Exploring management and outcomes of elderly patients with glioblastoma using data from two randomised trials (GEINO1401/EX-TEM).

PURPOSE: The impact of age on optimal management of glioblastoma remains unclear. A recent combined analysis of two randomised trials, GEINO14-01 and EX-TEM, found no benefit from extending post-radiation temozolomide in newly diagnosed glioblastoma. Here, we explore the impact of age. METHODS: Relevant intergroup statistics were used to identify differences in tumour, treatment and outcome characteristics based on age with elderly patients (EP) defined as age 65 years and over. Survival was estimated using the Kaplan Meier method. RESULTS: Of the combined 205 patients, 57 (28%) were EP. Of these, 95% were ECOG 0-1 and 65% underwent macroscopic resection compared with 97% and 61% of younger patients (YP) respectively. There were numerically less MGMT-methylated (56% vs. 63%, p = 0.4) and IDH-mutated (4% vs. 13%, p = 0.1) tumours in EP vs. YP. Following surgery, EP were more likely to receive short course chemoradiation (17.5% vs. 6%, p = 0.017). At recurrence, EP tended to receive or best supportive care (28.3% vs. 15.4%, p = 0.09) or non-surgical options (96.2% vs. 84.6%, p = 0.06), but were less likely to receive bevacizumab (23.1% vs. 49.5%, p < 0.01). Median PFS was similar at 9.3months in EP and 8.5months in YP, with similar median OS at 20months. CONCLUSION: In this trial population of predominantly fit EP, survival was similar to YP despite a proportion receiving less aggressive therapy at diagnosis and recurrence. Advancing age does not appear to be an adverse prognostic factor for glioblastoma when patients are fit for treatment, and a less aggressive approach in selected patients may not compromise outcomes.

A combined analysis of two prospective randomised studies exploring the impact of extended post-radiation temozolomide on survival outcomes in newly diagnosed glioblastoma.

PURPOSE: The optimal duration of post-radiation temozolomide in newly diagnosed glioblastoma remains unclear, with no published phase III randomised trials. Standard-of-care stipulates 6 months. However, in routine care, it is often extended to 12 months, despite lacking robust supporting data. METHODS: GEINO14-01 (Spain) and EX-TEM (Australia) studies enrolled glioblastoma patients without progression at the end of 6 months post-radiation temozolomide. Participants were randomised 1:1 to six additional months of temozolomide or observation. Primary endpoint was 6-month progression free survival from date of randomisation (6mPFS). Secondary endpoints included overall survival (OS) and toxicity. 204 patients were required to detect an improvement in 6mPFS from 50 to 60% (80% power). Neither study recruited sufficient patients. We performed a combined analysis of individual patient data. RESULTS: 205 patients were recruited: 159 in GEINO14-01 (2014-2018) and 46 in EX-TEM (2019-2022). Median follow-up was 20.0 and 14.5 months. Baseline characteristics were balanced. There was no significant improvement in 6mPFS (57.2% vs 64.0%, OR0.75, p = 0.4), nor across any subgroups, including MGMT methylated; PFS (HR0.92, p = 0.59, median 7.8 vs 9.7 months); or OS (HR1.03, p = 0.87, median 20.1 vs 19.4 months). During treatment extension, 64% experienced any grade adverse event, mainly fatigue and gastrointestinal (both 54%). Only a minority required treatment changes: 4.5% dose delay, 7.5% dose reduction, 1.5% temozolomide discontinuation. CONCLUSION: For glioblastoma patients, extending post-radiation temozolomide from 6 to 12 months is well tolerated but does not improve 6mPFS. We could not identify any subset that benefitted from extended treatment. Six months should remain standard-of-care.

SEOM clinical guidelines for diagnosis and treatment of glioblastoma (2017).

Glioblastoma (GB) is the most common brain malignancy and accounts for over 50% of all high-grade gliomas. Radiotherapy (RT) with concomitant and adjuvant temozolomide (TMZ) chemotherapy is the current standard of care for patients with newly diagnosed GB up to age 70. Recently, a new standard of care has been adopted for elderly patients (≥ 65 years) based on short course of RT and TMZ. Several clinically relevant molecular markers that assist in diagnosis and prognosis have recently been identified. The treatment for recurrent GB is not well defined, and decision-making is usually based on prior strategies as well as several clinical and radiological factors. The presence of neurologic deficits and seizures can significantly impact quality of life.

Material de seguridad para cateterización periférica venosa / Security material for venous peripheral. Catheterization evaluation in an emergency ward

La canalización venosa puede ser uno de los motivos másfrecuentes de accidentes por punción accidental. La realizaciónde actividades encaminadas a disminuir estos percances,de elevado riesgo biológico, debe ser una prioridad paralas instituciones sanitarias y para sus profesionales. Dentrode una estrategia global que incida en este aspecto y con elobjetivo de evaluar la idoneidad de estos dispositivos ennuestro centro, se realiza una valoración práctica de unaserie de ellos para conocer su viabilidad técnica y la apreciaciónsubjetiva de los profesionales que los prueben. Pormotivos relacionados con las prácticas del servicio en el quese desarrolla la investigación (Servicio de Urgencias), seseleccionan intencionalmente dos dispositivos pasivos,disponibles en el mercado, y tres enfermeros, que recibieron120 muestras de catéteres de seguridad (60 del producto A,60 del producto B) para realizar las prácticas clínicas habituales,junto con una hoja de incidencias. Con respecto aldispositivo A, se detectaron 30 incidencias (52,6%) y seprocedió a toma de muestras en 37 ocasiones. Con respectoal dispositivo B, se detectaron cuatro incidencias (7,01%)y se procedió a la toma de muestras en 47 ocasiones. En términosabsolutos, ninguno de los dos dispositivos ha mostradoproblemas con la práctica segura, es decir, no han provocadoincidencias relacionadas con la aparición de percancesasociados a punciones accidentales. La menor frecuencia deincidencias en el dispositivo B parece estar relacionada con eluso habitual del catéter convencional (no de seguridad) delmismo fabricante en nuestro centro. Trabajo subvencionadopor el Fondo de Investigaciones Sanitarias. PI 051265(AU)

Venous canalization can be one of the most frequent causesof accidents due to an accidental puncture. To carry out activitieswhich serve to lessen these misfortunes, bearing highbiological risk, should become a priority for sanitary institutionsand for their professionals. Inside a global strategywhich deals with this aspect and with the objective of evaluatingthe convenience these instruments have in our center,the authors made a practical evaluation on a series of themto discover their technical viability and their subjective considerationby professionals who employ them. For motives relatedto the practices of the ward in which this research tookplace, an emergency ward, the authors intentionally chosetwo passive instruments, available on the market, and threenurses who received 120 sample security catheters, 60 eachfor products A and B, to carry out habitual clinical practices,alongside a pad of paper on which to record any incidents.Regarding instrument A, 30 incidents, 52.6%, were detectedwhile 37 sample procedures occurred. Regarding instrumentB, 4 incidents, 7.01%, were detected while 47 sample proceduresoccurred. In absolute terms, neither of the two instrumentsdemonstrated problems of an insecure manner; whichis to say, neither produced a situation related to the appearanceof misfortunate incidents associated to accidentalpunctures. The lower number of incidents with instrument Bappears to be related to the habitual use of a conventionalcatheter, not a security one, produced by the same manufacturerin our center. This research project was subsidized bythe Sanitary Research Fund, PI 051265(AU)

[Ashy dermatosis (erithema dyschromicum perstans): prospective study of 23 patients]. / Dermatosis cenicienta (Erithema dyschromicum perstans): estudio prospectivo de 23 pacientes.

During the period between january 1984 to july 1987 in the Hospital Unit "Presidente Juárez" ISSSTE, Oaxaca (Mexico), for the first time was given dermatology consult to 2,683 patients among them, 23 who had ashy dermatosis (Erithema dyschromicum perstans), a study was done for the present time and the future of the same, discarding it as possible cause of that nosological entity: treponemal disease, parasitic, infectious, hepatic and renal. It is commented in relation with the ashy dermatosis and lichen planus, the clinicals variants and the possible sun etiology.

[In search of biological markers of affective disorders]. / En busca de marcadores biológicos de trastornos afectivos.

The field of biological markers of affective disorders is defined on its conceptual and methodological basis, and the results of some studies in this area conducted at the Mexican Institute of Psychiatry are reported. Urinary MHPG levels greater than 2800 micrograms/24 hs, suggest a poor response to conventional drug treatment. Allnight EEG recordings, showed that sleep architecture of depressed patients is substantially different from that of normal subjects; particularly REM sleep latency, which can reliably discriminate between patients and controls. The dexamethasone suppression test showed a diagnostic confidence of 77% which is similar to that reported from other centers. The author suggests caution on interpreting these results, as further prospective longitudinal studies are needed before firm conclusions can be drawn.

En busca de marcadores biológicos de trastornos afectivos. / [In search of biological markers of affective disorders]

The field of biological markers of affective disorders is defined on its conceptual and methodological basis, and the results of some studies in this area conducted at the Mexican Institute of Psychiatry are reported. Urinary MHPG levels greater than 2800 micrograms/24 hs, suggest a poor response to conventional drug treatment. Allnight EEG recordings, showed that sleep architecture of depressed patients is substantially different from that of normal subjects; particularly REM sleep latency, which can reliably discriminate between patients and controls. The dexamethasone suppression test showed a diagnostic confidence of 77

which is similar to that reported from other centers. The author suggests caution on interpreting these results, as further prospective longitudinal studies are needed before firm conclusions can be drawn.

Cuantificacion urinaria de 3-metoxi-4 hidroxifeniletilenglicol en sujetos sanos. / Determination of urinary 3-methoxy-4-hydroxiphenilethylenglicol in healthy subjects

Se describe un metodo para cuantificar la concentracion urinaria de MHPG, que es el principal metabolito de la norepinefrina cerebral, utilizando la cromatografia liquido-gas con detector de captura de electrones. Los resultados obtenidos en 27 sujetos sanos muestran un rango que oscila entre sanos y 3066 microgamo/24 ha con un promedio +/- E.E. de 2040 +/- 113 microgramo 24 hs. Los percentiles de los valores de referencia fueron" P5 = 1060 microgramo/24 hs P50 = 2015 microgramo/24 hs y P95 = 2820 microgramo/24 hs. Tanto la variacion del metodo como los valores encontrados, son consistentes con los reportados en otros paises. Los autores discuten la importancia del desarrollo de esta y otras metodologias similares para algunas areas de la investigacion en neurociencias