Effectiveness of Nonpharmacologic Interventions for Chemotherapy-Induced Peripheral Neuropathy in Patients With Breast Cancer

Background Chemotherapy-induced peripheral neuropathy (CIPN) is a common adverse effect in patients with breast cancer (BC) during treatment. Patients experiencing CIPN develop neuropathic symptoms, which could lead to the modification or discontinuation of chemotherapy. Nonpharmacological interventions can be simple and safe, but evidence of their effectiveness in patients with BC experiencing CIPN is currently insufficient.To compare and rank the effectiveness of nonpharmacologic interventions for CIPN in patients with BC.We conducted a systematic search of randomized controlled trials registered from database inception until October 2022 in 7 databases. We assessed studies that met the inclusion and exclusion criteria and evaluated the risk of bias. Network meta-analysis was conducted using Stata SE 17.0 (StataCorp, College Station, Texas).A total of 13 studies involving 9 nonpharmacologic interventions and comprising 571 participants were included. The results of the network meta-analysis showed that cryotherapy (standard mean difference, -1.22; 95% confidence interval, -2.26 to -0.17) exerted significant effects versus usual care. Cryotherapy (surface under the cumulative ranking area [SUCRA]: 0.74) was associated with the highest likelihood of effectively alleviating CIPN in patients with BC, followed by exercise (SUCRA: 0.62) and self-acupressure (SUCRA: 0.59).Cryotherapy was the most effective nonpharmacologic intervention for alleviating CIPN in patients with BC. Large-scale studies are required to verify the present findings.This study provides evidence regarding the effectiveness of nonpharmacologic interventions for CIPN. Physicians and nurses could incorporate cryotherapy into clinical practice to alleviate CIPN in patients with BC.Breast cancer (BC) is the most commonly diagnosed type of cancer and the leading cause of cancer-related mortality among women worldwide.1 In 2020, approximately 2.3 million new cases of BC were reported.1 Advancements in the treatment of BC have improved patient survival rates; the 5-year survival rate in patients with locally invasive BC exceeds 90%.2 Chemotherapy is a frequently used treatment for patients with BC. It has been shown that chemotherapy increases the survival rates, while decreasing the risk of metastasis and recurrence.3 However, the use of chemotherapeutic agents can cause adverse effects (eg, neurotoxicity and peripheral nerve damage), leading to chemotherapy-induced peripheral neuropathy (CIPN) (a common dose-limiting adverse effect).4 The incidence rate of CIPN among patients with BC ranges from 11% to 80%.5,6 Patients with CIPN may experience a variety of sensory, motor, and autonomic system symptoms, including numbness in the hands and feet, neuropathic pain, muscle weakness, decreased balance, and orthostatic hypotension.7-9 These symptoms could potentially lead to the modification or discontinuation of chemotherapy. Chemotherapy-induced peripheral neuropathy may persist for months or even years after treatment, significantly impacting the quality of life of patients.10Interventions for CIPN are categorized as pharmacologic or nonpharmacologic. According to the CIPN guidelines established by the American Society of Clinical Oncology in 2020, duloxetine is the only medication recommended for the treatment of patients with CIPN experiencing neuropathic pain.4 However, duloxetine has moderate benefits and can cause adverse effects (eg, fatigue, insomnia, and nausea),11 thereby limiting its usefulness in patients receiving chemotherapy. 12 Nonpharmacologic interventions are attracting attention owing to their cost-effectiveness and favorable safety profile.13 These interventions include acupuncture, acupressure, exercise, cryotherapy, classic massage, and so on.14-17 Several systematic reviews and meta-analyses have demonstrated the benefits of nonpharmacologic interventions in patients with CIPN.14,15,18 However, the most effective nonpharmacological intervention for CIPN in patients with BC remains unknown.Network meta-analysis (NMA) is a statistical method that enables the comparison of multiple interventions beyond a pairwise comparison by incorporating direct and indirect evidence. It ranks interventions based on the size of their effects, even in the absence of randomized controlled trials (RCTs) offering a direct comparison.19,20 In light of this, we conducted a systematic review and NMA to establish clinical nursing guidelines for managing CIPN in patients with BC through comparison and evaluation of various nonpharmacologic interventions. The aims of this systematic review and NMA were to compare different nonpharmacologic interventions for CIPN in patients with BC and rank them according to their effectiveness.Background Chemotherapy-induced peripheral neuropathy (CIPN) is a common adverse effect in patients with breast cancer (BC) during treatment. Patients experiencing CIPN develop neuropathic symptoms, which could lead to the modification or discontinuation of chemotherapy. Nonpharmacological interventions can be simple and safe, but evidence of their effectiveness in patients with BC experiencing CIPN is currently insufficient.To compare and rank the effectiveness of nonpharmacologic interventions for CIPN in patients with BC.We conducted a systematic search of randomized controlled trials registered from database inception until October 2022 in 7 databases. We assessed studies that met the inclusion and exclusion criteria and evaluated the risk of bias. Network meta-analysis was conducted using Stata SE 17.0 (StataCorp, College Station, Texas).A total of 13 studies involving 9 nonpharmacologic interventions and comprising 571 participants were included. The results of the network meta-analysis showed that cryotherapy (standard mean difference, -1.22; 95% confidence interval, -2.26 to -0.17) exerted significant effects versus usual care. Cryotherapy (surface under the cumulative ranking area [SUCRA]: 0.74) was associated with the highest likelihood of effectively alleviating CIPN in patients with BC, followed by exercise (SUCRA: 0.62) and self-acupressure (SUCRA: 0.59).Cryotherapy was the most effective nonpharmacologic intervention for alleviating CIPN in patients with BC. Large-scale studies are required to verify the present findings.This study provides evidence regarding the effectiveness of nonpharmacologic interventions for CIPN. Physicians and nurses could incorporate cryotherapy into clinical practice to alleviate CIPN in patients with BC.Breast cancer (BC) is the most commonly diagnosed type of cancer and the leading cause of cancer-related mortality among women worldwide.1 In 2020, approximately 2.3 million new cases of BC were reported.1 Advancements in the treatment of BC have improved patient survival rates; the 5-year survival rate in patients with locally invasive BC exceeds 90%.2 Chemotherapy is a frequently used treatment for patients with BC. It has been shown that chemotherapy increases the survival rates, while decreasing the risk of metastasis and recurrence. 3 However, the use of chemotherapeutic agents can cause adverse effects (eg, neurotoxicity and peripheral nerve damage), leading to chemotherapy-induced peripheral neuropathy (CIPN) (a common dose-limiting adverse effect).4 The incidence rate of CIPN among patients with BC ranges from 11% to 80%.5,6 Patients with CIPN may experience a variety of sensory, motor, and autonomic system symptoms, including numbness in the hands and feet, neuropathic pain, muscle weakness, decreased balance, and orthostatic hypotension.7-9 These symptoms could potentially lead to the modification or discontinuation of chemotherapy. Chemotherapy-induced peripheral neuropathy may persist for months or even years after treatment, significantly impacting the quality of life of patients.10Interventions for CIPN are categorized as pharmacologic or nonpharmacologic. According to the CIPN guidelines established by the American Society of Clinical Oncology in 2020, duloxetine is the only medication recommended for the treatment of patients with CIPN experiencing neuropathic pain.4 However, duloxetine has moderate benefits and can cause adverse effects (eg, fatigue, insomnia, and nausea),11 thereby limiting its usefulness in patients receiving chemotherapy.12 Nonpharmacologic interventions are attracting attention owing to their cost-effectiveness and favorable safety profile.13 These interventions include acupuncture, acupressure, exercise, cryotherapy, classic massage, and so on.14-17 Several systematic reviews and meta-analyses have demonstrated the benefits of nonpharmacologic interventions in patients with CIPN.14,15,18 However, the most effective nonpharmacological intervention for CIPN in patients with BC remains unknown.Network meta-analysis (NMA) is a statistical method that enables the comparison of multiple interventions beyond a pairwise comparison by incorporating direct and indirect evidence. It ranks interventions based on the size of their effects, even in the absence of randomized controlled trials (RCTs) offering a direct comparison.19,20 In light of this, we conducted a systematic review and NMA to establish clinical nursing guidelines for managing CIPN in patients with BC through comparison and evaluation of various nonpharmacologic interventions. The aims of this systematic review and NMA were to compare different nonpharmacologic interventions for CIPN in patients with BC and rank them according to their effectiveness.Background Chemotherapy-induced peripheral neuropathy (CIPN) is a common adverse effect in patients with breast cancer (BC) during treatment. Patients experiencing CIPN develop neuropathic symptoms, which could lead to the modification or discontinuation of chemotherapy. Nonpharmacological interventions can be simple and safe, but evidence of their effectiveness in patients with BC experiencing CIPN is currently insufficient.To compare and rank the effectiveness of nonpharmacologic interventions for CIPN in patients with BC.We conducted a systematic search of randomized controlled trials registered from database inception until October 2022 in 7 databases. We assessed studies that met the inclusion and exclusion criteria and evaluated the risk of bias. Network meta-analysis was conducted using Stata SE 17.0 (StataCorp, College Station, Texas).A total of 13 studies involving 9 nonpharmacologic interventions and comprising 571 participants were included. The results of the network meta-analysis showed that cryotherapy (standard mean difference, -1.22; 95% confidence interval, -2.26 to -0. 17) exerted significant effects versus usual care. Cryotherapy (surface under the cumulative ranking area [SUCRA]: 0.74) was associated with the highest likelihood of effectively alleviating CIPN in patients with BC, followed by exercise (SUCRA: 0.62) and self-acupressure (SUCRA: 0.59).Cryotherapy was the most effective nonpharmacologic intervention for alleviating CIPN in patients with BC. Large-scale studies are required to verify the present findings.This study provides evidence regarding the effectiveness of nonpharmacologic interventions for CIPN. Physicians and nurses could incorporate cryotherapy into clinical practice to alleviate CIPN in patients with BC.Breast cancer (BC) is the most commonly diagnosed type of cancer and the leading cause of cancer-related mortality among women worldwide.1 In 2020, approximately 2.3 million new cases of BC were reported.1 Advancements in the treatment of BC have improved patient survival rates; the 5-year survival rate in patients with locally invasive BC exceeds 90%.2 Chemotherapy is a frequently used treatment for patients with BC. It has been shown that chemotherapy increases the survival rates, while decreasing the risk of metastasis and recurrence.3 However, the use of chemotherapeutic agents can cause adverse effects (eg, neurotoxicity and peripheral nerve damage), leading to chemotherapy-induced peripheral neuropathy (CIPN) (a common dose-limiting adverse effect).4 The incidence rate of CIPN among patients with BC ranges from 11% to 80%.5,6 Patients with CIPN may experience a variety of sensory, motor, and autonomic system symptoms, including numbness in the hands and feet, neuropathic pain, muscle weakness, decreased balance, and orthostatic hypotension.7-9 These symptoms could potentially lead to the modification or discontinuation of chemotherapy. Chemotherapy-induced peripheral neuropathy may persist for months or even years after treatment, significantly impacting the quality of life of patients.10Interventions for CIPN are categorized as pharmacologic or nonpharmacologic. According to the CIPN guidelines established by the American Society of Clinical Oncology in 2020, duloxetine is the only medication recommended for the treatment of patients with CIPN experiencing neuropathic pain.4 However, duloxetine has moderate benefits and can cause adverse effects (eg, fatigue, insomnia, and nausea),11 thereby limiting its usefulness in patients receiving chemotherapy.12 Nonpharmacologic interventions are attracting attention owing to their cost-effectiveness and favorable safety profile.13 These interventions include acupuncture, acupressure, exercise, cryotherapy, classic massage, and so on.14-17 Several systematic reviews and meta-analyses have demonstrated the benefits of nonpharmacologic interventions in patients with CIPN.14,15,18 However, the most effective nonpharmacological intervention for CIPN in patients with BC remains unknown.Network meta-analysis (NMA) is a statistical method that enables the comparison of multiple interventions beyond a pairwise comparison by incorporating direct and indirect evidence. It ranks interventions based on the size of their effects, even in the absence of randomized controlled trials (RCTs) offering a direct comparison.19,20 In light of this, we conducted a systematic review and NMA to establish clinical nursing guidelines for managing CIPN in patients with BC through comparison and evaluation of various nonpharmacologic interventions. The aims of this systematic review and NMA were to compare different nonpharmacologic interventions for CIPN in patients with BC and rank them according to their effectiveness.Background Chemotherapy-induced peripheral neuropathy (CIPN) is a common adverse effect in patients with breast cancer (BC) during treatment. Patients experiencing CIPN develop neuropathic symptoms, which could lead to the modification or discontinuation of chemotherapy. Nonpharmacological interventions can be simple and safe, but evidence of their effectiveness in patients with BC experiencing CIPN is currently insufficient.To compare and rank the effectiveness of nonpharmacologic interventions for CIPN in patients with BC.We conducted a systematic search of randomized controlled trials registered from database inception until October 2022 in 7 databases. We assessed studies that met the inclusion and exclusion criteria and evaluated the risk of bias. Network meta-analysis was conducted using Stata SE 17.0 (StataCorp, College Station, Texas).A total of 13 studies involving 9 nonpharmacologic interventions and comprising 571 participants were included. The results of the network meta-analysis showed that cryotherapy (standard mean difference, -1.22; 95% confidence interval, -2.26 to -0.17) exerted significant effects versus usual care. Cryotherapy (surface under the cumulative ranking area [SUCRA]: 0.74) was associated with the highest likelihood of effectively alleviating CIPN in patients with BC, followed by exercise (SUCRA: 0.62) and self-acupressure (SUCRA: 0.59).Cryotherapy was the most effective nonpharmacologic intervention for alleviating CIPN in patients with BC. Large-scale studies are required to verify the present findings.This study provides evidence regarding the effectiveness of nonpharmacologic interventions for CIPN. Physicians and nurses could incorporate cryotherapy into clinical practice to alleviate CIPN in patients with BC.Breast cancer (BC) is the most commonly diagnosed type of cancer and the leading cause of cancer-related mortality among women worldwide.1 In 2020, approximately 2.3 million new cases of BC were reported.1 Advancements in the treatment of BC have improved patient survival rates; the 5-year survival rate in patients with locally invasive BC exceeds 90%.2 Chemotherapy is a frequently used treatment for patients with BC. It has been shown that chemotherapy increases the survival rates, while decreasing the risk of metastasis and recurrence.3 However, the use of chemotherapeutic agents can cause adverse effects (eg, neurotoxicity and peripheral nerve damage), leading to chemotherapy-induced peripheral neuropathy (CIPN) (a common dose-limiting adverse effect).4 The incidence rate of CIPN among patients with BC ranges from 11% to 80%.5,6 Patients with CIPN may experience a variety of sensory, motor, and autonomic system symptoms, including numbness in the hands and feet, neuropathic pain, muscle weakness, decreased balance, and orthostatic hypotension.7-9 These symptoms could potentially lead to the modification or discontinuation of chemotherapy. Chemotherapy-induced peripheral neuropathy may persist for months or even years after treatment, significantly impacting the quality of life of patients.10Interventions for CIPN are categorized as pharmacologic or nonpharmacologic. According to the CIPN guidelines established by the American Society of Clinical Oncology in 2020, duloxetine is the only medication recommended for the treatment of patients with CIPN experiencing neuropathic pain. 4 However, duloxetine has moderate benefits and can cause adverse effects (eg, fatigue, insomnia, and nausea),11 thereby limiting its usefulness in patients receiving chemotherapy.12 Nonpharmacologic interventions are attracting attention owing to their cost-effectiveness and favorable safety profile.13 These interventions include acupuncture, acupressure, exercise, cryotherapy, classic massage, and so on.14-17 Several systematic reviews and meta-analyses have demonstrated the benefits of nonpharmacologic interventions in patients with CIPN.14,15,18 However, the most effective nonpharmacological intervention for CIPN in patients with BC remains unknown.Network meta-analysis (NMA) is a statistical method that enables the comparison of multiple interventions beyond a pairwise comparison by incorporating direct and indirect evidence. It ranks interventions based on the size of their effects, even in the absence of randomized controlled trials (RCTs) offering a direct comparison.19,20 In light of this, we conducted a systematic review and NMA to establish clinical nursing guidelines for managing CIPN in patients with BC through comparison and evaluation of various nonpharmacologic interventions. The aims of this systematic review and NMA were to compare different nonpharmacologic interventions for CIPN in patients with BC and rank them according to their effectiveness.Background Chemotherapy-induced peripheral neuropathy (CIPN) is a common adverse effect in patients with breast cancer (BC) during treatment. Patients experiencing CIPN develop neuropathic symptoms, which could lead to the modification or discontinuation of chemotherapy. Nonpharmacological interventions can be simple and safe, but evidence of their effectiveness in patients with BC experiencing CIPN is currently insufficient.To compare and rank the effectiveness of nonpharmacologic interventions for CIPN in patients with BC.We conducted a systematic search of randomized controlled trials registered from database inception until October 2022 in 7 databases. We assessed studies that met the inclusion and exclusion criteria and evaluated the risk of bias. Network meta-analysis was conducted using Stata SE 17.0 (StataCorp, College Station, Texas).A total of 13 studies involving 9 nonpharmacologic interventions and comprising 571 participants were included. The results of the network meta-analysis showed that cryotherapy (standard mean difference, -1.22; 95% confidence interval, -2.26 to -0.17) exerted significant effects versus usual care. Cryotherapy (surface under the cumulative ranking area [SUCRA]: 0.74) was associated with the highest likelihood of effectively alleviating CIPN in patients with BC, followed by exercise (SUCRA: 0.62) and self-acupressure (SUCRA: 0.59).Cryotherapy was the most effective nonpharmacologic intervention for alleviating CIPN in patients with BC. Large-scale studies are required to verify the present findings.This study provides evidence regarding the effectiveness of nonpharmacologic interventions for CIPN. Physicians and nurses could incorporate cryotherapy into clinical practice to alleviate CIPN in patients with BC.Breast cancer (BC) is the most commonly diagnosed type of cancer and the leading cause of cancer-related mortality among women worldwide.1 In 2020, approximately 2.3 million new cases of BC were reported.1 Advancements in the treatment of BC have improved patient survival rates; the 5-year survival rate in patients with locally invasive BC exceeds 90%.2 Chemotherapy is a frequently used treatment for patients with BC. It has been shown that chemotherapy increases the survival rates, while decreasing the risk of metastasis and recurrence.3 However, the use of chemotherapeutic agents can cause adverse effects (eg, neurotoxicity and peripheral nerve damage), leading to chemotherapy-induced peripheral neuropathy (CIPN) (a common dose-limiting adverse effect).4 The incidence rate of CIPN among patients with BC ranges from 11% to 80%.5,6 Patients with CIPN may experience a variety of sensory, motor, and autonomic system symptoms, including numbness in the hands and feet, neuropathic pain, muscle weakness, decreased balance, and orthostatic hypotension.7-9 These symptoms could potentially lead to the modification or discontinuation of chemotherapy. Chemotherapy-induced peripheral neuropathy may persist for months or even years after treatment, significantly impacting the quality of life of patients.10Interventions for CIPN are categorized as pharmacologic or nonpharmacologic. According to the CIPN guidelines established by the American Society of Clinical Oncology in 2020, duloxetine is the only medication recommended for the treatment of patients with CIPN experiencing neuropathic pain.4 However, duloxetine has moderate benefits and can cause adverse effects (eg, fatigue, insomnia, and nausea),11 thereby limiting its usefulness in patients receiving chemotherapy.12 Nonpharmacologic interventions are attracting attention owing to their cost-effectiveness and favorable safety profile.13 These interventions include acupuncture, acupressure, exercise, cryotherapy, classic massage, and so on.14-17 Several systematic reviews and meta-analyses have demonstrated the benefits of nonpharmacologic interventions in patients with CIPN.14,15,18 However, the most effective nonpharmacological intervention for CIPN in patients with BC remains unknown.Network meta-analysis (NMA) is a statistical method that enables the comparison of multiple interventions beyond a pairwise comparison by incorporating direct and indirect evidence. It ranks interventions based on the size of their effects, even in the absence of randomized controlled trials (RCTs) offering a direct comparison.19,20 In light of this, we conducted a systematic review and NMA to establish clinical nursing guidelines for managing CIPN in patients with BC through comparison and evaluation of various nonpharmacologic interventions. The aims of this systematic review and NMA were to compare different nonpharmacologic interventions for CIPN in patients with BC and rank them according to their effectiveness.Background Chemotherapy-induced peripheral neuropathy (CIPN) is a common adverse effect in patients with breast cancer (BC) during treatment. Patients experiencing CIPN develop neuropathic symptoms, which could lead to the modification or discontinuation of chemotherapy. Nonpharmacological interventions can be simple and safe, but evidence of their effectiveness in patients with BC experiencing CIPN is currently insufficient.To compare and rank the effectiveness of nonpharmacologic interventions for CIPN in patients with BC.We conducted a systematic search of randomized controlled trials registered from database inception until October 2022 in 7 databases. We assessed studies that met the inclusion and exclusion criteria and evaluated the risk of bias. Network meta-analysis was conducted using Stata SE 17.0 (StataCorp, College Station, Texas).A total of 13 studies involving 9 nonpharmacologic interventions and comprising 571 participants were included. The results of the network meta-analysis showed that cryotherapy (standard mean difference, -1.22; 95% confidence interval, -2.26 to -0.17) exerted significant effects versus usual care. Cryotherapy (surface under the cumulative ranking area [SUCRA]: 0.74) was associated with the highest likelihood of effectively alleviating CIPN in patients with BC, followed by exercise (SUCRA: 0.62) and self-acupressure (SUCRA: 0.59).Cryotherapy was the most effective nonpharmacologic intervention for alleviating CIPN in patients with BC. Large-scale studies are required to verify the present findings.This study provides evidence regarding the effectiveness of nonpharmacologic interventions for CIPN. Physicians and nurses could incorporate cryotherapy into clinical practice to alleviate CIPN in patients with BC.Breast cancer (BC) is the most commonly diagnosed type of cancer and the leading cause of cancer-related mortality among women worldwide.1 In 2020, approximately 2.3 million new cases of BC were reported.1 Advancements in the treatment of BC have improved patient survival rates; the 5-year survival rate in patients with locally invasive BC exceeds 90%.2 Chemotherapy is a frequently used treatment for patients with BC. It has been shown that chemotherapy increases the survival rates, while decreasing the risk of metastasis and recurrence.3 However, the use of chemotherapeutic agents can cause adverse effects (eg, neurotoxicity and peripheral nerve damage), leading to chemotherapy-induced peripheral neuropathy (CIPN) (a common dose-limiting adverse effect).4 The incidence rate of CIPN among patients with BC ranges from 11% to 80%.5,6 Patients with CIPN may experience a variety of sensory, motor, and autonomic system symptoms, including numbness in the hands and feet, neuropathic pain, muscle weakness, decreased balance, and orthostatic hypotension.7-9 These symptoms could potentially lead to the modification or discontinuation of chemotherapy. Chemotherapy-induced peripheral neuropathy may persist for months or even years after treatment, significantly impacting the quality of life of patients.10Interventions for CIPN are categorized as pharmacologic or nonpharmacologic. According to the CIPN guidelines established by the American Society of Clinical Oncology in 2020, duloxetine is the only medication recommended for the treatment of patients with CIPN experiencing neuropathic pain.4 However, duloxetine has moderate benefits and can cause adverse effects (eg, fatigue, insomnia, and nausea),11 thereby limiting its usefulness in patients receiving chemotherapy.12 Nonpharmacologic interventions are attracting attention owing to their cost-effectiveness and favorable safety profile.13 These interventions include acupuncture, acupressure, exercise, cryotherapy, classic massage, and so on.14-17 Several systematic reviews and meta-analyses have demonstrated the benefits of nonpharmacologic interventions in patients with CIPN.14,15,18 However, the most effective nonpharmacological intervention for CIPN in patients with BC remains unknown.Network meta-analysis (NMA) is a statistical method that enables the comparison of multiple interventions beyond a pairwise comparison by incorporating direct and indirect evidence. It ranks interventions based on the size of their effects, even in the absence of randomized controlled trials (RCTs) offering a direct comparison. 19,20 In light of this, we conducted a systematic review and NMA to establish clinical nursing guidelines for managing CIPN in patients with BC through comparison and evaluation of various nonpharmacologic interventions. The aims of this systematic review and NMA were to compare different nonpharmacologic interventions for CIPN in patients with BC and rank them according to their effectiveness.Background Chemotherapy-induced peripheral neuropathy (CIPN) is a common adverse effect in patients with breast cancer (BC) during treatment. Patients experiencing CIPN develop neuropathic symptoms, which could lead to the modification or discontinuation of chemotherapy. Nonpharmacological interventions can be simple and safe, but evidence of their effectiveness in patients with BC experiencing CIPN is currently insufficient.To compare and rank the effectiveness of nonpharmacologic interventions for CIPN in patients with BC.We conducted a systematic search of randomized controlled trials registered from database inception until October 2022 in 7 databases. We assessed studies that met the inclusion and exclusion criteria and evaluated the risk of bias. Network meta-analysis was conducted using Stata SE 17.0 (StataCorp, College Station, Texas).A total of 13 studies involving 9 nonpharmacologic interventions and comprising 571 participants were included. The results of the network meta-analysis showed that cryotherapy (standard mean difference, -1.22; 95% confidence interval, -2.26 to -0.17) exerted significant effects versus usual care. Cryotherapy (surface under the cumulative ranking area [SUCRA]: 0.74) was associated with the highest likelihood of effectively alleviating CIPN in patients with BC, followed by exercise (SUCRA: 0.62) and self-acupressure (SUCRA: 0.59).Cryotherapy was the most effective nonpharmacologic intervention for alleviating CIPN in patients with BC. Large-scale studies are required to verify the present findings.This study provides evidence regarding the effectiveness of nonpharmacologic interventions for CIPN. Physicians and nurses could incorporate cryotherapy into clinical practice to alleviate CIPN in patients with BC.Breast cancer (BC) is the most commonly diagnosed type of cancer and the leading cause of cancer-related mortality among women worldwide.1 In 2020, approximately 2.3 million new cases of BC were reported.1 Advancements in the treatment of BC have improved patient survival rates; the 5-year survival rate in patients with locally invasive BC exceeds 90%.2 Chemotherapy is a frequently used treatment for patients with BC. It has been shown that chemotherapy increases the survival rates, while decreasing the risk of metastasis and recurrence.3 However, the use of chemotherapeutic agents can cause adverse effects (eg, neurotoxicity and peripheral nerve damage), leading to chemotherapy-induced peripheral neuropathy (CIPN) (a common dose-limiting adverse effect).4 The incidence rate of CIPN among patients with BC ranges from 11% to 80%.5,6 Patients with CIPN may experience a variety of sensory, motor, and autonomic system symptoms, including numbness in the hands and feet, neuropathic pain, muscle weakness, decreased balance, and orthostatic hypotension.7-9 These symptoms could potentially lead to the modification or discontinuation of chemotherapy. Chemotherapy-induced peripheral neuropathy may persist for months or even years after treatment, significantly impacting the quality of life of patients.10Interventions for CIPN are categorized as pharmacologic or nonpharmacologic. According to the CIPN guidelines established by the American Society of Clinical Oncology in 2020, duloxetine is the only medication recommended for the treatment of patients with CIPN experiencing neuropathic pain.4 However, duloxetine has moderate benefits and can cause adverse effects (eg, fatigue, insomnia, and nausea),11 thereby limiting its usefulness in patients receiving chemotherapy.12 Nonpharmacologic interventions are attracting attention owing to their cost-effectiveness and favorable safety profile.13 These interventions include acupuncture, acupressure, exercise, cryotherapy, classic massage, and so on.14-17 Several systematic reviews and meta-analyses have demonstrated the benefits of nonpharmacologic interventions in patients with CIPN.14,15,18 However, the most effective nonpharmacological intervention for CIPN in patients with BC remains unknown.Network meta-analysis (NMA) is a statistical method that enables the comparison of multiple interventions beyond a pairwise comparison by incorporating direct and indirect evidence. It ranks interventions based on the size of their effects, even in the absence of randomized controlled trials (RCTs) offering a direct comparison.19,20 In light of this, we conducted a systematic review and NMA to establish clinical nursing guidelines for managing CIPN in patients with BC through comparison and evaluation of various nonpharmacologic interventions. The aims of this systematic review and NMA were to compare different nonpharmacologic interventions for CIPN in patients with BC and rank them according to their effectiveness.Background Chemotherapy-induced peripheral neuropathy (CIPN) is a common adverse effect in patients with breast cancer (BC) during treatment. Patients experiencing CIPN develop neuropathic symptoms, which could lead to the modification or discontinuation of chemotherapy. Nonpharmacological interventions can be simple and safe, but evidence of their effectiveness in patients with BC experiencing CIPN is currently insufficient.To compare and rank the effectiveness of nonpharmacologic interventions for CIPN in patients with BC.We conducted a systematic search of randomized controlled trials registered from database inception until October 2022 in 7 databases. We assessed studies that met the inclusion and exclusion criteria and evaluated the risk of bias. Network meta-analysis was conducted using Stata SE 17.0 (StataCorp, College Station, Texas).A total of 13 studies involving 9 nonpharmacologic interventions and comprising 571 participants were included. The results of the network meta-analysis showed that cryotherapy (standard mean difference, -1.22; 95% confidence interval, -2.26 to -0.17) exerted significant effects versus usual care. Cryotherapy (surface under the cumulative ranking area [SUCRA]: 0.74) was associated with the highest likelihood of effectively alleviating CIPN in patients with BC, followed by exercise (SUCRA: 0.62) and self-acupressure (SUCRA: 0.59).Cryotherapy was the most effective nonpharmacologic intervention for alleviating CIPN in patients with BC. Large-scale studies are required to verify the present findings.This study provides evidence regarding the effectiveness of nonpharmacologic interventions for CIPN. Physicians and nurses could incorporate cryotherapy into clinical practice to alleviate CIPN in patients with BC.Breast cancer (BC) is the most commonly diagnosed type of cancer and the leading cause of cancer-related mortality among women worldwide.1 In 2020, approximately 2.3 million new cases of BC were reported. 1 Advancements in the treatment of BC have improved patient survival rates; the 5-year survival rate in patients with locally invasive BC exceeds 90%.2 Chemotherapy is a frequently used treatment for patients with BC. It has been shown that chemotherapy increases the survival rates, while decreasing the risk of metastasis and recurrence.3 However, the use of chemotherapeutic agents can cause adverse effects (eg, neurotoxicity and peripheral nerve damage), leading to chemotherapy-induced peripheral neuropathy (CIPN) (a common dose-limiting adverse effect).4 The incidence rate of CIPN among patients with BC ranges from 11% to 80%.5,6 Patients with CIPN may experience a variety of sensory, motor, and autonomic system symptoms, including numbness in the hands and feet, neuropathic pain, muscle weakness, decreased balance, and orthostatic hypotension.7-9 These symptoms could potentially lead to the modification or discontinuation of chemotherapy. Chemotherapy-induced peripheral neuropathy may persist for months or even years after treatment, significantly impacting the quality of life of patients.10Interventions for CIPN are categorized as pharmacologic or nonpharmacologic. According to the CIPN guidelines established by the American Society of Clinical Oncology in 2020, duloxetine is the only medication recommended for the treatment of patients with CIPN experiencing neuropathic pain.4 However, duloxetine has moderate benefits and can cause adverse effects (eg, fatigue, insomnia, and nausea),11 thereby limiting its usefulness in patients receiving chemotherapy.12 Nonpharmacologic interventions are attracting attention owing to their cost-effectiveness and favorable safety profile.13 These interventions include acupuncture, acupressure, exercise, cryotherapy, classic massage, and so on.14-17 Several systematic reviews and meta-analyses have demonstrated the benefits of nonpharmacologic interventions in patients with CIPN.14,15,18 However, the most effective nonpharmacological intervention for CIPN in patients with BC remains unknown.Network meta-analysis (NMA) is a statistical method that enables the comparison of multiple interventions beyond a pairwise comparison by incorporating direct and indirect evidence. It ranks interventions based on the size of their effects, even in the absence of randomized controlled trials (RCTs) offering a direct comparison.19,20 In light of this, we conducted a systematic review and NMA to establish clinical nursing guidelines for managing CIPN in patients with BC through comparison and evaluation of various nonpharmacologic interventions. The aims of this systematic review and NMA were to compare different nonpharmacologic interventions for CIPN in patients with BC and rank them according to their effectiveness.Background Chemotherapy-induced peripheral neuropathy (CIPN) is a common adverse effect in patients with breast cancer (BC) during treatment. Patients experiencing CIPN develop neuropathic symptoms, which could lead to the modification or discontinuation of chemotherapy. Nonpharmacological interventions can be simple and safe, but evidence of their effectiveness in patients with BC experiencing CIPN is currently insufficient.To compare and rank the effectiveness of nonpharmacologic interventions for CIPN in patients with BC.We conducted a systematic search of randomized controlled trials registered from database inception until October 2022 in 7 databases. We assessed studies that met the inclusion and exclusion criteria and evaluated the risk of bias. Network meta-analysis was conducted using Stata SE 17.0 (StataCorp, College Station, Texas).A total of 13 studies involving 9 nonpharmacologic interventions and comprising 571 participants were included. The results of the network meta-analysis showed that cryotherapy (standard mean difference, -1.22; 95% confidence interval, -2.26 to -0.17) exerted significant effects versus usual care. Cryotherapy (surface under the cumulative ranking area [SUCRA]: 0.74) was associated with the highest likelihood of effectively alleviating CIPN in patients with BC, followed by exercise (SUCRA: 0.62) and self-acupressure (SUCRA: 0.59).Cryotherapy was the most effective nonpharmacologic intervention for alleviating CIPN in patients with BC. Large-scale studies are required to verify the present findings.This study provides evidence regarding the effectiveness of nonpharmacologic interventions for CIPN. Physicians and nurses could incorporate cryotherapy into clinical practice to alleviate CIPN in patients with BC.Breast cancer (BC) is the most commonly diagnosed type of cancer and the leading cause of cancer-related mortality among women worldwide.1 In 2020, approximately 2.3 million new cases of BC were reported.1 Advancements in the treatment of BC have improved patient survival rates; the 5-year survival rate in patients with locally invasive BC exceeds 90%.2 Chemotherapy is a frequently used treatment for patients with BC. It has been shown that chemotherapy increases the survival rates, while decreasing the risk of metastasis and recurrence.3 However, the use of chemotherapeutic agents can cause adverse effects (eg, neurotoxicity and peripheral nerve damage), leading to chemotherapy-induced peripheral neuropathy (CIPN) (a common dose-limiting adverse effect).4 The incidence rate of CIPN among patients with BC ranges from 11% to 80%.5,6 Patients with CIPN may experience a variety of sensory, motor, and autonomic system symptoms, including numbness in the hands and feet, neuropathic pain, muscle weakness, decreased balance, and orthostatic hypotension.7-9 These symptoms could potentially lead to the modification or discontinuation of chemotherapy. Chemotherapy-induced peripheral neuropathy may persist for months or even years after treatment, significantly impacting the quality of life of patients.10Interventions for CIPN are categorized as pharmacologic or nonpharmacologic. According to the CIPN guidelines established by the American Society of Clinical Oncology in 2020, duloxetine is the only medication recommended for the treatment of patients with CIPN experiencing neuropathic pain.4 However, duloxetine has moderate benefits and can cause adverse effects (eg, fatigue, insomnia, and nausea),11 thereby limiting its usefulness in patients receiving chemotherapy.12 Nonpharmacologic interventions are attracting attention owing to their cost-effectiveness and favorable safety profile.13 These interventions include acupuncture, acupressure, exercise, cryotherapy, classic massage, and so on.14-17 Several systematic reviews and meta-analyses have demonstrated the benefits of nonpharmacologic interventions in patients with CIPN.14,15,18 However, the most effective nonpharmacological intervention for CIPN in patients with BC remains unknown.Network meta-analysis (NMA) is a statistical method that enables the comparison of multiple interventions beyond a pairwise comparison by incorporating direct and indirect evidence. It ranks interventions based on the size of their effects, even in the absence of randomized controlled trials (RCTs) offering a direct comparison.19,20 In light of this, we conducted a systematic review and NMA to establish clinical nursing guidelines for managing CIPN in patients with BC through comparison and evaluation of various nonpharmacologic interventions. The aims of this systematic review and NMA were to compare different nonpharmacologic interventions for CIPN in patients with BC and rank them according to their effectiveness.