Marti, J.M. (J.M.)

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    Prognostic value of serum paraprotein response kinetics in patients with newly diagnosed multiple myeloma
    (2022) Blanchard, M.J. (María Jesús); González, M.E. (María Esther); Cedena, M.T. (María Teresa); Casado, L.F. (Luis Felipe); Krsnik, I. (Isabel); Ríos, R. (Rafael) de los; Gironella, M. (Mercedes); Bladé, J. (Joan); Mateos, M.V. (María Victoria); Arriba, F. (Felipe) de; Troconiz, I.F. (Iñaki F.); Hernandez, M.T. (Miguel Teodoro); Rosiñol, L. (Laura); Puig, N. (Noemí); Lopez-Anglada, L. (Lucia); Arguiñano, J.M. (José María); Palomera, L. (Luis); Lahuerta, J.J. (Juan José); Rodriguez-Otero, P. (Paula); Paiva, B. (Bruno); Jarque, I. (Isidro); Oriol, A. (Albert); Marti, J.M. (J.M.); Sureda-Balari, A. M. (Anna Maria); González-Rodriguez, A.P. (Ana Pilar); Bargay, J. (Joan); Gonzalez-Montes, Y. (Yolanda); Jiménez-Ubieto, A. (Ana); San-Miguel, J.F. (Jesús F.); Tamariz-Amador, L.E. (Luis Esteban); Cabañas, V. (Valentín)
    Introduction Response kinetics is a well-established prognostic marker in acute lymphoblastic leukemia. The situation is not clear in multiple myeloma (MM) despite having a biomarker for response monitoring (monoclonal component [MC]). Materials and Methods We developed a mathematical model to assess the prognostic value of serum MC response kinetics during 6 induction cycles, in 373 NDMM transplanted patients treated in the GEM2012Menos65 clinical trial. The model calculated a “resistance” parameter that reflects the stagnation in the response after an initial descent. Results Two patient subgroups were defined based on low and high resistance, that respectively captured sensitive and refractory kinetics, with progression-free survival (PFS) at 5 years of 72% and 59% (HR 0.64, 95% CI 0.44-0.93; P = .02). Resistance significantly correlated with depth of response measured after consolidation (80.9% CR and 68.4% minimal residual disease negativity in patients with sensitive vs. 31% and 20% in those with refractory kinetics). Furthermore, it modulated the impact of reaching CR after consolidation; thus, within CR patients those with refractory kinetics had significantly shorter PFS than those with sensitive kinetics (median 54 months vs. NR; P = .02). Minimal residual disease negativity abrogated this effect. Our study also questions the benefit of rapid responders compared to late responders (5-year PFS 59.7% vs. 76.5%, respectively [P < .002]). Of note, 85% of patients considered as late responders were classified as having sensitive kinetics. Conclusion This semi-mechanistic modeling of M-component kinetics could be of great value to identify patients at risk of early treatment failure, who may benefit from early rescue intervention strategies.
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    Correlaciones entre la SPECT cerebral y la evaluación neuropsicológica en los estadios leve y moderado de la enfermedad de Alzheimer
    (Universidad de Navarra, 1999) Gamez, C. (C.); Martinez-Lage, J.M. (José M.); Richter, J.A. (José Ángel); Larumbe, R. (R.); Marti, J.M. (J.M.); Arbizu, J. (Javier)
    Se evaluaron 34 pacientes con enfermedad de Alzheimer (EA) probable (EA leve = 16; EA moderada = 18) y 12 controles mediante un estudio semicuantitativo de SPECT con 99mTc-HMPAO y la batería de tests neuropsicológicos CERAD. Resultados: La hipoperfusión temporal (p < 0,01) y los tests de memoria (p < 0,001) permitieron diferenciar los controles de los pacientes con EA leve. En estos pacientes se observaron también correlaciones significativas (p < 0,05) entre: test de recuerdo diferido-hipoperfusión temporal, test de aprendizaje-hipoperfusión temporoparietal y frontal y praxis visuoconstructiva-hipoperfusión temporal posterior. Los pacientes con EA moderada mostraron, respecto a la EA leve, una mayor hipoperfusión temporal (p < 0,01), parietal y frontal (p < 0,05), junto a un empeoramiento de la praxis (p < 0,001) y los test de memoria (p < 0,05). Conclusiones: La SPECT y la evaluación neuropsicológica permiten distinguir entre controles y pacientes con estadios leve y moderado de la EA, existiendo una estrecha correlación entre ambos métodos desde las etapas iniciales de la enfermedad.
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    Estudio de la actividad cortical auditiva mediante SPECT cerebral: validacion del metodo y aplicacion en la hipoacusia profunda bilateral
    (Gobierno de Navarra. Departamento de Salud, 1999) Insausti, R. (R.); Manrique, M. (Manuel); Richter, J.A. (José Ángel); Marti, J.M. (J.M.); Arbizu, J. (Javier)
    To evaluate the differences in the functional activity of the auditory cortex between normal hearing and profound deafness, a perfusion single photon emission tomography (SPECT) study was designed. SPECT stereotaxic localisation of the auditory cortex was previously validated in 2 brains by means of an anatomical study of the macroscopic localisation and cytoarchitecture of the auditory cortex. Additionally, 15 controls with normal hearing and 30 patients with profound bilateral deafness were scanned using external anatomical point sources (glabela, ineon) for stereotaxic location of the auditory cortex. The normal controls were scanned in auditive deprivation and, in 10 cases, during a monoaural tonal stimulation. Cerebral blood flow relative to cerebellum (relCBF) was assessed in the auditory cortex. The anatomical study showed that mean differences between the true auditory cortex size and the measured SPECT value were less than 2.5 mm. Nevertheless, only the caudal aspect of this area corresponded to the primary auditory cortex in the cytoarchitectonic study. During tonal stimulation, control subjects presented a significant increase of relCBF in the auditory cortex bilaterally, with significant differences in the asymmetry index (contralateral to the side of stimulation). The relCBF in the auditory cortex of controls in deprivation conditions was significantly higher than in deaf patients. There were no significant differences between groups of deaf patients, however the highest values were seen after cochlear implant. SPECT is a suitable method for studying changes in auditory cortex activity relative to different functional conditions, with a possible role in cochlear implant candidates in predicting the future benefit of the implantation.
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    Valor clínico de la tomografía de emisión de positrones con F-18-FDG en el seguimiento de pacientes con cáncer de ovario
    (Gobierno de Navarra. Departamento de Salud, 2002) Boan, J. (J.); Lopez-Garcia, G. (Guillermo); Meiriño, R. (Rosa); Richter, J.A. (José Ángel); Garcia-Velloso, M. J. (María José); Galan, M.J. (M. J.); Marti, J.M. (J.M.)
    Background. Positron emission tomography with fluor- 18-deoxyglucose (PET-FDG) is an efficient technique for the detection of tumoural tissue. The aim of the paper is to evaluate the PET-FDG in the diagnosis of residual disease or relapse in patients with cancer of the ovary. Methods. A total of 24 patients, diagnosed and treated for cancer of the ovary with surgery and subsequent chemotherapy, were included. With 12 patients the study was carried out prior to second-look surgery, and with the other 12 after objectivising an increase of the tumoural marker in the follow up. Abdominal-pelvic CAT, determination of the seric levels of CA-125 and PET-FDG of thorax, abdomen and pelvis were carried out on all patients. The PET-FDG was evaluated in a qualitative way through the visual study of the images, and quantitatively through the SUV or standard uptake value. The definitive diagnosis was confirmed through an anatomopathological study in 13 cases and through clinical follow up in the rest with an average of 11.2±5.4 months (range 6-24). Results. A CA-125 value higher than 35 UI/ml was considered positive, obtaining a sensitivity of 77% and a specificity of 100%. The sensitivity of the CAT was 23% and the specificity 91%. With the FDG-PET sensitivity was 92% and the specificity 90%. A SUV value ≥ 3 was considered pathological, obtaining the same results as with the visual evaluation. The FDG-PET was positive in 5 patients with non-conclusive CAT, 4 with negative CAT and 2 with negative CA-125. Conclusion. These preliminary results suggest that the FDG-PET could be useful in the follow up of patients treated for cancer of the ovary. The FDG-PET could be efficient in the differentiation between residual disease or recurrence, as opposed to sequels to the treatment, when the CAT is not conclusive due to anatomical distortion. The FDG-PET could be more sensitive than an increased marker value, and facing an increase of the latter it permits a non-invasive localisation of the disease.
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    Prognostic value of serum paraprotein response kinetics in patients with newly diagnosed multiple myeloma
    (2022) Blanchard, M.J. (María Jesús); González, M.E. (María Esther); Cedena, M.T. (María Teresa); Casado, L.F. (Luis Felipe); Krsnik, I. (Isabel); Ríos, R. (Rafael) de los; Gironella, M. (Mercedes); Bladé, J. (Joan); Mateos, M.V. (María Victoria); Arriba, F. (Felipe) de; Troconiz, I.F. (Iñaki F.); Hernandez, M.T. (Miguel Teodoro); Rosiñol, L. (Laura); Puig, N. (Noemí); Lopez-Anglada, L. (Lucia); Arguiñano, J.M. (José María); Palomera, L. (Luis); Lahuerta, J.J. (Juan José); Rodriguez-Otero, P. (Paula); Paiva, B. (Bruno); Jarque, I. (Isidro); Oriol, A. (Albert); Marti, J.M. (J.M.); Sureda-Balari, A. M. (Anna Maria); González-Rodriguez, A.P. (Ana Pilar); Bargay, J. (Joan); Gonzalez-Montes, Y. (Yolanda); Jiménez-Ubieto, A. (Ana); San-Miguel, J.F. (Jesús F.); Tamariz-Amador, L.E. (Luis Esteban); Cabañas, V. (Valentín)
    Introduction: Response kinetics is a well-established prognostic marker in acute lymphoblastic leukemia. The situation is not clear in multiple myeloma (MM) despite having a biomarker for response monitoring (monoclonal component [MC]). Materials and Methods: We developed a mathematical model to assess the prognostic value of serum MC response kinetics during 6 induction cycles, in 373 NDMM transplanted patients treated in the GEM2012Menos65 clinical trial. The model calculated a ¿resistance¿ parameter that reflects the stagnation in the response after an initial descent. Results: Two patient subgroups were defined based on low and high resistance, that respectively captured sensitive and refractory kinetics, with progression-free survival (PFS) at 5 years of 72% and 59% (HR 0.64, 95% CI 0.44-0.93; P =.02). Resistance significantly correlated with depth of response measured after consolidation (80.9% CR and 68.4% minimal residual disease negativity in patients with sensitive vs. 31% and 20% in those with refractory kinetics). Furthermore, it modulated the impact of reaching CR after consolidation; thus, within CR patients those with refractory kinetics had significantly shorter PFS than those with sensitive kinetics (median 54 months vs. NR; P =.02). Minimal residual disease negativity abrogated this effect. Our study also questions the benefit of rapid responders compared to late responders (5-year PFS 59.7% vs. 76.5%, respectively [P <.002]). Of note, 85% of patients considered as late responders were classified as having sensitive kinetics. Conclusion: This semi-mechanistic modeling of M-component kinetics could be of great value to identify patients at risk of early treatment failure, who may benefit from early rescue intervention strategies.
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    Tomografía de emisión de positrones con F-18-FDG: una nueva técnica en la evaluación de pacientes con neoplasias de cabeza y cuello
    (Gobierno de Navarra. Departamento de Salud, 1999) Peñuelas-Sanchez, I. (Ivan); Quesada, J. (J.); Richter, J.A. (José Ángel); Azinovic, I. (Ignacio); Garcia-Velloso, M. J. (María José); Alcalde, J. (Juan); Marti, J.M. (J.M.)
    INTRODUCTION: Positron emission tomography using fluoro-deoxyglucose (PET-FDG) imaging has been shown to be effective in detecting and staging malignancies based on tumor glucose metabolism. The aim of the study was to evaluate the use of PET-FDG for the detection of metastatic lesions as well as early recurrence in patients with head and neck tumors. MATERIAL AND METHODS: Eleven patients were examined with PET-FDG to study the reliability of PET in assessing regional nodal status and in identifying distant metastasis (group I) and 37 patients who had previously received curative treatment and who presented differential diagnostic problems were imaged to differentiate between scar and residual or recurrent cancer (group II). PET-FDG studies were compared to results of computed tomography (CT) in 35 patients, magnetic resonance imaging (MRI) in 4 patients and both techniques in 6 patients. RESULTS: All PET-FDG studies were positive in group I, while CT failed to detect metastatic lesions in three patients. In group II PET-FDG accurately detected recurrent disease in 22/25 patients, while CT/MRI were negative in 4 cases and equivocal in 6 cases. However, there was a false positive PET study with equivocal CT in a patient with local infection. CONCLUSION: PET-FDG was highly effective in detecting metastatic cervical lymph nodes in head and neck tumours. It was most helpful in differentiating residual or recurrent tumour from scar sequelae and it enhanced the diagnostic accuracy when CT and MRI were equivocal due to anatomical distortions.