Describing differences among populations of thoracic tumors patients under and over 80 years: Data analysis from the SLCG thoracic tumor registry.

OBJECTIVES: Cancer is a disease of old age; however, most studies usually included minority of patients fit elderly. The purpose is to investigate the clinical characteristics and genetic information of patients with thoracic tumors who are 80 years old or older compared to those under 80 years old. STUDY DESIGN AND METHODS: The Thoracic Tumor Registry (TTR) is a Spanish observational, prospective cohort study that included patients diagnosed with thoracic tumors. Data were collected from medical records related to sociodemographic, epidemiological, clinical, molecular/genetic, and treatment outcome variables. RESULTS: The total number of patients, recruited from August 2016 to April 2023, was 26.193 (93,1 % were younger than 80 years and 6,9 % were 80 years or older). In the group of older patients: the male ratio increased (72,9 % vs. 80 %); the number of elderly people who had never smoked or were ex-smokers increased (9,9 % vs. 21,1 % and 44,8 % vs. 61,3 %, respectively) and the number of current smokers decreased (43,3 % vs. 17,5 %); had higher ECOG performance status at diagnosis (for ECOG ≥ 2, 15 % vs. 32,9 %), and there were more patients with previous cancer (17,3 % vs. 28 %). The proportion of men is higher than that of women (73 % vs. 27 % in <80 years and 80 % vs. 20 % in ≥80 years). For all biomarkers, the proportion of patients who had a molecular determination was lower in older patients. There were no differences in terms of alterations in the biomarkers tested; except for EGFR, for which the positivity rate was higher in patients aged 80 years and older (25 % vs. 15,3 %). CONCLUSION: The proportion of older patients with targeted mutations is higher. So, at least at diagnosis, it should be proceeded in a standard way. Then, when it comes to treatment, comorbidities and patient's baseline situation should be considered. CLINICAL TRIAL REGISTRATION: NCT02941458.

Brief report: High incidence of peridiagnosis thromboembolic events in patients with BRAF-mutant lung cancer.

INTRODUCTION: We aimed to determine if advanced BRAF-mutant NSCLC has a higher thromboembolic events (TEE) rate than the expected. METHODS: Between 2008 and 2021, 182 patients with BRAF-mutant advanced NSCLC (BRAF V600E, n = 70; BRAF non-V600E, n = 112) were retrospectively identified from 18 centers in Spain. Patients received chemotherapy (n = 147), immunotherapy (n = 69), targeted therapy (n = 42), and immunotherapy + chemotherapy (n = 26). RESULTS: Incidence rate of TEE was 26.4 % (95%CI: 19.9 %-32.9 %). A total of 72 TEE were documented among 48 patients, as 18 patients (37.5 %) developed more than one event. Median time to TEE onset was 2 months, 69 % of TEE occurred in the peridiagnostic period (+/- 90 days from cancer diagnosis), and in 16 pts. (33 %) TEE was the form of lung cancer presentation. Although most TEE were only venous (82 %; PE, n = 33; DVT, n = 16), arterial events were reported in 31 % and occurred earlier, or TEE presented in atypical locations (13.9 %). TEE were related to high hospitalization rate (59 %), recurrence (23 %), and mortality (10.4 %) despite appropriate anticoagulant/antiaggregant treatment. Median OS in patients without-TEE was 19.4 months (95%CI: 4.6-34.1), and significantly shorter in patients with arterial-TEE vs venous-TEE vs both of them: 9.9 months (95%CI: 0-23.5) vs 41.7 months (95%CI: 11.3-72.2 m) vs 2.7 months (95%CI: 2.1-3.3), p = 0.001. Neither clinical or molecular features (BRAF V600E/non-V600E), nor cancer treatment was associated to TEE occurrence. Khorana score underperformed to predict thrombosis at cancer diagnosis, as only 19.2 % of patients were classified as high-risk. CONCLUSIONS: Thrombotic events represent a new clinical feature of BRAF-mutant lung cancer. Patients with almost a 30 % incidence of TEE should be offered systematic anticoagulation.

Sex Differences in the Efficacy of Immune Checkpoint Inhibitors in Neoadjuvant Therapy of Non-Small Cell Lung Cancer: A Meta-Analysis.

Non-small cell lung cancer (NSCLC) is one of the world's leading causes of morbidity and mortality. ICIs alone or combined with chemotherapy have become the standard first-line treatment of metastatic NSCLC. The impressive results obtained have stimulated our interest in applying these therapies in early disease stage treatments, as neoadjuvant immunotherapy has shown promising results. Among many of the factors that may influence responses, the role played by sex is attracting increased interest and needs to be addressed. Here, we aim to first review the state of the art regarding neoadjuvant ICIs, whether they are administered in monotherapy or in combination with chemotherapy at stages IB-IIIA, particularly at stage IIIA, before analyzing whether sex may influence responses. To this end, a meta-analysis of publicly available data comparing male and female major pathological responses (MPR) and pathological complete responses (pCR) was performed. In our meta-analysis, MPR was found to be significantly higher in females than in males, with an odds ratio (OR) of 1.82 (95% CI 1.13-2.93; p = 0.01), while pCR showed a trend to be more favorable in females than in males, but the OR of 1.62 was not statistically significant (95% CI 0.97-2.75; p = 0.08). Overall, our results showed that sex should be systematically considered in future clinical trials settings in order to establish the optimal treatment sequence.

Determination of hexanal and heptanal in saliva samples by an adapted magnetic headspace adsorptive microextraction for diagnosis of lung cancer.

In this work, an analytical method for the determination of two endogenous aldehydes (hexanal and heptanal) as lung cancer biomarkers in saliva samples is presented for the first time. The method is based on a modification of magnetic headspace adsorptive microextraction (M-HS-AME) followed by gas chromatography coupled to mass spectrometry (GC-MS). For this purpose, an external magnetic field generated by a neodymium magnet is used to hold the magnetic sorbent (i.e., CoFe2O4 magnetic nanoparticles embedded into a reversed-phase polymer) in the headspace of a microtube to extract the volatilized aldehydes. Subsequently, the analytes are desorbed in the appropriate solvent and the extract is injected into the GC-MS system for separation and determination. Under the optimized conditions, the method was validated and showed good analytical features in terms of linearity (at least up to 50 ng mL-1), limits of detection (0.22 and 0.26 ng mL-1 for hexanal and heptanal, respectively), and repeatability (RSD ≤12%). This new approach was successfully applied to saliva samples from healthy volunteers and those with lung cancer, obtaining notably differences between both groups. These results reveal the prospect of the method as potential diagnostic tool for lung cancer by saliva analysis. This work contributes to the Analytical Chemistry field presenting a double novelty: on the one hand, the use of M-HS-AME in bioanalysis is unprecedentedly proposed, thus expanding the analytical potential of this technique, and, on the other hand, the determination of hexanal and heptanal is carried out in saliva samples for the first time.

Particularities on Anatomy and Normal Postsurgical Appearances of the Hip.

Detailed knowledge of anatomy helps to understand pathologic processes. This article focuses on the anatomy and functionality of the hip, with emphasis on recently studied concepts and anatomic features that have an association with the development of symptoms. The most common anatomic variants posing a challenge for diagnosis and other common findings in asymptomatic patients are reviewed. Good understanding of the different surgical procedures helps in providing as much information as possible to guarantee a favorable outcome, improving prognosis. We review what are the commonly expected postsurgical appearances and the most common postsurgical complications.

Particularities on Anatomy and Normal Postsurgical Appearances of the Ankle and Foot.

The anatomy of the ankle and foot is complex, allowing for a wide range of functionality. The movements of the joints represent a complex dynamic interaction. A solid understanding of the characteristics and actions of the anatomic elements helps explain the mechanisms and patterns of injury. This article reviews the anatomy, with special focus on concepts that are the object of recent study and the features that favor the development of symptoms. Good understanding of the surgical procedures helps in providing information to guarantee a favorable outcome. We review the commonly expected postsurgical appearances and the most common postsurgical complications.

Imaging of Bone Marrow: From Science to Practice.

The study of the bone marrow may pose important challenges, due to its changing features over the life span, metabolic stress, and in cases of disease or treatment. Bone marrow adipocytes serve as storage tissue, but they also have endocrine and paracrine functions, contributing to local and systemic metabolism.Among different techniques, magnetic resonance (MR) has the benefit of imaging bone marrow directly. The use of advanced MR techniques for bone marrow study has rapidly found clinical applications. Beyond the clinical uses, it has opened up pathways to assess and quantify bone marrow components, establishing the groundwork for further study of its implications in physiologic and pathologic conditions.We summarize the features of the bone marrow as an organ, address the different modalities available for its study, with a special focus on MR advanced techniques and their addition to analysis in recent years, and review some of the challenges in interpreting the appearance of bone marrow.

Imaging of Metabolic Bone Diseases: The Spine View, Part I.

Metabolic bone diseases comprise a wide spectrum. Of them, osteoporosis is the most frequent and the most commonly found in the spine, with a high impact on health care systems and on morbidity due to vertebral fractures (VFs).This article discusses state-of-the-art techniques on the imaging of metabolic bone diseases in the spine, from the well-established methods to the latest improvements, recent developments, and future perspectives.We review the classical features of involvement of metabolic conditions involving the spine. Then we analyze the different imaging techniques for the diagnosis, characterization, and monitoring of metabolic bone disease: dual-energy X-ray absorptiometry (DXA) and DXA-based fracture risk assessment applications or indexes, such as the geometric parameters, Bone Strain Index, and Trabecular Bone Score; quantitative computed tomography; and magnetic resonance and ultrasonography-based techniques, such as radiofrequency echographic multi spectrometry. We also describe the current possibilities of imaging to guide the treatment of VFs secondary to metabolic bone disease.

Imaging of Metabolic Bone Diseases: The Spine View, Part II.

Metabolic bone diseases comprise a wide spectrum. Osteoporosis, the most frequent, characteristically involves the spine, with a high impact on health care systems and on the morbidity of patients due to the occurrence of vertebral fractures (VFs).Part II of this review completes an overview of state-of-the-art techniques on the imaging of metabolic bone diseases of the spine, focusing on specific populations and future perspectives. We address the relevance of diagnosis and current status on VF assessment and quantification. We also analyze the diagnostic techniques in the pediatric population and then review the assessment of body composition around the spine and its potential application. We conclude with a discussion of the future of osteoporosis screening, through opportunistic diagnosis and the application of artificial intelligence.

Effects of Radiation Therapy and Chemotherapy on the Musculoskeletal System.

The effects of radiation and chemotherapy on the musculoskeletal (MSK) system are diverse, and interpretation may be challenging. The different lines of treatment have effects on diseased and normal marrow, and they may lead to complications that must be differentiated from recurrence or progression. This review analyzes the changes induced by radiotherapy and chemotherapy in the MSK system in the adult and pediatric population, and the expected associated imaging findings. Treatments are often combined, so the effects may blend. Awareness of the spectrum of changes, complications, and their imaging appearances is paramount for the correct diagnosis. The assessment of body composition during and after treatment allows potential interventions to implement long-term outcomes and personalize treatments. Imaging techniques such as computed tomography or magnetic resonance imaging provide information on body composition that can be incorporated into clinical pathways. We also address future perspectives in posttreatment assessment.

Seroprevalence and immunological memory against SARS-CoV-2 in lung cancer patients: the SOLID study.

BACKGROUND: At present, we did not find any articles that studied seroprevalence and its persistence several months later in lung cancer patients in the setting of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Most patients with coronavirus disease 2019 (COVID-19) go on to develop antibodies (Abs) against viral proteins. However, it is not known how long these Abs last nor whether cancer treatments could affect the duration of immune response. METHODS: This prospective, longitudinal, multicenter serological study in the setting of SARS-CoV-2 infection was carried out in 50 Spanish hospitals. Eligibility criterion was the diagnosis of any lung cancer. The determination of anti-SARS-CoV-2 IgG Abs was performed by qualitative immuno-enzymatic assay using enzyme-linked immunosorbent assay (ELISA) kit from NovaLisa whose Abs target the recombinant antigen N of the nucleocapsid of SARS-CoV-2. The first Ab determination was performed between April 21 and June 3, 2020. The second Ab determination was performed in all previously seropositive patients, between September 10 and November 20, 2020. Study objectives were to prospectively determine seroprevalence in unselected lung cancer patients during the first wave of the pandemic; the persistence of immunity; protection or lack thereof against reinfection; and the influence of treatments on maintenance or loss of immunity. RESULTS: Of 1,500 patients, 128 were seropositive, overall prevalence of 8.5% seropositivity [95% confidence interval (CI): 7.2-10.1%]. Seventy-five percent were in active cancer treatment. Forty-seven point seven percent of IgG positive participants had experienced a symptomatic illness suspected of being infected with SARS-CoV-2 (95% CI: 38.8-56.6%). A second determination was performed on average 4.5 months later [interquartile range (IQR), 4.0-5.0 months] and obtained for 104 of the initially seropositive patients (81%), it could not be obtained in 24 patients, the majority due to death caused by disease progression (73%). In the second determination, IgG was not detected in 30.8% of patients. The severity of the infection, the need for hospitalization (P=0.032) and the presence of symptoms at diagnosis (P=0.02) were associated with persistence of immunity in the second determination. No variables or treatments received were associated with Abs loss. CONCLUSIONS: Immunity against SARS-CoV-2 does not appear to be compromised by treatment and persists beyond 4 months. Neither do mortality rates appear to be particularly high in this unselected population. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT04407143.

Characterization of Circulating T Cell Receptor Repertoire Provides Information about Clinical Outcome after PD-1 Blockade in Advanced Non-Small Cell Lung Cancer Patients.

Despite the success of immunotherapies in lung cancer, development of new biomarkers for patient selection is urgently needed. This study aims to explore minimally invasive approaches to characterize circulating T cell receptor beta chain (TCR-ß) repertoire in a cohort of advanced non-small cell lung cancer (NSCLC) patients treated with first-line pembrolizumab. Peripheral blood samples were obtained at two time points: i) pretreatment (PRE) and ii) first response assessment (FR). Next-generation sequencing (NGS) was used to analyze the hypervariable complementary determining region 3 (CDR3) of TCR-ß chain. Richness, evenness, convergence, and Jaccard similarity indexes plus variable (V) and joining (J)-gene usage were studied. Our results revealed that increased richness during treatment was associated with durable clinical benefit (DCB; p = 0.046), longer progression-free survival (PFS; p = 0.007) and overall survival (OS; p = 0.05). Patients with Jaccard similarity index ≥0.0605 between PRE and FR samples showed improved PFS (p = 0.021). Higher TRBV20-1 PRE usage was associated with DCB (p = 0.027). TRBV20-1 levels ≥9.14% in PRE and ≥9.02% in FR significantly increased PFS (p = 0.025 and p = 0.016) and OS (p = 0.035 and p = 0.018). Overall, analysis of circulating TCR-ß repertoire may provide information about the immune response in anti-PD-1 treated NSCLC patients; in this scenario, it can also offer important information about the clinical outcome.

Analysis of the Gut Microbiota: An Emerging Source of Biomarkers for Immune Checkpoint Blockade Therapy in Non-Small Cell Lung Cancer.

BACKGROUND: The human gut harbors around 1013-1014 microorganisms, collectively referred to as gut microbiota. Recent studies have found that the gut microbiota may have an impact on the interaction between immune regulation and anti-cancer immunotherapies. METHODS: In order to characterize the diversity and composition of commensal microbiota and its relationship with response to immune checkpoint blockade (ICB), 16S ribosomal DNA (rDNA) sequencing was performed on 69 stool samples from advanced non-small cell lung cancer (NSCLC) patients prior to treatment with ICB. RESULTS: The use of antibiotics and ICB-related skin toxicity were significantly associated with reduced gut microbiota diversity. However, antibiotics (ATB) usage was not related to low ICB efficacy. Phascolarctobacterium was enriched in patients with clinical benefit and correlated with prolonged progression-free survival, whereas Dialister was more represented in patients with progressive disease, and its higher relative abundance was associated with reduced progression-free survival and overall survival, with independent prognostic value in multivariate analysis. CONCLUSIONS: Our results corroborate the relation between the baseline gut microbiota composition and ICB clinical outcomes in advanced NSCLC patients, and provide novel potential predictive and prognostic biomarkers for immunotherapy in NSCLC.

Epidemiology, treatment, and survival in small cell lung cancer in Spain: Data from the Thoracic Tumor Registry.

BACKGROUND: Small-cell lung cancer (SCLC) is an aggressive disease with high metastatic potential and poor prognosis. Due to its low prevalence, epidemiological and clinical information of SCLC patients retrieved from lung cancer registries is scarce. PATIENTS AND METHODS: This was an observational multicenter study that enrolled patients with lung cancer and thoracic tumors, recruited from August 2016 to January 2020 at 50 Spanish hospitals. Demographic and clinical data, treatment patterns and survival of SCLC patients included in the Thoracic Tumor Registry (TTR) were analyzed. RESULTS: With a total of 956 cases, the age of 64.7 ± 9.1 years, 78.6% were men, 60.6% smokers, and ECOG PS 0, 1 or ≥ 2 in 23.1%, 53.0% and 23.8% of cases, respectively. Twenty percent of patients had brain metastases at the diagnosis. First-line chemotherapy (CT), mainly carboplatin or cisplatin plus etoposide was administered to >90% of patients. In total, 36.0% and 13.8% of patients received a second and third line of CT, respectively. Median overall survival was 9.5 months (95% CI 8.8-10.2 months), with an estimated rate of 70.3% (95% CI 67.2-73.4%), 38.9% (95% CI 35.4-42.4%), and 14.8% (95% CI 11.8-17.8%) at 6, 12 and 24 months respectively. Median progression-free survival was 6.3 months. Higher mortality and progression rates were significantly associated with male sex, older age, smoking habit, and ECOG PS 1-2. Long-term survival (> 2 years) was confirmed in 6.6% of patients, showing a positive correlation with better ECOG PS, poor smoking and absence of certain metastases at diagnosis. CONCLUSION: This study provides an updated overview of the clinical situation and treatment landscape of ES-SCLC in Spain. Our results might assist oncologists to improve current clinical practice towards a better prognosis for these patients.

Osimertinib in advanced EGFR-T790M mutation-positive non-small cell lung cancer patients treated within the Special Use Medication Program in Spain: OSIREX-Spanish Lung Cancer Group.

BACKGROUND: AURA study reported 61% objective response rate and progression-free survival of 9.6 months with osimertinib in patients with EGFR/T790M+ non-small cell lung cancer. Due to lack of real-world data, we proposed this study to describe the experience with osimertinib in Spain. METHODS: Post-authorization, non-interventional Special Use Medication Program, multicenter, retrospective study in advanced EGFR/T790M+ non-small cell lung cancer. One hundred-fifty five patients were enrolled (August 2016-December 2018) from 30 sites. PRIMARY OBJECTIVE: progression-free survival. Secondary objectives: toxicity profile, objective response rate, and use of health service resources. RESULTS: 70% women, median age 66. 63.9% were non-smokers and 99% had adenocarcinoma. Most patients had received at least one prior treatment (97%), 91.7% had received previous EGFR-tyrosine kinase inhibitors and 2.8% osimertinib as first-line treatment. At data cutoff, median follow-up was 11.8 months. One hundred-fifty five patients were evaluable for response, 1.3% complete response, 40.6% partial response, 31% stable disease and 11.6% disease progression. Objective response rate was 42%. Median progression-free survival was 9.4 months. Of the 155 patients who received treatment, 76 (49%) did not reported any adverse event, 51% presented some adverse event, most of which were grade 1 or 2. The resource cost study indicates early use is warranted. CONCLUSION: This study to assess the real-world clinical impact of osimertinib showed high drug activity in pretreated advanced EGFR/T790M+ non-small cell lung cancer, with manageable adverse events. TRIAL REGISTRATION: Clinical trial registration number: NCT03790397 .

High risk of thrombosis in patients with advanced lung cancer harboring rearrangements in ROS1.

INTRODUCTION: Based on the high incidence of thromboembolic events (TEs) observed in lung adenocarcinomas with ALK translocations and taking into account the biological proximity of ROS1 and ALK, we conducted a retrospective analysis of patients with advanced lung carcinoma carrying rearrangements in ROS1 from 23 centres in Spain and one centre in Portugal. METHODS: The main objective of the study was to analyse the incidence of TE in this population, looking for predictive risk factors, and its impact on overall survival. RESULTS: A total of 58 patients were included. The incidence of TEs throughout the disease was 46.6% (n = 27) with a median follow-up of 19 months (range: 1-78 months) and a median overall survival of 52 months in the total population and 50 months for the patients presenting TEs, with a hazards ratio of 1.12 (95% confidence interval: 0.47-2.65) p = 0.78. The majority of the events were venous (n = 24; 89%) and occurred in the ambulatory setting (n = 18; 67%). Almost half of the patients (n = 13; 48%) presented the TE in the peri-diagnostic period. CONCLUSIONS: The high incidence of thrombosis, especially during the cancer diagnosis process, requires special attention from a clinician. Despite the limitations of such a small descriptive study, its results are in accordance with previously reported data. It would be important to design prospective studies of antithrombotic prophylaxis in this population because of their possible impact in reducing the risk of TEs.

Sports and Metabolic Bone Disease.

Physical activity (PA) increases bone mass and bone strength through different mechanisms and also reduces the risk of falls in the elderly, through proprioception and balance training. The benefits seen in adolescence continue into adulthood. Exercise delays and attenuates the effects of osteoporosis, and particular sports activities may be recommended to improve bone mineral density (BMD) of the spine or regional BMD, improve balance, and prevent falls. Stress injuries related to exercise are more common in osteopenic and osteoporotic individuals.Sports activity may in some cases be detrimental for bone health, with nutrition restriction a frequent cause for negative effects of the practice of PA on bone. The examples are the so-called female athlete triad of menstrual dysfunction resulting in reduced estrogen levels, low energy due to malnutrition, and decreased BMD. A similar triad is described in male athletes. This review analyzes the effects of sport on bone metabolism and in particular its relationship with metabolic bone disease.

Fat and bone: the multiperspective analysis of a close relationship.

The study of bone has for many years been focused on the study of its mineralized component, and one of the main objects of study as radiology developed as a medical specialty. The assessment has until recently been almost limited to its role as principal component of the scaffolding of the human body. Bone is a very active tissue, in continuous cross-talk with other organs and systems, with functions that are endocrine and paracrine and that have an important involvement in metabolism, ageing and health in general. Bone is also the continent for the bone marrow, in the form of "yellow marrow" (mainly adipocytes) or "red marrow" (hematopoietic cells and adipocytes). Recently, numerous studies have focused on these adipocytes contained in the bone marrow, often referred to as marrow adipose tissue (MAT). Bone marrow adipocytes do not only work as storage tissue, but are also endocrine and paracrine cells, with the potential to contribute to local bone homeostasis and systemic metabolism. Many metabolic disorders (osteoporosis, obesity, diabetes) have a complex and still not well-established relationship with MAT. The development of imaging methods, in particular the development of cross-sectional imaging has helped us to understand how much more laid beyond our classical way to look at bone. The impact on the mineralized component of bone in some cases (e.g., osteoporosis) is well-established, and has been extensively analyzed and quantified through different radiological methods. The application of advanced magnetic resonance techniques has unlocked the possibility to access the detailed study, characterization and quantification of the bone marrow components in a non-invasive way. In this review, we will address what is the evidence on the physiological role of MAT in normal skeletal health (interaction with the other bone components), during the process of normal aging and in the context of some metabolic disorders, highlighting the role that imaging methods play in helping with quantification and diagnosis.