Your new experience awaits. Try the new design now and help us make it even better

SYSTEMATIC REVIEW article

Front. Oncol., 22 January 2026

Sec. Gastrointestinal Cancers: Colorectal Cancer

Volume 15 - 2025 | https://doi.org/10.3389/fonc.2025.1700525

This article is part of the Research TopicHarnessing natural products for novel anti-cancer strategies in gastrointestinal cancersView all 3 articles

Efficacy and safety of traditional Chinese medicine as an adjuvant to postoperative chemotherapy in colorectal cancer: a meta-analysis

Qinsi He&#x;Qinsi He1†Xiaodan Chen&#x;Xiaodan Chen1†Haotian ZengHaotian Zeng1Xinyu GaoXinyu Gao2Zhi ZhengZhi Zheng3Jun RaoJun Rao1Qun WenQun Wen1Xuchao YuXuchao Yu2Jiquan Zeng*Jiquan Zeng1*
  • 1Department of Integrated Traditional Chinese and Western Medicine, Jiangxi Cancer Hospital & Institute (The Second Affiliated Hospital of Nanchang Medical College), Nanchang, Jiangxi, China
  • 2Department of Anorectal Surgery, Affiliated Hospital of Jiangxi University of Traditional Chinese Medicine, Nanchang, Jiangxi, China
  • 3Department of Integrated Traditional Chinese and Western Medicine, Jiangxi Provincial People’s Hospital, Nanchang, Jiangxi, China

Objective: To systematically evaluate the efficacy and safety of traditional Chinese medicine (TCM) for postoperative adjuvant chemotherapy for colorectal cancer.

Methods: CNKI, VIP, Wanfang, CBM, PubMed, and Web of Science were searched for the randomized controlled trials (RCT) of TCM participating in postoperative adjuvant chemotherapy for colorectal cancer. The search period was from January 1, 2018 to December 31, 2024. Cochrane bias risk assessment tool was used to evaluate the quality of included studies, and RevMan5.4 was used for meta-analysis.

Results: A total of 41 randomized controlled trials involving 2918 patients with colorectal cancer was ultimately included. The results demonstrated that the combination of TCM with chemotherapy was superior to chemotherapy alone in several aspects. These included the objective response rate (ORR), improvement of TCM-related symptoms, levels of tumor markers CEA and CA199, immune function indicators (CD3+, CD4+, CD4+/CD8+, NK cells), and quality of life as measured by the KPS score. Additionally, the combination therapy reduced CD8+ levels and mitigated abnormal laboratory indicators caused by chemotherapy, such as leukopenia, thrombocytopenia, decreased hemoglobin, and abnormal liver and kidney function. Furthermore, it alleviated chemotherapy-related adverse effects (AEs), including nausea, vomiting, and peripheral nerve toxicity.

Conclusions: TCM may be associated with improvements in quality of life and reduce chemotherapy side effects in postoperative colorectal cancer patients, though large-scale rigorous trials are needed to confirm efficacy and safety.

Systematic Review Registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42025635900.

1 Introduction

Colorectal cancer (CRC) is one of the most commonly diagnosed malignancies worldwide and remains the third leading cause of cancer-related mortality. According to recent global cancer statistics, the incidence and mortality of CRC have shown a steady upward trend, particularly in low- and middle-income countries where urbanization, aging populations, and lifestyle shifts contribute to an increasing disease burden (1). The development of CRC is influenced by both modifiable and non-modifiable risk factors. Approximately 70–75% of cases are sporadic and linked to modifiable factors such as unhealthy diets, physical inactivity, obesity, smoking, and alcohol consumption. The remaining 25–30% arise from non-modifiable factors, including advanced age, family history, a personal history of colorectal adenomas or inflammatory bowel disease, and hereditary syndromes such as Lynch syndrome or familial adenomatous polyposis (1). Despite significant advancements in diagnostic and therapeutic approaches, prognosis remains stage-dependent and highly variable across regions. In high-income countries, the 5-year relative survival rate exceeds 65%, while in low-resource settings, it remains below 50% (2, 3).

Surgical resection followed by postoperative adjuvant chemotherapy is the standard treatment for early- and intermediate-stage CRC. However, recurrence rates remain concerning, affecting approximately 16% of stage II and up to 40% of stage III patients (4). This is often attributed to the inability of chemotherapy to eliminate microscopic residual disease and the adverse effects that lead to poor treatment compliance. Therefore, optimizing current treatment strategies through adjunctive approaches is of critical importance.

Traditional Chinese Medicine (TCM), with its holistic and multi-targeted therapeutic philosophy, has been increasingly recognized as a valuable adjunct in cancer care. Preclinical studies have shown that TCM exerts anti-cancer effects via multiple mechanisms, including apoptosis induction, immune modulation, anti-inflammatory activity, oxidative stress reduction, and regulation of gut microbiota (5).

Clinically, TCM has demonstrated potential in improving cancer-related symptoms, enhancing patients’ quality of life, mitigating chemotherapy-induced toxicities (e.g., nausea, vomiting, hematologic suppression, and peripheral neuropathy), and supporting immune and organ function. Several studies also report improvements in traditional Chinese medicine syndrome scores, Karnofsky Performance Status (KPS), tumor marker levels (CEA, CA19-9), and immune indices (CD3+, CD4+, CD8+, NK cells) following TCM-assisted chemotherapy (6, 7).

Nevertheless, existing clinical evidence remains fragmented, and a comprehensive synthesis of high-quality data is lacking. Therefore, this study aims to systematically evaluate the efficacy and safety of TCM as an adjuvant to postoperative chemotherapy in non-advanced colorectal cancer through a meta-analysis. By quantitatively analyzing objective response rates, symptom scores, immune and laboratory parameters, and chemotherapy-related toxicities, this study seeks to provide robust evidence to support the integration of TCM into standardized colorectal cancer management.

2 Materials and methods

This systematic review and meta-analysis were conducted following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines to ensure methodological rigor and transparency (8). The study protocol was prospectively registered with the International Prospective Register of Systematic Reviews (PROSPERO), under the registration number CRD42025635900.

2.1 Eligibility criteria

The inclusion and exclusion criteria of this meta-analysis were formulated based on the PICOS framework. Eligible studies were randomized controlled trials (RCTs) involving patients with pathologically confirmed colorectal cancer who underwent postoperative adjuvant chemotherapy, regardless of gender, race, or geographic region. In the intervention group, patients received TCM in combination with standard postoperative adjuvant chemotherapy, with no restriction on the type or formulation of TCM. The control group received postoperative adjuvant chemotherapy alone. Studies were excluded if they involved patients with unclear tumor staging, CRC with metastasis, absence of adjuvant chemotherapy, non-primary colorectal cancer or concurrent malignancies, or if they were non-RCTs, lacked key outcome data, or did not provide sufficient statistical information for inclusion.

2.2 Outcomes

The primary outcomes of this study encompassed both efficacy and safety indicators. Efficacy outcomes included objective response rate (ORR), quality of life (QoL), tumor marker levels, and immune function parameters. ORR was defined as the proportion of patients achieving complete response (CR) or partial response (PR), based on the World Health Organization (WHO) criteria or the Response Evaluation Criteria in Solid Tumors (RECIST); rates of stable disease (SD) and progressive disease (PD) were also reported when available. QoL was assessed using the Karnofsky Performance Status (KPS) score. Tumor markers evaluated included carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9). Immune function was measured by levels of CD3+, CD4+, and CD8+ T lymphocytes, the CD4+/CD8+ ratio, and natural killer (NK) cell counts. Safety outcomes comprised hematologic toxicity (anemia, thrombocytopenia, leukopenia), hepatic and renal dysfunction, gastrointestinal adverse events (nausea and vomiting), and peripheral neurotoxicity.

2.3 Search strategy and study selection

A comprehensive literature search was performed to identify relevant RCTs evaluating TCM combined with postoperative adjuvant chemotherapy for colorectal cancer. The search was conducted independently by two reviewers (Qinsi He and Xinyu Gao) using both Medical Subject Headings (MeSH) terms and free-text keywords. The following electronic databases were searched from January 1, 2018, to December 31, 2024, Chinese Biomedical Literature Database (CBM), China National Knowledge Infrastructure (CNKI), Chongqing VIP Database (VIP), and Wanfang Data for Chinese databases, and PubMed and Web of Science for international databases.

The search strategy combined terms related to colorectal cancer (e.g., “colorectal cancer, “ “colorectal neoplasm, “ “colorectal tumors”), Traditional Chinese Medicine (e.g., “herbal medicine, “ “Chinese herbal medicine, “ “traditional Chinese medicine”), and study design (e.g., “randomized, “ “randomized controlled trial”). The detailed search strategies were shown in Supplementary Table S1. Boolean operators (AND, OR) were used to combine terms appropriately to maximize search sensitivity. The titles and abstracts of all retrieved records were screened for relevance, and full texts of potentially eligible articles were then assessed against the inclusion criteria. Any disagreements between the two reviewers were resolved by discussion with a third researcher (Xiaodan Chen) to reach consensus.

The search strategy was adapted to the specific requirements of each database to ensure comprehensive coverage. Reference lists of included studies and relevant reviews were also manually searched to identify additional eligible studies.

2.4 Data extraction

Data extraction was independently performed by two reviewers, and extracted information included the first author, year of publication, sample size, types of medications, cancer staging system (TNM stage), Karnofsky Performance Status (KPS), details of the TCM intervention, standard treatment regimen, and outcome measures. Any discrepancies were resolved through discussion and consensus.

2.5 Assessment of risk of bias

Quality assessment was performed according to the Cochrane Handbook criteria, categorizing risk of bias as low risk, some concerns, or unclear risk based on the evaluation of six domains: selection bias, performance bias, detection bias, attrition bias, reporting bias, and other potential biases. Two researchers independently conducted and cross-checked the quality assessment, with any disagreements resolved through discussion involving a third researcher.

2.6 Statistical analyses

Data were analyzed using RevMan 5.4 software. Categorical variables were presented as odds ratios (ORs) with 95% confidence intervals (CI), while continuous variables were expressed as mean differences (MDs) with 95% CI. Heterogeneity among studies was assessed using the I² statistic. When P > 0.1 and I² < 50%, heterogeneity was considered low, and a fixed-effects model was applied; otherwise, a random-effects model was used. Sensitivity analysis was conducted by excluding articles one by one. In addition, funnel plot, Begg test, and Egger test were used to detect publication bias.

3 Results

3.1 Literature search and basic characteristics

A total of 2, 838 records were initially retrieved from six major, after removing 1, 028 duplicates, 1, 810 records remained for title and abstract screening. Ultimately, 41 RCTs met eligibility criteria and were included in the final meta-analysis (Figure 1). A total of 41 RCTs published between 2018 and 2024 were included in this study, involving postoperative patients with colorectal cancer. The experimental groups received oral TCM interventions—such as formulas for tonifying qi and spleen, resolving phlegm, or detoxifying the kidney—while the control groups were treated with standardized chemotherapy regimens, including FOLFOX, XELOX, or CapeOX. Treatment durations generally ranged from 2 to 12 cycles. Most participants were diagnosed with stage II–III CRC, with some studies also including stage I or high-risk stage II cases. Reported outcomes encompassed tumor efficacy, tumor markers (e.g., CEA, CA199), improvement in TCM syndromes, immune function, quality of life (measured by KPS score), laboratory parameters, and chemotherapy-related AEs, reflecting the multidimensional clinical effects of integrative therapy. The detailed information was shown in Table 1.

Table 1
www.frontiersin.org

Table 1. Characteristics of the included studies.

Figure 1
Flowchart illustrating the identification of studies via databases. Initially, 2,838 records were identified. After removing 1,028 duplicates, 1,810 records were screened. Of these, 1,603 were excluded after reviewing the title and abstract. Consequently, 207 reports were sought for retrieval, but 166 were not retrieved. Ultimately, 41 reports were assessed for eligibility, with all included in the study.

Figure 1. The flow chart of included studies.

3.2 Risk of bias assessment for included studies

Characteristics and quality of all included studies are presented in Supplementary Figures 1, 2.

3.3 Tumor objective efficacy - objective response rate

The efficacy evaluation followed the WHO or RECIST 1.1 criteria, categorizing outcomes into complete response (CR), partial response (PR), stable disease (SD), and progressive disease (PD). The ORR was calculated as: ORR=(CR+PR) cases/Total Cases×100%. A total of three RCTs (911), including 263 patients, reported on objective response rate. Heterogeneity among the studies was not statistically significant (P = 0.52, I² = 0.000%), indicating consistency across trials; therefore, a fixed-effects model was applied for the pooled analysis. The meta-analysis demonstrated that the combination of TCM with postoperative adjuvant chemotherapy significantly improved ORR compared with chemotherapy alone (OR = 3.32, 95% CI: 1.99–5.33, Z = 4.59, P < 0.001). These results suggested that TCM as an adjunct to postoperative adjuvant chemotherapy may improve the therapeutic response in patients with CRC (Figure 2A).

Figure 2
Two forest plots labeled A and B display meta-analysis results. Section A shows mean differences between experimental and control groups with three studies, indicating a combined mean difference of 4.06 favoring experimental. Section B presents odds ratios for several studies with an overall odds ratio of 5.79, again favoring experimental. Each plot includes confidence intervals and test statistics, with indicators for heterogeneity and overall effect significance.

Figure 2. (A) The forest plot of objective response rate; (B) Forest plot of the total effective rate of TCM syndrome improvement. TCM, traditional Chinese medicine.

3.4 The total effective rate of TCM syndrome improvement

TCM symptom scoring criteria referred to the Guiding Principles for Clinical Research of New Chinese Medicine, which were divided into obvious, effective, ineffective, total effective rate (%) = (obvious + effective) cases/total cases ×100%. 17 RCTs (1228) mentioned the total effective rate of TCM syndrome improvement. The pooled results demonstrated a significant difference between the two groups (OR = 5.79, 95% CI: 4.37–7.67, P < 0.001; I² = 50%; Figure 2B). Compared with postoperative adjuvant chemotherapy alone, the combination of TCM and postoperative adjuvant chemotherapy was associated with a markedly greater improvement in TCM syndrome scores among patients with colorectal cancer.

3.5 Tumor marker levels—CEA and CA19-9

After combining 19 studies (1013, 15, 1719, 2225, 2733)of CEA and 15 studies (1013, 17, 19, 22, 24, 25, 2833) of CA199 (Figure 3), TCM combined with postoperative adjuvant chemotherapy group exerted a better protective effect on tumor marker lever (CEA MD = -3.57, 95% CI = -4.64 to -2.5, P < 0.001, CA199 MD = -3.13, 95% CI = -4.83 to -1.44, P < 0.001) than control group. However, CEA I2 = 96% and CA199 I2 = 82%, representing large heterogeneity, Sensitivity analysis was performed for each outcome, and no significant source of heterogeneity was found during the analysis, and the results of meta-analysis showed good stability and statistical significance (P < 0.001). This indicated that TCM combined with postoperative adjuvant chemotherapy group significantly reduced the tumor markers lever (CEA, CA199) compared with the control group.

Figure 3
Forest plot showing comparative analysis of experimental and control groups across multiple studies. Two main subgroups, CEA and CA199, are analyzed. Each study shows mean differences, confidence intervals, and weight. Overall effects favor the control group. Heterogeneity and statistical test results provided at the bottom.

Figure 3. The forest plot of tumor marker levels (CEA and CA19-9) comparing TCM plus chemotherapy versus chemotherapy alone. Data presented as mean difference (MD) with 95% confidence intervals. Negative values favor the intervention group. CEA, carcinoembryonic antigen; CA19-9, carbohydrate antigen 19-9; TCM, traditional Chinese medicine.

3.6 Immune function

There were 12, 16, 14, 13 and three RCTs contributed to the analysis of CD3+ (9, 10, 1315, 17, 22, 24, 30, 3436), CD4+ (911, 1315, 17, 21, 22, 24, 27, 30, 32, 3436), CD8+ (911, 14, 15, 17, 21, 22, 24, 27, 32, 3436), CD4+/CD8+ (9, 1315, 17, 22, 24, 27, 30, 32, 3436), NK (911) respectively, representing statistical heterogeneity in CD3+ T cells (I2 = 61%), CD4+ T cells (I2 = 90%), CD8+ T cells (I2 = 96%), CD4+/CD8+ T cells ratio (I2 = 90%), and NK cells (I2 = 96%), hence, the random-effects model was adopted, The results of I² value and combined effect size showed no significant changes after removing literatures one by one, which proved that the study results were stable and reliable. The meta-analysis results showed that TCM plus postoperative adjuvant chemotherapy improved the CD3+ (MD, 7.05 [5.49, 8.60], P < 0.001) (Figure 4A), CD4+ (MD, 6.07 [4.41, 7.72], P < 0.001) (Figure 4B), CD4+/CD8+T cells ratio (MD, 0.40 [0.25, 0.54], P < 0.001) (Figure 4C), and NK cells (MD, 4.06 [0.65, 7.46], P = 0.002, Supplementary Figure 3A) and reduced the CD8+ (MD, -2.86 [-5.18, -0.54], P = 0.020) (Figure 4D) compared with postoperative adjuvant chemotherapy alone.

Figure 4
Forest plots labeled A, B, C, and D display meta-analysis results from various studies comparing experimental and control groups. Each plot lists studies with means, standard deviations, and weight percentages, followed by mean differences and confidence intervals. Vertical lines at zero mark null effects, and diamonds at the bottom represent pooled effect sizes. Plots A and B favor experimental interventions, while C and D show mixed outcomes, with varied heterogeneity among studies.

Figure 4. (A) The forest plot of CD3+; (B) The forest plot of CD4+; (C) The forest plot of CD8+; (D) The forest plot of the ratio of CD4+/CD8+.

3.7 Quality of life KPS score

The quality of life was evaluated according to the Karnofsky (KPS) patient health status rating scale, and evaluated once before and after treatment. The heterogeneity analysis of the result contained a total of 16 studies (10, 12, 18, 19, 2123, 28, 31, 34, 35, 3740, 44) included 1209 patients showed I2 = 95%, and the random-effect model was applied, the meta-analysis showed good stability and statistical significance (P < 0.001). Compared with the control group treated with postoperative adjuvant chemotherapy alone, quality of life KPS score of non-advanced colorectal cancer patients in the treatment group treated with TCM combined with postoperative adjuvant chemotherapy was significantly improved. [MD = 6.75, 95%CI (4.65, 8.86), P < 0.001] (Supplementary Figure 3B).

3.8 Laboratory examination

There were 12, 11, 15, and 4 RCTs contributed to the analysis of leukopenia (9, 13, 15, 19, 23, 28, 30, 36, 4144), hemoglobin (13, 19, 23, 24, 28, 4146), thrombocytopenia (9, 13, 15, 23, 24, 27, 28, 30, 36, 4146), abnormal liver and kidney function respectively (15, 30, 40, 42), representing low heterogeneity in leukopenia (I2 = 24%), hemoglobin (I2 = 26%), thrombocytopenia (I2 = 0), and abnormal liver and kidney function (I2 = 0), hence, the fixed-effects model was adopted. The meta-analysis results showed that TCM plus postoperative adjuvant chemotherapy reduced the risk of the leukopenia (OR, 0.39 [0.29, 0.53], P < 0.001), hemoglobin (OR, 0.50 [0.37, 0.67], P < 0.001), thrombocytopenia (OR, 0.49 [0.36, 0.65], P < 0.001) and abnormal liver and kidney function (OR, 0.31 [0.14, 0.67], P = 0.003) compared with postoperative adjuvant chemotherapy alone (Supplementary Figures 4A–D).

3.9 Adverse reactions

3.9.1 Nausea and vomiting

16 RCTs (1113, 15, 17, 19, 23, 24, 27, 28, 30, 34, 40, 43, 45, 47) mentioned AEs nausea and vomiting, owing to the low heterogeneity, the fixed effect model was selected for further calculation, and the results showed significant difference between two groups (OR, 0.34 [0.25, 0.47], P < 0.001, I2 = 30%). Compared with postoperative adjuvant chemotherapy group, TCM combined with postoperative adjuvant chemotherapy group could reduce the incidence of AEs nausea and vomiting of CRC patients (Supplementary Figure 5).

3.9.2 Peripheral nerve toxicity

13 RCTs (12, 15, 17, 19, 22, 23, 28, 31, 37, 41, 4345) mentioned AEs peripheral nerve toxicity, owing to the low heterogeneity, the fixed effect model was applied, showed significant difference between two groups (OR, 0.49 [0.35, 0.67], P < 0.001, I2 = 26%). Indicating that in the treatment of CRC, compared with postoperative adjuvant chemotherapy group, TCM combined with postoperative adjuvant chemotherapy group could reduce the incidence of AEs peripheral nerve toxicity (Supplementary Figure 6).

4 Discussion

This meta-analysis of 41 trials involving 2918 CRC patients without metastasis demonstrates that the integration of TCM with postoperative adjuvant chemotherapy offers significant clinical advantages over chemotherapy alone. TCM significantly enhanced tumor response, improved immune function, reduced tumor marker levels (CEA, CA19-9), and mitigated treatment-related toxicities. Notably, it also contributed to better quality of life and a lower incidence of hematologic and organ toxicities, highlighting its potential as a safe and effective adjunct to conventional therapy.

Despite advances in surgical techniques and adjuvant therapies, CRC recurrence remains a major clinical challenge. Recurrence is primarily driven by minimal residual disease, adverse tumor biology (e.g., RAS/BRAF mutations, MSS status), lymphovascular invasion, inadequate resection margins, and non-adherence to postoperative treatment or follow-up (48, 49). Strategies to reduce recurrence include high-quality standardized surgery, risk-adapted adjuvant therapy, and rigorous surveillance. Although surgical resection, chemotherapy, radiotherapy, and targeted therapies have significantly improved patient survival, recurrence remains a critical factor affecting long-term prognosis. Increasing evidence suggests that integrating TCM with postoperative adjuvant chemotherapy may offer clinical benefits in CRC management. TCM has shown potential in alleviating chemotherapy-induced toxicity, improving gastrointestinal symptoms, enhancing immune function, and modulating tumor microenvironment (50, 51).

Our results showed that TCM involvement in adjuvant chemotherapy was positive and aligned with the findings of the following studies on TCM in cancer (50, 52). Researches had consistently shown that TCM not only relieved symptoms like fatigue, chronic pain, anorexia/cachexia, and insomnia in cancer patients, enhancing their QOL, but also mitigated the side effects and complications caused by chemotherapy, radiotherapy, and targeted treatments (53). Moreover, TCM possessed anti-tumor properties, Sijunzi Decoction could promote apoptosis and autophagy of CRC cells through PI3K/Akt/mTOR pathway (54). However, Other systematic studies focus on the combination of TCM with specific chemotherapy drugs, the use of TCM in injectable forms, and its efficacy and safety in managing specific chemotherapy-induced side effects, such as diarrhea (50, 55, 56). The outcome indicators in our study were consistent with those reported in previous research. Tumor response, reflected by improvements in ORR, was enhanced with the addition of TCM. Common AEs associated with postoperative adjuvant chemotherapy—such as nausea, vomiting, and peripheral neurotoxicity—were significantly reduced. Hematologic and organ function safety profiles also improved, with lower incidences of leukopenia, anemia, thrombocytopenia, and abnormal liver and kidney function. Furthermore, immune parameters, including elevated CD3+, CD4+, and CD4+/CD8+ ratios, alongside reduced CD8+ levels, indicated a shift toward an activated, non-immunosuppressive state (57). This immune modulation may enhance immune surveillance and reduce the risk of tumor recurrence and metastasis (58). The interpretation of these findings requires careful clinical context. While CD8+ cytotoxic T cells are crucial for anti-tumor immunity, their functional state—rather than their absolute number alone—determines their overall effect. A depressed immune state, often induced by chemotherapy, is characterized not only by low CD4+ counts but also by an inverted CD4+/CD8+ ratio. Therefore, the key finding is the restoration of a more balanced CD4+/CD8+ ratio, which is a recognized indicator of improved overall immune competence and is often associated with better clinical outcomes in cancer patients.

sCrucially, these favorable shifts in immune parameters were observed alongside direct patient benefits documented in our analysis: namely, improved control of chemotherapy-related symptoms (e.g., nausea, vomiting), enhanced quality of life (KPS score), and a reduction in hematologic toxicity. This correlation suggests that the immunomodulatory effects of TCM are part of a broader biological response that may contribute to better treatment tolerance and patient well-being. It should be noted that the decrease in CD8+ T cells could reflect a reduction in exhausted or regulatory subsets; however, in the absence of more specific T-cell phenotyping data, we refrain from concluding a direct anti-tumor benefit from the CD8+ decrease alone. The collective improvement in multiple immune subsets and, more importantly, their correlation with tangible clinical endpoints, supports the potential role of TCM in mitigating chemotherapy-induced immunosuppression.

Despite providing supportive evidence for the efficacy and safety of TCM as an adjuvant to postoperative chemotherapy in CRC, this study has several limitations. First, substantial heterogeneity was observed across the included trials, arising from differences in TCM formulations, individual herbal components, chemotherapy regimens, treatment durations, follow-up periods, and definitions of clinical outcomes. This heterogeneity may reduce the reliability and consistency of the pooled estimates. Additionally, potential publication and selection biases, particularly the underreporting of negative or inconclusive results in TCM research, may have skewed the findings. Second, many studies had small sample sizes and lacked rigorous methodological design, limiting the statistical power and external validity of the results. Furthermore, a key limitation of this study is the inability to perform a stratified analysis by tumor stage, as the included studies predominantly involved patients with stages I-III without providing sufficiently granular data for distinct stage-based comparisons.

Future studies should focus on the standardization of TCM interventions for specific clinical stages of CRC, including the selection of dosage forms (e.g., injections, decoctions, or granules), drug categories (e.g., tonifying or detoxifying agents), dosage, duration, and optimal initiation timing. Well-designed, large-scale, multicenter RCTs are needed to further confirm the clinical benefits and safety profile of TCM. Moreover, mechanistic studies should be strengthened to elucidate the pharmacological basis of TCM interventions and support evidence-based clinical application.

5 Conclusions

TCM may be a complementary approach that warrants further investigation for its potential to improve QOL and reduce chemotherapy-related AEs. Existing studies indicate that TCM interventions might contribute to QOL improvement, mitigation of chemotherapy-related AEs, and immunomodulatory benefits. However, it should be emphasized that current evidence remains insufficient to draw definitive conclusions, as most available studies are limited by small sample sizes, methodological heterogeneity, and potential publication bias. Large-scale, rigorously designed RCTs with standardized outcome measures are required to establish robust evidence regarding the efficacy, safety profiles, and underlying mechanisms of TCM in this clinical context.

Data availability statement

The original contributions presented in the study are included in the article/Supplementary Material. Further inquiries can be directed to the corresponding author.

Author contributions

QH: Conceptualization, Methodology, Project administration, Writing – original draft, Writing – review & editing. XC: Formal analysis, Writing – review & editing. HZ: Formal analysis, Writing – review & editing. XG: Formal analysis, Writing – review & editing. ZZ: Data curation, Resources, Writing – review & editing. JR: Data curation, Visualization, Writing – review & editing. QW: Investigation, Writing – review & editing. XY: Software, Writing – review & editing. JZ: Conceptualization, Methodology, Project administration, Writing – review & editing.

Funding

The author(s) declared that financial support was received for this work and/or its publication. This work was supported by the Jiangxi Provincial Science and Technology Department funded project [grant number 20212BAG70040], Jiangxi Province (provincial units) old Chinese medicine experts academic experience inheritance work “project number: (Gan Chinese Medicine Science and education word (2022) No. 18 ”, Jiangxi Provincial Department of Education Youth Project Project [grant number GJJ2203557], Jiangxi Provincial Natural Science Foundation Project [grant number 20242BAB25541], Jiangxi Provincial Health Commission Science and Technology Project [grant number 202510508], Jiangxi Provincial Traditional Chinese Medicine Research Project [grant number 2019B089].

Conflict of interest

The authors declared that this work was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Generative AI statement

The author(s) declared that generative AI was not used in the creation of this manuscript.

Any alternative text (alt text) provided alongside figures in this article has been generated by Frontiers with the support of artificial intelligence and reasonable efforts have been made to ensure accuracy, including review by the authors wherever possible. If you identify any issues, please contact us.

Publisher’s note

All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.

Supplementary material

The Supplementary Material for this article can be found online at: https://www.frontiersin.org/articles/10.3389/fonc.2025.1700525/full#supplementary-material

References

1. Sharma R, Abbasi-Kangevari M, Abd-Rabu R, Abidi H, Abu-Gharbieh E, Acuna JM, et al. Global, regional, and national burden of colorectal cancer and its risk factors, 1990–2019: a systematic analysis for the Global Burden of Disease Study 2019. Lancet Gastroenterol Hepatol. (2022) 7:627–47. doi: 10.1016/S2468-1253(22)00044-9

PubMed Abstract | Crossref Full Text | Google Scholar

2. Brenner H, Kloor M, and Pox CP. Colorectal cancer. Lancet (London England). (2014) 383:1490–502. doi: 10.1016/S0140-6736(13)61649-9

PubMed Abstract | Crossref Full Text | Google Scholar

3. Fu MS, Pan SX, Cai XQ, and Pan QC. Urban vs. rural: colorectal cancer survival and prognostic disparities from 2000 to 2019. Front Public Health. (2024) 12:1319977. doi: 10.3389/fpubh.2024.1319977

PubMed Abstract | Crossref Full Text | Google Scholar

4. Li X, Yang GY, Li XX, Zhang Y, Yang JL, Chang J, et al. Traditional Chinese medicine in cancer care: A review of controlled clinical studies published in chinese. PLoS One. (2013) 8:e60338. doi: 10.1371/journal.pone.0060338

PubMed Abstract | Crossref Full Text | Google Scholar

5. Bai FC, Huang ZG, Luo J, Qiu Y, Huang SW, Huang CL, et al. Bibliometric and visual analysis in the field of traditional Chinese medicine in cancer from 2002 to 2022. Front Pharmacol. (2023) 14:1164425. doi: 10.3389/fphar.2023.1164425

PubMed Abstract | Crossref Full Text | Google Scholar

6. Jiang B, Meng ZY, Hu YJ, Chen JJ, Zong L, Xu LY, et al. Huachansu injection enhances anti-colorectal cancer efficacy of irinotecan and alleviates its induced intestinal toxicity through upregulating UGT1A1-OATP1B3 expression in vitro and in vivo. J Integr Med. (2025) 23:576–90. doi: 10.1016/j.joim.2025.06.006

PubMed Abstract | Crossref Full Text | Google Scholar

7. Yuan C, Zhang W, Wang J, Huang C, Shu B, Liang Q, et al. Chinese medicine phenomics (Chinmedphenomics): personalized, precise and promising. Phenomics (Cham Switzerland). (2022) 2:383–8. doi: 10.1007/s43657-022-00074-x

PubMed Abstract | Crossref Full Text | Google Scholar

8. Page MJ, McKenzie JE, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD, et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ (Clinical Res ed). (2021) 372:n71. doi: 10.1136/bmj.n71

PubMed Abstract | Crossref Full Text | Google Scholar

9. Liu YP and Xue CH. Effects of Sijunzi Decoction combined with modified Liuwei Dihuang Decoction on the functional status of the body after radical surgery for stage II and III rectal cancer. Mod. J. Integr. Tradit. Chin. West. Med. (2022) 31:2563–5. doi: 10.3969/j.issn.1008-8849.2022.18.017

Crossref Full Text | Google Scholar

10. Xiao G, Jiang J, Luo L, Li J, and Yang DZ. Efficacy of Fuzheng Yi'ai Decoction supplemented with laparoscopic radical resection of rectal cancer in the treatment of early rectal cancer. Hebei Med. (2023) 29:1051–6. doi: 10.3969/j.issn.1006-6233.2023.06.033

Crossref Full Text | Google Scholar

11. Fan Y, Ma Y, Wang QL, Zhang X, Sheng H, and Deng WL. Clinical efficacy observation of Chinese medicine Yiqi Fusheng Decoction in treating colorectal cancer patients with postoperative chemotherapy. J. Shanghai Univ. Tradit. Chin. Med. (2018) 32:19–22. doi: 10.16306/j.1008-861x.2018.06.006

Crossref Full Text | Google Scholar

12. Li C. Clinical study of Shenling Baizhu Decoction and Sishen Pill combined with FOLFOX6 chemotherapy in the treatment of postoperative colorectal cancer with spleen-kidney Yang deficiency (dissertation/bachelor's thesis). Anhui University of Chinese Medicine, Hefei (2019). doi: 10.26922/d.cnki.ganzc.2019.000126

Crossref Full Text | Google Scholar

13. Fan GY. Observation on the clinical efficacy of Jianpi Huashi Formula combined with chemotherapy on postoperative colorectal cancer patients with spleen deficiency and dampness obstruction syndrome (dissertation/master's thesis). Fujian University of Chinese Medicine, Fuzhou. (2019).

Google Scholar

14. Lai ML. Clinical observation of Renshen Yangrong Decoction on postoperative colorectal cancer chemotherapy patients with deficiency of both qi and blood (dissertation/master's thesis). Fujian University of Chinese Medicine, Fuzhou. (2021).

Google Scholar

15. Lan Y, Peng F, and Xiao H. Effect analysis of modified Shenling Baizhu Decoction combined with chemotherapy in the treatment of colon cancer. Oncol. Prog. (2020) 18:23. doi: 10.11877/j.issn.1672-1535.2020.18.23.21

Crossref Full Text | Google Scholar

16. Lv L, Shen X, Zhang J, Li Q, Wu J, Wu Y, et al. Clinical Observation of Fuzheng Xiaoji Granule in the Treatment of Stage IIIC Colorectal Cancer. Evid. Based Complement. Alternat. Med.. (2022) 2022:4618342. doi: 10.1155/2022/4618342

PubMed Abstract | Crossref Full Text | Google Scholar

17. Ma T, Yang D, Chu J, et al. Clinical efficacy of Buqi Yichang Formula combined with chemotherapy in postoperative colorectal cancer patients and its effect on immune function. World J. Integr. Tradit. West. Med.. (2020) 15:2161–2165,2172. doi: 10.13935/j.cnki.sjzx.20120

Crossref Full Text | Google Scholar

18. Qi L. Clinical study on Postoperative Colorectal Cancer treated by Peishi Qingchang Guben Decoction combined with FOLFOX Chemotherapy. (dissertation/master's thesis). Lanzhou: Gansu University of Traditional Chinese Medicine (2018).

Google Scholar

19. Tang YB. Clinical observation of Angelica sinensis blood tonic soup combined with mFolFox6 regimen for the treatment of postoperative colorectal cancer with qi and blood deficiency type. (dissertation/bachelor's thesis) Hunan University of Traditional Chinese Medicine, Changsha (2022). doi: 10.27138/d.cnki.ghuzc.2022.000500

Crossref Full Text | Google Scholar

20. Wang YY, Wang L, Yin XL, Yu LY, Gao K, Sui KY, et al. Clinical study on zengyi formula combined with chemotherapy in treatment of patients with spleen deficiency syndrome after operation for colorectal cancer. Shandong J Traditional Chin Med. (2021) 40:5. doi: 10.16295/j.cnki.0257-358x.2021.05.006

Crossref Full Text | Google Scholar

21. Wu T. Short-term clinical observation of Zi Shen Gusui Decoction combined with m-FOLFOX6 chemotherapeutic Regimen Affects the mid-term colorectal cancer After Operation. (dissertation/bachelor's thesis) Guangzhou University of Traditional Chinese Medicine, Guangzhou (2019).

Google Scholar

22. Wu WT. Effects of jianpi Jiedu Decoction on Postoperative Colorectal Cancer Patients with CapeOX Chemotherapy. (dissertation/bachelor's thesis) Shanghai University of Traditional Chinese Medicine, Shanghai (2019). doi: 10.27320/d.cnki.gszyu.2019.000813

Crossref Full Text | Google Scholar

23. Xue W. Clinical study on the efficacy of Yiqi Nourishing Yin and Resolving Phlegm Formula combined with XELOX regimen in the treatment of colorectal cancer after surgery (dissertation/bachelor's thesis). Guizhou University of Traditional Chinese Medicine, Guiyang. (2019).

Google Scholar

24. Zeng D, Zhang CM, Guo JP, et al. Curative effect of Qutan Sanjie Formula on postoperative patients with colorectal cancer and its influence on immune function. Chin. J. Inf. Tradit. Chin. Med. (2023) 30:148–152.

Google Scholar

25. Zhang MD. Clinical Study on the Effect of Xiaoliu Decoction on the Expression of Vascular Endothelial Growth Factor in Postoperative Patients with Colorectal Cancer. (dissertation/bachelor's thesis) Guangxi University of Traditional Chinese Medicine, Nanning (2019).

Google Scholar

26. Zhang XB. Clinical effective observation on treating chemotherapy after radical operation of rectal cancer of Qizhi Xueyu type with the Zengxiao Jiandu decoction. Clin J Of Chin Med. (2018) 10:77–80. doi: 10.3969/j.issn.1674-7860.2018.21.036

Crossref Full Text | Google Scholar

27. Zhang YD and Zhu PF. Observation on the Curative Effect of Shenling Baizhu Powder and Sishen Pill Combined with Chemotherapy for Radical Resection of Colorectal Cancer. Chin. J. Integr. Tradit. West. Med. Surg.. (2021) 27:592–596. doi: 10.3969/j.issn.1007-6948.2021.04.009

Crossref Full Text | Google Scholar

28. Zhang YS. Clinical study of Fuzheng Qingdu Decoction combined with Chemotherapy Intervening in Postoperative patients with colorectal cancer. (dissertation/bachelor's thesis) Yangzhou University, Traditional Chinese Medicine, Yangzhou (2023).

Google Scholar

29. Chen CY, He JH, and Chen YQ. Curative effect of yiqi jianpi tang combined with chemotherapy on patients with colon cancer after radical treatment. New Chin Med. (2021) 53:159–62.

Google Scholar

30. Chen WJ, He JS, and Lu XP. Clinical efficacy of Erling Coixi Ren Tang combined with conventional Western medicine in the treatment of postoperative colon cancer and its effect on cellular immune function status and serological indexes. Zhejiang J Traditional Chin Med. (2019) 54:664–5. doi: 10.13633/j.cnki.zjtcm.2019.09.028

Crossref Full Text | Google Scholar

31. Jiang WL. Observation on the clinical application effect and anal preservation rate of Garcinia cambogia tonic and Chinese herbal medicine soup combined with neoadjuvant chemotherapy in the treatment of low rectal cancer. China Health Nutr. (2019) 29:335. doi: 10.3969/j.issn.1004-7484.2019.06.315

Crossref Full Text | Google Scholar

32. Jin YT, Wang YP, and Xia LM. Efficacy observation of Qingdu formula and chemotherapy on postoperative rectal cancer with syndrome of toxin stagnation and qi deficiency. Shanxi J Traditional Chin Med. (2023) 39:30–2.

Google Scholar

33. Wang SP and Zheng QH. Observation on the efficacy of Jingqi Shengxue Decoction combined with FOLFOX6 regimen in adjuvant chemotherapy for rectal cancer. J. Med. Sci. Cent. South China. (2019) 47:1. doi: CNKI:SUN:HYYY.0.2019-01-009

Google Scholar

34. Zheng L, Dongfeng Y, Wei W, Xinwei Z, Lijiang Z, and Jun Y. Efficacy of Yiqi Jianpi anti-cancer prescription combined with chemotherapy in patients with colorectal cancer after operation. World J. Clin. Cases. (2021) 9:9869–9877. doi: 10.12998/WJCC.V9.I32.9869

PubMed Abstract | Crossref Full Text | Google Scholar

35. Xiao C, Cao B, Li ML, Li K, Wang ZM, and Zhang XB. Effect of Yiqi Yangyin Huatan recipe combined with xelox chemotherapy on immune function in patients with colorectal cancer surgery. Acta Med Mediterranea. (2020) 36:3729–36. doi: 10.19193/0393-6384_2020_6_591

Crossref Full Text | Google Scholar

36. Yang C and Chen P. Application of warm kidney and spleen tonic to adjuvant chemotherapy in the treatment of postoperative colorectal cancer patients. Mod. Med. Health Res.. (2021) 5:72–75.

Google Scholar

37. Fang XJ. The Clinical Observation of Using Xiaoliu Decoction Combined with XELOX Program in Postoperative Patients with Colorectal Cancer (dissertation/bachelor's thesis). Wenzhou Medical University, Wenzhou (2018).

Google Scholar

38. Huang M. Study on the clinical effect of Fuzheng Xiaocai Granules on postoperative colorectal cancer (dissertation/bachelor's thesis). Guangxi University of Chinese Medicine, Nanning (2021).

Google Scholar

39. Tong Y. Clinical observation of Dahuang Mudan Decoction combined with chemotherapy in postoperative patients with colon cancer. China J. Pharm. Econ.. (2018) 13:73–75. doi: 10.12010/j.issn.1673-5846.2018.08.022

Crossref Full Text | Google Scholar

40. Zhang BW and Li Z. Observation on the clinical efficacy of combining the combination of Hua Jie Wu Tumour Elimination Soup and Traditional Chinese Medicine Burial for patients with colorectal cancer treated with postoperative chemotherapy. J Hubei Institute Sci Technol (Medical Edition). (2023) 37:541–4.

Google Scholar

41. Chen X. Comparative analysis of clinical efficacy and FACT-C score of adjuvant intravenous chemotherapy combined with traditional Chinese medicine after radical surgery for colon cancer. J Med Forum. (2020) 41:131–3.

Google Scholar

42. Miao X, Tao YH, Gu XX, and Shen SJ. Jisheng decoction combined with postoperative adjuvant chemotherapy in treating Patients undergoing chemotherapy post II period colorectal cancer operation and its effect on intestinal flora. Chin J Surg Oncol. (2019) 11:346–9.

Google Scholar

43. Shi TT. The clinical observation of Qidi Buyuan decoction combined with chemotherapy in treating patients with liver-yin and kidney-yin deficiency after colon cancer surgery. (dissertation/master's thesis) Hei Long Jiang University of Traditional Chinese Medicine, Harbin (2019).

Google Scholar

44. Zhou GY, Lin L, Feng DK, Ming L, Lu SF, and Gan LZ. Clinical efficacy of adjuvant intravenous chemotherapy combined with traditional Chinese medicine after radical surgery for colorectal cancer. Modern Digest Intervent Diagnosis Treat. (2018) 23:471–3.

Google Scholar

45. Jia R. Effect and Mechanism of Preventing Colorectal Cancer Metastasis of Bushen Jiedu Recipe. (dissertation/doctoral thesis) Shanghai: Shanghai university of traditional chinese medicine (2020). doi: 10.27320/d.cnki.gszyu.2020.000790

Crossref Full Text | Google Scholar

46. Wang YY, Wang L, Yin XL, Yu LY, Gao K, Sui KY, et al. Clinical study on Zengyi Formula combined with chemotherapy in treatment of patients with spleen deficiency syndrome after operation for colorectal cancer. Shandong J. Tradit. Chin. Med.. (2021) 40:476–481. doi: 10.16295/j.cnki.0257-358x.2021.05.006

Crossref Full Text | Google Scholar

47. Zhang YF. Efficacy analysis of yiqi Jianpi Decoction combined with FOLFOX4 chemothe rapy for postoperative colorectal cancer patients. Contemp Med. (2022) 20:169–71. doi: 10.3969/j.issn.2095-7629.2022.04.053

Crossref Full Text | Google Scholar

48. Parikh AR, Van Seventer EE, Siravegna G, Hartwig AV, Jaimovich A, He Y, et al. Minimal residual disease detection using a plasma-only circulating tumor DNA assay in patients with colorectal cancer. Clin Cancer Res. (2021) 27:5586–94. doi: 10.1158/1078-0432.CCR-21-0410

PubMed Abstract | Crossref Full Text | Google Scholar

49. Scheithauer W, Schiessel R, Schüller J, Karall M, Ernst F, Sebesta C, et al. Treatment of patients with advanced colorectal cancer with cisplatin, 5-fluorouracil, and leucovorin. Cancer. (1991) 67:1294–8. doi: 10.1002/1097-0142(19910301)67:5<1294::AID-CNCR2820670504>3.0.CO;2-M

Crossref Full Text | Google Scholar

50. Jiang HZ, Jiang YL, Yang B, Long FX, Yang Z, and Tang DX. Traditional Chinese medicines and capecitabine-based chemotherapy for colorectal cancer treatment: A meta-analysis. Cancer Med. (2023) 12:236–55. doi: 10.1002/cam4.4896

PubMed Abstract | Crossref Full Text | Google Scholar

51. Su Z, Li Y, Zhou Z, Feng B, Chen H, and Zheng G. Herbal medicine for colorectal cancer treatment: molecular mechanisms and clinical applications. Cell Prolifer. (2025) 58:e70065. doi: 10.1111/cpr.70065

PubMed Abstract | Crossref Full Text | Google Scholar

52. Li R, Zhang T, Yan SH, Yan YZ, Ding YC, Wang YS, et al. Chinese medicine combined with adjuvant chemotherapy for improving myelosuppression in colorectal cancer patients: A systematic review and network meta-analysis. Chin J Integr Med. (2024) 30:643–52. doi: 10.1007/s11655-023-3558-7

PubMed Abstract | Crossref Full Text | Google Scholar

53. Zhang X, Qiu H, Li CS, Cai PP, and Qi FH. The positive role of traditional Chinese medicine as an adjunctive therapy for cancer. BioSc Trends. (2021) 15:283–98. doi: 10.5582/bst.2021.01318

PubMed Abstract | Crossref Full Text | Google Scholar

54. Shang LR, Wang YC, Li JX, Zhou FY, Xiao KM, Liu YH, et al. Mechanism of Sijunzi Decoction in the treatment of colorectal cancer based on network pharmacology and experimental validation. J Ethnopharmacol. (2023) 302. doi: 10.1016/j.jep.2022.115876

PubMed Abstract | Crossref Full Text | Google Scholar

55. Liu SZ, Zhang K, and Hu XF. Comparative efficacy and safety of Chinese medicine injections combined with capecitabine and oxaliplatin chemotherapies in treatment of colorectal cancer: A bayesian network meta-analysis. Front Pharmacol. (2022) 13. doi: 10.3389/fphar.2022.1004259

PubMed Abstract | Crossref Full Text | Google Scholar

56. Chen YY, Cheng CS, Tan H, Tam CW, Wang N, and Feng YB. Efficacy of herbal medicines intervention for colorectal cancer patients with chemotherapy-induced gastrointestinal toxicity — a systematic review and meta-analysis. Front Oncol. (2021) 11. doi: 10.3389/fonc.2021.629132

PubMed Abstract | Crossref Full Text | Google Scholar

57. Chen Y, Lai X, Zhang Y, Qiu C, Qin Y, Fan T, et al. Huang-Lian-Jie-Du decoction enhances Capecitabine-Oxaliplatin efficacy via Akkermansia muciniphila and CD8(+) T cells in colorectal cancer. Phytomed: Int J Phytother Phytopharmacol. (2025) 148:157233. doi: 10.1016/j.phymed.2025.157233

PubMed Abstract | Crossref Full Text | Google Scholar

58. Li N, Liu L, Wang X, and Hao S. Traditional Chinese medicine in the management of colorectal cancer liver metastasis: mechanisms, challenges, and perspectives. Pharmacology. (2025), 1–17. doi: 10.1159/000549133

PubMed Abstract | Crossref Full Text | Google Scholar

Keywords: adjuvant chemotherapy, colorectal cancer, meta-analysis, TCM, traditional Chinese medicine

Citation: He Q, Chen X, Zeng H, Gao X, Zheng Z, Rao J, Wen Q, Yu X and Zeng J (2026) Efficacy and safety of traditional Chinese medicine as an adjuvant to postoperative chemotherapy in colorectal cancer: a meta-analysis. Front. Oncol. 15:1700525. doi: 10.3389/fonc.2025.1700525

Received: 19 September 2025; Accepted: 16 December 2025; Revised: 01 December 2025;
Published: 22 January 2026.

Edited by:

Ahmed Elissawy, Ain Shams University, Egypt

Reviewed by:

Chang-quan Ling, Second Military Medical University, China
Chih-Chen, Tzang, National Taiwan University, Taiwan

Copyright © 2026 He, Chen, Zeng, Gao, Zheng, Rao, Wen, Yu and Zeng. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

*Correspondence: Jiquan Zeng, anhuY3pqcUAxNjMuY29t

These authors have contributed equally to this work

Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.