Identifying causes of balance impairment and exploring sensory contributions to balance in pediatric oncology: A Scoping Review

Abstract

PURPOSE:

To identify causes of balance impairment in children undergoing treatment for cancer and childhood cancer survivors.

METHODS:

A systematic search was performed according to PRISMA guidelines. Studies were included if participants were 0-19 years of age with a current/past diagnosis of cancer, an objective balance measure was reported, and a cause of balance impairment was either stated or implied.

RESULTS:

The 64 full text studies included identified balance impairments as sequelae secondary to CNS tumors, and/or as an effect of medical treatment including chemotherapy, radiation, and/or surgery. Cancer treatment can result in damage to the visual, vestibular and/or somatosensory systems which in turn can contribute to balance dysfunction.

CONCLUSIONS:

Balance impairments were caused by the cancer itself or the result of medical treatment. Oncology professionals are integral in recognition and treatment of factors affecting balance impairments in childhood cancer; however, further research is needed to identify interventions targeting specific causes of balance impairment.

1. Introduction

Over the past decade, childhood cancer survival rates have improved significantly, with 5-year survival rates of greater than 80%, and up to 90% in some cancers.^1,2 Improved childhood cancer survival rates are attributable to advances in medical treatment, including improved chemotherapy regimens.² While such advances in treatments have more than doubled the survival rates for childhood leukemia in the last 50 years,² these treatments are not without complications. Many medical treatment agents result in unfavorable short- and long-term side effects, termed “late effects”³ Reported late effects of childhood cancer include neuromotor impairments including but not limited to peripheral neuropathy, ototoxicity, impaired nerve conduction velocity, slowed cognitive processing speed, reduced fine and gross motor skills, and impaired balance.^1,3-5

Children of all ages rely on balance to safely play and participate in activities.^6,7 Maintaining balance involves the complex interplay between many systems, including integration of sensory input and motor output to maintain the body’s center of mass over its base of support.^7,8 Sensory information from the eyes, skin, muscles and joints, and vestibular system is carried through afferent sensory neurons to the brain (Figure 1;B).^7,9,10 These signals are integrated, and the brain creates a corresponding motor signal. This motor output signal, most commonly originating from the primary motor cortex (M1) and associated motor areas (AMAs), is then relayed via efferent motor neurons to specific musculature of the trunk and extremities to maintain postural control of the body in an upright position (Figure 1; C).^7,9,10 The sensory systems then detect this change in motor control, and this cycle of balance perpetuates to maintain postural control (Figure 1; C). If any aspect of this cycle is damaged, the body will have a reduced capacity to maintain balance.

Fig. 1.

Effects of Medical Treatments on Sensory Contributions to Balance. (A) Sensory impairments and their respective causes. (B) Sensory inputs to balance. (C) Cycle of balance maintenance: sensory input from the periphery is integrated in the brain, brain creates a motor output signal and sends this signal to the periphery, postural muscles are activated to maintain control of balance, motor output is sensed by the sensory organs in the periphery, cycle continues. Abbreviation: CIPN = Chemotherapy induced peripheral neuropathy.

Balance dysfunction is commonly reported among children with cancer as a symptom of primary tumor, metastatic disease, or an effect of medical treatment.^11-13 Brain and central nervous system (CNS) tumors are the second most common forms of childhood cancer.¹⁴ Tumors of the CNS may impede the integration of sensory signals, the creation of a motor output signal, or both; therefore, it can be hypothesized that balance deficits may occur as a result of the tumor. Children affected by non-CNS cancers, such as blood cancers (e.g., leukemias and lymphomas) and solid tumors (e.g., bone tumors and retinoblastoma) may experience balance deficits as a secondary result of medical treatments used to treat their cancer, including chemotherapy, radiation, and surgery. These medical treatments may cause damage to a portion of the patient’s balance system (Figure 1; C). For example, the integration of sensory input from the visual, vestibular, and somatosensory systems is required to maintain balance (Figure 1; B).⁹ Thus, if one or more of these sensory systems has been damaged, a child may have difficulty maintaining balance to the degree that is expected of children with all sensory systems intact.

It has been well documented that children undergoing treatment for cancer as well as childhood cancer survivors (CCS) demonstrate impaired balance as compared to healthy peers,¹⁵ but little is known regarding the specific causes of balance impairments within this population. Previous studies have demonstrated that intervention programs are effective in improving balance in children with cancer;^16-24 however, these programs vary immensely in content and are often not targeted to treat the specific cause of balance impairment. Balance impairments have been recorded as long as five years into survivorship.²⁵ Given balance impairments have been reported in children both undergoing cancer treatment and in those well into survivorship, it is important to ask two questions: 1) What are the specific causes of balance impairment in children undergoing treatment for cancer and CCS; and 2) how should healthcare professionals address these balance impairments? This scoping review aims to answer the first question, in hopes that providing a map of the specific causes of balance impairment in this population will guide clinicians to further examine the utility of assessment tools and to tailor interventions specific to these impairments. While previous systematic reviews have aimed to address balance in pediatric oncology populations, these studies have narrowed their research question to include only survivors of childhood blood cancers¹⁵ or to summarize evaluations of balance.¹² The purpose of this scoping review is to identify specific causes of balance impairment and explore the effects of medical treatments on sensory contributions to balance through a broad, yet critical examination of the literature including both children undergoing treatment for cancer and CCS.

2. Methods

This scoping review provides the ability to map balance impairments in pediatric oncology, in order to summarize and disseminate findings to practitioners.²⁶ The five-step methodological framework proposed by Arksey and O’Malley²⁶ was used to identify studies to be included in this review.

2.1. Identifying the research question

To guide this review, the following research questions were posed: what are the specific causes of balance impairment in children undergoing treatment for cancer and CCS; and what sensory deficits could be contributing to this balance impairment?

2.2. Identifying relevant studies

To identify inclusion and exclusion criteria for this scoping review, the authors worked with a medical librarian to develop detailed search strategies for each database. The medical librarian developed the search for PubMed (NLM) and translated the search for every database searched. The PubMed (NLM) search strategy was reviewed by the research team to check for accuracy and term relevancy, and all final searches were peerreviewed by another medical librarian. The databases included in this search are PubMed, Embase (embase.com), the Cochrane Central Register of Controlled Trials (Wiley), CINAHL (EBSCOhost), and PEDro (pedro.org.au), which were searched using a combination of keywords and subject headings. There were no date restrictions to the search. The initial search was performed on November 12, 2021. A search update was conducted in all databases on September 22, 2023. The full search strategies as reported by the librarian are provided in Appendix (A).

2.3. Study selection

Criteria for inclusion were: (1) the sample included children ages 0-19 years with a current or past diagnosis of cancer; (2) an objective balance outcome measure was reported; and (3) the study reported a cause of balance impairment. Studies were excluded if: (1) the sample included adult participants (>19 years); (2) the participants did not have a current or past diagnosis of cancer; (3) the study did not include an objective measure of balance or (4) the study included a measure of ataxia or gait without an additional explicit measure of balance; (5) the study was written in a language other than English; (6) the study was a systematic, scoping or umbrella review without a meta-analysis; or (7) the item was an expert opinion, editorial, abstract, or noncomplete study.

The search resulted in 10,243 studies; duplicate studies were removed using software (Covidence systematic review software, Veritas Health Innovation, Melbourne, Australia). This resulted in 7,876 records to screen from databases. Studies were screened by title and abstract by two blinded and independent reviewers (EM and KR). If a tiebreaker was needed, a third reviewer was used (TM). This process was repeated for full-text screening (EM and KR, tiebreakers TM or CF) and data were extracted (EM). 859 studies were retained for full-text review and 64 studies were included in the review (Figure 2).

Fig. 2.

PRISMA Flow Diagram

2.4. Charting the data

Extracted data is provided in Table 1. Predetermined categories included first author, publication year, balance assessment utilized, implied cause of balance impairment (cancer or medical treatment) and reported sensory impairments. For each study, a brief synopsis of study findings related to balance outcomes was provided (Table 1).

Table 1.

Summary of study characteristics and reported balance impairments

First Author	Year	Study Design	Sample Size	Subjects	On/Off Treatment		Balance Measure	Suspected Cause of Balance Impairment		Reported Sensory Impairment
					On	Off		Cancer	Medical Treatment
Agamanolis33	2012	Case reports (3)	Small	Three children, ages 4, 5 and 9 years, with superficially disseminated glioma (brain, cerebellum, spinal cord, ventricular lesions)	x		Rhomberg Test	√
Akyay71	2014	Cross-sectional	Medium	Children ages 4.5-17 years newly diagnosed with ALL (group 1) and children ages 5-21 years 2-60 months “off treatment” for ALL (group 2)	x	x	TUG		C
Ansell13	2010	Retrospective	Large	Children ages 1-14 years newly diagnosed with brain tumors (astrocytoma, MB, other)	x		Other: Unsteadine ss on feet as defined by ICD-10 coding system	√		Audiometric, Vision
Benzing32	2021	RCT	Large	CCS (CNS and non-CNS cancers), ages 6-17 years		x	German Motor Test - coordination subtest	√	C, R, S
Beulertz27	2013	Cross-sectional	Small	Children ages 4-17 years currently undergoing treatment or within 5 years of treatment for cancer (CNS and non-CNS cancers)	x	x	MOT4-6 - balance and coordinatio n subtests; DMT6-18 - two coordinatio n subtests
Beulertz17	2016	Quasi-experimental	Medium	Children ages 4-17 years currently undergoing maintenance therapy or within 5 years of treatment for cancer (CNS and non-CNS cancers)	x	x	MOT4-6 - balance and coordinatio n subtests; DMT6-18 - two coordination subtests		C, R, S	Vestibular
Bogg80	2015	RCT	Small	Children ages 6-17 years currently undergoing HSCT for treatment of ALL, AML, AA, MPD, or ALCL	x		Other: Single leg balance on a flat surface (seconds)		I (HSCT)
Camet34	2018	Cross-sectional	Medium	CCS (CNS and non-CNS cancers), ages 6-17 years, who received ototoxic therapy (radiation to the head/neck, cisplatin/carbop latin)		x	mCTSIB	√	C, R, S	Vestibular
Chechelnitskaia35	2019	Retrospective	Large	Survivors of PFTs (MB, P-AST, EPD, diffuse stem tumors, AA, ganglioglioma), ages 5-18 years		x	Posturography; Rhomberg Test	√	C, R, S	Vision, Vestibular
Davis36	2010	Cross-sectional	Large	Survivors of cerebellar tumors (MB, EPD, P-AST), ages 4-14 years		x	BOT-2 - body coordination subtest	√	C, R, S
Decock45	2022	Retrospective	Medium	Children ages 0-15 years currently undergoing treatment for PFTs (MB, EPD, P-AST)	x		BOT-2 - body coordinatio n subtest; PDMS-2 - stationary subtest	√	S
DeLuca69	2013	Cross-sectional	Medium	Survivors of ALL (diagnosed between ages 2-5 years), ages 5-12 years		x	BOT-2; m-ABC - balance subtest		C
Doan70	2011	Case report	Small	12-year-old child following consolidation chemotherapy for AML	x		Rhomberg Test		C	Audiometric, Vision Vestibular
Dreneva16	2020	Quasi-experimental	Medium	Survivors of PFT (MB, P-AST, EPD, ganglioglioma, malignant neoplasm of cerebellum, ages 7-17 years		x	Posturography; Rhomberg Test	√	C, R, S	Vision, Vestibular
Flowers18	2020	Case study	Small	4-year-old survivor of astrocytoma with PFS		x	mCTSIB; PBS	√	S	Vestibular
Fontana19	2021	RCT	Small	Children ages 6-18 years with a diagnosis of cancer, regardless of stage of treatment (CNS and non-CNS cancers)	x	x	m-ABC - balance subtest		C, R, S
Galea74	2004	Cross-sectional	Large	Survivors of ALL, ages 0-17 years		x	Posturography; Rhomberg Test		C, R
Gaser52	2022	Cross-sectional	Medium	Children ages 4–18 years newly diagnosed with ALL, AML, or NHL	x		MOON		C
Gaser53	2022	RCT	Medium	Children ages 4–18 years diagnosed with ALL, AML, or NHL	x		MOON		C
Gielis46	2022	Cross-sectional	Medium	Survivors of brain tumors (P-AST, MB, other), ages 3-16 years		x	BOT-2 - balance subtest; m-ABC – balance subtest	√	C, R, S
Gilchrist11	2018	Longitudinal	Medium	Children ages 5-18 years undergoing treatment for leukemia, lymphoma, or non-CNS solid tumors	x		BOT-2 -balance subtest		C	CIPN
Götte72	2015	Cross-sectional	Medium	Children ages 6-18 years undergoing treatment for cancer prior to maintenance therapy (CNS and non-CNS cancers)	x		MOON		C
Gülnerman51	2021	Cross-sectional	Medium	Survivors of ALL, ages 7-12 ages 7-12 years		x	BOT-SF		C
Hamari65	2020	Longitudinal, includes secondary analyses of RCT	Medium	Children ages 3-16 years diagnosed with cancer outside of the CNS who were treated with vincristine	x		m-ABC		C
Harbourne20	2014	Case series	Small	Two survivors of brain tumors (MB, cerebellar tumor) who suffered from PFS, ages 6 and 14 years		x	BBT-P; bOT-2 -balance subtest; posturography; Other: Static standing balance on foam (sec)	√	C, S
Hartman66	2006	Cross-sectional	Large	Survivors of ALL, WT, B-NHL, MMT, ages 4-12 years		x	m-ABC		C
Hartman67	2013	Longitudinal	Medium	Survivors of ALL, ages 9-18 years		x	m-ABC		C
Hooke75	2016	Longitudinal	Small	Survivors of any pediatric cancer, ages 10-17 years		x	BOT-2 -balance subtest		C, R, S
Hung28	2017	Cross-sectional	Small	Survivors of ALL, ages 8-13 years		x	BOT-2 SF
Kasatkin21	2021	Quasi-experimental	Medium	Survivors of PFT (MB, astrocytoma, EPD, ganglioglioma), ages 6-17 years		x	BOT-2	√	C, R, S	Vision
Keiser29	2020	Cross-sectional	Medium	Children ages 6-18 years with a diagnosis of cancer (CNS and non-CNS cancers), during maintenance therapy or follow-up care	x	x	MOON
Kesting30	2015	Cross-sectional	Small	Survivors of pediatric bone tumors, ages 10-19 years		x	MOON
Kristiansen25	2021	Cross-sectional	Small	Survivors of P-AST, ages 9-17 years		x	BOT-2 -balance subtest; Mini-BESTest	√	C, S
Küper37	2013	Longitudinal	Small	Survivors of cerebellar tumor (P-AST, MB, EPD, GB), ages 6-17 years		x	Other: postural sway as measured by ultrasound-based motion analysis system	√	S	Vision, Vestibular
Lee22	2021	Case study	Small	5-year-old child wlth brainstem glioma	x		PBS	√	S
Leone64	2014	Cross-sectional	Small	Survivors of ALL, ages 9-11 years		x	UQAC-UQAM -balance subtest		C
Marchese4	2004	Longitudinal	Small	Children ages 4-15 years undergoing treatment for ALL	x		TUG		C
Marchese 62	2017	Cross-sectional	Small	Survivors of ALL, ages 6-17 years		x	BOT-2 -balance subtest; TUG		C
Marchese63	2021	Cross-sectional	Small	Survivors of ALL, ages 7-16 years		x	BOT-2; Posturography; TUG		C
Marchese50	2022	Quasi-experimental	Small	Survivors of ALL, ages 6-14 years		x	BOT-2 - balance subtest		C
Mohanty47	2022	Case study	Small	14-year-old child with Ewing’s sarcoma following rotationplasty	x		Posturography	√	S
Müller38	2017	Longitudinal	Medium	Children ages 4-18 years undergoing treatment for brain tumors, bone and soft tissue sarcomas	x		Posturography	√	C, R, S
Nama61	2020	Cross-sectional	Medium	Children ages 2-18 years currently receiving vincristine as a treatment for leukemia or lymphoma	x		BOT-2 -balance subtest; TUG		C	CIPN
Nielsen31	2018	Longitudinal	Medium	Children ages 6-18 years with leukemia, lymphoma, extracranial solid tumor or CNS tumor who were treated with chemotherapy or radiation	x		Flamingo balance; TUG	√	C, R, S
Nielsen23	2020	Quasi-experimental	Large	Children ages 6-17 years with leukemia, lymphoma, extracranial solid tumor or CNS tumor who were treated with chemotherapy or radiation	x		Flamingo balance; TUG		C, R, S
Piscione39	2014	Cross-sectional	Small	Survivors of PFTs (MB, cerebellar astrocytoma, EPD, brainstem glioma), ages 4-18 years		x	BOT-2 - balance subtest	√	S
Piscione40	2017	Quasi-experimental	Small	Survivors of PFTs (AA, EPD, anaplastic EPD, MB, pineoblastoma, sarcoma, GCT, astroblastoma), who were treated with surgery and radiation, ages 6-17 years		x	BOT-2 - balance subtest	√	R, S
Ramchandren60	2009	Cross-sectional	Medium	Survivors of ALL, ages 8-18 years		x	BOT-2		C	CIPN
Reinders-Messelink41	1999	Cross-sectional	Medium	Children ages 4-12 years undergoing treatment for ALL	x		m-ABC - balance subtest	√	C
Ross79	2001	Cross-sectional	Medium	Children 6-40 months old, with unilateral or bilateral retinoblastoma	x		Bayley - motor ability subtest		C, R, S, Other: Cryother apy, Laser therapy	Vision
Sabel42	2016	RCT	Small	Survivors of CNS tumor (PFT, supratentorial tumor AA, choroid plexus carcinoma; GCT, MB, P-AST, primitive neuroectoderm al tumor), ages 7-16 years who had undergone radiation		x	BOT-2 - balance subtest	√	C, R, S	Vision
Şahin58	2020	RCT	Medium	Children ages 5-16 years currently undergoing chemotherapy treatment for cancer (CNS and non-CNS cancers)	x		BOT2 - balance subtest		C
Selim48	2023	RCT	Small	Children ages 5-10 years with MB, immediately following surgical resection	x		PBS; posturography	√	S
Syczewska43	2006	Cross-sectional	Medium	Survivors of CNS tumors (MB, PFT, midline tumors, left hemisphere tumors, right hemisphere tumors, brain stem tumors, and spinal cord tumors), ages 6-17 years		x	Posturography	√	C, R, S	Vision, Vestibular
Takken59	2009	Feasibility, Longitudinal	Small	Survivors of ALL, ages 6-14 years		x	TUG; TUDS		C
Tanner24	2019	Quasi-experimental	Small	Survivors of ALL, ages 5-18 years		x	BOT-2 - balance subtest		C
Tay57	2017	Cross-sectional	Large	Survivors of ALL, ages 4-18 years		x	BOT-2		C	CIPN
Toy44	2006	Case study	Small	12-year-old survivor of medulloblasto ma with posterior fossa syndrome		x	BOT-2 - balance subtest; PBS	√	S
Usama49	2023	RCT	Medium	Children ages 5-12 years currently undergoing maintenance therapy for PFT	x		BOT-2; mCTSIB; posturography	√	C, R, S
Wiernikowski73	2005	Longitudinal	Small	Children 3-15 years currently undergoing maintenance therapy for treatment of ALL or NHL	x		BOT-2 - balance, subtest; TUDS		C, Other: Alendronate
Wright56	1998	Cross-sectional	Medium	Survivors of ALL, ages 5-15 years		x	BOT-2 - balance subtest		C
Wright76	2005	Cross-sectional	Large	Survivors of ALL, ages 5 - 17 years		x	BOT-2 - balance subtest		C, R	Vision
Yildiz Kabak54	2021	Cross-sectional	Medium	Children ages 4-18 years undergoing induction or consolidation chemotherapy for treatment of ALL	x		BOT-SF - balance subtest		C
Yildiz Kabak55	2021	Cross-sectional	Small	Children ages 5-15 years undergoing maintenance therapy for treatment of ALL	x		BOT-2; TUG		C

Abbreviations: AA, anaplastic astrocytoma; ALCL, acute large cell lymphoma; ALL, Acute lymphoblastic leukemia; AML, Acute myeloid leukemia; AMPS, assessment of motor and processing skills; B-NHL, B-cell non-Hodgkin lymphoma; BARS, Brief Ataxia rating scale; BBT-P, Berg balance test for pediatrics; BOT-2, Bruininks-Oseretsky Test of Motor Proficiency 2^nd Edition; BOT-SF, Bruininks-Oseretsky Test of Motor Proficiency - Short Form; CANTAB, Cambridge Neuropsychological Test Automated Battery; CIPN, Chemotherapy induced peripheral neuropathy; CVFQ, Children's Visual Function Questionnaire; CNS, Central Nervous System; COP, center of pressure; COPe, center of pressure excursion; COPv, center of pressure velocity; CPET, cardiopulmonary exercise test; CSAPPA, Children’s Self-perceptions of Adequacy in and Predilection for Physical Activity Scale; DCDQ-07, Developmental Coordination Disorder Questionnaire-07; DMT, Deutscher Motor Ability Test; DVA, Dynamic Visual Acuity; EPD, ependymoma; GCT, Germ Cell Tumor; GB, Glioblastoma; GMFM, gross motor function measure; HRQoL, health-related quality of life; HSCT, hematopoietic stem cell transplant; ICARS, International Ataxia Rating Scale; ICD-10, International Classification of Diseases, Tenth Revision; LGG, low-grade gliomas; m-ABC, Movement Assessment Battery for Children; MB, Medulloblastoma; mCTSIB, Modified Clinical Test of Sensory Interaction on Balance; Mini-BESTest, mini-balance evaluation systems test; MMT, malignant mesenchymal tumor; MOON, motor performance test in oncology; MOT4-6, Motor proficiency test; MPD, myeloproliferative disorder; NHL, non-Hodgkin's Lymphoma; P-AST, pilocytic astrocytoma; PBS, pediatric balance scale; PCS, Pediatric Cancer Survivors; PDMS-2, Peabody Developmental Motor Scales 2^nd Edition; PEDI, Pediatric evaluation of disability index; Ped-mTNS, pediatric-modified total neuropathy score; PFBT/PFT, posterior fossa (brain) tumors; PFS, Posterior Fossa Syndrome; PVSQ, Pediatric Vestibular Symptom Questionnaire; RB, retinoblastoma; RCT, randomized control trial; RVP, Rapid visual processing; SARA, Scale for the assessment and rating of ataxia; SD; standard deviation; ToRP, total ossicular replacement prosthesis; TUDS, Timed Up and Down Stairs test; TUG, Timed Up and Go test; UQAC-UQAM test battery, University of Quebec in Chicoutimi-University of Quebec in Montreal (UQAM) test battery; VCR, vincristine; WT, Wilms Tumor; 6MWT, six-minute walk test.

Sample size was defined as follows: small: n≤30, medium: n=31-99, large: n≥100.

2.5. Collating, summarizing, and reporting the results

Extracted data were discussed amongst team members. Utilizing an iterative approach, the content of the studies was reviewed to identify and summarize key findings and implications for research and clinical practice. Two authors collaborated to identify key findings within the literature and the results were reviewed by all team members to achieve consensus on key findings.

3. Results

3.1. Summary of search results

A total of 64 full-text studies were included in the review. Twenty-two outcome measures were used to assess balance, represented in Figure 3, and listed in Table 1. Twenty-five studies examined balance in children currently undergoing treatment, thirty-four studies examined balance in CCS, and five studies included a population of both children undergoing treatment and CCS (Table 1). While it was generally reported that children who were undergoing treatment for cancer and CCS have impaired balance compared to their peers, four of the sixty-four included studies (6.25%) did not find significant impairments in balance as compared to published norms or controls.^27-30 Balance impairments were attributed to cancerous tumor or the result of medical treatment, including chemotherapy, radiation, or surgical resection. Specific contributing factors to balance impairments are summarized in Figure 4. Multiple studies identified balance impairments as a direct result of damage to the CNS. Additional studies identified balance impairments as sequelae secondary to medical treatments provided to treat cancer, including chemotherapy, radiotherapy, and surgical treatments. Multiple studies reported cumulative effects on balance impairments as the result of one or more medical interventions (e.g., chemotherapy, radiation, or surgery used together).

Fig. 3.

Frequency of outcome measures to assess balance. Abbreviations: BBT-P = Berg balance test for pediatrics; BOT-2 = Bruininks-Oseretsky Test of Motor Proficiency 2nd Edition; DMT6-18 = Deutscher Motor Ability Test ages 6-18 years; m-ABC = Movement Assessment Battery for Children; mCTSIB = Modified Clinical Test of Sensory Interaction on Balance; Mini-BESTest = mini-balance evaluation systems test; MOON = motor performance test in oncology; MOT4-6 = Motor proficiency test; PBS = pediatric balance scale; PDMS-2 = Peabody Developmental Motor Scales 2nd Edition; TUDS = Timed Up and Down Stairs test; TUG = Timed Up and Go test; UQAC-UQAM = University of Quebec in Chicoutimi-University of Quebec in Montreal (UQAM) test battery.

Fig. 4.

Contributing factors to balance impairments in pediatric oncology.

3.2. Summary of key findings

3.2.1. Balance impairments as a result of cancerous tumor

Twenty-six studies reported balance impairments that were implied to be the result of the cancer itself.^{13,16,18,20-22,25,31-49} One study reported balance impairments attributable to bone tumors,⁴⁷ another in children diagnosed with acute lymphoblastic leukemia (ALL),⁴¹ and the remaining twenty-four studies reported balance impairments attributable to tumors of the central nervous system (CNS).^{13,16,18,20-22,25,31-40,42-46,48,49} prior to the initiation of medical treatment, two studies reported balance impairments in children with CNS tumors,^13,33 and one study reported balance deficits in children diagnosed with ALL.⁴¹ No studies reported the effects of bone tumors on balance prior to children receiving medical treatment (e.g., before surgical resection). Few studies differentiated balance deficits attributed to the tumor itself, prior to surgery, to the surgical removal of that tumor, and thus it is difficult to delineate deficits attributable to the tumor, or the surgical process associated with removing the tumor, or a combination of the two. Posterior fossa tumors (PFTs), including medulloblastoma, astrocytoma, ependymoma, and gliomas, were the most reported CNS malignancies. Additional CNS tumor types included brainstem gliomas, spinal cord lesions, supratentorial tumors, choroid plexus carcinomas, germ cell tumors, and primitive neuroectodermal tumors (Table 1). Tumors of the CNS generally resulted in impaired balance regardless of specific location (brain, brainstem, cerebellum, spinal cord), a finding that was unsurprising, as the maintenance of balance requires complex interplay between various neural structures (Figure 1; C). Three studies reported that children with cancer involving the CNS demonstrated more impaired balance than children with non-CNS cancer diagnoses, again suggesting balance deficits that can be attributed to the specific type of cancer rather than the treatment.^32,34,38 One study noted children with CNS tumors demonstrated improved balance outcomes 3 months into treatment compared to baseline, in contrast to children with non-CNS tumors who demonstrated worse balance 3 months into treatment.³¹ The authors suggested that balance impairments in children with CNS tumors are likely caused by the tumor itself and may partially or fully resolve with medical treatments such as surgical resection. In contrast, balance impairments in children with non-CNS cancers likely worsen with medical treatments such as chemotherapy. Despite this, studies of CCS diagnosed with CNS cancers continued to demonstrate balance impairments which were reported even more than five years post-treatment.²⁵ Two studies reported differences in balance function as related to type of CNS tumor, reporting that children with astrocytoma demonstrated improved balance as compared to children with ependymoma and medulloblastoma.^21,36 Three studies reported that tumors of the fourth ventricle,²¹ lesions of the inferior cerebellar vermis,^37,39 and lesions of the deep cerebellar nuclei have a larger impact on balance impairments than other tumor locations.³⁷

3.2.2. Balance impairments as a result of medical treatment

Fifty-eight studies reported balance impairments in children that were implied to be a consequence of medical treatments including chemotherapy, radiation, surgery, or other treatment used to target metastatic disease including hematopoietic stem cell transplant (HSCT), alendronate, cryotherapy, or laser therapy (Table 1). Most studies reported chemotherapy used in conjunction with radiation or surgery; however, twenty-six studies described chemotherapy used in isolation.^{4,11,24,41,50-71} Specific chemotherapeutic agents reported included vinca alkaloids (e.g., vincristine), anthracyclines (e.g., cytarabine), antimetabolites (e.g., methotrexate), enzymes (e.g., asparaginase), and platinum-based agents (e.g., cisplatin). A number of studies reported balance outcomes of children during specific phases of chemotherapy treatment including induction or consolidation (n=7),^{4,52-54,70-72} or maintenance (n=5) therapy.^{17,29,49,55,73} Nine studies enrolled children undergoing cancer treatment, regardless of phase of chemotherapy or reported outcomes across multiple phases of chemotherapy,^{11,19,23,31,38,41,58,61,65} and twenty-seven studies specifically reported chemo-related late-effects during survivorship.^{16,20,21,24,25,32,34-36,42,43,46,50,51,56,57,59,60,62-64,66,67,69,74-76} The overwhelming consensus within the literature was that children who receive chemotherapy are likely to demonstrate impaired balance both during and after treatment. Reported chemotherapy-related impairments included, but were not limited to, sensory and motor neuropathies, often termed peripheral neuropathy, or chemotherapy-induced peripheral neuropathy (CIPN),^61-65 ototoxicity, or the “functional impairment and cellular degeneration of the tissues of the inner ear caused by therapeutic agents,”^77,78 processing impairments such as impaired reaction time,^29,30,64,68 and hearing loss.^13,70 One study reported there was no correlation between cumulative corticosteroid dose and balance.⁶⁶ CIPN was the most commonly reported chemotherapy-related impairment, reported specifically in four studies.^11,57,60,61

Radiation was a medical treatment reported in twenty studies.^{16,17,19,21,23,31,32,34-36,38,40,42,43,46,49,74-76,79} Radiation was always reported as an adjunct to other medical treatments such as surgery or chemotherapy, making it difficult to discern the specific role of radiation in children on active treatment and CCS in contributing to balance deficits. One study reported improvements in balance in children with CNS tumors following radiation and/or surgery, suggesting radiation did not play a role in impairing balance in those studies.³¹ One study by Wright et al.⁵⁶ found no significant differences in balance between children who received cranial radiation and those who did not. A later study⁷⁶ by the same authors reported that cranial radiation predicted a minimal amount of variability in balance scores, suggesting that radiation contributes minimally to balance impairments. Another study only included children treated with radiation to the head/neck, indicating the impact of radiation may be location-specific.³⁴ Taken together, these findings imply that balance impairments are multi-factorial and the specific role of radiation is not yet known.

Twenty-nine studies described children who received surgery as a medical treatment for their cancer,^{16-23,25,30-32,34-40,42-49,75,79} and nine studies reported surgery as the sole medical treatment reported.^{18,22,30,37,39,44,45,47,48} Of these, two studies examined surgical removal of bone tumors,^30,47 and seven studies examined surgical removal of CNS tumors.^{18,22,37,39,44,45,48} Studies reported mixed conclusions regarding the impact of surgery on balance. Some studies reported worsened balance outcomes following surgery,^34,45,47 while other studies reported surgery as a treatment that resulted in minimal changes to balance,^30,36 or even improved balance.^31,37 Following surgical treatment for bone tumors, one study did not identify balance impairments; however, this study assessed balance on the non-affected lower extremity.³⁰ An additional topic area identified was the presence of hydrocephalus (fluid accumulation in the brain) following surgical removal of brain tumors. The reported effects of hydrocephalus on balance outcomes were conflicting, with one study reporting children with severe hydrocephalus post-resection demonstrated significantly worse balance,³⁶ and another reporting no significant differences in balance between children who required treatment for hydrocephalus and those who did not.³⁹ A study of children with retinoblastoma who underwent enucleation (the surgical removal of one eye) as their sole cancer treatment demonstrated improved balance compared with children who received either chemotherapy or radiation in addition to enucleation.⁷⁹

In reviewing other medical treatments reported, one study examined the impact of immunotherapy by investigating the effect of a therapeutic exercise program on balance in children undergoing HSCT.⁸⁰ This study reported balance did not improve following the therapeutic exercise program. However, the study lacked a control group, so the specific effects of the HSCT on balance function remain unclear. Wiernikowski et al.⁷³ studied the effects of alendronate (bone density medication) on osteopenia in children with blood cancer. This study reported children who received alendronate had significantly improved strength and Timed Up and Down Stairs (TUDS), but did not demonstrate improved balance as measured by the Bruininks-Oseretsky Test of Motor Proficiency 2nd Edition (BOT-2) balance subtest.⁷³ An additional study reported the use of cryotherapy/laser therapy for the treatment of retinoblastoma and reported following treatment for retinoblastoma, children had average scores on balance.⁷⁹ This study specifically reported children treated with multiple treatments including either cryotherapy or laser therapy were more likely to be referred for therapeutic services, although this finding was not tied specifically to children’s balance function.⁷⁹

Studies often reported cumulative effects of medical treatments (e.g., any combination of chemotherapy, radiation, surgery) on balance impairments. For example, children who received a higher number of treatment methods or a higher dose of one treatment demonstrated worse balance.^70,79 For example, Ross et al.⁷⁹ reported children who underwent multiple treatments were more likely to be referred for visuomotor therapy, and Doan et al.⁷⁰ reported worsened balance with cumulative doses of chemotherapy.

3.2.3. Sensory impairments which may impact balance

Classes of chemotherapeutic agents used to treat childhood cancer include vinca-alkaloids, platinum-based therapeutics, and anthracyclines, which can cause peripheral neuropathy, ototoxicity, and oculomotor deficits, respectively.^70,78,81-83 Additionally, radiation to the head/neck is known to cause ototoxicity.⁷⁸ These toxic agents have the potential to inflict damage to the visual, vestibular, and somatosensory systems and thus disrupt sensory systems which are integral for the maintenance of postural control and balance (Figure 1; A).

To further examine the effects of medical treatment on balance, a sub-analysis investigated sensory impairments that had the potential to negatively impact balance outcomes in children (Figure 1; A), as sensory input from the visual, vestibular, and somatosensory systems significantly contribute to one’s ability to maintain balance (Figure 1; B).^7,9 The number of studies that reported sensory impairments in relation to balance deficits can be found in Figure 5.

Fig. 5.

Reported sensory impairments.

Ten studies reported visual impairments in conjunction with balance outcomes (Figure 5).^{13,16,21,35,37,42,43,70,76,79} Visual impairments were reported in children affected by CNS tumors (7 studies),^{13,16,21,35,37,42,43} and children with a diagnosis of non-CNS cancer (3 studies).^70,76,84 In children with CNS tumors, one study reported visual problems as a primary sign/symptom in 44% of children,¹³ and another study reported visual impairments in two survivors of CNS tumors.⁴² Reported visual deficits were not isolated to children with CNS tumors. One study reported oculomotor deficits as the result of cumulative chemotherapeutic exposure in a child with acute myeloid leukemia (AML),⁷⁰ and another study reported three ALL CCS with cataracts and one ALL CCS with poor visual acuity.⁷⁶ In each of these studies, the link between vision and balance was not explicitly explored. One study examined children with retinoblastoma (RB) and found of children with unilateral or bilateral RB, the majority had normal visual acuity in at least one eye (94%), and the remaining children had at least partial visual acuity in one eye.⁷⁹ This study reported children with bilateral RB had poorer balance as compared to children with a unilateral tumor, although they scored within the normal range compared to normative data.⁷⁹ Children with bilateral RB were more likely to have received >1 medical treatment, including enucleation, and were more likely to be referred for visual services including visuomotor intervention and visual training.⁷⁹ An interesting key finding in the literature was identified regarding visual impairments in children with CNS tumors. In this population, balance during visually occluded conditions (i.e., eyes closed) was often similar to or even better than balance during non-visually occluded conditions (i.e., eyes open).^16,35,37,43 These findings imply that children with CNS tumors may have an inability to use vision to improve balance function. One such study which reported an improvement in balance with eyes closed reported these findings were related to saccadic dysmetria, postulating damage to oculomotor muscles as the root cause of improved balance without visual input.³⁵ A study of PFT survivors found that the location of cerebellar tumor was significantly related to oculomotor activity; whereas, tumors of the fourth ventricle had worse oculomotor outcomes, and tumors of the cerebellar hemispheres caused the least harm to oculomotor activity.²¹

During scenarios when vision is occluded, humans are more reliant on alternative sensory systems to maintain balance.^9,85 In total, eight studies discussed vestibular impairments (Figure 5).^{16-18,34,35,37,43,70} Studies that found children were unable to use vision to improve balance function associated this phenomenon with vestibular dysfunction.^16,35,37,43 While four additional studies reported vestibular impairments,^17,18,34,70 the link between vestibular and balance function was not as clear. Doan et al.⁷⁰ reported the presence of vestibular symptoms including nystagmus, saccadic dysmetria, and impaired pursuit in addition to balance deficits in a child following chemotherapy; however, this study did not explore relationships between vestibular symptoms and balance. Another study reported one participant was unable to perform a complex balancing task due to severe vestibular disorder; however, no additional details were provided.¹⁷ Flowers et al¹⁸ reported mixed results after the use of a vestibular rehabilitation program to improve balance in a child who survived a CNS tumor. The child demonstrated improved balance and visual acuity, but worse postural sway following the intervention.¹⁸ One study screened for vestibular function in CCS following ototoxic therapies.³⁴ This study demonstrated vestibular screening failures in 60% of CCS who received ototoxic treatments, highlighting significant vestibular damage in CCS.³⁴

Hearing loss is a known late-effect of childhood cancer.⁸⁶ As emerging evidence supports increased incidence of balance deficits in children with hearing loss, often thought to be linked to vestibular dysfunction,^87,88 audiometric findings/reported hearing impairments were also recorded. Two studies reported impairments in hearing function (Figure 5).^13,70 Ansell et al.¹³ reported 11% of children with brain tumors reported hearing problems, while Doan et al.⁷⁰ presented a case report of a child who demonstrated ototoxic findings, including unilateral high-frequency hearing loss, vestibular dysfunction and balance deficits, following significant anthracycline exposure (Table 1).

It is well established that chemotherapeutic agents used to treat childhood cancer can cause damage to sensory and motor peripheral nerves, termed CIPN.^81,82,89-91 Only four studies reported somatosensory impairments in conjunction with balance impairments in children during and after cancer treatment (Figure 5).^11,57,60,61 All four studies cited vincristine, a chemotherapeutic agent commonly used in the treatment of pediatric blood cancers,^82,91 as the cause of CIPN. Two studies reported somatosensory deficits in children undergoing treatment for cancer.^11,61 Gilchrist and Tanner¹¹ reported balance outcomes both during and off-treatment were significantly associated with CIPN, meaning those with worse neuropathy demonstrated poorer balance both during and off-treatment. Nama et al.⁶¹ reported that 50% of children undergoing treatment demonstrated impaired vibratory sense in their lower extremities, while 32% demonstrated impaired vibratory sense in their upper extremities. This study reported children undergoing treatment for blood cancer had poor balance, but did not examine the relationship between vibratory sense and balance function.⁶¹ Two studies reported somatosensory deficits in CCS.^57,60 Ramchandren et al.⁶⁰ reported 95% of ALL survivors demonstrated neuropathy on the reduced version of the total neuropathy score (TNSr), while 30% of survivors demonstrated neuropathy as measured by nerve conduction velocity tests. Despite the large percentage of survivors affected by neuropathy, this study did not find a significant difference in balance between those with and without CIPN.⁶⁰ Similar findings were reported by Tay et al,⁵⁷ who found 26% of survivors demonstrated clinical neuropathy, while 68% demonstrated electrophysiological neuropathy. This study also neglected to find a significant difference in balance function between those with and without CIPN.⁵⁷

3.2.4. Interventions to improve balance

Twenty-three studies investigated the effect of implementing an intervention for balance in children during and after cancer treatment.^{16-24,38,40,42,44,45,48-50,53,58,59,73,75,80} Twelve studies examined the effect of balance interventions while the children were undergoing treatment,^{17,19,22,23,38,45,48,49,53,58,73,80} while eleven studies examined the effect of interventions on balance during survivorship.^{16,18,20,21,24,40,42,44,50,59,75} Interventions varied immensely in content and dosage. Interventions ranged from 11 days to 6 months in length. Fourteen of the twenty-three intervention studies (60.9%) reported a positive effect of the intervention on improving balance.^{16-23,38,44,45,48,49,58} Interventions that were successful at improving balance included targeted exercise interventions/task-specific training,^17,22,58 gaming biofeedback and postural control exercises,¹⁶ vestibular rehabilitation,¹⁸ physical activity in combination with attentional training,^19,48 balance or coordination training,^18,20,44,49 cognitive and visuomotor training,²¹ inpatient rehabilitation,^38,45 and peer-support through co-admission of a healthy classmate.²³ Nine of the twenty-three intervention studies (39.1%) found no improvement in balance following the implementation of an intervention.^{24,40,42,50,53,59,73,75,80} Interventions that did not result in significantly mitigating balance impairments included alendronate administration,⁷³ targeted exercise during admission for HSCT,⁸⁰ yoga,⁷⁵ group exercise,⁴⁰ exergaming,⁴² exercise training,⁵⁹ strength training,⁵³ jumping rope,⁵⁰ and a proactive physical therapy program (Stoplight Program, SLP).²⁴

4. Discussion

Although it is well documented that children undergoing treatment for cancer and CCS have balance deficits which can persist up to 10 years from diagnosis,^{11,12,15,40,41,56,62} to our knowledge this is the first review to explore the specific causes of balance impairments within this population, specifically discussing sensory impairments and their contributions to balance. While there was consensus within this review that children with cancer and CCS have difficulties with balance, one key finding identified through the large scope of evidence reviewed was the heterogeneity of assessments and criteria available to evaluate balance. Specifically, this review found twenty-two different outcome measures were reported to measure balance within this population (Figure 3). Such heterogeneity in assessment can explain differences in findings of balance function within the population, as different measures assess different components of balance (e.g., static, dynamic, reactive).

We found that in children with a diagnosis of CNS tumor, balance is often impaired as a result of direct insult to the central nervous system. Children with CNS tumors generally demonstrate impaired balance as an initial sign/symptom of tumor pathology and often have worse balance than children with non-CNS cancers. Children with CNS tumors are unique, as balance impairments in this population may improve following surgical resection of the tumor.^31,37 Despite successful treatment for CNS tumors, balance difficulties in this population do not fully resolve and persist in survivors of CNS cancers,²⁵ which is likely a consequence of compounded medical treatments used to treat their metastatic disease.

Additionally, our review discusses balance impairments as a secondary consequence following medical treatments for pediatric cancer. Striking improvements in childhood cancer survival statistics highlight the success of modern chemotherapy and radiation regimens as well as successful surgical methods in treating childhood cancer.² These medical treatments are not without consequence and often result in the late effect of balance dysfunction in children.³ Modern practice includes maximizing survival while attempting to minimize long-term toxicities, and recent studies support trends in a reduction of long-term adverse outcomes following cancer treatment.¹ For example, as radiation has many known adverse effects, the use of radiation in treatment of solid tumors has reduced significantly over time, and modern treatment often includes newer approaches to delivery of radiation as well as multi-modal approaches to cancer treatment, rather than the use of radiation as the sole treatment modality.¹ This is reflected in our study where radiation was always reported as an adjunct to other medical treatments such as surgery or chemotherapy. As trends in survivorship continue to improve, we hypothesize that future research will thereby shift from attempts to cure the malignancy to the mitigation of late effects, including balance impairment.

Our review is unique as it is the first to map sensory impairments alongside balance impairments, highlighting potential sensory contributions to balance dysfunction during or after treatment for childhood cancer. Potential sensory contributions, summarized in Figure 1, include 1) ototoxicity, or damage to the tissues of the inner ear, caused by platinum-based therapeutics or radiation to the head/neck, 2) visual difficulties such as oculomotor deficits caused by anthracyclines or a direct result of CNS tumor, or monocular vision as a result of enucleation, and 3) somatosensory deficits, specifically CIPN caused by vinca alkaloids.

5. Limitations

In attempts to clearly differentiate balance impairments within the literature, we chose to exclude studies that reported gait abnormalities or measures of ataxia without a specific outcome measure of balance. As ataxia is often considered a balance impairment, this may be considered a limitation of our study. Additionally, to appropriately summarize outcome measures used to measure balance function in a pediatric population, studies with adult participants were excluded. While this decision was made so that pediatric balance assessments in this population could be summarized and reported, there are many adult survivors of childhood cancers, and thus our findings may be less applicable to adult survivors of pediatric cancers. In keeping with scoping review practices, the search was not limited by study design, thus several case studies, case series, and case reports were included. Case studies, series and reports provide an opportunity to highlight under-researched populations and as such were included in our review. As case studies, series and reports have unique limitations due to the small number of participants, the results of these studies should be interpreted with caution. Many studies reported cognitive or motor impairments that accompany balance deficits, including impairments in coordination, reaction time, and strength, which may contribute to findings of impaired balance and potentially confound results.

6. Implications for research and clinical practice

The maintenance of balance requires the appropriate integration of three sensory inputs (vision, vestibular, somatosensory) and the generation of an appropriate motor signal to maintain control of one’s upright posture (Figure 1; C). The role of sensory impairments, which may contribute to balance dysfunction in children who have undergone cancer treatment, has been explored in this paper. Yet, the role of these sensory contributions in balance control is not well understood. This review aims to highlight the potential for sensory deficits to contribute to the ability to control balance in childhood cancer during and after treatment, although a direct and causal link between sensory impairment and balance function cannot be made with the current level of evidence. Additionally, children undergoing treatment for cancer have reduced strength, slowed motor nerve conduction velocity and reduced rate of muscle activation,^4,63 and further studies are needed to determine the effects of motor function impairments on balance control in this population.

The relationship between age and sensory contributions to balance has been well studied.^7-9 However, the effect of age on sensory impairments, such as CIPN and ototoxicity, is not well understood. The effects of age on CIPN have not yet been determined and evidence on age-related effects of neuropathy is conflicted. In a systematic review by Tay et al.,⁵⁷ two studies reported a higher prevalence of vincristine-induced CIPN in younger children, five studies reported a higher prevalence in older children, and seven studies reported no association between age and CIPN.²⁶ While the effects of age on cisplatin-related ototoxicity are also debated, it has been demonstrated that children are more susceptible to ototoxicity from platinum-based chemotherapeutics than adults.⁸⁶ One possible explanation for increased susceptibility to ototoxic damage is that children have been shown to have a reduced ability to use their vestibular system to control balance as compared to adults, especially in conditions in which visual and somatosensory input are reduced.^92,93 Even though the vestibular system is anatomically and structurally fully developed at birth,⁹⁴ the physiologic function of the vestibular system continues to mature and develop as the child grows, much later than the other two sensory systems, vision, and somatosensation.⁷ The slowed physiologic development of a child’s vestibular system may put them at increased risk of developing ototoxicity compared to adults; however, further research is needed to clarify the age-related effects of ototoxicity.

Identifying the specific causes of balance impairment can assist researchers and clinicians in targeting interventions specific to the patient and their source of balance dysfunction. Understanding the causes of balance impairment can guide rehabilitation scientists to develop and implement interventions that improve balance for children both during and after cancer treatment. Specifically, oncology professionals play a pivotal role in the recognition and treatment of factors affecting balance impairments within pediatric oncology; however, referral rates to physical rehabilitation are very low within this population.^95,96 We speculate as survival rates of pediatric cancer continue to improve, it will become even more important to establish proactive surveillance and multi-disciplinary survivorship clinics to assist in the identification of late effects from cancer treatment and implementation of intervention strategies early on in treatment/survivorship. These clinics can then refer survivors with late effects from cancer therapy such as hearing loss or balance impairment, to the appropriate disciplines, such as audiology or physical therapy. For rehabilitation science professionals, knowledge of specific sensory impairments experienced by a child with cancer or CCS may guide individualized treatment and care planning. Further research is needed to identify and provide an evidencebased scientific rationale for sensory-specific interventions to improve balance in this population.

Table 2.

Strengths, weaknesses and study conclusions

First Author	Year	Study Conclusions	Study Limitations
Agamanolis33	2012	Balance deficits (+ Rhomberg sign) were noted in a child with a superficially disseminated glioma.	Small sample size (three case reports)
Akyay71	2014	Following induction therapy, children newly diagnosed with ALL (group 1) had significantly longer TUG scores than children off therapy (group 2) Both group 1 and group 2 had significantly poorer TUG scores as compared to controls.	Results limited to induction phase of treatment
Ansell13	2010	Children with brain tumors reported visual problems (44%), unsteadiness on their feet (42%), and hearing problems (11%).	Relationships between vision, hearing, and balance were not explicitly studied
Benzing32	2021	CCS (CNS and non-CNS cancers) demonstrated poorer motor ability compared to controls with the largest effect size seen for coordination. Survivors of CNS malignancies had significantly poorer coordination than survivors without CNS involvement.	Heterogeneity of cancer diagnosis, treatment type/phase, age, and time off treatment
Beulertz27	2013	While global motor performance was significantly reduced in children on treatment and in CCS compared to healthy children of the same age, balance and coordination subtests of the MOT4-6 did not differ significantly. Coordination (time pressure and precision pressure) on the DMT6-18 was significantly lower in children currently on treatment and CCS compared to norms. No significant differences were observed between patients treated with vincristine and those treated without vincristine.	Small sample size Heterogeneity of cancer diagnosis, treatment type/phase, age, and time off treatment
Beulertz17	2016	Balance was significantly impaired in children with a diagnosis of cancer as compared to healthy age-matched peers. A six-month (60 min, 1x/week) targeted, supervised therapeutic exercise intervention significantly improved balance and coordination in children with cancer to the point where balance was not significantly different as compared to controls. One child was unable to perform the balance test due to severe vestibular disorder.	Group selection bias introduced as individual participants chose their intervention group
Bogg80	2015	A targeted, supervised therapeutic exercise intervention (2x/day, 5x/wk while hospitalized) for children undergoing treatment with HSCT demonstrated a moderate decline in balance performance. Study suggests an inpatient exercise program for children with HSCT has the potential to mitigate the loss of strength but not balance.	Small sample size Lack of a control group Specific effects of HSCT on balance function remain unclear
Camet34	2018	Vestibular screening failures were observed in 60% of CCS who received ototoxic therapy. CCS with brain tumor diagnosis or who underwent brain surgery for cancer treatment were at increased risk for failures compared to other CCS. Patients with a longer duration between the end of treatment and vestibular screening had a reduced risk of failures, with an almost 20% decrease for each year.	Missing audiometric data limited ability to make conclusions regarding relationships between audiometric, vestibular, and balance outcomes
Chechelnitskaia35	2019	Survivors of PFT demonstrated significantly larger postural sway compared to healthy controls. Survivors of PFT demonstrated an improvement of postural control with their eyes closed, in connection with saccadic dysmetria. The authors hypothesize this finding is related to potential damage to oculomotor function.	Conclusions regarding oculomotor function during vison-occluded conditions were assumed, however oculomotor muscle activity was not directly measured with the participant’s eyes closed
Davis36	2010	27% of survivors of cerebellar tumors demonstrated significant impairments in body coordination (balance and bilateral coordination). Children with severe hydrocephalus performed significantly lower on the bilateral coordination subtest. Survivors of P-AST treated with surgery only had the highest body coordination scores, while survivors of EPD treated with chemotherapy had the lowest scores.	While total sample size was large, study included a small sample of CCS (n=15) High level of withinsubject variability Neurological factors including cerebellar mutism syndrome, ataxia and pyramidal symptoms not assessed
Decock45	2022	Following surgical resection but prior to rehabilitation, children currently undergoing treatment for PFTs demonstrated impaired balance compared to normative data. Following a multidisciplinary rehabilitation intervention (3-5x/wk), children currently undergoing treatment for PFTs demonstrated improved balance compared to baseline, however, continued to demonstrate impairments compared to normative data.	Retrospective analysis of data over 15 years, therefore different editions of some outcome measures were included Missing data limited ability to make conclusions regarding differences in outcomes before/after rehabilitation
DeLuca69	2013	10.8% of ALL CCS demonstrated impaired balance on the balance subtest of the m-ABC, while 16.2% of CCS demonstrated impaired scores on the BOT-2. Balance deficits did not improve with time off treatment (0-60 months). All participants (ALL CCS) were treated with chemotherapy (including vincristine and methotrexate), and impaired performance was not significantly associated with any particular chemotherapy protocol.	Inclusion of neurological assessment such as NCV would have strengthened findings Use of normative data rather than age-matched control group
Doan70	2011	A case report of a 12-year-old child with AML demonstrated adverse side-effects following consolidation chemotherapy as a result of cumulative cytarabine exposure. Following consolidation therapy, the child demonstrated unilateral high-frequency hearing loss, oculomotor deficits, vestibular deficits, and balance deficits.	Small sample size (case report) Relationships between hearing, vision, vestibular and balance outcomes were not explicitly studied
Dreneva16	2020	Survivors of PFT demonstrated impaired balance as measured by COP parameters (COPe, COPv, mean root square oscillations) when compared to healthy controls. Differences were greater with eyes open as compared to eyes closed, indicating they were unable to appropriately use visual information to correct postural balance. Following a 2-week gaming biofeedback and postural control intervention (15 min, 3x/wk + traditional rehabilitation), participants demonstrated significantly improved postural stability with eyes open.	Large age variation in the participants Short duration of the training program
Flowers18	2020	Following a 10-week intervention comprised of vestibular rehabilitation in combination with standard balance training and physical therapy, a child with PFS following astrocytoma resection demonstrated improved balance (PBS) and gaze stability (DVA), with worsened postural sway (mCTSIB). Head impulse testing was positive pre- and post-intervention.	Small sample size (case study) Relationships between vestibular and balance outcomes were not specifically studied
Fontana19	2021	Children with cancer enrolled in a physical activity + physical/attentional training intervention program demonstrated significant improvements in balance as measured by the m-ABC balance subtest. No significant differences were found on the Ped-mTNS between time points.	Small sample size Lack of a control group
Galea74	2004	32% of ALL CCS were unable to complete a challenging balance task, Rhomberg eyes closed, with only 2% of controls being unable to complete the task. ALL CCS showed variable (increased or decreased from control) sway responses in the other balance tasks (Rhomberg eyes open, normal surface eyes open/closed, foam surface eyes open/closed).	Task-related variability in balance performance Heterogeneity of age and time off treatment
Gaser52	2022	50% of children who were newly diagnosed with ALL, AML, or NHL, in their first few weeks of treatment, demonstrated significant impairments in static balance compared to standard reference values.	Heterogeneity of age, gender distribution and cancer diagnosis
Gaser53	2022	Children with ALL, AML or NHL demonstrated impaired balance compared to age-matched norms immediately after diagnosis and after consolidation treatment. Following a strength training + standard care exercise program intervention (30 min, 2-3x/wk), neither intervention nor control groups (standard care exercise program alone) demonstrated significant improvements in balance.	Heterogeneity of age, gender distribution and cancer diagnosis Variability in standardized strength training protocol throughout long study duration
Gielis46	2022	Survivors of brain tumors demonstrated significantly poorer balance compared to published norms on both BOT-2 and m-ABC tests. 59% of parents reported their children had difficulties with balance, while 70% of participants demonstrated impaired balance on the BOT-2, suggesting a general underestimation of long-term balance deficits in this population. Lower scores on the m-ABC were associated with adjuvant treatment in addition to surgery, while lower scores on the BOT-2 were significantly associated with younger age at diagnosis (<5 years).	Lack of a control group Test battery was not validated for childhood brain tumor survivors
Gilchrist11	2018	78% of children undergoing treatment for non-CNS cancer scored 1 SD or more below population means on the balance subtest of the BOT-2. Participants' balance improved 6 months post-treatment, although greater than half of the participants (53%) continued to demonstrate balance impairments. Children with leukemia had the poorest balance both on- and off-treatment. Balance scores on- and off-treatment were significantly associated with CIPN as measured by the ped-mTNS.	Exclusion of participants who were lost to follow-up A higher-level dynamic balance test may have been more sensitive in detecting mild balance deficits
Götte72	2015	Children undergoing treatment for cancer, prior to maintenance therapy, had significantly poorer static balance as measured with the MOON as compared to age- and gender-matched norms. Three participants were unable to perform the static balance test. Children who received vincristine did not differ significantly on total MOON score than participants who did not receive vincristine.	Lack of a control group Heterogeneity of age and cancer diagnosis
Gülnerman51	2021	ALL CCS demonstrated significantly poorer balance compared to a group of healthy controls. Children who had been off treatment for a period of >49 months had significantly better balance compared to children who had been off treatment for <49 months.	Lack of a control group Variability in time off treatment
Hamari65	2020	When measured over time, children diagnosed with cancer outside the CNS performed most poorly on balance testing 2-months from diagnosis. Balance was affected more in children with ALL than children with other cancer diagnoses. Balance in children with ALL improved significantly over the first year after the drop at 2-6 months post-diagnosis, most likely reflecting the course of ALL treatment. Balance in the non-ALL group continued to decrease after 12 months despite completion of treatment, possibly reflecting long-term effects of vincristine.	Lack of a control group Heterogeneity of age and cancer diagnosis
Harbourne20	2014	Following an 8-week balance training intervention (5 days/wk) using electrical stimulation of the tongue to provide feedback regarding postural orientation, two PFS CCS demonstrated improved balance on the BBT-P, BOT-2 balance subtest, static standing on foam, and posturography measures (COPv, COPe).	Small sample size (case series)
Hartman66	2006	m-ABC scores of ALL, WT, B-NHL, and MMT CCS were significantly lower than those of the normal population, however, there were no differences in scores noted between children with ALL, WT, B-NHL, or MMT. There were no correlations between motor performance and cumulative dose of vincristine, corticosteroids, or methotrexate.	Lack of a control group Heterogeneity of age and cancer diagnosis
Hartman67	2013	m-ABC scores of ALL CCS improved significantly from end-of treatment to follow-up (>5 years following the end of treatment). The treatment regimen had no effect on motor performance at cessation of treatment, however, at follow-up children treated with a high-risk chemotherapy regimen performed significantly better than those treated with a non-high-risk regimen.	Lack of a control group Heterogeneity of age and time off treatment
Hooke75	2016	Compared to healthy norms, 66% of CCS were more than 1 SD below age- and gender-matched normative values on balance testing. Balance scores did not improve significantly following a sixweek yoga intervention.	Small sample size Heterogeneity of cancer diagnosis, treatment type/phase, age, and time off treatment
Hung28	2017	The majority of ALL CCS achieved average scores on the BOT-2 SF compared to healthy norms. One participant scored below average on the BOT-2 compared to healthy norms.	Small sample size Heterogeneity of age and time off treatment
Kasatkin21	2021	In PFT CCS, MB CCS demonstrated poorer balance as compared to AST CCS. Following an 11-day cognitive and visuomotor training intervention, PFT CCS demonstrated improved balance as measured with the BOT-2 in addition to improved visual-motor integration and visual processing speeds. There was a significant effect of age on visual outcomes. Location of PFT had significant effects on oculomotor activity, with tumors in the fourth ventricle being the most harmful and tumors in the cerebellar hemispheres the least harmful.	Heterogeneity of tumor localization, tumor malignancy and time off treatment
Keiser29	2020	Static balance in participants with a diagnosis of cancer was not significantly different than healthy norms. Participants with higher BMIs had significantly poorer static balance as compared to participants with lower BMIs.	Heterogeneity of cancer diagnosis, treatment type/phase, age, and time off treatment
Kesting30	2015	Static balance was not significantly different between survivors of bone tumors and healthy norms. Participants showed significantly reduced reaction time compared to healthy norms. A longer period after cessation of treatment was associated with fewer ground contacts and therefore significantly better values in static balance, independent from tumor localization.	Small sample size Testing was performed in non-affected limb, which could have influenced results
Kristiansen25	2021	Greater than five years post-treatment for P-AST, survivors demonstrated significantly poorer balance compared to healthy norms as measured by the BOT-2, balance subtest and the Mini-BESTest. 45% of participants had a result below 1 SD in the balance subtest of the BOT-2.	Small sample size limiting ability to make conclusions based on tumor size and location
Küper37	2013	Following tumor resection, balance function progressively improved over time in cerebellar tumor CCS with 62.5% of participants exhibiting abnormal sway in the acute post-surgical stage, 35.4% at 3 months, and 9.3% at 1 year. Brain mapping showed lesions of the inferior vermis and the deep cerebellar nuclei were associated with significantly increased postural sway. The authors argue that lesion site is a more important prognostic factor and has more influence on post-surgical balance than age. Participants who demonstrated increased sway with vision occluded were unable to use vision to compensate for balance when vision was made available, consistent with vestibular damage, specifically vestibulocerebellar dysfunction.	Small sample size Heterogeneity of tumor type, VP-shunt surgery, and postoperative treatment
Lee22	2021	In a 5-year-old child with brainstem glioma, following resection and an 8-week (40 min, 1x/wk with PT, 2x/day at home) problem-based task training intervention, balance significantly improved at 3, 6, and 12 months. Change in the PBS scores from baseline to post-intervention met the criteria for the minimal detectable change (MDC) and minimal clinically important difference (MCID).	Small sample size (case study)
Leone64	2014	Survivors of ALL demonstrated significantly poorer balance on both balance subtest measures of the UQAC-UQAM (single-leg balance eyes open, single-leg balance eyes closed) as compared to age-matched norms. 20% and 65% of participants scored below the 15th percentile on the balance eyes open and balance eyes closed, respectively.	Small sample size Heterogeneity in treatment protocol and time off treatment
Marchese4	2004	Prior to delayed intensification therapy, children undergoing treatment for ALL had significantly poorer balance than controls as measured by the TUG. Knee extension strength was correlated with TUG scores, indicating a potential relationship between strength and balance.	Small sample size
Marchese 62	2017	ALL CCS demonstrated significantly poorer balance as measured on the BOT-2 balance subtest as compared to typically developing controls. ALL CCS also had significantly longer TUG times indicating worse balance.	Small sample size Heterogeneity in time off treatment
Marchese63	2021	ALL CCS had poorer balance as measured by the BOT-2 balance subtest and took longer to complete the TUG compared to age-matched peers. Time off-treatment had a positive correlation with BOT-2 balance performance.	Small sample size Heterogeneity in treatment protocol and time off treatment
Marchese50	2022	At baseline 60% of ALL CCS demonstrated below-average balance as compared to normative data. Following a 6-week jumping rope intervention (60 min, 3x/wk), ALL CCS balance improved, with only 20% of survivors demonstrating below-average balance, but this change did not reach statistical significance.	Small sample size Lack of a control group
Mohanty47	2022	A 14-year-old child with Ewing’s sarcoma following rotationplasty demonstrated a reduced COP path excursion and COP velocity in unilateral and bilateral static standing with a custom prosthesis following standard rehabilitation, as compared to baseline testing.	Small sample size (case study)
Müller38	2017	Following a 4-week inpatient rehabilitation intervention program consisting of physical therapy, aquatic therapy and hippotherapy, children undergoing treatment for brain, bone, or soft tissue tumors demonstrated significantly improved postural sway as measured by reduced COP velocity and significantly improved SLS time. When comparing tumor type and after controlling for age, participants with brain tumors demonstrated significantly impaired postural control compared to patients with sarcomas.	Heterogeneity of cancer diagnosis, and treatment type Ceiling effect of SLS Lack of control group
Nama61	2020	Approximately 50% of children undergoing treatment for leukemia or lymphoma scored below average or well-below average on the balance subtest of the BOT-2 both during treatment as well as at the end of treatment. TUG times improved from mid-treatment to end of treatment, however 11% of participants demonstrated significantly longer TUG times compared to norms. 50% of participants had impaired vibration sensibility in their lower extremities, while only 32% had impaired vibratory sense in the upper extremities. There was no significant effect of dose on vibratory outcomes.	Baseline assessments were performed after first dose of vincristine
Nielsen31	2018	A significant decline in flamingo balance scores and TUG time was seen in children diagnosed with leukemia from the time of diagnosis to 3 months into treatment, highlighting the negative effects of chemotherapy on balance. A significant improvement was seen in flamingo balance scores in children with CNS tumors from the time of diagnosis to 3 months into treatment, highlighting balance impairments in this population are likely caused by the tumor itself and may resolve with treatments such as surgery or radiation.	Heterogeneity of age, gender distribution, cancer diagnosis and treatment protocol Underrepresentation of children with CNS tumors included in sample
Nielsen23	2020	At baseline, children undergoing treatment for cancer performed significantly poorer on the TUG than age-matched controls. Following a classmate-supported (co-admission), controlled supervised physical activity program held within the hospital (3x/wk individual, 2x/wk with peer), the intervention group performed significantly better than the control group on the TUG and flamingo balance tests at all time points (at diagnosis, 3 months and 6 months).	Low participation rate in control group
Piscione39	2014	PFT CCS had significantly poorer balance on the BOT-2 balance compared to a normative sample. 47% of the participants had below-average balance, and 23% were well-below average balance, indicating a total of 70% of participants had clear balance deficits. Scores on the balance subtest did not differ based on tumor type or age at diagnosis. Survivors who had tumors that infiltrated the vermis had significantly poorer scores on balance and bilateral coordination. There were no significant differences on the balance subtest of survivors based on various treatments (need for permanent hydrocephalus treatment, chemotherapy, radiotherapy) or prevalence of postoperative mutism.	Small sample size Individuals who chose to complete physical testing may not be representative of entire PFT CCS population
Piscione40	2017	PFT CCS demonstrated significantly poorer balance at all time points (baseline, 12 weeks, 24 weeks) compared to normative data. There were no significant improvements in balance scores following a 12-week group or home/group combination exercise intervention program (90 min, 3x/wk).	Small sample size
Ramchandren60	2009	Survivors of ALL had significantly poorer balance compared to normative data, however, no significant correlations were observed between balance, nerve conduction amplitudes, TNSr scores, or cumulative vincristine dose. 100% of participants demonstrated symptoms of CIPN as measured by the TNSr, with 94.6% of participants scoring significantly higher than the cut-off TNSr score. Nerve conduction study abnormalities were seen in 29.7% of children who were longer than 2 years off therapy.	Heterogeneity in treatment provided in addition to vincristine
Reinders-Messelink41	1999	Children undergoing treatment for ALL demonstrated poorer balance as compared to age-matched controls at all test periods (diagnosis, prior to chemotherapy, after vincristine dose 4, before vincristine dose 5, after vincristine dose 8, 6 months after vincristine dose 8). At baseline, prior to treatment, children diagnosed with ALL had significantly poorer balance with 50% of the children with ALL scoring below the 15th percentile. Balance worsened with induction chemo (69% of children with ALL scoring below the 15th percentile) and then improved with reinduction chemo (47% and 44% scoring below the 15th percentile at weeks 16 and 21, respectively). 6 months following the final vincristine dose only 4% of children with ALL scored below the 15th percentile in balance.	Dose-dependent relationships not examined Severity of peripheral neuropathy was not known
Ross79	2001	Children with unilateral or bilateral RB scored within the average range on motor development as measured by the motor ability subtest of the Bayley, as compared to normative data, although children with bilateral RB scored significantly poorer on motor ability than children with unilateral RB. All but three children (94%) had normal visual acuity in at least one eye, and the remaining 3 children had at least partial visual acuity in one eye. Children with bilateral RB were more likely to be referred for visuomotor intervention as compared to children with unilateral RB. Of all children with RB, 46% of children were referred for therapeutic services, 39% specifically for visuomotor intervention, and 7% for visual training. Children with bilateral RB were more likely to undergo multiple treatments than children with unilateral RB and children who underwent multiple treatments were significantly more likely to be referred for visuomotor problems than children who underwent enucleation only.	Less specific measure of balance Relationships between vision and balance were not explicitly studied
Sabel42	2016	At baseline, survivors of CNS tumors had significantly lower BOT-2 balance and bilateral coordination scores when compared to normative data. Following a 10-week active video game intervention (Wii games, 5x/wk, 45 min/session), survivors of brain tumors demonstrated a 17% improvement in bilateral coordination over the intervention period, while there were no significant changes in balance. Two children had unilateral visual impairment.	Small sample size Relationships between vision and balance were not explicitly studied
Şahin58	2020	In children undergoing treatment for cancer, following a 4-week inpatient task-oriented rehabilitation intervention (ToRP) intervention (45 min/day, 20 sessions total), children randomized to the ToRP program demonstrated significantly improved balance as compared to the control group. Both groups demonstrated significantly improved balance as compared to baseline.	Heterogeneity of age, gender distribution, cancer diagnosis and treatment protocol
Selim48	2023	Following surgical resection of MB, children with ataxia who received an 8-week dual-task cognitive training intervention (60 min, 3x/wk) in addition to standard physical therapy demonstrated significantly improved balance as compared to physical therapy alone.	Small sample size Intervention group had greater time in training than control group
Syczewska43	2006	Balance deficits (significantly increased COP path) were noted in 51% of CNS tumor CCS. CNS tumor CCS with balance deficits were on average 3.7 years from treatment, while those without balance deficits were significantly further removed from treatment (5.8 years). Most participants with balance deficits had abnormalities of balance during both the eyes-open and eyes-closed conditions, thus participants were unable to compensate for balance deficits with visual feedback. It was noted that children with impaired balance demonstrated a compensatory gait strategy in attempts to improve/maintain balance. Tumor location did not significantly affect balance outcomes or gait deviations.	Heterogeneity of age, gender distribution, tumor location, cancer diagnosis, treatment type, and time off treatment
Takken59	2009	In ALL CCS no significant improvements in balance occurred following a 12-week exercise training intervention program (2x/wk with PT, 2x/wk at home, 45 min sessions).	Small sample size
Tanner24	2019	ALL CCS who had undergone a proactive physical therapy intervention (Stoplight Program, SLP), had significantly improved body coordination scores (balance and bilateral coordination) of the BOT-2 compared to those not in the SLP. Those who underwent the SLP had significantly better scores on bilateral coordination but not balance as compared to survivors who did not undergo the SLP, suggesting balance specifically is an impairment that is persistent over time.	Participants who completed the program may have been highly motivated, introducing selection bias into the study Severity of peripheral neuropathy was not known for each group
Tay57	2017	12.9% of ALL CCS had below-average or well-below average scores on the motor sections of the BOT-BF, and no significant differences between patients with or without CIPN were demonstrated. 26.7% of ALL CCS had abnormal clinical neuropathy (cTNS) scores and 68.3% had electrophysiological evidence of neuropathy as measured with nerve conduction velocities (10.2% sensory only, 18.8% motor only, 71% sensory and motor). 15.8% of participants had both clinical and electrophysiological neuropathy. Participants who were classified in the intermediate- or high-risk treatment stratification arms had a higher risk of developing CIPN.	Heterogeneity in treatment provided in addition to vincristine BOT-2 Brief Form was designed as a screening tool for motor proficiency and thus may not have been sensitive enough to register the impact of peripheral neuropathy
Toy44	2006	An outpatient balance training intervention program (8 weeks), consisting of static and dynamic balance activities, was successful in significantly improving balance in a 12-year-old MB CCS who was 19 months post-surgical resection of MB.	Small sample size (case study)
Usama49	2023	Children undergoing maintenance therapy for PFT who participated in a 12-week balance and coordination intervention (30 min, 3x/wk) in addition to standard physical therapy demonstrated significantly improved postural control, balance, and coordination as compared to children who received standard therapy alone.	Heterogeneity of age, gender distribution, tumor location, cancer diagnosis, and treatment type
Wiernikowski73	2005	In children currently undergoing maintenance therapy for ALL or NHL who were receiving alendronate, there were no significant changes in BOT-2 balance score. Participants demonstrated significant improvements in TUDS from baseline to 24 weeks, indicating alendronate may improve strength and TUDS, however, not necessarily balance in children undergoing maintenance chemotherapy.	Small sample size limiting ability to make conclusions regarding the effect of alendronate on balance
Wright56	1998	ALL CCS had significantly poorer balance scores on the BOT-2 compared to age-matched controls. 25% of survivors scored greater than 2 standard deviations below an established normal mean on the balance subtest. There were no significant differences between children who had received cranial radiation and those that did not, nor were there any statistically significant relationships between balance and the time off therapy.	Heterogeneity of age, treatment type/protocol
Wright76	2005	ALL CCS had significantly lower scores on the balance subtest of the BOT-2 as compared to a control group. Cranial radiation, being overweight, and longer time off treatment were predictors of poorer balance but accounted for only 18.7% of the variability in balance scores, indicating the etiology of balance problems is most likely multifactorial and variable. Three children were reported to have cataracts and one child was reported to have poor visual acuity.	Relationships between vision and balance were not explicitly studied Findings specific to ALL CCS who had been on DFCI protocols, limiting generalizability of findings
Yildiz Kabak54	2021	Children undergoing induction or consolidation chemotherapy for ALL had significantly lower scores on the BOT-SF balance subtest as compared to age-matched controls.	Cross-sectional study design limited ability to draw dose-specific and treatment specific conclusions regarding balance function
Yildiz Kabak55	2021	Children with ALL undergoing maintenance therapy had significantly slower times on the TUG compared to normative values. 56% of children with ALL scored below average scores on the BOT-2 balance. subtest	Children diagnosed with peripheral neuropathy, who received cranial radiation, and with history of CNS leukemia were excluded, limiting generalizability of findings Lack of a control group

Abbreviations: AA, anaplastic astrocytoma; ALCL, acute large cell lymphoma; ALL, Acute lymphoblastic leukemia; AML, Acute myeloid leukemia; AMPS, assessment of motor and processing skills; B-NHL, B-cell non-Hodgkin lymphoma; BARS, Brief Ataxia rating scale; BBT-P, Berg balance test for pediatrics; BOT-2, Bruininks-Oseretsky Test of Motor Proficiency 2^nd Edition; BOT-SF, Bruininks-Oseretsky Test of Motor Proficiency - Short Form; CANTAB, Cambridge Neuropsychological Test Automated Battery; CIPN, Chemotherapy induced peripheral neuropathy; CVFQ, Children's Visual Function Questionnaire; CNS, Central Nervous System; COP, center of pressure; COPe, center of pressure excursion; COPv, center of pressure velocity; CPET, cardiopulmonary exercise test; CSAPPA, Children’s Self-perceptions of Adequacy in and Predilection for Physical Activity Scale; DCDQ-07, Developmental Coordination Disorder Questionnaire-07; DMT, Deutscher Motor Ability Test; DVA, Dynamic Visual Acuity; EPD, ependymoma; GCT, Germ Cell Tumor; GB, Glioblastoma; GMFM, gross motor function measure; HRQoL, health-related quality of life; HSCT, hematopoietic stem cell transplant; ICARS, International Ataxia Rating Scale; ICD-10, International Classification of Diseases, Tenth Revision; LGG, low-grade gliomas; m-ABC, Movement Assessment Battery for Children; MB, Medulloblastoma; mCTSIB, Modified Clinical Test of Sensory Interaction on Balance; Mini-BESTest, mini-balance evaluation systems test; MMT, malignant mesenchymal tumor; MOON, motor performance test in oncology; MOT4-6, Motor proficiency test; MPD, myeloproliferative disorder; NCV, nerve conduction velocity; NHL, non-Hodgkin's Lymphoma; P-AST, pilocytic astrocytoma; PBS, pediatric balance scale; PCS, Pediatric Cancer Survivors; PDMS-2, Peabody Developmental Motor Scales 2^nd Edition; PEDI, Pediatric evaluation of disability index; Ped-mTNS, pediatric-modified total neuropathy score; PFBT/PFT, posterior fossa (brain) tumors; PFS, Posterior Fossa Syndrome; PVSQ, Pediatric Vestibular Symptom Questionnaire; RB, retinoblastoma; RCT, randomized control trial; RVP, Rapid visual processing; SARA, Scale for the assessment and rating of ataxia; SD; standard deviation; ToRP, total ossicular replacement prosthesis; TUDS, Timed Up and Down Stairs test; TUG, Timed Up and Go test; UQAC–UQAM test battery, University of Quebec in Chicoutimi-University of Quebec in Montreal (UQAM) test battery; VCR, vincristine; WT, Wilms Tumor; 6MWT, six-minute walk test.

Sample size was defined as follows: small: n≤30, medium: n=31-99, large: n≥100.

Highlights.

• Balance impairments can be caused by cancerous tumor and/or medical treatment

• Sensory impairments can contribute to balance dysfunction

• Wide heterogeneity of balance assessments are employed

Biographies

Emily McCarthy has a D.P.T. from Northwestern University and is a Physical Rehabilitation Science Ph.D. Candidate within the Department of Physical Therapy and Rehabilitation Science at the University of Maryland, School of Medicine. Her research interests focus on sensory impairments and balance dysfunction in childhood cancer patients and survivors.

Victoria Marchese is the Jane Kroh Satterfield Professor of Physical Therapy and Rehabilitation Science and Chair of the Department of Physical Therapy and Rehabilitation Science at the University of Maryland, School of Medicine. She earned her Ph.D. in Rehabilitation Sciences from the Medical College of Pennsylvania/Hahnemann University and has over 25 years of experience as a pediatric physical therapist. Her research focuses on the neuromotor mechanisms that contribute to physical function in children with hematological and oncological conditions.

Andrea Goldstein Shipper has a M.S.L.I.S. and is Public Health and Social Sciences Librarian at the Charles Library at Temple University. Her research interests focus on systematic review methodology and expert literature searching.

Kelly Rock (@PedsHemOncPT) has a D.P.T. from Ithaca College and a Ph.D. in physical rehabilitation science from the University of Maryland School of Medicine. She is currently a postdoctoral fellow in the Department of Physical Therapy at the University of Florida. Her research interests focus on skeletal muscle properties and gross motor performance in individuals with chronic health conditions across the lifespan.

Cara Felter (@PTeducator4SDOL) has a D.P.T. from Belmont University, an M.P.H. from Johns Hopkins Bloomberg School of Public Health, and a Ph.D. in Health Professions Education from the University of Maryland, Baltimore. She is the Chief Learning Officer for PALLA and an Associate Professor in the Graduate School at the University of Maryland, Baltimore (UMB). She is an educational researcher with projects spanning social determinants of learning, interview-based learning, and the role of patient-educators in health professions education.

Appendix A. Search Strategies

PubMed (NLM, 1809-present)

(motor performance[tiab] OR ototox*[tiab] OR vestibular dysfunction[tiab] OR vestibular rehabilitation[tiab] OR imbalance[tiab] OR balance[tiab] OR postural control[tiab] OR postural stability[tiab] OR proprioception[tiab] OR visuo vestibul*[tiab] OR visuovestibul*[tiab] OR chemotherapy induced peripheral neuropathy[tiab] OR vestibulotox*[tiab] OR neurotox*[tiab] OR “vestibular diseases”[mesh] OR ototoxicity[mesh] OR “postural balance”[mesh] OR “psychomotor performance” [mesh] OR proprioception[mesh]) AND ((pediatric cancer[tiab] OR childhood cancer[tiab] OR pediatric oncology[tiab]) OR (acute lymphocytic leukemia[tiab] OR lymphoblastic leukemia[tiab] OR acute myeloid leukemia[tiab] OR central nervous system cancer*[tiab] OR CNS cancer*[tiab] OR central nervous system tumor* [tiab] OR central nervous system tumour* [tiab] OR CNS tumor*[tiab] OR CNS tumour*[tiab] OR central nervous system neoplasm*[tiab] OR CNS neoplasm*[tiab] OR astrocytoma*[tiab] OR brain stem glioma*[tiab] OR atypical teratoid[tiab] OR rhabdoid tumor*[tiab] OR rhabdoid tumour*[tiab]OR germ cell tumor*[tiab] OR germ cell tumour*[tiab] OR craniopharyngioma*[tiab] OR ependymoma*[tiab] OR medulloblastoma*[tiab] OR embryonal tumor*[tiab] OR embryonal tumour*[tiab] OR embryonal cancer*[tiab] OR lymphoma*[tiab] OR osteosarcoma*[tiab] OR “precursor cell lymphoblastic leukemia lymphoma”[mesh] OR “leukemia, myeloid, acute”[mesh] OR “central nervous system neoplasms”[mesh] OR astrocytoma[mesh] OR “teratoid tumor, atypical”[supplementary concept] OR “rhabdoid tumor” [mesh] OR “neoplasms, germ cell and embryonal” [mesh] OR craniopharyngioma[mesh] OR ependymoma[mesh] OR medulloblastoma[mesh] OR lymphoma[mesh] OR osteosarcoma[mesh]) AND (child*[tiab] OR pediatric[tiab] OR infan*[tiab] OR adolescen*[tiab] OR child[mesh] OR infant[mesh] OR adolescent[mesh]))

Embase (Elsevier, embase.com, 1974-present)

#1	(‘motor performance’:ab,ti OR ‘vestibular dysfunction’:ab,ti OR ‘vestibular rehabilitation’:ab,ti OR ototox*:ab,ti OR imbalance:ab,ti OR balance:ab,ti OR ‘postural control’:ab,ti OR ‘postural stability’:ab,ti ORproprioception:ab,ti OR ‘visuo-vestibul*’:ab,ti OR visuovestibul* :ab,ti OR ‘chemotherapy-induced peripheral neuropathy’:ab,ti OR vestibulotox*:ab,ti OR neurotox*:ab,ti OR ‘balance disorder’/exp OR ‘vestibular function’/exp OR ‘motor performance’/de OR ‘vestibular disorder’/exp OR ototoxicity/de OR proprioception/de)
#2	((‘pediatric cancer’:ab,ti OR ‘childhood cancer’:ab,ti OR ‘pediatric oncology’:ab,ti OR ‘childhood cancer’/exp)
#3	(‘acute lymphocytic leukemia’:ab,ti OR ‘lymphoblastic leukemia’:ab,ti OR ‘acute myeloid leukemia’:ab,ti OR ‘central nervous system cancer*’:ab,ti OR ‘CNS cancer*’:ab,ti OR ‘central nervous system tum*r*’:ab,ti OR ‘CNS tum*r*’:ab,ti OR ‘central nervous system neoplasm*’:ab,ti OR ‘CNS neoplasm*’:ab,ti OR astrocytoma*:ab,ti OR ‘brain stem glioma*’:ab,ti OR ‘atypical teratoid’:ab,ti OR ‘rhabdoid tum*r*’:ab,ti OR ‘germ cell tum*r*’:ab,ti OR craniopharyngioma*:ab,ti OR ependymoma*:ab,ti OR medulloblastoma*:ab,ti OR ‘embryonal tum*r*’:ab,ti OR ‘embryonal cancer*’:ab,ti OR lymphoma*:ab,ti OR osteosarcoma*:ab,ti OR ‘acute lymphoblastic leukemia’/de OR ‘acute myeloid leukemia’/exp OR ‘central nervous system cancer’/exp OR astrocytoma/exp OR ‘atypical teratoid rhabdoid tumor’/de OR ‘germ cell tumor’/exp OR craniopharyngioma/exp OR ependymoma/exp OR medulloblastoma/de OR lymphoma/exp OR osteosarcoma/de)
#4	(child*:ab,ti OR pediatric:ab,ti OR infan*:ab,ti OR adolescen*:ab,ti OR [newborn]/lim OR [infant]/lim OR [child]/lim OR [adolescent]/lim))
#5	#3 and #4
#6	#2 or #5
#7	#1 and #6

Cochrane CENTRAL Register of Controlled Trials (Wiley)

#1	(“motor performance” OR ototox* OR “vestibular dysfunction” OR “vestibular rehabilitation” OR imbalance OR balance OR “postural control” OR “postural stability” OR proprioception OR “visuo-vestibul*” OR visuovestibul* OR “chemotherapy-induced peripheral neuropathy” OR vestibulotox* OR neurotox*):ti,ab,kw
#2	((“pediatric cancer” OR “childhood cancer” OR “pediatric oncology”):ti,ab,kw
#3	(“acute lymphocytic leukemia” OR “lymphoblastic leukemia” OR “acute myeloid leukemia” OR (“central nervous system” NEXT cancer*) OR (CNS NEXT cancer*) OR (“central nervous system” NEXT tum*r*) OR (CNS NEXT tum*r*) OR (“central nervous system” NEXT neoplasm*) OR (CNS NEXT neoplasm*) OR astrocytoma* OR (“brain stem” NEXT glioma*) OR “atypical teratoid” OR (rhabdoid NEXT tum*r*) OR (“germ cell” NEXT tum*r*) OR craniopharyngioma* OR ependymoma* OR medulloblastoma* OR (embryonal NEXT tum*r*) OR (embryonal NEXT cancer*) OR lymphoma* OR osteosarcoma*):ab,ti,kw
#4	(child* or pediatric or infan* or adolescen*):ab,ti,kw
#5	#3 and #4
#6	#2 or #5
#7	#1 and #6

CINAHL (EBSCOhost, 1976-present)

S1	(“motor performance” OR ototox* OR “vestibular dysfunction” OR “vestibular rehabilitation” OR imbalance OR balance OR “postural control” OR “postural stability” OR proprioception OR “visuo-vestibul*” OR visuovestibul* OR “chemotherapy-induced peripheral neuropathy” OR vestibulotox* OR neurotox*)
S2	(“pediatric cancer” OR “childhood cancer” OR “pediatric oncology”)
S3	(“acute lymphocytic leukemia” OR “lymphoblastic leukemia” OR “acute myeloid leukemia” OR “central nervous system cancer*” OR “CNS cancer*” OR “central nervous system tumo#r*” OR “CNS tumo#r*” OR “central nervous system neoplasm*” OR “CNS neoplasm*” OR astrocytoma* OR “brain stem glioma*” OR “atypical teratoid” OR “rhabdoid tumo#r*” OR “germ cell tumo#r*” OR craniopharyngioma* OR ependymoma* OR medulloblastoma* OR “embryonal tumo#r*” OR “embryonal cancer*” OR lymphoma* OR osteosarcoma*) AND (child* or pediatric or infan* or adolescen*))
S4	S2 or S3
S5	S1 and S4

Physiotherapy Evidence Database (pedro.org.au)

#1	“motor performance” cancer
#2	Vestibular cancer
#3	Balance cancer

A summary of the search results from databases:

• PubMed (NLM, 1809-present): 2,719 results

• Embase (Elsevier, embase.com, 1974-present): 6,578 results

• Cochrane CENTRAL Register of Controlled Trials (Wiley): 308 results

• CINAHL (EBSCOhost, 1976-present): 566 results

• Physiotherapy Evidence Database (pedro.org.au): 80 results