Accelerated hyperfractionation plus temozolomide in glioblastoma

Einführung: Gliome sind der häufigste primäre Tumor des zentralen Nervensystems bei Erwachsenen. Der häufigste und bösartigste Typ des Glioms ist das Glioblastom. Derzeitige Behandlungsstandards bestehen aus Resektion, adjuvanter normal fraktionierter Radiotherapie mit gleichzeitiger Gabe von Temozolomid und Temozolomid Gabe nach Radiotherapie. Hyperfraktionierte Radiotherapien oder hyperfraktionierte akzelerierte Radiotherapien (HART) werden aufgrund einer hypothetischen Reduktion später Bestrahlungsschäden sowie einer Verhinderung der Repopulation des Tumorbetts diskutiert. Die hyperfraktionierte Radiotherapie und die HART wurden vor Einführung von Temozolomid als Standard in der Chemotherapie des Glioblastoms ausgiebig untersucht, ohne eindeutige Ergebnisse. In dieser Studie untersuchten wir die Rolle der hyperfraktionierten akzelerierten Radiotherapie in der Temozolomid Ära. Material und Methoden: Wir verglichen für den Behandlungszeitraum von Februar 2009 bis Oktober 2014 vierundsechzig Patienten, behandelt mit HART, mit siebenundsechzig Patienten, die mit klassischer, normal fraktionierter Radiotherapie behandelt wurden. 62 der mit einer HART behandelten und 64 der mit klassischer Radiotherapie behandelten Patienten erhielten Temozolomid. Follow-up Daten wurden bis Januar 2015 analysiert. Ergebnisse: Das mediane Overall-survival (OS) betrug 13 Monate für alle Patienten. Für mit klassischer RT behandelte Patienten betrug das mediane OS 15 Monate, für mit HART behandelte Patienten 10 Monate. In der univariablen und multivariablen Analyse besaß das Regime der Fraktionierung keinen Vorhersagewert für das Überleben. Diskussion: In der univariablen und multivariablen Analyse ließen sich keine signifikanten Unterschiede zwischen den klassischen RT und HART Regimen nachweisen. Die Vorzüge sind offenkundig: das akzelerierte Regime verkürzt bedeutsam die Dauer der Hospitalisierung für ein Patientenkollektiv mit stark eingeschränkter Lebenserwartung. Wir schlagen eine weitere Untersuchung der Rolle einer HART in Kombination mit Temozolomid in zukünftigen prospektiv angelegten Studien vor.Introduction: Gliomas are the most common primary tumors of the central nervous system in adults. The most common and most malignant type of glioma is glioblastoma. Current standard of care comprises resection, adjuvant normofractionated radiotherapy with concurrent temozolomide and post-RT temozolomide. Hyperfractionated (HFRT) or accelerated hyperfractionated radiotherapy (AHFRT) have been discussed based on a hypothesized reduction of late radiation injury and prevention of repopulation. HFRT and AHFRT have been examined extensively in the pre-Temozolomide era with inconclusive results. In this study we examined the role of accelerated hyperfractionation in the Temozolomide era. Materials and methods: Sixty-four patients who underwent AHFRT (62 of which received Temozolomide) were compared to sixty-seven patients who underwent normofractionated (64 of which received Temozolomide) between 02/2009 and 10/2014. Follow-up data were analyzed until 01/2015. Results: Median overall survival (OS) was 13 months for all patients. For patients treated with NFRT median OS was 15 months, for patients treated with AHFRT median OS was 10 months. The fractionation regimen was not a predictor of survival in univariable- or multivariable analysis. Discussion: Univariable and multivariable analysis did not show significant differences between the NFRT and AHFRT fractionation regimens. The benefits are immanent: the regimen does significantly shorten hospitalization time in a patient collective with a highly impaired life expectancy. We propose that the role of AHFRT in combination with Temozolomide should be further examined in future prospective trials

Understanding Brain Mechanisms of Reactive Aggression

PURPOSE OF REVIEW To review the current literature on biobehavioral mechanisms involved in reactive aggression in a transdiagnostic approach. RECENT FINDINGS Aggressive reactions are closely related to activations in the brain's threat circuitry. They occur in response to social threat that is experienced as inescapable, which, in turn, facilitates angry approach rather than fearful avoidance. Provocation-induced aggression is strongly associated with anger and deficits in cognitive control including emotion regulation and inhibitory control. Furthermore, the brain's reward system plays a particular role in anger-related, tit-for-tat-like retaliatory aggression in response to frustration. More research is needed to further disentangle specific brain responses to social threat, provocation, and frustration. A better understanding of the psychological and neurobiological mechanisms involved in reactive aggression may pave the way for specific mechanism-based treatments, involving biological or psychotherapeutic approaches or a combination of the two

Accelerated hyperfractionation plus temozolomide in glioblastoma

Introduction Hyperfractionated (HFRT) or accelerated hyperfractionated radiotherapy (AHFRT) have been discussed as a potential treatment for glioblastoma based on a hypothesized reduction of late radiation injury and prevention of repopulation. HFRT and AHFRT have been examined extensively in the pre-Temozolomide era with inconclusive results. In this study we examined the role of accelerated hyperfractionation in the Temozolomide era. Materials and methods Sixty-four patients who underwent AHFRT (62 of which received Temozolomide) were compared to 67 patients who underwent normofractionated radiotherapy (NFRT) (64 of which received TMZ) between 02/2009 and 10/2014. Follow-up data were analyzed until 01/2015. Results Median progression-free survival (PFS) was 6 months for the entire cohort. For patients treated with NFRT median PFS was 7 months, for patients treated with AHFRT median PFS was 6 months. Median overall survival (OS) was 13 months for all patients. For patients treated with NFRT median OS was 15 months, for patients treated with AHFRT median OS was 10 months. The fractionation regimen was not a predictor of PFS or OS in univariable- or multivariable analysis. There was no difference in acute toxicity profiles between the two treatment groups. Conclusions Univariable and multivariable analysis did not show significant differences between NFRT and AHFRT fractionation regimens in terms of PFS or OS. The benefits are immanent: the regimen does significantly shorten hospitalization time in a patient collective with highly impaired life expectancy. We propose that the role of AHFRT + TMZ should be further examined in future prospective trials

The parenting experience of those with borderline personality disorder traits: practitioner and parent perspectives

Background: Borderline Personality Disorder (BPD) is associated with challenges around emotional intensity and interpersonal difficulties. The children of parents with BPD are at risk of poorer outcomes in terms of their own mental health, educational outcomes and wellbeing. The challenges of being a parent can also exacerbate the symptoms of those with BPD traits. There is a pressing need to understand the experience of these parents and to determine what support would be appropriate and useful. Aim: To explore and compare the experiences and support needs of parents with BPD traits with the experiences and understanding of practitioners who work with them. Methods: Interviews with 12 parents with BPD traits and 21 practitioners with experience of working with individuals with BPD. The two strands of interviews were analyzed independently using a thematic framework approach, after which the superordinate and subordinate themes were subject to comparison. Results: Parents with BPD traits represent themselves as experiencing considerable challenges in their role as a parent. These included the impact of emotional intensity, social isolation and lack of a positive parenting models to draw upon. Practitioners demonstrated a strong degree of shared understanding into these difficulties. Both groups highlighted a lack of appropriate support for these parents. Conclusion: This research highlights the clinical need for parenting-focused support for individuals with BPD traits. Preliminary suggestions for format and content are given