Genetic counselling legislation and practice in cancer in EU Member States.

BACKGROUND: Somatic and germline genetic alterations are significant drivers of cancer. Increasing integration of new technologies which profile these alterations requires timely, equitable and high-quality genetic counselling to facilitate accurate diagnoses and informed decision-making by patients and their families in preventive and clinical settings. This article aims to provide an overview of genetic counselling legislation and practice across European Union (EU) Member States to serve as a foundation for future European recommendations and action. METHODS: National legislative databases of all 27 Member States were searched using terms relevant to genetic counselling, translated as appropriate. Interviews with relevant experts from each Member State were conducted to validate legislative search results and provide detailed insights into genetic counselling practice in each country. RESULTS: Genetic counselling is included in national legislative documents of 22 of 27 Member States, with substantial variation in legal mechanisms and prescribed details (i.e. the 'who, what, when and where' of counselling). Practice is similarly varied. Workforce capacity (25 of 27 Member States) and genetic literacy (all Member States) were common reported barriers. Recognition and/or better integration of genetic counsellors and updated legislation and were most commonly noted as the 'most important change' which would improve practice. CONCLUSIONS: This review highlights substantial variability in genetic counselling across EU Member States, as well as common barriers notwithstanding this variation. Future recommendations and action should focus on addressing literacy and capacity challenges through legislative, regulatory and/or strategic approaches at EU, national, regional and/or local levels.

Acute Neuromuscular Fatigability and Perceived Exertion in High-Level University Pianists: An Electromyography and Maximum Force Capacity Study.

PURPOSE: Musicians are labelled 'fine motor athletes' due to the significant demands of practice and performance. In response, sports medical concepts and expertise have been adapted and mobilized to address musicians' health considerations. However, understanding distinct differences between the sports and performing arts medical contexts is critical. Mismanagement of fatigue and acute fatigability are identified as key risk factors for deleterious symptoms and injuries in musicians. Acute fatigability in athletes and musicians have been assumed to occur similarly, although this has yet to be empirically demonstrated. This study aimed to evaluate acute muscular performance fatigability during piano performance of varied intensities. METHODS: Fourteen university pianists attended a single experimental session and performed three pieces of randomly ordered repertoire for 10 minutes each. Repertoire were self-selected to be physically easy (rating of perceived exertion [RPE] 9/20), somewhat hard (RPE 13/20), or hard (RPE 17/20). At baseline, after each repertoire performance, and following a concluding 10-minute silent sitting period, participants completed maximum voluntary contraction (MVC) grip and shoulder strength tests. Surface electromyographic (EMG) data were obtained from bilateral upper trapezius and forearm flexor and extensor muscles. Data were analyzed using uni- and multivariate repeated measures analyses of variance (ANOVAs). RESULTS: No evidence of muscular performance fatigability was found in study pianists at any intensity. Mean EMG amplitude and average median EMG frequency did not significantly vary during any repertoire performances or MVC tests (F≤1.72; p>0.09). Additionally, no changes in force or EMG parameters were found during any MVC tests (F≤1.19; p>0.31). CONCLUSIONS: The absence of muscular performance fatigability during even the most intense piano performances suggests substantially differing mechanisms of fatigability and perceived exertion in pianists versus those commonly seen in sport athletes. Further research is needed to understand the mechanisms of acute fatigability in musicians and develop musician-specific management strategies.

Assessing Performing Artists in Medical and Health Practice - The Dancers, Instrumentalists, Vocalists, and Actors Screening Protocol.

ABSTRACT: Training in the performing arts exposes individuals to often extreme physical and psychological demands, which are linked to high occupational injury rates. The intense demands of performing artists have been likened to those of sport athletes. However, distinct differences in these demands necessitate specialized approaches to the health care of performing artists. Through the Athletes and the Arts collaboration, the American College of Sports Medicine and Performing Arts Medicine Association identified that the creation of a specialized preparticipation screening tool for performing artists would likely enhance health care for performing artists significantly. Based on a thorough review of established assessments and an extensive consultation process with domain experts, a consensus best-practice screening tool was developed: the Dancer, Instrumentalist, Vocalist, Actor (DIVA) Preparticipation Screening. This screening tool is modeled on the athletic preparticipation examination (PPE) in its structure and 30-min target duration. However, DIVA diverges considerably from the PPE in its content to address the specific risks and needs of performing artists. In particular, screening questions and physical examination procedures focus strongly on musculoskeletal injuries and mental health conditions, in response to the preponderance and interactions of these conditions appearing in performing artists. The DIVA tool presented is intended as a "living tool," which can be modified in the future to include new effective assessment techniques as appropriate. Training in the DIVA preparticipation physical examination is included as a core component of the essentials of performing arts medicine continuing education course described in detail in a companion manuscript in this issue.

Self-Report Fatigue Management for Instrumental Musicians: A Delphi Survey.

BACKGROUND: Mismanagement of fatigue and playing load have been consistently identified as risk factors for playing-related pain and injuries. Studies in sport demonstrate that fatigue management strategies can predict and prevent overuse syndromes and related injuries through consistent assessment of playing load and physical/psychological stress. Self-report strategies show particular responsiveness to both the short and long-term impacts of training. No equivalent fatigue management strategies exist for musicians. Establish key items and feasibility parameters to inform the development of a self-report fatigue management tool for musicians. METHODS: A working party of international experts in musicians' medicine was invited to complete a two-phase Delphi survey. In Phase I, working party members rated established items from sport (REST-Q subscales with demonstrated responsiveness to both acute and chronic training stresses) with respect to relevance and prospective utility for musicians. Members could also propose additional items and were asked to indicate a maximum feasible questionnaire length. In Phase II, working party members ranked top performing items from Phase I. Consensus best items were determined based on Phase II rankings. RESULTS: A 28-member working party was assembled (15 clinicians, 13 researchers). Of 20 researcher proposed items and 58 working party proposed items, 5 items met consensus criteria: I had pain; I had to play too much; I felt physically fit; I did not get enough sleep; I recovered well physically. A strong majority (89%) of working party members indicated that regular use of a fatigue questionnaire with up to 10 items is feasible. CONCLUSIONS: Key questionnaire items and feasibility parameters for a novel fatigue management tool for musicians are established. Future research in musicians is needed to validate study results and this novel fatigue management tool.

Balance Deficits and Functional Disability in Cancer Survivors Exposed to Neurotoxic Cancer Treatments.

BACKGROUND: Chemotherapy-induced peripheral neuropathy (CIPN) persists after treatment in up to 40% of cancer survivors and has been linked with increased balance deficits, disabilities, and fall occurrences. This study aimed to comprehensively assess the links between CIPN, balance deficits, and functional disability and to inform the development of clinical screening tools for patients at risk of these events. PATIENTS AND METHODS: A total of 190 cancer survivors exposed to neurotoxic chemotherapies (age, 57 ± 13 years; average time from completion of neurotoxic therapy, 12 ± 11 months) attended a neurology research clinic for a single cross-sectional assessment of patient-reported and objective CIPN, standing balance in 4 conditions of increasing difficulty, and functional disability. RESULTS: Most patients (68%) reported CIPN symptoms at assessment. Symptomatic patients displayed increased functional disability (F=39.4; P<.001) and balance deficits (F=34.5; P<.001), with degree of balance impairments consistent with a healthy elderly population (age ≥65 years) reporting multiple falls over the subsequent year. Increasing CIPN severity correlated with increasing functional disability (clinically assessed R2=0.46; patient-reported R2=0.49; P<.001) and balance deficits (clinically assessed R2=0.41; patient-reported R2=0.30; P<.001). A 5-factor model of key independent correlates-patient-reported numbness/tingling, weakness, and balance deficit; age; and vibration perception-was strongly linked to balance deficits (R2=0.46; P<.001) and functional disability (R2=0.56; P<.001). CONCLUSIONS: This study confirms links between increasing CIPN severity and increasing balance deficits and functional disability using comprehensive CIPN assessment methodology. The extent of balance deficits in patients with CIPN underscores the functional consequences of neurotoxicity. A 5-factor model provides a foundation for clinical screening tools to assess balance deficits and functional disability in patients exposed to neurotoxic chemotherapies.

Chemotherapy-induced peripheral neuropathy-patient-reported outcomes compared with NCI-CTCAE grade.

BACKGROUND: Patient-reported outcomes (PRO) are becoming increasingly recognised as essential to comprehensively collect chemotherapy-induced peripheral neuropathy (CIPN) symptom information. MATERIALS AND METHODS: This study aimed to evaluate the utility and feasibility of CIPN PRO assessment tools in a real-world clinical setting through investigation of the correlation of PRO with NCI-CTCAE assessments particularly in relation to cumulative dose of chemotherapy. Patients receiving oxaliplatin or paclitaxel chemotherapy in Sydney, Australia, completed a questionnaire containing standardised CIPN PRO assessments (EORTC CIPN-20, PRO-CTCAE) via tablet device. PRO assessment scores were correlated with NCI-CTCAE grade determined by nursing assessment and analysed with respect to cumulative dose of chemotherapy. RESULTS: There were 87 patients who completed a total of 145 questionnaires, 68 in patients receiving oxaliplatin and 77 in patients receiving paclitaxel. CIPN PRO scores were associated with NCI-CTCAE grade, for EORTC CIPN-20 (r2 = 0.19, p < 0.01) and PRO-CTCAE (r2 = 0.41, p < 0.01), although individual patient correlation was poor. PRO assessments, however, identified higher grade symptoms, in particular symptoms causing functional impairment, at lower doses of cumulative chemotherapy compared to NCI-CTCAE. CONCLUSION: This study demonstrated that CIPN PRO may provide complementary information to nursing assessed NCI-CTCAE grade, particularly in earlier stages of chemotherapy and can be considered an important component in the comprehensive assessment of neuropathy.

Exercise-based rehabilitation for cancer survivors with chemotherapy-induced peripheral neuropathy.

PURPOSE: Chemotherapy-induced peripheral neuropathy (CIPN) affects up to 40% of cancer survivors and is associated with functional deficits and an increased falls incidence. There are presently no strongly recommended treatment strategies for CIPN. The aim of this study was to evaluate the impact of a multimodal exercise intervention on CIPN symptoms and related functional deficits, as well as neurophysiologic parameters. METHODS: All outcomes were assessed before and after an 8-week exercise intervention (3-weekly sessions) and preceding 8-week control period at baseline, pre-exercise and post-exercise. Outcome measures were objective and patient-reported CIPN, standing and dynamic balance, mobility, quality of life, and sensory and motor nerve excitability and conduction studies. RESULTS: Twenty-nine cancer survivors (8 male, 21 female; mean age 61.6 ± 11.8 years) with CIPN symptoms affecting function completed all assessments. Objective and patient-reported CIPN, dynamic balance, standing balance in eyes open conditions, mobility and quality of life were improved from pre- to post-exercise (4.0 < F < 10.2; p < .05), with no changes over the control period (p > .21). No changes were observed in sensory or motor neurophysiologic parameters (p > .23). CONCLUSIONS: This study provides encouraging evidence of the rehabilitative potential of multimodal exercise for persisting CIPN in a post-treatment cohort. Large randomised controlled trials are justified to confirm observed benefits and determine the mechanisms and clinical significance.

Optimal clinical assessment strategies for chemotherapy-induced peripheral neuropathy (CIPN): a systematic review and Delphi survey.

BACKGROUND/PURPOSE: Chemotherapy-induced peripheral neuropathy (CIPN) is a prominent side effect of the treatment of cancer. Despite this frequent complication, there has been no comprehensive review and quality appraisal of CIPN assessments. The purpose of this study is to provide a definitive quality appraisal of CIPN assessment strategies for clinical use. METHODS: Relevant studies were identified through database searches of Medline, Embase, CINAHL, and Cochrane. CIPN assessment strategies from included articles were extracted and initially rated by an oncologist and neurophysiologist according to criteria related to assessment depth, comprehensiveness, appropriateness, and reliability. The six highest scoring assessment strategies were the focus of a two-round Delphi survey of a working party of 32 physicians, nurses, and consumers to achieve consensus on the highest rated assessments for each criterion. RESULTS: The database search yielded 117 distinct CIPN assessments that were extracted from 2373 articles. Three patient-reported outcome surveys and three clinician-based assessments were included in the Delphi survey. No consensus was generated regarding the best overall CIPN assessment, although good (≥70%) consensus was achieved regarding the best assessment within each criterion. The Participant Neurotoxicity Questionnaire (PNQ) was rated the highest overall and patient-reported outcome (PRO) assessment, while the Total Neuropathy Score clinical version (TNSc) was the highest rated clinician-based assessment. CONCLUSIONS: A diverse range of CIPN assessments currently exists. While several assessments assess CIPN symptoms with adequate comprehensiveness, depth, language, and feasibility, the consensus 'gold standard' clinical assessment remains to be established.

An Intensive Continuing Education Course to Enhance Care of the Performing Arts Athlete: The "Essentials of Performing Arts Medicine".

High occupational injury rates have been reported in performing artists, yet the quality of preventive and clinical care remains highly variable. Through the Athletes and the Arts collaboration, The Performing Arts Medicine Association, and the American College of Sports Medicine identified that health care practitioners' existing expertise should be enhanced to address the complex psychophysical needs of performing artists. In response, a 2-d continuing education course, "The Essentials of Performing Arts Medicine" (EOPAM), was developed and has been delivered at least annually since 2016. This course has been well-received by 149 physicians and 240 allied health professionals to date (average ratings, ≥3.5/5 from 2018 to present), with course quality significantly improved by a transition to online delivery in 2020 (average ratings ≥4.5/5; P < 0.01). Accordingly, EOPAM demonstrates that a brief continuing education course can enhance health professionals' understanding of the unique needs and demands of performing artists, addressing a key barrier to improved care.

A systematic review of the effects of upper body warm-up on performance and injury.

PURPOSE: This systematic review was conducted to identify the impact of upper body warm-up on performance and injury prevention outcomes. METHODS: Web of Science, MEDLINE, SPORTDiscus, PsycINFO and Cochrane databases were searched using terms related to upper extremity warm-up. Inclusion criteria were English language randomised controlled trials from peer-reviewed journals in which investigation of upper body warm-up on performance and injury prevention outcomes was a primary aim. Included studies were assessed for methodological quality using the PEDro scale. A wide variety of warm-up modes and outcomes precluded meta-analysis except for one group of studies. The majority of warm-ups were assessed as having 'positive', 'neutral', 'negative' or 'specific' effects on outcomes. RESULTS: Thirty-one studies met the inclusion criteria with 21 rated as having 'good' methodological quality. The studies investigated a total of 25 warm-up modes and 43 outcome factors that could be grouped into eight mode and performance outcome categories. No studies of upper body warm-up effects on injury prevention were discovered. CONCLUSIONS: Strong research-based evidence was found for the following: high-load dynamic warm-ups enhance power and strength performance; warm-up swings with a standard weight baseball bat are most effective for enhancing bat speed; short-duration static stretching warm-up has no effect on power outcomes; and passive heating/cooling is a largely ineffective warm-up mode. A clear knowledge gap in upper body warm-up literature is the lack of investigation of injury prevention outcomes.

An artificial intelligence-assisted clinical framework to facilitate diagnostics and translational discovery in hematologic neoplasia.

BACKGROUND: The increasing volume and intricacy of sequencing data, along with other clinical and diagnostic data, like drug responses and measurable residual disease, creates challenges for efficient clinical comprehension and interpretation. Using paediatric B-cell precursor acute lymphoblastic leukaemia (BCP-ALL) as a use case, we present an artificial intelligence (AI)-assisted clinical framework clinALL that integrates genomic and clinical data into a user-friendly interface to support routine diagnostics and reveal translational insights for hematologic neoplasia. METHODS: We performed targeted RNA sequencing in 1365 cases with haematological neoplasms, primarily paediatric B-cell precursor acute lymphoblastic leukaemia (BCP-ALL) from the AIEOP-BFM ALL study. We carried out fluorescence in situ hybridization (FISH), karyotyping and arrayCGH as part of the routine diagnostics. The analysis results of these assays as well as additional clinical information were integrated into an interactive web interface using Bokeh, where the main graph is based on Uniform Manifold Approximation and Projection (UMAP) analysis of the gene expression data. At the backend of the clinALL, we built both shallow machine learning models and a deep neural network using Scikit-learn and PyTorch respectively. FINDINGS: By applying clinALL, 78% of undetermined patients under the current diagnostic protocol were stratified, and ambiguous cases were investigated. Translational insights were discovered, including IKZF1plus status dependent subpopulations of BCR::ABL1 positive patients, and a subpopulation within ETV6::RUNX1 positive patients that has a high relapse frequency. Our best machine learning models, LDA and PASNET-like neural network models, achieve F1 scores above 97% in predicting patients' subgroups. INTERPRETATION: An AI-assisted clinical framework that integrates both genomic and clinical data can take full advantage of the available data, improve point-of-care decision-making and reveal clinically relevant insights promptly. Such a lightweight and easily transferable framework works for both whole transcriptome data as well as the cost-effective targeted RNA-seq, enabling efficient and equitable delivery of personalized medicine in small clinics in developing countries. FUNDING: German Ministry of Education and Research (BMBF), German Research Foundation (DFG) and Foundation for Polish Science.

Rhythm in sport: Adapted rhythmic training to optimize timing and enhance performance in athletes.

Precise timing, the ability to control exactly when something should be done, integrates physical characteristics like strength, power, and technique into highly skilled sporting actions. Despite timing's indispensability to peak athletic performance, there exist few timing-specific training methods. The authors present a new training approach which adapts exercises from drummers, the elite timing experts, to athletes. This progressive series of rhythmic exercises cultivates a detailed, 'top down' cognitive framework of time which promises to enhance movement precision and efficiency. Use cases demonstrate broad applications of this new training approach across individual and team sports.

Association of Music Interventions With Health-Related Quality of Life: A Systematic Review and Meta-analysis.

Importance: Increasing evidence supports the ability of music to broadly promote well-being and health-related quality of life (HRQOL). However, the magnitude of music's positive association with HRQOL is still unclear, particularly relative to established interventions, limiting inclusion of music interventions in health policy and care. Objective: To synthesize results of studies investigating outcomes of music interventions in terms of HRQOL, as assessed by the 36- and 12-Item Health Survey Short Forms (SF-36 and SF-12). Data Sources: MEDLINE, Embase, Web of Science, PsycINFO, ClinicalTrials.gov, and International Clinical Trials Registry Platform (searched July 30, 2021, with no restrictions). Study Selection: Inclusion criteria were randomized and single-group studies of music interventions reporting SF-36 data at time points before and after the intervention. Observational studies were excluded. Studies were reviewed independently by 2 authors. Data Extraction and Synthesis: Data were independently extracted and appraised using GRADE criteria (Grading of Recommendations, Assessment, Development, and Evaluations) by multiple authors. Inverse-variance random-effects meta-analyses quantified changes in SF-36 mental and physical component summary (respectively, MCS and PCS) scores from preintervention to postintervention and vs common control groups. Main Outcomes and Measures: SF-36 or SF-12 MCS and PCS scores, defined a priori. Results: Analyses included 779 participants from 26 studies (mean [SD] age, 60 [11] years). Music interventions (music listening, 10 studies; music therapy, 7 studies; singing, 8 studies; gospel music, 1 study) were associated with significant improvements in MCS scores (total mean difference, 2.95 points; 95% CI, 1.39-4.51 points; P < .001) and PCS scores (total mean difference, 1.09 points; 95% CI, 0.15-2.03 points; P = .02). In subgroup analysis (8 studies), the addition of music to standard treatment for a range of conditions was associated with significant improvements in MCS scores vs standard treatment alone (mean difference, 3.72 points; 95% CI, 0.40-7.05 points; P = .03). Effect sizes did not vary between music intervention types or doses; no evidence of small study or publication biases was present in any analysis. Mean difference in MCS scores met SF-36 minimum important difference thresholds (mean difference 3 or greater). Conclusions and Relevance: In this systematic review and meta-analysis, music interventions were associated with clinically meaningful improvements in HRQOL; however, substantial individual variation in intervention outcomes precluded conclusions regarding optimal music interventions and doses for distinct clinical and public health scenarios.

Load and fatigue monitoring in musicians using an online app: A pilot study.

Background/aims: High occupational injury rates are reported in musicians, with a career prevalence of up to 89%. Fatigue and playing (over)load are identified as key risk factors for musicians' injuries. Self-report fatigue management strategies in sport have demonstrated preventive effects. A self-report fatigue management tool for musicians was developed based on a Delphi survey of international experts and hosted in an online app. The aims of this study are to evaluate the content validity and uptake of this new tool, and explore associations between collected performance quality, physical/psychological stress, pain, injury and fatigue data. Methods: University and professional musicians were asked to provide entries into the online app twice per week for 1-6 months. Entries into the app were designed to take 2-3 min to complete and consisted of the following: 6 questions regarding playing load over the previous 72 h; 5 questions regarding current levels in key physical/psychological stress domains (sleep, recovery, overplaying, pain, fitness); one question self-rating of performance quality over the previous day; one question regarding current musculoskeletal symptoms; a reaction time task to evaluate psychomotor fatigue. Results: N = 96 participants provided an average of 2 app entries (range 0-43). Increased playing time, rating of perceived exertion (RPE), and feelings of having to "play too much" were consistently associated with increased self-rated performance quality (p ≤ 0.004; 6.7 <| t |< 2148.5). Increased ratings of feeling fit and recovering well were consistently associated with reduced pain severity (p < 0.001; 3.8 <| t |< 20.4). Pain severity was increased (6.5/10 vs. 2.5/10; p < 0.001) in participants reporting playing-related musculoskeletal disorders (PRMDs; symptoms affecting playing). Conclusion: The prospective value of regular individual self-report playing load, stress, and performance data collection in musicians is clear. However, limited uptake of the online fatigue management app piloted in this study indicates that new approaches to the collection of these data are needed to realize their potential impact.

Mechanisms of Music Impact: Autonomic Tone and the Physical Activity Roadmap to Advancing Understanding and Evidence-Based Policy.

Research demonstrates that both music-making and music listening have an ability to modulate autonomic nervous system activity. The majority of studies have highlighted acute autonomic changes occurring during or immediately following a single session of music engagement. Several studies also suggest that repeated music-making and listening may have longer-term effects on autonomic tone-the prevailing balance of sympathetic vs. parasympathetic activity. Autonomic imbalance is associated with a range of neurodegenerative and neurodevelopmental disorders, mental health conditions and non-communicable diseases. Established behavioral interventions capable of restoring healthy autonomic tone (e.g., physical activity; smoking cessation) have demonstrated remarkable efficacy in broadly promoting health and preventing disease and up to 7.2 million annual deaths. Accordingly, this article proposes that music's suggested ability to modulate autonomic tone may be a key central mechanism underpinning the broad health benefits of music-making and listening reported in several recent reviews. Further, this article highlights how physical activity research provides a relevant roadmap to efficiently advancing understanding of music's effects on both autonomic tone and health more broadly, as well as translating this understanding into evidence-based policy and prescriptions. In particular, adapting FITT-Frequency, Intensity, Timing, Type-criteria to evaluate and prescribe music-making and listening in observational and intervention studies has excellent prospective utility.

Performing arts as a health resource? An umbrella review of the health impacts of music and dance participation.

An increasing body of evidence notes the health benefits of arts engagement and participation. However, specific health effects and optimal modes and 'doses' of arts participation remain unclear, limiting evidence-based recommendations and prescriptions. The performing arts are the most popular form of arts participation, presenting substantial scope for established interest to be leveraged into positive health outcomes. Results of a three-component umbrella review (PROSPERO ID #: CRD42020191991) of relevant systematic reviews (33), epidemiologic studies (9) and descriptive studies (87) demonstrate that performing arts participation is broadly health promoting activity. Beneficial effects of performing arts participation were reported in healthy (non-clinical) children, adolescents, adults, and older adults across 17 health domains (9 supported by moderate-high quality evidence (GRADE criteria)). Positive health effects were associated with as little as 30 (acute effects) to 60 minutes (sustained weekly participation) of performing arts participation, with drumming and both expressive (ballroom, social) and exercise-based (aerobic dance, Zumba) modes of dance linked to the broadest health benefits. Links between specific health effects and performing arts modes/doses remain unclear and specific conclusions are limited by a still young and disparate evidence base. Further research is necessary, with this umbrella review providing a critical knowledge foundation.

Mobility in survivors with chemotherapy-induced peripheral neuropathy and utility of the 6-min walk test.

BACKGROUND: Chemotherapy-induced peripheral neuropathy (CIPN) is a significant and often lasting side effect of cancer treatment, with increasing CIPN severity associated with increasing deficits in balance, gait, and mobility. The 6-min walk test (6MWT) is a widely validated and utilized measure of general physical functioning and mobility, although its utility in a CIPN context is unclear. This study aimed to determine the utility of the 6MWT as an assessment of mobility deficits in a CIPN cohort and utilize the 6MWT to compare mobility data from CIPN patients to those of healthy and clinical populations. METHODS: Cancer survivors exposed to neurotoxic chemotherapies (N = 100; mean 17 ± 13 months post-treatment; mean age 59 ± 13 years) completed a single cross-sectional assessment of patient-reported and objective CIPN, mobility (6MWT), and disability. RESULTS: CIPN symptoms were reported in the majority of the cohort (87%). Increasing age, patient-reported and objective CIPN symptoms, and disability were associated with decreasing 6MWT distance (.48 ≤ R ≤ .63; p < .001) in bivariate models. Multiple regression models of 6MWT distance included age, sex, and patient-reported or objective CIPN severity as significant independent correlates (.62 ≤ R ≤ .64; p < .03). 6MWT distances in patients with CIPN symptom severity above the cohort mean were consistent with mean values reported in diabetic neuropathy and clinical populations. CONCLUSIONS: Increased CIPN symptoms are associated with increased mobility deficits. The 6MWT demonstrates promising utility as a mobility assessment in a CIPN cohort. IMPLICATIONS FOR CANCER SURVIVORS: The impact of the progression of CIPN on mobility deficits in survivors emphasizes the need for effective interventions to treat and prevent CIPN.

Optimizing Clinical Screening for Chemotherapy-Induced Peripheral Neuropathy.

CONTEXT: Efficient and accurate clinical screening for treatment-related toxicities is a critical component of optimal patient management. A number of alternate screening tools for chemotherapy-induced peripheral neuropathy (CIPN) have been proposed in response to demonstrated limitations with standard clinical screening, although their relative diagnostic value is unclear. OBJECTIVES: The aim of this study is to evaluate the relative construct validity and discriminant properties of available CIPN screening tools. METHODS: Patients treated with known potentially neurotoxic therapies underwent CIPN evaluation at one or multiple timepoints (N = 316 patients; age = 56 ± 13 years). At each testing session (N = 644 testing sessions), patients were evaluated using screening tools and comprehensive CIPN assessments. Comprehensive assessments were clinician-rated (Total Neuropathy Score, reduced) or patient-reported outcome (PRO; Functional Assessment of Cancer Therapy-Gynecologic Oncology Group/Neurotoxicity questionnaire). Similarly, screening tools were clinician-rated (National Cancer Institute Common Terminology Criteria for Adverse Events [NCI-CTCAE]) or PRO (Patient Neurotoxicity Questionnaire, PRO-CTCAE). RESULTS: Analyses revealed moderate-to-high correlations between screening tools and comprehensive assessments (0.55 ≤ rho ≤ 0.75; P < 0.001) and similar discriminant properties across screening tools (P > 0.01). Screening tool grading corresponding to clinically significant (grade 2/3) vs. low-grade (grade 0/1) CIPN would correspond to greater ratings of CIPN severity by more comprehensive assessments in a predicted 77%-91% of cases (c-statistic = 0.77-0.91; P < 0.01). CONCLUSIONS: PRO screening tools provide adequate CIPN screening while avoiding potential biases demonstrated to limit currently used clinician-rated screening tools. Addition of a brief objective test did not add value to PRO screening. Up to 23% of patients would be misidentified through screening, providing quantitative evidence of the limitations of available screening tools. More extensive CIPN evaluations are critical in patients at risk of serious neurotoxicity.