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La caracterització molecular dels tumors dels pacients i l'estudi de la seva evolució amb el temps són decisius pel correcte tractament del càncer. Tradicionalment, els tumors cerebrals s'han analitzat a partir d'una biòpsia de teixit, que suposa un risc pel pacient i no sempre permet accedir a una part representativa del tumor. Recentment, l'equip de Joan Seoane ha proposat utilitzar el líquid cefaloraquidi per fer-ne una biòpsia líquida. La tècnica és molt menys invasiva i permet detectar millor les mutacions en el tumor. La caracterización molecular de los tumores de los pacientes y el estudio de su evolución con el tiempo son decisivos para el correcto tratamiento del cáncer. Tradicionalmente, los tumores cerebrales se han analizado a partir de una biopsia de tejido, que supone un riesgo para el paciente y no siempre permite acceder a una parte representativa del tumor. Recientemente, el equipo de Joan Seoane ha propuesto utilizar el líquido cefalorraquídeo para hacer una biopsia líquida. La técnica es mucho menos invasiva y permite detectar mejor las mutaciones en el tumor. The identification of each tumour type along with its respective individual molecular makeup is critical in tackling cancer with greater precision. To date, the analysis of brain tumours has consisted of a biopsy, which poses a risk in itself and does not necessarily facilitate access to a representative part of the tumour. Recently, Joan Seoane's group proposed using cerebrospinal fluid for a liquid biopsy. This technique is much less invasive and allows detecting cancer mutations.

La caracterització molecular dels tumors dels pacients i l'estudi de la seva evolució amb el temps són decisius pel correcte tractament del càncer. Tradicionalment, els tumors cerebrals s'han analitzat a partir d'una biòpsia de teixit, que suposa un risc pel pacient i no sempre permet accedir a una part representativa del tumor. Recentment, l'equip de Joan Seoane ha proposat utilitzar el líquid cefaloraquidi per fer-ne una biòpsia líquida. La tècnica és molt menys invasiva i permet detectar millor les mutacions en el tumor. La caracterización molecular de los tumores de los pacientes y el estudio de su evolución con el tiempo son decisivos para el correcto tratamiento del cáncer. Tradicionalmente, los tumores cerebrales se han analizado a partir de una biopsia de tejido, que supone un riesgo para el paciente y no siempre permite acceder a una parte representativa del tumor. Recientemente, el equipo de Joan Seoane ha propuesto utilizar el líquido cefalorraquídeo para hacer una biopsia líquida. La técnica es mucho menos invasiva y permite detectar mejor las mutaciones en el tumor. The identification of each tumour type along with its respective individual molecular makeup is critical in tackling cancer with greater precision. To date, the analysis of brain tumours has consisted of a biopsy, which poses a risk in itself and does not necessarily facilitate access to a representative part of the tumour. Recently, Joan Seoane's group proposed using cerebrospinal fluid for a liquid biopsy. This technique is much less invasive and allows detecting cancer mutations.

BACKGROUND: During the last decade, the use of 5-aminolevulinic acid (5-ALA) has been steadily increasing in neurosurgery. The study's main objectives were to prospectively evaluate the effectiveness and safety of 5-ALA when used in clinical practice setting on high-grade gliomas' patients. METHODS: National, multicenter and prospective observational study. INCLUSION CRITERIA: authorized conditions of use of 5-ALA. EXCLUSION CRITERIA: contraindication to 5-ALA, inoperable or partial resected tumors, pregnancy and children. Epidemiological, clinical, laboratory, radiological, and safety data were collected. Effectiveness was assessed using complete resection of the tumor, and progression-free and overall survival probabilities. RESULTS: Between May 2010 and September 2014, 85 patients treated with 5-ALA were included, and 77 were suitable for the effectiveness analysis. Complete resection was achieved in 41 patients (54%). Surgeons considered suboptimal the fluorescence of 5-ALA in 40% of the patients assessed. The median duration of follow-up was 12.3 months. The progression-free survival probability at 6 months was 58%. The median duration overall survival was 14.2 months. Progression tumor risk factors were grade of glioma, age and resection degree; and death risk factors were grade of glioma and gender. No severe adverse effects were reported. At one month after surgery, new or increased neurological morbidity was 6.5%. Hepatic enzymes were frequently increased within the first month after surgery; however, they subsequently normalized, and this was found to have no clinical significance. CONCLUSION: In clinical practice, the 5-ALA showed a good safety profile, but the benefits related to 5-ALA have not been yet clearly shown. The improved differentiation expected by fluorescence between normal and tumor cerebral tissue was suboptimal in a relevant number of patients; in addition, the expected higher degree of resection was lower than in clinical trials as well as incomplete resection was not identified as a prognostic factor risk for death. Because optimal fluorescence was correlated to higher complete resection rate, further research is needed to identify patients (or tumors) with more surgery benefits when using the 5-ALA. Funding for this work was provided by the Spanish Ministry of Health (through two research projects which codes were: TRA-085 [convocatoria de ayudas para el fomento de la traslación de la aplicación de terapéutica de medicamentos de uso humano, huérfanos y terapias avanzadas de la Orden Ministerial SAS 2481/2009] and EC11-040 [convocatoria de ayudas para la investigación clínica independiente de la Orden Ministerial SPI 2885/ 2011]).

BACKGROUND: Antiangiogenic therapies for glioblastoma (GBM) such as bevacizumab (BVZ), have been unable to extend survival in large patient cohorts. However, a subset of patients having angiogenesis-dependent tumors might benefit from these therapies. Currently, there are no biomarkers allowing to discriminate responders from non-responders before the start of the therapy. METHODS: 40 patients from the randomized GENOM009 study complied the inclusion criteria (quality of images, clinical data available). Of those, 23 patients received first line temozolomide (TMZ) for eight weeks and then concomitant radiotherapy and TMZ. 17 patients received BVZ+TMZ for seven weeks and then added radiotherapy to the treatment. Clinical variables were collected, tumors segmented and several geometrical measures computed including: Contrast enhancing (CE), necrotic, and total volumes; equivalent spherical CE width; several geometric measures of the CE 'rim' geometry and a set of image texture measures. The significance of the results was studied using Kaplan-Meier and Cox proportional hazards analysis. Correlations were assessed using Spearman correlation coefficients. RESULTS: Kaplan-Meier and Cox proportional hazards analysis showed that total, CE and inner volume (p = 0.019, HR = 4.258) and geometric heterogeneity of the CE areas (p = 0.011, HR = 3.931) were significant parameters identifying response to BVZ. The group of patients with either regular CE areas (small geometric heterogeneity, median difference survival 15.88 months, p = 0.011) or those with small necrotic volume (median survival difference 14.50 months, p = 0.047) benefited substantially from BVZ. CONCLUSION: Imaging biomarkers related to the irregularity of contrast enhancing areas and the necrotic volume were able to discriminate GBM patients with a substantial survival benefit from BVZ. A prospective study is needed to validate our results. This work has been supported by Ministerio de Economía y Competitividad/FEDER, Spain [grant number MTM2015-71200-R], Consejería de Educación Cultura y Deporte from Junta de Comunidades de Castilla-La Mancha, Spain [grant number PEII-2014-031-P] and James S. Mc. Donnell Foundation 21st Century Science Initiative in Mathematical and Complex Systems Approaches for Brain Cancer [Special Initiative Collaborative – Planning Grant 220020420 and Collaborative award 220020450]. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

BackgroundPattern Recognition techniques can provide invaluable insights in the field of neuro-oncology. This is because the clinical analysis of brain tumors requires the use of non-invasive methods that generate complex data in electronic format. Magnetic Resonance (MR), in the modalities of spectroscopy (MRS) and spectroscopic imaging (MRSI), has been widely applied to this purpose. The heterogeneity of the tissue in the brain volumes analyzed by MR remains a challenge in terms of pathological area delimitation.Methodology/principal findingsA pre-clinical study was carried out using seven brain tumor-bearing mice. Imaging and spectroscopy information was acquired from the brain tissue. A methodology is proposed to extract tissue type-specific sources from these signals by applying Convex Non-negative Matrix Factorization (Convex-NMF). Its suitability for the delimitation of pathological brain area from MRSI is experimentally confirmed by comparing the images obtained with its application to selected target regions, and to the gold standard of registered histopathology data. The former showed good accuracy for the solid tumor region (proliferation index (PI)>30%). The latter yielded (i) high sensitivity and specificity in most cases, (ii) acquisition conditions for safe thresholds in tumor and non-tumor regions (PI>30% for solid tumoral region; ≤5% for non-tumor), and (iii) fairly good results when borderline pixels were considered.Conclusions/significanceThe unsupervised nature of Convex-NMF, which does not use prior information regarding the tumor area for its delimitation, places this approach one step ahead of classical label-requiring supervised methods for discrimination between tissue types, minimizing the negative effect of using mislabeled voxels. Convex-NMF also relaxes the non-negativity constraints on the observed data, which allows for a natural representation of the MRSI signal. This should help radiologists to accurately tackle one of the main sources of uncertainty in the clinical management of brain tumors, which is the difficulty of appropriately delimiting the pathological area.