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.

Public-private mix for tuberculosis care and control in Myanmar: a strategy to scale up?

Setting: The public-private mix (PPM) tuberculosis (TB) project implemented by the Myanmar Medical Association (MMA) in 105 townships in Myanmar. Objectives: 1) To assess the contribution of the MMA-PPM-TB project to total TB patient notification in the project townships; 2) to evaluate the outcomes of patients treated at the MMA-PPM clinics; and 3) to identify factors associated with unfavourable treatment outcomes, from January to December 2013. Design: A retrospective cohort study. Results: The MMA-PPM-TB project contributed 7501 (12%) of 60 905 TB patient notifications to the National Tuberculosis Programme (NTP) in 105 study townships. Of 2975 TB patients diagnosed and treated at private MMA-PPM clinics, 92% had a favourable outcome (32% cured, 60% completed treatment) and 8% had an unfavourable outcome (2.9% died, 2.5% lost to follow-up, 1.9% failure, 0.6% transfer out). Patient characteristics significantly associated with an unfavourable treatment outcome were age ⩾65 years (adjusted risk ratio [aRR] 5.7, 95% confidence interval [CI] 4.20-7.68), retreatment (aRR 2.44, 95%CI 1.79-3.33) and female sex (aRR 1.44, 95%CI 1.14-1.82). Conclusion: This study supports the continuation and expansion of the MMA-PPM-TB model and/or similar PPM approaches in Myanmar that engage all health providers in the ambitious goals of achieving universal health coverage in this country in transition and ending its TB epidemic by 2035.

Contexte : Le projet mixe public-privé (PPM) pour la tuberculose (TB) mis en œuvre par l'association médicale du Myanmar (MMA) dans 105 townships, Myanmar.Objectifs : 1) Evaluer la contribution du projet TB MMA-PPM à la notification totale des patients TB dans les townships du projet ; 2) évaluer le devenir des patients traités dans les centres de santé MMA-PPM ; et 3) identifier les facteurs associés avec un résultat défavorable du traitement de janvier à décembre 2013.Schéma : Étude rétrospective de cohorte.Résultats : Le projet MMA-PPM-TB a contribué à 7501 (12%) des 60 905 notifications de patients TB au Programme National TB dans les 105 townships de l'étude. Parmi 2975 patients TB diagnostiqués et traités dans les centres privés du MMA-PPM, 92% ont eu un résultat favorable (32% de guérison, 60% d'achèvement) et 8% des patients ont eu un résultat défavorable (2,9% sont décédés, 2,5% ont été perdus de vue, 1,9% ont eu un échec du traitement et 0,6% ont déménagé). Les caractéristiques des patients significativement associées avec un résultat défavorable du traitement ont été l'âge ⩾65 ans (ratio de risque ajusté [aRR] 5,7 ; intervalle de confiance [IC] 95% 4,20­7,68), le retraitement (aRR 2,44 ; IC95% 1,79­3,33) et le sexe féminin (aRR 1,44 ; IC95% 1,14­1,82).Conclusion : Cette étude est en faveur de la poursuite et de l'expansion du modèle MMA-PPM-TB et/ou d'approches similaires public-privé au Myanmar, engageant tous les prestataires de santé, car ce pays en transition présente une vision audacieuse consistant à offrir une couverture santé universelle et à mettre fin à l'épidémie de TB d'ici 2035.

Marco de referencia: El proyecto de colaboración público-privada (PPM) en materia de tuberculosis (TB) puesta en práctica por la Asociación Médica de Myanmar (MMA) en 105 municipios de Birmania.Objetivos: 1) Evaluar la contribución del MMA-PPM-TB en Birmania al total de notificaciones de casos de TB en los municipios que participaron; 2) evaluar los desenlaces clínicos de los pacientes tratados en los consultorios participantes; y 3) definir los factores que se asociaron con los desenlaces terapéuticos desfavorables, de enero a diciembre del 2013.Método: Fue este un estudio retrospectivo de cohortes.Resultados: El MMA-PPM-TB aportó 7501 casos (12%) a las 60 905 notificaciones de pacientes al Programa Nacional contra la TB en los 105 municipios que participaron en el estudio. De los 2975 pacientes diagnosticados con TB y tratados en los consultorios del MMA-PPM-TB, el 92% logró un desenlace terapéutico favorable (32% curaciones y 60% tratamientos completos) y el 8% obtuvo un desenlace desfavorable (2,9% defunciones, 2,5% pérdidas durante el seguimiento, 1,9% fracasos y 0,6% transferencias a otros centros). Las características que se asociaron de manera significativa con un desenlace desfavorable fueron la edad ⩾65 años (riesgo relativo ajustado [RRa] 5,7; intervalo de confianza [IC] del 95% 4,20­7,68), los pacientes en retratamiento (RRa 2,44; IC95% 1,79­3,33) y el sexo femenino (RRa 1,44; IC95% 1,14­1,82).Conclusión: Los resultados del presente estudio respaldan la continuación y la ampliación del modelo de MMA-PPM-TB y de otras iniciativas equivalentes de PPM en Birmania que vinculen a todos los profesionales de salud, pues el país en un momento de transición pone en marcha una perspectiva ambiciosa de cobertura universal de salud y de erradicación de la epidemia de TB en el 2035.

Negotiating palliative care in the context of culturally and linguistically diverse patients.

There is an increasing emphasis on meeting the healthcare needs of culturally and linguistically diverse (CALD) communities in Australia. Negotiating the point of futility and the transition to specialist palliative care requires not only effective communication but also sensitivity to cultural and linguistic specificities. This can be a challenging process for clinicians, patients and families. Here, we outline some of the key challenges currently facing many clinicians in the context of CALD patients, with particular reference to the transitioning of patients to specialist palliative care. We suggest a focus on further research that can systematically document and model existing CALD-specific clinical processes and pathways, which can then support the development of targeted educational interventions. This includes developing a multi-stakeholder understanding of the CALD experience that moves beyond cultural stereotyping and predicting need.