Survivors of Childhood Extracranial Malignancy Who Received Chemotherapy Are Likely to Have Long-Term Neurological Toxicity

Assessing the presence and extent of neurotoxicity is an important element of screening in long-term cancer survivors

Long-term peripheral neuropathy commonly is present in cancer survivors who underwent chemotherapy at a young age with diverse chemotherapy agents for extracranial malignancies, according to a recent article appearing in the JAMA Neurology. 

Tejaswi Kandula, School of Women’s and Children’s Health, University of New South Wales Medicine, University of New South Wales Sydney, in New South Wales, Australia and an Australian team investigated the long-term functional effect of chemotherapy in survivors of childhood cancer. 

They conducted a cross-sectional study to assess the extent of chemotherapy-induced peripheral neuropathy in childhood cancer survivors, to define the disease burden, the long-term functional effect of chemotherapy, and to inform screening recommendations. 

The study enrolled 169 cancer survivors who had received chemotherapy for extracranial malignancy prior to the age of 17 years. They were enrolled consecutively from April 2015 to December 2016 in a tertiary hospital-based comprehensive cancer survivorship clinic. The investigators were blinded to the type of chemotherapy that had been administered. 

Of the registered patients, 48 (28.4%) individuals were unable to be contacted or declined participation. The remaining 121 subjects were compared with healthy age-matched controls by a clinical peripheral neurological assessment using the Total Neuropathy Score and the associations with neurophysiological, functional, and patient reported outcome measures were determined. The Total Neuropathy Score is a composite measurement tool that is used to assess chemotherapy-induced peripheral neuropathy. 

Just over half, 65 (53.7%) of the childhood cancer survivors were male, and the median age of the subjects at the time of the neurotoxicity assessments was 16 (range, 7 to 47) years. The assessments were performed at a median 8.5 (range, 1.5 to 29) years after completion of treatment. 

Long-term deficits in clinical, electrophysiological, and functional measures of peripheral neuropathy were common in survivors of childhood cancer who had received chemotherapy 

The Total Neuropathy Score evaluation revealed that clinical abnormalities in manual dexterity, distal sensation, and balance that were consistent with peripheral neuropathy were present in 53 of 100 participants (53.0%) who had been treated with neurotoxic chemotherapy. 

The functional deficits in the subjects were reflected in the patient reported outcomes. 

An association was determined between the Total Neuropathy Score and the patient reported outcomes describing a reduction in global quality of life and physical functioning. 

Cisplatin resulted in a greater neurotoxicity profile than vinca alkaloids 

Long-term neurotoxicity was more likely to result following the use of cisplatin than vinca alkaloids. Increased scores more often observed when cisplatin had been used, which yielded a score increase of 2.1 (95% CI 1.4, 2.9; p < 0.001) points. 

This score increase was associated with lower limb predominant sensory axonal neuropathy, which was demonstrated by a mean amplitude reduction of 5.8 μV (95% CI 2.8, 8.8; p < 0.001). 

Conclusions 

This study found that persisting, long-term clinical neurological abnormalities attributable to peripheral neuropathy were common in childhood cancer survivors, which were reflected in patient reported outcomes. 

The authors concluded that making a targeted clinical neurological assessment is important in screening survivors for long-term neuropathy, as well as having information on the type of neurotoxic agent that was used. 

Based on these findings, the authors called for further development of peripheral neuropathy specific paediatric assessment tools to implement research into neuroprotective strategies and for ways to aid rehabilitation of long-term cancer survivors with chemotherapy induced neuropathy. 

Based on excellent long-term survival of childhood cancer patients, the investigators advise that it is imperative to screen for factors affecting health, function, and quality of life in long-term survivors. 

Regarding the use of neurotoxic chemotherapy, the type of neurotoxic agent used can have different long-term effects. A targeted clinical neurological assessment is an important consideration when screening childhood cancer survivors for long-term neuropathy.  

Disclosure 

No external funding was disclosed. 

Reference 

Kandula T, Farrar MA, Cohn RJ, et al. Chemotherapy-Induced Peripheral Neuropathy in Long-term Survivors of Childhood Cancer: Clinical, Neurophysiological, Functional, and Patient-Reported Outcomes. JAMA Neurology. Published online May 14, 2018. doi:10.1001/jamaneurol.2018.0963