Abstract
Primary glioblastoma multiforme is the main primary brain cancer in adults. It is a diagnosis that carries with it a devastatingly poor prognosis. Best current practice, consisting of debulking surgery, radiation therapy and Temozolomide chemotherapy, results in a mean overall survival of 15-20 months after diagnosis. There is no standard treatment for relapsed high grade glioma. The most promising chemotherapy regimens, using Temozolomide, Bevacizumab and Irinotecan, have resulted in a mean overall survival of 8.8 to 9.3 months from salvage therapy. Several clinical studies have reported a mean overall survival of 3.9 - 12.5 months after salvage hypo-fractionated radiation therapy. The aim of salvage treatment for high grade glioma patients is the palliation of symptoms and maintenance of quality of life.
The research presented in this thesis follows the journey of seven patients with recurrent high-grade glioma through their salvage radiation therapy and beyond at Auckland Radiation Oncology between September 2014 and December 2015. The objectives were to 1] gain an insight into the impact of hypo-fractioned re-irradiation on Health Related Quality of Life during and after the completion of salvage treatment and to 2] determine the nature and severity of tumour associated symptoms before, during and after completion of hypo-fractioned re-irradiation.
A prospective observational study design was used with a variety of methods of gathering information to document the patients’ journeys. Patients completed the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 and BN-20 quality of life questionnaires to capture self-reported severity of symptoms scores, overall health and quality of life at baseline, during and after treatment. The author attended follow-up consultations with the radiation oncologist to gain an insight into the disease and treatment-related symptoms and their effect on day-to-day life. Any notes taken during the consultations were cross referenced with notes from the treatment radiation therapists and radiation oncologist in the patient file. The author also reviewed patient notes and CT and MRI scans to understand the disease trajectory from primary diagnosis to recurrence and gain details of the radiation therapy treatment plan. The intent was to document treatment-related side effects using the Common Terminology for Adverse Events (CTCAE) adverse events criteria. CTCAE scoring was discontinued after the first patient due to the burden of an additional interview with these vulnerable patients and the similarity of the CTCAE items to those covered in the quality of life questionnaires. Side effects were also discussed during consultations with the radiation oncologist, which the author attended.
The journey of each of the seven patients was very distinct. Patient expectations regarding their health and quality of life throughout salvage therapy depended on a combination of age, stage in life, time to relapse, severity of disease symptoms and the extent to which they had accepted their prognosis. All of the patients experienced some level of psychosocial distress. Six patients reported at least “a little worry or depression”; patients also reported feeling at least “a little uncertain about their future”.
Salvage re-irradiation to a median dose of 35Gy in 10 fractions was found to be well tolerated although a decrease in overall health and quality of life from baseline was reported in five of the seven patients during the two weeks of treatment. Fatigue, exacerbation of tumour symptoms and disruption to daily life worsened during radiation treatment. A majority of patients responded to salvage re-irradiation with a partial response and six patients had further salvage chemotherapy. Most patients reported an increase in or reasonably stable overall health and quality of life scores after completion of radiation treatment.
Limitations of the study included cohort demographics and a short and varied follow-up time. Because of the time constraints of an honours thesis project, only a small number of patients participated. Patients enrolled early in the study were followed for a much longer period of time (up to 15 months) than patients who enrolled later (minimum of five months). Even though this small cohort was very heterogeneous with respect to age, stage in life, time to relapse and salvage treatment, they all attended a private clinic and most likely belonged to a higher socioeconomic class where the pressures of having to keep working to provide for the family were not key factors. The cohort also lacked ethnic diversity as all patients identified themselves as NZ European.
The patients themselves were supposed to fill in quality of life questionnaires at the start, during treatment and follow. This did not happen for all time points for all patients because in a few instances the author was not advised of a change in follow-up appointments or could not be released from clinical duties to hand out the questionnaires and in some cases patients were too sick to fill them in.
Overall, the experience of this small cohort of patients suggests that hypo-fractionated radiation may be a salvage therapy option for at least some patients with relapsed high grade glioma. One of the major costs of salvage radiation therapy for patients is disruption to everyday life due to the logistics of attending daily treatment sessions. It is therefore appropriate that it is delivered over a relatively short period of two weeks. The study further identified the need for more research into the physical and psychosocial wellbeing of high grade glioma patients and the best ways to support them in coping with the challenges that living with an incurable brain tumour presents.