Bulletin of Rehabilitation MedicineBulletin of Rehabilitation MedicineВестник восстановительной медицины2078-19622713-2625National Medical Research Center for Rehabilitation and Balneology62608510.38025/2078-1962-2023-22-5-72-82ArticlesСтатьиResearch ArticleHigh-Intensity Pulsed Magnetotherapy in the Rehabilitation Programme of Patients with Chemotherapy-Induced Peripheral Polyneuropathy: a Prospective Randomized Clinical StudyВысокоинтенсивная импульсная магнитотерапия в реабилитационной программе пациентов с периферической полинейропатией, индуцированной химиотерапией: проспективное рандомизированное клиническое исследованиеhttps://orcid.org/0000-0002-7785-9767KulchitskayaDetelina B.КульчицкаяД. Б.
Russian Federation

Dr. Sci. (Med.), Professor, Chief Researcher, Department of Rhysiotherapy and Reflexology

kulchitskayadb@nmicrk.ruhttps://orcid.org/0000-0003-3097-8889FesyunAnatoliy D.ФесюнА. Д.
Russian Federation

Dr. Sci. (Med.), Professor, Department of Healthcare Organization and Health Resorts, Acting Director, President of the National Association of Experts in Spa Treatment

kulchitskayadb@nmicrk.ruhttps://orcid.org/0000-0001-7626-5521YurovaOlga V.ЮроваО. В.
Russian Federation

Dr. Sci. (Med.), Professor, Deputy Director, Research and Educational Activities

kulchitskayadb@nmicrk.ruhttps://orcid.org/0000-0003-0991-8988KonchugovaTatiana V.КончуговаТ. В.
Russian Federation

Dr. Sci. (Med.), Professor, Head of the Chair of Restorative Medicine, Physical Therapy and Medical Rehabilitation

kulchitskayadb@nmicrk.ruhttps://orcid.org/0000-0002-5260-8304YakovlevMaxim Yu.ЯковлевМ. Ю.
Russian Federation

Dr. Sci. (Med.), Deputy Director, Strategic Development of Medical Activities

kulchitskayadb@nmicrk.ruhttps://orcid.org/0000-0003-3852-2050ApkhanovaTatiana V.АпхановаТ. В.
Russian Federation

Dr. Sci. (Med.), Chief Researcher, of the Department of Physiotherapy and Reflexology

kulchitskayadb@nmicrk.ruhttps://orcid.org/0000-0001-7069-4472GushchinaNadezha V.ГущинаН. В.
Russian Federation

Ph.D., Senior Researcher of the Department of Physiotherapy and Reflexology

kulchitskayadb@nmicrk.ruhttps://orcid.org/0000-0002-5466-5513KudryavtsevAlexey E.КудрявцевА. Е.
Russian Federation

Ph.D., student

kulchitskayadb@nmicrk.ruNational Medical Research Center for Rehabilitation and BalneologyФГБУ «Национальный медицинский исследовательский центр реабилитации и курортологии» Минздрава России15112023225728226012024Copyright ©; 2023, Kulchitskaya D.B., Fesyun A.D., Yurova O.V., Konchugova T.V., Yakovlev M.Y., Apkhanova T.V., Gushchina N.V., Kudryavtsev A.E.Copyright ©; 2023, Кульчицкая Д.Б., Фесюн А.Д., Юрова О.В., Кончугова Т.В., Яковлев М.Ю., Апханова Т.В., Гущина Н.В., Кудрявцев А.Е.2023Kulchitskaya D.B., Fesyun A.D., Yurova O.V., Konchugova T.V., Yakovlev M.Y., Apkhanova T.V., Gushchina N.V., Kudryavtsev A.E.Кульчицкая Д.Б., Фесюн А.Д., Юрова О.В., Кончугова Т.В., Яковлев М.Ю., Апханова Т.В., Гущина Н.В., Кудрявцев А.Е.https://creativecommons.org/licenses/by/4.0https://journals.eco-vector.com/2078-1962/article/view/626085

INTRODUCTION. Chemotherapy-induced peripheral polyneuropathy (CIPN) is one of the most frequent side effects caused by anticancer drugs, with a prevalence ranging from 19 % to 85 %. For effective multicomponent rehabilitation of patients with CIPN at different stages, a number of non-medicinal methods are recommended to improve the tolerance of chemotherapy and reduce the side effects of the antitumor treatment performed.

AIM. Study of the effect of high-intensity pulsed magnetotherapy on clinical manifestations and microcirculation state in patients with CIPN.

DESIGN. This is a randomized controlled study.

SETTING. Randomization, organization of the study and data analysis were performed on the premises of the Department of Medical Rehabilitation in National Medical Research Centre for Rehabilitation and Balneology, Moscow, Russia.

POPULATION. Sixty patients with CIPN were included in this study and were randomized by a simple random distribution method in a ratio of 1:1 into 2 groups of 30 people.

METHODS. Sixty patients with CIPN four weeks after completion of chemotherapy were examined. The first group, the main group, included patients who received high-intensity pulsed magnetotherapy (HIPMT) in combination with drug therapy. In the second group (control group), the patients received only drug therapy. The EORTC-QLQ-C30 questionnaire (version 3) was used to assess the quality of life. The HADS scale was used to assess the severity of anxiety and depression symptoms. The state of microcirculation was assessed using laser Doppler flowmetry (LDF). The severity of CIPN was assessed according to the CTS-NCIC scale, version 3.0.

RESULTS. According to the results of this study, there is a statistically significant difference in the scores on the EORTC-QLQ-C30 questionnaire (version 3), HADS scale and LDF data between the groups in favour of the group receiving HIPMT in combination with drug therapy.

CONCLUSION. Based on the LDF study, significant disturbances at the microcirculatory level were detected for the first time in patients with CIPN. The obtained results convincingly demonstrate that the use of HIPMT in patients with CIPN leads not only to improvement of microcirculation in the extremities due to normalisation of arterial vessel tone, elimination of venous stasis and increase in the nutritive blood flow, but also has an analgesic effect, improves initially impaired sensitivity, and improves the quality of life of these patients.

CLINICAL REHABILITATION IMPACT. The use of HIPMT in combination with drug therapy in patients with CIPN was more effective than drug therapy alone.

ВВЕДЕНИЕ. Периферическая полинейропатия, индуцированная химиотерапией (ПНПИХ), является одним из наиболее частых побочных эффектов, вызываемых противоопухолевыми препаратами, с распространенностью от 19 % до 85 %. Для эффективной многокомпонентной реабилитации пациентов с ПНПИХ на различных этапах рекомендован ряд немедикаментозных методов с целью улучшения переносимости химиотерапии и снижения побочных эффектов проводимого противоопухолевого лечения.

ЦЕЛЬ. Изучение влияния высокоинтенсивной импульсной магнитотерапии (ВИМТ) на клинические проявления и состояние микроциркуляции у пациентов с ПНПИХ.

ДИЗАЙН. Это рандомизированное контролируемое исследование.

МЕСТО ПРОВЕДЕНИЯ ИССЛЕДОВАНИЯ: Рандомизация, организация исследования и анализ данных были выполнены на базе отделения медицинской реабилитации ФГБУ «НМИЦ РК» Минздрава России, Москва, Россия.

НАСЕЛЕНИЕ. В это исследование были включены 60 пациентов с ПНПИХ, которые были рандомизированы в соотношении 1:1 на 2 группы по 30 человек.

МЕТОДЫ. Были обследованы 60 пациентов с ПНПИХ спустя четыре недели после завершения химиотерапии. Первая группа — основная включала пациентов, которые получали ВИМТ в сочетании с медикаментозной терапией. Во второй группе (контрольной) пациенты получали только медикаментозную терапию. Для оценки качества жизни использовали опросник EORTC-QLQ-C30 (версия 3). Для оценки выраженности симптомов тревожности и депрессии применяли шкалу HADS. Состояние микроциркуляции оценивали, применяя лазерную доплеровскую флоуметрию (LDF). Степень тяжести ПНПИХ оценивали согласно шкале СТС-NCIC, версия 3.0.

РЕЗУЛЬТАТЫ. Согласно результатам этого исследования, существует статистически значимая разница в оценках по опроснику EORTC-QLQ-C30 (версия 3), шкале HADS и по данным лазерной допплеровской флоуметрии (ЛДФ) между группами в пользу группы получавших ВИМТ в сочетании с медикаментозной терапией.

ЗАКЛЮЧЕНИЕ. На основании проведенного исследования с помощью ЛДФ впервые у пациентов с ПНПИХ были выявлены существенные нарушения на микроциркуляторном уровне. Полученные результаты убедительно демонстрируют, что применение ВИМТ у пациентов с ПНПИХ приводит не только к улучшению микроциркуляции в конечностях за счет нормализации тонуса артериальных сосудов, устранения венозного застоя и увеличения нутритивного кровотока, но и оказывает обезболивающее действие, улучшает исходно нарушенную чувствительность, а также улучшает качество жизни данных пациентов.

ВЛИЯНИЕ РЕАБИЛИТАЦИИ. Применения ВИМТ в сочетании с медикаментозной терапией у пациентов с ПНПИХ было более эффективно чем применение только медикаментозной терапии.

CIPNcancer rehabilitationchemotherapymagnetic field therapypolyneuropathyполинейропатия, индуцированная химиотерапиейреабилитация при ракехимиотерапиятерапия магнитным полемполинейропатияZajączkowska R., Kocot-Kępska M., Leppert W. et al. Mechanisms of Chemotherapy-Induced Peripheral Neuropathy. International Journal of Molecular Sciences. 2019; 20(6): 1451. https://doi.org/10.3390/ijms20061451Bakogeorgos M., Georgoulias V. Risk-reduction and treatment of chemotherapy-induced peripheral neuropathy. Expert Review of Anticancer Therapy. 2017; 17(11): 1045–1060. https://doi.org/10.1080/14737140.2017.1374856Miltenburg N.C., Boogerd W. Chemotherapy-induced neuropathy: A comprehensive survey. Cancer Treatment Reviews. 2014; 40(7): 872–882. https://doi.org/10.1016/j.ctrv.2014.04.004Li K., Giustini D., Seely D. A systematic review of acupuncture for chemotherapy-induced peripheral neuropathy. Current Oncology. 2019; 26(2): 147–154. https://doi.org/10.3747/co.26.4261Kleckner I.R., Kamen C., Gewandter J.S. et al. Effects of exercise during chemotherapy on chemotherapy-induced peripheral neuropathy: a multicenter, randomized controlled trial. Supportive Care in Cancer. 2018; 26(4):1019–1028. https://doi.org/10.1007/s00520-017-4013-0Blan, K.A., Kirkham A.A., Bovard J. et al. Effect of Exercise on Taxane Chemotherapy-Induced Peripheral Neuropathy in Women with Breast Cancer: a Randomized Controlled Trial. Clinical Breast Cancer. 2019; 19(6): 411–422. https://doi.org/10.1016/j.clbc.2019.05.013Vollmers P.L., Mundhenke C., Maass N. et al. Evaluation of the effects of sensorimotor exercise on physical and psychological parameters in breast cancer patients undergoing neurotoxic chemotherapy. Journal of Cancer Research and Clinical Oncology. 2018; 144: 1785–179. https://doi.org/10.1007/s00432-018-2686-5Streckmann F., Kneis S., Leifert J.A. et al. Exercise program improves therapy-related side-effects and quality of life in lymphoma patients undergoing therapy. Annals of Oncology. 2014; 25: 493–499. https://doi.org/10.1093/annonc/mdt568Dhawan S., Andrews R., Kumar L. et al., A randomized controlled trial to assess the effectiveness of muscle strengthening and balancing exercises on chemotherapy-induced peripheral neuropathic pain and quality of life among cancer patients. Cancer Nursing. 2020; 43: 269–280. https://doi.org/10.1097/NCC.0000000000000693Duregon F., Vendramin B., Bullo V. et al. Effects of exercise on cancer patients suffering chemotherapy-induced peripheral neuropathy undergoing treatment: a systematic review. Critical reviews in oncology/hematology. 2018; 121: 90–100. https://doi.org/10.1016/j.critrevonc.2017.11.002Gui Q., Li D., Zhuge Y., Xu, C. Efficacy of exercise rehabilitation program in relieving oxaliplatin induced peripheral neurotoxicity. Asian Pacific Journal of Cancer Prevention. 2021; 22 (3): 705–709. https://doi.org/10.31557/APJCP.2021.22.3.705Alrida N.A., Ababneh A.M.T., Sumaqa Y.A. Effect of Exercise in Management of chemotherapy induced peripheral neuropathy: Evidence — Based Review. European Chemical Bulletin. 2023; 12(7): 2237–2243.Lin W.L., Wang R.H., Chou F.H. et al., The effects of exercise on chemotherapy-induced peripheral neuropathy symptoms in cancer patients: a systematic review and meta-analysis. Support. Care Cancer 2021; 29: 5303–5311. https://doi.org/10.1007/s00520-021-06082-3Streckmann F., Lehmann H., Balke M. et al. Sensorimotor training and whole-body vibration training have the potential to reduce motor and sensory symptoms of chemotherapy-induced peripheral neuropathy-a randomized controlled pilot trial. Support Care Cancer. 2019; 27(7): 2471–2478. https://doi.org/10.1007/s00520-018-4531-4Tonezzer T., Caffaro L.A.M., Menon K.R.S. et al. Effects of transcutaneous electrical nerve stimulation on chemotherapy-induced peripheral neuropathy symptoms (CIPN): a preliminary case-control study. Journal of Physical Therapy Science. 2017; 29(4): 685–692. https://doi.org/10.1589/jpts.29.685Sundar R., Bandla A., Tan S.S. et al. Limb hypothermia for preventing paclitaxel-induced peripheral neuropathy in breast Cancer patients: a pilot study. Frontiers in Oncology. 2017; 6: 274. https://doi.org/10.3389/fonc.2016.00274Simsek N.Y., Demir A. Cold application and exercise on development of peripheral neuropathy during taxane chemotherapy in breast Cancer patients: a randomized controlled trial. Asia-Pacific Journal of Oncology Nursing. 2021; 8: 255–266. https://doi.org/10.4103/apjon.apjon-2075Beijers A.J.M., Bonhof C.S., Mols F. et al. Multicenter randomized controlled trial to evaluate the efficacy and tolerability of frozen gloves for the prevention of chemotherapy-induced peripheral neuropathy. Annals of Oncology. 2020; 31: 131–136. https://doi.org/10.1016/j.annonc.2019.09.006Griffiths C., Kwon N., Beaumont J.L., Paice J.A. Cold therapy to prevent paclitaxel-induced peripheral neuropathy. Support. Care Cancer. 2018; 26: 3461–3469. https://doi.org/10.1007/s00520-018-4199-9Hanai A., Ishiguro H., Sozu T. et al. Effects of cryotherapy on objective and subjective symptoms of paclitaxel-induced neuropathy: prospective self-controlled trial. Journal of the National Cancer Institute. 2018; 110: 141–148. https://doi.org/10.1093/jnci/djx178Jang C.E., Jung M.S., Sohn E.H. et al. The evaluation of changes in peripheral neuropathy and quality-of-life using low-frequency electrostimulation in patients treated with chemotherapy for breast cancer: a study protocol. Trials. 2018; 19(1): 526. https://doi.org/10.1186/s13063-018-2874-2Geiger G., Mikus E., Dertinger H., Rick O. Low frequency magnetic field therapy in patients with cytostatic-induced polyneuropathy: a phase II pilot study. Bioelectromagnetics. 2015; 36(3): 251–254. https://doi.org/10.1002/bem.21897Childs D.S., Le-Rademacher J.G., McMurray R. et al. Randomized trial of scrambler therapy for chemotherapy-induced peripheral neuropathy: crossover analysis. J. Pain Symptom Manage. 2021; 61: 1247–1253. https://doi.org/10.1016/j.jpainsymman.2020.11.025Smith T.J., Razzak A.R., Blackford A.L. et al. A pilot randomized sham-controlled trial of MC5-A scrambler therapy in the treatment of chronic chemotherapy-induced peripheral neuropathy (CIPN). Journal of Palliative Care. 2020; 35: 53–58. https://doi.org/10.1177/0825859719827589Song S.Y., Park J.H., Lee J.S. et al. A randomized, placebo-controlled trial evaluating changes in peripheral neuropathy and quality of life by using low-frequency electrostimulation on breast Cancer patients treated with chemotherapy. Integrative Cancer Therapies. 2020; 19: 1534735420925519. https://doi.org/10.1177/1534735420925519Rick O., von Hehn U., Mikus E. et al. Magnetic field therapy in patients with cytostatics-induced polyneuropathy: A prospective randomized placebo-controlled phase-III study. Bioelectromagnetics. 2017; 38(2): 85–94. https://doi.org/10.1002/bem.22005Schulz, K.F., Altman, D.G., Moher, D. et al. CONSORT 2010 Statement: updated guidelines for reporting parallel group randomised trials. 2010; BMC Med 8, 18. https://doi.org/10.1186/1741-7015-8-18Grushina T.I. Reabilitaciya v onkologii: fizioterapiya. Moscow: GEOTAR-Media. 2006; 240 р. (In Russ.)Jones K.F., Wechsler S., Zulewski D., Wood L. Pharmacological and Nonpharmacological Management of Chemotherapy-Induced Peripheral Neuropathy: A Scoping Review of Randomized Controlled Trials. Journal of Palliative Medicine. 2022; 25(6): 964–995. https://doi.org/10.1089/jpm.2021.0512Smith T.L., Wong-Gibbons D., Maultsby J. Microcirculatory effects of pulsed electromagnetic fields. Journal of Orthopaedic Research. 2004; 22(1): 80–84. https://doi.org/10.1016/S0736-0266(03)00157-8Tepper O.M., Callaghan M.J., Chang E.I et al., Electromagnetic fields increase in vitro and in vivo angiogenesis through endothelial release of FGF-2. The FASEB Journal. 2004; 18(11): 1231–1233. https://doi.org/10.1096/fj.03-0847fjeDiniz P., Soejima K., Ito G. Nitric oxide mediates the effects of pulsed electromagnetic field stimulation on th osteoblast proliferation and differentiation. Nitric Oxide. 2002; 7(1): 18–23. https://doi.org/10.1016/S1089-8603(02)00004-6Klopp R.C., Niemer W. Schmidt W. Effects of various physical treatment methods on arteriolar vasomotion and microhemodynamic functional characteristics in case of deficient regulation of organ blood flow. Results of a placebo-controlled, double-blind study. Journal of Complementary and Integrative Medicine. 2013; 10(Suppl): S39–S46. https://doi.org/10.1515/jcim-2013-0035