Clinical trial NCT04006561: Prospective Neurobehavioral Functions in Newly-diagnosed Patients With Primary CNS Lymphoma Treated With Hyperfractionated Conformal Whole-brain Radiation Therapy Plus Simultaneous Integrated Boost
Official title: Prospective Neurobehavioral Evaluation in Newly-diagnosed Patients With Primary CNS Lymphoma Treated With Hyperfractionated Conformal Whole-brain Radiation Therapy Plus Simultaneous Integrated Boost
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Primary CNS Lymphoma
Brain Lymphoma
Keywords: Primary CNS Lymphoma
Neurobehavioral Assessment
Neurocognitive Function (NCF)
Whole-Brain Radiation Therapy (WBRT)
Simultaneous Integrated Boost (SIB)
Hyperfractionation
Radiotherapy
Chemotherapy
Neurotoxicity
Lead sponsor: Chang Gung Memorial Hospital
Sponsor class: OTHER
First posted: 2019-07-05
Enrollment: 36
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: newly-diagnosed patients with primary CNS lymphoma

Brief summary: Primary central nervous system lymphoma (PCNSL) is an uncommon disease. Conventional treatment has consisted of either whole-brain radiation therapy (WBRT) or methotrexate (MTX)-based combined modality therapy integrating chemotherapy with cranial irradiation in a sandwiched manner. No matter whether the dosage of MTX is high or conventional, combining chemotherapy with WBRT greatly improves intracranial tumor control and even survival outcomes. However, delayed treatment-related neurotoxicity and neurocognitive sequelae emerged as a significant debilitating complication in PCNSL patients, especially when effective combined chemoradiation can achieve disease control and long-term survival rates. Therefore, by delivering hyperfractionated conformal WBRT plus SIB, this prospective cohort study aims to accomplish both optimal intracranial control and minimal WBRT induced neurocognitive decline. Additionally, by administering objective multi-domain neurobehavioral/neurocognitive assessments, the change in neurocognitive functions (NCFs) before and after the course of hyperfractionated conformal WBRT will be investigated and analyzed.

According to the treatment guidelines for treating newly-diagnosed PCNSL patients, combined chemoradiation in which the WBRT course is sandwiched between initial courses of MTX and the later courses of chemotherapy with Ara-C is the treatment of mainstay at our institute. Employing the technique of a conformal CT treatment planning, the WBRT course is delivered in the manner of hyperfractionation with a reduced cumulative dose of 3600 cGy in 30 fractions during 3-4 weeks, administered twice daily in 1.2 Gy - fractions with at least 6 hours between fractions. By virtue of multidisciplinary management and teamwork including neurosurgery, hematology, radiation oncology, and neuroimaging expertise, it is attempted to recruit all potentially eligible patients with newly-diagnosed PCNSL. Most importantly, a professional neuropsychologist participates in this research project to integrate neurobehavioral outcomes into the prospective study. Accordingly, a battery of neuropsychological measures is used to evaluate predetermined NCFs for the studied patients. The test battery is composed of six standardized neuropsychological tests, covering four domains sensitive to disease and treatment effects (executive function, attention, verbal memory, information processing). The primary outcome measure is the change in patients' capability of information processing indicated by the Paced Auditory Serial Addition Test-Revised (PASAT-R), from the baseline before receiving the WBRT course to the follow-up after undergoing the entire courses of combined chemoradiation.

This prospective cohort study aims to thoroughly examine newly diagnosed PCNSL patients by using a standard battery of neurobehavioral/neurocognitive functions. Additionally, a better intracranial disease control is expected since the WBRT course relies on a highly conformal treatment planning integrated with the individualized arrangement of simultaneous integrated boost (SIB) to escalate the focal dose irradiating the originally involved site(s). Moreover, WBRT-related neurocognitive sequelae might be significantly less likely to occur because the WBRT course is delivered in the fashion of hyperfractionation, indicating a significantly lower dose per fraction and a reduced cumulative dose. Furthermore, it is anticipated the investigators will analyze which neurobehavioral domain would predict the treatment-related neurocognitive impacts to the largest extent in newly diagnosed PCNSL patients treated with cranial RT combined with or without MTX based chemotherapy according to the multidisciplinary treatment guidelines implemented at a single institute.


Eligibility criteria: 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

Primary outcomes:
measure: The primary endpoint is the change in patients' capability of information processing, as determined by the assessment (the Paced Auditory Serial Addition Test-Revised) from baseline up to 30 months after completing all courses of chemoradiation.
timeFrame: one week before the WBRT course, up to 30 months after completing all courses of chemoradiation
measure: The primary endpoint is delayed recall, as determined by the change/decline in verbal memory (Word Sequence Learning Test) from baseline up to 30 months after completing all courses of chemoradiation.
timeFrame: one week before the WBRT course, up to 30 months after completing all courses of chemoradiation
measure: The primary endpoint is the change of executive function, as determined by three different domains assessments from baseline up to 30 months after completing all courses of chemoradiation.
timeFrame: one week before the WBRT course, up to 30 months after completing all courses of chemoradiation
measure: The primary endpoint is the change of executive function, as determined by three different domains assessments from baseline up to 30 months after completing all courses of chemoradiation.
timeFrame: one week before the WBRT course, up to 30 months after completing all courses of chemoradiation
measure: The primary endpoint is the change of executive function, as determined by three different domains assessments from baseline up to 30 months after completing all courses of chemoradiation.
timeFrame: one week before the WBRT course, up to 30 months after completing all courses of chemoradiation
measure: The change in attention functions from baseline up to 30 months after completing all courses of chemoradiation.
timeFrame: one week before the WBRT course, up to 30 months after completing all courses of chemoradiation
Secondary outcomes:
measure: The time from the date of recruitment to that of intracranial progression/failure noted on brain MRI
timeFrame: Baseline before the WBRT course; 2 months after completing all courses of chemoradiation, and follow up to 30 months
measure: Depression Inventory questionnaires.
timeFrame: Baseline before the WBRT course; one month after completing the WBRT course; 2 months after completing all courses of chemoradiation, and follow up to 30 months
measure: Anxiety Inventory questionnaires.
timeFrame: Baseline before the WBRT course; one month after completing the WBRT course; 2 months after completing all courses of chemoradiation, and follow up to 30 months
measure: Self & family Evaluation questionnaires.
timeFrame: Baseline before the WBRT course; one month after completing the WBRT course; 2 months after completing all courses of chemoradiation, and follow up to 30 months
Other outcomes:
Locations:
city: Taoyuan
country: Taiwan
facility: Chang Gung Memorial Hospital
Study officials:
References: