Obesity as a Potential Risk Factor for Vincristine-induced Peripheral Neuropathy.

Acute lymphoblastic leukemia (ALL) is the most common pediatric cancer. Vincristine is a core chemotherapeutic agent for patients with ALL; unfortunately, ∼78% will develop vincristine-induced peripheral neuropathy (VIPN). VIPN can result in vincristine dose reductions that decrease therapeutic efficacy: making it important to understand which children are at highest risk for VIPN. We hypothesized that pediatric ALL patients who were obese at diagnosis would develop worse VIPN than healthy weight children with ALL within the first year. Our results confirmed that obese pediatric patients have significantly (P=0.03) worse VIPN than patients of healthy weight.

Impact of using a broad-based multi-institutional approach to build capacity for non-communicable disease research in Thailand.

Thailand's transition to high middle-income country status has been accompanied by demographic changes and associated shifts in the nation's public health challenges. These changes have necessitated a significant shift in public health focus from the treatment of infectious diseases to the more expensive and protracted management of non-communicable diseases (NCDs) in older adults.In 2010, in response to this shift in focus, the University of Michigan and colleagues at the Praboromarajchanok Institute for Health Workforce Development in Thailand began work on a broad-based multi-institutional programme for NCD research capacity-building in Thailand.To begin to build a base of intervention research we paired our programme's funded Thai postdoctoral fellows with United States mentors who have strong programmes of intervention research. One direct impact of the programme was the development of research 'hubs' focused upon similar areas of investigative focus such as self-management of cancer symptoms, self-management of HIV/AIDS and health technology information applications for use in community settings. Within these hubs, interventions with proven efficacy in the United States were used as a foundation for culturally relevant interventions in Thailand. The programme also aimed to develop the research support structures necessary within departments and colleges for grant writing and management, dissemination of new knowledge, and ethical conduct of human subject research.In an effort to capitalise on large national health datasets and big data now available in Thailand, several of the programme's postdoctoral fellows began projects that use data science methods to mine this asset. The investigators involved in these ground-breaking projects form the core of a network of research hubs that will be able to capitalise on the availability of lifespan health data from across Thailand and provide a robust working foundation for expansion of research using data science approaches.Going forward, it is vitally important to leverage this groundwork in order to continue fostering rapid growth in NCD research and training as well as to capitalise upon these early gains to create a sustaining influence for Thailand to lead in NCD research, improve the health of its citizens, and provide ongoing leadership in Southeast Asia.

Pharmacometabolomics reveals a role for histidine, phenylalanine, and threonine in the development of paclitaxel-induced peripheral neuropathy.

PURPOSE: Approximately 25% of breast cancer patients experience treatment delays or discontinuation due to paclitaxel-induced peripheral neuropathy (PN). Currently, there are no predictive biomarkers of PN. Pharmacometabolomics is an informative tool for biomarker discovery of drug toxicity. We conducted a secondary whole blood pharmacometabolomics analysis to assess the association between pretreatment metabolome, early treatment-induced metabolic changes, and the development of PN. METHODS: Whole blood samples were collected pre-treatment (BL), just before the end of the first paclitaxel infusion (EOI), and 24 h after the first infusion (24H) from sixty patients with breast cancer receiving (80 mg/m2) weekly treatment. Neuropathy was assessed at BL and prior to each infusion using the sensory subscale (CIPN8) of the EORTC CIPN20 questionnaire. Blood metabolites were quantified from 1-D-1H-nuclear magnetic resonance spectra using Chenomx® software. Metabolite concentrations were normalized in preparation for Pearson correlation and one-way repeated measures ANOVA with multiple comparisons corrected by false discovery rate (FDR). RESULTS: Pretreatment histidine, phenylalanine, and threonine concentrations were inversely associated with maximum change in CIPN8 (ΔCIPN8) (p < 0.02; FDR ≤ 25%). Paclitaxel caused a significant change in concentrations of 2-hydroxybutyrate, 3-hydroxybutyrate, pyruvate, o-acetylcarnitine, and several amino acids from BL to EOI and/or 24H (p < 0.05; FDR ≤ 25%), although these changes were not associated with ΔCIPN8. CONCLUSIONS: Whole blood metabolomics is a feasible approach to identify potential biomarker candidates of paclitaxel-induced PN. The findings suggest that pretreatment concentrations of histidine, phenylalanine, and threonine may be predictive of the severity of future PN and paclitaxel-induced metabolic changes may be related to disruption of energy homeostasis.

Estimating the Frequency, Severity, and Clustering of SPADE Symptoms in Chronic Painful Chemotherapy-Induced Peripheral Neuropathy.

BACKGROUND: Patients undergoing treatment for cancer commonly experience symptoms such as sleep disturbance, pain, anxiety, depression, and low energy/fatigue (SPADE), subsequently altering physical function and complicating effective symptom management. However, little is known about the frequency, severity, and clustering of SPADE symptoms in individuals with chronic painful chemotherapy-induced peripheral neuropathy (CIPN). Aims/Design: The purpose of this cross-sectional, secondary analysis was to describe the frequency, severity, and clustering of SPADE symptoms and their association with physical function in individuals with chronic painful CIPN. Participants/Subjects: Sixty individuals with chronic painful CIPN were recruited from five academic and community oncology outpatient center to participate in a randomized controlled pilot trial designed to test the efficacy of a cognitive behavioral therapy-based pain management program. METHODS: Participants completed the 0-10 Average CIPN Pain Numerical Rating Scale and Patient-Reported Outcome Measurement Information System measures for sleep-related impairment, anxiety, depression, fatigue, and pain interference via tablet before being randomly assigned to a study arm. The frequency, severity, and clustering of SPADE symptoms were calculated via descriptive statistics and Partitioning Around Medoids cluster analysis. Spearman rank correlation was performed to determine the association between number of SPADE symptoms and pain interference severity. RESULTS AND CONCLUSIONS: Participants (n = 59) experienced numerous SPADE symptoms. 66.1% of participants experienced at least two SPADE symptoms concurrently. The cluster analysis revealed high (n = 36) and low (n = 23) severity subgroups. There was a moderate correlation (r = 0.48) between the number of SPADE symptoms and pain interference severity. Determining the clustering of SPADE symptoms in individuals with chronic painful CIPN may lead to targeted multifaceted interventions to improve physical function.

Potential mediators of improvement in painful chemotherapy-induced peripheral neuropathy via a web-based cognitive behavioural intervention.

PURPOSE: Preliminary evidence suggests that a self-guided cognitive and behaviourally-based pain management intervention (PROSPECT) is effective for chronic painful chemotherapy-induced peripheral neuropathy (CIPN), but its mechanism of action is unknown. The purpose of this secondary analysis was to explore if changes in anxiety, depression, sleep-related impairment, or fatigue mediated improvements in worst pain following PROSPECT in individuals with chronic painful CIPN. METHODS: Sixty participants were randomized to receive self-guided cognitive behavioural pain management (access for eight weeks) or treatment as usual. A seven-day worst CIPN pain diary and the PROMIS measures of anxiety, depression, fatigue, and sleep-related impairment were administered pre/posttest (eight-weeks). Causal mediation analysis was used to quantify mediators of worst pain improvement. RESULTS: None of the hypothesized mediators had a statistically significant effect on worst pain (n=38). IMPLICATIONS: Further research is needed to identify potential mediators of pain intensity that can be targeted by specific cognitive behavioural strategies to improve painful CIPN severity.

Implementation of a Survivorship Care Plan Program in a Community-Based Oncology Clinic.

There is conflicting evidence from the small number of randomized controlled trials (RCTs) that have assessed the benefit of survivorship care plans (SCPs) on improving patient outcomes. Yet, published quasi-experimental and descriptive studies provide preliminary evidence suggesting that using survivorship care plans in practice may improve patient knowledge, decrease worry and anxiety, and lead to patient and primary care physician satisfaction. Given the conflicting evidence and the paucity of RCTs, further research is needed to more fully explore the effect of SCP on patient outcomes. To address this knowledge gap, an SCP program was implemented in a community-based oncology clinic and used quality improvement methodology to assess the effect on patient knowledge of diagnosis, treatment, and follow-up, and to understand patients' satisfaction with the current SCP program. A total of 30 cancer patients were recruited in Southeast Michigan to participate in an SCP quality improvement project and completed surveys to evaluate the SCP program. Data were collected between December 2017 and March 2018. We observed a statistically significant (p = .028) difference between pre- and postintervention (survivorship care plan visit) knowledge scores about cancer diagnosis, treatment received, and follow-up recommendations. Moreover, participants were satisfied with the survivorship care plan and visit.

Characterizing patient-clinician chemotherapy-induced peripheral neuropathy assessment and management communication approaches.

OBJECTIVE: To describe the frequency and characteristics of chemotherapy-induced peripheral neuropathy (CIPN) assessment and management communication approaches between patients receiving neurotoxic chemotherapy and clinicians. METHODS: The data used in this analysis originated from a randomized controlled trial in which adults with cancer self-reported treatment-related symptoms using web-based symptom assessment technology. Three-to-six weeks after study initiation, each participant's outpatient visit was audio-recorded. Audio recordings and associated clinician notes for 159 participants who received platinum and/or taxane-based chemotherapy were coded for the presence of several CIPN assessment and management communication characteristics. RESULTS: Participants received low cumulative neurotoxic chemotherapy doses (75%) at the time of audio recording. CIPN was discussed and documented in 44% and 46% of participant-clinician encounters. In symptomatic participants, clinicians asked an average of 0.7 open-ended questions, appropriately managed 70% of cases, and asked upper and lower extremity CIPN questions in 25% of cases. CONCLUSIONS: Clinicians infrequently discussed and documented CIPN in participants with low CIPN severity, however appropriately managed mild CIPN. Development of interventions to translate existing recommended CIPN communication approaches into practice are required. PRACTICE IMPLICATIONS: Effective participant-clinician communication is required at each clinic visit during chemotherapy treatment to identify initial signs of CIPN and offer appropriate treatment.

Genetic Variants Associated With Vincristine-Induced Peripheral Neuropathy in Two Populations of Children With Acute Lymphoblastic Leukemia.

Vincristine is one of the core chemotherapy agents used in the treatment of pediatric acute lymphoblastic leukemia (ALL). However, one of the major toxicities resulting from vincristine exposure is vincristine-induced peripheral neuropathy (VIPN). When VIPN results in significant morbidity, the vincristine dose may need to be reduced, thus potentially decreasing the effectiveness of treatment. To date, there are no robust biomarkers used clinically to determine which patients will be at risk for worse neuropathy. The current study included genomewide association study (GWAS) in two independent cohorts: Pediatric Oncology Group (POG) ALL trials and a multicenter study based at Indiana University in children with ALL. A meta-analysis of the cohorts identified two single-nucleotide polymorphisms (SNPs), rs1045644 and rs7963521, as being significantly (P value threshold 0.05/4749 = 1.05E-05) associated with neuropathy. Subsequently these SNPs may be effective biomarkers of VIPN in children with ALL.

Chemotherapy-Induced Peripheral Neuropathy: Use of an Electronic Care Planning System to Improve Adherence to Recommended Assessment and Management Practices.

BACKGROUND: Chemotherapy-induced peripheral neuropathy (CIPN) is often inadequately assessed and managed by advanced practice providers. OBJECTIVES: The aim is to explore the impact of CIPN assessment training and electronic care planning system (CPS) use on CIPN assessment documentation and guidelines adherence. METHODS: The authors used a pre-/post-test, prospective design with two retrospective chart reviews. Six providers received CIPN assessment training and used the CPS to manage CIPN for 75 women receiving neurotoxic chemotherapy. FINDINGS: CPS use significantly improved documentation of numbness and nonpainful CIPN management strategies but had no effect on documentation of additional assessment variables or painful CIPN management.

Self-Guided Online Cognitive Behavioral Strategies for Chemotherapy-Induced Peripheral Neuropathy: A Multicenter, Pilot, Randomized, Wait-List Controlled Trial.

The purpose of this pilot, parallel, randomized controlled trial was to examine the efficacy of a self-guided online cognitive and behaviorally-based pain management intervention (Proactive Self-Management Program for Effects of Cancer Treatment [PROSPECT]) to reduce "worst" pain for individuals with chronic painful chemotherapy-induced peripheral neuropathy (CIPN). Secondary outcomes included "average" pain, nonpainful CIPN symptom severity, impression of change, and pain interference. Sixty patients with chronic painful CIPN were recruited from 5 outpatient academic and community cancer centers. Patients were randomized in a 1:1 ratio to receive either 8 weeks of PROSPECT or usual care. A 7-day electronic "worst" pain intensity diary and standardized measures of pain interference, nonpainful CIPN symptom severity, impression of change, and "average" pain were administered pre/post intervention. Postintervention mean scores were evaluated between groups using analysis of covariance adjusting for baseline. Individuals who received the PROSPECT intervention (n = 19) had significantly greater improvements in "worst pain" compared with individuals receiving usual care (n = 19; P = .046, d = .58). There were no significant differences in mean scores between groups for the secondary outcomes (n = 42). A larger, adequately powered study testing the PROSPECT intervention is needed to determine if improvements in pain may be sustained, evaluate the effect of the intervention on the secondary outcomes, and identify mediators of pain intensity-related improvement. PERSPECTIVE: This study explores the efficacy of an 8-week online cognitive behavioral pain management intervention for chronic painful CIPN. Intervention use resulted in greater improvements in "worst" pain than usual care alone. The findings provide preliminary support for the efficacy of a nonpharmacological intervention for chronic painful 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.

Clinical Course of Oxaliplatin-Induced Neuropathy: Results From the Randomized Phase III Trial N08CB (Alliance).

PURPOSE: Given that the clinical course of oxaliplatin-induced neuropathy is not well defined, the current study was performed to better understand clinical parameters associated with its presentation. METHODS: Acute and chronic neuropathy was evaluated in patients receiving adjuvant FOLFOX (fluorouracil, leucovorin, and oxaliplatin) on study N08CB (North Central Cancer Treatment Group, Alliance). Acute neuropathy was assessed by having patients complete daily questionnaires for 6 days with each cycle of FOLFOX. Before each dose of FOLFOX and as long as 18 months after chemotherapy cessation, chronic neurotoxicity was assessed with use of the 20-item, European Organisation for Research and Treatment of Cancer quality-of-life questionnaire for patients with chemotherapy-induced peripheral neuropathy. RESULTS: Three hundred eight (89%) of the 346 patients had at least one symptom of acute neuropathy with the first cycle of FOLFOX; these symptoms included sensitivity to touching cold items (71%), sensitivity to swallowing cold items (71%), throat discomfort (63%), or muscle cramps (42%). Acute symptoms peaked at day 3 and improved, although they did not always resolve completely between treatments. These symptoms were about twice as severe in cycles 2 through 12 as they were in cycle 1. For chronic neurotoxicity, tingling was the most severe symptom, followed by numbness and then pain. During chemotherapy, symptoms in the hands were more prominent than they were in the feet; by 18 months, symptoms were more severe in the feet than they were in the hands. Patients with more severe acute neuropathy during the first cycle of therapy experienced more chronic sensory neurotoxicity (P < .0001). CONCLUSION: Acute oxaliplatin-induced neuropathy symptoms do not always completely resolve between treatment cycles and are only half as severe on the first cycle as compared with subsequent cycles. There is a correlation between the severities of acute and chronic neuropathies.