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01
Nov
2018

COGNO 2018 - Targeting Survival: Living well with brain cancer in the era of precision treatments

Doctor Mark Gilbert outlines his work in brain cancer research at COGNO 2018

The Cooperative Trials Group for Neuro-Oncology (COGNO) is an Australian network of clinicians, researchers, consumer representatives and allied health professionals, whose mission is to achieve better health outcomes for patients and those affected by brain tumours through quality clinical trials research. 

Earlier this month, COGNO held their 11th annual scientific meeting in Brisbane, which focused on patient survivorship and precision treatments. Cure Brain Cancer Foundation sponsored and attended the event, as this fits with our strategy of encouraging collaboration and shared knowledge among Australian researchers, international researchers and clinicians in brain cancer research.

Among those in attendance were COGNO members, including clinicians, researchers, nurses, allied health professionals, people living with brain cancer and philanthropic organisations like Cure Brain Cancer Foundation.

Over 40 presentations were given by both Australian and international experts, highlighting some of the exciting advancements in brain cancer research. Speakers addressed new, experimental agents and approaches such as immunotherapies, and described the issues with current treatments and challenges involved in the discovery, testing and translation of new medicines.  The conference also highlighted the importance of patient-centred research, symptom management and caregiver health, whilst providing updates on COGNO-run clinical trials and research in the field.  Included below are some of the highlights from COGNO, including a brief snapshot of the exciting research being undertaken in brain cancer around the world.

Immunotherapies

One of the hot topics at COGNO this year was the emergence of experimental immunotherapies, which aim to activate the body’s immune system to fight a cancer. Immunotherapies have shown great promise in multiple cancers, and now there are several research efforts to apply this to brain cancer. Neurosurgeon Professor David Walker from BrizBrain and Spine discussed his involvement in researching adoptive T cell therapy for glioblastoma. His research aims to use the cytomegalovirus, a virus from the herpes family, to target glioblastoma cells with an immunotherapy agent.  This approach was tested recently in an early phase clinical trial, which appeared promising in a subset of patients on the trial with primary and recurrent glioblastoma. 

Speakers also addressed some of the challenges in testing immunotherapies for brain cancer.  Professor Mark Gilbert from the National Cancer Institute (USA) discussed these challenges in his plenary talk. He mentioned that some patients have suppressed immunity within the tumour environment, which can make it more difficult to lodge an immune response against a brain tumour. Professor Gilbert also highlighted the need for quality clinical trials to consider the differences immunotherapies pose to standard clinical trial design. For example, some possible side effects may not appear until months after the treatment is first administered. This means that trials need to account for these delays and ensure that patients are monitored for any side effects from treatment that arise. To date, immunotherapies are not standard treatments in brain tumours.

Imaging

Another prominent topic at COGNO was the imaging and visualisation of tumours in the brain, which is important for the diagnosis and monitoring of the disease. Mentioned several times by Professor Gilbert and others, was the concept of pseudo-progression. This refers to the phenomenon whereby a scan will look like a tumour has progressed, when it is really just an inflammatory response to certain treatments. This can make it difficult to understand the true progression of a disease, particularly when testing immunotherapies. Research is ongoing to improve imaging techniques that provide more extensive and accurate information to clinicians to guide patient treatment.

Radiotherapy

Radiotherapies continue to be a standard therapy in brain cancers, and this was discussed particularly in regard to metastases at COGNO 2018. Professor Erik Sulman, a radiation oncologist from the Brain Tumour Center (USA) expressed that clinical trials for brain metastases must share a ‘common language’, using the same functional endpoints in trials to accurately and comparatively measure disease progression. Professor Sulman also observed that cognitive decline in patients with metastatic brain tumours is not so affected by the number of metastatic tumours in the brain, but rather the tumour volume. This was further emphasised by Associate Professor Michael Izard, who reported on Gamma Knife surgery at Macquarie University Hospital. A/Prof Izard detailed that in his research, the number of metastases was not indicative of survival, but rather the size of the tumours that was most important. Significantly, both speakers impressed the importance of a multidisciplinary team approach to treating patients with both primary and metastatic brain cancers.

Clinical Trials Update

Several national and international clinical trials were discussed, which provided updates and introduced new trials to those in attendance. This included COGNO’s VERTU clinical trial, led by Associate Professor Mustafa Khasraw through the NHMRC Clinical Trials Centre and part funded by Cure Brain Cancer Foundation.  This trial tests veliparib, a PARP inhibitor, in combination with radiotherapy and chemotherapy drug temozolomide, in patients with newly-diagnosed unmethylated MGMT glioblastoma. The VERTU trial to date has had no unexpected side effects and will soon meet its intended patient recruitment target. The NUTMEG clinical trial, also conducted by A/Prof Khasraw, has recently opened for recruitment and will study nivolumab and temozolomide in elderly patients with newly diagnosed glioblastoma. Dr Lucy Gately from St Vincent’s Hospital Melbourne presented the first registry trial for oncology worldwide. Registry trials use cheap, simple and pragmatic minimal data collection to answer questions around variations in standard care. This randomised phase III registry trial will examine whether 12 months is better than 6 months administration of temozolomide for patients with newly diagnosed glioblastoma.

Patient-Centred Research

A central theme of the annual scientific meeting at COGNO was the importance of patient-centred research. Dr Terri Armstrong from the National Cancer Institute (USA) gave several presentations and emphasised the importance of patient experience and the symptoms that they experience being recorded both in and out of clinical trials. Dr Armstrong reported that half of patients have at least 10 concurrent symptoms which can include fatigue, cognitive decline, anxiety and depression. With brain tumour patients being highly symptomatic, Dr Armstrong asserts that it is “important to manage the symptoms as well as the disease itself”. By monitoring these symptoms, clinicians and researchers have the data and understanding to improve patient care and possibly improve survival.

In a study performed at the Memorial Sloan Kettering Hospital (USA), researchers found that overall survival increased for patients who monitored their symptoms using an online tool which reported back to their clinical team. These patients felt more control over their diagnosis, were less frequently admitted into the emergency department and were able to communicate with their clinicians with ease about their disease. Importantly, the study found that the greatest survival advantage was in elderly people who were not computer proficient and were taught to log their symptoms at visits to the hospital and clinic. Additionally, this symptom data collected can help researchers understand the impact of brain tumours and treatments on patients’ quality of life. 

Dr Nick Gottardo, a paediatric oncologist from Perth also touched on symptom management during his talk, in the context of developing new treatments. Notably, Dr Gottardo highlighted the “price of [a] cure’’, meaning we “need to ensure that the treatment isn’t worse than the disease.’’

Caregiver Health

Many patients diagnosed with a brain tumour are reliant on a caregiver, and there is a distinct understanding among clinicians and researchers that the health of this caregiver is paramount to the patient. Professor Susan Chang from the University of California, San Francisco (USA) talked about the importance of assisting caregivers, and the transition from person-centred, to family-centred care. During this presentation, the need to provide care, education and training to caregivers was emphasised, to improve caregiver’s confidence in their ability to manage daily care challenges.  Professor Chang added that this support and information should be delivered appropriately a different timepoints across the trajectory of a patient’s illness, as caregiver burden varies with changes in patient health. This essential support allows caregivers to provide quality care.

Exercise Medicine

A different approach to patient health and wellbeing was discussed by Associate Professor Prue Cormie from the Clinical Oncology Society of Australia Exercise Cancer Group on the importance of exercise medicine in cancer management. A/Prof Cormie reported on the benefits of exercise in rehabilitation and symptom management, encouraging clinicians to integrate exercise as a standard component of routine care. Importantly, patients should only be as physically active as their health allows, to prevent further injury. However, if a patient is well enough, physical activity does have significant benefits. In brain cancer patients, exercise has been shown to decrease fatigue, functional decline, cognitive impairments, depression and anxiety. A/Prof Cormie also demonstrated that exercising during chemotherapy can increase the treatment tolerance of a patient, with fewer symptoms and side-effects.

Concluding Remarks

COGNO fosters global collaboration that is essential for furthering developments in brain cancer research. Cure Brain Cancer Foundation finds great value participating with COGNO and attending this annual scientific meeting. It is conferences like these that are critical to fostering partnerships and open communication in research, as clinicians, healthcare professionals and researchers alike all strive to improve treatments, quality of life and survival for brain cancer patients.

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