HRQL and Symptom Assessment for Patients With DIPG or Recurrent and Re-irradiated Brain Tumours and Their Caregivers
HRQL and Symptom Assessment for Patients With DIPG or Recurrent and Re-irradiated Brain Tumours and Their Caregivers
Although many children with brain tumours are successfully cured of their disease, a
 substantial proportion of patients suffer disease recurrence and require further treatment.
 This therapy may involve a repeat course of radiation (RT2). Based on retrospective data,
 re-irradiation may provide palliative and even potentially curative benefit. However, such
 retrospective data are subject to bias, which may over-report survival and under-report
 toxicity. Furthermore, we do not know how re-irradiation affects patients' HRQOL. The goal of
 this research is to prospectively describe the HRQOL of patients diagnosed with DIPG and
 recurrent brain tumors and their families before and after re-irradiation to more accurately
 assess the benefit versus the toxicity of this treatment.

 In addition, if we are able to demonstrate the feasibility of collecting HRQOL information on
 a routine basis we will be able to justify the need to conduct this research further and
 implement HRQOL screening as a standard of care for these patients. Re-irradiation for
 children with DIPG and recurrent brain tumours will not cure these children from their
 disease but may improve neurological function and wellbeing. We postulate that the
 opportunity of more time to say the final good bye and creating memories will facilitate
 bereavement and prevent psychological dysfunction of parents and siblings. A greater
 understanding of what helps these families may enable clinicians to better support these
 children and their families in this difficult disease course. Ultimately our goal is to
 improve the psychological experience of these patients and their families.
Many children diagnosed with brain tumours are at significant risk of disease recurrence
 following their initial treatment, with recurrence rates ranging from 30-100% depending on
 the type of brain tumour. Disease recurrence represents a serious clinical issue in brain
 tumour patients and when this occurs, additional treatment is needed. These treatments may
 result in further damage to the surrounding normal brain tissue, resulting in neurocognitive
 decline (brain or mental function) and reduced quality of life. A novel treatment option for
 these patients is to administer a second course of radiation (re-irradiation). However, the
 effects of re-irradiation on quality-of-life are poorly studied. This study aims to increase
 the knowledge surrounding re-irradiation, particularly with regards to HRQOL.

 The primary objective of the proposed study is to describe the HRQOL and symptoms for
 children diagnosed with DIPG or recurrent brain tumours treated with repeat radiation and
 their caregivers over time.

 We have four Aims. Aim 1: To describe the HRQOL trajectory and symptoms for children
 diagnosed with DIPG and in children treated with re-irradiation for a recurrent brain tumour
 and their caregivers over time. Aim 2: To identify critical time points of HRQOL difficulty
 across the trajectory of DIPG/recurrent brain tumour treatment and to ascertain demographic
 and/or medical sequelae that are related to HRQOL outcomes. Aim 3: To determine the
 feasibility of conducting routine assessment of HRQL in children diagnosed with
 DIPG/recurrent brain tumours and their caregivers based on recruitment and retention rates.
 Aim 4: To report the incidence of radiation necrosis (RN), local control, progression-free
 survival and overall survival after re-irradiation.

 Our goal to is enroll 25 to 30 patient/caregiver dyads diagnosed with DIPG and 32
 patient/caregiver dyads treated with re-RT for a recurrent/progressive brain tumour onto the
 trial over the study period and to follow patients until their disease progresses again,
 which has been, on average, 6 months after completion of RT2.

 Once deemed eligible, individual patient recruitment will be the responsibility of the
 institution Clinical Research Assistant (CRA). Upon consenting to take part in the study,
 patients and families will be contacted using an online administration and scoring program.
 HRQOL assessments will take 15-25 minutes to complete at each time point. Baseline
 questionnaires will be completed at the time of recurrence or progressive DIPG or other brain
 tumor (+/- 7 days from start of treatment, maximum 14 days). Patients will then complete
 HRQOL measures at the end of re-irradiation and then again every two months.

 Necrosis and local tumour control will be assessed using MRI ordered as part of
 standard-of-care follow-up (recommended scan interval every 3-6 months until 5 years
 post-treatment). Necrosis and other toxicities, if present without evidence of disease
 recurrence, will be graded at baseline and each post-RT2 standard-of-care visit using CTCAE
 v5.0 (a rating scale of side effects). Steroid use and Lansky play score will be recorded at
 each visit. Progression and death will be collected from the health record. Re-irradiation
 dosimetry (in electronic RT-DICOM format) will be requested for all enrolled patients.

 Study measures will be available in both English and French. HRQOL measures will include: the
 Pediatric Quality of Life (PedsQL) General module; the PedsQL Brain Tumour module; the PedsQL
 Family Impact module; and the Short Form 36 (SF-36), to assess parent quality of life via
 physical and mental health functioning subscales. Children who require help completing
 questionnaires will be aided by a CRA. For those 2 to 5 years of age or those who have
 cognitive disability that impairs their ability to self-report as assessed by their parents,
 proxy-report by parent or caregiver will be used.

 The Symptom Screening in Pediatrics Tool (SSPedi) will also be used to screen for pediatric
 cancer symptoms.

 The Patient Reported Outcomes Measurement Information System (PROMIS) Anxiety, Depressive
 Symptoms, and Pain Interference measures short forms will be administered to screen for
 current symptoms of anxiety, depression and assess pain interference.

 A linear mixed models approach will be used to compare HRQOL outcomes over time. Further,
 HRQOL outcomes will be compared across assessment time points and paired sample t-tests will
 be conducted to identify critical periods of significantly lower and/or higher HRQOL for
 patients and caregivers. Correlational analyses will be used to explore variables that might
 emerge as related to HRQL outcome scores. Recruitment rates (patients participating vs.
 patients eligible) and retention rates (non-completion, lost to follow-up) will be examined.
 Finally, all incident cases of radiation necrosis without obvious tumour progression will be
 examined, while accounting for competing risks of disease progression and death from any
 cause.
Inclusion Criteria:

 1. Patient aged >2 and <21 years treated with a repeat course of radiation for DIPG or
 other recurrent or progressive brain tumour.

 2. Radiation for the first tumour must be a primary brain neoplasm (i.e. not leukemia).

 3. Enrollment within 14 days of starting re-irradiation (RT2).

 4. Patients with malignant transformation of the first tumour are eligible.

 5. There are no restrictions on histology or RT1/RT2 dose-fractionation or RT2 body site.
 In other words, RT2 may be directed at a different location to RT1.

 6. The patient is treated at a site where the study is approved by the local ethics board

 7. Consent, and, if applicable, assent, has been obtained according to institutional
 standards

 Exclusion Criteria:

 1. Inability to complete questionnaires in English or French.