Adult acute lymphoblastic leukaemia in Denmark. A national population‐based retrospective study on acute lymphoblastic leukaemia in Denmark 1998–2008

Since July 2008, children and adults 1–45 years, diagnosed with acute lymphoblastic leukaemia (ALL) in Denmark have been treated according to the common Nordic Society for Paediatric Haematology and Oncology ALL2008 protocol. To explore whether this strategy will improve survival compared with historical controls, we performed a retrospective national population‐based study of adult ALL between 1998 and 2008. Patients were identified through the Danish Patobank and the Danish Cancer Registry; data was collected from patient files, and included 277 patients (median age, 47 years, range 15–91 years). The 5‐year projected event‐free survival (pEFS_5y) and overall survival (pOS_5y) for the whole cohort was 27·5% [95% confidence interval (CI) 22·4–33·6] and 34·1% (95% CI 28·7–40·4), respectively. No patient above 65 years survived beyond 5 years from diagnosis. For patients receiving curatively intended treatment, the pEFS_5y and pOS_5y were 36·6% and 44·1%, respectively, with a significantly higher pOS_5y for patients 15–35 years compared with patients 36–65 years (50·7% vs. 38·9%, P = 0·006). Cox multiple regression analysis identified age (Hazard Ratio = 1·7, P < 0·006) as a statistically significant predictor of EFS. The cure rates, not least for the elderly, are unacceptably low, and call for new strategies in the treatment of adult ALL in all age groups.     

Association of adrenocortical carcinoma with familial cancer susceptibility syndromes

Our knowledge about inherited susceptibility to adrenocortical carcinoma (ACC) almost exclusively stems from experiences with familial cancer susceptibility syndromes, which are caused by single gene mutations (e.g. Li-Fraumeni syndrome (LFS)). Population-based studies are largely unavailable. ACC diagnosed during childhood is known to be commonly part of hereditary cancer syndromes. Childhood ACC is part of the classical tumor spectrum of LFS and Beckwith-Wiedemann syndrome (BWS). In adults ACC has been reported in patients with multiple endocrine neoplasia (MEN1), familial adenomatous polyposis coli (FAP) and neurofibromatosis type 1 (NF1). However, the evidence associating ACC with these syndromes is less well substantiated. Here, we will review the evidence for genetic predisposition in general and the association with known familial cancer susceptibility syndromes in particular. We will also review current recommendations regarding screening and surveillance of these patients as they apply to a specialized ACC or endocrine cancer clinic.     

The art of gene therapy for glioma： a review of the challenging road to the bedside

Glioblastoma muhiforme （GBM） is a highly invasive brain tumour that is unvaryingly fatal in humans clesplte even aggres- sive therapeutic approaches such as surgical resection followed by chemotherapy and radiotherapy. Unconventional treatment options such as gene therapy provide an intriguing option for curbing glioma related deaths. To date, gene therapy has yielded encouraging results in preclinical animal models as well as promising safety profiles in phase I clinical trials, but has failed to demonstrate significant therapeutic efficacy in phase III clinical trials. The most widely studied antiglioma gene therapy strategies are suicide gene therapy, genetic immuno- therapy and oncolytic virotherapy, and we have attributed the challenging transition of these modalities into the clinic to four major road- blocks ： （ 1 ） anatomical features of the central nervous system, （2） the host immune system, （3） heterogeneity and invasiveness of GBM and （4） limitations in current GBM animal models. In this review, we discuss possible ways to jump these hurdles and develop new gene therapies that may be used alone or in synergy with other modalities to provide a powerful treatment option for patients with GBM.     

The tower of Babel: Survey on concepts and terminology in electrical status epilepticus in sleep and continuous spikes and waves during sleep in North America

Purpose: The terms “electrical status epilepticus during sleep (ESES)” and “continuous spikes and waves during sleep (CSWS)” have been used interchangeably when referring to related but different concepts. In addition, the quantification of epileptiform activity has not been standardized, and different approaches to quantification have been used. The aim of this study was to evaluate the extent to which pediatric neurologists and epileptologists use a homogeneous terminology and conceptualization in CSWS and ESES and to characterize the current understanding of these conditions. Methods: A survey addressing the use of terminology in “ESES” and “CSWS” and the understanding of related concepts was distributed online to all members of the Child Neurology Society and the American Epilepsy Society mailing lists. Surveys were self‐administered and collected using an online survey website ( http://www.surveymonkey.com ). Key Findings: Two hundred nineteen surveys were completed, 137 from the Child Neurology Society mailing list and 82 from the American Epilepsy Society mailing list. ESES and CSWS were considered synonymous by 117 respondents, not synonymous by 61, 21 respondents did not know, and 20 did not respond. Most respondents (63.1%) considered CSWS as a devastating epileptic encephalopathy with severe sequelae even if treated correctly, but 25.1% of respondents indicated that it does not leave sequelae if epilepsy was treated early and another 11.8% noted that cognitive difficulties resolved with age. Cognitive and/or language regression were considered mandatory for the diagnosis of CSWS by only 27% of the respondents. The diagnosis of CSWS was based on electroencephalography (EEG) assessment alone by 31% of respondents. Respondents used different methods for calculation of the epileptiform activity, different EEG samples for calculation, and considered differently the lateralized epileptiform activity. The cut‐off values for percentage of the sleep record occupied by spike‐waves were variable depending on the respondent. There was no agreement on whether these cutoff values were mandatory for the diagnosis of ESES and CSWS. Significance: Our data show that the professionals caring for children with ESES and CSWS in North America use the terms, concepts, and defining features heterogeneously. The lack of a common language may complicate communication among clinicians and jeopardize research in this field. We anticipate that our data will fuel the development of much needed common terminology and conceptualization of ESES and CSWS.