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Trends in clinical trials of acupuncture for chemotherapy-related cognitive impairment: A Scoping Review

Article information

J Korean Med. 2025;46(1):181-204
Publication date (electronic) : 2025 March 01
doi : https://doi.org/10.13048/jkm.25013
Mikyung Kim1,orcid_icon, Chang-ho Han2orcid_icon
1Department of Internal Medicine, Dongguk University Ilsan Oriental Hospital
2Department of Internal Medicine, College of Korean Medicine, Dongguk University WISE Campus
Correspondence to: Mikyung Kim, Dongguk University Ilsan Oriental Hospital, 27, Dongguk-ro Ilsandong-gu, Goyang-si, Gyeonggi-do, 10326, Tel: +82-31-961-9045, E-mail: 01mkkim@gmail.com
Received 2025 January 19; Revised 2025 February 17; Accepted 2025 February 17.

Abstract

Objectives

This study was aimed to review and analyze trends in clinical trials of acupuncture for chemotherapy-related cognitive impairment (CRCI).

Methods

On December 20, 2024, three core databases (PubMed, Embase, and Cochrane Library), the International Clinical Trials Registry Platform, and ClinicalTrials.gov were searched to obtain clinical trial reports and protocols that evaluated the effects of acupuncture on cognitive function in patients with CRCI.

Results

A total of five reports and six protocols were retrieved. All five reports were conducted in East Asia, including China, Hong Kong, and Korea, and only two of them were randomized controlled trials (RCTs). These studies suggest that acupuncture may be beneficial in improving CRCI. All protocols were RCTs, and were scheduled to be conducted in China, Italy, and the United States. Most of them planned to conduct cognitive function tests but also measure biomarkers.

Conclusion

Only a few small trials have been published so far, even though they claimed results supporting the benefit of acupuncture. Current RCTs that are ongoing or planned to be conducted tend to be larger in scale and more diverse in quality compared to previous trials. Therefore, it is expected that we will soon be able to secure the evidence necessary to draw more definitive conclusions about the effect of acupuncture on CRCI. However, future trials need to be carefully designed to complement the limitations of existing reports and protocols.

Keywords: chemotherapy-related cognitive impairment; chemotherapy-induced cognitive impairment; chemobrain; chemofog; acupuncture; review
Fig 1

Flow diagram of literature search

Characteristics of previously published clinical studies on the effect of acupuncture for chemotherapy-related cognitive impairment

Details of interventions conducted in previously published clinical studies on the effect of acupuncture for chemotherapy-related cognitive impairment

Outcome measures used in previously published clinical studies on the effect of acupuncture for chemotherapy-related cognitive impairment

Acupoints used in the previously published and of yet-to-be-published clinical studies on the effect of acupuncture for chemotherapy-related cognitive impairment

Characteristics of yet-to-be-published clinical studies on the effect of acupuncture for chemotherapy-related cognitive impairment

Details of interventions conducted in yet-to-be-published clinical studies on the effect of acupuncture for chemotherapy-related cognitive impairment

Outcome measures used in yet-to-be-published clinical studies on the effect of acupuncture for chemotherapy-related cognitive impairment

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Article information Continued

Fig 1

Fig 1

Flow diagram of literature search

Table 1-1

Characteristics of previously published clinical studies on the effect of acupuncture for chemotherapy-related cognitive impairment

Study id Study method Presentation type Location country Settings Study period Restrictions for selecting participants Study design No. of participants
Age Gender Nationality Cancer type Anticancer Tx Cog. imp. criteria registered completed
Tong18 [18] RCT Academic journal Mainland China University Hospital May–Oct 2017 21–55* Female NR Br (0–III) Under adj CTx Subjective 2-arm, acu vs nonacu 40 vs 40 39 vs 36
Zeng18 [19] Prospective pilot cohort Academic journal Mainland China & HK University Hospital NR 18–65 Female Chinese Gyn (I–III) Under adj CTx Objective 2-arm, acu vs nonacu 3 vs 3 3 vs 3
Zhang20 [20] RCT Academic journal HK University Hospital Oct 2015–Dec 2018 18–65 Female Chinese Br (I–IIIa) Under adj CTx or recently completed Objective† 2-arm, EA vs mini EA 46 vs 47 40 vs 43
Lyu22 [21] Prospective pre-post Academic journal Republic of Korea University Hospital Nov 2016–Jan 2018 19–75 No NR Solid cancer Completion of anticancer Tx > 6 mn Subjective 1-arm, pre-post EA 12 10
Lv23 [22] Retrospective chart review Conference abstract Mainland China NR 2019–2022 NR (the Elderly) NR NR NR CTx Clinically confirmed 2-arm, EA+HD vs CM 83 vs 85 83 vs 85

RCT, randomized controlled trial; HK, Hong Kong; NR, not reported; Br, breast cancer; Gyn, gynecological cancer; Tx, treatment; adj., adjuvant; CTx, chemotherapy; cog. imp.: cognitive impairment; mn, months; acu, acupuncture; mini, minimal; EA, electroacupuncture; HD, herbal decoction; CM, conventional medicine

*

premenopausal

†

Since this study assessed the preventive effect for chemobrain, it is an outcome measure, not a selection criteria.

Table 1-2

Details of interventions conducted in previously published clinical studies on the effect of acupuncture for chemotherapy-related cognitive impairment

Study id Tx int. Control int.
Tx period Freq/wk Session Acu dur Size (mm) Depth (mm) EA freq. Acupoints
Tong18 [18] 8 wk 5 40 30 min 0.25x25,40 10–35 NA GV20, GB24, EX-1, ST36, KI3, KI4, GB39 No Acu
Zeng18 [19] 4–6 wk 2 10 30 min 0.25x40 25–40 NA GV20, EX-HN1, EX-HN3, EX-HN5, GB8, GB15, ST8 No Acu
Zhang20 [20] 8 wk 2 16 30 min 0.30x25,40 10–30 2 Hz GV26, HT7, LI4, TE5, ST36, ST40, SP6, CV4, CV12 Mini EA
Lyu22 [21] 8 wk 2 16 30 min 0.25x30 PD 2 Hz GV20, GV24, EX-HN1, GB20, HT7, PC6, KI3 NA
Lv23 [22] 8 wk 2 16 NR NR NR NR NR CM

Tx, treatment; int., intervention; wk, week; freq, frequency; session, number of acu session; acu, acupuncture; dur, duration; min, minute; NR, not reported; size, acupuncture needle size; depth; depth of acupuncture needling; PD; at practitioner’s decision; EA, electroacupuncture; NA, not applicable; Auri, auriculoacupuncture; Mini, minimal; NA, not applicable; CM, conventional medicine

Table 1-3

Outcome measures used in previously published clinical studies on the effect of acupuncture for chemotherapy-related cognitive impairment

Study id Time points (wk) Outcome measures Results
Cognitive function-related outcomes Others
Subjective Objective Biomarkers Brain imaging QOL Function Emotion CTx. Tox Safety
Tong18 [18] 0, 8 FACT-Cog v3 AVLT, VFT, SDMT, CDT, TMT-B sBDNF FACT-Cog & AVLT-3 (recognition), CDT, sBDNF: only acu gr showed sig. imp.
Zeng18 [19] 0, 4–6 AVLT, TMT-A&B, WAIS-III DST, COWA Brain MRI (DTI & MRS) All cognitive scores: acu gr > con gr
Brain imaging: better preservation of WM integrity in lt hippo in acu gr.
Zhang20 [20] 0,2,4,6,8 MoCA, f&rDST, chemobrain prevalence EORTC QLQ-C30 & Br23 CTx,-related AEs Only in rDST: EA gr showed sig. imp. over the con gr.
MoCA, fDST, chemobrain prevalence (MoCA<26): not sig. dif. btw grs.
Diarrhea, tenseness, worrisome, irritation, headache, tinnitus: EA gr. < con gr.
Lyu22 [21] 0,4,8,12 FACT-Cog v3 MoCA, SNSB EORTC QLQ-C30 HADS VS, BT, AE PCI subscale of FACT-Cog, MoCA: sig. imp.
Subsccales for language & related function and memory in SNSB: sig. imp.
FACT-Cog total score & QOL: imp. but not statistically different.
Emotional scale: stay stable
No SAE.
Lv23 [22] 0,2,8 MoCA, DST QoL ECOG rDST: acu gr showed sig. imp. over the con gr
Total score of MoCA & chemobrain prevalence: not sig. different btw grs.
Functional scale imp.: acu gr > con gr.

Wk, week; FACT-Cog, functional assessment of cancer treatment cognition; v3, version 3; AVLT, auditory-verbal learning test; VFT, verbal fluency test; SDMT, symbol digit modality test; CDT, clock-drawing test; TBT, trail-making test; WAIS, Wechsler adult intelligence scale; DST, digit span test; COWA, controlled oral word association test; MoCA, Montreal cognitive assessment; f&r, forward and reverse; SNSB, Seoul neuropsychological screening battery; sBDNR, serum blood-derived neurotrophic factor; MRI, magnetic resonance imaging; DTI, diffusion tensor imaging; MRS, magnetic resonance spectroscopy; QOL, quality of life; EORTC QLQ-C30, European organization for research and treatment of cancer quality of life questionnaire core 30; BR, breast cancer; ECOG, Eastern cooperation oncology group performance status; HADS, hospital anxiety and depression scale; Tox, toxicity; AE, adverse event; VS, vital signs; BT, blood test; acu, acupuncture; gr, group; sig, significant; imp, improvement; con, control; WM, white matter; lt, left; hippo, hippocampus; dif., difference; btw, between; PCI, perceived cognitive impairment; SAE, serious AE

*

Statistical significance: P < 0.05

Table 2

Acupoints used in the previously published and of yet-to-be-published clinical studies on the effect of acupuncture for chemotherapy-related cognitive impairment

Body parts Acupoints Number of clinical studies using the acupoint
Previously published studies (n=4) Yet-to-be-published studies (n=4)
Head and neck GV20 (Baihui, 百會) 4 4
EX-HN1 (Sishencong, 四神聰) 4 2
GV24 (Shenting, 神庭) 2 1
EX-HN3 (Yintang, 印堂) 2 3
GB20 (Fengchi, 風池) 2 0
EX-HN5 (Taiyang, 太陽) 2 1
GB8 (Shuaigu, 率谷) 2 0
GB15 (Toulinqi, 頭臨泣) 2 1
GV26 (Shougou, 水溝) 1 0
ST8 (Touwei, 頭維) 1 0
Trunk CV12 (Zhongwan, 中脘) 1 2
CV4 (Guanyuan, 關元) 1 2
CV17 (Danzhong, 膻中) 0 1
CV6 (Qihai, 氣海) 0 1
Upper limbs HT7 (Shenmen, 神門) 2 3
LI4 (Hegu, 合谷) 1 2
TE5 (Waiguan, 外關) 1 1
PC6 (Neiguan, 內關) 1 1
Lower limbs ST36 (Zusanli, 足三里) 2 3
SP6 (Sanyinjiao, 三陰交) 1 2
KI3 (Taixi, 太谿) 1 3
KI4 (Dazhong, 大鐘) 1 0
GB39 (Xuanzhong, 懸鍾) 1 0
ST40 (Fenglong, 豊隆) 1 1
LR3 (Taichong, 太衝) 1 1
KI6 (Zhaohai, 照海) 0 1
Auricular points Shenmen, 神門 0 1
No specific points mentioned 0 1

Table 3-1

Characteristics of yet-to-be-published clinical studies on the effect of acupuncture for chemotherapy-related cognitive impairment

Study id Study method Presentation type Location country Settings Study period Restrictions for selecting participants Study design No. of participants
Age Gender Nationality Cancer type Anticancer Tx Cog. imp. criteria
Rossi20 [23] RCT Conference abstract Italy Homeopathi c clinic of Regional Hospital NR 18–70 F NR Br (I–IIIa) Adj. CTx and/or Endo Tx. NR 3-arm, Acu/auri+R/D vs Homeo+R/D vs R/D 100 vs 100 vs 100
Rossi24 [24] RCT Conference abstract Italy Regional Integrative Medicine center Feb 2021-NR 18–65 NR NR Br* (I–IIIa) Adj. CTx and/or Endo Tx. NR 4-arm, Acu/auri +Homeo+R/D vs Acu/auri+R/D vs Homeo+R/D vs R/D Total 320
Gao24 [25] RCT Clinical trial registry Mainland China University Hospital Jan 2024–Apr 2025 18–65 NR NR Triple negative Br + TCM PI† CTx MCI within 3 yrs after CTx. 2-arm, acu§ vs mini acu 25 vs 25
Xie23 [26] RCT Academic journal United States of America University &Regional Hospital Apr 2022–Dec 2025 ≥ 16 No NR NR Have received anticancer Tx. Including subjective Cog. imp‡ 2-arm, EA vs mini EA 32 vs 32
Yan23 [27] RCT Clinical trial registry Mainland China NR Aug 2023–Dec 2024 18–75 NR NR Br (I–III) Scheduled to undergo CTx. Cog. test score at or below 1.5 SDs 2-arm, EA vs mini EA Total 100
Zhao24 [28] RCT Academic journal Mainland China University Hospital Sep 2023–Dec 2025 ≥ 60 NR NR No Under or scheduled to undergo CTx. Cog. test score at or below 1.5 SDs 2-arm, EA vs mini EA Total 168

RCT, randomized controlled trial; NR, not reported; F, female; Br, breast cancer; TCM, traditional Chinese medicine; PI, pattern identification (辨證), Tx, treatment; Adj, adjuvant; CTx, chemotherapy; Endo, endocrine; cog., cognitive; imp., impairment; MCI, mild cognitive impairment; yrs, year; SD, standard deviation; acu, acupuncture; auri, auricular acupuncture; Homeo, homeopathy; R/D, rehabilitation exercises and diet; mini, minimal; EA, electroacupuncture.

*

Br cancer diagnosed within 12 months.

†

Patients identified as having a “disturbance of qi and blood (氣血失調)” pattern in diagnosis based on traditional Chinese medicine theory.

‡

Those who experienced two of the following symptoms for more than 7 days: cancer-related memory impairment/attention deficit, fatigue, insomnia, depression, and anxiety were included in the study participants.

§

Reconciling qi and blood & tonifying heart and mind method.

Table 3-2

Details of interventions conducted in yet-to-be-published clinical studies on the effect of acupuncture for chemotherapy-related cognitive impairment

Study id Tx int. Control int.
Tx period Freq/wk Session Acu dur Size (mm) Depth (mm) EA freq. Acupoints
Rossi20 [23] 12 wk 1 12 NR NR NR NA GV20, EX-HN1, KI3, Auricular point (NR) No Acu, Homeo
Rossi24 [24] 16/20 wk* 1 16 NR NR NR NA GV20, EX-HN3, CV4, CV17, HT7, ST25, KI3, auricular point (Shenmen) No Acu, Homeo, Acu+Homeo
Gao24 [25] NR, but estimated 8–14 wk NR NR NR NR NR NA NR Mini Acu
Xie23 [26] 10 wk 1 10 30 min 0.20 x 25 9–24 mm 2 Hz GV20, GV24, EX-HN1, CV4, CV12, PC6, HT7, LI4, ST36, SP6, KI3, KI6, LR3 Mini EA
Yan23 [27] TBC according to CTx. cycle† 2 TBC† NR NR Assumed to be > 3–5‡ 2 Hz NR Mini EA
Zhao24 [28] 8 wk 2 16 30 min 0.30 x 25, 40 10–30 2–5 Hz GV20, EX-HN1, EX-HN3, EX-HN5, GB15, CV12, CV6, TE5, HT7, LI4, ST36, ST40, SP6 Mini EA

Tx, treatment; int, intervention; wk, week; NR, not reported; TBC, to be confirmed; CTx, chemotherapy; freq, frequency; Acu, acupuncture; dur, duration; min, minute; EA, electroacupuncture; NA, Not applicable; Homeo, homeopathy; mini, minimal

*

8 wks of acu Tx., 4 wks of pause, and then 8 wks of acu Tx. again.

†

Varies depending on the CTx cycle. To start 1 wk before CTx and complete 3 wks after CTx.. One cycle of CTx = about 4 wks.

‡

The depth of the acu group was not described. However, since the depth of needling performed in the control group is 3–5 mm, the needling depth of the acu group is expected to be the same or deeper.

Table 3-3

Outcome measures used in yet-to-be-published clinical studies on the effect of acupuncture for chemotherapy-related cognitive impairment

Study id Time points (wk) Outcome measures
Cognitive function-related outcomes Others
Subjective Objective Biomarkers Brain imaging QOL Fatigue Anxiety Insomnia CTx. Tox Safety
Rossi20 [23] 0, 12 Assessed by a neuropsychologist Serum BDNF, proinflammatory cytokines
Rossi24 [24] 0, 12, End of CTx, 24 FACT-Cog Assessed by a neuropsychologist including BSCE Serum BDNF, proinflammatory cytokines
Gao24 [25] 0, 8, 14 MoCA, MMSE proinflammatory cytokines EORTC QLQ-C30
Xie23 [26] 0, 5, 10, 14 FACT-Cog v3 CANTAB Serum BDNF, proinflammatory cytokines, mtDNA Brain MRI EORTC QLQ-C30 EQ-5D-5L, RSCL MFSI-SF CTCAE
Yan23 [27] 0, one day before 3rd CTx, 3 wks after final CTx FACT-Cog MoCA FACT-General, PHQ-9 GAD-7 ISI PRO-CTCAE AE
Zhao24 [28] 0, 2, 4, 6, 8 FACT-Cog MoCA EORTC QLQ-C30 FACT, FACIT-fatigue FAACT, FACT-BRM CTCAE

Wk, week; CTx, chemotherapy; FACT-Cog, functional assessment of cancer treatment cognition; v3, version 3; BSCE, brief cognitive status exam; MoCA, Montreal cognitive assessment; MMSE, mini-mental state examination; CANTAB, Cambridge neuropsychological test automated battery; BDNF, blood-derived neurotrophic factor; mtDNA, mitochondrial DNA; MRI, magnetic resonance imaging; QOL, quality of life; EORTC QLQ-C30; European organization for research and treatment of cancer quality of life questionnaire core 30; EQ-5D-5L, Euro-Qol 5 dimensions 5 level questionnaire; RSCL, Rotterdam symptom checklist; FACT, functional assessment of cancer Tx; PHQ, patient health questionnaire; FACIT, functional assessment of chronic illness therapy; MFSI, multidimensional fatigue symptom inventory-short form; GAD, generalized anxiety disorder; ISI, insomnia severity index; Tox, toxicity; CTCAE, common terminology criteria for adverse events; PRO, patient reported outcomes; FAACT, functional assessment of anorexia/cachexia therapy; BRM, biologic response modifier; AE, adverse event