Improving Survivorship and Health-related Quality of Life in Patients With Primary Brain Tumours

NCT06014398 | Unknown

• 1 other identifier: 23-127
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 2

Brief Summary

Background: Approximately 480 primary, non-pituitary, brain tumours were diagnosed in Ireland each year between 1994 and 2013. Recent developments in treatment have greatly improved survival for younger patients in the 15-54 age range. The Irish National Neurosurgical Centre and the St Luke's Radiation Oncology Centre at Beaumont Hospital and treat approximately 200 patients with brain tumours per year with a combination of surgery, radiotherapy (RT) and chemotherapy with RT being the most commonly used treatment modality. With improved survivorship, the prospect of individuals living for several decades with co-morbidities induced by the tumour itself or surgical and RT treatments, raises new and complex issues for patients and clinicians. The hypothalamus and pituitary gland in the brain are the key regulators of hormone action. They control several hormone systems including reproductive function (FSH, LH) growth (growth hormone), thyroid (TSH) and adrenal function (ACTH) as well as many other homeostatic mechanisms. It has long been recognised that therapeutic cranial RT to the pituitary gland causes hypothalamic-pituitary dysfunction (hypopituitarism). Traditionally, high-risk groups for post-irradiation hypopituitarism were considered to be patients with pituitary tumours, survivors of childhood cancer and patients who received high-dose RT to treat nasopharyngeal cancers. The potential for cranial radiotherapy to cause significant pituitary dysfunction in adult patients with brain tumours has received little attention. The assumption has been that the hypothalamic-pituitary axis is more resistant in adults than in children to the effect of cranial RT. However, it is likely that the higher doses of RT, used to treat primary brain tumours in adults, causes significant hypothalamic-pituitary dysfunction resulting in hypopituitarism. Preliminary data from the National Pituitary Centre in Beaumont Hospital has revealed that adult patients, treated with cranial radiotherapy for primary, non-pituitary brain tumours, are at risk of hypopituitarism. Approximately 40% of patients had pituitary deficiencies in at least one hormone axis, while 25% of patients had deficiencies in multiple hormone axes. Hypopituitarism confers significant morbidity and increased mortality to patients. At present, adult survivors of brain tumours are referred to the pituitary service for assessment on an ad-hoc basis meaning that many patients with hypopituitarism may go undiagnosed. In addition to the challenges caused by hypopituitarism, long-term neuropsychological outcomes following a brain tumour cause significant functional impairments and reduced HR-QOL. Patients can present with impairments in specific cognitive domains such as memory and executive functioning or more global systems such as attention as well as significant issues with fatigue. In addition to these primary deficits, patients can also present with significant distress, fluctuant mood and anxiety. Despite the impact of brain tumours can exert, the National Cancer Control Program's National Survivorship Needs Assessment Review (2019) did not identify any studies reporting the needs of adult survivors of brain tumours in Ireland. There is an urgent need to understand the impact of hypopituitarism and its treatment on HR-QOL and neuropsychological functioning. The proposed study will add to the limited existing literature on the prevalence of hypopituitarism in adult survivors of brain tumours treated with radiotherapy and generate detailed information on deficiency rates for individual pituitary hormones and how these deficiencies emerge over time. This will also be the first study to examine if treatment of radiotherapy-induced hypopituitarism (as part of routine clinical care) is associated with improved HR-QOL and neuropsychological functioning.

Conditions

Hypopituitarism; Radiotherapy-Induced Hypopituitarism; Brain Tumor

Outcome Measures

Primary Outcomes (1)

• Prevalence of radiotherapy-induced hypopituitarism

  Prevalence of pituitary hormone deficiencies in adult survivors of primary, non-pituitary brain tumours, previously treated with radiotherapy.

  Assessed at Baseline

Secondary Outcomes (2)

• HR-QOL

  Assessed at baseline

• Change in HR-QOL

  Assessed at 4 months

Study Arms (1)

Study investigation

EXPERIMENTAL

All enrolled patients will undergo standardised pituitary hormone assessments.

Diagnostic Test: Dynamic testing of Pituitary Function

Interventions

Dynamic testing of Pituitary Function DIAGNOSTIC_TEST

Pituitary Function Assessment: Baseline assessment of pituitary function by measuring ACTH, cortisol, FSH, LH, oestrogen (in females), testosterone (in males), sex hormone binding globulin, thyroid function tests, prolactin and IGF-1\]. Dynamic testing of pituitary function: * Patients will undergo dynamic testing of the ACTH and growth hormone axes using a glucagon stimulation test (GST). * Patients whose GST identifies cortisol deficiency will undergo a short synacthen test to confirm adrenal insufficiency as the GST has a false positive rate of approximately 20% for ACTH deficiency.

Study investigation

Eligibility Criteria

• Age: 16 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Adults (at least 18 years old) with a history of a primary, non-pituitary brain tumour which was previously treated with radiotherapy.
• Participants must have been at least 16 years old at the time of undergoing radiotherapy.
• A minimum of one year has elapsed since radiotherapy was completed.
• Capacity and willingness to provide informed consent.

You may not qualify if:

• Diagnosed with malignant astrocytic brain tumour with life expectancy of less than six months.
• Brain tumour infiltration of the hypothalamus or pituitary pre-operatively.
• Previously diagnosis of hypopituitarism.
• Oral glucocorticoid use within the last three months.
• Pregnant or breastfeeding women at the time of recruitment.
• Opinion of the radiation oncology or research team that participation in the study is not in the best interest of the patient for any reason.

Sponsors & Collaborators

• Royal College of Surgeons, Ireland: lead
• Beaumont Hospital: collaborator

Study Sites (2)

Beaumont Hospital

Dublin, Ireland

Location

St Luke's Radiation oncology Centre, Beaumont Hopsital

Dublin, Ireland

Location

MeSH Terms

Conditions

Hypopituitarism; Brain Neoplasms

Condition Hierarchy (Ancestors)

Pituitary Diseases; Hypothalamic Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Endocrine System Diseases; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Neoplasms

Central Study Contacts

Mark Sherlock, MD PhD

CONTACT

01-809 2811; marksherlock@rcsi.ie

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 24, 2023
• First Posted: August 28, 2023
• Study Start: September 1, 2023
• Primary Completion: September 1, 2025
• Study Completion: September 1, 2025
• Last Updated: August 28, 2023

Record last verified: 2023-07

Data Sharing

• IPD Sharing: Will not share

Locations

IE (2)