Preventive Effect of Neuromuscular Training on Chemotherapy-Induced Neuropathy: A Randomized Clinical Trial.

Importance: Chemotherapy-induced peripheral neuropathy (CIPN) is a highly prevalent and clinically relevant adverse effect of chemotherapy, negatively impacting patient quality of life. The lack of effective preventive or therapeutic options regarding CIPN often requires changes in cancer therapy, potentially resulting in reduced survival. Objective: To determine whether sensorimotor training (SMT) and whole-body vibration (WBV) training reduce symptoms and decrease the onset of CIPN. Design, Setting, and Participants: This prospective multicenter randomized clinical trial (STOP) followed up patients over 5 years at 4 centers in or near Cologne, Germany. Patients undergoing treatment with oxaliplatin or vinca alkaloids were recruited. Participants were recruited from May 2014 to November 2020. Data were last analyzed in June 2021. Interventions: Participants in the intervention groups performed supervised SMT or WBV training sessions twice a week, each lasting approximately 15 to 30 minutes, concomitant to medical therapy. Main Outcomes and Measures: The primary end point was the incidence of CIPN. Secondary end points included subjective neuropathy symptoms, balance control, physical activity levels, quality of life, and clinical outcome. For cross-stratum evaluations, the Mantel-Haenszel test (MH) was used, and within individual strata, Fisher exact test was used for analysis. Results: A total of 1605 patients were screened, and 1196 patients did not meet all inclusion criteria, with 251 further excluded or declining participation. A total of 158 patients (mean [SD] age, 49.1 [18.0-82.0] years; 93 [58.9%] male) were randomized into 1 of 3 groups: 55 (34.8%) in SMT, 53 (33.5%) in WBV, and 50 (31.6%) in treatment as usual (TAU). The incidence of CIPN in participants was significantly lower in both intervention groups compared to the control group (TAU): (SMT, 12 of 40 [30.0%; 95% CI, 17.9%-42.1%] and WBV, 14 of 34 [41.2%; 95% CI, 27.9%-54.5%] vs TAU, 24 of 34 [70.6%; 95% CI, 58.0%-83.2%]; P = .002 for intention to treat-MH). Patients receiving vinca alkaloids and performing SMT benefited the most. Results were more pronounced in a per-protocol analysis (>75% participation in the intervention) (SMT, 8 of 28 [28.6%; 95% CI, 16.6%-40.5%] and WBV, 9 of 24 [37.5%; 95% CI, 24.4%-50.5%] vs TAU, 22 of 30 [73.3%; 95% CI, 61.6%-85.6%]). Improvements in favor of SMT compared to TAU were found for balance control bipedal with eyes open; bipedal with eyes closed; monopedal, vibration sensitivity, sense of touch, lower leg strength, pain reduction, burning sensation, chemotherapy dose reductions, and mortality. Conclusion and Relevance: This randomized clinical trial provides initial evidence that neuromuscular training decreases the onset of CIPN. Trial Registration: German Clinical Trials Register: DRKS00006088.

Balance training during acute medical treatment for pediatric cancer - subjective benefits and preliminary effects on selected physical abilities.

BACKGROUND: As balance training seems to be a promising training method to improve physical limitations of the lower limbs, this study aims to evaluate feasibility, subjective benefits and preliminary effects on physical abilities of balance training in pediatric cancer patients. PATIENTS: 11 pediatric cancer patients (5-21 years) undergoing acute medical treatment were included in the study. METHOD: Participants took part in a 4-week balance training intervention. 3 trainings/week were conducted either supervised or self-administered. Subjective benefits were evaluated using a questionnaire, effects on selected physical abilities were assessed using functional-motor assessments. RESULTS: Participants completed 71.21+37.34% of balance training sessions, no adverse events occurred. Participants were satisfied with the intervention and described various subjective benefits. Significant improvements were found in functional strength of the lower limbs as well as positive trends in balance. DISCUSSION: Balance training seems feasible with pediatric cancer patients undergoing acute medical treatment potentially improving functions of the lower limbs relevant for daily physical activity. CONCLUSION: Balance training can be a valuable conjunct to general exercise programs in pediatric oncology. HINTERGRUND: Da ein Gleichgewichtstraining eine vielversprechende Trainingsmethode zur Verbesserung körperlicher Beeinträchtigungen der unteren Extremitäten darstellt, untersucht die vorliegende Studie die Machbarkeit, subjektive und erste objektive Effekte eines Gleichgewichtstrainings auf körperliche Fähigkeiten bei onkologisch erkrankten Kindern. PATIENTEN: 11 Kinder und Jugendliche (5-21 Jahre) während der akutmedizinischen Behandlung einer onkologischen Erkrankung wurden in die Studie eingeschlossen. METHODIK: Die Patient*innen nahmen an einem 4-wöchigen Gleichgewichtstraining teil. 3 Trainingseinheiten/Woche wurden entweder supervidiert oder selbstständig umgesetzt. Subjektive Effekte wurden mit einem Fragebogen und die Effekte auf ausgewählte körperliche Fähigkeiten mittels funktionell-motorischer Testungen evaluiert. ERGEBNISSE: Die Teilnehmer*innen absolvierten 71.21+37.34% der Trainingseinheiten und es traten keine trainingsbedingten Zwischenfälle auf. Die Kinder waren zufrieden mit der Intervention und beschrieben verschiedene subjektive Effekte. Positive Veränderungen zeigten sich im Bereich der funktionellen Kraft der unteren Extremitäten und des Gleichgewichts. DISKUSSION: Ein Gleichgewichtstraining während der akutmedizinischen Behandlung in der Kinderonkologie scheint machbar und zeigt potenziell positive Effekte auf relevante Funktionen der unteren Extremitäten. SCHLUSSFOLGERUNG: Ein Gleichgewichtstraining kann eine wertvolle Ergänzung allgemeiner Bewegungsprogramme in der pädiatrischen Onkologie darstellen.

Physical and functional performance assessment in pediatric oncology: a systematic review.

BACKGROUND: Research indicates reduced physical performance from diagnosis into survivorship of pediatric cancer patients. However, there is no systematic information or guideline available on the methods to assess physical performance and function in this population. The purpose was to systematically compile and describe assessments of physical performance and function in patients and survivors of pediatric cancer, including cardiorespiratory fitness, muscle strength, speed, balance, flexibility, functional mobility, gait and motor performance test batteries. METHODS: We searched the databases PubMed, SPORTDiscus, and Cochrane Database and performed abstract and full-text selection of 2619 articles according to the Cochrane Handbook of Systematic Reviews. Information on patients characteristics, assessments, information on validity and reliability, and relevant references was extracted. RESULTS: In summary, 63 different assessments were found in 149 studies including 11639 participants. Most studies evaluated cardiorespiratory fitness and muscle strength with the majority conducted off treatment. Some outcomes (e.g. speed) and diagnoses (e.g. neuroblastoma) were severely underrepresented. With the exception of gait, leukemia patients represented the largest group of individuals tested. CONCLUSIONS: Insufficient data and patient heterogeneity complicate uniform recommendations for assessments. Our results support researchers and practitioners in selecting appropriate assessment to meet their specific research questions or individual daily practice needs. IMPACT: This systematic review includes 149 studies and provides a comprehensive summary of 63 assessments to evaluate cardiorespiratory fitness, muscle strength, speed, balance, flexibility, functional mobility, gait or motor performance test batteries in patients and survivors of pediatric cancer. We present the most studied fields within the pediatric cancer population, which are cardiorespiratory fitness and muscle strength, off treatment phase, and leukemia patients. We propose research priorities by identification of subgroups in terms of cancer type, phase of treatment, and outcome of interest that are underrepresented in studies currently available.

Individually tailored whole-body vibration training to reduce symptoms of chemotherapy-induced peripheral neuropathy: study protocol of a randomised controlled trial-VANISH.

INTRODUCTION: Chemotherapy-induced peripheral neuropathy (CIPN) is a prevalent and clinically meaningful side effect of cancer treatment. CIPN is induced by neurotoxic agents, causing severe sensory and/or motor deficits, resulting in disability and poor recovery, reducing patients' quality of life and limiting medical therapy. To date, effective treatment options are lacking. Whole-body vibration (WBV) training can attenuate motor and sensory deficits. We are conducting a two-armed, multicentre, assessor-blinded, randomised controlled trial, to investigate the effects of WBV on relevant symptoms of CIPN and determine the training characteristics. METHODS AND ANALYSIS: In this ongoing study, 44 patients who have completed therapy in the past 3 months, with a neurologically confirmed CIPN are assessed before and after a 12-week intervention and follow-up. The intervention group receives WBV twice a week. Exercises are individually tailored according to the initially determined optimal neuromuscular response. The control group receives care as usual.Primary endpoint is the patient reported reduction of CIPN-related symptoms (Functional Assessment of Cancer Therapy/Gynaecology Oncology Group-Neurotoxicity). Secondary endpoints are compound muscle action potentials, distal motor latency, conduction velocity, F-waves from the tibial and peroneal nerve, antidromic sensory nerve conduction studies of the sural nerve, normalised electromyographic activity, peripheral deep sensitivity, proprioception, balance, pain, the feasibility of training settings, quality of life and the level of physical activity. AIM, ETHICS AND DISSEMINATION: The study was approved by both responsible ethics committees. (1) Our results may contribute to a better understanding of the effects of WBV on motor and sensory functions and (2) may provide information whether WBV at the most effective setting, is feasible for neuropathic patients. (3) Our results may also contribute to improve supportive care in oncology, thereby enhancing quality of life and enabling the optimal medical therapy. All results will be published in international peer-reviewed journals as well as a manual for clinical practice. TRIAL REGISTRATION NUMBER: NCT03032718.

Limited Walking Abilities and Impaired Ankle Dorsiflexion Function in Children After Intense Cancer Treatment.

BACKGROUND: With improved survival rates in pediatric oncology, the detection of adverse side- and late-effects is gaining increased interest. This cross-sectional study investigated walking abilities and ankle dorsiflexion function in children with cancer. PATIENTS: Study participants included 16 children with various cancers (4-20 years, patient group) after completion of the intense treatment and 16 age- and gender-matched healthy peers (comparison group). METHOD: Walking speed (10-meter-walking-test, treadmill test assessing preferred transition speed), walking capacity (2-minute-walk-test), walking balance (Timed-Up-And-Go-Test), active/passive ankle dorsiflexion range of motion (ROM) (goniometer) and ankle dorsiflexion strength (hand-held dynamometer) were comprehensively assessed. RESULTS: Significant lower values in the patient group were found for walking capacity, maximum walking speed, ankle dorsiflexion ROM and strength. No significant differences between the groups were found for preferred walking speed and walking balance. DISCUSSION: Limited walking abilities and ankle dorsiflexion dysfunctions are prominent in children with cancer; having the potential to impact children's community mobility and physical activity. CONCLUSIONS: To provide holistic care, the development of specific supportive strategies such as exercise interventions and its translation into clinical practice needs to be accelerated.