Pan, Xueliang

Individuals diagnosed with chemotherapy-induced peripheral neuropathy (CIPN) demonstrate impaired balance and carry an increased risk of falling. However, prior investigations of postural instability have only compared these individuals against healthy controls, limiting the understanding of impairments associated with CIPN. Therefore, the purpose of this study was to better isolate postural control impairments that are associated with CIPN. Twenty cancer survivors previously diagnosed with breast or colorectal cancer participated. Participants were separated into 3 groups: no prior chemotherapy exposure (CON, n = 6), and recent treatment with taxane- or oxaliplatin-based chemotherapy with no/mild symptoms of CIPN (−CIPN, n = 8) or moderate/severe symptoms of CIPN (+CIPN, n = 6). Postural control was assessed by measuring center of pressure during standing balance conditions that systematically interfered with somatosensory, visual, and/or vestibular information. The presence of CIPN sensory symptoms was associated with impaired postural control, particularly during eyes-closed balance conditions ( P < .05). Additionally, medial-lateral postural instability was more pronounced in the +CIPN group compared with the −CIPN group and CON participants ( P < .05). Greater postural instability during eyes-closed balance in individuals with CIPN is consistent with impaired peripheral sensation. Balance impairments in cancer survivors with CIPN demonstrate the unique challenges in this population and motivate the need for targeted efforts to mitigate postural control deficits that have previously been associated with fall risk.

Context: The fourth edition of the Preparticipation Physical Evaluation recommends functional testing for the musculoskeletal portion of the examination; however, normative data across sex and grade level are limited. Establishing normative data can provide clinicians reference points with which to compare their patients, potentially aiding in the development of future injury-risk assessments and injury-mitigation programs.Objective: To establish normative functional performance and limb-symmetry data for high school-aged male and female athletes in the United States.Design: Cross-sectional study.Setting: Athletic training facilities and gymnasiums across the United States.Patients or Other Participants: A total of 3951 male and female athletes who participated on high school-sponsored basketball, football, lacrosse, or soccer teams enrolled in this nationwide study.Main Outcome Measure(s): Functional performance testing consisted of 3 evaluations. Ankle-joint range of motion, balance, and lower extremity muscular power and landing control were assessed via the weight-bearing ankle-dorsiflexion–lunge, single-legged anterior-reach, and anterior single-legged hop-for-distance (SLHOP) tests, respectively. We used 2-way analyses of variance and χ2 analyses to examine the effects of sex and grade level on ankle-dorsiflexion–lunge, single-legged anterior-reach, and SLHOP test performance and symmetry.Results: The SLHOP performance differed between sexes (males = 187.8% ± 33.1% of limb length, females = 157.5% ± 27.8% of limb length; t = 30.3, P &lt; .001). A Cohen d value of 0.97 indicated a large effect of sex on SLHOP performance. We observed differences for SLHOP and ankle-dorsiflexion–lunge performance among grade levels, but these differences were not clinically meaningful.Conclusions: We demonstrated differences in normative data for lower extremity functional performance during preparticipation physical evaluations across sex and grade levels. The results of this study will allow clinicians to compare sex- and grade-specific functional performances and implement approaches for preventing musculoskeletal injuries in high school-aged athletes.

Abstract Introduction Chemotherapy-induced peripheral neuropathy (CIPN) is a dose-limiting toxicity of several chemotherapy drug classes, including taxanes. Peripheral neuropathies have been shown to lead to pain, falls, and difficulty in walking and performing activities of daily living in a variety of patient populations. Although the prevalence of CIPN has been noted in cancer patients, the development of self-reported symptoms, gait changes and balance changes during treatment have not been well explored to date. We hypothesized that the use of taxane-based chemotherapy will result in significant changes in spatiotemporal gait and balance parameters, as well as self-reported quality of life and function. Methods We characterized the alterations in gait and balance that occur in non-metastatic breast cancer patients during taxane chemotherapy. We evaluated (1) spatiotemporal gait parameters, including cadence and step length, and (2) balance parameters, including time-to-contact and 95% ellipse area, using each patient as her own control. Laboratory assessment of gait and balance was conducted at baseline and at completion of therapy in selected patients. We compared the natural history of changes in gait and balance parameters with changes in CIPN status as measured by validated patient reported outcomes, including EORTC QLQ-C30, CIPN-20, and Brief Pain Inventory Short Form (BPI-SF), and the Duke Activity Status Index (DASI). Time points included pre-chemotherapy, after each cycle of chemotherapy, and one month after the end of therapy to collect information on neuropathy, pain and functional capacity. The preliminary data were illustrated using individual plots; trend lines (changing over time) were based on least square means at each time point, which were estimated using the linear mixed models for repeated measures. Results To date, 15 patients with localized breast cancer have been enrolled; patient recruitment is ongoing. The median age is 42 years (range 25-67). Ten patients (67%) received weekly paclitaxel, 1 patient (7%) received paclitaxel every 2 weeks, and 4 patients (27%) received docetaxel every 3 weeks. Preliminary results with these 15 patients, based on least square means at each timepoint, showed trends in several parameters. As treatments progressed, patients tended to develop more difficulty in quiet balance and in their ability to actively shift weight in the sagittal and frontal planes. From the CIPN-20, they also tended to develop increased difficulty with sensory and motor systems. From the QLQ-C30, their global health status also tended to worsen. For most of these parameters, the largest changes were observed between the 2nd and 3rd treatments, though some changes were not observed until the 4th treatment. From the BPI-SF, no trends in pain symptoms or pain interference were observed within this preliminary cohort. Conclusions Gait and balance testing is feasible in the clinical setting. Preliminary observations suggest that balance, function and quality of life may all be affected by taxane therapy, even without pain symptoms. The findings of this study will enable us to better characterize the neurotoxic effect of taxanes and to ultimately test the effectiveness of preventative measures and interventions. Funding by NCI R03CA182165-01. Citation Format: Maryam B Lustberg, Scott Monfort, Janani Singaravelu, Raquel E Reinbolt, Xueliang Pan, Bhuvaneswari Ramaswamy, Rachel M Layman, Robert Wesolowski, Ewa Mrozek, Erin Macrae, Charles Shapiro, Robyn Patrick, Charles L Loprinzi, Ajit Chaudhari. Longitudinal evaluation of taxane-induced neuropathy in early stage breast cancer [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P1-09-04.

Abstract Introduction: AI-induced joint symptoms negatively impact drug adherence and quality of life. Based on observations that n-3 polyunsaturated fatty acids (PUFAs) have anti-inflammatory effects and that the mechanism of AI-induced joint symptoms may be partly due to inflammation, we hypothesized that women taking more n-3 PUFAs are less likely to develop AI-induced joint symptoms. Methods: We conducted a randomized, double-blind, placebo-controlled study comparing n-3 PUFA vs placebo in postmenopausal breast cancer patients starting adjuvant AIs. Participants were randomized to n-3 supplements [2.58 g eicosapentaenoic acid + 1.74 g docosahexaenoic acid/day; Marine Nutriceuticals, Mt. Bethel, PA] vs matched placebo for 24 weeks (wks). Primary endpoints was feasibility; secondary outcomes were self-reported symptoms as assessed by the Brief Pain Inventory short form (BPI-SF), Functional Assessment of Cancer Treatment, Breast & Endocrine Symptoms (FACTB-ES), and Stanford's Health Assessment and Disability Index (HAQ) at baseline prior to AI receipt, 12 and 24 wks. Compliance and toxicity were evaluated monthly. Serial peripheral blood n-3 PUFA levels and inflammatory cytokines (IL-6, TNFR2, IL-17) were drawn. MRI of hands/wrists was performed in selected patients using a 3 Tesla dedicated wrist coil at baseline and treatment end. Results: Forty-four women were enrolled and randomized to study drug; 42 received ≥1 cycle (4 wks) of treatment; 36 had ≥1 post treatment evaluation at wk 12 or 24. Median age was 59.5 (range 43-76); history of prior taxane (n=15, 34%). The two groups’ baseline characteristics were similar. Overall, 93% and 88% of patients took &gt;80% of the placebo and n-3 PUFA doses, respectively. Baseline erythrocyte n-3 PUFA was similar for both groups (6.6% ± 1.6%, 7.2% ±1.9%, p=0.20), but higher in the n-3 PUFA arm by wk 24 (6.5%±1.0% vs 15.0%±3.3%, p&lt;0.001). Most toxicities were grade 1; the n-3 PUFA arm had only 1 (2.5%) grade 3 toxicity (diarrhea). The n-3 PUFA arm reported lower mean BPI-SF scores after treatment [(-.0.28/ -0.25 at week 12/24); but not statistically significant compared to placebo (p=0.494 and 0.601)]. Based on BPI-SF, the n-3 PUFA arm reported less interference of pain symptoms compared to placebo at 12 weeks (-.72, p=0.08). This arm also had a decreased walking, activity and working (WAW) score on BPI-SF at 12 weeks (-.81 p=0.05), and reported significantly greater pain relief from medications at 12 (p=0.043) and 24 weeks (p=0.011). Both arms had similar baseline and wk 24 serum IL-6 levels; levels decreased from baseline to wk 24 in the n-3 PUFA arm (-0.54±0.25, p=0.048). There was a non-significant trend (p= 0.2) toward decreased wrist inflammation by MRI imaging at 24 wks in the n-3 PUFA arm. Conclusions: This is the first randomized pilot study to show that n-3 PUFA supplementation to prevent AI-induced joint symptoms is feasible and well tolerated. There is preliminary evidence that this intervention may help reduce the burden of AI-induced arthralgias. OSU Study #11022; ClinicalTrials.gov Identifier: NCT01478477. Grants from the National Cancer Institute (CA037447-26) to the Alliance for Clinical Trials in Oncology supported this pilot study. Citation Format: Maryam B Lustberg, Tonya Orchard, Xueliang Pan, Raquel Reinbolt, Amanda Logan, Joanne Lester, Rachel M Layman, Erin Macrae, Ewa Mrozek, Bhuvaneswari Ramaswamy, Robert Wesolowski, Michael Berger, Michael Knopp, Charles Loprinzi, Charles L Shapiro, Lisa Yee. Prevention of aromatase Inhibitor (AI)-induced joint symptoms with omega-3 fatty acid supplementation: A randomized placebo-controlled pilot study [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P1-09-03.