ASCO and avastin (bevacizumab): The results of two important clinical trials involving Avastin and glioblastoma were presented at the annual meeting of the American Society of Clinical Oncology (ASCO) held in Chicago during 31 May – 4 June 2013. The two trials were RTOG 0825 (a double-blind placebo-controlled trial of Avastin in patients with newly-diagnosed GBM) and AVAglio (progression-free survival and health-related Quality of life involving Avastin, Temozolomide and Radiotherapy in newly-diagnosed GBM).

The results created discussion and controversy, with one of the more balanced reports being by Anette Breindl in Bioworld.

Dr Mark Gilbert, from the MD Anderson Cancer Center, who presented the RTOG 0825 results was reported as stating that in relation to using bevacizumab in newly-diagnosed GBM:  “Our study would strongly suggest that it is not beneficial to do it as front-line treatment but to reserve it as second-line or salvage therapy”.

Some commentators worried that the overall results might have an adverse effect on the US Food and Drug Administration’s (FDA) “sort of conditional” approval for Avastin and brain tumours in 2009. The “worry” revolves around the survival advantage as expressed by progression-free survival (PFS) and overall survival (OS) but Dr Richard Pazdur from the FDA was reported in the New York Times as stating “We have approved a lot of drugs without a survival advantage”.

Brain Tumour patient advocates need to be alert to this on-going debate about the measurement of the survival advantage of new therapies for brain tumours and express their views when necessary.

Meanwhile, in a relatively little-reported media release by Roche on 17 June it was stated that Avastin had been approved in Japan for newly-diagnosed GBM in combination with radiotherapy and temozolomide and as monotherpy for recurrent GBM. The approval was based on the Phase II BRAIN study, a Japanese Phase II study (JO22506) and the Phase III AVAglio study. Furthermore, it was stated that applications for first-line treatment have been filed in the European Union and Switzerland.

Pratt and Whitney inquiry results: An 11-year study, costing $12 million, of 222,123 men and women who worked in one or more Connecticut (USA) Pratt and Whitney jet engine plants between 1976-2004, found no statistically significant elevations of the rate of cancer among workers. The study was overseen by the State Department of Health and undertaken by researchers at the University of Pittsburgh and the University of Illinois at Chicago and was prompted by the identification of an apparently disproportionate incidence of brain tumors among former workers.

The researchers also reviewed 11 chemical or physical agents on the basis of known or suspected carcinogenic potential that could affect the CNS or other organs. Garry Marsh, from the University of Pittsburgh, who led the study, was reported as saying "Let's face it: Brain cancer is a terrible disease and anyone who suffers from it or had a loved one suffer from it wants to know why they got that disease ... We looked at everything conceivable as a possible cause of brain cancer".

Utah scan for clusters: The Utah Department of Health is conducting a statewide scan for clusters of gliomas but Dr Howard Colman, a member of the brain Tumor and clinical research team at the Huntsman Cancer Institute has commented: "What I would say about the incidence of cancer clusters (is) in many cases when these have been investigated, there hasn't been a significant increased risk over what you would expect in the general population".

Dr Stanislaw Burzynski: Dr Burzynski from Texas is a controversial clinician. The UK BBC television program “Panorama” recently screened an item “Curing Cancer: Or Selling ‘Hope’ To The Vulnerable?” about his procedures and track record in treating brain tumors. UK readers can view the program here and non-UK readers can view it at this link.

Therapeutic developments: Researchers in Sydney, Australia, believe that microvesicles play an important role in the changes to blood vessels seen in high grade brain tumours and may provide a new target for future treatments.

North American researchers claim that a combination of the myxoma virus and the immune suppressant rapamycin can kill brain tumour stem cells and differentiated compartments of GBM.

Professor Harry T Whelan at Children's Hospital of Wisconsin is seeking to recruit patients for a Phase 1 Photodynamic Therapy (PDT) protocol for childhood brain tumours. See here for further details.

Company personnel and therapy developments: Cotara is a brain tumor therapy that has been under development for several years by Peregrine Pharmaceuticals Inc. Company staff told the IBTA at the recent ASCO meeting that they are seeking a partner to participate in their Global Phase III trial and to commercialize the product.

Fascinating insights into the Novocure Company, which produces the TTF device for brain tumour treatment, are contained in an interview with Novocure CEO Asaf Danziger.

The German company Magforce AG, which is progressing its Nanotherm technology for brain tumours, has appointed former Fresenius Medical Care AG CEO Ben Lipps as its new CEO.

Novartis is supporting a phase III randomized trial of LDE225 (Sonidegib) versus temozolomide in recurrent, relapsed or refractory sonic-hedgehog (SHH) positive medulloblastoma in both adult and pediatric patients. The clinical trial includes a new 5-gene signature test that can easily identify patients with SHH activated tumors and requires only a small amount of archival tissue. The clinical trial will be open at 88 different sites in 17 countries (Australia, Belgium, Brazil, Canada, France, Germany, Hungary, Israel, Italy, Netherlands, Poland, Russia, Spain, Sweden, Switzerland, UK, US) and is open for accrual. Investigators told the IBTA at the recent ASCO meeting that they were interested in including Asian sites in their coverage.

Dr Sean Lawler, originally from the Leeds Institute of Molecular Medicine (UK) and now at Brigham and Women's, has told the IBTA that he is working in the GBM context on an Astra Zeneca compound AZD1080 which is a GSK 3 beta inhibitor. This has come about through a UK Medical Research Council and Astra Zeneca initiative.

Brain tumour researchers from the German Cancer Research Center (DKFZ) are collaborating with Bayer Healthcare in searching for agents that might be specifically directed against the BCAT1 enzyme which could be cooperating with IDH in the decomposition of branched-chain amino acids.

Wrong diagnosis judgment: Fort Harrison VA Medical Center (USA) has been ordered to pay $60,000 to a man in his seventies wrongly diagnosed with brain cancer and told he had just a few months to live. The patient, Mark Templin, quit his job, sold his pickup truck, celebrated a ‘last’ birthday, bought a prearranged funeral and contemplated suicide. His son-in-law built a box for his ashes. The Judge awarded Templin $500 a day for the initial period of severe mental and emotional distress and $300 per day for the latter period until Templin received his new diagnosis (a stroke). The Judge ordered VA to repay Templin for the cost of the birthday party and (prepaid) funeral.

Meanwhile, an inquest in the UK has been told that National Health Service staff treated a man suffering from a previously diagnosed brain tumour 'just like another drunk' in the vital hours before his death. He had been rushed to hospital with head pains and vomiting but his brain tumour diagnosis had not been noted.

Steroid effects: A devoted father of three, aged 55 years, smashed his way through a closed window in the Queen’s Medical Centre in Nottingham (UK) in March 2012 and plunged 50 feet to his death after steroid drugs made him believe he was Jesus, an Inquest heard. The episode occurred the day after he had a successful operation for a Malignant brain tumour. The Inquest was told that the man suffered from euphoric and paranoid episodes caused by the dexamethasone he took to reduce swelling of the brain. A doctor and twenty people in the Ward tried to prevent him from jumping to his death. Comment: Is there a case for more effective warnings about the possibility of steroid-induced psychoses and diabetes from some high doses of dexamethasone?

Smoking and the risks of neurosurgery: In a review of the impact of smoking on neurosurgical outcomes in the Journal of Neurosurgery the three authors state that in a study of 453 patients who underwent Craniotomy for tumor removal, there were higher rates of Intraoperative blood loss and postoperative complications and a low rate of one-year survival in active smokers compared with non-smokers. Patients who quit smoking before surgery did not have the higher risk of complications and one-year mortality.

Shunt blockage: A 15 year old English schoolboy who had been successfully treated for a brain tumour and had raised thousands of pounds for the Royal Marsden Cancer Charity (UK) died from blockage of his shunt by cell debris, according to a Coroner’s Court. His death occurred on a bus returning from a school trip to Austria when he went to sleep, resting his head against his brother.

Brain tumour patient fathers baby girl despite odds: A 34 year old brain tumour patient, Ben Lindon from the UK, has fathered a baby girl despite being told he would most likely be infertile following 54 rounds of Chemotherapy. After his initial treatment he took up running and changed jobs from being a journalist and retrained as a tree surgeon. “Being out in the fresh air was incredibly therapeutic”, he said. He is now raising money for the UK charity Brain Tumour Research.

Meetings and deadlines: The deadline for eight US $1500 scholarships to colleagues in developing regions to attend the 4th Quadrennial Meeting of the World Federation of Neuro-Oncology and the 18th SNO ASM is 1 July 2013. The annual meeting of the British Society for Neuro-Oncology (BNOS) will be held in Durham (UK) during 10-12 July 2013.

IBTA Survey: Thank you to the 760 people who participated in our recent survey about the IBTA's publications and its projects. 81.5% described the monthly E News as either "useful" or "most useful" and the vast majority looked forward to receiving the IBTA's Brain Tumour magazine. Most believed we had the balance right between "hope" and "realism" in the content of our magazine. The responses to this particular question will be reported on in more detail as a poster at the forthcoming Australian Palliative Care Conference. Among the survey results were dozens and dozens of very helpful suggestions as to how to improve our work and publications and we will analyse these very carefully.

Dainere Anthoney: We are sad to report the passing on 24 June of 15 year-old Dainere Anthoney from Canberra, Australia, who was diagnosed with a medulloblastoma brain tumour in 2009 and despite undergoing heavy-duty chemotherapy and radiotherapy she managed to maintain a web blog, attend school, take part in athletics for the disabled, and write two books. Dainere also reviewed a children's book for the IBTA's Brain Tumour magazine in 2011 which can be viewed here. There is also a link to our review of her first book here.

Thank you for all your continuing support.

Denis Strangman (Chair and Co-Director)
International Brain Tumour Alliance IBTA

Kathy Oliver (Co-Director)
PO Box 244, Tadworth, Surrey
KT20 5WQ, United Kingdom
Tel:+ (44) + (0) + 1737 813872
Fax: + (44) + (0) +1737 812712
Mob: + (44) + (0) + 777 571 2569