Importance Chemotherapy induced peripheral neuropathy is a common side effect of neurotoxic chemotherapy resulting in pain, sensory loss and decreased quality of life. Few studies have prospectively examined the relationship between sensory neuropathy symptoms, falls and fall related injuries in those receiving neurotoxic chemotherapy. Objective Determine the association between the symptoms of chemotherapy induced peripheral neuropathy (CIPN) and fall risk in those receiving neurotoxic chemotherapy. Design Patients starting neurotoxic chemotherapy with a taxane or platinum called a novel automated phone system daily for one full course of chemotherapy. The phone system, “Symptom Care @ Home” utilized a series of relevant CIPN questions to track symptoms on a 0–10 ordinal scale and contained a questionnaire about falls. Those reporting a numbness and tingling severity of 3 or greater for at least 10 days were considered to have significant CIPN symptoms and were compared to those who did not. Setting Ambulatory participants at an academic cancer center. Participants A consecutive sample of breast, ovarian and lung cancer patients beginning neurotoxic chemotherapy was recruited from oncology clinics. The study population was largely female (94%) and Caucasian (96%). Exposures Chemotherapy with a neurotoxic taxane or platinum agent. Main Outcome Measure Patient reported fall events (falls or near falls) and fall related injuries. The hypothesis was generated after data collection but prior to data analysis. Results 32/116 patients met the predetermined criteria for CIPN symptoms. The mean duration of follow up was 62 days with 51 calls completed per participant. 74 fall events were reported. Those with CIPN symptoms were nearly 3 times more likely to have a fall event than those without (HR 2.67, CI 1.62–4.41, p<0.001). The CIPN group was more likely to obtain medical care for falls (25.0% vs. 7.1%, p=0.013). Conclusions and Relevance These findings suggest the sensory symptoms of CIPN are an indicator of increased fall risk and health care utilization. This study demonstrates the utility of a novel phone based system to track neuropathy symptoms. Careful monitoring and coaching of patients receiving neurotoxic chemotherapy for new sensory symptoms may facilitate more effective fall prevention strategies.

Expanding the US Food and Drug Administration–approved indications for immune checkpoint inhibitors in patients with cancer has resulted in therapeutic success and immune-related adverse events (irAEs). Neurologic irAEs (irAE-Ns) have an incidence of 1%–12% and a high fatality rate relative to other irAEs. Lack of standardized disease definitions and accurate phenotyping leads to syndrome misclassification and impedes development of evidence-based treatments and translational research. The objective of this study was to develop consensus guidance for an approach to irAE-Ns including disease definitions and severity grading. A working group of four neurologists drafted irAE-N consensus guidance and definitions, which were reviewed by the multidisciplinary Neuro irAE Disease Definition Panel including oncologists and irAE experts. A modified Delphi consensus process was used, with two rounds of anonymous ratings by panelists and two meetings to discuss areas of controversy. Panelists rated content for usability, appropriateness and accuracy on 9-point scales in electronic surveys and provided free text comments. Aggregated survey responses were incorporated into revised definitions. Consensus was based on numeric ratings using the RAND/University of California Los Angeles (UCLA) Appropriateness Method with prespecified definitions. 27 panelists from 15 academic medical centers voted on a total of 53 rating scales (6 general guidance, 24 central and 18 peripheral nervous system disease definition components, 3 severity criteria and 2 clinical trial adjudication statements); of these, 77% (41/53) received first round consensus. After revisions, all items received second round consensus. Consensus definitions were achieved for seven core disorders: irMeningitis, irEncephalitis, irDemyelinating disease, irVasculitis, irNeuropathy, irNeuromuscular junction disorders and irMyopathy. For each disorder, six descriptors of diagnostic components are used: disease subtype, diagnostic certainty, severity, autoantibody association, exacerbation of pre-existing disease or de novo presentation, and presence or absence of concurrent irAE(s). These disease definitions standardize irAE-N classification. Diagnostic certainty is not always directly linked to certainty to treat as an irAE-N (ie, one might treat events in the probable or possible category). Given consensus on accuracy and usability from a representative panel group, we anticipate that the definitions will be used broadly across clinical and research settings.

Objective:To present standardized diagnostic criteria for idiopathic distal sensory polyneuropathy (iDSP) and its subtypes: idiopathic mixed fiber sensory neuropathy (iMFN), idiopathic small fiber sensory neuropathy (iSFN), and idiopathic large fiber sensory neuropathy (iLFN) for use in research.Methods:The Analgesic, Anesthetic, and Addiction Clinical Trial Translations, Innovations, Opportunities and Networks (ACTTION) public-private partnership with the Food and Drug Administration convened a meeting to develop consensus diagnostic criteria for iMFN, iSFN, and iLFN. After background presentations, a collaborative, iterative approach was used to develop expert consensus for new criteria.Results:An iDSP diagnosis requires at least one small fiber (SF) or large fiber (LF) symptom, at least one SF or LF sign, abnormalities in sensory nerve conduction studies (NCS) or distal intra-epidermal nerve fiber density (IENFD), and exclusion of known etiologies. An iMFN diagnosis requires that at least one of the above clinical features is SF and one clinical feature is LF. Diagnostic criteria for iSFN require at least one SF symptom and at least one SF sign with abnormal IENFD, normal sensory NCS, and the absence of LF symptoms and signs. Diagnostic criteria for iLFN require at least one LF symptom and at least one LF sign with normal IENFD, abnormal NCS, and absence of SF symptoms and signs.Conclusions:Adoption of these standardized diagnostic criteria will advance research and clinical trials and spur development of novel therapies for iDSPs..