Researchers have developed a novel tool that may help to predict the risk of experiencing peripheral neuropathy following treatment with taxanes in patients with breast cancer, according to a recent study published by Engvall et al in npj Precision Oncology. The findings may aid physicians in adapting treatments to avoid persistent side effects in those at risk.
Background
An increasing number of cancer survivors continue to live with the side effects of cancer therapy. For instance, many women treated for breast cancer with taxanes often experience side effects in the nervous system.
“Side effects in the form of nerve damage are very common after treatment with taxanes for breast cancer, and they often persist for several years. For those affected, it is extremely stressful, and it has a major impact on quality of life. So, it is a major clinical problem, which has received more attention in recent years, but there has been no way to know which [patients] are at greatest risk of side effects,” stressed lead study author Kristina Engvall, PhD, a physician at the oncology clinic at Ryhov County Hospital in Jönköping.
Study Methods and Results
In this study, the researchers asked 337 patients with breast cancer to describe their side effects—including the severity of peripheral neuropathy—following treatment with the taxanes docetaxel or paclitaxel. They noted that between 2 and 6 years had passed since treatment.
The most common side effect was found to be cramping in the feet, experienced by more than 25% of patients who participated in the study. Other side effects included difficulty opening a jar, numbness or tingling in the feet, and difficulty climbing stairs.
The researchers then sequenced the patients’ genes and then built two models linking their genetic characteristics to various taxane-related side effects. This type of prediction model allowed the researchers to predict the risk of peripheral neuropathy and had not previously existed for this side effect. The researchers highlighted that they were able to successfully model the risk of persistent numbness and tingling in the feet.
The two models were capable of separating patients into two clinically relevant groups: those with a high risk of persistent side effects and a group that corresponded to the frequency of peripheral neuropathy in the normal population. The researchers used two-thirds of the data to train the models through machine learning. They then used the remaining one-third of the patients to validate the models—which was found to be effective.
Conclusions
In the long term, the prediction model could be adopted as routine in health-care settings. However, the researchers indicated that validating the effectiveness of the models in different patient groups may be a critical step to improving risk prediction for peripheral neuropathy in this patient population.
“It also emerged that three of the five symptoms we focused on are so biologically complex that we could not model them. They include, for example, difficulty opening cans. Opening a can involves both motor and sensory nerves, which makes it very difficult to predict which [patients] are at greatest risk of developing that symptom,” underscored senior study author Henrik Gréen, MSc, PhD, Professor at Linköping University. “This is the first time a prediction model has been developed that can predict the risk of [peripheral neuropathy] from taxane treatment. Women who have been treated with taxanes after breast cancer surgery make up a very large group in health care worldwide, so this is a major and clinically relevant problem,” he added.
“This can be a tool to individualize treatment, and not only to look at the benefits, but also to look at the risks for the individual patient. Today, we are so good at treating breast cancer that we need to focus more on the risk of complications and side effects that affect the patient long after treatment,” Dr. Engvall concluded.
Disclosure: The research in this study was funded in part by the Swedish Cancer Society, ALF funding, the Medical Research Council of Southeast Sweden, and Futurum in Region Jönköping. For full disclosures of the study authors, visit nature.com.
