Pilot trial testing the effects of exercise on chemotherapy-induced peripheral neurotoxicity (CIPN) and the interoceptive brain system.

IF 2.8 3区医学 Q2 HEALTH CARE SCIENCES & SERVICES Supportive Care in Cancer Pub Date : 2024-09-21 DOI:10.1007/s00520-024-08855-y

Ian R Kleckner, Thushini Manuweera, Po-Ju Lin, Kaitlin H Chung, Amber S Kleckner, Jennifer S Gewandter, Eva Culakova, Madalina E Tivarus, Richard F Dunne, Kah Poh Loh, Nimish A Mohile, Shelli R Kesler, Karen M Mustian

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Abstract

Purpose: Chemotherapy-induced peripheral neurotoxicity (CIPN) is a prevalent, dose-limiting, tough-to-treat toxicity involving numbness, tingling, and pain in the extremities with enigmatic pathophysiology. This randomized controlled pilot study explored the feasibility and preliminary efficacy of exercise during chemotherapy on CIPN and the role of the interoceptive brain system, which processes bodily sensations.

Methods: Nineteen patients (65 ± 11 years old, 52% women; cancer type: breast, gastrointestinal, multiple myeloma) starting neurotoxic chemotherapy were randomized to 12 weeks of exercise (home-based, individually tailored, moderate intensity, progressive walking, and resistance training) or active control (nutrition education). At pre-, mid-, and post-intervention, we assessed CIPN symptoms (primary clinical outcome: CIPN-20), CIPN signs (tactile sensitivity using monofilaments), and physical function (leg strength). At pre- and post-intervention, we used task-free ("resting") fMRI to assess functional connectivity in the interoceptive brain system, involving the salience and default mode networks.

Results: The study was feasible (74-89% complete data across measures) and acceptable (95% retention). We observed moderate/large beneficial effects of exercise on CIPN symptoms (CIPN-20, 0-100 scale: - 7.9 ± 5.7, effect size [ES] = - 0.9 at mid-intervention; - 4.8 ± 7.3, ES = - 0.5 at post-intervention), CIPN signs (ES = - 1.0 and - 0.1), and physical function (ES = 0.4 and 0.3). Patients with worse CIPN after neurotoxic chemotherapy had lower functional connectivity within the default mode network (R² = 40-60%) and higher functional connectivity within the salience network (R² = 20-40%). Exercise tended to increase hypoconnectivity and decrease hyperconnectivity seen in CIPN (R² = 12%).

Conclusion: Exercise during neurotoxic chemotherapy is feasible and may attenuate CIPN symptoms and signs, perhaps via changes in interoceptive brain circuitry. Future work should test for replication with larger samples.

Trial registration: Registered Jan 2017 on ClinicalTrials.gov as NCT03021174.

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测试运动对化疗引起的外周神经毒性（CIPN）和大脑互感系统影响的试点试验。

目的：化疗诱导的周围神经毒性（CIPN）是一种普遍存在的、剂量限制性的、难以治疗的毒性反应，包括四肢麻木、刺痛和疼痛，其病理生理学十分神秘。这项随机对照试验研究探讨了化疗期间运动对 CIPN 的可行性和初步疗效，以及处理身体感觉的大脑互感系统的作用：19名开始接受神经毒性化疗的患者（65±11岁，52%为女性；癌症类型：乳腺癌、胃肠道癌、多发性骨髓瘤）被随机分配到为期12周的运动（以家庭为基础、个人定制、中等强度、渐进式步行和阻力训练）或积极对照组（营养教育）。在干预前、干预中和干预后，我们评估了CIPN症状（主要临床结果：CIPN-20）、CIPN体征（使用单丝的触觉敏感性）和身体功能（腿部力量）。在干预前和干预后，我们使用无任务（"静息"）fMRI来评估感知间大脑系统的功能连接，包括显著性和默认模式网络：这项研究是可行的（74-89% 的数据完整），也是可以接受的（95% 的保留率）。我们观察到运动对 CIPN 症状（CIPN-20，0-100 分：干预中期为 - 7.9 ± 5.7，效应大小 [ES] = - 0.9；干预后为 - 4.8 ± 7.3，效应大小 [ES] = - 0.5）、CIPN 体征（效应大小 [ES] = - 1.0 和 - 0.1）和身体功能（效应大小 [ES] = 0.4 和 0.3）有中等/较大的有益影响。神经毒性化疗后CIPN恶化的患者，其默认模式网络的功能连通性较低（R2 = 40-60%），而显著性网络的功能连通性较高（R2 = 20-40%）。运动倾向于增加低连接性，降低CIPN中的高连接性（R2 = 12%）：结论：在神经毒性化疗期间进行锻炼是可行的，而且可能会减轻 CIPN 的症状和体征，这或许是通过改变感知间脑回路实现的。未来的工作应使用更大的样本进行重复测试：2017年1月在ClinicalTrials.gov上注册为NCT03021174。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Supportive Care in Cancer 医学-康复医学

CiteScore

5.70

自引率

9.70%

发文量

751

审稿时长

3 months

期刊介绍： Supportive Care in Cancer provides members of the Multinational Association of Supportive Care in Cancer (MASCC) and all other interested individuals, groups and institutions with the most recent scientific and social information on all aspects of supportive care in cancer patients. It covers primarily medical, technical and surgical topics concerning supportive therapy and care which may supplement or substitute basic cancer treatment at all stages of the disease. Nursing, rehabilitative, psychosocial and spiritual issues of support are also included.