Study of Radiation-Induced Peripheral Neuropathy of Cancer Survivors

Abstract

Cancer remains a critical global health challenge, accounting for nearly 10 million deaths in 2020, with approximately 1.5 million in Bangladesh alone. While radiation therapy is a cornerstone of cancer treatment, it often leads to complications like radiation-induced peripheral neuropathy (RIPN), including specific conditions such as radiation-induced brachial plexopathy (RIBP) and lumbosacral plexopathy (RILSP). Electrophysiological tests—namely nerve conduction velocity (NCV) and electromyography (EMG)—are essential for evaluating these conditions. In Bangladesh, limited research and awareness of RIPN pose challenges to accurate diagnosis and effective management, affecting the quality of life for many survivors. This study seeks to compare nerve conduction parameters between irradiated cancer survivors and matched controls at a premium hospital in Bangladesh, utilizing statistical analysis to deepen understanding of the incidence of RIPN in Bangladesh which may lead to increased awareness among radiotherapy providers for taking up steps towards improved cancer care. Particularly, this study explores motor nerve conduction in patients who received spinal radiation, focusing on the Median and Ulnar nerves of the Brachial Plexus and the Tibial and Common Peroneal nerves of the Lumbosacral Plexus. Experimental participants were selected based on criteria such as confirmed cancer diagnosis and a WHO performance status of up to 2, with exclusions for pregnant women, those with metastatic disease, and individuals with a history of diabetic neuropathy. Due to time constraints, sensory nerve conduction was not included, and data were collected from patients who had undergone treatment between two months to 30 months prior to the measurements. Control data were retrospectively sourced from individuals with no history of cancer or radiotherapy. Primary measurements included Nerve Conduction Velocity (NCV), Response Amplitude (AMP), and Area Under the Curve (AUC), averaged bilaterally and grouped by 10-year age intervals. EMG/EP equipment with supramaximal stimulation was used for accurate measurements across the above mentioned four nerves. One tailed test model was used for all the nerve conduction parameters as these are normal if above a certain respective critical value. v For the first analysis, Mann-Whitney U-test was used to assess if there are significant differences between the experimental and control groups, as this appeared to be more appropriate in view of non-Gaussian distribution of the experimental data. However, t-tests were also performed in order to assess whether this more popular test may provide useful assessment of neuropathy, the outcomes compared with that obtained using MWU tests. Then the control data, which were assumed to be normally distributed, were used to obtain critical values to identify individual cases of potential neuropathy using which an evaluation of the incidence of RIPN were obtained for each nerve conduction parameter tested, for each age group. Mann Whitney U test results showed that except for Common Peroneal nerve for the age groups of 51-60 and 61-70, the null hypothesis was rejected for all other nerves tested for all the three age groups. These results suggest that there exist significant differences in the nerve conduction parameters tested between the experimental and the control groups. These tables also indicate how a combination of the three nerve conduction parameters, NCV, AMP, and AUC, used in this study gives a higher incidence of neuropathy than could have been obtained using a single parameter, such as NCV, which has been performed by most the researchers around the globe. This may have been the reason for obtaining low incidences of RIPN by different research groups. Of course, diagnosis, treatment planning and application of radiotherapy, all may have contributions which need to be highlighted. Again, t-tests in comparison to MWU test (which we considered as the gold standard) with regards to acceptance or rejection of the null hypothesis, the overall agreement was about 77.8%, which is a good value and speaks of the robustness of the t-test even in cases where the experimental group may not have a Gaussian distribution. Considering the whole age group of 41-70 years combined, the incidences of neuropathy in the experimental groups were obtained as 69.8% for RIBP and 48.5% for RILSP. The corresponding figures were, 78.3% and 81.8% for age group 41-50, 84.6% and 66.7% for age group 51-60, and 47.1% and 18.8% for age group 61-70, which seems to indicate that the values got lowered mainly due to the oldest age group. It may be that even control subjects of this age vi group had neuropathy due to other factors which lowered the critical values, which then possibly contributed to the lower incidence of neuropathy in the experimental group. This work appears to set an example of a thorough study on nerve conduction measurements in irradiated cancer survivors in order to assess RIPN which may have significant contribution in the future for improved awareness and improved treatment planning in Bangladesh and in other countries, specially the LMICs. vii