Has the survival of patients with glioblastoma changed over the years?

BACKGROUND: Over the last decade, the approach to the management of brain tumours and the understanding of glioblastoma tumour biology has advanced and a number of therapeutic interventions have evolved, some of which have shown statistically significant effects on overall survival (OS) and progression-free survival in glioblastoma. The aim of this study is to compare survival in glioblastoma patients over a 10-year period (1999-2000 and 2009-2010). METHODS: A retrospective cohort study was performed. Identification of all histologically confirmed glioblastoma in a single centre in years 1999, 2000, 2009 and 2010, and production of survival analysis comparing 1999-2000 and 2009-2010 were achieved. RESULTS: A total of 317 patients were included in the analysis (133 in year 1999-2000, and 184 in year 2009-2010). Cox regression analysis showed that the survival was significantly longer in patients in years 2009-2010 than those in 1999-2000 at P<0.001 with HR=0.56, confidence interval (CI) (0.45-0.71). The 1- and 3-year survival rates were 20.7% and 4.4%, respectively, for patients in 1999-2000, improving to 40.0% and 10.3%, respectively, for patients in 2009-2010. The comparisons between the two groups in survival at 1, 2 and 3 years are all statistically significant at P<0.001, respectively. The median OS was 0.36 and 0.74 in 1999-2000 and 2009-2010 groups, respectively. CONCLUSIONS: Over this period, OS from glioblastoma has increased significantly in our unit. We believe this is due to the institution of evidence-based surgical and oncological strategies practised in a multidisciplinary setting.

Neurobehavioural changes in patients following brain tumour: patients and relatives perspective.

PURPOSE: Patients and relatives experiences of behavioural and personality changes following brain tumour were assessed to determine whether these changes are more prominent in the experience of patients with frontal tumours and their relatives as a first step to evaluate the need to develop appropriate support and management of such changes, which have a substantial impact on social functioning, and ultimately to improve quality of life. METHODS: Patients and relatives rated the patients' current levels of apathy, disinhibition and executive dysfunction on the Frontal Systems Behaviour Scale. Patients also completed the Hospital Anxiety and Depression Scale. The data from 28 patients with frontal tumours and 24 of their relatives, and 27 patients with nonfrontal tumours and 25 of their relatives, were analysed. RESULTS: Patients with frontal tumours rated themselves significantly higher than patients with nonfrontal tumours on all frontal systems-related behaviours. The number of patients reporting clinical levels of difficulty was significantly greater in patients with frontal tumours for disinhibition. The ratings of relatives of patients with frontal tumours were significantly higher than those of relatives of patients with nonfrontal tumours for apathy. Clinically significant levels of apathy and executive dysfunction were however reported by at least 40 % of patients and relatives regardless of tumour location. Clinical levels of anxiety were reported by significantly more patients with frontal tumours than those with nonfrontal tumours. CONCLUSION: Support and management of behavioural and personality change for patients with brain tumours and their relatives, regardless of tumour location, would be most appropriate.

Current and investigational drug strategies for glioblastoma.

Medical treatments for glioblastoma face several challenges. Lipophilic alkylators remain the mainstay of treatment, emphasising the primacy of good blood-brain barrier penetration. Temozolomide has emerged as a major contributor to improved patient survival. The roles of procarbazine and vincristine in the procarbazine, lomustine and vincristine (PCV) schedule have attracted scrutiny and several lines of evidence now support the use of lomustine as effective single-agent therapy. Bevacizumab has had a convoluted development history, but clearly now has no major role in first-line treatment, and may even be detrimental to quality of life in this setting. In later disease, clinically meaningful benefits are achievable in some patients, but more impressively the combination of bevacizumab and lomustine shows early promise. Over the last decade, investigational strategies in glioblastoma have largely subscribed to the targeted kinase inhibitor paradigm and have mostly failed. Low prevalence dominant driver lesions such as the FGFR-TACC fusion may represent a niche role for this agent class. Immunological, metabolic and radiosensitising approaches are being pursued and offer more generalised efficacy. Finally, trial design is a crucial consideration. Progress in clinical glioblastoma research would be greatly facilitated by improved methodologies incorporating: (i) routine pharmacokinetic and pharmacodynamic assessments by preoperative dosing; and (ii) multi-stage, multi-arm protocols incorporating new therapy approaches and high-resolution biology in order to guide necessary improvements in science.

Cost of managing women presenting with stage IV breast cancer in the United Kingdom.

This study estimated lifetime cost of treatment for patients in the United Kingdom (UK) presenting with stage IV breast cancer. To determine patterns of treatment and resource use in the absence of direct observational data, a cancer physician panel was surveyed. The survey questionnaire described four predefined treatment phases: active treatment; follow-up after active treatment until disease progression; active supportive care after progression; and end-of-life care. Physicians were asked their major treatment strategies for each phase. Monthly cost and average lifetime cost per patient were calculated. Only five cancer registries in the UK document the proportion of breast cancer patients diagnosed with stage IV disease. Their data was used to estimate the incidence of metastatic breast cancer at presentation throughout the UK. This value, together with lifetime cost per patient and projected survival time, allowed approximation of the overall cost for this population of cancer patients in the UK. Annual incidence of stage IV breast cancer at presentation in the UK is approximately 2100; according to treatment practice in 2002, lifetime cost per patient is pound 12 500 and total population cost is approximately pound 26 million. The substantial economic burden associated with patients diagnosed with metastatic breast cancer should be considered when developing strategies for reducing its incidence such as increased awareness, screening and preventative measures.

Radiotherapy in the treatment of benign meningioma of the skull base.

OBJECT: This study was undertaken to assess the long-term efficacy and toxicity of conventional fractionated external-beam radiation in the treatment of benign skull base meningioma. METHODS: This is a retrospective study of 82 patients with histologically verified benign skull base meningioma treated by surgery followed by fractionated external-beam radiation at the Royal Marsden Hospital between 1962 and 1992. The 5- and 10-year progression-free survival (PFS) rates were 92% and 83%, respectively, with the site of disease being the only independent prognostic factor for tumor control according to multivariate analysis. The 10-year PFS rate for patients with sphenoid ridge meningiomas was 69% compared with 90% for those with tumors in the parasellar region. The overall 10-year survival rate was 71%, with performance status and patient age found to be significant independent prognostic factors. Six patients had worsening vision, which was due to cataract in five cases and retinopathy in one. There were no recorded cases of cranial nerve neuropathy. CONCLUSIONS: The excellent long-term tumor control and length of survival with minimal toxicity associated with conventional external-beam radiation should serve as a baseline for evaluation of new treatment strategies such as radiosurgery and skull base surgery.

Verbally administered Barthel Index as functional assessment in brain tumour patients.

OBJECTIVE: To investigate verbally administered Barthel Index as a measure of functional status in patients with high grade gliomas. BACKGROUND: Barthel Index (BI) is a performance score of activities of daily living which has been validated in patients with neurological disability. While any assessment of quality of life in brain tumour patients should include all the aspects of CNS function we concentrated on measurement of physical performance status and evaluated the role of BI as a measure of palliative effect of treatment in patients with high grade glioma undergoing radiotherapy. METHODS: BI was verbally administered on 504 occasions in 107 patients with high grade glioma. The BI scores were correlated with Karnofsky performance score (KPS), and neurological performance score (NPS) as a measure of inter-index reliability. The BI's prognostic value was assessed using actuarial survival data. RESULTS: BI was sensitive to change and reflected the degree of functional impairment. In patients with high grade glioma BI correlated with KPS, and NPS (R2 = 0.872 and 0.658 respectively). BI score was also of prognostic value in terms of survival. The median survival of patients with functional independence was 9 months with moderate disability 5 months and with severe disability 4 months. CONCLUSION: Verbally administered Barthel Index is easy to use, reliable and sensitive to change and is of prognostic value. It is a useful tool in the management of patients with gliomas, as an objective evaluation of palliative effectiveness of treatment in patients with functional disability.

Medullary cell carcinoma of the thyroid: metastases to the central nervous system.

We document a case of a patient who had been treated for a medullary cell carcinoma of the thyroid three years previously and who presented with a three month history of ataxia, weakness and headache. A CT scan showed contrast enhancing lesions in the posterior fossa. An MIBG uptake scan showed that there was some uptake in the cerebellar lesions; however, it was not sufficient to rely on this alone for treatment. The larger of these lesions was therefore surgically resected. Immunocytochemistry, using CAM 5.2, CEA and chromogranin, demonstrated a positive reaction which strongly favoured a diagnosis of metastases from a medullary cell carcinoma of the thyroid. However, absolute confirmation of the diagnosis was obtained using immunocytochemistry with calcitonin. Medullary cell carcinomas of the thyroid usually spread locally and metastasis to the brain has never before been reported.