Prospective Neurobehavioral Outcomes Follow-up in Primary CNS Lymphoma Patients Treated With Cranial Radiotherapy Combined With or Without MTX-based Chemotherapy According to the Multidisciplinary Treatment Guidelines Implemented at a Single Institute

Primary Central Nervous System Lymphoma Clinical Trial

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02655744
• Other study ID #: 102-5392B
• Status: Recruiting
• Start date: November 1, 2015
• Est. completion date: December 31, 2025

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: Observational

Clinical Trial Summary

Background. Primary central nervous system lymphoma (PCNSL) is an uncommon disease. Conventional treatment has consisted of either whole brain radiotherapy (WBRT) or methotrexate (MTX)-based combined modality therapy combining chemotherapy and cranial irradiation. The treatment principles at our institute have been quite consistent in the past, sticking to the treatment protocol reported by Memorial Sloan-Kettering Cancer Center in 1990s. No matter what the dosage of MTX is, it is well-established that the addition of chemotherapy to cranial RT significantly improved survival outcomes. However, it was found that delayed treatment-related cognitive sequelae emerged as a significant debilitating complication of combined modality treatment in patients with PCNSL, especially when effective treatment can achieve disease control and better survival rates. Furthermore, the specific contribution of the disease per se and various treatment modalities to cognitive impairment remains to be clarified because the neurotoxic potential of combined modality treatments is difficult to differentiate when each can result in cognitive dysfunctions respectively.

Treatment-related neurotoxicity could be demonstrated by virtue of several meaningful indicators, including neurobehavioral assessments, neuroimaging outcomes, and even measures of quality-of-life (QoL).

Methods. Therefore, this one-year individual research will be a prospective observational cohort study with a longitudinal assessment of neurobehavioral functions, neuroimaging, and quality of life for newly-diagnosed patients with primary CNS lymphoma at our institute. According to our cancer center, it is estimated that there would be around 25 cases of newly-diagnosed primary CNS lymphoma at our institute every year. By virtue of multidisciplinary management and teamwork consisting of neurosurgery, hematology, radiation oncology, neuroimaging expertise, and surgical pathology, investigators will attempt to recruit all potentially eligible patients with newly-diagnosed primary CNS lymphoma. Most importantly, the neuropsychologists will participate in our research project, in an effort to integrate the neurobehavioral outcomes into this prospective study. Accordingly, a battery of neuropsychological measures is used to evaluate neurobehavioral functions for the studied patients. The battery is composed of ten standardized neuropsychological tests, covering four domains sensitive to disease and treatment effects (executive function, attention, verbal memory, psychomotor speed), and QoL questionnaires.

Expected results. This prospective cohort study aims to explore and evaluate patients with PCNSL who are newly-diagnosed by using a standard battery of neurobehavioral functions plus neuroimaging studies. It is anticipated investigators will investigate and correlate neurotoxicity indicators in newly-diagnosed patients with PCNSL who are treated with cranial radiotherapy combined with or without MTX-based chemotherapy according to the multidisciplinary treatment guidelines implemented at a single institute.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 25
• Est. completion date: December 31, 2025
• Est. primary completion date: December 31, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 84 Years

Eligibility

Inclusion Criteria:

• All patients must have a histopathologic diagnosis of non-Hodgkin's lymphoma (NHL) by brain biopsy

• A typical MRI/CT scan for primary CNS lymphoma is defined as the presence of hypo, iso, or hyperintense parenchymal contrast-enhancing (usually homogeneously) mass lesion(s)

• Patients must have a normal or negative pre-treatment systemic evaluation including:

i. A bone marrow aspirate and biopsy ii. CT scans of the chest, abdomen and pelvis iii. Patients must have adequate bone marrow reserve

• Patients must be HIV-1 negative

• Men and women of reproductive potential must agree to use an acceptable method of birth control during treatment and for six months after completion of treatment

Exclusion Criteria:

• A past history of major psychiatric disease

• Prior cranial irradiation for any reasons

• Other active primary cancer with the exception of basal cell carcinoma of skin and cervical carcinoma in situ

• Pre-existing immunodeficiency such as renal transplant recipient

Related Conditions & MeSH terms

• Lymphoma
• Primary Central Nervous System Lymphoma

Intervention

Radiation:
• Standard treatment protocol with combined chemoradiation

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 change in neurocognitive functions from baseline up to 4 months after completing all courses of chemoradiation.	Neurocognitive assessment including : Trail Making Test.	one week before the WBRT course, up to 4 months after completing all courses of chemoradiation
Primary	The change in memory functions from baseline up to 4 months after completing all courses of chemoradiation.	Neurocognitive assessment including : Word Sequence Learning Test.	one week before the WBRT course, up to 4 months after completing all courses of chemoradiation
Primary	The change in general cognitive functions from baseline up to 4 months after completing all courses of chemoradiation.	Neurocognitive assessment including : Mini Mental Status Examination.	one week before the WBRT course, up to 4 months after completing all courses of chemoradiation
Primary	The change in attention functions from baseline up to 4 months after completing all courses of chemoradiation.	Neurocognitive assessment including : Paced Auditory Serial Addition Test-Revised	one week before the WBRT course, up to 4 months after completing all courses of chemoradiation
Primary	The change in executive functions from baseline up to 4 months after completing all courses of chemoradiation.	Neurocognitive assessment including : Modified Card Sorting Test.	one week before the WBRT course, up to 4 months after completing all courses of chemoradiation
Primary	The change in verbal fluency from baseline up to 4 months after completing all courses of chemoradiation.	Neurocognitive assessment including : Semantic association of verbal fluency.	one week before the WBRT course, up to 4 months after completing all courses of chemoradiation
Primary	The change in Intelligence from baseline up to 4 months after completing all courses of chemoradiation.	Neurocognitive assessment including : Wechsler Adult Intelligence Scale (WAIS-III-R).	one week before the WBRT course, up to 4 months after completing all courses of chemoradiation
Secondary	The time from the date of recruitment to that of intracranial progression/failure noted on brain MRI		Baseline before the WBRT course; 2 months after completing all courses of chemoradiation, and then 4 months later.
Secondary	Depression Inventory questionnaires.	Questionnaires include: Beck Depression Inventory.	Baseline before the WBRT course; one month after completing the WBRT course; 2 months after completing all courses of chemoradiation, and then 4 months later.
Secondary	Anxiety Inventory questionnaires.	Questionnaires include: Beck Anxiety Inventory.	Baseline before the WBRT course; one month after completing the WBRT course; 2 months after completing all courses of chemoradiation, and then 4 months later.
Secondary	Self- Evaluation questionnaires.	Questionnaires include: National Taiwan University Irritability Scale Self- Evaluation (NTUIS-Self).	Baseline before the WBRT course; one month after completing the WBRT course; 2 months after completing all courses of chemoradiation, and then 4 months later.
Secondary	Family Evaluation questionnaires.	Questionnaires include: National Taiwan University Irritability Scale-Family Evaluation (NTUIS-Family).	Baseline before the WBRT course; one month after completing the WBRT course; 2 months after completing all courses of chemoradiation, and then 4 months later.