A Prospective Study of the Impact of Hippocampal Avoidance During Whole Brain Radiotherapy on Neurocognitive Function Decline

Brain Metastases Clinical Trial

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02504788
• Other study ID #: 101-4151B
• Status: Recruiting
• Phase: N/A
• Start date: January 18, 2013
• Est. completion date: December 31, 2028

Study information

• Verified date: April 2023
• Source: Chang Gung Memorial Hospital
• Contact: Chi-Cheng Chuang, M.D.
• Phone: +886-33281200
• Email: ccc2915[@]cgmh.org.tw
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Whole brain radiotherapy (WBRT) has long been a practical and effective therapeutic modality for various settings of management in radiation oncology. For example, the indications for WBRT should include brain metastasis or metastases, the setting of prophylactic cranial irradiation (PCI) used mainly for patients with limited-stage small cell lung cancer, and even some patients with extensive-stage small cell lung cancer. The rationales for WBRT are essentially based on that it can target both microscopic and gross intracranial disease.

In addition to providing rapid alleviation of neurologic symptoms and enhanced intracranial disease control, WBRT might also prolong the time to develop neurocognitive function (NCF) decline. However, paradoxically NCF decline can also occur due to a sequel of WBRT. In terms of the time course of WBRT-induced NCF decline, it might vary considerably according to the specific domains which are selected to be measured. Early neurocognitive decline occurs within the first 1 - 4 months after WBRT for brain metastases. The domains of early neurocognitive decline principally involve verbal and short-term memory recall.

Since several decades ago, it has been understood that hippocampus plays an essential role in memory function. Not little evidence supports that radiation-induced damage to hippocampus should be strongly associated with NCF impairment. Furthermore, several studies have shown that isodose distribution in hippocampus is closely related to neurocognitive function in patients with benign or low-grade brain tumors. As a consequence, it is hypothesized that conformal hippocampal sparing during the course of WBRT (HS-WBRT) might provide significant preservation in terms of cognitive function.

This prospective cohort study aims to explore and evaluate the impact of the delivery of HS-WBRT on the pattern of NCF change and the extent of NCF decline in patients receiving prophylactic or therapeutic WBRT. As compared with previous related and relevant studies, it will also be investigated whether neurocognitive functional preservation can be achieved via the integration of hippocampal sparing with the course of WBRT.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 100
• Est. completion date: December 31, 2028
• Est. primary completion date: December 31, 2028
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 84 Years

Eligibility

Inclusion Criteria:

• Patients with pathologically-confirmed non-hematopoietic malignancy who are referred for therapeutic or prophylactic WBRT

• Good performance status no worse than Eastern Cooperative Group (ECOG) of 2 or a general status of Karnofsky Score (KPS) at least 70 %

• The number and extent of brain metastatic lesions should be no more than three metastatic foci with a greatest diameter no more than 4 cm

Exclusion Criteria:

• Patients with MRI-identified metastasis within 5 mm perihippocampally

• Clinical suspicion of leptomeningeal spreading

• History of prior radiotherapy including stereotactic radiosurgery delivered to brain/head region for any reasons

Related Conditions & MeSH terms

• Brain Metastases
• Brain Metastasis
• Brain Neoplasms
• Neoplasm Metastasis

Intervention

Radiation:
• hippocampal-sparing WBRT

Locations

Country	Name	City	State
Taiwan	Chang Gung Memorial Hospital	Taoyuan

Sponsors (1)

Lead Sponsor	Collaborator
Chang Gung Memorial Hospital

Country where clinical trial is conducted

Taiwan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The primary endpoint is delayed recall, as determined by the change/decline in verbal memory (WMS III- Word List score) from the baseline assessment to 4 months after the start of HS-WBRT.	Neurocognitive assessment: including memory, executive functions, and psychomotor speed. This neurocognitive outcome was delayed recall, as determined by the change/decline in either verbal memory [Wechsler Memory Scale - 3rd edition (WMS III) - Word List score] or non-verbal memory (WMS III- Visual Reproduction score) from the baseline assessment to 4 months after the start of the course of WBRT with hippocampus sparing (HS-WBRT). Additionally, the follow-up of neurocognitive assessment will also be administered at 12 months and up to 18 months after the start of HS-WBRT.	4 months after the start of HS-WBRT
Primary	The primary endpoint is delayed recall, as determined by the change/decline in non-verbal memory (WMS III- Visual Reproduction score) from the baseline assessment to 4 months after the start of HS-WBRT.	Neurocognitive assessment: including memory, executive functions, and psychomotor speed. This neurocognitive outcome was delayed recall, as determined by the change/decline in either verbal memory [Wechsler Memory Scale - 3rd edition (WMS III) - Word List score] or non-verbal memory (WMS III- Visual Reproduction score) from the baseline assessment to 4 months after the start of the course of WBRT with hippocampus sparing (HS-WBRT). Additionally, the follow-up of neurocognitive assessment will also be administered at 12 months and up to 18 months after the start of HS-WBRT.	4 months after the start of HS-WBRT
Secondary	Overall survival time, indicated by the time from the date of recruitment to the date of expiring		up to 18 months
Secondary	The time from the date of recruitment to that of intracranial progression/failure noted on brain MRI or CT		up to 18 months