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Systematic Review

Effectiveness and Safety of Acupuncture for Nausea and Vomiting in Cancer Patients: A Systematic Review and Meta-Analysis

1
Department of Clinical Korean Medicine, Graduate School, Kyung Hee University, Seoul 02447, Republic of Korea
2
Epidemiology Group, Aberdeen Centre for Arthritis and Musculoskeletal Health, University of Aberdeen, Aberdeen AB24 3FX, UK
3
Research Institute of Korean Medicine, Sangji University, Wonju 26339, Republic of Korea
4
Research Group of Pain and Neuroscience, WHO Collaborating Center for Traditional Medicine, East-West Medical Research Institute, Kyung Hee University, Seoul 02447, Republic of Korea
5
Department of Meridian and Acupoint, College of Korean Medicine, Kyung Hee University, Seoul 02447, Republic of Korea
*
Authors to whom correspondence should be addressed.
Medicina 2025, 61(7), 1287; https://doi.org/10.3390/medicina61071287
Submission received: 20 June 2025 / Revised: 8 July 2025 / Accepted: 15 July 2025 / Published: 17 July 2025
(This article belongs to the Section Oncology)

Abstract

Background and Objectives: Nausea and vomiting (NV) are common and distressing adverse effects among cancer patients undergoing treatment. Despite the widespread use of pharmacological antiemetics, these medications are often insufficient for controlling nausea and may cause medication interactions and side effects. Acupuncture has been proposed as a complementary therapy; however, the comprehensive analysis of its effects on NV across all emetogenic cancer treatments remains limited. This systematic review and meta-analysis aimed to evaluate the effectiveness and safety of acupuncture in managing NV in cancer patients undergoing chemotherapy, radiotherapy, or surgery. Materials and Methods: We conducted a comprehensive search across three electronic databases and two clinical registry platforms from inception to December 2024. Randomized controlled trials (RCTs) evaluating acupuncture for NV in cancer patients were included. Risk ratios (RRs) and 95% confidence intervals (CIs) were calculated using a random-effects model. Safety outcomes were assessed based on the Common Terminology Criteria for Adverse Events (CTCAE). Results: Seventeen RCTs met the inclusion criteria, with twelve studies included in the meta-analysis. Acupuncture did not demonstrate significant effects on acute nausea (RR: 0.98; 95% CI: 0.84–1.15; p = 0.80) or acute vomiting (RR: 0.93; 95% CI: 0.65–1.32; p = 0.67). However, it significantly reduced delayed vomiting (RR: 0.76; 95% CI: 0.61–0.95; p = 0.02). Subgroup analysis demonstrated significant effects when acupuncture was administered for at least five days (RR: 0.56; 95% CI: 0.39–0.81; p = 0.002). The most frequently used acupoints were PC6, ST36, CV12, LI4, LR3, and ST25. No serious adverse events related to acupuncture treatments were reported, with only minor AEs such as localized bleeding and mild bruising observed. Conclusions: Acupuncture represents a safe and effective complementary therapy for managing delayed vomiting in cancer patients receiving emetogenic treatments. Clinicians can anticipate optimal benefits from at least five days of treatment, particularly using acupoints PC6, ST36, CV12, LI4, LR3, and ST25. Further high-quality studies are needed to establish standardized treatment regimens and explore its comprehensive effects on NV.

1. Introduction

Nausea and vomiting (NV) are prevalent and distressing symptoms experienced by over 80% of cancer patients undergoing chemotherapy, radiotherapy, or surgery [1]. These symptoms not only compromise patients’ quality of life but can also lead to serious complications including dehydration, malnutrition, and decreased treatment adherence [2]. Current pharmacological interventions, including 5-HT3 and NK-1 receptor antagonists, have demonstrated effectiveness in controlling vomiting; however, they are less effective in alleviating nausea [3]. Additionally, these medications may cause side effects including sedation, constipation, and, in rare cases, cardiac arrhythmias [4]. Consequently, many patients seek effective, safe, and sustainable multidisciplinary approaches to alleviate symptoms and enhance overall well-being.
Acupuncture has emerged as a promising non-pharmacological therapy for managing NV among cancer patients. Acupuncture stimulates various physiological responses, including the release of endorphins and the modulation of the autonomic nervous system, which can alleviate NV symptoms [5]. Notably, the PC6 (Neiguan) acupuncture point has been shown to modulate the vomiting center in the brainstem, providing relief from NV [6]. Beyond its biological effects, cancer patients who have received regular acupuncture treatments have reported significant improvements in physical complaints, psychological well-being, and enhanced coping strategies [7]. Furthermore, acupuncture has been recognized as being as safe as non-invasive sham acupuncture or active controls in oncological patients [8].
However, while previous meta-analyses have investigated the effectiveness of acupuncture, most studies have predominantly focused on chemotherapy-induced nausea and vomiting (CINV), often overlooking NV resulting from other cancer therapies such as radiotherapy and surgery [9]. Moreover, existing reviews have not adequately addressed the safety profile of acupuncture and exhibit heterogeneity in results due to variability in study designs, acupuncture techniques, and outcome measures. As acupuncture continues to be integrated into cancer care, it is essential to establish robust evidence supporting both its effectiveness and safety, especially among diverse and complex cancer populations [10].
The primary objective of this systematic review and meta-analysis was to comprehensively evaluate the effectiveness and safety of acupuncture in managing NV in cancer patients undergoing various emetogenic treatments including chemotherapy, radiotherapy, and surgery. In addition, we thoroughly analyzed acupuncture protocols according to the STandards for Reporting Interventions in Clinical Trials of Acupuncture (STRICTA) guidelines to provide clinicians with evidence-based guidance on acupuncture utilization, ultimately improving patient outcomes in cancer care.

2. Materials and Methods

This systematic review and meta-analysis were performed in compliance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We registered the protocol in the PROSPERO database (registration number: CRD42022333811) and published the study protocol [11].

2.1. Criteria for Inclusion and Exclusion

2.1.1. Types of Studies

Only RCTs evaluating the effectiveness and safety of acupuncture treatments for nausea and vomiting (NV) in cancer patients were included. We systematically included cancer patients undergoing oncology-related treatments (such as chemotherapy, radiotherapy, or surgery) known to trigger NV.

2.1.2. Types of Participants

Studies encompassing patients of all types of cancer (e.g., solid tumors, hematological malignancies), regardless of age, gender, nationality, ethnicity, or underlying cause of their symptoms, were eligible.

2.1.3. Types of Interventions

We included studies with needle-based acupuncture interventions such as manual acupuncture, electroacupuncture, intradermal acupuncture, auricular acupuncture, and laser acupuncture. All these involved skin puncture through an acupuncture needle or laser. This included various methods such as manual acupuncture (direct insertion of needles), electroacupuncture (needles with electronic stimulation), intradermal acupuncture (short needles embedded with tape for several days), auricular acupuncture (needles placed in the ear), and laser acupuncture (non-needle-based but still involving point stimulation). We included acupuncture sessions conducted either prior to or following cancer treatment. Non-needle-based acupuncture treatments, such as acupressure, cupping, moxibustion, transcutaneous electrical acupoint stimulation, and other similar methods, were excluded. These therapies do not involve skin puncture or stimulation with needles.

2.1.4. Types of Comparators

Comparison interventions included active therapies, sham acupuncture (non-penetrating sham acupuncture, pseudoacupuncture interventions, sham acupuncture at non-acupoints, and needling at inappropriate acupoints), and no treatment. Studies where acupuncture was used either alone or in combination with therapies that were the same as the comparison intervention were included.

2.1.5. Types of Outcome Measures

Studies were included if they reported both effectiveness and safety outcomes. The primary outcome for effectiveness was the incidence of NV, which was determined by analyzing completely controlled events at different endpoints. Secondary outcomes with various patient-reported scales included the Multinational Association of Supportive Care in Cancer Antiemesis Tool (MAT), Functional Living Index Emesis tool (FLIE), the Rhodes Index of Nausea, Vomiting, and Retching (RINVR), numeric rating scale (NRS), and other validated instruments for assessing both symptomatic and preventive effects of acupuncture. Safety outcomes included the types, grade, and incidence of adverse events.

2.2. Literature Searches

Studies published up to December 2024 were retrieved from the following three databases: MEDLINE via PubMed, EMBASE via Ovid, and the Cochrane Central Register of Controlled Trials. Two clinical registries, the National Institutes of Health Clinical Registry (ClinicalTrials.gov) and the World Health Organization International Clinical Trials Registry Platform, were also screened to mitigate the risk of publication bias. To identify any potentially missing eligible studies, we manually scanned the reference lists of other systematic reviews using the following search terms: cancer, tumor/tumor, neoplasm, nausea, vomiting, emesis, acupuncture, and RCTs. These terms were utilized alone or in combinations using “and,” “or”. The search strategy was tailored for each respective database. There was no language restriction.

2.3. Data Selection

The titles and abstracts of the studies were reviewed by two independent researchers (S.A.K. and S.B.N.L.) following the retrieval of all eligible studies in EndNote 21 (Clarivate Analytics), with duplicate publications being removed. The full texts of all potentially eligible studies were retrieved. Any disagreements regarding data selection were addressed by an arbiter (Y.S.J.). A PRISMA flow diagram shows the study search and screening process (Figure 1).

2.4. Data Extraction

Data extraction was conducted independently by two reviewers (S.A.K. and S.B.N.L.) using a pre-specified and standardized data extraction form. This form was pilot-tested on a subset of studies to ensure consistency in capturing relevant information, such as on participant characteristics, interventions, control conditions, outcome measures, and adverse events. In instances of incomplete or unclear data, we reached out to the original study authors for clarification. The extracted data included the total number of patients randomized, specifics of the acupuncture intervention, and the primary and secondary outcomes reported by each study. In light of the complexity of acupuncture intervention, we conducted an additional data extraction of the treatment protocol in accordance with the STRICTA guideline [12]. Disagreements between the reviewers were addressed through discussion. If consensus could not be achieved, a third reviewer (Y.S.J.) was consulted.

2.5. Quality Assessment of Included Studies

Two authors (S.A.K. and S.B.N.L.) independently evaluated the risk of bias (ROB) using the Cochrane Collaboration assessment method [13]. The biases assessed included selection, performance, attrition, detection, reporting, and other potential sources of bias. Judgments regarding these biases were categorized as low, high, or unclear. The results were summarized graphically through the plotting of bias assessments. Any discrepancies in bias assessment were resolved by the arbiter (Y.S.J.).

2.6. Data Analysis

A meta-analysis of aggregated data was conducted to analyze the incidence of NV and adverse events as individual patient data was not accessible. A meta-analysis was conducted using data from dichotomous events of nausea or vomiting occurring in acute (within 24 h) and delayed phases (24 h or later), compared to sham acupuncture or usual care. In multi-arm studies, when multiple control or intervention groups were present, double counting was avoided by appropriately selecting the most relevant comparisons. If more than two groups were relevant, groups were combined to create a single pair-wise comparison [14]. For the analysis of complete control effect of the treatment, we included any instance of nausea or vomiting as an event. A random-effects model was employed to calculate risk ratios (RRs) with 95% confidence intervals (CIs), due to the substantial statistical heterogeneity observed among the included studies. An RR less than 1 indicated that the acupuncture treatment group experienced more effective complete control of NV. Heterogeneity was evaluated for quantifying inconsistency using the I2 test and statistical heterogeneity was identified through the standard χ2 test. If the I2 value > 50% or the p-value was <0.100, studies were considered to have significant heterogeneity, which prompted the conduct of subgroup analyses to investigate potential causes. Statistical significance was defined as p < 0.05. If the data from the trials were not appropriate to be merged for meta-analysis, we conducted a descriptive analysis instead. We did not conduct a sensitivity analysis due to the limited number of available studies included in meta-analysis. Safety analysis was conducted to classify the grade of AEs according to the Common Terminology Criteria for Adverse Events (CTCAE): Grade 1 (mild or asymptomatic, only clinical observations only), Grade 2 (moderate, local or noninvasive interventions required), Grade 3 (severe, medically significant by not immediately life-threatening), Grade 4 (life-threatening, urgent intervention required), and Grade 5 (death related to AE) [15]. To assess reporting biases, funnel plots were analyzed by Egger’s test when more than ten studies were included for nausea and vomiting. Data analyses were performed using R (R Version 4.3.1, Windows) and RevMan Version 5.4 software (Cochrane Collaboration, Oxford, UK).

3. Results

3.1. Study Characteristics

A total of 1314 publications were identified from databases and clinical registries, with three additional records identified from other sources. After removing duplicate records, we screened the titles and abstracts of 852 studies. Fifty full-text articles were subsequently assessed for eligibility, resulting in the inclusion of fifteen studies in this review. The search procedures are presented in the PRISMA 2020 flowchart in Figure 1.
These seventeen studies included a total of 2036 patients, with sample sizes ranging from 32 to 324. The types of cancer varied; seven studies focused exclusively on patients with a single cancer type (e.g., breast, colorectal, gynecologic, or lung cancer) whereas ten studies comprehensively included multiple carcinoma types. The causes of NV included chemotherapy, blood stem cell transplantation, surgery, and radiotherapy. Among these causes, 14 studies (82.4%) investigated patients experiencing CINV, with eight of these studies reporting on the type of anticancer drugs utilized.
Among the seventeen studies, four studies employed a three-arm RCT design, two studies applied a four-arm design, and eleven studies adopted a two-arm RCT design. Within the six studies featuring three-arm or four-arm RCT design, two studies investigated acupuncture therapy as an adjunct to pharmacotherapy compared to both sham acupuncture combined with pharmacotherapy and pharmacotherapy alone. The remaining four studies compared multiple intervention groups based on different treatment sessions or timelines, such as before versus after chemotherapies. Regarding intervention methods, seven studies (41.2%) used manual acupuncture, another eight studies (47.1%) utilized electroacupuncture, and two studies (11.8%) implemented intradermal acupuncture. Additionally, complementary pharmacotherapies were administered alongside acupuncture treatment in 15 studies (88.2%). For the control groups, seven studies (41.2%) used sham acupuncture, five studies (29.4%) incorporated pharmacotherapy, two studies (11.8%) employed only usual care, one study (5.9%) used a no-treatment control, and two studies (11.8%) utilized a three-arm design, featuring two control groups that included both sham acupuncture and pharmacotherapy. Among nine studies using sham acupuncture, the control groups varied from non-penetrating sham acupuncture to minimal acupuncture at non-acupoint sites.
Outcome measures included the incidence of NV, with additional patient self-assessment scales like the effective rate; numeric rating scale (NRS); Rhodes Index of Nausea, Vomiting, and Retching (RINVR); and Multinational Association of Supportive Care in Cancer Antiemesis Tool (MAT). Excluding two studies that did not report adverse events (AEs), it was found that seven studies reported no AEs, eight studies reported only minor-to-moderate AEs, and no serious AEs were observed. Most studies demonstrated the symptomatic effectiveness of acupuncture, particularly in managing delayed vomiting. While a few studies explored the preventive effects of acupuncture on NV, the overall evidence regarding prevention remained inconclusive. The main findings were identified as positive in thirteen studies while four studies concluded with unclear or negative results (Table 1).

3.2. Acupuncture Treatment Protocol Analysis

A total of 11 acupuncture points were used across the 17 trials. Each point was used 1–15 times in various combinations. The most frequently used point was PC6, which was prescribed in 15 of the 17 studies. The second most frequently used point was ST36, which was selected in 12 studies. The following points were infrequently used in two or three studies: CV12, LI4, LR3, and ST25. Points rarely used in one study were CV6, LR13, PC5, ST37, and ST39 (Figure 2). The sites of acupuncture points with the anatomical location terms are presented in Appendix A Table A1 [33].
Needle stimulation types included manual acupuncture (41.2%), electroacupuncture (47.1%), and intradermal acupuncture treatment (11.8%). In electroacupuncture treatment, the frequency used in most studies was 2–20 Hz, and one study used a mixed frequency of 2/100 Hz. De-qi was elicited in fourteen studies using techniques such as rotation, twirling, lifting, or thrusting whereas three studies did not report whether it was induced. The number of needle insertions varied between two and fourteen. For the needle retention time, 30 min was most frequently used (47.1%), and the next most used was 20 min (29.4%). Exceptionally, intradermal acupuncture was maintained for 3 or 4 days. For patients with CINV, the treatment time ranged from 10 min to 2 h, most commonly before chemotherapy, with 30 min being the most frequently used duration. In other patients, acupuncture treatment was performed 1 and 2 days after surgery, whereas it was implemented before or after the radiotherapy sessions. The number of treatment sessions varied from one to twelve (Table 2).

3.3. Quality of Included Studies

The overall results of the ROB analysis are summarized in Figure 3. In terms of random sequence generation, fifteen studies had a low risk while two studies had an unclear risk. For allocation concealment, eleven studies had a low risk and six studies had an unclear risk. Regarding the blinding of patients and personnel, four studies had a low risk, three studies had an unclear risk, and ten studies had a high risk. Concerning the blinding of the outcome assessment, nine studies had a low risk and eight studies had an unclear risk. With respect to incomplete outcome data, sixteen studies were at low risk and one study had a high risk. In the area of selective reporting, seven studies were at low risk and ten studies were at unclear risk. All studies had a low ROB with regard to other biases (e.g., conflict of interest, deviations from the protocol, or problems related to cross-over design).
Funnel plots were not analyzed because fewer than 10 studies each were available for nausea and vomiting.

3.4. Effects of Acupuncture on Nausea

A meta-analysis was conducted to evaluate the effectiveness of acupuncture treatment on acute (within 24 h) and delayed phases (24 h or later) of nausea in comparison to sham acupuncture or usual care. In the acute phase, acupuncture had no significant effect on patients with nausea (RR: 0.98; 95% CI: 0.84 to 1.15; p = 0.80; I2 = 26%; 8 RCTs; n = 791). In the delayed phase, acupuncture had no significant effect on patients with nausea (RR: 0.88; 95% CI: 0.75 to 1.04; p = 0.12; I2 = 64%; 9 RCTs; n = 1003) (Figure 4).

3.5. Effects of Acupuncture on Vomiting

A meta-analysis was conducted to evaluate the effectiveness of acupuncture treatment during both the acute and delayed phases of vomiting compared to sham acupuncture or usual care. In the acute phase, acupuncture had no significant effect on patients with vomiting (RR: 0.93; 95% CI: 0.65 to 1.32; p = 0.67; I2 = 59%; 8 RCTs; n = 788). In the delayed phase, acupuncture had a significant effect on patients with vomiting (RR: 0.76; 95% CI: 0.61 to 0.95; p = 0.02; I2 = 36%; 9 RCTs; n = 859) (Figure 5).
A day-by-day subgroup meta-analysis of acupuncture treatment was performed for the subgroup analysis. Studies were categorized into groups for days 1, 2, 3, 4, and 5 or more. On day 1, defined as the acute phase, the results aligned with those of the acute phase of vomiting. On days 2, 3, and 4, acupuncture had no significant effect on patients with vomiting (RR: 0.83; 95% CI: 0.66 to 1.05; p = 0.12; I2 = 30%; 5 RCTs; n = 434, for day 2; RR: 0.84; 95% CI: 0.67 to 1.06; p = 0.15; I2 = 28%; 5 RCTs; n = 424, for day 3; RR: 0.76; 95% CI: 0.44 to 1.32; p = 0.33; I2 = 0%; 2 RCTs; n = 284, for day 4). On day 5 or beyond, two studies indicated that acupuncture had a significant effect on patients with vomiting (RR: 0.56; 95% CI: 0.39 to 0.81; p = 0.002; I2 = 0%; 2 RCTs; n = 92) (Figure 6).

3.6. Safety of Acupuncture

Regarding the safety of acupuncture, six studies did not report adverse events (AEs), three studies reported no AEs, and eight studies reported AEs. Among the eleven studies that documented AEs, eight studies reported AEs from both intervention and control groups. Due to the limited information available, we were unable to analyze the incidence rate; however, we narratively summarized the types, grades, and incidence of AEs in Appendix A Table A2.
According to the CTCAE, a total of 192 AEs in intervention groups (eleven RCTs, n = 620) and 116 AEs in control groups (eight RCTs, n = 516) were classified as Grade 1, minor AEs. No additional interventions were required for these AEs. Localized bleeding around needle insertion points and needling pain were commonly reported, followed by constipation, tiredness, symptom aggravation, etc. One study reported Grade 2, moderate AEs, which involved symptom exacerbation in participants experiencing CINV, with 17 AEs in the intervention group and 22 AEs in the control group requiring rescue medication. One study reported five cases of serious AEs due to cancer; however, the author did not specify what they were, merely noting that they were not associated with acupuncture treatment (Appendix A Table A2).

4. Discussion

Seventeen RCTs were included for qualitative synthesis and ten RCTs were analyzed for quantitative synthesis. The overall effect of acupuncture on NV was not significant in the acute phase. However, there was a significant reduction in delayed vomiting when compared to sham acupuncture or no treatment. No serious or infectious AEs related to acupuncture treatments were reported, supporting the safety of acupuncture. These findings highlight that acupuncture may serve as an effective and safe complementary therapy for managing delayed symptoms in cancer patients.
This study presented several strengths. Firstly, this study applied rigorous outcome measures in a meta-analysis, prioritizing complete symptom control over partial improvement, and identified the long-term effects of acupuncture. While this conservative approach may have contributed to smaller overall effect sizes and non-significant pooled results, it is noteworthy that some individual studies reported significant improvements in secondary outcomes using validated scales such as the Visual Analogue Scale (VAS); the Rhodes Index of Nausea, Vomiting and Retching (RINVR); and the MASCC Antiemesis Tool (MAT), even when complete symptom control was not achieved [18,29,32]. This suggests that acupuncture may provide meaningful clinical benefits in reducing symptom severity, improving the overall quality of life, and alleviating subjective distress that are not captured by binary incidence measures alone. Instead, subsequent subgroup analyses stratified by treatment duration addressed the heterogeneity of the studies and confirmed the effectiveness. This aligned with previous research indicating that acupuncture may exert more pronounced therapeutic effects over time, as opposed to producing immediate symptomatic relief [34]. Although we cannot entirely rule out the possibility of spontaneous remission over time, the observed significant impact of acupuncture on delayed vomiting, rather than on acute symptoms, may be attributable to the distinct and complex pathophysiology underlying these two phases of NV. Acute symptoms are primarily mediated by the rapid release of serotonin (5-HT3) in the small intestine, which are effectively controlled by standard antiemetics, particularly 5-HT3 receptor antagonists, which immediately block these fast-acting neurotransmitter pathways [35]. Conversely, delayed vomiting involves the prolonged activation of substance P and neurokinin-1 receptor pathways and dysregulation of the hypothalamic–pituitary–adrenal axis [36]. These processes extend beyond simple neurotransmitter release, encompassing broader neuroendocrine and inflammatory cascades that develop over time. Acupuncture influences serotonin pathways differently from mechanisms involved in the acute phase, potentially by modulating serotonin synthesis and metabolism rather than receptor blockade [37]. Consequently, the preferential effectiveness of acupuncture in regulating gastric motility and restoring normal gastrointestinal function may be particularly relevant for managing delayed vomiting, in contrast to the more immediate, peripheral mechanisms that primarily influence acute NV [38]. This has critical implications for clinicians in determining treatment methodologies, particularly for patients experiencing breakthrough delayed symptoms despite optimal pharmacological management.
Secondly, we systematically extracted data on treatment regimens from each of the included studies. Among the acupuncture points prescribed, PC6 was the most frequently used, followed by ST36. Additional points, including CV12, LI4, LR3, and ST25, were also used multiple times across the total eleven acupuncture points analyzed. In previous network analyses, the acupuncture points CV12, ST25, ST36, and LR3 were identified as the main acupuncture points for treating gastrointestinal dysfunction. This was achieved through the modulation of the 5-hydroxytryptamine system, reductions in visceral hypersensitivity, the enhancement of gastrointestinal motility, the improvement of mucosal permeability, and the promotion of neuropeptide hormone secretion [39,40]. Recent findings regarding ST36 have newly determined that modulation of the vagal–adrenal axis via somatosensory–autonomic reflexes may further alleviate NV [41]. These acupuncture points are also frequently applied to address fatigue, pain, sleep disorders, and psychological symptoms in cancer patients. Since these comorbidities are also recognized as risk factors for NV, concurrently managing these symptoms may improve NV control [39,42,43]. Furthermore, these acupuncture points have been confirmed to have a low incidence of AEs due to their anatomical locations in the abdomen or limbs [44]. Therefore, we affirmed both the effectiveness and safety of these points, suggesting that their combined application could be a valuable treatment option in clinical practice.
Third, we raised concerns regarding the adequacy of several acupuncture parameters in the protocols, specifically in terms of dosage. Establishing a treatment regimen with sufficient dosage tailored for specific symptoms is critical in RCTs. Moreover, as acupuncture comprises a complex and multifaceted intervention, numerous components of acupuncture needling procedures, such as the insertion depth, needle size, treatment period, frequency, and number of needles, must be considered. In this review, most studies implemented treatment across five sessions with fewer than ten needles. Even for conditions like pain, recommended dosages are known to be at least two sessions per week for a duration of six to twelve weeks [45]. Our findings suggest that the dosage of acupuncture treatment may not have been adequate to attain an optimal therapeutic response. The subtherapeutic dosing incorporated in the included RCTs may have been insufficient to elicit a measurable effect, particularly concerning acute NV symptoms. Additionally, the absence of standardization in acupuncture protocols, including variation in acupoint selection, the number of treatment sessions, and the number of needle insertions, may have diluted the treatment effects.
Fourth, we found an inadequate reporting of safety outcomes in these included studies. Only eight out of the seventeen included studies reported AEs, and even among those, two studies did not report AEs in the control groups. Moreover, AE descriptions were generally limited to symptom listings and were not reported using structured criteria such as the CTCAE, a widely accepted framework in oncology trials. Although no serious AEs were reported, the lack of comprehensive AE reporting is particularly concerning in cancer populations, who are often more vulnerable to complications. A standardized and thorough approach to safety monitoring is essential in future research in full accordance with CTCAE, including the type, severity, and causality of AEs across all study arms. This would not only enhance transparency but also facilitate the accurate assessment of acupuncture’s safety profile in this sensitive population.
This study had several limitations. First, we did not find any significant effects of acupuncture on nausea or vomiting in the acute phase. Our meta-analysis performed on the incidence of NV reflected only complete symptom control. Although there were a few validated outcome measurements, such as the RINVR and MAT, most of the included studies did not apply these outcome measures. Incorporating these outcomes, which evaluate symptom frequency, duration, and patient discomfort, would provide researchers with valuable data and demonstrate gradual improvements through numerical scoring. Additionally, a more comprehensive approach that considers other psychological or symptom-related factors (e.g., anxiety, sleep disorders, fatigue, or reducing AEs from pharmacotherapy) as secondary outcome measures would be valuable for understanding cancer patients’ experiences. We also attempted subgroup analyses according to concomitant treatments and timelines of treatment implementation. However, we could not find any significant results or reductions in heterogeneity from these analyses. Second, we focused not only on preventive and symptomatic effectiveness of acupuncture but also on its safety. While we initially aimed to analyze the incidence rate of AEs using a forest plot, the majority of the studies included did not adequately report the information related to AEs. Considering that cancer patients face risks associated with immunocompromised states, a fear of needles, and possibilities of neuropathy and edema, it would be necessary to review the safety of acupuncture in cancer populations minutely. Future clinical trials should evaluate the types and grade of AEs in detail, using standardized scales such as the CTCAE [15]. Third, substantial heterogeneity in acupuncture treatment protocols and control group designs may have contributed to an underestimation of treatment effects. In addition, most importantly, 14 out of the 17 included trials (82.4%) administered acupuncture in combination with standard antiemetic treatments, which limited the ability to assess the independent therapeutic effects of acupuncture. While a sensitivity analysis excluding combination therapy arms would have been informative for isolating the standalone efficacy of acupuncture, this was not feasible due to the small number of monotherapy trials available. Similarly, although meta-regression analysis could provide valuable insights into potential treatment effect modifiers such as the number of needle insertions, depth of insertion, or needle stimulation techniques, our sample size was insufficient to conduct a statistically robust analysis. Future systematic reviews should be designed with sufficient data to enable subgroup and sensitivity analyses comparing monotherapy versus combination approaches, as well as meta-regression to better understand the influence of specific acupuncture parameters on treatment outcomes.
Based on these identified research gaps, this review highlights several areas requiring attention in future research to strengthen the evidence base and clinical application of acupuncture for cancer-related NV. First, future studies should focus on various emetogenic factors. Although we attempted to comprehensively assess emetic factors affecting cancer patients, the majority of studies concentrated on CINV, despite the fact that cancer patients frequently experience NV from other causes, including radiotherapy, surgery, and tumor invasion, particularly in gastrointestinal or advanced-stage cancers. Furthermore, all studies primarily investigated acute or delayed phases of NV, leaving anticipatory NV largely unexamined. Future studies should explore acupuncture’s potential in preventing not only acute and delayed NV but also anticipatory NV, which remains a major and distressing challenge for cancer patients [46]. This limited scope represents a significant research gap, and future studies should expand their inclusion criteria to evaluate acupuncture’s potential across a broader range of NV etiologies to better reflect real-world clinical settings. In addition, overall methodological limitations and heterogeneity in study designs should be improved. A substantial proportion of studies demonstrated high or unclear risk of bias in the domains of participant/personnel blinding and outcome assessment. While blinding is inherently challenging in acupuncture research, methodological strategies such as the use of independent outcome assessors, centralized data collection, the assessment of blinding, or validated sham techniques can help mitigate performance and detection biases [47]. Regarding improvements in reporting methodology, the detailed documentation of trial processes and safety monitoring according to well-established guidelines, including the CONsolidated Standards Of Reporting Trials (CONSORT), STRICTA, and CTCAE, are essential for enhancing the credibility and reproducibility of future trials. Furthermore, the optimal acupuncture regimen for cancer-related NV remains still unclear despite numerous trials having been conducted. Key dosage parameters, including the number of sessions and needle retention times, varied widely and were often below thresholds suggested by previous research as therapeutically effective. This highlights the need for well-designed dose–response studies and consensus-driven guidelines to standardize acupuncture protocols, ensuring both efficacy and practical applicability. Finally, based on our comprehensive analysis across different cancer types and emetogenic factors, future clinical trials can incorporate long-term follow-up periods in specific oncological populations and treatment settings.

5. Conclusions

This systematic review and meta-analysis provided evidence that acupuncture treatment is an effective and safe complementary therapy for delayed vomiting in cancer patients undergoing emetogenic therapies. However, its effects on acute NV remain inconclusive, and we encountered challenges in determining the adequate acupuncture treatment dosages for optimal therapeutic responses. Clinicians should consider incorporating acupuncture into a multimodal approach, particularly for patients experiencing delayed emesis. Further high-quality research should focus on refining acupuncture parameters, including robust AE reporting, and investigating its preventive potential for anticipatory NV, an area of significant unmet need in cancer care.

Author Contributions

Conceptualization: S.L.; methodology: S.-A.K. and S.L.; software: S.-A.K.; investigation: S.-A.K. and S.L.; data curation: S.Y.; writing—original draft: S.-A.K.; writing—review and editing: S.L. and S.Y.; visualization: S.-A.K.; supervision: S.L. All authors have read and agreed to the published version of the manuscript.

Funding

This research received no external funding.

Institutional Review Board Statement

Ethical review and approval were not required for this study, as it does not involve the collection of original data.

Informed Consent Statement

Not applicable.

Data Availability Statement

The original contributions presented in the study have been included in the article; further inquiries can be directed to the corresponding authors.

Conflicts of Interest

The authors declare no conflicts of interest.

Appendix A

Table A1. The Sites of Acupuncture Points.
Table A1. The Sites of Acupuncture Points.
PC6On the anterior aspect of the forearm, between the tendons of the palmaris longus and the flexor carpi radialis, 2 cun proximal to the palmar wrist crease.
With the fist clenched, the wrist supinated and the elbow slightly flexed, the two tendons become more prominent. PC6 is located 2 cun proximal to PC7. The posterior point corresponding to PC6 is TE5.
ST36On the anterior aspect of the leg, on the line connecting ST35 with ST41, 3 cun inferior to ST35.
ST36 is located on the tibialis anterior muscle.
CV12On the upper abdomen, 4 cun superior to the center of the umbilicus, on the anterior median line.
CV12 is located at the midpoint of the line connecting the xiphisternal junction and the center of umbilicus.
LI4On the dorsum of the hand, radial to the midpoint of the second metacarpal bone.
LR3On the dorsum of the foot, between the first and second metatarsal bones, in the depression distal to the junction of the bases of the two bones, over the dorsalis pedis artery.
LR3 can be felt in the depression when moving proximally from LR2 in the gap between the first and second metatarsal bones towards the base of two metatarsal bones.
ST25On the upper abdomen, 2 cun lateral to the center of the umbilicus.
CV6On the lower abdomen, 1.5 cun inferior to the center of the umbilicus, on the anterior median line.
LR13On the lateral abdomen, inferior to the free extremity of the 11th rib.
LR13 can be located while the subject is lying on the side with the shoulder flexed. The free extremity of the 11th rib can be palpated below the inferior border of the costal arch.
PC5On the anterior aspect of the forearm, between the tendons of the palmaris longus and the flexor carpi radialis, 3 cun proximal to the palmar wrist crease.
With the fist clenched, the wrist supinated and the elbow slightly flexed, the two tendons become more prominent. PC5 is located 3 cun proximal to PC7.
ST37On the anterior aspect of the leg, on the line connecting ST35 with ST41, 6 cun inferior to ST35.
ST37 is located on the tibialis anterior muscle.
ST39On the anterior aspect of the leg, on the line connecting ST35 with ST41, 9 cun inferior to ST35.
ST39 is located on the tibialis anterior muscle, at the same level as GB35 and GB36.
cun: 1cun is equal to 1 unit which is measured as dividing the height of the human body into 75 equal units.
Table A2. Incidence of Adverse Events in Safety Assessment.
Table A2. Incidence of Adverse Events in Safety Assessment.
Grade 1 (Mild)Grade 2 (Moderate)Grade 3~5
InterventionControl Intervention Control Intervention Control
Constipation19330000
Diarrhea290000
Dizziness850000
Dyspepsia870000
Electric shock sensation100000
Headache9100000
Insomnia2110000
Localized bleeding around needle points78100000
Localized skin irritation500000
Needle scratch0100000
Needling pain2600000
Symptom aggravation
Symptoms of CINV (e.g., tingling sensation)121172200
Increased Alanine transaminase (ALT)010000
Increased urea nitrogen and creatinine100000
Sedation640000
Tiredness15150000
Not mentioned000041
Total192116172241
Groups: intervention group (11 RCTs, n = 620); control group (8 RCTs, n = 516).

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Figure 1. Study flow chart.
Figure 1. Study flow chart.
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Figure 2. Acupuncture point frequency.
Figure 2. Acupuncture point frequency.
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Figure 3. Bias assessment of acupuncture treatment.
Figure 3. Bias assessment of acupuncture treatment.
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Figure 4. Meta-analysis of acupuncture treatment for patients with nausea [17,20,22,24,26,27,28,31,32].
Figure 4. Meta-analysis of acupuncture treatment for patients with nausea [17,20,22,24,26,27,28,31,32].
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Figure 5. Meta-analysis of acupuncture treatment for patients with vomiting [16,17,22,24,26,27,28,31,32].
Figure 5. Meta-analysis of acupuncture treatment for patients with vomiting [16,17,22,24,26,27,28,31,32].
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Figure 6. Daily meta-analysis of acupuncture treatment for patients with vomiting [16,17,22,24,26,27,28,31,32].
Figure 6. Daily meta-analysis of acupuncture treatment for patients with vomiting [16,17,22,24,26,27,28,31,32].
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Table 1. Characteristics of the included studies.
Table 1. Characteristics of the included studies.
Author
Year
CountryCancer
Type
Cause of NVSample Size Mean Age (years)InterventionControlOutcome MeasuresMain FindingsAdverse Events
Shen
2000
[16]
USABreast cancerChemotherapy (Cyclophosphamide, cisplatin, carmustine)10446EA + PT(1) SEA + PT
(2) PT
Episodes of vomitingAdjunct EA was more effective in controlling emesis than minimal needling or antiemetic pharmacotherapy alone although the observed effect had a limited duration.Minor adverse events (electrical shock sensation, tingling sensation aggravation)
Streitberger
2003
[17]
GermanyMultiple myeloma, breast cancer, hodgkin lymphoma, etc.Chemotherapy (mainly melphalan), BSCT8054AT + PTSA + PTNumber of patients with NV, vomiting, episodes of NVAT has no additional effect for the prevention of acute NV in high-dose chemotherapy.None observed
Mehling
2007
[18]
USAAbdominal/pelvic, prostate/testicular, bladder/kidney, breast cancerSurgery13856AT + MassageUsual care+ MassageNRSA bedside service of massage and AT resulted in decreased pain and depressive mood among postoperative cancer patients when compared with usual care alone.Not mentioned
Yang
2009
[19]
ChinaDiverse cancer (not reported)Chemotherapy 24651EA + PTPTEffective rate,
NRS
EA at ST36 can significantly alleviate the symptoms such as NV caused by chemotherapy of the patients.Minor adverse events (bleeding around acupoints)
Enblom
2012
[20]
SwedenGynecologic, colon, rectal, anal, testicular cancer, etc.Radiotherapy32454AT + PTSA + PTEpisodes of NVAT is not more effective than sham in radiotherapy-induced nausea, but in this study, nearly all patients in both groups experienced that the treatment was effective for nausea.Minor adverse events (bleeding around acupoints, tiredness, dizziness, needle scratch on skin)
Beith
2012
[21]
AustraliaBreast cancerChemotherapy (Doxorubicin, cyclophosphamide, others)3252EA + PTSEA + PTMAT, episodes of NV, number of patients with NVEA during chemotherapy is a promising option for controlling the side effects of chemotherapy.None observed
Zhang
2014
[22]
ChinaLung, colon, breast cancer, etc.Chemotherapy 7259EA + PTSEA + PTEpisodes of NV, complete control rateEA at PC6 and PC5 combined with Granisetron could obviously relieve nausea in chemotherapy patients at the delay stage.None observed
McKeon
2015
[23]
AustraliaBreast, colorectal, gynecological cancer, etc.Chemotherapy 6058EA + PT(1) SEA + PT
(2) PT
FLIE, NRS, episodes of
nausea and vomiting
It was not possible to determine whether EA improved CINV compared to standard care.Minor adverse events (needling pain, bruising, localized skin irritation)
Rithirangsriroj
2015
[24]
ThailandGynecologic cancerChemotherapy (Paclitaxel, carboplatin)7052AT + PTPTComplete response rate, functional assessment of cancer therapy-generalAT is effective in preventing delayed CINV and promoting a better quality of life with fewer adverse effects.Minor adverse events (needling pain, soreness)
Wang
2018 [25]
ChinaColorectal cancerSurgery8051EA
(1) 1 sessions of treatment
(2) 2 sessions of treatment
(3) 3 sessions of treatment
No treatmentNumber of patients with nausea, vomitingEA treatment combined with intravenous anesthesia conducted before and after surgery is effective in promoting the recovery of gastrointestinal function in patients undergoing colorectal cancer laparotomy and is obviously better than simple pre-operative EA.None observed
Wang
2019 [26]
ChinaLung cancerChemotherapy 14054AT + PT
(1) before chemotherapy
(2) after chemotherapy
PTEffective rate, Karnofsky performance scaleAT combined with the slow intravenous injection of Tropisetron hydrochloride achieves a satisfactory effect in prevention and treatment. AT before chemotherapy greatly improves the effect on the NV induced by chemotherapy of lung cancer.Minor adverse events (dizziness)
Li
2020 [27]
ChinaBreast, ovarian, cervical, endometrial, lung cancer, etc.Chemotherapy (Cisplatinum, anthracycline, taxane)13459EA + PTSEA + PTComplete control rate, common terminology criteria for
adverse events
AT as an adjunctive approach could alleviate the severity of CINV compared to the sham control, even though the effect of AT in preventing CINV occurrence is relatively modest.None observed
Cheng
2020 [28]
ChinaLung cancerChemotherapy (cisplatin)10059AT + PT
(1) before chemotherapy
(2) after chemotherapy
PTComplete control rate, INVR, national cancer institute common toxicity criteria 4.0AT before chemotherapy can effectively reduce the frequency of NV associated with cisplatin chemotherapy in lung cancer patients, improve the effectiveness of CINV treatment, and be widely promoted in clinics.Not mentioned
Maeng
2022 [29]
Republic of KoreaSolid tumorChemotherapy (Cisplatin, doxorubicin, cyclophosphamide)4264AT + PTPTRINVR, MATDelayed nausea after highly emetogenic chemotherapy tended to decrease with AT using the RINVR score, though it was also not significant. With the MAT assessment, delayed NV was significantly improved with AT, suggesting a promising effect of AT.None observed
Bintoro
2022 [30]
IndonesiaLeukemia, renal, liver cancer, etc.Chemotherapy 6011IA + PTSIA + PTRINVRIA treatment is able to reduce the RINVR score and can be applied to pediatric patients because of its minimal side effects.None observed
Michel-Cherqui
2024 [31]
FranceSolid tumorChemotherapy11564IAUsual careNumber of patients with nausea, vomiting, MATIA treatment reduces intensity of acute and delayed nausea in patients treated by optimal antiemetic treatment.Minor adverse events (discomfort)
Shen
2024 [32]
ChinaBreast cancerChemotherapy23951EA + PTSEA + PTComplete control rate, VASAdding EA to standard triple antiemetic therapy significantly enhances the efficacy of CINV treatment in patients with breast cancer receiving highly emetogenic chemotherapy.One discontinuation. Minor adverse events (bruising)
Abbreviations—AT, acupuncture treatment; BSCT, blood stem cell transplantation; CINV, chemotherapy-induced nausea and vomiting; EA, electroacupuncture treatment; FLIE, Functional Living Index Emesis tool; IA, intradermal acupuncture; MAT, Multinational Association of Supportive Care in Cancer Antiemesis Tool; NRS, numeric rating scale; NV, nausea and vomiting; PT, pharmacotherapy; RINVR, the Rhodes Index of Nausea, Vomiting, and Retching; SA, sham acupuncture; SEA, sham electroacupuncture, SIA, sham intradermal acupuncture.
Table 2. Summary of acupuncture treatment protocols using STRICTA criteria.
Table 2. Summary of acupuncture treatment protocols using STRICTA criteria.
Author
Year
Names of AcupointsNumber of Needle InsertionsDepth of Insertion (mm)Needle TypeNeedle StimulationNeedle Retention Time Number of Treatment SessionsTreatment TimeSetting and Context of TreatmentDescription of Participating Acupuncturists
Shen
2000 [16]
PC6, ST36430~4536-gauge (Seirin, Shizuoka, Japan)Electrical (2~10 Hz, <26 mA),
De qi (rotation)
20 min52 h before chemotherapyInpatient (oncology center at a university medical center)Acupuncture clinician with 3 and 20 years of acupuncture training
Streitberger
2003 [17]
PC62NM0.25 × 40 mm (Asia med, Pullach im Isartal, Germany)Manual,
De qi
20 min230 min before chemotherapyUniversity of HeidelbergTwo trained acupuncturists
Mehling
2007 [18]
PC6, ST36, additional points according to patients4~143~9034-gauge (Seirin, Shizuoka, Japan)Manual,
De qi
20 min21, 2 days after surgeryUniversity
of California, San Francisco
Two licensed acupuncturists
Yang
2009 [19]
ST36225~300.30 × 40 mmElectrical (NM),
De qi (rotation)
30 min1030 min before chemotherapyJilin Hospital at Changchun, ChinaNM
Enblom
2012 [20]
PC62150.30 × 40 mm (Dongbang, Seongnam, Republic of Korea)Manual,
De qi (twirling and lifting)
30 min12Before or after the radiotherapy sessionTwo Swedish university hospitalsSeven acupuncture-trained physiotherapists with experience (range 2–12 years)
Beith
2012 [21]
PC6, ST36, LI4,4NM0.20 × 25 mm (Viva, China)Electrical (2 Hz, for a 1.5-s duration pulse width),
De qi (rotation)
20 min42 h before chemotherapy (each first, second cycles of chemotherapy)Oncology clinic at the Royal Prince Alfred Hospital, AustraliaTwo acupuncturists with more than 6 years of training and 10 years of experience
Zhang
2014 [22]
PC6, PC5413~23 0.30 × 25 mm (Jiangsu med, Changzhou, China.)Electrical (20 Hz, 0~10 mA),
De qi
60 min630 min before chemotherapyInpatient of first affiliated hospital of China medical university, Zhejiang, ChinaNM
McKeon
2015 [23]
PC6, ST36, LI4, LR382~15 0.20 × 30 mm (Sensei, Melbourne, Australia)Electrical (10 Hz, <10 mA),
De qi (thrusting, twirling)
30 min210 min before chemotherapyMater Health Services Adults Day Oncology Unit, Brisbane, AustraliaA trained acupuncturist with an advanced diploma of acupuncture with 6 years of clinical practice at the time of the study
Rithirangsriroj
2015 [24]
PC62NMNMManual,
De qi (rotation)
30 min230 min before chemotherapyKing Chulalongkorn Memorial Hospital Bangkok, ThailandA third author of this study
Wang
2018 [25]
PC6, ST36, ST37, ST39 (+CV12, ST25)630~70 NMElectrical (2 Hz, 2~3 mA),
De qi (rotation)
30 min1~3(1) 1 day before chemotherapy (2) 1 day and 30 min before chemotherapy (3) 1 day, 30 min before, 1 day after chemotherapyNingxia Medical University, Yinchuan, ChinaNM
Wang
2019 [26]
PC6, CV12, ST36520~300.25 × 40 mmManual,
De qi
30 min330 min before or after chemotherapyZhejiang Chinese Medical University, ChinaNM
Li
2020 [27]
PC6, CV12, CV6, ST25, ST36, LR131010–350.25 × 40 mm (Ande, Guizhou, China)Electrical (2/100 Hz),
De qi
30 min6Twice on the first day of chemotherapy and once consecutively on the following 4 daysBeijing Shijitan Hospital, Beijing Friendship Hospital, Beijing Hospital of Traditional Chinese Medicine, and Guang’ Anmen HospitalAll the acupuncturists who participated in this trial were major in acupuncture for more than 3 years with Chinese medicine practitioner license and had undergone rigorous training in conducting this trial
Cheng
2020 [28]
PC6, ST364NM0.25 × 40 mm (Andi med, China)Manual,
De qi (twirling, rotating)
30 min530 min before or after chemotherapyBeijing Traditional Chinese Medicine HospitalPhysicians with 3 years of experience performed the acupuncture for patients
Maeng
2022 [29]
PC6, ST36, LI4, LR3 + (HT8, SP2, LR1, SP1, or GB41, SI5, LI1, ST45)8NM0.25 × 40 mm (Dongbang, Seongnam, Republic of Korea)Manual,
NM
20 min31 h before chemotherapyKyung Hee University HospitalKorean medical doctors
Bintoro
2022 [30]
PC6, ST364NMNMIntradermal,
NM
3 days1Before chemotherapyInpatient, Dr. Cipto Mangunkusumo Hospital, JakartaNM
Michel-Cherqui
2024 [31]
PC6, diaphragm, additional ear points5NM0.2 × 0.9 mm (semi-permanent needles, Seirin, Shizuoka, Japan)NM4 days1Before chemotherapyMulti-center (tertiary-care university hospital/cancer center/general hospital) Experienced physicians with more than seven years of practice
Shen
2024 [32]
PC6, ST36, LI46NMNMElectrical (2 Hz, <10 mA), De qi45 min4Before chemotherapyMulti-center (six centers in China)Trained acupuncturists, each with over 3 years of experience in oncology
Abbreviations—AT, acupuncture treatment; BSCT, Blood stem cell transplantation; CINV, chemotherapy-induced nausea and vomiting; EA, electroacupuncture treatment; FLIE, Functional Living Index Emesis tool; IA, intradermal acupuncture; MAT, Multinational Association of Supportive Care in Cancer Antiemesis Tool; NRS, numeric rating scale; NV, nausea and vomiting; PT, pharmacotherapy; RINVR, the Rhodes Index of Nausea, Vomiting, and Retching; SA, sham acupuncture; SEA, sham electroacupuncture, SIA, sham intradermal acupuncture.
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Kim, S.-A.; Yeo, S.; Lim, S. Effectiveness and Safety of Acupuncture for Nausea and Vomiting in Cancer Patients: A Systematic Review and Meta-Analysis. Medicina 2025, 61, 1287. https://doi.org/10.3390/medicina61071287

AMA Style

Kim S-A, Yeo S, Lim S. Effectiveness and Safety of Acupuncture for Nausea and Vomiting in Cancer Patients: A Systematic Review and Meta-Analysis. Medicina. 2025; 61(7):1287. https://doi.org/10.3390/medicina61071287

Chicago/Turabian Style

Kim, Sung-A, Sujung Yeo, and Sabina Lim. 2025. "Effectiveness and Safety of Acupuncture for Nausea and Vomiting in Cancer Patients: A Systematic Review and Meta-Analysis" Medicina 61, no. 7: 1287. https://doi.org/10.3390/medicina61071287

APA Style

Kim, S.-A., Yeo, S., & Lim, S. (2025). Effectiveness and Safety of Acupuncture for Nausea and Vomiting in Cancer Patients: A Systematic Review and Meta-Analysis. Medicina, 61(7), 1287. https://doi.org/10.3390/medicina61071287

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