Análisis coste-efectividad de la cirugía del glioma maligno guiada por fluorescencia con ácido 5-aminolevulínico / Cost-effectiveness of 5-aminolevulinic acid-induced fluorescence in malignant glioma surgery

Objetivo: Evaluar el coste-efectividad del ácido 5-aminolevulínico (5-ALA, Gliolan(R)) en pacientes intervenidos quirúrgicamente de glioma maligno, en condiciones de práctica médica habitual en España. Material y métodos: Se determinaron las ratios de coste incremental por resección completa (RC) y de coste incremental por año de vida ajustado por calidad (AVAC) ganado, sobre la base de los datos recogidos en el estudio observacional VISIONA. Resultados. El coste incremental con 5-ALA frente a la cirugía convencional con luz blanca asciende a 4.550 Euros por RC adicional conseguida y a 9.021 Euros por AVAC ganado. Estos resultados se muestran consistentes en un análisis de sensibilidad. Conclusión: La cirugía del glioma maligno guiada por fluorescencia con 5-ALA conlleva un incremento de costes moderado respecto a la práctica quirúrgica actual y muestra una relación coste-efectividad favorable

Objective: This study evaluates the cost-effectiveness of 5-aminolevulinic acid (5-ALA, Gliolan®) in patients undergoing surgery for malignant glioma, in standard clinical practice conditions in Spain. Material and methods: Cost-effectiveness ratios were determined in terms of incremental cost per complete resection (CR) and incremental cost per additional quality-adjusted life year (QALY), based on data collected in the VISIONA observational study. Results: Incremental cost with 5-ALA versus conventional surgery using white light only amounts to Euros 4550 per additional CR achieved and Euros 9021 per QALY gained. A sensitivity analysis shows these results to be robust. Conclusion: Malignant glioma surgery guided by 5-ALA fluorescence entails a moderate increase in hospital costs compared to current surgical practice and can be considered a cost-effective innovation

Cost-effectiveness of 5-aminolevulinic acid-induced fluorescence in malignant glioma surgery.

OBJECTIVE: This study evaluates the cost-effectiveness of 5-aminolevulinic acid (5-ALA, Gliolan®) in patients undergoing surgery for malignant glioma, in standard clinical practice conditions in Spain. MATERIAL AND METHODS: Cost-effectiveness ratios were determined in terms of incremental cost per complete resection (CR) and incremental cost per additional quality-adjusted life year (QALY), based on data collected in the VISIONA observational study. RESULTS: Incremental cost with 5-ALA versus conventional surgery using white light only amounts to € 4550 per additional CR achieved and € 9021 per QALY gained. A sensitivity analysis shows these results to be robust. CONCLUSION: Malignant glioma surgery guided by 5-ALA fluorescence entails a moderate increase in hospital costs compared to current surgical practice and can be considered a cost-effective innovation.

Estudio observacional retrospectivo sobre la efectividad del ácido 5-aminolevulínico en la cirugía de los gliomas malignos en España (Estudio VISIONA) / Observational, retrospective study of the effectiveness of 5-aminolevulinic acid in malignant glioma surgery in Spain (The VISIONA study)

Objetivo: Evaluar la efectividad del ácido 5-aminolevulínico (5-ALA, Gliolan(R)) mediante la tasa de resecciones completas (RC) y supervivencia libre de progresión a los 6 meses (SLP6) en pacientes intervenidos quirúrgicamente de glioma maligno, en condiciones de práctica médica habitual en España. Material y métodos: Revisión retrospectiva en 18 servicios de neurocirugía, divididos en centros que usan habitualmente 5-ALA y centros que no. Se incluyó a pacientes adultos con sospecha de glioma maligno, en los que la intención de tratar incluyó resección completa y posterior radioterapia y quimioterapia con temozolomida. Era necesaria la existencia de resonancia magnética posquirúrgica y datos clínicos al menos durante 6 meses. Se comparó la diferencia entre pacientes con o sin 5-ALA en la tasa de RC y en la SLP6. Resultados: Se obtuvieron 251 casos evaluables. La tasa de RC y la tasa de SLP6 fueron significativamente mayores en el grupo de pacientes operados con 5-ALA: RC, 67% frente a 45%, p = 0,000, y SLP6 en el caso de los gliomas de grado IV , 69% frente a 48%; p = 0,002. Estas diferencias se mantuvieron relevantes y significativas tras ajustarlas por todas las covariables estudiadas, que incluyeron edad, estado funcional y localización en área elocuente o no. Conclusiones: En esta serie retrospectiva, el uso de 5-ALA en la cirugía del glioma maligno en la práctica habitual en España se asoció a un incremento en la tasa de resecciones completas y, en el caso de los gliomas de grado IV , a un incremento en la supervivencia libre de progresión a los 6 meses

Objective: To assess effectiveness of 5-aminolevulinic acid (5-ALA, Gliolan(R)) in patients treated for malignant glioma under typical daily practice conditions in Spain, using complete resection rate (CR) and progression free survival at 6 months (PFS6). Materials and methods: Retrospective review of data from 18 neurosurgery departments that were categorised as either using or not using 5-ALA. The study included adult patients with suspected malignant gliomas for whom the intended treatment plan included complete resection followed by radiotherapy and chemotherapy with temozolomide. Postoperative MRI and clinical data representing at least 6 months were required for inclusion. Rates of CR and PFS6 were compared between patients with 5-ALA treatment and those without. Results: The study included 251 evaluable cases. CR and PFS6 rates were significantly higher in the group of patients treated surgically with 5-ALA: CR, 67% versus 45%, P = .000; PFS6 for patients with grade IV tumours, 69% versus 48%; P = .002. The differences retained their significance and magnitude after adjusting for all covariates including age, functional status, and whether gliomas were located in eloquent areas. Conclusions: In this retrospective series, use of 5-ALA during habitual surgical procedures in Spain was associated with a higher complete resection rate for malignant glioma and increased PFS6 for grade IV glioma

Observational, retrospective study of the effectiveness of 5-aminolevulinic acid in malignant glioma surgery in Spain (The VISIONA study).

OBJECTIVE: To assess effectiveness of 5-aminolevulinic acid (5-ALA, Gliolan(®)) in patients treated for malignant glioma under typical daily practice conditions in Spain, using complete resection rate (CR) and progression free survival at 6 months (PFS6). MATERIAL AND METHODS: Retrospective review of data from 18 neurosurgery departments that were categorised as either using or not using 5-ALA. The study included adult patients with suspected malignant gliomas for whom the intended treatment plan included complete resection followed by radiotherapy and chemotherapy with temozolomide. Postoperative MRI and clinical data representing at least 6 months were required for inclusion. Rates of CR and PFS6 were compared between patients with 5-ALA treatment and those without. RESULTS: The study included 251 evaluable cases. CR and PFS6 rates were significantly higher in the group of patients treated surgically with 5-ALA: CR, 67% versus 45%, p=.000; PFS6 for patients with grade IV tumours, 69% versus 48%; p=.002. The differences retained their significance and magnitude after adjusting for all covariates including age, functional status, and whether gliomas were located in eloquent areas. CONCLUSIONS: In this retrospective series, use of 5-ALA during habitual surgical procedures in Spain was associated with a higher complete resection rate for malignant glioma and increased PFS6 for grade iv glioma.

Quantitative volumetric analysis of gliomas with sequential MRI and ¹¹C-methionine PET assessment: patterns of integration in therapy planning.

PURPOSE: The aim of the study was to evaluate the volumetric integration patterns of standard MRI and (11)C-methionine positron emission tomography (PET) images in the surgery planning of gliomas and their relationship to the histological grade. METHODS: We studied 23 patients with suspected or previously treated glioma who underwent preoperative (11)C-methionine PET because MRI was imprecise in defining the surgical target contour. Images were transferred to the treatment planning system, coregistered and fused (BrainLAB). Tumour delineation was performed by (11)C-methionine PET thresholding (vPET) and manual segmentation over MRI (vMRI). A 3-D volumetric study was conducted to evaluate the contribution of each modality to tumour target volume. All cases were surgically treated and histological classification was performed according to WHO grades. Additionally, several biopsy samples were taken according to the results derived either from PET or from MRI and analysed separately. RESULTS: Fifteen patients had high-grade tumours [ten glioblastoma multiforme (GBM) and five anaplastic), whereas eight patients had low-grade tumours. Biopsies from areas with high (11)C-methionine uptake without correspondence in MRI showed tumour proliferation, including infiltrative zones, distinguishing them from dysplasia and radionecrosis. Two main PET/MRI integration patterns emerged after analysis of volumetric data: pattern vMRI-in-vPET (11/23) and pattern vPET-in-vMRI (9/23). Besides, a possible third pattern with differences in both directions (vMRI-diff-vPET) could also be observed (3/23). There was a statistically significant association between the tumour classification and integration patterns described above (p < 0.001, κ = 0.72). GBM was associated with pattern vMRI-in-vPET (9/10), low-grade with pattern vPET-in-vMRI (7/8) and anaplastic with pattern vMRI-diff-vPET (3/5). CONCLUSION: The metabolically active tumour volume observed in (11)C-methionine PET differs from the volume of MRI by showing areas of infiltrative tumour and distinguishing from non-tumour lesions. Differences in (11)C-methionine PET/MRI integration patterns can be assigned to tumour grades according to the WHO classification. This finding may improve tumour delineation and therapy planning for gliomas.

Neuroimagen de los tumores cerebrales / Neuroimaging in brain tumors

Aunque el estudio neuropatológico es insustituible para conseguir el mejor control posible de los tumores craneales, el diagnóstico, el tratamiento y el seguimiento posterior ha ido progresando en buena medida conforme han avanzado las técnicas de neuroimagen. Tanto la cirugía como la radioterapia son técnicas dependientes de la imagen para su planificación. En el momento actual, la RM es un estándar que permite conocer de forma muy precisa la localización de la lesión y su relación anatómica con las estructuras vecinas. En gliomas de alto grado, se acepta que la parte de tumor captante de contraste en la TC o en las secuencias T1 de RM tras la administración de gadolinio, corresponde a tumor sólido. Sin embargo, la relación entre la imagen y la parte invasiva del tumor queda mucho menos definida. Por tanto, se acepta que la RM convencional no es suficiente para discriminar la extensión de la parte invasiva del tumor. En los últimos años las técnicas de PET con FDG o radiofármacos aminoácidos (metionina, FDOPA, FET), SPECT con talio, así como secuencias avanzadas de RM como la perfusión, la difusión, el tensor de difusión y la tractografía, y la RM funcional están aportando una información complementaria de gran importancia en la caracterización, planificación terapéutica y diagnóstico diferencial de la recidiva de los tumores cerebrales. En este artículo de formación continuada sobre tumores cerebrales se tratan desde un punto de vista multidisciplinar los diferentes aspectos técnicos y aplicaciones clínicas de las principales técnicas de neuroimagen(AU)

Advances in neuroimaging have modified diagnosis, treatment and clinical management of brain tumors. However, neuropathological study remains necessary in order to get the best clinical management. Surgery and radiotherapy planning are imaging-dependent procedures, and MRI is the standard imaging modality for determining precisely tumor location and its anatomical relationship with surrounding brain structures. In high-grade tumors it has been accepted that tumoral areas with contrast uptake in CT, or T1-weighted MRI contrast enhancement corresponds to solid tumor. However, relationship between MRI and invasive tumor areas remains less defined. Therefore, it is generally accepted that conventional MRI is not sufficient to delineate the real extension of brain tumors. In recent years, PET using 18FDG and amino acid radiotracers (11C-Methionine, 18FDOPA, 18FET) and SPECT with 201-Thallium, as well as advanced MRI sequences (Perfusion, Diffusion-weighted, Diffusion tensor imaging and tractography), and functional MRI, have added important complementary information in the characterization, therapy planning and recurrence differential diagnosis of brain tumors. In this continuing education review of neuroimaging in brain tumors, technical aspects and clinical applications of different imaging modalities are approached in a multidisciplinary way(AU)

[Neuroimaging in brain tumors]. / Neuroimagen de los tumores cerebrales.

Advances in neuroimaging have modified diagnosis, treatment and clinical management of brain tumors. However, neuropathological study remains necessary in order to get the best clinical management. Surgery and radiotherapy planning are imaging-dependent procedures, and MRI is the standard imaging modality for determining precisely tumor location and its anatomical relationship with surrounding brain structures. In high-grade tumors it has been accepted that tumoral areas with contrast uptake in CT, or T1-weighted MRI contrast enhancement corresponds to solid tumor. However, relationship between MRI and invasive tumor areas remains less defined. Therefore, it is generally accepted that conventional MRI is not sufficient to delineate the real extension of brain tumors. In recent years, PET using 18FDG and amino acid radiotracers ((11)C-Methionine, (18)FDOPA, (18)FET) and SPECT with (201-)Thallium, as well as advanced MRI sequences (Perfusion, Diffusion-weighted, Diffusion tensor imaging and tractography), and functional MRI, have added important complementary information in the characterization, therapy planning and recurrence differential diagnosis of brain tumors. In this continuing education review of neuroimaging in brain tumors, technical aspects and clinical applications of different imaging modalities are approached in a multidisciplinary way.

Infratentorial hygroma secondary to decompressive craniectomy after cerebellar infarction.

We present a case of expansive CSF collection in the cerebellar convexity. The patient was a 74 years old lady who one month before had suffered a cerebellar infarct complicated with acute hydrocephalus. She had good evolution after decompressive craniectomy without shunting. Fifteen days after surgery, the patient started with new positional vertigo, nausea and vomiting and a wound CSF fistula that needed ventriculoperitoneal shunt (medium pressure) because conservative treatment failed. After shunting, the fistula closed, but the patient symptoms worsened. The MRI showed normal ventricular size with a cerebellar hygroma, extending to the posterior interhemispheric fissure. The collection had no blood signal and expanded during observation. A catheter was implanted in the collection and connected to the shunt. The patient became asymptomatic after surgery, and the hygromas had disappeared in control CT at one month. This case shows an infrequent problem of CSF circulation at posterior fossa that resulted in vertigo of central origin. A higroma-ventricle-peritoneal shunt solved the symptoms of the patient.

Infratentorial hygroma secondary to decompressive craniectomy after cerebellarinfarction

We present a case of expansive CSF collection in thecerebellar convexity. The patient was a 74 years old ladywho one month before had suffered a cerebellar infarctcomplicated with acute hydrocephalus. She had goodevolution after decompressive craniectomy withoutshunting. Fifteen days after surgery, the patient startedwith new positional vertigo, nausea and vomiting anda wound CSF fistula that needed ventriculoperitonealshunt (medium pressure) because conservative treatmentfailed. After shunting, the fistula closed, but thepatient symptoms worsened. The MRI showed normalventricular size with a cerebellar hygroma, extendingto the posterior interhemispheric fissure. The collectionhad no blood signal and expanded during observation.A catheter was implanted in the collection and connectedto the shunt. The patient became asymptomaticafter surgery, and the hygromas had disappeared incontrol CT at one month.This case shows an infrequent problem of CSF circulationat posterior fossa that resulted in vertigo of centralorigin. A higroma-ventricle-peritoneal shunt solvedthe symptoms of the patient (AU)

Presentamos el caso de una paciente con una colecciónexpansiva de LCR sobre la convexidad del cerebelo.La paciente, de 74 años de edad, había sido intervenidade urgencia un mes antes por un infarto de hemisferiocerebeloso e hidrocefalia aguda, con buena evolucióntras la craniectomía descompresiva de fosa posterior ysin necesitar válvula. A los 15 días de la intervención, lapaciente comenzó con un cuadro de vértigo posicional,náuseas, vómitos y una fístula de LCR, que al no responderal tratamiento conservador fue tratada con unaválvula VP de presión media. Tras implantar la válvulala fístula se cerró, pero el cuadro clínico de la pacienteempeoró.En una resonancia magnética se objetivó un tamañoventricular normal e higromas infratentoriales que seextendían hacia la fisura interhemisférica posterior. Enlos higromas no se objetivó señal de sangrado y fueronaumentando de tamaño. Se implantó un catéter a niveldel higroma de mayor tamaño en la fosa posterior y seconectó a la válvula que portaba la paciente, evolucionandode forma favorable clínica y radiológicamente.Al mes de la intervención los higromas habían desaparecidoen el TAC de control.Este caso muestra una situación infrecuente dealteración del flujo de LCR a nivel de la fosa posteriorque da lugar a un cuadro de vértigo de origen central.El drenaje de los higromas, mediante un catéter conectadoa una válvula ventriculo peritoneal, solucionó lasintomatología (AU)