The impact of financial crisis and austerity policies in Andalusia, Spain: disentangling the mechanisms of social inequalities in health through the perceptions and experiences of experts and the general population.

BACKGROUND: Andalusia has been one of the regions most damaged by the economic crisis in Spain. A qualitative study of the effects of the economic crisis and austerity policies in this region has been conducted within the framework of the IMPACT-A project. This research seeks to analyse the perceived impact of the crisis upon the health of the Andalusian population through the first-hand discourses of professionals from the health and social sectors on the one hand, and citizens of different socioeconomic status (SES) on the other. METHODS: A total of five focus groups and ten semi-structured interviews were conducted and analysed following an inductive process based on Grounded Theory (GT). RESULTS: Our results show a general perception among professionals: the financial crisis has either directly or indirectly affected population health in Andalusia, though mostly impacting low-income individuals who were already at risk of social exclusion. Professionals' perceptions have been confirmed through the discourses of citizens of a lower SES, which differ from those of middle and upper SES. CONCLUSION: Findings reveal some of the most salient consequences on the socially vulnerable groups and people at risk of social exclusion. In particular, our study highlights the importance of addressing three areas of priority action: mental health, unmet (basic and medical) needs, and decline in the health system.

Hereditary pancreatic cancer: related syndromes and clinical perspective.

Pancreatic cancer is a very aggressive disease with a poor prognosis. The majority of them are attributed to sporadic causes, especially to many modifiable risk factors such as tobacco or alcohol abuse. The principal histologic subtype of pancreatic cancer is ductal adenocarcinoma. Pancreatic neuroendocrine tumors, which constitute a more indolent entity, represent second type of pancreatic cancer in terms of incidence. Individuals with a family history of pancreatic cancer carry an increased risk of developing the disease, which may be related to an underlying hereditary component. Unfortunately, in the majority of these families the suspected germline genetic cause responsible of the disease will not be identified, but approximately in a 20% of the cases a hereditary cancer predisposition syndrome with increased risk of pancreatic cancer development can be recognized. This review will be focused on the leading hereditary cancer syndromes related to pancreatic ductal adenocarcinoma and pancreatic neuroendocrine tumors. Additionally, we will try to explain clinical aspects related to the identification of germline mutations in pancreatic cancer patients and their potential implications in oncologic treatment decisions.

Detection of genomic alterations in liquid biopsies from patients with non-small cell lung cancer using FoundationOne Liquid CDx: a cost-effectiveness analysis.

OBJECTIVE: Liquid biopsy (LB) is a non-invasive technique to detect genetic alterations by next-generation sequencing (NGS) when tissue biopsy is not available. This study aims to estimate in the Spanish setting, the cost-effectiveness of using FoundationOne Liquid CDx (F1L CDx), a novel blood-derived LB test based on NGS, versus non-molecular diagnosis (non-mDx) in patients with advanced non-small cell lung cancer (NSCLC) in whom tissue sampling is not feasible. METHODS: A joint model was developed combining a decision-tree with partitioned survival models to calculate the costs and health outcomes over a lifetime horizon, comparing F1L CDx in LB versus non-mDx. Only direct costs (expressed in € of 2023) were included and a 3% discount rate for future costs and effects was considered. Health outcomes were expressed in Life Years (LYs) and Quality-Adjusted Life Years (QALYs). Utilities and treatment efficacy were obtained from the literature. An expert panel of 11 Spanish oncologists determined the treatment allocation and validated all model inputs and assumptions. Several sensitivity analyses were performed to assess the robustness of the results. RESULTS: In a hypothetical cohort of 1,000 patients, LB using F1L CDx would detect 386 alterations, so those patients could be treated with targeted therapies or enrolled in clinical trials. Cost-effectiveness results showed that F1L CDx provides greater effectiveness than non-mDx (+383.95 LYs and +305.94 QALYs), with an additional cost of €2,898,308. The incremental cost-utility ratio was €9,473/QALY gained. The probabilistic sensitivity analysis confirmed the robustness of the cost-effectiveness results. LIMITATIONS: Various limitations inherent to cost-effectiveness analyses were described. CONCLUSION: LB with F1L CDx test is a cost-effective strategy in Spain for patients with advanced NSCLC without tissue sample available for molecular diagnosis, improving the personalized treatment of these patients.

Assessment of a New ROS1 Immunohistochemistry Clone (SP384) for the Identification of ROS1 Rearrangements in Patients with Non-Small Cell Lung Carcinoma: the ROSING Study.

INTRODUCTION: The ROS1 gene rearrangement has become an important biomarker in NSCLC. The College of American Pathologists/International Association for the Study of Lung Cancer/Association for Molecular Pathology testing guidelines support the use of ROS1 immunohistochemistry (IHC) as a screening test, followed by confirmation with fluorescence in situ hybridization (FISH) or a molecular test in all positive results. We have evaluated a novel anti-ROS1 IHC antibody (SP384) in a large multicenter series to obtain real-world data. METHODS: A total of 43 ROS1 FISH-positive and 193 ROS1 FISH-negative NSCLC samples were studied. All specimens were screened by using two antibodies (clone D4D6 from Cell Signaling Technology and clone SP384 from Ventana Medical Systems), and the different interpretation criteria were compared with break-apart FISH (Vysis). FISH-positive samples were also analyzed with next-generation sequencing (Oncomine Dx Target Test Panel, Thermo Fisher Scientific). RESULTS: An H-score of 150 or higher or the presence of at least 70% of tumor cells with an intensity of staining of 2+ or higher by the SP384 clone was the optimal cutoff value (both with 93% sensitivity and 100% specificity). The D4D6 clone showed similar results, with an H-score of at least 100 (91% sensitivity and 100% specificity). ROS1 expression in normal lung was more frequent with use of the SP384 clone (p < 0.0001). The ezrin gene (EZR)-ROS1 variant was associated with membranous staining and an isolated green signal FISH pattern (p = 0.001 and p = 0.017, respectively). CONCLUSIONS: The new SP384 ROS1 IHC clone showed excellent sensitivity without compromising specificity, so it is another excellent analytical option for the proposed testing algorithm.

Metástasis en hueso malar de tumor neuroendocrino oncocítico pulmonar / Malar bone metastasis of oncocytic neuroendocrine tumour of the lung

Las metástasis en hueso malar de tumores sólidos infraclaviculares son excepcionales. En aquellos de estirpe neuroendocrina, se debe considerar la expresión de receptores de somatostatina mediante diferentes técnicas de medicina nuclear para realizar terapias dirigidas. Se presenta un caso clínico de un varón de 66 años con neoplasia pulmonar con diferenciación oncocítica, cuyo debut es una metástasis malar de lenta evolución. Es tratado con lanreotido y ácido zolendrónico con enfermedad estable al año de seguimiento

Malar bone metastases of solid infraclavicular tumours are exceptional. Expression of somatostatin receptors should be considered in neuroendocrine strains, in order to carry out targeted therapies. We report a clinical case of a 66-year-old man with a tumour of the lung with oncocytic features, which debut is a malar metastasis of slow evolution. He is treated with Lanreotide and Zolendronic acid with stable disease at 1-year follow-up

Thymidylate synthase expression determines pemetrexed targets and resistance development in tumour cells.

Although treatment options for cancer patients are increasing every year, the drug resistance problem remains very present. It is very difficult to find a drug that acts equally on tumours of the same histology as the individual's genetic characteristics often determine the response to treatment. Furthermore, tumours that initially respond to anti-tumour therapy are able to adapt and develop resistance to the drug, while others do not. In addition, this usually implies resistance development to agents to which the cells have not been exposed, a phenomenon called cross-resistance or multidrug resistance. Given this situation, it has been suggested that the most appropriate treatment would be able to act in parallel on multiple pathways constitutively altered in tumour cells. Pemetrexed is a multitargeted antifolate that exerts its activity against folate-dependent enzymes involved in de novo pyrimidine and purine synthesis. It is currently in use in combination with cisplatin against malignant pleural mesothelioma and non-squamous non-small cell lung cancer with favourable results. By real-time RT-PCR gene expression assays and restoration viability assays we demonstrated that Pemetrexed targets folate-dependent enzymes involved in de novo biosynthesis of purines differently depending on the intrinsic genetic characteristics of the tumour. These differences did not, however, interfere either with the initial response to the drug or with the activation of apoptotic pathways. In addition, these genetic fingerprints can differentiate two groups of tumours: those capable of developing resistance to antifolate, and not capable. These results may be useful to employ targets gene expression as resistance markers, a valuable tool for identifying patients likely to receive combination therapy to prevent the development of resistance.