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Abstract: 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. [Copyright &y& Elsevier]

Abstract: Aims: Technical developments in radiotherapy have increased very rapidly over recent years, resulting in the processes of radiotherapy planning and delivery changing significantly. It is essential that alongside these developments, optimal methods for accurate target volume definition become a priority. The Radiotherapy Imaging for Delivery of Radiotherapy Working Party was formed to create a framework for imaging for radiotherapy planning and delivery: the areas of interest were interpretation of imaging for planning, optimum acquisition of imaging for radiotherapy planning and training and assessment across all staff groups involved with radiotherapy planning. A detailed assessment of the current situation in the UK was needed to prepare for this document. A national survey was undertaken and the results are reported in this paper. Materials and methods: A questionnaire was sent to all NHS radiotherapy departments in the UK on 3 occasions in 2007. A total of 48 replies were received from 58 centres giving a response rate of 83%. Results: Approximately half of centres (46%) in the UK use IMRT. Thirteen centres are using IMRT in the routine management of patients. Nine centres indicated that they use IMRT routinely within the research setting. Twenty-six centres are not using IMRT but 10 centres are planning to implement the technology within 12 months. Only 4 centres in the UK routinely use IGRT and 6 centres report use of image guidance in the research setting. Twelve centres are planning to implement this over 12 months. Few oncologists have dedicated radiology input for planning. Twenty-seven centres had help from radiologists on an ad hoc basis only and 10 centres had no input at all. Only 2 centres have formal radiology training for trainees and 9 centres report ad hoc time with diagnostic radiologists or cite the FRCR course as the main sources of training. Twelve centres have structured training for radiographers and 4 centres for medical physicists. Conclusions: This survey assessed radiotherapy planning and delivery within the UK in 2007. The most significant findings were the lack of implementation of IMRT and IGRT which appeared to mainly to be due to lack of available staff, such as medical physicists, insufficient access to existing equipment, lack of time for more complex radiotherapy planning and insufficient funding. A further concern is the lack of formal training in tumour and normal tissue outlining across several staff groups. [Copyright &y& Elsevier]

AIMS: The assessment of the risk of developing cancer is largely based on family history. This study aimed to confirm as many cancer diagnoses as possible in families of patients with second primary tumours after index squamous cell carcinoma of the head, single squamous cell carcinoma and spouse controls. MATERIALS AND METHODS: Eighty patients with second primary tumours, 67 with single squamous cell carcinoma and 47 spouse controls were recruited into the study. A detailed interview was undertaken on all study participants, including information on all first-degree relatives for causes of death and possible diagnoses of cancer. RESULTS: Details were available from 1340 first-degree relatives: second primary tumour group 570 relatives, single squamous cell carcinoma 429 relatives and the spouse controls 341 relatives. There were 174 cases of cancer (76, 56 and 42, respectively). For those relatives that had died, submissions were made to the Office of National Statistics to confirm the cause and date of death. One hundred and thirty-three cases were submitted for Office of National Statistics flagging (58, 42 and 33, respectively). Seventy-four of the first-degree relatives with cancer were successfully traced. Tracing confirmed a cancer diagnosis but no further details of the primary site in 31 of the relatives. Thirty-eight of the first-degree relatives were confirmed to have the cancer site of diagnosis reported by the study participants. Thirteen of the reported diagnoses in the first-degree relatives were inaccurate with regard to the cancer site of origin. Five of the first-degree relatives did not have a cancer diagnosis confirmed on the death certificate. CONCLUSIONS: This study highlights the difficulties encountered in confirming cancer diagnoses among first-degree relatives within this cancer site. To improve such studies and our routine collection of data within the clinic setting, more robust systems are needed to interlink cancer registries, population data and hospital records. [ABSTRACT FROM AUTHOR]

Summary: We investigated the association between genetic polymorphisms in GPX1 gene amongst patients who had index squamous cell carcinoma (SCCHN) and a second primary tumour (SPT) after a primary SCCHN in a case-control study. GPX1 genotypes were determined for 61 patients with SPT and for 259 control subjects by a PCR technique using a fluorescent-labelled primer. Analysis was by an ABI automated fluorescent sequencer. The associations between specific genotypes and the development of SPT were examined by logistic regression. A significant difference was found between the control group and the SPT cases in allele frequencies of GPX1 ALA∗6 and ALA∗7 (p trend =0.04). These results suggest that polymorphisms in the GPX1 gene may be a marker for SPT development and further studies are indicated. [Copyright &y& Elsevier]

Glioblastoma (GBM) is a common brain tumour in adults, which, despite multimodality treatment, has a poor median survival. Efficacy of therapy is assessed by clinical examination and magnetic resonance imaging (MRI) features. There is now a recognised subset of treated patients with imaging features that indicate "progressive disease" according to Macdonald's criteria, but subsequently, show stabilisation or resolution without a change in treatment. In these cases of "pseudoprogression", it is believed that non-tumoural causes lead to increased contrast enhancement and conventional MRI is inadequate in distinguishing this from true tumour progression. Incorrect diagnosis is important, as failure to identify pseudoprogression could lead to an inappropriate change of effective therapy. The purpose of this review is to outline the current research into radiological assessment with MRI and molecular imaging of post-treatment GBMs, specifically the differentiation between pseudoprogression and tumour progression. [ABSTRACT FROM AUTHOR]

Abstract: 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. Guidelines are given with respect to radiological imaging modality, mode and frequency. Further biological and clinical insights into these phenomena require carefully designed prospective studies. [Copyright &y& Elsevier]

Abstract: Aims: To quantify the changes in contours of the target and organs at risk and the differences between planned and delivered doses to the target and organs at risk during the course of radiotherapy in head and neck cancer patients treated with intensity-modulated radiotherapy on the TomoTherapy HiArt™ system. Materials and methods: Five patients with squamous cell carcinoma of the head and neck treated with radical chemoradiotherapy using the TomoTherapy HiArt system were included in the study. The target volumes were treated to three different dose levels depending on the level of clinical risk for harbouring disease. Patient positions were assessed daily with megavoltage computed tomography (MVCT) and positional correction made before each treatment when necessary. MVCTs were superimposed on to the planning kilovoltage computed tomography images for each patient and target volumes and organ at risk volumes were re-outlined on MVCT images. Doses to clinical target volumes and organs at risk were recalculated to show the actual delivered doses. Results: There was shrinkage in the volume of the parotid glands during treatment in all cases. The mean volume reduction in the ipsilateral parotid gland was more marked at 30.2%, compared with the contralateral parotid glands. However, the mean percentage dose per fraction increase was higher in the contralateral parotid glands at 24%, compared with the ipsilateral parotids. The calculated doses were higher than the planned doses in all CTV-54, CTV-60 and CTV-68, but the mean dose differences were modest, in the range 1.3–2.4%. Conclusions: We have shown that there were considerable changes in the volume and dose to the parotids during treatment. The changes in volume and dose to the clinical target volume were more modest in comparison. Adaptive radiotherapy planning can be helpful in improving the dose to the parotid glands. However, its role in the optimisation of the dosage to the clinical target volume is less likely to result in a significant clinical benefit. [ABSTRACT FROM AUTHOR]