JPOXXX10.1177/1043454218762705Journal of Pediatric Oncology NursingSmolik et al. research-article7627052018

Article

Journal of Pediatric Oncology Nursing 2018, Vol. 35(4) 267­–275 Assessment Tools for Peripheral © 2018 by Association of Pediatric Hematology/Oncology Nurses Reprints and permissions: Neuropathy in Pediatric Oncology: sagepub.com/journalsPermissions.nav DOI:https://doi.org/10.1177/1043454218762705 10.1177/1043454218762705 A Systematic Review From the journals.sagepub.com/home/jpo Children’s Oncology Group

Suzanne Smolik, RN, MSN, CPNP, CPON1, Lesley Arland, MS, PA-C1, Mary Ann Hensley, RN, BSN, CNOR, ONC1, Debra Schissel, RN, CPON, CCRP1, Barbara Shepperd, RN, CPHON, CCRP1, Kristin Thomas, PT, DPT1, and Cheryl Rodgers, PhD, RN, CPNP, CPON2

Abstract Peripheral neuropathy is a known side effect of several agents, including and platinum- based chemotherapy. Early recognition and monitoring of this side effect is an important role of the pediatric oncology nurse. There are a variety of peripheral neuropathy assessment tools currently in use, but the usefulness of these tools in identifying and grading neuropathy in children varies, and there is currently no standardized tool in place to evaluate peripheral neuropathy in pediatric oncology. A systematic review was performed to identify the peripheral neuropathy assessment tools that best evaluate the early onset and progression of peripheral neuropathy in pediatric patients receiving . Because of the limited information available in pediatric oncology, this review was extended to any pediatric patient with neuropathy. A total of 8 studies were included in the evidence synthesis. Based on available evidence, the pediatric–modified Total Neuropathy Scale (ped-m TNS) and the Total Neuropathy Score–pediatric version (TNS-PV) are recommended for the assessment of vincristine-induced peripheral neuropathy in children 6 years of age and older. In addition, several studies demonstrated that subjective symptoms alone are not adequate to assess for vincristine-induced peripheral neuropathy. Nursing assessment of peripheral neuropathy should be an integral and regular part of patient care throughout the course of chemotherapy treatment.

Keywords systematic review, pediatrics, peripheral neuropathy, assessment tools

Cancer treatment is associated with significant side sensory, motor, and autonomic neuropathy in children effects that impair individuals’ daily activities and health- (Gilchrist, 2012). These symptoms and physical assess- related quality of life. Side effects associated with che- ment findings are described in Table 1. A systematic review motherapy are numerous and well described in the of CIPN by Kandula, Park, Cohn, Krishnan, & Farrer literature. One side effect of chemotherapy that has a sig- (2016) found that vincristine-related neurotoxicity was nificant impact on the individual is peripheral neuropa- reported in 32 (52%) of the 61 studies. The most common thy, which can decrease mobility and limit independence vincristine-induced manifestations of CIPN are distal sen- with activities of daily living. Chemotherapy-induced sory loss in the lower extremities (sensory), distal symmet- peripheral neuropathy (CIPN) includes any injury, ric weakness in lower limbs progressing to foot drop inflammation, or degeneration of the peripheral nerves (motor), and constipation (autonomic) (Loprinzi, 2017). due to administration of a chemotherapeutic agent (Gilchrist, 2012), and may result in motor, sensory, and 1Children’s Hospital Colorado, Aurora, CO, USA autonomic nervous system symptoms. 2 Duke University School of Nursing, Durham, NC, USA Early and accurate identification of CIPN among pedi- atric patients with cancer is important. Vincristine and Corresponding Author: similar vinca agents are essential in the treatment Suzanne Smolik, RN, MSN, CPNP, CPON, Solid Tumor Oncology, Children’s Hospital Colorado, 13123 East 16th Avenue, B-115, of many pediatric cancers, but they may also cause acute Aurora, CO 80045, USA. and long-term damage to peripheral nerves, leading to Email: [email protected] 268 Journal of Pediatric Oncology Nursing 35(4)

Table 1. Symptoms and Physical Assessment Findings Associated With Chemotherapy-Induced Peripheral Neuropathy.a

Sensory Motor Autonomic Paresthesia Weakness (usually in lower limbs) Constipation Dysesthesia (abnormal sensations) Foot drop Blood pressure alterations Pain Gait or balance disturbance Urinary retention Numbness and tingling Fine motor skills dysfunction Diminished or absent reflexes Diminished or absent vibratory sensations Diminished or absent cutaneous sensation aInformation from Loprinzi (2017) and Biedrzycki (2015).

The incidence of vincristine-induced acute neuropa- physical therapist, orthopedic surgical registered nurse, thy has been noted to be as high as 100% in children, and 2 research oncology registered nurses. A doctorally while severe peripheral neuropathy occurs in approxi- prepared nurse researcher from the COG Nursing mately 10% of the children with cancer (Kandula et al., Discipline served as the project mentor. 2016). Most CIPN resolves within 3 months after com- A medical librarian and research assistant conducted pletion of chemotherapy; however, some symptoms the electronic search of 4 databases, including PubMed, may persist, especially symptoms caused by vincristine CINAHL, Cochrane, and the National Guidelines (Loprinzi, 2017). Clearinghouse. Key terms guiding the search were Monitoring and accurately reporting side effects dur- peripheral neuropathy, pediatric, and assessment. ing clinical trials of treatment regimens for cancer is vital. Vincristine and oncology were not included as key terms There are a variety of peripheral neuropathy assessment to obtain all available evidence focused on pediatric tools currently in use, but the accuracy of these tools in peripheral neuropathy assessment. Due to the limited lit- identifying neuropathy in children varies. Young children erature related to pediatric patients with cancer with with limited vocabulary may be unable to describe the peripheral neuropathy, the search was expanded to all sensations or deficits that are associated with peripheral pediatric diseases. All published years were included in neuropathy. Reliable tools must be identified and used the literature search with English used as the only limit. when evaluating neuropathy in children during and after The original search yielded 182 articles, with 2 additional they receive chemotherapy. Currently, there is not one articles located by hand searching, which were duplicates consistently used tool to measure CIPN in children with (Figure 1). No clinical guidelines relevant to the PICOT cancer. Therefore, a systematic review was performed to question were identified. The team reviewed all 182 describe the reliability of CIPN assessment tools for chil- abstracts to determine if the articles met the inclusion cri- dren receiving vincristine. teria. The inclusion criteria consisted of research-based A PICOT question was developed to focus the system- articles that included an evaluation of a peripheral neu- atic review. PICOT represents Patient, Intervention or ropathy assessment tool with participants aged 1 to 18 Issue of Interest, Comparison, Outcome, and Time years. After excluding articles that did not meet the inclu- (Melnyk & Fineout-Overholt, 2015). The following sion criteria, the number of available articles for use as PICOT question was used to guide this review: “In pedi- evidence sources was reduced to 8. Five articles were atric patients receiving vincristine, what assessment tools focused on children with cancer, and 3 articles were best evaluate early onset and progression of peripheral focused on children with type 1 diabetes. neuropathy?” Matrix tables (Garrard, 2014) were used to extract key information and to summarize the following components Systematic Review Methods of each article: purpose, design, variables, settings/sub- jects, measurement and instruments, and results/implica- An evidence-based practice (EBP) project proposal was tions. In addition, the quality of each article was evaluated submitted and approved by the Children’s Oncology Group using the Grading of Recommendations, Assessment, (COG) Nursing Discipline under the COG Nursing Development, and Evaluations (GRADE) criteria (Guyatt Evidence-Based Practice initiative. This initiative is et al., 2011) and issues with methodological flaws, incon- designed to address clinical issues not typically broached sistencies, indirectness, imprecision, and publication bias in protocols but pertinent to the nursing care of patients were noted on the matrix tables. The matrix table for each throughout therapy. The evidence-based review team con- article was completed by 1 team member, who then sisted of a pediatric nurse practitioner, physician assistant, presented the information to the group via a monthly Smolik et al. 269

Figure 1. PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) flow diagram. conference call, where the summary and quality issues Peripheral Neuropathy Assessment Tool were reviewed and agreed upon by group consensus. Evidence A total of 8 studies are included in the evidence synthesis. Evidence Review Three studies evaluated the ped-m TNS tool among pedi- Peripheral Neuropathy Assessment Tools atric patients with cancer, 2 studies evaluated the TNS-PV tool among pediatric patients with cancer, and the remain- Ten pediatric peripheral neuropathy assessment tools ing 3 studies evaluated neurological assessments among were identified from the evidence. Three instruments, pediatric patients with diabetes (Table 3). the Common Terminology Criteria for Adverse Events The ped-m TNS is a peripheral neuropathy assessment (CTCAEv3.0/v4.0), the pediatric–modified Total tool that includes both symptom assessment and physical Neuropathy Scale (ped-m TNS), and the Total Neuropathy evaluation. Gilchrist, Tanner and Hooke (2009) imple- Scale–Pediatric Version (TNS-PV), include subjective mented a feasibility test among 20 pediatric patients with and objective assessments to evaluate the presence and cancer and demonstrated that all patients aged 5 to 18 extent of peripheral neuropathy. One instrument, the years were able to complete the ped-m TNS assessment. Wong-Baker FACES pain scale, is a subjective report of Results indicated that sensory symptoms (feelings of tin- current pain perceptions conveyed on a Likert-type scale. gling, numbness, or pain) did not correlate with pin sensi- The remaining 5 assessment tools, nerve conduction tivity (p = .549) or vibration sensibility (p = .595). study, neurological exam, current perception threshold However, motor symptoms (difficulty buttoning shirts or (CPT), tactile perception threshold (TPT), and vibration tying shoes, difficulty walking or going up stairs, and dif- perception threshold (VPT) are objective evaluations of ficulty extending arm over his or her head) moderately peripheral neuropathy determined by physical assess- correlated with strength (rs = 0.544, p = .011), deep tendon ments. These tools are described further in Table 2. reflexes (rs = 0.456, p = .043), and vibration (rs = 0.613, 270 Journal of Pediatric Oncology Nursing 35(4)

Table 2. Peripheral Neuropathy Assessment Tools.

Instrument Brief Description Scoring/Measurement Psychometric Properties

CTCAEv3.0/v4.0 (Common Developed by the National Grade 1: mild adverse event Good construct validity Terminology Criteria for Cancer Institute to classify Grade 2: moderate adverse event Test-retest reliability = 0.7 Adverse Events) the severity of adverse events Grade 3: severe adverse event (Dueck et al., 2015) within oncology: Peripheral Grade 4: life-threatening adverse neuropathy is divided into event motor and sensory subscales Grade 5: fatal adverse event ped-m TNS (Pediatric–Modified Combined subjective and Eight items scored 0 to 4 on Likert- Internal consistency (α = 0.76) Total Neuropathy Scale) objective scale assessing type scale. Total scores can range Test-retest reliability (ICC = 0.99) nerve function for children from 0 to 32; score of 5 or greater Interrater reliability (ICC = 0.98) 5 to 18 years old; detects indicates neuropathy (Gilchrist & Tanner, 2013) sensory, motor, and and higher score indicates more autonomic neuropathy severe neuropathy Scripted questions: •• Sensory symptoms •• Motor symptoms •• Autonomic symptoms Clinical testing: •• Light touch •• Pin sensation •• Vibration sensation •• Manual muscle testing of distal extremities •• Deep tendon reflexes TNS-PV (Total Neuropathy Combined subjective and Seven items scored 0-4 on Likert-type Correlation: moderately strong Scale–Pediatric Version) objective scale assessing scale. Total scores can range from 0 (r = 0.51-0.87) among nerve function for children to 28; higher score indicates more paresthesia, numbness, 1-19 years old; detects severe peripheral neuropathy neuropathic pain; low (r = 0.13) sensory, motor, and among laryngeal and autonomic autonomic neuropathy neuropathy Version A evaluates hands or Items assess Internal consistency (α = 0.68) feet, and version B combines •• subjective symptoms Interrater reliability

scores of hands and feet •• temperature (Kw = 0.54-0.99) for all items •• vibration except paresthesia (Kw = 0.15) •• strength No significant difference from •• tendon reflexes versions A and B of the TNS-PV •• autonomic neuropathy (Lavoie Smith et al., 2013) (constipation) •• laryngeal neuropathy (hoarseness) FACES Pain Scale Cartoon drawings of faces Six faces numbered from left to Most preferred pain rating scale representing a range of pain right ranging from a smiling face by children; excellent criteria- intensities representing no pain (0) to a crying related validity (Wong & Baker, face representing extreme pain (5) 1988) Nerve Conduction Study Nerve conduction velocity Measurement of speed of electrical Neuropathy assumed in adults measured using surface impulse through a nerve when conduction velocity is less electrodes than 42 m/s in plantar nerve or less than 40 m/s in post tibial nerve; children <5 years of age, conduction velocity is half of the adult values (Liveson, 1992) Neurological Exam Typically includes both Objective assessment may include Not applicable objective/physical assessment •• Physical exam and subjective symptoms •• Deep tendon reflexes •• Cranial nerve exam •• Muscle strength •• Muscle tone •• Sensation •• Coordination Subjective symptom assessment may include: •• Numbness •• Tingling •• Fatigue •• Pain (continued) Smolik et al. 271

Table 2. (continued)

Instrument Brief Description Scoring/Measurement Psychometric Properties

Current perception threshold Quantitative measurement of Neurometer used to produce Healthy sample: interclass (CPT) peripheral sensory nerve transcutaneous electrical stimulation correlation = 0.84 (95% CI: function through nerve fiber (buzz or tingle sensation) at different 0.66-0.95; Gaudreault et al., conduction frequencies (2000, 250, 5 Hz) 2015) Tactile perception threshold Quantitative measurement of Different size monofilaments exerting Healthy sample: tactile sensitivity (TPT) peripheral sensory nerve different amounts of pressure to differed across skin sites; function through tactile assess tactile perception (quantified forehead and palm are most sensation as yes/no to the sensation) sensitive to touch (P < .001; Ackerley, Carlsson, Wester, Olausson, & Backlund Wasling, 2014) Vibration perception threshold Quantitative measurement of Electromechanical instrument Healthy sample: vibration (VPT) large sensory nerve fibers produces vibration at different sensitivity differed among through vibration amplitudes expressed as vibration gender, age, and temperature of units to determine lowest amplitude skin (Halonen, 1986) that vibration is detected; higher Reliability varies among different vibration unit indicates greater instruments dysfunction

Note. ICC = intraclass correlation coefficient. p = .004). Gilchrist and Tanner (2013) further investigated and temperature could not be measured in 87% of the chil- the validity of the ped-m TNS with a group of 41 children dren ≤3 years old and numbness, paresthesia, and neuro- aged 5 to 18 years old. There was a negative association pathic pain could not be measured in 48% of 3-year-old with the ped-m TNS score and balance (rs = −0.626, p < children; however, 91% of all children were cooperative .001) and manual dexterity (rs = −0.461, p < .001) such for the reflex testing, and 78% of all children participated that higher scores on the tool indicated worse balance and in the strength testing. All the items on the TNS-PV were manual dexterity. Interestingly, there was no correlation attainable in children ≥6 years old. `found between the cumulative vincristine dose and the When evaluating vincristine cumulative dose and neu- ped-m TNS score. ropathy assessment scores in children, the TNS-PV more Using the sample from the previous study, Gilchrist, closely correlated with the cumulative dosage (r = 0.53, Marais, and Tanner (2014) extended the findings by com- P = .01) than the CTCAEv4.0 sensory measure (r = 0.31, paring the ped-m TNS with the CTCAEv3.0. There was P = .05) and the CTCAEv3.0 motor measure (nonsignifi- no correlation noted between the ped-m TNS scores and cant) (Lavoie Smith et al., 2013). The TNS-PV identified the combined sensory and motor CTCAEv3.0 scores. more children with vincristine-induced peripheral neurop- Most participants with some degree of neuropathy (84%, athy than the CTCAEv4.0 (Lavoie Smith et al., 2015). n = 16) were missed by the CTCAEv3.0 scoring. There Subjective symptoms alone on the TNS-PV were was no correlation between the sensory symptom scores unreliable for detecting peripheral neuropathy. An eval- on the ped-m TNS and the sensory scores on the uation of 1539 assessments among 128 children receiv- CTCAEv3.0, and no correlation between motor symp- ing vincristine found that 44% of children reported pain toms on the ped-m TNS and motor scores on the on the subjective symptom item, but 78% had peripheral CTCAEv3.0; however, there was moderate association neuropathy (Lavoie Smith et al., 2013). Furthermore, between strength testing on the ped-m TNS and the motor children’s ratings on the FACES pain scale demon- portion of the CTCAEv3.0 (rs = 0.43, P < .01). strated only a weak correlation with the TNS-PV scale Lavoie Smith and colleagues (2013) developed 2 ver- (r = 0.38, P = .01). sions of the TNS-PV scale: an original version (version A) Two studies assessed children with type 1 diabetes and to evaluate lower or upper extremity symptoms and an demonstrated a low sensitivity in diagnosing peripheral alternative version (version B) to score lower and upper neuropathy when using a clinical examination compared extremity symptoms by a trained evaluator. An item analy- with nerve conduction studies (Holiner et al., 2013; sis showed no statistical difference between versions A and Nelson et al., 2006). Out of 73 children with type 1 diabe- B. Among the 7 items on the TNS-PV, tendon reflexes and tes, 42 (57%) were diagnosed with neuropathy by using vibration were the most responsive items, which correlated nerve conduction studies, but only 26 (36%) had an closely to the overall TNS-PV scores (effect size = 0.65, abnormal neurological exam (Nelson et al., 2006). P < .0001). It is important to note that some items on the Another study of 39 children with type 1 diabetes identi- scale were difficult to obtain in young children. Vibration fied 15 children (38%) with abnormal nerve conduction 272 Journal of Pediatric Oncology Nursing 35(4)

Table 3. Evidence Summary.

First Author, Year Study Design, Sample Assessment Tools Results Gilchrist, 2009 Pilot study, 20 oncology ped-m TNS, CTCAEv3.0 Testing time <10 min patients aged 5-18 years Spearman correlation: Motor symptoms and strength 0.554, P < .05 Motor symptoms and sensory symptoms 0.487, P < .05 Motor symptoms and vibration sensitivity 0.613, P < .01 Motor symptoms and deep tendon reflexes 0.456, P = .017 Motor symptoms and pin and vibration sensitivity 0.539, P < .05 Pin and vibration sensitivity not correlated with each other Gilchrist, 2013 Descriptive, 82 oncology ped-m TNS, Bruininks- No correlation with cumulative dose patients aged 5-18 Osteretsky Test of vincristine and neuropathy score or with years and 35 healthy Motor Proficiency cumulative vincristine dose and balance children version 2 and manual dexterity Cancer patients had worse ped-m TNS scores (2-18) than controls (0-4) Neuropathy measures found negative

associations with balance (rs = −0.626, P < .001) and manual dexterity

(rs = −0.461, P < .001) Gilchrist, 2014 Descriptive, 60 oncology ped-m TNS, CTCAEv3.0 Median ped-m TNS score 9, range 2-19 patients aged 5-18 Median CTCAE sensory score 0, range 0-3 years Median CTCAE motor score 2, range 0-3 No patients received score of 0 on ped-m TNS; one-third of participants received 0 score on CTCAE version 3.0 No correlation between ped-m TNS and combined sensory/motor CTCAE scores (P = .07) Sensitivity of CTCAE sensory score 0.2, specificity 0.8 Sensitivity of CTCAE motor score 0.7, specificity 1.0 Lavoie Smith, 2013 Descriptive, 65 children TNS-PV, CTCAEv4.0, Responsiveness to change over time: Reflex, with leukemia Balis Pediatric Scale of temperature, and vibration items most Peripheral Neuropathies, responsive (effect size = 0.31-0.66, Tuning fork, FACES P = .006 to <.0001) TNS-PV version A correlation with CTC and Balis scores (r = 0.48-0.52, P = .01) TNS-PV not highly correlated with FACES (r = 0.20, P = .01). Lavoie Smith, 2015 Descriptive, 109 children TNS-PV, CTCAEv4.0, TNS-PV: 78% diagnosed with peripheral with leukemia Modified Balis Pediatric neuropathy Scale of Peripheral FACES: 96% completed tool and 44% Neuropathy, Pediatric reported neuropathy pain Neuropathy Pain Scale, CTCAEv4.0 sensory score: 74% diagnosed Pediatric Neuropathic with Grade 1 to 4 neuropathy Pain scale-5 (PNPS-5), CTCAEv4.0 motor score: 69% diagnosed FACES with Grade 1 to 4 neuropathy Balis Scale scores similar to CTCAEv4.0 scores (continued) Smolik et al. 273

Table 3. (continued)

First Author, Year Study Design, Sample Assessment Tools Results CTCAEv4.0 and TNS-PV scores higher with older children; no differences in race or gender Nelson, 2006 Descriptive, 73 children Neurological exam, nerve 36% abnormal neurological exam (done with type 1 diabetes conduction studies before NCS performed) (NCS), tactile perception NCS 42 participants (57%) had neuropathy, threshold (TPT), of that 26 (62%) had abnormal VPT vibration perception 20 (48%) abnormal neuro exam, 8 (19%) had threshold (VBT) abnormal TPT 19 participants (26%) had abnormal TPT 31 participants (51%) had abnormal VPT Using NCS as gold standard: VPT sensitivity (62%) and specificity (65%) TPT sensitivity (19%) specificity (64%) Abnormal neuro exam sensitivity (48%) and specificity (81%) VPT unreliable in younger patients Holiner, 2013 Descriptive, 39 children Neurological exam Clinical and biochemical characteristics: Of with type 1 diabetes based on Neuropathy 39 patients, 6 (15%) had clinically evident Disability Score (NDS), (NDS or NSS > 3) diabetic peripheral Neuropathy Symptom neuropathy (DPN). Score (NSS), and Neurological findings were evaluated with Neurophysiologic the NSS > 3 implying DPN recordings (NCV studies) Sensitivity and specificity for diagnosis of DPN were 40% and 100%, respectively. Positive and negative predictive values were 100% and 72.7%, respectively Nerve conduction velocity (NCV): 15 (38%) had abnormal NCV Demonstrates it is not possible to diagnose DPN by clinical exam and recording of symptoms Lv, 2015 Prospective cohort, 52 NDS, NSS, CPT At 2000 Hz, 250 Hz and 5 Hz, CPT values in adolescent and young diabetic patients were significantly lower adults with type 1 in bilateral median and sural nerve exams diabetes and 40 age- than healthy patients (P = .001-.009) matched adolescents Among diabetic patients, 67% had and young adults neuropathy symptoms and lower limb peripheral nerves more vulnerable than upper limb peripheral nerves (P ≤.01)

Note. ped-m TNS = pediatric–modified Total Neuropathy Scale; CTCAE = Common Terminology Criteria for Adverse Events; TNS-PV = Total Neuropathy Score–pediatric version. studies, but only 6 of these children had clinical evidence lowest level of vibration and/or tactile stimulation. A total of peripheral neuropathy using neuropathy symptom of 73 children with diabetes were evaluated for peripheral scores or neuropathy disability scores; 9 of the children neuropathy using the perception threshold and found to were asymptomatic (Holiner et al., 2013). While specific- have low sensitivity and specificity of the VPT (62% and ity of peripheral neuropathy using the neurological exam 65%) and the TPT (19% and 64%; Nelson et al., 2006). was high in both studies (81% and 100%), sensitivity or The authors concluded that both VPT and TPT should not probability of detection of peripheral neuropathy using be used as a screening tool for peripheral neuropathy in the neurological exam remained low (48% and 40%) children (Nelson et al., 2006). (Holiner et al., 2013; Nelson et al., 2006). Another perception threshold tool is the CPT, a nonin- Perception threshold is another method to identify vasive measurement of peripheral neuropathy that uses a peripheral neuropathy and evaluates detection of the neurometer to determine at what amplitude the patient 274 Journal of Pediatric Oncology Nursing 35(4) can detect a buzzing or tingling sensation (Lv et al., Findings regarding the relationship between cumu- 2015). A study of 52 patients with diabetes and 40 lative dosing of vincristine and severity of peripheral matched healthy controls found significantly lower CPTs neuropathy have been found to differ between the stud- at 2000, 250, and 5 Hz among the patients with diabetes ies using ped-m TNS and TNS-PV. Lavoie Smith and when compared with healthy controls (P = .001-.009; Lv colleagues 2013 found that cumulative vincristine dose et al., 2015). Thus, CPT appears to provide early detec- was related to worse peripheral neuropathy using the tion of peripheral neuropathy. TNS-PV tool. This is in contrast to Gilchrist and col- leagues 2013, who found no relation between cumula- Appraisal of the Quality of Evidence tive vincristine dose and severity of peripheral neuropathy using the ped-m TNS. Additional research The quality of the peripheral neuropathy assessment tool is necessary to determine whether the cumulative dose evidence is based on 8 research articles. The majority of of vincristine has an impact on severity of CIPN. these studies consisted of descriptive designs. Small sam- Determining if cumulative dosing correlates with wors- ple sizes were of concern related to the methodology of ening peripheral neuropathy will guide timing and fre- the evidence, but no other methodological flaws were quency of assessments and interventions. identified. There were no issues with inconsistency, indi- Because vincristine is a mainstay pediatric chemother- rectness, imprecision, or publication bias. The overall rat- apeutic agent known to cause peripheral neuropathy, it is ing of the quality of the body of evidence is low quality. essential that pediatric oncology health care providers are well versed in the assessment of peripheral neuropathy Recommendations signs and symptoms. Nurses are commonly on the front line of patient care in both inpatient and outpatient set- 1. There is a strong recommendation that all pediat- tings, where children are receiving vincristine and other ric patients receiving vincristine should receive a chemotherapeutic agents that may cause peripheral neu- formal assessment for peripheral neuropathy. ropathy. Nursing assessment of peripheral neuropathy 2. There is a strong recommendation that the ped-m should be integral and standard assessment in patient care TNS or TNS-PV should be used for the assess- throughout the course of treatment. Peripheral neuropa- ment of vincristine-induced peripheral neuropa- thy assessment must go beyond solely asking subjective thy in children ≥6 years old. symptom questions and expand to the use objective mea- 3. There is a strong recommendation against the use sures to evaluate peripheral neuropathy. Underreporting of subjective symptoms alone to assess for periph- of peripheral neuropathy has been found when using sub- eral neuropathy in children receiving vincristine. jective assessment alone, causing some patients with peripheral neuropathy to go undiagnosed (Lavoie Smith Discussion et al., 2013). Detecting peripheral neuropathy early, and effectively addressing signs and symptoms that cause Despite the importance of assessment of peripheral neu- pain, discomfort, and functional decline, has the potential ropathy, a reliable and valid assessment tool specific to to improve health-related quality of life in children under- pediatric patients is not widely used. Through this sys- going cancer treatment. tematic review, the CTCAEv3.0 was found to underre- port peripheral neuropathy, especially in the pediatric Acknowledgments population, and the tool missed most participants who The authors would like to recognize Cory Beebe, MS, in the had some degree of neuropathy (Gilchrist et al., 2014). Musculoskeletal Research Center at Children’s Hospital These findings suggest that the CTCAEv3.0 may not be Colorado for his assistance with the literature search. an appropriate assessment tool for identifying peripheral neuropathy in pediatric patients. Declaration of Conflicting Interests Two assessment tools for peripheral neuropathy— The author(s) declared no potential conflicts of interest with ped-m TNS and TNS-PV—show promise for evaluating respect to the research, authorship, and/or publication of this peripheral neuropathy in children; however, additional article. research is necessary to determine the usability and reli- ability in children younger than 6 years. CPT has also Funding demonstrated promise in identifying peripheral neuropa- The author(s) disclosed receipt of the following financial sup- thy in adolescents and young adults, but further research port for the research, authorship, and/or publication of this arti- is needed to determine if neuropathy can be identified cle: This study was supported by the National Cancer Institute/ with this tool in younger children and in patients receiv- National Clinical Trials Network Group Operations Center ing vincristine. Grant (U10CA180886; Principal Investigator: Adamson). Smolik et al. 275

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Disorders at the Children’s Hospital Colorado, Aurora, Colorado. Kandula, T., Park, S. B., Cohn, R. J., Krishnan, A. V., & Farrer, Kristin Thomas, PT, DPT, is a pediatric physical therapist in M. A. (2016). Pediatric chemotherapy induced peripheral the Center for Cancer and Blood Disorders at the Children’s neuropathy: A systematic review of the current knowledge. Hospital Colorado, Aurora, Colorado. Cancer Treatment Reviews, 50, 118-128. Lavoie Smith, E. M., Li, L., Chiang, C. W., Thomas, K., Cheryl Rodgers, PhD, RN, CPNP, CPON, is an assistant pro- Hitchinson, R. J., Wells, E. M., . . . Renbarger, J. (2015). fessor at Duke University School of Nursing, Durham, North Patterns and severity of vincristine-induced neuropathy in Carolina.