Comparison of Content and Psychometric Properties for Assessment Tools Used for Brain Tumor Patients: a Systemic Literature Review

Aims: To determine the most frequently utilized functional status assessment instruments for patients with brain tumors, compare their contents, using the International Classication of Functioning, Disability and Health (ICF), and their psychometric properties. Methods: a systematic literature search was performed for identication of the frequently used functional assessment tool in clinical trials in PubMed, ScienceDirect and ProQuest databases. The content of most used instruments was linked to the ICF categories. Psychometric qualities of these assessment tools were systematically searched and analyzed. Results: Nine most used assessment tools in clinical trials were identied. The Karnofsky Performance Scale was the only generic tool for oncologic patients. Out of four self-assessment tools, three were disease-specic (EORTC QLQ-C30, EORTC QLQ-BN20 and FACT-Br) and one used for different diagnosis (SF-36). The Functional Independence Measure and the Barthel Index were two objective assessment tools that described functioning, but two were neuropsychological tests (MMSE and Trial Making Test). Two hundred eighty-three meaningful concepts were identied and linked to 102 most relevant second-level categories covering all components of the ICF. Forty-nine studies reporting psychometric properties of those nine assessment tools were identied, indicating good reliability and validity for all the instruments. Conclusion: Nine most frequently utilized functional status assessment instruments for patients with brain tumors represent all components of the ICF and have good psychometric properties. However, the choice of the tool depends on the clinical question posed and the aim of its use.


Introduction
Based on 2015 statistics, patients with brain tumors make up a total of 5% of all oncology patients in Latvia. (1) As the medical industry, diagnostic capabilities, and technologies for treating primary tumors evolve, the survival rates for individuals diagnosed with primary brain tumors has increased signi cantly. (1,2) Tumor localization, anatomical distribution, and volume are determinants before and after primary treatment. The most common symptoms for brain tumors usually include headache, nausea, vomiting, partial and generalized seizures, cognitive impairment, and ataxia. These symptoms may also arise from common treatment strategies used for brain tumor patients such as chemotherapy, radiation therapy and surgery. It is estimated that in 75% of all patients with brain tumors show symptoms of focal neurological de ciency (3), which greatly affects one's level of functioning, as well as quality of life.
Numerous articles discuss the role of rehabilitation in tumor cases, while others discuss the positive effects of rehabilitation for patients with brain tumors compared to patients with stroke or after a traumatic brain injury. (4,5) All of these articles demonstrate positive outcomes in restoring functioning (6, 7) Bartolo M. et al. have demonstrated that rehabilitation is very effective if it is initiated as early as possible after primary treatment for brain tumor patients. (5) To assess the rehabilitation needs and outcomes for this population, a speci c functional disability assessment tool is necessary. (8) The use of appropriate assessment tools could improve rehabilitation planning that in turn would lead to better outcomes, including patients' quality of life.
Currently no standardized protocols are provided for evaluation of persons with brain tumors. The International Classi cation of Functioning, Disability and Health (ICF) provides a framework for coding large-scale health information, a common standardized language for identifying and comparing functional assessment tools and provides valuable information to develop an evidence-based standardized evaluation protocol for patients with brain tumor. (9) The aim of this study was to determine the most frequently utilized functional assessment instruments for patients with brain tumors, compare their contents, using the International Classi cation of Functioning, Disability and Health, and analyze their psychometric properties.

Methods
Identi cation of assessment tools Data collection was based on Cochrane Handbook for Systematic Reviews of Interventions. (11) General study data (year of publication, country, study design), available data on participants (number, diagnosis) and assessment tools used in the study were recorded. Assessment tools that were used in more than 10% of all studies were included in the systematic review using frequency analysis.
Linking to the ICF All assessment instruments identi ed in the study meeting selection criteria were classi ed using the ICF linking guidelines. The ICF linking guidelines state that before starting the process of linking health-status measures to the ICF categories, identi cation of all meaningful concepts within each item of the health status measure needs to be performed. According to the rules, the interval of time cannot be linked to the ICF, also, if a meaningful concept of an item is explained by examples, both the concept and the examples are to be linked, while technical measures can be linked by de ning the purpose and then linking it with the ICF category. (12,13). Two independent medical professionals (authors LG and SS) separately identi ed the meaningful concepts within the analyzed instruments and linked them to the ICF concepts. The raters met and discussed any discrepancies to achieve a consensus classi cation for the instruments and GB served as a third rater, in case the consensus could not be reached. Perspective adopted in health information and categorization of response for self-assessment tools were also reported. (12) Psychometric properties Following the search methodology developed by PubMed (14), the electronic database MEDLINE (PubMed) was searched for studies that re ect the psychometric properties of a particular assessment tool. First, a search was performed using a diagnosis speci c MeSH terms and key words identi ed in the search methodology, and the names of assessment tools. Headline screening identi ed studies that re ected one of the psychometric properties of a given instrument (reliability: internal coherence; test/retest method, evaluator reliability. Validity: content validity; criterion validity; construct validity) speci c to patients with brain tumor. If speci c psychometric properties for chosen assessment tools were not identi ed, the search was repeated excluding diagnosis speci c MeSH terms, thus conducting a search for studies covering different diagnoses. Headline screening then identi ed studies that re ected one of the psychometric properties of a given instrument for various diagnoses. The interpretation of the psychometric properties is given in Table 1.

Identi cation of assessment tools
The initial search strategy returned 9721 articles. The duplicates were removed, titles and abstracts were reviewed and after excluding articles which did not meet the selection criteria, and a pool of 56 articles was subject to further examination. To make the search as comprehensive as possible, references from the included articles were studied and an additional 32 articles were included after applying the selection criteria.
As a result, a total of 88 studies were included in the report; 31 were administered in the United States, 42 in Europe (8 in Italy, 8 in the Netherlands, 6 in Norway, 4 in France, Germany and England each 3, Austria, Turkey, Sweden 2 studies each, Poland, Switzerland, Denmark and Finland each 1), 2 in Australia, 7 in Canada, and 4 in Asian countries (Korea, Israel, Iran). The studies look at groups of patients with various brain tumor diagnosis. The 74 articles included patients with primary tumors, of which 26 were diagnosed with glioma, 3-oligodendroglioma, 1-oligoastrocytoma, 3-astrocytoma, 4-adenoma, 1-meningioma, 1 case study had a mixed group with patients suffering from meningioma and glioblastomas. 28 of the studies did not categorize patients by their histologic type; instead, patients with primary brain tumors were evaluated. 9 studies evaluated patients with secondary brain tumors or with brain metastases. In 4 of the included studies, the functional abilities of patients with brain tumors are compared to those of a stroke patient or a patient with a brain injury.
All instruments mentioned in the articles were identi ed, yielding 86 assessment tools. According to research methodology, 9 assessment tools that were used in more than 10% of the research articles included in the study were used for further analysis: A list of these instruments, their abbreviations and the number of articles that have used that instrument are summarized in Table 2. Out of nine instruments included in the study, three are speci c for patients with brain tumors:  Functional Assessment of Cancer Therapy-Brain FACT-BR 8 9 36-Item Short Form Health Survey SF-36 8 9 Linking to the ICF In total, 283 meaningful concepts were identi ed within all nine assessment instruments and linked to 394 most precise categories of the ICF. The detailed description on the linking is shown in    x: 1 or 2 items included, xxx: 3 or more items included

Discussion
This study identi ed nine rehabilitation assessment instruments that have most commonly been referred to in the literature for adults with brain tumors, that covers all components of the ICF, and has good psychometric properties. As far as the authors are aware, this is the only systematic review of assessment instruments used for adults with brain tumors. However, this systematic review did not identify one unique assessment instrument for the target group. This patient group is speci c in a way that there is no unifying patient-speci c clinical set of symptoms and their symptoms depend on various other factors. (15) Five of these tools are used for objective assessment: KPS, MMSE, FIM, TMT, BI, four are self-assessment tools: FACT-Br, SF-36, EORTC QLQ-C30, EORTC QLQ-BN20.
The most frequently used assessment instrument is the Karnofsky Performance Scale as it is used as a criterion for the selection of participants by measuring their level of physical activity. (16) This assessment tool is developed for general assessment of oncological patients (17) and re ects overall ability to perform usual daily activities (component of Activities and Participation of the ICF) in the context of help needed from other people (Environmental Factors).
Only three of these instruments are speci cally intended for evaluation in patients with brain tumors: EORTC QLQ-C30; EORTC QLQ-BN20; FACT-Br; they are all linked to the quality of life. Moreover, the EORTC team recommends that QLQ-C30 and QLQ-BN20 tools be used together. (18) These two tools cover both functioning components of the ICF and from the perspective of content, complement each other. QLQ-C30 contains more speci c questions on problems speci c to patients with brain tumors. (19,20) The QLQ-C30 and the QLQ-BN20 provide comprehensive information about the patient's quality of life, but this is often overlooked in studies identi ed in this systematic review. The FACT-Br questionnaire has been used less and it has as good properties in terms of intra-rater reliability and structural validity as other two speci c quality of life measurements, contains problems that has not been included in any of previous tools, and can clearly be important for this population, such as handling stress or driving a car. It also considers important Environmental factors, such as help and attitudes of family members and friends, as well as health professionals. Some important concepts also overlap with the SF-36 that have developed as a multipurpose tool that is used for assessment of functional health and wellbeing (21) and has been widely used for patient-reported outcomes in populations with different diagnosis. (22) Therefore, this could be good choice to use the SF-36, if the comparison between populations is needed.
Between the most used assessment tools, the FIM and BI has been listed. As SF-36, these instruments are non-speci c to diagnosis, and both have been widely used in different rehabilitation populations. (23)(24)(25) Both scales, the FIM and the BI, are performance based assessment tools and both analyze the level of independence in most important activities of daily living, psychometric properties have been profoundly analyzed, and the ceiling effect for the BI can be observed when compared to the FIM.(26) However, the psychometric properties of the objective assessment instruments speci c for the patient group have not been proven; therefore, their psychometric properties were demonstrated in patients suffering from stroke, traumatic brain injury (TBI) or similar neurological condition. Interestingly, two neuropsychological assessment tools (the MMSE and the TMT) are mentioned between the most frequently for persons with brain tumors. It can be explained with the fact that cognitive impairments are a common symptom in patients with brain tumors. Using the ICF framework, it was possible to link the majority of elements identi ed in the assessment instruments to certain categories. Some elements could not be linked since they covered topics such as quality of life, personal factors, or certain elements not de ned in the ICF. Body Function categories were dominated by MMSE, TMT, EORTC QLQ-BN20, EORTC QLQ-C30, activity and participation categories -FIM, BI, KPS, but FACT-Br viewed these two domains equally. Environmental factors were assessed by EORTC QLQ-30, FACT-Br, FIM, BI and KPS. Given that the clinical picture of brain tumor patients is similar to that of other neurological conditions, such as stroke (6) or TBI (7), the ICF Core Sets were reviewed for stroke and TBI (27) and their categories were compared to categories identi ed in this systematic review. Comprehensive core sets for stroke listed 13 categories in body functions and structures, 14 in activities and participation, and 23 categories in environmental factors that were not identi ed in assessment instruments analyzed in this study. Comprehensive core sets for TBI listed 10 categories in body functions domain, 22 in activities and participation, and 28 categories in environmental factor domain that were not identi ed in any of 9 assessment instruments analyzed within this study. This can be explained by the fact that the most frequently used assessment instruments do not cover all the possible impairments for people with brain tumors.
Given that the ICF Core Sets for stroke and TBI were compared to categories identi ed in this review and they proved to be overall covering similar areas it can be concluded that all 9 assessment tools identi ed in this study can be appropriate and speci c assessment instruments for patients with brain tumors, as they have been proven valid, reliable and responsive to a variety of neurological conditions. Further research is recommended to assess reliability, validity, and responsiveness of assessment instruments speci cally for brain tumor patient groups.

Conclusions
Between the nine most frequently used assessment instruments in clinical studies one was a generic tool for overall description of activity level for patients with diagnosis of cancer, three were diagnosis speci c self-assessment tools, one was multipurpose tool for assessment of functionality and health status, two were widely used tools in rehabilitation for assessment of activities of daily living, and two were neurocognitive tests. These tools cover all components of the International Classi cation of Functioning, Disability and Health and have proven to have good psychometric properties; however, the assessment tools that are not diagnosis speci c, still have to be validated for the brain tumor population.
Since the content and administration varies, the choice of the tool used for assessment of patients with brain tumor depends on the clinical question posed, as well as the aim of the use of this tool.

Declarations
Ethics approval and consent to participate