What matters most to patients?
A previous study involving brain tumor patients identified that when anti-tumor treatment is understood to be ‘the only option’, the risk and impact of side effects may not be adequately explained to and understood by patients. It was also noted that there is a strong desire for more information to be provided regarding support services. These results suggest that the impact of side effects is important to patients but not always adequately communicated by treatment teams.
Oligodendroglioma (ODG) is an uncommon brain tumor. Standard treatment involves surgery to remove as much tumor as possible, followed by radiotherapy (RT) and chemotherapy to help control the tumor. While ODG has a good outlook, the standard form of RT treatment (photon RT) can cause long-term side effects that may develop several years after treatment. These can include difficulties with neurocognition: things like problems with, for example, memory, processing information and problem-solving.
In some cases, photon RT can also cause abnormalities in hormone levels several years after treatment. Such problems can impact day-to-day life and quality of life (QoL), and this is compounded by the fact that patients with ODG are often young, in employment and with caring responsibilities of their own.
Such patients have expressed a strong desire to have control over their QoL, with healthcare professionals further highlighting the importance of maintaining the independence of patients and providing emotional support. In light of this, we think that it is important for studies to not only consider which treatments are most effective in treating tumors, but also which treatments provide patients with better overall QoL (even in cases where such treatment may not provide any additional anti-tumor benefit).
With this context in mind, UK neuro-oncologists and multidisciplinary colleagues, together with the Leeds Institute of Clinical Trials Research, have developed the APPROACH study. APPROACH is one of the first randomized research studies to compare QoL, neurocognitive function and other late effects in adults with ODG following either PBT or standard photon RT.
The standard form of RT treatment for adults with ODG is RT using photon beams. Photon RT is given as lots of small treatments on weekdays over about 6 weeks and is currently the best way to control the tumor whilst minimizing side effects in normal brain tissue.
PBT is an advanced type of RT, also given on weekdays over about 6 weeks (but currently only available in London and Manchester). It requires expensive technology but can reduce the dose of RT delivered to the normal brain, including parts of the brain used for memory and information processing. This might mean that PBT can reduce long-term side effects in patients with ODG, though we do not know this for certain. We hope to answer this question in the APPROACH trial.
In addition to having a strong desire for control over their QoL, patients have also been identified as having a strong desire to be “involved, consider alternatives and voice what matters to them” when it comes to their treatment. In light of this, the APPROACH trial team sought patient and caregiver engagement during each stage of study design and set-up to ensure that their views were incorporated into the study proposals and protocol.
A focus group was conducted with patients and caregivers that provided an invaluable opportunity to help guide our trial design and at least three Patient and Public Involvement (PPI) team members will be involved in trial management throughout the length of the trial. As a result, we believe APPROACH will be stronger and more relevant to patients, caregivers and health professionals.
Through our patient engagement, it was identified that patients often consider that standard QoL questionnaires “fail to address some important areas reflecting daily wellbeing and fatigue”. For example, there was a specific observation that standard questionnaires do not address “difficulty getting going in the morning, which causes frustration and impacts significantly on family life, work and mood”.
The fact that assessments currently considered as gold standard do not always address areas that patients consider important is worthy of further reflection and in light of this, the APPROACH trial makes use of additional questionnaires designed to provide a more accurate and valid assessment of a patient’s QoL.
Patients and their caregivers have “strongly endorsed and supported” the APPROACH study proposal and “positively highlighted the opportunity to access PBT within a clinical trial”, even recognizing and supporting the need for randomization, specifically favoring 1:1 randomization in recognition that we currently do not know if PBT will offer long-term benefits over photon RT (rather than 2:1 as with some previous PBT trials such as TORPEdO).
While it is not expected that there will be any difference in controlling the growth of the tumor as the equivalent dose of RT is given to the tumor whether PBT or photon RT is used, it is important for more research to be conducted to determine if the lower normal brain doses achieved with PBT result in fewer long-term side-effects and ultimately a better QoL for patients – benefits to QoL that are ultimately priceless to patients.