeting angiogenesis from multiple pathways simultaneously: BIBF 1120, an investigational novel triple angiokinase inhibitor.

Angiogenesis is considered one of the major components of tumor progression and metastasis. Interfering with the formation and stabilization of tumor blood vessels could increase tumor response rates and may translate into improved clinical outcomes in cancer patients. The clinical efficacy demonstrated in phase III trials with bevacizumab, a monoclonal antibody that targets vascular endothelial growth factor ligand, suggests that targeting angiogenesis is a rational approach to cancer management. Agents that target additional proangiogenic intracellular signaling pathways also have the potential to contribute to our anticancer armamentarium. Novel targeted agents that have antiangiogenic properties have been developed in recent years such as sorafenib, sunitinib, vandetanib, and others. Many of them inhibit additional pathways beyond vascular endothelial growth factor signaling. One of these investigational targeted agents is a triple angiokinase inhibitor known as BIBF 1120. This compound targets not only vascular endothelial growth factor receptors, but also fibroblast growth factor receptors, and platelet-derived growth factor receptors. The preliminary clinical efficacy of BIBF 1120 is discussed in the context of the most relevant clinical data in several malignancies including non-small cell lung cancer.

Variation of the origin of aortic arch branches: in relationship with plates of atheroma / Variación del origen de las ramas del arco aórtico: relación con placas de ateromas

The aortic arch branches variations have called the attention of several authors, who have handled studies and classifications, both human and in different animals. The common trunk, which is between the brachiocephalic trunk and the common left carotid artery, is the most common variation. We conducted a descriptive and randomized study of the presence of the trunk mentioned before, trying to establish the possible relationship between this variation and the distribution plates of atheroma. The lumen observation makes it possible to define and check the distribution of the ostium, among the common ostium and the ones with common trunks. Regarding the plates of atheroma, it was found that there is a slight prevalence in common trunks cases, with respect to the classics (no variety) or the ones who had common ostium. In all cases, the presence of a plaque in the distal aortic arch was certified near the left subclavian artery. The knowledge of the existence of the common trunk sets up an act of academic interest, as practice interventions and diagnostic imaging and clinical work, since the presence of the common trunk might be related to the prevalence of the plates of atheroma at the level of its origin.

Las variaciones de las ramas del arco aórtico han llamado la atención de diversos autores, quienes han realizados estudios y clasificaciones, tanto en humanos, como en diferentes animales. El tronco común, entre el tronco braquiocefálico y la arteria carótida común izquierda, es la variación más frecuente. Realizamos un estudio descriptivo y randomizado de la presencia del mencionado tronco, tratando de verificar la posible relación entre dicha variación y la distribución de placas de ateroma. La observación luminal permitió precisar, entre los casos de ostios comunes y aquellos con troncos comunes, y comprobar la distribución de los ostios. En cuanto a las placas de ateroma, se observó una leve prevalencia en los casos de troncos comunes respecto de los clásicos (sin variedad) o de los que presentaron ostios comunes. En todos los casos se verificó la presencia de una placa en el arco aórtico distal, inmediato a la arteria subclavia izquierda. El conocimiento de la existencia del tronco común, constituye un hecho de interés académico, como práctico en intervencionismo, diagnóstico por imagen y la clínica. La presencia del tronco común pareciera estar relacionada con cierta prevalencia de placas de ateroma a nivel de su origen.