Nuestros investigadores

Jaime Gállego Pérez de Larraya

Publicaciones científicas más recientes (desde 2010)

Autores: Velasco, R., (Autor de correspondencia); Mercadal, S. ; Vidal, N.; et al.
Revista: JOURNAL OF NEURO-ONCOLOGY
ISSN 0167-594X  Vol. 148  Nº 3  2020  págs. 545 - 554
Introduction To assess the management of immunocompetent patients with primary central nervous system lymphomas (PCNSL) in Spain. Methods Retrospective analysis of 327 immunocompetent patients with histologically confirmed PCNSL diagnosed between 2005 and 2014 in 27 Spanish hospitals. Results Median age was 64 years (range: 19-84; 33% >= 70 years), 54% were men, and 59% had a performance status (PS) >= 2 at diagnosis. Median delay to diagnosis was 47 days (IQR 24-81). Diagnostic delay > 47 days was associated with PS >= 2 (OR 1.99; 95% CI 1.13-3.50; p = 0.016) and treatment with corticosteroids (OR 2.47; 95% CI 1.14-5.40; p = 0.023), and it did not improve over the years. Patients treated with corticosteroids (62%) had a higher risk of additional biopsies (11.7% vs 4.0%, p = 0.04) but corticosteroids withdrawal before surgery did not reduce this risk and increased the diagnostic delay (64 vs 40 days, p = 0.04). Median overall survival (OS) was 8.9 months [95% CI 5.9-11.7] for the whole series, including 52 (16%) patients that were not treated, and 14.1 months (95%CI 7.7-20.5) for the 240 (73.4%) patients that received high-dose methotrexate (HD-MTX)-based chemotherapy. Median OS was shorter in patients >= 70 years (4.1 vs. 13.4 months; p < 0.0001). Multivariate analysis identified age >= 65 years, PS >= 2, no treatment, and cognitive/psychiatric symptoms at diagnosis as independent predictors of short survival. Conclusions Corticosteroids withdrawal before surgery does not decrease the risk of a negative biopsy but delays diagnosis. In this community-based study, only 73.4% of patients could receive HD-MTX-based chemotherapy and OS remains poor, particularly in elderly patients >= 70 years.
Autores: Puigdelloses Vallcorba, Montserrat; González Huarriz, María Soledad; García Moure, Marc; et al.
Revista: NEURO-ONCOLOGY ADVANCES
ISSN 2632-2498  Vol. 2  Nº 1  2020  págs. vdaa010
Background: Glioblastoma (GBM) is the most common malignant primary brain tumor in adults. Circulating biomarkers may assist in the processes of differential diagnosis and response assessment. GBM cells release extracellular vesicles containing a subset of proteins and nucleic acids. We previously demonstrated that exosomes isolated from the serum of GBM patients had an increased expression of RNU6-1 compared to healthy subjects. In this exploratory study, we investigated the role of this small noncoding RNA as a diagnostic biomarker for GBM versus other brain lesions with some potential radiological similarities. Methods: We analyzed the expression of RNU6-1 in circulating exosomes of GBM patients (n = 18), healthy controls (n = 30), and patients with subacute stroke (n = 30), acute/subacute hemorrhage (n = 30), acute demyelinating lesions (n = 18), brain metastases (n = 21), and primary central nervous system lymphoma (PCNSL; n = 12) using digital droplet PCR. Results: Expression of RNU6-1 was significantly higher in GBM patients than in healthy controls (P = .002). RNU6-1 levels were also significantly higher in exosomes from GBM patients than from patients with non-neoplastic lesions (stroke [P = .05], hemorrhage [P = .01], demyelinating lesions [P = .019]) and PCNSL (P = .004). In contrast, no significant differences were found between patients with GBM and brain metastases (P = .573). Receiver operator characteristic curve analyses supported the role of this biomarker in differentiating GBM from subacute stroke, acute/subacute hemorrhage, acute demyelinating lesions, and PCNSL (P < .05), but again not from brain metastases (P = .575). Conclusions: Our data suggest that the expression of RNU6-1 in circulating exosomes could be useful for the differentiation of GBM from non-neoplastic brain lesions and PCNSL, but not from brain metastases.
Autores: Valentí Azcárate, Rafael (Autor de correspondencia); Esparragosa Vázquez, Inés; Toledano Illán, Carlos; et al.
Revista: NEUROMUSCULAR DISORDERS
ISSN 0960-8966  Vol. 30  Nº 1  2020  págs. 67 - 69
The rapidly growing field of cancer immunotherapy has led to the development of new treatments such as immune checkpoint inhibitors. These agents are monoclonal antibodies that enable tumor-reactive T cells to overcome regulatory mechanisms and produce effective antitumor responses. The use of immune checkpoint inhibitors is expected to progressively increase because they have shown promising therapeutic outcomes in multiple types of cancer and clinicians should be aware of their possible side-effects. We report a case of a man diagnosed with a non-microcytic lung carcinoma who started treatment with a combination of immune checkpoint inhibitors (Nivolumab and Ipilimumab). He subsequently developed binocular diplopia, fatigue, mild dyspnea and upper back pain resembling a myasthenia gravis presentation. Finally, a diagnosis of immune checkpoint inhibitor-related myositis and myocarditis was made. The detection of GFAP antibodies in CSF has unclear clinical and pathogenic significance and they may rather represent an epiphenomenon of the immune inflammation process.
Autores: Moreno Ajona, David; Prieto Azcárate, Elena; Grisanti Vollbracht, Fabiana Lucrecia; et al.
Revista: DIAGNOSTICS
ISSN 2075-4418  Vol. 10  Nº 6  2020  págs. 356
Brain positron emission tomography imaging with 18Fluorine-fluorodeoxyglucose (FDG-PET) has demonstrated utility in suspected autoimmune encephalitis. Visual and/or assisted image reading is not well established to evaluate hypometabolism/hypermetabolism. We retrospectively evaluated patients with autoimmune encephalitis between 2003 and 2018. Patients underwent EEG, brain magnetic resonance imaging (MRI), cerebrospinal fluid (CSF) sampling and autoantibodies testing. Individual FDG-PET images were evaluated by standard visual reading and assisted by voxel-based analyses, compared to a normal database. For the latter, three different methods were performed: two based on statistical surface projections (Siemens syngo.via Database Comparison, and 3D-SSP Neurostat) and one based on statistical parametric mapping (SPM12). Hypometabolic and hypermetabolic findings were grouped to identify specific patterns. We found six cases with definite diagnosis of autoimmune encephalitis. Two cases had anti-LGI1, one had anti-NMDA-R and two anti-CASPR2 antibodies, and one was seronegative.F-18-FDG-PET metabolic abnormalities were present in all cases, regardless of the method of analysis. Medial-temporal and extra-limbic hypermetabolism were more clearly depicted by voxel-based analyses. We found autoantibody-specific patterns in line with the literature. Statistical surface projection (SSP) methods (Neurostat and syngo.via Database Comparison) were more sensitive and localized larger hypermetabolic areas. As it may lead to comparable and accurate results, visual analysis of FDG-PET studies for the diagnosis of autoimmune encephalitis benefits from voxel-based analysis, beyond the approach based on MRI, CSF sample and EEG.
Autores: Martínez Velez, Naiara; García Moure, Marc; Marigil Sánchez, Miguel; et al.
Revista: NATURE COMMUNICATIONS
ISSN 2041-1723  Vol. 10  Nº 1  2019  págs. 2235
Pediatric high-grade glioma (pHGG) and diffuse intrinsic pontine gliomas (DIPGs) are aggressive pediatric brain tumors in desperate need of a curative treatment. Oncolytic virotherapy is emerging as a solid therapeutic approach. Delta-24-RGD is a replication competent adenovirus engineered to replicate in tumor cells with an aberrant RB pathway. This virus has proven to be safe and effective in adult gliomas. Here we report that the administration of Delta-24-RGD is safe in mice and results in a significant increase in survival in immunodeficient and immunocompetent models of pHGG and DIPGs. Our results show that the Delta-24-RGD antiglioma effect is mediated by the oncolytic effect and the immune response elicited against the tumor. Altogether, our data highlight the potential of this virus as treatment for patients with these tumors. Of clinical significance, these data have led to the start of a phase I/II clinical trial at our institution for newly diagnosed DIPG (NCT03178032).
Autores: Jablonska, Paola Anna (Autor de correspondencia); Diez Valle, Ricardo; Gállego Pérez de Larraya, Jaime; et al.
Revista: PLOS ONE
ISSN 1932-6203  Vol. 14  Nº 6  2019  págs. e0217881
Background Hypofractionated radiation therapy is a feasible and safe treatment option in elderly and frail patients with glioblastoma. The aim of this study was to evaluate the effectiveness of hypofractionated radiation therapy with concurrent temozolomide in terms of feasibility and disease control in primary glioblastoma patients with poor prognostic factors other than advanced age, such as post-surgical neurological complications, high tumor burden, unresectable or multifocal lesions, and potential low treatment compliance due to social factors or rapidly progressive disease. Material and methods GTV included the surgical cavity plus disease visible in T1WI-MRI, FLAIR-MRI and in the MET-uptake. The CTV was defined as the GTV plus 1.5-2 cm margin; the PTV was the CTV+0.3 cm margin. Forty, fourty-five, and fifty grays in 15 fractions were prescribed to 95% of PTV, CTV, and GTV, respectively. Treatment was delivered using IMRT or the VMAT technique. Simultaneously, 75 mg/m(2)/day of temozolomide were administered. Results Between January 2010 and November 2017, we treated a total of 17 patients. The median age at diagnosis was 68-years; median KPS was 50-70%. MGMT-methylation status was negative in 5 patients, and 8 patients were IDH-wildtype. Eight of 18 patients were younger than 65-years. Median tumor volume was 26.95cc; median PTV volume was 322cc. Four lesions were unresectable; 6 patients underwent complete surgical resection. Median residual volume was 1.14cc. Progression-free survival was 60% at 6 months, 33% at 1-year and 13% at 2-years (median OS = 7 months). No acute grade 3-5 toxicities were documented. Symptomatic grade 3 radiation necrosis was observed in one patient. Conclusions Patients with poor clinical factors other than advanced age can be selected for hypofractionated radiotherapy. The OS and PFS rates obtained in our series are similar to those in patients treated with standard fractionation, assuring good treatment adherence, low rates of toxicity and probable improved cost-effectiveness.
Autores: Schalper, K. A. ; Rodriguez-Ruiz, M. E.; Diez Valle, Ricardo; et al.
Revista: NATURE MEDICINE
ISSN 1078-8956  Vol. 25  Nº 3  2019  págs. 470 - 476
Glioblastoma is the most common primary central nervous system malignancy and has a poor prognosis. Standard first-line treatment, which includes surgery followed by adjuvant radio-chemotherapy, produces only modest benefits to survival1,2. Here, to explore the feasibility, safety and immunobiological effects of PD-1 blockade in patients undergoing surgery for glioblastoma, we conducted a single-arm phase II clinical trial (NCT02550249) in which we tested a presurgical dose of nivolumab followed by postsurgical nivolumab until disease progression or unacceptable toxicity in 30 patients (27 salvage surgeries for recurrent cases and 3¿cases of primary surgery for newly diagnosed patients). Availability of tumor tissue pre- and post-nivolumab dosing and from additional patients who did not receive nivolumab allowed the evaluation of changes in the tumor immune microenvironment using multiple molecular and cellular analyses. Neoadjuvant nivolumab resulted in enhanced expression of chemokine transcripts, higher immune cell infiltration and augmented TCR clonal diversity among tumor-infiltrating T lymphocytes, supporting a local immunomodulatory effect of treatment. Although no obvious clinical benefit was substantiated following salvage surgery, two of the three patients treated with nivolumab before and after primary surgery remain alive 33 and 28 months later.
Autores: Laspidea Ustés, Virginia; Puigdelloses Vallcorba, Montserrat; García Moure, Marc; et al.
Revista: NEURO-ONCOLOGY
ISSN 1522-8517  Vol. 21  2019  págs. 36 - 36
Autores: Laspidea Ustés, Virginia; Puigdelloses Vallcorba, Montserrat; Íñigo Marco, Ignacio; et al.
Revista: NEURO-ONCOLOGY
ISSN 1522-8517  Vol. 21  Nº Supl. 6  2019  págs. 122
Autores: Gállego Pérez de Larraya, Jaime; Esparragosa Vázquez, Inés; Puigdelloses Vallcorba, Montserrat; et al.
Revista: NEURO-ONCOLOGY
ISSN 1522-8517  Vol. 21  2019  págs. 37 - 38
Autores: Puigdelloses Vallcorba, Montserrat; Martínez Velez, Naiara; García Moure, Marc; et al.
Revista: NEURO-ONCOLOGY
ISSN 1522-8517  Vol. 21  2019  págs. 56 - 56
Autores: Aldave, G.; González Huarriz, María Soledad; Rubio Díaz-Cordoves, Ángel; et al.
Revista: NEURO-ONCOLOGY
ISSN 1522-8517  Vol. 20  Nº 7  2018  págs. 930 - 941
Background: Glioblastoma, the most aggressive primary brain tumor, is genetically heterogeneous. Alternative splicing (AS) plays a key role in numerous pathologies, including cancer. The objectives of our study were to determine whether aberrant AS could play a role in the malignant phenotype of glioma and to understand the mechanism underlying its aberrant regulation. Methods: We obtained surgical samples from patients with glioblastoma who underwent 5-aminolevulinic fluorescence-guided surgery. Biopsies were taken from the tumor center as well as from adjacent normal-appearing tissue. We used a global splicing array to identify candidate genes aberrantly spliced in these glioblastoma samples. Mechanistic and functional studies were performed to elucidate the role of our top candidate splice variant, BAF45d, in glioblastoma. Results: BAF45d is part of the switch/sucrose nonfermentable complex and plays a key role in the development of the CNS. The BAF45d/6A isoform is present in 85% of over 200 glioma samples that have been analyzed and contributes to the malignant glioma phenotype through the maintenance of an undifferentiated cellular state. We demonstrate that BAF45d splicing is mediated by polypyrimidine tract-binding protein 1 (PTBP1) and that BAF45d regulates PTBP1, uncovering a reciprocal interplay between RNA splicing regulation and transcription. Conclusions: Our data indicate that AS is a mechanism that contributes to the malignant phenotype of glioblastoma. Understanding the consequences of this biological process will uncover new therapeutic targets for this devastating disease.
Autores: Cayuela, N.; Simo, M. ; Majos, C.; et al.
Revista: EUROPEAN JOURNAL OF NEUROLOGY
ISSN 1351-5101  Vol. 25  Nº 2  2018  págs. 387 - 394
Background and purposeThe main aim of this study was to identify which patients with glioblastoma multiforme (GBM) have a higher risk of presenting seizures during follow-up. MethodsPatients with newly diagnosed GBM were reviewed (n = 306) and classified as patients with (Group 1) and without (Group 2) seizures at onset. Group 2 was split into patients with seizures during follow-up (Group 2A) and patients who never had seizures (Group 2B). The anatomical location of GBM was identified and compared by voxel-based lesion symptom mapping (discovery set). Seizure-susceptible brain regions obtained were assessed visually and automatically in external GBM validation series (n = 85). ResultsIn patients with GBM who had no seizures at onset, an increased risk of presenting seizures during follow-up was identified in the superior frontal and inferior occipital lobe, as well as in inferoposterior regions of the temporal lobe. Conversely, those patients with GBM located in medial and inferoanterior temporal areas had a significantly lower risk of suffering from seizures during follow-up. Additionally, the seizure-susceptible brain region maps obtained classified patients in the validation set with high positive and negative predictive values. ConclusionsTumor location is a useful marker to identify patients with GBM who are at risk of suffering from seizures during follow-up. These results may help to support the use of antiepileptic prophylaxis in a selected GBM population and to improve stratification in antiepileptic clinical trials.
Autores: Moreno Ajona, David; Yuste Ara, José Ramón; Martín Moreno, Paloma Leticia; et al.
Revista: JOURNAL OF NEUROVIROLOGY
ISSN 1355-0284  Vol. 24  Nº 4  2018  págs. 523 - 525
The human T-lymphotropic virus type 1 (HTLV-1) is a RNA retrovirus that infects a minimum of 5-10 million people worldwide. Transmission by cell-containing blood products and solid organ transplantation has been reported. Clinical disease occurs in about 5-10% of infected individuals and consists mainly in adult T cell leukemia and HTLV-1-associated myelopathy (HAM). We present a 54-year-old woman who underwent kidney transplant from cadaveric donor in March 2015. Donor also underwent cornea extraction for another recipient (corneal transplant protocol includes HTLV-1/2 serology). Twenty-four hours after completion of kidney transplant donor, HTLV-1 serology was revealed positive. Following experts' recommendations, once donor seropositivity was demonstrated, antiviral prophylaxis including zidovudine and raltegravir was initially given to our patient, in spite of which the patient developed HAM. Once the diagnosis of HAM was established, antiretroviral therapy was restarted, and intravenous pulses of methylprednisolone were periodically administered with transient initial improvement. Later on, the patient experienced neurological deterioration becoming wheelchair dependent. Since the occurrence of this case, HTLV-1 screening has become mandatory for solid organ transplantation in the Spanish province of Navarra, and the same should happen worldwide.
Autores: Diez Valle, Ricardo (Autor de correspondencia); Becerra Castro, María Victoria; Marigil Sánchez, Miguel; et al.
Revista: WORLD NEUROSURGERY
ISSN 1878-8750  Vol. 109  2018  págs. e845 - e852
BACKGROUND: Corticosteroids are routinely used to treat brain tumors. Although steroids have an immediate clinical benefit, their use can lead to a number of relevant complications, and a negative association with overall survival has been shown in glioblastoma (GBM) patients. There is no evidence in the literature regarding the ideal dose. We assessed the use of steroids in patients with GBM after resection surgery. METHODS: This is a cohort study of 131 newly diagnosed GBM patients that underwent tumor resection surgery. Dose of steroids was as low as possible, without a formal guideline. Fifteen patients were lost at baseline (retention rate, 88.5%). Our population for analysis included 114 patients that were still at risk of death at a landmark time point 2 months after surgery. RESULTS: Within 1 month of surgery, 93.9% of patients came off steroids, and 84.7% came off steroids before 2 weeks. One month after radiotherapy, 86 (75.4%) patients remained steroid-free and 28 (24.6%) were steroid-dependent. During 2235 person-months of follow-up, we documented 101 incident deaths. After adjusting for age, sex, Karnofsky Performance Scale score, MGMT promoter methylation, and extent of tumor resection, and time to surgery, the hazard ratio for the steroid-free group of patients was 0.46 (95% confidence interval, 0.28-0.77) compared with steroid-dependent patients. CONCLUSIONS: This study provides evidence for an inverse association between the lack of steroid dependency and mortality risk in patients whose steroid dosage was rapidly tapered after surgery. After resection, most patients can stop steroids within 2 weeks and finish radiotherapy without steroids.
Autores: Puigdelloses Vallcorba, Montserrat; González Huarriz, María Soledad; Zandio, B. ; et al.
Revista: NEURO-ONCOLOGY
ISSN 1522-8517  Vol. 20  Nº Supl. 3  2018  págs. 216 - 217
Autores: Esparragosa Vázquez, Inés; Inoges Sancho, Susana Inmaculada; López Díaz de Cerio, Ascensión; et al.
Revista: NEURO-ONCOLOGY
ISSN 1522-8517  Vol. 20  Nº Supl. 3  2018  págs. 243 - 243
Autores: Puigdelloses Vallcorba, Montserrat; Varela Guruceaga, Maider; González Huarriz, María Soledad; et al.
Revista: NEURO-ONCOLOGY
ISSN 1522-8517  Vol. 20  Nº Supl. 6  2018  págs. 36 - 36
Autores: Arbizu Lostao, Javier (Autor de correspondencia); Giuliani, A.; Gállego Pérez de Larraya, Jaime; et al.
Revista: THE QUARTERLY JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING
ISSN 1824-4785  Vol. 61  Nº 4  2017  págs. 386 - 404
PET using F-18-2-fluoro-2-deoxy-D-glucose (FDG-PET) has been gradually introduced in the diagnostic clinical criteria of the most prevalent neurodegenerative diseases. Moreover, an increasing amount of literature has shown that the information provided by FDG-PET enhances the sensitivity of standard imaging biomarkers in less frequent disorders in which an early differential diagnosis can be of paramount relevance for patient management and outcome. Therefore emerging uses of FDG-PET may be important in prion diseases, autoimmune encephalitis (AE) and amyotrophic lateral sclerosis. Interestingly, FDG-PET findings can also be observed in the early phases of these conditions, even in the presence of normal magnetic resonance imaging scans. Thalamic hypometabolism is a common finding in sporadic Creutzfeldt-Jacob disease and fatal familiar insomnia patients, with further cortical synaptic dysfunction in the former. Limbic and extra-limbic metabolic abnormalities (more often hypermetabolism) can be observed in AE, although specific patterns may be seen within different syndromes associated with antibodies that target neuronal surface or synaptic antigens. FDG-PET shows its usefulness by discriminating patients with amyotrophic lateral sclerosis associated to upper motor neuron onset that evolve to frontotemporal dementia. Besides visual and voxel based image analysis, multivariate analysis as interregional correlation analysis and independent/principal component analysis have been successfully implemented to PET images increasing the accuracy of the discrimination of neurodegenerative diseases. The clinical presentation and current diagnostic criteria of these neurologic disorders as well as the emerging usefulness of FDG-PET in the diagnostic workup are presented and discussed in this review.
Autores: Inoges Sancho, Susana Inmaculada; Tejada Solís, Sonia; López Díaz de Cerio, Ascensión; et al.
Revista: JOURNAL OF TRANSLATIONAL MEDICINE
ISSN 1479-5876  Vol. 15  Nº 1  2017  págs. Article number 104
Background: Prognosis of patients with glioblastoma multiforme (GBM) remains dismal, with median overall survival (OS) of about 15 months. It is therefore crucial to search alternative strategies that improve these results obtained with conventional treatments. In this context, immunotherapy seems to be a promising therapeutic option. We hypothesized that the addition of tumor lysate-pulsed autologous dendritic cells (DCs) vaccination to maximal safe resection followed by radiotherapy and concomitant and adjuvant temozolomide could improve patients' survival. Methods: We conducted a phase-II clinical trial of autologous DCs vaccination in patients with newly diagnosed patients GBM who were candidates to complete or near complete resection. Candidates were finally included if residual tumor volume was lower than 1 cc on postoperative radiological examination. Autologous DCs were generated from peripheral blood monocytes and pulsed with autologous whole tumor lysate. The vaccination calendar started before radiotherapy and was continued during adjuvant chemotherapy. Progression free survival (PFS) and OS were analyzed with the Kaplan-Meier method. Immune response were assessed in blood samples obtained before each vaccines. Results: Thirty-two consecutive patients were screened, one of which was a screening failure due to insufficient resection. Median age was 61 years (range 42-70). Karnofsky performance score (KPS) was 90-100 in 29%, 80 in 35.5% and 60-70 in 35.5% of cases. MGMT (O6-methylguanine-DNA-methyltransferase) promoter was methylated in 45.2% of patients. No severe adverse effects related to immunotherapy were registered. Median PFS was 12.7 months (CI 95% 7-16) and median OS was 23.4 months (95% CI 16-33.1). Increase in post-vaccination tumor specific immune response after vaccines (proliferation or cytokine production) was detected in 11/27 evaluated patients. No correlation between immune response and survival was found. Conclusions: Our results suggest that the addition of tumor lysate-pulsed autologous DCs vaccination to tumor resection and combined radio-chemotherapy is feasible and safe. A multicenter randomized clinical trial is warranted to evaluate the potential survival benefit of this therapeutic approach. Trial registration This phase-II trial was registered as EudraCT: 2009-009879-35 and ClinicalTrials.gov Identifier: NCT01006044 retrospectively registered.
Autores: Puigdelloses Vallcorba, Montserrat; González Huarriz, María Soledad; García Moure, Marc; et al.
Revista: NEURO-ONCOLOGY
ISSN 1522-8517  Vol. 19  Nº Supl 6  2017  págs. 34
Autores: Villar Fernández, Sara; Marcos Jubilar, María; Figueroa Mora, María del Rocío; et al.
Revista: HAEMATOLOGICA
ISSN 0390-6078  Vol. 101  Nº Supl.4  2016  págs. 231 - 231
Autores: Simonelli, M.; Sepulveda, J.; Brandes, A.; et al.
Revista: NEURO-ONCOLOGY
ISSN 1522-8517  Vol. 18  Nº Supl. 6  2016  págs. 24
BACKGROUND: CC-122 is a novel cereblon binding agent with multiple biological activities including potent immunomodulatory and anti-angiogenic effects. METHODS: Following establishment of oral CC-122 3mg daily (QD) as the maximum tolerated dose (Blood 122:2905 2013), patients with CNS tumors were enrolled in an expansion cohort. RESULTS: As of Jan. 13, 2016, 47 patients with relapsed/refractory GBM and other brain tumors were enrolled: GBM (n=39), grade IV oligodendroglioma (n=1), grade III anaplastic oligoastrocytoma (1) grade II-III astrocytomas (n=4) and PCNSL (n=2). CC-122 was well tolerated at 3¿mg QD (n=28), therefore, further dose escalation was explored in additional patients (n=19) at 4mg, 5mg or 6mg given either QD or on a 5/7days schedule. There were no DLTs, however, dose reduction (n=1) and interruptions (n=8) due to AEs were observed. The most common (¿ 5%) grade 3/4 AEs were neutropenia (10.6%), asthenia (6.4%) and general deterioration (6.4%). Drug-related serious AEs included febrile neutropenia, tumor hemorrhage, increase intracranial pressure, pulmonary embolism, interstitial lung disease, and acute respiratory distress syndrome (ARDS). AEs led to discontinuation in 10.6% of patients. 32 patients were evaluable for efficacy as of the cutoff date. The median PFS for patients was 58 days (Min-Max: 17-295, 95% CI: 50-111), while 21% of patients were progression-free at 6 months. CC-122 treatment resulted in a median increase from baseline of 86%, 133% and 165% in activated and memory cytotoxic T cells and activated helper T cells (all P<0.05), respectively, at Cycle 1 Day 15 in peripheral blood. CC-122 also activated T cells ex vivo as measured by increased levels of IFNg (131%) and IL-2 (685%) compared to baseline (both P<0.05). Preliminary CC-122 PK data suggest dose proportional increase in exposure in GBM patients. CONCLUSION: CC-122 is well tolerated. PK/PD analyses with correlation to clinical response are ongoing.
Autores: Tejada Solís, Sonia; Diez Valle, Ricardo; Gállego Pérez de Larraya, Jaime; et al.
Revista: NEURO-ONCOLOGY
ISSN 1522-8517  Vol. 18  Nº Supl.6  2016  págs. 4
Autores: Ortega Cubero, Sara; Pagola Lorz, María Inmaculada; Luquin Piudo, María Rosario Isabel; et al.
Revista: NEUROLOGÍA (BARCELONA. ED. IMPRESA)
ISSN 0213-4853  Vol. 30  Nº 3  2014  págs. 144 - 152
Introducción Las prionopatías representan hasta el 62% de los casos de demencia rápidamente progresiva (DRP) en los que se alcanza un diagnóstico definitivo. La variabilidad de los síntomas y signos iniciales y las diferencias en su evolución dificultan el diagnóstico precoz. Métodos Estudio retrospectivo en el que se incluye a pacientes con prionopatía probable o definitiva, que acudieron a la consulta de Neurología de nuestro centro durante el periodo 1999-2012. Se describen las características clínicas y los resultados de las exploraciones complementarias (proteína 14-3-3, EEG, RM, PET-FDG y análisis genético), con la finalidad de identificar qué marcadores permiten un diagnóstico precoz. Resultados Se describe a 14 pacientes: 6 con enfermedad de Creutzfeldt-Jakob esporádica (ECJe) definitiva, 3 con ECJe probable, 4 con insomnio familiar fatal y uno con la nueva variante de la enfermedad de Creutzfeldt-Jakob. La mediana de edad al diagnóstico fue de 54 años y la mediana de supervivencia de 9,5 meses. El trastorno del ánimo fue el síntoma inicial más frecuente, seguido de inestabilidad de la marcha y deterioro cognitivo. La proteína 14-3-3 fue positiva en el líquido cefalorraquídeo en 7 de 11 pacientes y el EEG mostró signos típicos en 2 de 12 pacientes explorados. El estudio de neuroimagen mostró alteraciones en 13 de los 14 pacientes. Conclusiones Además de la DRP, el trastorno conductual y de la marcha son síntomas iniciales frecuentes en las prionopatías. En nuestra serie, las pruebas complementarias más útiles para apoyar el diagnóstico fueron la RM y la PET-FDG.
Autores: Tejada Solís, Sonia; Aldave Orzaiz, Guillermo; Marigil Sánchez, Miguel; et al.
Revista: JOURNAL OF NEURO-ONCOLOGY
ISSN 0167-594X  Vol. 116  Nº 1  2014  págs. 169-175
Our purpose was to analyze the pattern of failure in glioblastoma (GBM) patients at first recurrence after radiotherapy and temozolomide and its relationship with different factors. From 77 consecutive GBM patients treated at our institution with fluorescence guided surgery and standard radiochemotherapy, 58 first recurrences were identified and included in a retrospective review. Clinical data including age, Karnofsky performance score, preoperative tumor volume and location, extend of resection, MGMT promoter methylation status, time to progression (PFS), overall survival (OS) and adjuvant therapies were reviewed for every patient. Recurrent tumor location respect the original lesion was the end point of the study. The recurrence pattern was local only in 65.5% of patients and non-local in 34.5%. The univariate and multivariate analysis showed that greater preoperative tumor volume in T1 gadolinium enhanced sequences, was the only variable with statistical signification (p < 0.001) for increased rate of non-local recurrences, although patients with MGMT methylation and complete resection of enhancing tumor presented non-local recurrences more frequently. PFS was longer in patients with non-local recurrences (13.8 vs. 6.4 months; p = 0.019, log-rank). However, OS was not significantly different in both groups (24.0 non-local vs. 19.3 local; p = 0.9). Rate of non-local recurrences in our series of patients treated with fluorescence guided surgery and standard radiochemotherap
Autores: Palma Carazo, José Alberto; Fernández Torrón, Roberto; Esteve Belloch, Patricia; et al.
Revista: CLINICAL NEUROLOGY AND NEUROSURGERY
ISSN 0303-8467  Vol. 115  Nº 1  2013  págs. 19-25
Introduction: Leptomeningeal carcinomatosis (LC) is a devastating complication occurring in 5% of all patients with cancer. To date there are no well-established prognostic markers in patients with LC, except for the presence of cerebrospinal fluid (CSF) blocks and the Karnofsky performance status scale (KPS). We aimed to identify clinical, neuroradiologic and CSF prognostic factors related to LC survival and to develop an easy-to-use Prognostic Scoring Scale (PSS) to identify patients who are more likely to benefit from receiving treatment. Methods: Single-center retrospective study evaluating patients who had a diagnosis of LC during a 10-year period. Diagnosis was made by malignant cytology or imaging; suspicious cases treated as LC were also included. Results: Fifty patients with LC were analyzed (58% women). Median age was 54.4 years, and KPS was 60%. The most common types of tumor were breast (35%), lung (24%), and hematologic malignancies (16%). Thirty-two percent of patients were diagnosed by imaging, 22% by cytology, and 40% by both. Median overall survival (OS) was 10 weeks (95% confidence interval 5.1-14.9). Median OS for patients who received specific treatment was 21.2 weeks vs. 6.38 weeks for patients receiving supportive care only (p < 0.001). In multivariate analysis, initial KPS, initial CSF protein level (<112 mg/dL) and time from diagnosis of primary tumor to diagnosis of LC (>67 weeks) were significant and independent predictors of increased survival. Conclusions: Prognosis remains poor in LC. The predictive factors for patients with LC here identified could help to improve the selection of patients who are more likely to benefit from receiving treatment. (C) 2012 Elsevier B.V. All rights reserved.
Autores: Gállego Pérez de Larraya, Jaime; Irimia Sieira, Pablo; Martínez Vila, Eduardo Antonio; et al.
Revista: JOURNAL OF CLINICAL ULTRASOUND
ISSN 0091-2751  Vol. 40  Nº 8  2012  págs. 479 - 485
Background. The assessment of carotid intima-media thickness (CIMT) may improve cardiovascular risk prediction. The optimal protocol for CIMT measurement is unclear. CIMT may be measured in the common carotid artery (CCA), carotid bifurcation (CB), and internal carotid artery (ICA), but measurements from CB and ICA are more difficult to obtain. We studied the influence of body mass index (BMI) and atheroma plaques on the capacity to obtain CIMT measurements at different carotid sites. Methods. Using an automatic system, CIMT was measured in 700 subjects aged 4575, in the near and far walls of CCA, CB, and ICA bilaterally. The presence of atheroma plaques, BMI and vascular risk factors were recorded. Results. CIMT measurements in CCA were possible in all except one subject. It was not possible to obtain CIMT measurements at CB or ICA in 24.1% of normal weight and 58.8% of obese subjects. The likelihood of obtaining CIMT measurement at all carotid sites decreased as the BMI increased. Atheroma plaques in a carotid segment did not preclude CIMT measurement at this site. Conclusions. CIMT measurements in distal carotid segments are more challenging in obese subjects. Measuring CIMT at CCA remains feasible in obese subjects and should be the primary endpoint in these subjects. Nevertheless, CB and ICA measurements, when feasible, would improve risk classification.
Autores: Diez Valle, Ricardo; López Díaz de Cerio, Ascensión; Inoges Sancho, Susana Inmaculada; et al.
Revista: WORLD JOURNAL OF CLINICAL ONCOLOGY
ISSN 2218-4333  Vol. 3  Nº 11  2012  págs. 142-149
Active immunotherapy with tumor lysate-pulsed, autologous dendritic cells is feasible, safe, well tolerated and biologically efficacious. A phase-II study is ongoing to possibly improve further on our very encouraging clinical results.
Autores: Gállego Pérez de Larraya, Jaime; Palma Carazo, José Alberto; Carmona Iragui, María; et al.
Revista: JOURNAL OF NEURO-ONCOLOGY
ISSN 0167-594X  Vol. 103  Nº 3  2011  págs. 603 - 609
Central nervous system (CNS) prophylaxis is required during initial treatment of non-Hodgkin lymphoma (NHL) subtypes that carry a high risk of CNS involvement. Intrathecal (IT) liposomal cytarabine, a formulation with prolonged half-life, has been shown to be safe and effective in the treatment of meningeal disease in patients with high-grade lymphoma. We retrospectively reviewed all adult patients with high-grade NHL that received prophylactic therapy with IT liposomal cytarabine and developed neurologic complications in our institution between April 2007 and May 2009. We recorded information on hospital admission, chemotherapy regimens, clinical features, neuroimaging, cerebrospinal fluid, neurophysiology data, and outcome. Neurotoxicity was graded according to the National Cancer Institute Common Toxicity Criteria (NCI-CTC). Four of fourteen patients (28%) developed moderate or severe neurotoxicity (grades 2 and 3 of the NCI-CTC), manifested as conus medullaris/cauda equine syndrome or pseudotumour cerebri-like syndrome, after a median of 3.5 IT courses of liposomal cytarabine. All patients had received corticosteroids to prevent arachnoiditis. Liposomal cytarabine given via the IT route, even with concomitant corticosteroid administration, can result in significant neurotoxicity in some patients. We discuss the potential pathogenesis of these effects and suggest hypothetical therapeutic measures to prevent these complications. Specialists should be aware of these possible complications when administering prophylactic IT liposomal cytarabine in high-grade NHL patients, and additional prospective studies should be conducted to more clearly delineate the frequency and characteristics of these complications.
Autores: Arbizu Lostao, Javier; Caicedo Zamudio, Carlos Javier; Gállego Pérez de Larraya, Jaime; et al.
Libro:  Medicina Nuclear en la práctica clínica
2012  págs. 355-378
Autores: Irimia Sieira, Pablo; Gállego Pérez de Larraya, Jaime; Martínez Vila, Eduardo Antonio
Libro:  Neurosonología. Aplicaciones diagnósticas para la práctica clínica
2011  págs. 93 - 102