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..

Chemotherapy-induced peripheral neurotoxicity (CIPN) is a major toxicity of cancer treatment, leading to dose reduction and premature treatment cessation, potentially affecting patient function, and quality of life. The development of accurate and sensitive assessment tools for CIPN is essential to enable clinical monitoring during treatment, follow-up of long-term outcomes and measurement of toxicity in clinical trials.This review examines CIPN clinical assessment scales incorporating clinician-based, composite, and patient-reported outcomes (PROs), providing a systematic review of their properties and an updated critical analysis of recommendations on current evidence for their use. This systematic review of CIPN assessment tools identified 50 papers containing 41 assessment tools, across 4 categories (common toxicity criteria; composite neurological scale; PROs; pain scale). The majority of these tools were PROs, underscoring the importance of patient-based assessment of symptoms.While there has been considerable work in the field over the past 10 years, this review highlights significant gaps, including a lack of evaluation of responsiveness and problematic neuropathic pain evaluation. There remains a need for consensus on the best available tool and the need to modify existing instruments to improve utility. K E Y W O R D S assessment, chemotherapy, CIPN, neuropathy, neurotoxicity, outcome measures 1 | INTRODUCTION Chemotherapy-induced peripheral neurotoxicity (CIPN) is a prominent adverse event of cancer treatment, leading to dose reduction and premature treatment cessation, potentially affecting patient function and quality of life. The development of accurate and sensitive assessment tools for CIPN is essential to enable clinical monitoring during treatment, follow-up of long-term outcomes and measurement of toxicity in clinical trials. As with all treatment toxicities, a balanced approach between patient report, objective examination and clinician discretion is warranted. It is likely that tailored assessment strategies will be required to facilitate appropriate assessment in different contexts ranging from routine clinical screening tools to comprehensive multimodal assessments and outcome measures in clinical trials. Assessment tools which do not require specialised equipment are most accessible for routine clinical use. While common toxicity criteria (CTC) are the most commonly utilised assessment tools for a range of cancer treatment toxicities including CIPN, validated patient-reported outcome (PRO) measures provide sensitive assessment of neuropathy symptoms and significance for the patient. Composite neurological assessments containing a combination of symptom report and neurological examination findings provide another method of CIPN evaluation. Given the importance of selecting appropriate outcome measures, including in drug development and for regulatory approval, review of the properties of CIPN assessment tools is warranted.From this search, a total of 50 papers meeting inclusion criteria wer...

The SCH system effectively identified neuropathic symptoms and their severity and, paired with NP follow-up, reduced symptom prevalence, severity, and distress compared to usual care.

Chemotherapy-induced peripheral neuropathy (CIPN) occurs in approximately 68% of patients who receive neurotoxic chemotherapy and lasts at least 6 months post-chemotherapy in approximately 30% of individuals. CIPN is associated with decreased quality of life and functional impairments. Evidence suggests that CIPN symptoms are caused, in part, by enhanced excitability and impaired inhibition in the central nervous system. Transcutaneous electrical nerve stimulation (TENS) decreases pain by counteracting both of these mechanisms and is efficacious in other conditions associated with neuropathic pain. This single-arm study (n = 29) assessed the feasibility of investigating TENS for CIPN after chemotherapy completion using a wireless, home-based TENS device. Eighty-one percent of eligible patients who were approached enrolled, and 85% of participants who received the TENS device completed the primary (6-week) study term. Qualitative interview data suggest that use of the device on the continuous setting that automatically alternates between 1-h stimulation and rest periods for 5 h/day would be acceptable to most participants. Significant (i.e., p < 0.05) improvements were observed with the EORTC-CIPN20 (percent change from baseline: 13%), SF-MPQ-2 (52%), numeric rating scale of pain (38%), tingling (30%), numbness (20%), and cramping (53%), and UENS large fiber sensation subscore (48%). Preliminary data that support the reliability and construct validity of the UENS for CIPN in cancer survivors are also provided. Together these data suggest that it is feasible to evaluate TENS for CIPN using a wireless, home-based device and that further evaluation of TENS for CIPN in a randomized clinical trial is warranted.

Vinca alkaloids, thalidomide, and eribulin are widely used to treat patients with childhood acute lymphoblastic leukemia (ALL), adults affected by multiple myeloma and locally invasive or metastatic breast cancer, respectively. However, soon after their introduction into clinical practice, chemotherapy-induced peripheral neurotoxicity (CIPN) emerged as their main non-hematological and among dose-limiting adverse events. It is generally perceived that vinca alkaloids and the antiangiogenic agent thalidomide are more neurotoxic, compared to eribulin. The exposure to these chemotherapeutic agents is associated with an axonal, length-dependent, sensory polyneuropathy of mild to moderate severity, whereas it is considered that the peripheral nerve damage, unless severe, usually resolves soon after treatment discontinuation. Advanced age, high initial and prolonged dosing, coadministration of other neurotoxic chemotherapeutic agents and pre-existing neuropathy are the common risk factors. Pharmacogenetic biomarkers might be used to define patients at increased susceptibility of CIPN. Currently, there is no established therapy for CIPN prevention or treatment; symptomatic treatment for neuropathic pain and dose reduction or withdrawal in severe cases is considered, at the cost of reduced cancer therapeutic efficacy. This review critically examines the pathogenesis, epidemiology, risk factors (both clinical and pharmacogenetic), clinical phenotype and management of CIPN as a result of exposure to vinca alkaloids, thalidomide and its analogue lenalidomide as also eribulin. K E Y W O R D S assessment, eribulin, peripheral neurotoxicity, thalidomide, vinca alkaloids

Immune checkpoint inhibitor (ICPI) therapy unleashes the body's natural immune system to fight cancer. ICPIs improve overall cancer survival, however, the unbridling of the immune system may induce a variety of immune-related adverse events. Neuromuscular immune complications are rare but they can be severe. Myasthenia gravis and inflammatory neuropathy are the most common neuromuscular adverse events but a variety of others including inflammatory myopathy are reported. The pathophysiologic mechanism of these autoimmune disorders may differ from that of non-ICPI-related immune diseases. Accordingly, while the optimal treatment for ICPI-related neuromuscular disorders generally follows a traditional paradigm, there are important novel considerations in selecting appropriate immunosuppressive therapy. This review presents 2 new cases, a summary of neuromuscular ICPI complications, and an approach to the diagnosis and treatment of these disorders. Muscle Nerve, 2018.