Multidisciplinary rehabilitation for follow‐up after primary brain tumour treatment
Abstract
This is a protocol for a Cochrane Review (Intervention). The objectives are as follows:
To assess the effectiveness of multidisciplinary rehabilitation in persons after primary brain tumour treatment, and specifically to explore the following areas:
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Does organised multidisciplinary rehabilitation achieve better outcomes than the absence of such services in persons after primary brain tumour treatment?
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Which type of programmes are effective and in which setting?
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Does a greater intensity (time and expertise, or both) of rehabilitation lead to greater gains?
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Which specific outcomes are influenced (survival, dependency, social integration, mood, quality of life)?
Background
Description of the condition
Primary brain tumours are a diverse group of neoplasms that account for 2% of all cancers (Arber 2010) and affect approximately seven persons per 100,000 population annually worldwide (Parkin 2005). There is evidence to support the increasing overall incidence of primary brain tumours, with the highest increase noted in patients over 60 years of age (Flowers 2000). In 2009, there were 22,070 estimated new cases of primary brain tumours in the United States (Jemal 2009). In the United Kingdom, 3000 new cases of primary brain tumours are reported each year, with approximately 2500 deaths per annum (Arber 2010). A similarly high incidence rate is also reported in Australia, with approximately 1400 new cases and more than 1200 deaths from malignant and benign brain tumours annually (Brain Foundation 2011).
Significant medical advancements in the treatment of primary brain tumours have resulted in a marked increase in the number of survivors (Huang 2000; Poggi 2009). Radiation therapy remains the primary treatment for brain tumours; adjuvant chemotherapy and surgical treatment have recently gained more support as a means of prolonging survival (Huang 2000). Despite these treatment options, brain tumours remain a significant source of functional and psychosocial impairment for this patient population, limiting them in everyday activity and often restricting them from participation in community and social life due to many issues (Huang 2000; Tang 2008). Furthermore, the treatment regimens can produce significant adverse effects (Aziz 2003; Tang 2008). The diagnosis of brain tumour can have a distressing psychological impact, significant costs and socioeconomic implications, increasing the demand for health care, social and vocational services, and further burdening the caregiver (Tang 2008).
Persons with primary brain tumour can present with various combinations of problems, such as physical, cognitive, psychosocial, behavioural and environmental issues. The World Health Organization (WHO) developed the International Classification of Functioning, Disability and Health (ICF), which defines a common language for describing the impact of disease at different levels: impairment (body structure and function), limitation in activity and participation (WHO 2001). Within this framework, primary brain tumour‐related impairments can limit ‘activity’ or function and ‘participation’ in society and life situations, and reduce life span. Many people diagnosed with brain tumour may have ongoing concerns (relationship, employment, recurrence) (Ownsworth 2009). The limitation in function (disability) can have a cumulative effect over time and cause considerable distress to the cancer survivor and their families, and reduce quality of life (Ness 2010). Patients discharged back to the community are confronted by various adjustment issues, such as the patient's perceptions of self worth, self image and role reversal within the family. Families often struggle to cope with new demands associated with increased care needs, inability to drive and return to work, financial constraints, marital stress and general limitation in patients’ participation. Ongoing monitoring, education and counselling of the patient (and family) are important.
The care needs of persons after treatment for primary brain tumours (surgery, chemotherapy and radiotherapy) are varied, given the complex, multifactorial nature and multiple disabilities (which may progress) in these persons. These are best met with a co‐ordinated multidisciplinary, multifaceted approach, which includes acute medical and surgical care, rehabilitation, palliative and other supportive interventions (Gabanelli 2005).
Description of the intervention
Rehabilitation is defined as "a problem‐solving educational process aimed at reducing disability and handicap (participation) experienced by someone as a result of disease or injury" (Wade 1992).
In this review, multidisciplinary rehabilitation is defined as the co‐ordinated delivery of multidimensional rehabilitation intervention provided by two or more disciplines (such as physiotherapy, occupational therapy, social work, psychology and other allied health, nursing), under medical supervision (surgeon, oncologist, rehabilitation and/or palliative physician). This multidisciplinary approach provides patients with skills needed to manage their own care to improve their coping ability, knowledge base and quality of life (Corner 2007). A multidisciplinary intervention prioritises patient‐centred care and focuses on a person's function/disability, usually for a limited time period. It aims to maximise activity and participation (social integration) using a holistic biopsychosocial model (which encompasses physical and psychosocial aspects) of care.
Although uni‐disciplinary intervention in rehabilitation (physical therapy alone), or modalities delivered by a single discipline (gym, gait training, strengthening programme) are commonly described in clinical practice, this review addresses only multidisciplinary rehabilitation as defined above.
Persons after primary brain tumour treatment can present to rehabilitation settings with a range of difficulties which may be physical, emotional, psychosocial and/or environmental. Multidisciplinary rehabilitation encompasses the framework and common language for describing the impact of disease at different levels using the ICF (WHO 2001). For example, in persons after brain tumour treatment:
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'impairments' are problems with body (anatomical) structures or function (headaches, seizures, neurocognitive dysfunction, muscle weakness, aphasia, visual impairments);
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'activity limitation' (disability) are difficulties faced by a person executing everyday tasks (mobility or self care);
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'restriction in participation' relates to problems experienced by a person which limit involvement in societal participation and life situations (that is, employment, family life, social reintegration);
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'contextual factors' are:
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‘environmental’ which make up the physical, social and attitudinal environment in which a person lives their life (construction the same as above); and
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‘personal' (such as gender, race, coping style, social and educational background) which may affect the person’s experience of living with their condition.
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Many systematic reviews support various treatment modalities such as chemotherapy (Stewart 2002) and symptomatic pharmacological therapy, radiotherapy (Andrews 2004) or surgery (Pirzkall 1998) for persons with primary brain tumour. A number of reviews also address uni‐disciplinary rehabilitation for this population, such as psychological interventions (Ownsworth 2009; Sheard 1999). However, none address multidisciplinary rehabilitative care in these patients. This review will evaluate the effectiveness of multidisciplinary rehabilitation in persons following treatment for primary brain tumours aimed at improving their function, quality of life and social reintegration, and guide treating clinicians on best practice.
How the intervention might work
Multidisciplinary rehabilitation in persons following primary brain tumour treatment can utilise various categories in domains comprising the structured framework outlined by the ICF, for targeted intervention and therapy. It provides clinicians with specific categories within relevant domains for intervention, for example, ‘activity and participation’ domain (relating to mobility, self care, domestic life, major life areas), and environmental factors (transport, access to places, relationships, attitudes).
Many impairments (hemiparesis, dysphasia, cognitive deficits) seen in the brain tumour population are also common in other neurological conditions such as acquired brain injury, stroke and multiple sclerosis. There is strong evidence to support multidisciplinary rehabilitation in various neurological conditions, such as multiple sclerosis (Khan 2007), acquired brain injury (Turner Stokes 2005) and stroke (SUTC 2007). A number of studies show that patients with brain tumours undergoing rehabilitation appear to make significant functional gains (Geler‐Kulcu 2009; Greenberg 2006; Huang 2001; Marciniak 2001; O’Dell 1998; Tang 2008), in line with those seen in patients affected by other cerebral pathologies such as traumatic brain injury or stroke (Kirshblum 2001). Furthermore, there is strong evidence for uni‐disciplinary interventions such as exercise and physical therapies that enhance physiological and functional outcomes and improve quality of life in cancer survivors (MacVicar 1986; MacVicar 1989; Markes 2006; McNeely 2010).
Why it is important to do this review
There are no systematic reviews for multidisciplinary rehabilitation following treatment in primary brain tumour survivors to date. Other reasons to do this review include the following.
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Brain tumour rehabilitation is complex and challenging (Kirshblum 2001) and there is a need to address the long‐term needs of cancer survivors in light of recent initiatives as outlined in the United States National Coalition for Cancer Survivorship (NCCS 2009), which aims to produce evidence‐based guidelines and implement survivorship care plans. In addition, this systematic review could help inform the implementation of a National Cancer Survivorship Initiative (Cancer Reform Strategy 2007) which explores individualised approaches to survivorship care (education, nutrition, self management) and the provision of rehabilitation programmes.
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Advances in medical care and increased life expectancy among persons with disabilities: ongoing health and well being become increasingly important and require long‐term planning (Campbell 1999; Turk 2001). From the rehabilitation perspective, the challenge is not just about helping the brain tumour survivor to overcome the symptoms and improving the patient’s performance status, but helping them stay independent in the community in the face of changes with aging.
A systematic review on this topic therefore is required to summarise the best available evidence to date. This review aims to identify the existing evidence for multidisciplinary rehabilitation in persons after primary brain tumour treatment, guide treating clinicians and identify gaps in current knowledge.
Objectives
To assess the effectiveness of multidisciplinary rehabilitation in persons after primary brain tumour treatment, and specifically to explore the following areas:
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Does organised multidisciplinary rehabilitation achieve better outcomes than the absence of such services in persons after primary brain tumour treatment?
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Which type of programmes are effective and in which setting?
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Does a greater intensity (time and expertise, or both) of rehabilitation lead to greater gains?
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Which specific outcomes are influenced (survival, dependency, social integration, mood, quality of life)?
Methods
Criteria for considering studies for this review
Types of studies
All randomised controlled trials (RCTs) and clinical controlled trials (CCTs), which will include quasi‐randomised and quasi‐experimental designs with comparative controls (controlled before‐and‐after studies).
Types of participants
Inclusion criteria
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Adults (aged 18 years and older).
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Confirmed diagnosis of brain tumour, regardless of time of onset or disease stage according to the WHO classification of Tumours of the Central Nervous System (CNS) (Louis 2007) to include: astrocytic tumours; oligodendroglial tumours; ependymal tumours; choroid plexus tumours; other neuroepithelial tumours; neuronal and mixed neuronal‐glial tumours; tumours of the pineal region; embryonal tumours; tumours of the haemopoietic system; germ cell tumours; meningeal tumours; tumours of the sellar region.
We will include studies involving participants with a range of cancers or other diagnoses where data are specifically provided for persons with primary brain tumour.
Exclusion criteria
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Studies recruiting only participants with metastatic (i.e. non‐primary) brain tumour.
Types of interventions
Multidisciplinary rehabilitation is defined as any intervention delivered by two or more disciplines (such as physiotherapy, occupational therapy, social work, psychology and other allied health, nursing), under medical supervision (surgeon, oncologist, rehabilitation and/or palliative physician), which aims to maximise activity and participation, as defined by the ICF (WHO 2001).
Multidisciplinary rehabilitation interventions and programmes have no definite classification and can be broadly described in terms of settings and content (Turner Stokes 2011). Multidisciplinary rehabilitation settings may include ‘inpatient’ settings, where care is delivered 24 hours a day in a hospital ward or specialist rehabilitation or palliative care unit; ‘ambulatory/outpatient settings’ which may be within a hospital or in the community; and ‘home‐based settings’ which are set within the patient’s own home and local community.
Multidisciplinary rehabilitation varies in its content, intensity and frequency, and is tailored to an individual’s needs. The common terms used in the literature regarding rehabilitation programme content include: physical rehabilitation; cognitive and behavioural therapy; vocational and recreational rehabilitation; psychological and counselling input. However, the actual content of any two programmes within the same category may vary greatly, and similar programmes may have been given different labels (Turner Stokes 2011).
We will consider all studies that state or imply multidisciplinary rehabilitation provided it satisfies the definition above and compares it to some form of control condition for inclusion in this review. Control conditions will include:
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lower level or different types of interventions such as 'routinely available local services' (for example, medical and nursing care);
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minimal interventions (such as 'information only');
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waiting list controls or no treatment;
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interventions given in different settings and lower intensity of interventions.
We will exclude those studies that assess the effect of therapy from a single discipline (for example, physiotherapy only) or any uni‐disciplinary intervention or modality (for example, physical exercise).
Types of outcome measures
Primary outcomes
Primary outcomes will reflect the burden of disease on patients and on the services provided for them.
They will be categorised according to the ICF (WHO 2001) into those that focus on:
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impairment, for example, headache, seizures, muscle weakness, aphasia, visual impairments, pain;
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disability (limitation in activity), measured by validated tools such as the Functional Independence Measure (FIM) (Granger 1998), Barthel index (BI) (Mahoney 1965), Cancer Rehabilitation Evaluation System‐short form (CARES‐SF) (Ganz 1992; Schag 1991), Cancer Survivor Unmet Needs (CaSUN) measure (Hodgkinson 2007) and Perceived Impact of Problem Profile (PIPP) (Pallant 2006);
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restriction in participation and/or environmental or personal context, for example, quality of life (SF‐36; Ware 1993), fatigue (Fatigue Impacts Scale; Fisk 1994), psychological (Depression Anxiety Stress Scale; Lovibond 1995) and vocational outcomes (Work Instability Scale; Gilworth 2003), patient satisfaction measures and others.
Secondary outcomes
Secondary outcomes will include outcomes that reflect service utilisation, such as the duration of hospital stay in both acute and subacute settings, readmission, the cost of care and the extent of services used at the time of discharge.
Any adverse events that may have resulted from the intervention, defined as those events that are life‐threatening or requiring prolonged hospitalisation.
Search methods for identification of studies
We will consider articles in all languages, with a view to translation if necessary.
Electronic searches
We will search the following sources.
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The Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library) (see Appendix 1).
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MEDLINE (via OvidSP) (from 1950).
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EMBASE (via OvidSP) (from January 1980).
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PEDro (from January 1985).
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LILACS (from January 1982).
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The WHO International Clinical Trials Registry Platform (ICTRP) search portal (http://apps.who.int/trialsearch/Default.aspx) for all prospectively registered and ongoing trials.
The search strategy will also include searches of: the Cochrane Cancer Network (CCN), CancerLit, Biosis and Science Citation Index. We will use the same principle to search each database. This will include: (i) the terms and phrases identifying randomised or clinical controlled trials and clinical controlled trials combined using the Boolean “OR”; (ii) all the terms and phrases describing brain neoplasm combined with “OR” and (iii) all terms used to identify the interventions of interest, i.e. multidisciplinary rehabilitation, combined with “OR”. We will then grouped these terms with the Boolean operator “AND” and perform the final search of the articles from the displayed results. We will use wild cards and truncation symbols to ensure terms with alternative spellings and/or endings are not missed. We will explode all MeSH terms.
Searching other resources
We will check the bibliographies of studies identified and contact the study authors and known experts in the field seeking published and unpublished trials. We will also handsearch the most relevant journals (Brain, Cancer, Supportive Care in Cancer, Journal of Cancer Therapy, American Journal of Clinical Oncology: Cancer Clinical Trials, Annals of Cancer Research and Therapy, Journal of Surgical Oncology, Journal of Oncology, European Journal of Cancer and Clinical Oncology, Journal of the Cancer Institute, Neuro‐oncology, Journal of Neuro‐oncology, Journal of Neurology, Neurosurgery and Psychiatry, Physical Therapy, Archives of Physical Medicine and Rehabilitation, Clinical Rehabilitation).
We will also undertake an expanded search by using the related articles feature (via PubMed), Proquest Dissertations and Theses, searching key authors (via Web of Science) and searching SIGLE (System for Information on Grey Literature in Europe).
Data collection and analysis
Selection of studies
Three review authors (BA, LN, FK) will independently screen and short‐list all abstracts and titles of studies identified by the search strategy for appropriateness based on the selection criteria. Two review authors (BA, LN) will independently evaluate each study from the short‐list of potentially appropriate studies for inclusion or exclusion. If necessary, we will obtain the full text of the article for further assessment to determine if the study meets the inclusion/exclusion criteria. If no consensus is met about the possible inclusion/exclusion of any individual study, we will make a final consensus decision by discussion amongst all the review authors. If there is still no consensus agreement regarding the inclusion/exclusion of a study, then we will submit the full article to the editorial board for arbitration. Review authors will not be masked to the name(s) of the author(s), institution(s) or publication source at any level of the review.
We will seek further information about the method of randomisation or the complete description of the multidisciplinary rehabilitation interventions from the trialists, where necessary. Only studies with sufficient details about the multidisciplinary rehabilitation programme will be included.
We will exclude studies with fatal flaws (for instance, withdrawals by more than 40% of the participants or nearly total non‐adherence to the protocol or very poor or non adjusted comparability in the baseline criteria).
Data extraction and management
Review authors (FK, BA, LN) will independently extract the data from each study that meets the inclusion criteria, using a data collection form. We will resolve disagreements through discussion and coming to a consensus. If necessary, we will contact study authors of potentially eligible studies to provide clarification. We will summarise all studies that meet the inclusion criteria in the 'Characteristics of Included Studies' table provided in the Review Manager 5 software developed by The Cochrane Collaboration (RevMan 5) to include details on design, participants, interventions and outcomes. We will include the following information:
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publication details;
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study design, study setting, inclusion/exclusion criteria, method of allocation, risk of bias;
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patient population, for example age, type of surgical procedure, type of tumour;
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details of the intervention;
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outcome measures; and
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withdrawals, length and method of follow‐up and the number of participants followed up.
Assessment of risk of bias in included studies
Two review authors (BA, LN) will independently assess the methodological quality of the included studies using Cochrane's 'Risk of bias' tool (Higgins 2011). We will assess the allocation sequence generation, allocation concealment, blinding of participants, therapists and outcome assessors, incomplete outcome data and selective outcome reporting. A judgement of ‘low risk’ will indicate a low risk of bias, ‘high risk’ will indicate a high risk of bias, and ‘unclear’ will indicate either unclear or unknown risk of bias (see Table 1).
| Judgement of risk of bias | Quality rating of study |
| Risk of bias of all domains low | High methodological quality = ‘high‐quality study’ |
| Unclear or high risk of bias for one or more domains | Low methodological quality = ‘low‐quality study’ |
| High risk of bias for most domains | Very low methodological quality = ‘very low‐quality study’ |
We will consider studies to be of high methodological quality if the risk of bias for all domains is low. We will term these studies 'high‐quality studies'. We will rate studies as low methodological quality if there is unclear or high risk of bias for one or more domains and will term these 'low‐quality studies' (see Table 2). Any disagreements or lack of consensus will be resolved by a third review author (FK).
| Underlying methodology | Quality rating |
| Randomised trials or double‐upgraded observational studies | High |
| Downgraded randomised trials or upgraded observational studies | Moderate |
| Double‐downgraded randomised trials or observational studies | Low |
| Triple‐downgraded randomised trials or downgraded observational studies or case series/case reports | Very low |
Measures of treatment effect
We will enter and analyse all quantitative data in the RevMan software (RevMan 5). We will calculate, for each outcome of interest, summary estimates of treatment effect (with 95% confidence interval (CI)) for each comparison. Where possible, we will calculate risk ratio (RR) with 95% CIs for dichotomous data while we will calculate difference in means or standardised difference in means (SMD) with 95% CIs for continuous data. We will discuss and present the results of individual studies in table and graphical format, where data aggregation is not possible.
Unit of analysis issues
We anticipate that the appropriate unit of analysis will be by type, intensity and setting of multidisciplinary rehabilitation. We expect a limited number of RCTs and CCTs. We will attempt a qualitative analysis using GRADE for existing evidence.
Dealing with missing data
If insufficient data are available, we will contact study authors of potentially eligible studies to provide data and clarification. If the data remain unavailable or insufficient, we will report the study but not include it in the final analysis.
Assessment of heterogeneity
We will conduct statistical analysis as described in the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011). We will assess clinical heterogeneity by examining the characteristics of the studies, the similarity between the types of participants, the interventions and the outcomes, as specified in the criteria for included studies. To check for statistical heterogeneity between studies, we will use both the I2 statistic and the Chi2 test of heterogeneity as well as visual inspection of the forest plots.
Assessment of reporting biases
We will minimise publication bias (Egger 1998) by sourcing unpublished data where possible. Where data are not reported in full for certain outcomes, we will contact the authors for the full data set or the reason for not publishing the data.
Data synthesis
We will pool the results from clinically similar studies for the meta‐analysis, if sufficient studies are available. We will attempt a quantitative analysis if there is clinical homogeneity and the methods and available data in each study allow. If appropriate, we will calculate a weighted treatment effect across studies using Review Manager 5 software. We will express the results as risk ratios (RRs) with 95% confidence intervals (CIs) and risk differences (RDs) with 95% CIs for dichotomous outcomes and mean differences (MDs) and 95% CIs for continuous outcomes.
We will initially use a fixed‐effect model and approximate Chi² tests for heterogeneity to assess the outcome data for compatibility with the assumption of a uniform RR (P > 0.10). In the presence of significant heterogeneity (P < 0.10), we will use the random‐effects meta‐analysis instead.
We will use the GRADE approach to grade the quality of evidence, as described in Chapter 12 of the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011).
Subgroup analysis and investigation of heterogeneity
We will perform subgroup analysis for the following subgroups if data are available, as this will provide information to guide clinical practice:
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type of surgery (total resection, partial resection);
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age (< 50 years of age versus > 50 years of age);
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type of rehabilitation programme (that is, inpatient, ambulatory care);
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intensity of treatment (high‐intensity, low‐intensity multidisciplinary rehabilitation);
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time from definitive treatment (surgery, radiotherapy and chemotherapy) to commencement of multidisciplinary rehabilitation (acute: < six weeks, intermediate: six weeks to six months, and longer term: > six months). We will review participants randomised in the acute stages following definitive treatment (≤ six weeks) as a separate group from participants randomised in the later or convalescent stages (> six weeks following treatment).
Factors considered in heterogeneity will include: setting, type and intensity of multidisciplinary rehabilitation.
Sensitivity analysis
If heterogeneity is found across studies, we will undertake a sensitivity analyses to determine the effect of omitting studies with a high risk of bias.
| Judgement of risk of bias | Quality rating of study |
| Risk of bias of all domains low | High methodological quality = ‘high‐quality study’ |
| Unclear or high risk of bias for one or more domains | Low methodological quality = ‘low‐quality study’ |
| High risk of bias for most domains | Very low methodological quality = ‘very low‐quality study’ |
| Underlying methodology | Quality rating |
| Randomised trials or double‐upgraded observational studies | High |
| Downgraded randomised trials or upgraded observational studies | Moderate |
| Double‐downgraded randomised trials or observational studies | Low |
| Triple‐downgraded randomised trials or downgraded observational studies or case series/case reports | Very low |
