Pediatric chemotherapy induced peripheral neuropathy: A systematic review of current knowledge.
BACKGROUND
The dramatic increase in the number of childhood cancer survivors over the last 60years has made monitoring and minimising long term side effects of cancer treatment increasingly important. Chemotherapy induced peripheral neuropathy (CIPN) has been described with many commonly used chemotherapy agents. This article provides a critical overview of pediatric CIPN, its incidence, clinical manifestations, late effects, and recent advances in understanding of risk factors and pharmacogenomics as well as evaluating current assessment strategies and treatment approaches.


METHODS
Neurotoxicity data was systematically collated from Medline, Embase and Pubmed and analysed for quality, relevance and originality in three stages prior to inclusion. Quality scoring was done using the QUALSYST assessment tool.


RESULTS
A total of 61 studies met inclusion criteria. Peripheral neuropathy is common and may be long lasting with characteristics specific to each chemotherapy agent. There is significant variability in reported incidence and natural history, related to challenges in clinical assessment and diagnosis. Emerging risk factors for CIPN include treatment factors such as dose, duration and concurrent medication and patient factors such as age and inherited susceptibilities. Recent identification of individual genetic variations has advanced understanding of pathomechanisms and may direct future treatment approaches.


CONCLUSIONS
While these studies guide suggestions for current clinical practice, further systematic research with development of strategies for amelioration and prevention of CIPN is necessary. Standardised assessment protocols and objective outcomes measures of CIPN applicable to patients of different ages are critical to enabling the development of novel treatments and facilitation of future clinical trials and treatment individualisation.
Discipline of Pediatrics, School of Women's and Children's Health, UNSW Medicine, The University of New South Wales, Randwick, NSW 2031, Australia; Department of Neurology, Sydney Children's Hospital, Randwick, NSW 2031, Australia.
Tejaswi
T
Kandula
Brain & Mind Centre, University of Sydney, 94-100 Mallett Street, Camperdown, NSW 2050, Australia; Prince of Wales Clinical School, UNSW Medicine, The University of New South Wales, Randwick, NSW 2031, Australia.
Susanna B
SB
Park
Discipline of Pediatrics, School of Women's and Children's Health, UNSW Medicine, The University of New South Wales, Randwick, NSW 2031, Australia; Kids Cancer Centre, Department of Oncology, Sydney Children's Hospital, Randwick, NSW 2031, Australia.
Richard J
RJ
Cohn
Prince of Wales Clinical School, UNSW Medicine, The University of New South Wales, Randwick, NSW 2031, Australia.
Arun V
AV
Krishnan
Discipline of Pediatrics, School of Women's and Children's Health, UNSW Medicine, The University of New South Wales, Randwick, NSW 2031, Australia; Department of Neurology, Sydney Children's Hospital, Randwick, NSW 2031, Australia. Electronic address: m.farrar@unsw.edu.au.
Michelle A
MA
Farrar
D000293:Adolescent; D000367:Age Factors; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects*; D002648:Child; D018450:Disease Progression; D006801:Humans; D015994:Incidence; D009369:Neoplasms / Q000188:drug therapy*; D020258:Neurotoxicity Syndromes / Q000453:epidemiology / Q000209:etiology* / Q000503:physiopathology; D010523:Peripheral Nervous System Diseases / Q000139:chemically induced* / Q000453:epidemiology / Q000503:physiopathology; D012307:Risk Factors
D000970:Antineoplastic Agents
Cancer survivorship; Chemotherapy complication; Chemotherapy induced peripheral neuropathy; Peripheral neuropathy; Systematic review