PrediCTC, liquid biopsy in precision oncology: a technology transfer experience in the Spanish health system.

PURPOSE: Management of metastatic disease in oncology includes monitoring of therapy response principally by imaging techniques like CT scan. In addition to some limitations, the irruption of liquid biopsy and its application in personalized medicine has encouraged the development of more efficient technologies for prognosis and follow-up of patients in advanced disease. METHODS: PrediCTC constitutes a panel of genes for the assessment of circulating tumor cells (CTC) in metastatic colorectal cancer patients, with demonstrated improved efficiency compared to CT scan for the evaluation of early therapy response in a multicenter prospective study. In this work, we designed and developed a technology transfer strategy to define the market opportunity for an eventual implementation of PrediCTC in the clinical practice. RESULTS: This included the definition of the regulatory framework, the analysis of the regulatory roadmap needed for CE mark, a benchmarking study, the design of a product development strategy, a revision of intellectual property, a cost-effectiveness study and an expert panel consultation. CONCLUSION: The definition and analysis of an appropriate technology transfer strategy and the correct balance among regulatory, financial and technical determinants are critical for the transformation of a promising technology into a viable technology, and for the decision of implementing liquid biopsy in the monitoring of therapy response in advanced disease.

Heterogeneity of breast cancer: etiology and clinical relevance.

Cancer progression is a dynamic process of clonal adaptation to changing microenvironments. From the single founder cell until the clinical detection of tumours, there are consecutive clonal expansions and a constant acquisition of genetic and epigenetic alterations, events that contribute to the generation of intra-tumor heterogeneity. In breast cancer intra-tumor heterogeneity can arise from the differentiation of stem-like cells along with the clonal selection during tumor progression, and represents a major challenge for the design of effective therapies. To infer breast cancer progression and its response to particular treatments it is important to understand the origins of the inter- and intra-tumor heterogeneity and the forces that control tumor evolution. Insights about the evolution of breast cancer heterogeneity would contribute to the design of most effective therapeutic strategies to target the tumors at single clon level. This review is intended to give a general overview about the origins of breast cancer heterogeneity and its impact in the clinical management of the disease.

[Efficacy, cost-effectiveness, and effects on quality of life of nutritional supplementation]. / Eficacia, coste-efectividad y efectos sobre la calidad de vida de la suplementación nutricional.

This article summarizes the main results and conclusions presented in the Symposium "Nutritional supplementation: evidences and experiences" that took place in the XXIIIrd SENPE Congress (2008). Protein energy malnutrition, that can affect 30-50% of hospitalized patients, increases both time of hospitalization and costs of medical care of this kind of patients. There is a lot of scientific evidences demonstrating that the use of nutritional supplementation improves nutritional status or prevents malnutrition in those patients who do not meet their nutritional needs with a conventional diet or an adapted one with no replacing intake from normal food. This is strengthened by the results that demonstrate the rol of nutritional supplements improving nutritional and functional parameters. Current bibliographic reviews focused on certain clinical frameworks (i.g. geriatrics, oncology), prove that nutritional supplements reduce complications related to pathology and to nutritional status, and also reduce length of hospitalization and mortality. More studies regarding to efficacy of oral nutritional supplements are needed. These studies should be carried out with a period of follow-up longer than the current published studies have. As well as effective, nutritional supplements become a save therapeutic intervention with no important adverse events that, according to bibliography, improve patient's functionality and quality of life. It is worth mentioning that nutritional supplements can be effective on certain kind of patients, for instance, malnourished elderly or elderly in risk of malnourishment, and hospitalized surgical patients. Scientific literature refers that it is necessary to carry out more studies, with an accurate methodology, which assess the effect of nutritional supplements on quality of life and its cost-effectiveness on malnourished patients regarding specific clinical situations. That would allow physicians to make clinical decisions based on evidences and cost analysis.

Incidence of obesity is lower in persons who consume olive oil.

We undertook a population-based cohort study in Pizarra (Spain). Anthropometric and nutritional variables were recorded for 613 persons. The type of fat used was determined by measurement of the fatty acids contained in cooking oil. Serum fatty acid was used as a biological marker of the type of fat consumed. Obesity incidence in persons who were not obese at baseline was greater in those who consumed sunflower oil (Group 1: 41.5 (95% CI, 25.4-67.8) cases per 1000 person-years) than in those who consumed olive oil or a mixture of oils (Group 2: 17.3 (95% CI, 11.6-25.8) cases per 1000 person-years). The risk of developing obesity over 6 years, adjusted for age, sex, physical activity, smoking, instruction level, energy intake and baseline BMI, was 2.3 (95% CI, 1.06-5.02) in group 1 compared with that in group 2. The increase in the prevalence of obesity in the free-living population is associated with the type of fatty acids in the diet.

[Pituitary apoplexy: retrospective study of 9 patients with hypophyseal adenoma]. / Apoplejía pituitaria: análisis retrospectivo en 9 pacientes con adenomas hipofisarios.

Pituitary apoplexy is an acute hemorrhage or ischemia infarction of the pituitary gland, almost invariably occurring in the presence of an pituitary adenoma. Although intratumoral bleeding occur in about 9.5 to 25% of pituitary adenomas, various series suggest that clinical apoplexy may be diagnosed in about 2% to 10% of the adenomas. In a retrospective study from 1988 to 1998 of 110 patients with hypophyseal adenomas, there were 9 cases with pituitary apoplexy, yielding an incidence of 8.2%. Their mean age was 52.4 +/- 12.8 años years, with a male to female ratio of 7:2. Symptoms observed were headache (89%), sudden visual deterioration (78%), vomiting (78%) and oculomotor nerves paresis (33%). The diagnosis of pituitary apoplexy was established by computerized tomographic scans, and hypophyseal macroadenoma with intratumoral bleeding was observed in every patient. Five patients underwent transphenoidal surgery. Improvement of visual deficit was observed in 3/4 (75%) and ocular paresis in 3/3 (100%) of affected patients. Four patients were treated conservatively with steroids. Two patients who had visual deficit recovered it completely without surgery. Two hypophyseal adenomas were resolved spontaneously after bleeding, one stayed unchanged and another presented recurrence of bleeding at six years of follow-up. Steroid and thyroid hormone replacement therapy was required in 62.5% of patients.