A Cancer Research UK First Time in Human Phase I Trial of IMA950 (Novel Multipeptide Therapeutic Vaccine) in Patients with Newly Diagnosed Glioblastoma.

Purpose: To perform a two-cohort, phase I safety and immunogenicity study of IMA950 in addition to standard chemoradiotherapy and adjuvant temozolomide in patients with newly diagnosed glioblastoma. IMA950 is a novel glioblastoma-specific therapeutic vaccine containing 11 tumor-associated peptides (TUMAP), identified on human leukocyte antigen (HLA) surface receptors in primary human glioblastoma tissue.

Experimental Design: Patients were HLA-A*02-positive and had undergone tumor resection.

Management of central nervous system tumours in the elderly.

Brain tumours in the elderly show differences from the general population in their spectrum of incidence, their molecular profile and their response to treatment. Furthermore, this population also finds it more difficult to tolerate the treatments applied to younger patients. For these reasons it is justified to investigate older patients separately and to devise treatments applicable specifically to this population.

The frequency, longitudinal course, clinical associations, and causes of emotional distress during primary treatment of cerebral glioma.

Background: Relatively little is known about the frequency, longitudinal course, independent associations, and reported causes of emotional distress in adults with primary cerebral glioma. We aimed to describe these features in an observational study.

Methods: This was a twin-center prospective cohort study.

Screening for major depressive disorder in adults with glioma using the PHQ-9: a comparison of patient versus proxy reports.

When screening for depression in glioma patients, the utility of proxy carer report is unknown. We studied how patients and proxies differed in the frequency, severity and agreement of reported depressive symptoms, the external validity of these reports, and whether patient-proxy agreement was associated with cognitive function. This was a cross-sectional study within a prospective cohort study of depression in glioma.

Screening for major depressive disorder in adults with cerebral glioma: an initial validation of 3 self-report instruments.

No depression screening tool is validated for use in cases of cerebral glioma. To address this, we studied the operating characteristics of the Hospital Anxiety and Depression Scale (Depression subscale) (HAD-D), the Patient Health Questionnaire-9 (PHQ-9), and the Distress Thermometer (DT) in glioma patients.We conducted a twin-center prospective observational cohort study of major depressive disorder (MDD), according to the Diagnostic and Statistical Manual, 4th edition, in adults with a new diagnosis of cerebral glioma receiving active management or "watchful waiting.

New prognostic factors and calculators for outcome prediction in patients with recurrent glioblastoma: a pooled analysis of EORTC Brain Tumour Group phase I and II clinical trials.

Background: Prognostic models have been developed to predict survival of patients with newly diagnosed glioblastoma (GBM). To improve predictions, models should be updated with information at the recurrence. We performed a pooled analysis of European Organization for Research and Treatment of Cancer (EORTC) trials on recurrent glioblastoma to validate existing clinical prognostic factors, identify new markers, and derive new predictions for overall survival (OS) and progression free survival (PFS).

A phase I study of LY317615 (enzastaurin) and temozolomide in patients with gliomas (EORTC trial 26054).

We report a phase 1 study to examine the safety and recommended dose of the oral protein kinase C-beta inhibitor (anti-angiogenic) enzastaurin in combination with single-agent temozolomide. The study was conducted in patients with recurrent glioblastoma or newly diagnosed disease that was not treatable with standard (chemo)radiotherapy. Patients were treated with standard dose temozolomide (200 mg/m(2) for 5 days every 4 weeks) together with daily oral enzastaurin.

Frequency, clinical associations, and longitudinal course of major depressive disorder in adults with cerebral glioma.

Purpose: There is a need for high-quality evidence regarding the frequency, independent clinical associations, and longitudinal course of depression in patients with cerebral glioma.

Patients And Methods: This was a twin-center, prospective, observational cohort study with 6-month follow-up. Consenting adults with a new diagnosis of cerebral glioma received the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition to diagnose major depressive disorder (MDD).

Chk1 is essential for chemical carcinogen-induced mouse skin tumorigenesis.

Chk1 is a key regulator of DNA damage checkpoint responses and genome stability in eukaryotes. To better understand how checkpoint proficiency relates to cancer development, we investigated the effects of genetic ablation of Chk1 in the mouse skin on tumors induced by chemical carcinogens. We found that homozygous deletion of Chk1 immediately before carcinogen exposure strongly suppressed benign tumor (papilloma) formation, and that the few, small lesions that formed in the ablated skin always retained Chk1 expression.

The concepts, diagnosis and management of early imaging changes after therapy for glioblastomas.

Since postoperative radiotherapy plus concomitant temozolomide followed by adjuvant temozolomide has become standard treatment for glioblastoma, the phenomenon of early post-treatment enlargement of the imaged tumour volume, usually without clinical deterioration, has become widely recognised. The term pseudoprogression has been used to describe a poorly understood pathophysiological process. In this review, the pathophysiological concepts, relevance, diagnosis and management of patients with 'pseudoprogression' and 'pseudoresponse' are discussed.

Temozolomide versus procarbazine, lomustine, and vincristine in recurrent high-grade glioma.

Purpose: Temozolomide (TMZ) is an alkylating agent licensed for treatment of high-grade glioma (HGG). No prospective comparison with nitrosourea-based chemotherapy exists. We report, to our knowledge, the first randomized trial of procarbazine, lomustine, and vincristine (PCV) versus TMZ in chemotherapy-naive patients with recurrent HGG.

Randomized phase II trial of erlotinib versus temozolomide or carmustine in recurrent glioblastoma: EORTC brain tumor group study 26034.

Purpose: Approximately 50% of glioblastomas (GBMs) are characterized by overexpression of the epidermal growth factor receptor (EGFR) and EGFR gene amplification. In approximately 25% of instances, constitutively activated EGFR mutants are present. These observations make EGFR-inhibiting drugs a logical approach for trials in recurrent GBM.

Phase II study of imatinib in patients with recurrent gliomas of various histologies: a European Organisation for Research and Treatment of Cancer Brain Tumor Group Study.

Purpose: To evaluate the safety and the efficacy of imatinib in recurrent malignant gliomas.

Patients And Methods: This was a single-arm, phase II study. Eligible patients had recurrent glioma after prior radiotherapy with an enhancing lesion on magnetic resonance imaging.

Hypoxia-selective targeting by the bioreductive prodrug AQ4N in patients with solid tumors: results of a phase I study.

Purpose: AQ4N is a novel bioreductive prodrug under clinical investigation. Preclinical evidence shows that AQ4N penetrates deeply within tumors and undergoes selective activation to form AQ4, a potent topoisomerase II inhibitor, in hypoxic regions of solid tumors. This proof-of-principle, phase I study evaluated the activation, hypoxic selectivity, and safety of AQ4N in patients with advanced solid tumors.

Assessment of 123I-FIAU imaging of herpes simplex viral gene expression in the treatment of glioma.

Background: Herpes simplex virus 1716 (HSV1716), a selectively replication competent mutant of HSV1, is under investigation as an oncolytic viral therapy in human malignant glioma. As with similar therapies, a technique for measurement of viral replication and distribution over time following virus administration is required. Imaging expression of the HSV-thymidine kinase (HSV-tk) gene offers an opportunity for non-invasive assessment of viral distribution in living subjects.

Assessment in vitro of a novel therapeutic strategy for glioma, combining herpes simplex virus HSV1716-mediated oncolysis with gene transfer and targeted radiotherapy.

Genetically engineered herpes simplex virus ICP34.5 null mutants replicate only in dividing cells and have shown potential for the treatment of malignant disease, including glioma. Phase I trials have demonstrated the safety of these viruses in various clinical settings but it is envisaged that for full efficacy they will be used in combination with other therapeutic modalities.

HSV1716 injection into the brain adjacent to tumour following surgical resection of high-grade glioma: safety data and long-term survival.

Following standard treatment, the prognosis remains poor in patients with high-grade glioma and new therapies are urgently required. Herpes simplex virus 1716 (HSV1716) is an ICP34.5 null mutant that is selectively replication competent and shown to be safe and to replicate following injection into high-grade glioma.

Updated European core curriculum for radiotherapists (radiation oncologists). Recommended curriculum for the specialist training of medical practitioners in radiotherapy (radiation oncology) within Europe.

Aim: To produce updated state-of-the-art recommendations for harmonised medical specialist training in radiotherapy within Europe.

Material And Methods: The Minimum Curriculum for the Theoretical Education in Radiation Oncology in Europe from 1991 was updated under consideration of new developments in medicine in general, and in radiotherapy and its basic sciences in particular. Recent medical developments, national guidelines and training programmes from European countries, as well as equivalent documents from the USA and Australia were reviewed by an expert panel jointly appointed by the European Society of Therapeutic Radiology and Oncology and the European Board of Radiotherapy.

Involvement of apolipoprotein E in glioblastoma: immunohistochemistry and clinical outcome.

We hypothesised that apolipoprotein E (apoE) influences brain tumours by delivery of lipids to tumour cells and by analogy with other brain insults. APOE gene analysis was performed for 126 glioblastomas, the commonest primary brain tumour. Neither APOE epsilon2 nor epsilon4 alleles were significantly associated with differences in post-operative survival.

Don't wait for a sensory level--listen to the symptoms: a prospective audit of the delays in diagnosis of malignant cord compression.

Aim: To report details concerning symptoms (especially pain) preceding the development of malignant cord compression (MCC); delays between onset/reporting of symptoms and confirmed diagnosis of MCC; accuracy of investigations carried out.

Methods: A prospective observational study examined the diagnosis, management and outcome of 319 patients diagnosed with MCC at three Scottish cancer centres between January 1998-April 1999. The process was considered from the perspectives of the patient, the GP and the hospital doctor.

Phase II study of XR5000 (DACA) administered as a 120-h infusion in patients with recurrent glioblastoma multiforme.

Background: XR5000 is a tricyclic carboxamide that intercalates DNA and inhibits both topoisomerase I and II. The aim of this study was to evaluate the efficacy and tolerability of XR5000 in patients with recurrent glioblastoma multiforme previously untreated with chemotherapy at relapse.

Patients And Methods: Patients received XR5000 at a dose of 3010 mg/m2 as a 120-h central venous infusion every 3 weeks.

The potential for efficacy of the modified (ICP 34.5(-)) herpes simplex virus HSV1716 following intratumoural injection into human malignant glioma: a proof of principle study.

We have previously demonstrated the safety of intratumoural administration of the selectively replication-competent herpes simplex virus mutant HSV1716 in patients with high-grade glioma (HGG). Here we show its potential for efficacy by demonstrating that the virus survives and replicates when injected into the tumours of patients. Since HSV replication is a cytolytic process it must result in tumour cell killing.

Multicenter phase II trial of temozolomide in patients with glioblastoma multiforme at first relapse.

Background: Recurrent glioblastoma multiforme (GBM) is resistant to most therapeutic endeavors, with low response rates and survival rarely exceeding six months. There are no clearly established chemotherapeutic regimens and the aim of treatment is palliation with improvement in the quality of life.

Patients And Methods: We report an open-label, uncontrolled, multicenter phase II trial of temozolomide in 138 patients (intent-to-treat [ITT] population) with glioblastoma multiforme at first relapse and a Karnofsky performance status (KPS) > or = 70.

Long-term survival following extra-neural metastasis from a pineoblastoma.

A young woman presented with a pineoblastoma treated initially with whole neuraxis radiotherapy. She had biopsy confirmed metastatic disease to the left lateral pelvis which was treated on 2 separate occasions, and biopsy confirmed metastatic disease to the subcutaneous tissues of the left thigh. She currently remains well 8 years after the primary diagnosis and 6 years after the first systemic relapse.