Assessment of Pediatric Chemotherapy-Induced Peripheral Neuropathy Using a New Patient-Reported Outcome Measure: The P-CIN.

Background: Chemotherapy-induced peripheral neuropathy (CIPN) is commonly experienced by children receiving neurotoxic chemotherapy. No validated pediatric CIPN patient-reported outcome (PRO) measures exist. Purpose: To test sensitivity, internal consistency reliability, content and convergent validity, and feasibility of the Pediatric Chemotherapy-Induced Neuropathy (P-CIN), an electronic PRO measure for assessing CIPN in children who received neurotoxic chemotherapy. Method: Five experts evaluated content validity of the 14-item P-CIN. Children 5 to 17 years old with CIPN (N = 79) completed the P-CIN via tablet computer; a subset (n = 26) also underwent neurological examinations using the Pediatric-Modified Total Neuropathy Score. Following preliminary analyses, one item was deleted and three others modified. The revised P-CIN was retested with patients (n = 6) who also completed the Bruininks-Oseretsky Test of Motor Proficiency motor function assessment. Means, item response ranges, standard deviations, content validity indexes, Cronbach's alphas, and correlation coefficients were calculated. Results: Mean participant age was 11.25 (SD = 4.0) years. Most had acute leukemia (62.5%) and received vincristine (98.7%). Content validity index coefficients ranged from .80 to 1.0 (p = .05). For 9 of 14 items, responses ranged from 0 to 4 or 5; response ranges for toe numbness, pick up a coin, and three of four pain items were 0 to 3. After deleting one item, Cronbach's alpha coefficient was .83. P-CIN scores were strongly associated with Pediatric-Modified Total Neuropathy Score (r = .52, p < .01) and Bruininks-Oseretsky Test of Motor Proficiency (r = -.83, p = .04) scores. Sixty-eight percent of children 6 to 17 years old completed P-CIN independently. Discussion: Preliminary evidence suggests that the 13-item P-CIN is internally consistent, is valid, and can be completed independently by children ≥ 6 years. However, we recommend additional testing.

Approaches to measure paediatric chemotherapy-induced peripheral neurotoxicity: a systematic review.

In children who receive neurotoxic chemotherapy, peripheral neurotoxicity occurs frequently, necessitates dose reduction or treatment cessation, and affects function and long-term quality of life. No treatments exist for peripheral neurotoxicity and few assessment measures are specific to children. We did a systematic review to analyse the published literature concerning the evaluation of assessment measures for paediatric chemotherapy-induced peripheral neurotoxicity. We searched PubMed, CINAHL, PsycINFO, and Embase on Nov 7-8, 2018; of 1409 articles, seven met the inclusion criteria. A total of 335 children (excluding ten healthy controls) were enrolled in the seven studies and the sample sizes ranged from 17 to 86 individuals. 276 (82%) of the 335 children were actively undergoing chemotherapy treatment. Most studies did not comprehensively evaluate the psychometric properties of assessment measures for chemotherapy-induced peripheral neurotoxicity. By use of a narrative analysis that combined approaches from the Joanna Briggs Institute (Adelaide, SA, Australia) and the quality of diagnostic accuracy studies assessment method (known as QUADAS), only one study was deemed high quality. We identified two variants of the Total Neuropathy Score, two grading scales, two semi-objective tests, one patient-reported outcome, and several mobility measures. The National Cancer Institute Common Terminology Criteria for Adverse Events and the Balis grading scales showed lower sensitivity and specificity than the items of the Total Neuropathy Score. Although there is insufficient evidence to support the use of most approaches to assess chemotherapy-induced peripheral neurotoxicity in children, two variants of the Total Neuropathy Score, the pediatric-modified Total Neuropathy Score and the Total Neuropathy Score-pediatric vincristine, are promising but require further testing. Other approaches are less sensitive or less feasible. A patient-reported outcome measure for chemotherapy-induced peripheral neurotoxicity in children is needed.

Childhood Trauma Predicts Cancer Treatment-Related Pain in Breast Cancer Survivors.

BACKGROUND: Childhood trauma has been linked to neuropathic pain in noncancer populations, but its relationship with cancer treatment-related neuropathic pain is unknown. OBJECTIVE: This secondary data analysis of a prospective, longitudinal, observational study aimed to explore the relationship of childhood trauma experience with pain severity, pain interference, and neuropathic symptom severity (NSS) 12 months after surgery in women receiving treatment for stage 0 to III breast cancer. METHODS: Women (N = 44) recruited from a comprehensive cancer center self-reported childhood trauma experience, pain severity, pain interference, NSS, co-occurring symptoms, and pain beliefs via questionnaires. Descriptive statistics were used to describe childhood trauma experience. Linear regression was used to model childhood trauma and other predictors on pain variables 12 months after surgery. RESULTS: Childhood trauma predicted pain severity and pain interference 12 months after surgery (P < .05), as did baseline pain severities and helplessness-pain catastrophizing. Age predicted only NSS. Together, the best models predicted 31.6% to 40.9% of the variance in pain severities at 12 months (P < .001). CONCLUSIONS: Childhood trauma exposure was a significant predictor of pain 12 months after breast cancer surgery and adjuvant treatment. Younger and helplessness-pain catastrophizing women are also at risk. Research is needed to identify preventive neuropathic pain interventions for high-risk women. IMPLICATIONS FOR PRACTICE: Women receiving breast cancer treatment should proactively be assessed for childhood trauma history, possibly by using discreet previsit questionnaires. Childhood trauma survivors may be at high risk for poor pain outcomes and may benefit from tailored pain interventions.

Mechanisms, Predictors, and Challenges in Assessing and Managing Painful Chemotherapy-Induced Peripheral Neuropathy.

OBJECTIVE: To describe the known predictors and pathophysiological mechanisms of chronic painful chemotherapy-induced peripheral neuropathy (CIPN) in cancer survivors and the challenges in assessing and managing it. DATA SOURCES: PubMed/Medline, CINAHL, Scopus, and PsycINFO. CONCLUSION: The research on chronic painful CIPN is limited. Additional research is needed to identify the predictors and pathophysiological mechanisms of chronic painful CIPN to inform the development of assessment tools and management options for this painful and possibly debilitating condition. IMPLICATIONS FOR NURSING PRACTICE: Recognition of the predictors of chronic painful CIPN and proactive CIPN assessment and palliative management are important steps in reducing its impact on physical function and quality of life.

Psychometric Testing of the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Chemotherapy-Induced Peripheral Neuropathy 20-Item Scale Using Pooled Chemotherapy-Induced Peripheral Neuropathy Outcome Measures Standardization and Alliance for Clinical Trials in Oncology A151408 Study Data.

BACKGROUND: No criterion-standard patient-reported outcome measure of chemotherapy-induced peripheral neuropathy (CIPN) exists. OBJECTIVES: The aims of this study were to reevaluate the sensitivity, reliability, and validity of the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-CIPN (QLQ-CIPN20) measure and suggest possible revisions that could strengthen it. METHODS: Cross-sectional QLQ-CIPN20 data from 8 European countries (n = 271) were pooled with data from 4 North American multisite CIPN intervention trials (n = 884). The combined sample (N = 1155) included patients with varied cancer diagnoses who had received neurotoxic chemotherapy. Item score ranges, Cronbach's α, and exploratory factor analysis were used to evaluate sensitivity, internal consistency, and structural validity. RESULTS: Individual item mean scores ranged from 1.21 to 2.34 (SD range, 0.55-1.17). All item scores encompassed the entire 1 to 4 range. We recommend that 4 items be removed because of low item-item score correlations (r < 0.30). On the basis of the remaining 16 items, 88% of the variance was explained by 2 factors whose Cronbach's α coefficients were .90 and .85. However, items lacked conceptual alignment with previously published factor structures. CONCLUSION: Using a large, diverse sample of European and North American participants, the reduced 16-item QLQ-CIPN20 is sensitive and internally consistent. However, factor analysis results revealed an unstable factor structure. IMPLICATIONS FOR PRACTICE: The use of a reliable, valid, and sensitive criterion-standard QLQ-CIPN20 variant in clinical practice settings could improve function, quality of life, and CIPN symptom control by facilitating patient reporting and thereby clinician awareness of this underrecognized consequence of cancer therapy.

Pressure Pain Phenotypes in Women Before Breast Cancer Treatment.

OBJECTIVES: To explore associations between quantitative sensory testing (QST) and pretreatment pain, physical, and psychological characteristics in women with breast cancer. SAMPLE & SETTING: 41 women with treatment-naive stage 0-III breast cancer at the University of Michigan Comprehensive Cancer Center in Ann Arbor. METHODS & VARIABLES: Participants completed self-report surveys and QST within the month before breast surgery. Pressure pain thresholds (PPTs) were measured bilaterally at each trapezius with a manual QST algometer. PPT values were split, yielding low, moderate, and high pain sensitivity subgroups. Subgroup self-reported characteristics were compared using Spearman's correlation, chi-square, and one-way analysis of variance. RESULTS: Lower PPT (higher sensitivity) was associated with higher levels of pain interference and maladaptive pain cognitions. The high-sensitivity group reported higher pain severities, interference, and catastrophizing and lower belief in internal locus of pain control than the low-sensitivity group. IMPLICATIONS FOR NURSING: Individualized interventions for maladaptive pain cognitions before surgery may reduce pain sensitivity and the severity of chronic pain developed after surgery.

In Search of a Gold Standard Patient-Reported Outcome Measure for Use in Chemotherapy- Induced Peripheral Neuropathy Clinical Trials.

PURPOSE: To test a reduced version-CIPN15-of the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Chemotherapy-Induced Peripheral Neuropathy scale (QLQ-CIPN20) to establish a possible gold-standard patient-reported outcome measure for chemotherapy-induced peripheral neuropathy (CIPN). METHODS: Using a prospective, longitudinal, case-control design, patients (n = 121) receiving neurotoxic chemotherapy completed the CIPN15 at baseline and 12 weeks and underwent objective neurological assessment using the 5-item Total Neuropathy Score-Clinical (TNSc). Healthy controls (n = 30) completed the CIPN15 once. Structural validity was evaluated using factor analysis. Because a stable factor structure was not found, a sum score was used to evaluate measures of the CIPN15's psychometric properties-reliability, validity, sensitivity, and responsiveness-as follows: internal consistency via Cronbach's α and item-item correlations; test-retest reliability via correlation between 2 CIPN15 scores from each patient; concurrent validity via correlation between CIPN15 and 5-item TNSc scores; contrasting group validity via comparison of CIPN15 scores from patients and healthy controls; sensitivity via descriptive statistics (means, standard deviation, ranges); and responsiveness via Cohen's d effect size. RESULTS: Most patients received single agent oxaliplatin (33.7%), paclitaxel (21.2%), or more than 1 neurotoxic drug concurrently (29.8%). Factor analysis revealed no stable factor structure. Cronbach's α for the CIPN15 sum score was 0.91 (confidence interval [CI] = 0.89-0.93). Test-retest reliability was demonstrated based on strong correlations between the 2 scores obtained at the 12-week time point ( r = 0.86; CI = 0.80-0.90). The CIPN15 and 5-item TNSc items reflecting symptoms (not signs) were moderately correlated ( r range 0.57-0.72): concurrent validity. Statistically significant differences were found between patient and healthy control CIPN15 mean scores ( P < .0001): contrasting group validity. All items encompassed the full score range but the CIPN15 linearly converted sum score did not: sensitivity. The CIPN15 was responsive based on a Cohen's d of 0.52 (CI = 0.25-0.79). CONCLUSION: The sum-scored CIPN15 is reliable, valid, sensitive, and responsive when used to assess taxane- and platinum-induced CIPN.

Pilot Study of an Internet-Based Self-Management Program for Symptom Control in Patients With Early-Stage Breast Cancer.

PURPOSE: Many survivors of breast cancer experience an array of chronic symptoms, including pain, insomnia, and fatigue. Few effective therapies have been identified. Behavioral management programs to address similar symptom clusters in other chronic conditions have been effective. The objective of this study was to determine the effect of an Internet-based lifestyle and behavioral self-management program on cancer-related symptoms. PATIENTS AND METHODS: Women with stage 0 to 3 breast cancer who reported insomnia, pain, or fatigue as their primary symptom of concern during the 7 days before enrollment were enrolled. Local therapies and/or chemotherapy were completed at least 3 months before enrollment. Patients were assessed at baseline and after 8 weeks, and they completed the Patient-Reported Outcomes Measurement Information System (PROMIS)-29 Profile and Patient Global Impression of Change (PGIC) questionnaire electronically. Change in each of the eight symptom domains was assessed. RESULTS: Fifty patients enrolled. In the 45 patients with both baseline and 8-week PROMIS data, statistically significant improvements in anxiety, sleep, fatigue, activity level, and pain severity were reported. Of the 35 patients who responded to the PGIC, 62.9% reported improvement in their primary symptom. Those who reported fatigue as their primary symptom reported greatest overall benefit in multiple symptom improvement, including improvements in fatigue, anxiety, pain severity, pain interference, and participation in social activities. CONCLUSIONS: These findings suggest that this lifestyle and behavioral management program may improve multiple symptoms in breast cancer survivors when delivered via the Internet. Randomized studies are warranted to evaluate the efficacy of the online intervention compared with standard symptom management approaches and to identify patients most likely to benefit.

Patterns and severity of vincristine-induced peripheral neuropathy in children with acute lymphoblastic leukemia.

Vincristine, a critical component of combination chemotherapy treatment for pediatric acute lymphoblastic leukemia (ALL), can lead to vincristine-induced peripheral neuropathy (VIPN). Longitudinal VIPN assessments were obtained over 12 months from newly diagnosed children with ALL (N = 128) aged 1-18 years who received vincristine at one of four academic children's hospitals. VIPN assessments were obtained using the Total Neuropathy Score-Pediatric Vincristine (TNS©-PV), National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE©), Balis© grading scale, and Pediatric Neuropathic Pain Scale©-Five (PNPS©-5). Of children who provided a full TNS©-PV score, 85/109 (78%) developed VIPN (TNS©-PV ≥4). Mean TNS©-PV, grading scale, and pain scores were low. CTCAE©-derived grades 3 and 4 sensory and motor VIPN occurred in 1.6%/0%, and 1.9%/0% of subjects, respectively. VIPN did not resolve in months 8-12 despite decreasing dose density. VIPN was worse in older children. Partition cluster analysis revealed 2-3 patient clusters; one cluster (n = 14) experienced severe VIPN. In this population, VIPN occurs more commonly than previous research suggests, persists throughout the first year of treatment, and can be severe.

Cancer treatment-related neuropathic pain syndromes--epidemiology and treatment: an update.

Cancer treatment-related chronic neuropathic pain (NP) is a pervasive and distressing problem that negatively influences function and quality of life for countless cancer survivors. It occurs because of cancer treatment-induced damage to peripheral and central nervous system structures. NP becomes chronic when pain signal transmission persists, eventually sensitizing neurons in the dorsal horn and other pain-processing regions in the central nervous system. Frequently overlooked, NP due to cancer treatment has been understudied. Consequently, only a few pharmacologic interventions have been shown to be effective based on the results of randomized controlled trials. Future research designed to explore pathophysiologic mechanisms and effective mechanism-targeted interventions is sorely needed.

What about Alice? Peripheral neuropathy from taxane-containing treatment for advanced nonsmall cell lung cancer.

PURPOSE: In this review, we discuss the plight of Alice, a patient with advanced nonsmall cell lung cancer (NSCLC) who struggles with taxane-related peripheral neuropathy (PN). Using this unique point of view helps us to appreciate the implications of PN on daily activities as well as the difficulty in decision-making regarding continuation of treatment. In addition, published reports of phase 3 trials are reviewed to identify the incidence and severity of chemotherapy-induced PN as well as the assessment tools used in these studies. METHODS: A literature review spanning the years 1998-2012 was performed. Phase 3 studies and a meta-analysis of taxane-based therapy in advanced NSCLC were selected for review for their findings regarding the incidence and severity of chemotherapy-induced PN. RESULTS: In total, 16 phase 3 studies and 1 meta-analysis were reviewed. Use of grading scales and PN assessment tools was inconsistent across the studies, and some studies did not report PN at all. CONCLUSIONS: The true incidence and severity of chemotherapy-induced PN in clinical trials may be masked by nonstandardized reporting; thus, a more standardized approach to grading, assessing, and reporting PN in clinical trials is greatly needed to allow for appropriate comparisons across studies. Understanding chemotherapy-induced PN from the patient's perspective as well as the development of PN at the clinical trial level will help health care providers anticipate the development of PN and improve their ability to manage it.