Abstract
Background
Although many systematic reviews and meta-analyses have explored Traditional Chinese Medicine (TCM) for non-small cell lung carcinoma (NSCLC), uncertainty remains about the pooled efficacy, safety, and methodological quality of these reviews and the interventions they assessed. This study aimed to address this gap by analyzing TCM treatments for NSCLC using evidence mapping.
Methods
A comprehensive search across six databases identified relevant systematic reviews and meta-analyses up to August 2025. The AMSTAR-2 tool was used to assess methodological quality, and Python was used for statistical analysis and visualization. Evidence maps were created to group reviews by treatment types (chemotherapy, targeted therapy, radiotherapy, immunotherapy and supportive care) and by specific outcomes such as objective response rate (ORR), leukopenia, and quality of life (QoL).
Results
Out of 196 systematic reviews, 42 TCM interventions and 55 outcomes were identified. Most reviews examined TCM combined with chemotherapy, particularly Aidi, Kanglaite, and Shenqi Fuzheng injections. These combinations showed potential benefits in ORR, QoL, and chemotherapy-induced leukopenia. TCM combined with targeted therapies, such as EGFR-TKIs and Astragalus, also indicated benefits in progression-free survival and immune function. However, most systematic reviews were of "critically low" quality, limiting evidence reliability.
Conclusion
While TCM shows promise in enhancing conventional NSCLC treatments, high-quality, rigorously conducted randomised trials and reviews are essential to confirm these findings and guide clinical integration.
Keywords: Traditional Chinese medicine, Non-small cell lung carcinoma, Evidence mapping, Systematic review, Adjuvant therapy
1. Introduction
With an estimated 2.2 million new cases and 1.8 million deaths per year, lung cancer is the second most diagnosed cancer and the leading cause of cancer-related deaths worldwide.1 Non-small cell lung carcinoma (NSCLC) accounts for up to 85 % of all lung cancer cases.2 In many cases, patients with NSCLC are diagnosed at advanced stages with local invasion or metastasis, making surgical management impractical.3 However, substantial advances in treatment, particularly in targeted therapy and immunotherapy, have led to remarkable progress and improved outcomes for these patients. Nevertheless, current therapeutic options often lead to resistance over time and can result in high toxicity, highlighting the urgency to identify alternative approaches that increase effectiveness, reduce adverse effects, and improve the quality of life (QoL) for NSCLC patients.4
Guided by the ancient theoretical system of syndrome differentiation and combined with modern pharmaceutics, Traditional Chinese Medicine (TCM) is increasingly popular as a complementary or alternative therapy to enhance therapeutic effect and reduce adverse events in lung cancer treatment in China and other East Asian countries.5, 6, 7, 8 According to the basic TCM theory, the pathogenesis of lung cancer involves Qi stagnation, blood stasis, phlegm accumulation, and cancer toxins, making Chinese herbal medicine (CHM) particularly interesting for its pharmacological effects in counteracting these factors.9 Network pharmacology and experimental validation studies have demonstrated that key compounds achieve this by regulating signaling pathways, inducing apoptosis, and inhibiting tumor cell proliferation and migration.10, 11, 12, 13 Numerous studies have reported the effectiveness of TCM treatments as adjuvant therapies for NSCLC, in combination with chemotherapy, radiotherapy, targeted therapy, and best supportive care (BSC).14 However, the abundance of existing systematic reviews and meta-analyses, each focusing on specific formulas or drugs, makes it difficult to comprehensively demonstrate the advantages of TCM for NSCLC. This leads to a waste of research resources and challenges for clinical implementation.15 Furthermore, uncertainty about the methodological quality of current research can overwhelm stakeholders when making policy decisions.16
To address this gap in the synthesis of the extensive and varied evidence, and to provide a clearer, more comprehensive overview of the benefits and limitations of TCM as adjuvant therapy for NSCLC, we conducted this evidence mapping study. Evidence mapping summarizes the results of clinical research to provide a broad overview of the quantity, characteristics and outcomes of related research.17, 18, 19 In this study, we retrived and organized systematic reviews and meta-analyses on TCM for NSCLC, gathered general information and assessed the methodological quality of each review. After synthesizing and summarizing the evidence, we visually displayed the findings to support clinical decision-making and to identify research gaps for the use of TCM in NSCLC.
2. Methods
2.1. Search strategy
Our search strategy incorporated three key concepts, combined using the Boolean operator 'AND'. These were TCM, NSCLC, and systematic review. To maximize the sensitivity of the search, we also tracked citations and manually checked the references in included reviews.20 Starting with a primary search strategy developed for PubMed, we adapted subject headings and syntax for the other databases. We searched PubMed, Embase, Web of Science, China National Knowledge Infrastructure (CNKI), Chinese Scientific Journals Database (VIP), and Wanfang Database. The date range was from database inception to August 25, 2025. A prior investigation about current common TCM intervention in NSCLC was conducted, and specific herbs, drugs, therapies, and principles were added to our searches alongside the general idea of TCM. Publication languages were restricted to English and Chinese. Detailed search strategies are reported in the Supplementary Material.
2.2. Inclusion and exclusion criteria
Inclusion criteria: a) Systematic reviews and meta-analyses that exclusively incorporated randomized controlled trials (RCTs); b) Participants pathologically diagnosed with NSCLC, with no specific restrictions on age, gender, disease stage, complications, or prior treatments; c) At least one group in the included RCTs received TCM interventions, which could include, but were not limited to, water decoctions, extracts, granules, injections, or other treatment principles and therapies, regardless of dosage or administration route; d) The control group in the included RCTs could consist of chemotherapy, radiotherapy, targeted therapy, immunotherapy, maintenance treatment, or palliative care, with no limitations on the outcomes measured.
Exclusion Criteria: a) RCTs that did not adhere to the treatment regimens recommended by the 2024 NCCN guidelines for NSCLC, specifically carboplatin-combination therapy with options including albumin-bound paclitaxel, docetaxel, etoposide, gemcitabine, vinorelbine, paclitaxel, or pemetrexed;21 b) RCTs where the comparison group included more than one type of conventional therapy; c) Reviews using inappropriate statistical methods; d) Meta-analyses with only head-to-head comparison between two types of TCM; e) Duplicate reviews.
2.3. Review selection and data extraction
We used EndNote 20 software (Clarivate Analytics, Philadelphia, PA, USA) supplemented by manual verification to remove duplicate records. Two reviewers (ZD and CT) independently selected articles according to the eligibility criteria. First, they independently screened all titles and abstracts retrieved from the database search for eligibility and then performed a full-text screen to exclude irrelevant systematic reviews. Disagreements between reviewers were resolved by discussion, with an additional reviewer (YZ) consulted when necessary. We used Endnote 20 software to manage and cite the references.
We developed a data extraction form to record the main characteristics and quality assessments of the included systematic reviews. Two authors (ZD and CT) independently extracted and checked all data. The review conclusions were categorized as: "harmful," "no effect," "potentially beneficial," and "beneficial." We assigned "harmful," "no effect," and "beneficial" based on a review’s conclusions, and assigned "potentially beneficial" when positive effects were reported in the review’s results, but the conclusions did not definitively assert a significant benefit.
2.4. Methodological quality assessment
We critically appraised the methodological quality of the included systematic reviews using the AMSTAR-2 tool (Assessing the Methodological Quality of Systematic Reviews).22 This validated 16-item instrument allowed us to assess quality and bias using ratings of "yes", "partial yes", or "no". We judged our overall confidence in the results of the systematic review using four categories: "high" for none or one noncritical weakness, "moderate" for more than one noncritical weakness, "low" for one critical flaw with or without noncritical weaknesses, and "critically low" for more than one critical flaw with or without noncritical weaknesses. We used the R package “amstar2Vis” to present the critical appraisal results.23 Quality assessments were conducted by two independent reviewers (ZD and YW), and a third reviewer (YZ) monitored the whole process.
2.5. Data synthesis and evidence map presentation
TCM interventions were categorized primarily by their generic names or therapy types. For drugs with defined dosage forms, such as injections or pills, we specified these after the generic name (e.g., Aidi injection, Cinobufacin capsule). For drugs lacking commercial names, we used the names of their herbal components (e.g., Disodium Cantharidinate, Lentinan). Therapies based on general principles without specifying particular drugs were named according to those principles (e.g., Tonifying Qi and Nourishing Yin). For TCM interventions that did not specify individual drugs or included multiple types of CHM, we classified them as Multicomponent TCM.Quantitative descriptions and graphical displays, including line charts and two types of bubble plots, were created using Microsoft Excel 2016 and Python (Matplotlib, pandas). The first type of bubble plot is designed to show the distribution of evidence and provide an overview of the quantity and effectiveness of studies employing TCM in treating NSCLC in combination with various regimens. In these plots, bubbles represent the linkages between each intervention and outcome type. The size and color of the bubbles indicate the number of included systematic reviews and the proportion of these supporting the efficacy of TCM, respectively. Interventions (columns) are mapped onto different outcomes (rows). Other outcomes are displayed in the Supplementary Material.
The second type of bubble plot visualizes the non-overlapping systematic reviews for the three most frequently reported outcomes when TCM is used alongside chemotherapy: objective response rate (ORR), leukopenia, and QoL. In these plots, each bubble represents the most recent systematic review for each TCM intervention. When multiple reviews were published in the same year for a particular intervention, the one including the most RCTs was selected. The size of each bubble represents the number of included RCTs, while the color indicates the results of the AMSTAR-2 quality assessment. Research quality is represented across columns, mapped against different effects along the rows. All outcomes reported by the systematic reviews are provided in the Supplementary Material.
3. Results
3.1. Study sample and design characteristics
We included 196 SRs, involving a total of 3979 RCTs and 317,964 participants (some of whom were included in more than one review and therefore counted multiple times). The details of the 196 SRs are shown in the Supplementary Material. Fig. 1 shows the PRISMA flow diagram for the study selection process. Among all the included reviews, 159 investigated the use of TCM as an adjunct to chemotherapy, 22 in conjunction with EGFR-TKIs, 9 with radiotherapy, 1 with immunotherapy, and 5 with best supportive care. There were a total of 42 types of interventions and 55 types of outcomes. Among the meta-analyses, 122 used commercial TCM injections, 12 used oral TCM administration, 13 used TCM therapies/principles, and 49 others either did not specify the dosage form or included mixed types of TCM. The outcomes were categorized into three types: (1) survival-related, including ORR, Disease Control Rate (DCR), Progression-Free Survival (PFS), Median Survival Time (MST), half-year, 1-year, 2-year, 3-year, and overall survival rates; (2) laboratory blood tests, including Leukopenia, Neutropenia, Anemia, Thrombocytopenia, CD4/CD8, CD3, CD4, CD8, NKC, Bone Marrow Suppression, IL-2 and TNF-α, IgM, IgG, IgA, PT, APTT, FIB, VEGF, Tumor Markers, and markers of Liver and Renal dysfunction; and (3) therapy-induced symptoms, covering nausea and vomiting, QoL according to the Karnofsky Performance Scale (KPS), diarrhea, neurotoxicity, improvement of TCM symptoms, hand-foot syndrome, tumor pain, oral mucositis, body weight, gastrointestinal toxicity, alopecia, rash, dry skin, cough, fatigue, poor appetite, chest pain, phlebitis, radiation pneumonia, radiation esophagitis, constipation, allergy, improvement of clinical symptoms, interstitial lung disease, and cardiovascular toxicity.
Fig. 1.
Flow diagram of the study selection process.
3.2. Trends in the year of publication
The 196 SRs of TCM for NSCLC were published between June 2007 and August 2025. There were 83 published in English and 113 published in Chinese. Supplement 4 shows the trends in the year of publication for both languages. The number of reviews increased from 2007 to 2016, peaking at 22 in 2016. There was a decline in 2017 with 11 reviews, followed by a peak in 2020 with 25 reviews. The number of English-language studies peaked in 2021 with 15 reviews, while the peak year for Chinese-language studies was 2016, with 13 reviews. More than 80 % of the included systematic reviews were published after 2015.
3.3. Quality of systematic reviews
We rated overall confidence as "low" for 17 systematic reviews, and "critically low" for the other 179. The lack of reporting on two domains which can critically affect the validity of a review is the main reason for the overall poor quality. These were having a written protocol with independent verification (AMSTAR-2 item 2) and a listing of excluded studies (item 7). The most commonly reported domains were using PICO framework (item 1, 194/196), describing the included studies in adequate detail (item 8, 193/196), assessing the risk of bias (RoB) in individual studies (item 9, 195/196), and using appropriate methods for statistical combination of results (item 11, 196/196). On the contrary, none of the 196 systematic reviews reported the sources of funding for the RCTs included in them (item 10), and only 1 review explained their selection of the study designs (item 3). The AMSTAR-2 standardized domain scores for each systematic reviews and its overall assessment are shown in Supplement 3. The tacked bar plot of the distribution of ratings (“Yes,” “Partial Yes,” “No,” “No MA”) as percentage of all the included systematic reviews for each AMSTAR-2 item produced by amstar2_barplot() function is shown in Supplement 5, and the “Half-donut” plot using discrete colors from the “magma” palette and an inset table with frequencies and percentages produced by amstar2_overall() function showing the overall confidence ratings (“Critically Low,” “Low,” “Moderate,” or “High”) is shown in Supplement 6.
3.4. Intervention components described in included reviews
The 196 included systematic reviews contained a total of 42 types of TCM intervention in NSCLC treatment. This includes 21 types of herbal injections: Aidi Injection, Astragalus Injection, Brucea Javanica Oil Emulsion Injection, Chinese herbal Injections, Cinobufacin Injection, Compound Kushen Injection, Delisheng Injection, Elemene Injection, Ginseng polysaccharide Injection, Kang Ai Injection, Kanglaite Injection, Lentinan Injection, Shenfu Injection, Shengmai Injection, Shenmai Injection, Shenqi Fuzheng Injection, Venenum Bufonis Injection, Xiaoaiping Injection, and Yiqifuzheng Injection. We also identified 9 types of oral drugs, including Cinobufacin Capsule, Compound Taxus Chinensis Capsule, Ginseng and its active components, Huisheng Oral Solution Adjunct, Shashen Maidong Decoction, Shenyi Capsule, Xiaoji Decoction, Yiqi Buxue prescriptions, and Zilongjin Tablet. Furthermore, there are 6 types of TCM therapies/principles, namely Benefiting Qi and Dissipating Phlegm, Buzhong Yiqi Decoction, Invigorating Qi and Activating Blood Circulation, Reinforcing Earth to Strengthen Metal, Tonifying Qi and Nourishing Yin, and YQFZQX method. The remaining undefined categories include Astragalus-containing TCM, Lentinan, Multicomponent TCM, Qi-replenishing and Blood-activating therapy, Ruanjian Sanjie, TCM from Sputum, Wenyang Compound, and Zhenqi Fuzheng.
3.5. Evidence maps
3.5.1. Chemotherapy
Among the 196 included systematic reviews, 159 identified the effect of TCM combined with chemotherapy. Among all outcomes, 9 outcomes consistently demonstrated beneficial results. These were overall survival, bone marrow suppression, IL-2 and TNF-α, IgG, FIB, tumor pain, body weight, poor appetite, and improvement of clinical symptoms. Positive results (reported in more than 80 % of reviews) were found for 14 outcomes, including ORR, DCR, MST, leukopenia, neutropenia, thrombocytopenia, CD4/CD8, CD3( %), CD4( %), NKC, nausea and vomiting, QoL, diarrhea, and improvement of TCM symptoms. Between 50 and 80 % of reviews reported positive results for 13 outcomes: 1-year survival, 2-year survival, 3-year survival, anemia, CD8( %), IgM, IgA, tumor markers, VEGF, liver dysfunction, gastrointestinal toxicity, alopecia, and fatigue. Conversely, more than half of the reviews reported ineffective results for 14 outcomes: PFS, half-year survival, PT, APTT, renal dysfunction, neurotoxicity, oral mucositis, rash, cough, chest pain, phlebitis, constipation, allergy, and cardiovascular toxicity. Fig. 2 illustrates the evidence map of TCM interventions to outcomes when combined with chemotherapy.
Fig. 2.
Evidence Map of TCM Interventions to outcomes when combined with chemotherapy. X-axis: outcomes divided into three sections (ORR to 3-year survival: survival; Leukopenia to Renal dysfunction: Laboratory tests; Nausea and vomiting to Improvement of clinical symptoms: symptoms;). Y-axis: TCM interventions ranked by alphabetical order. Color: green part of the bubbles indicates that the systematic reviews showed a beneficial or probably beneficial effect on corresponding outcomes, on the contrary, red part of the bubbles indicate a harmful effect or no effect. Bubble size: number of systematic reviews on the topic.
3.5.2. Targeted therapy
Of the 196 included systematic reviews, 22 identified the effect of TCM combined with targeted therapy, all of which were EGFR-TKIs. Among all outcomes, consistent beneficial results were found for 11 outcomes: disease control rate, progression-free survival, 2-year survival, CD4/CD8 ratio, CD4 %, natural killer cells, quality of life, improvement of TCM symptoms, hand-foot syndrome, cough, and fatigue. One outcome, objective response rate, was positive in more than 80 % of the reviews. Between 50 and 80 % of reviews reported positive results for five outcomes: 1-year survival, CD3 %, nausea and vomiting, diarrhea, and rash. Conversely, more than half of the reviews reported ineffective results for seven outcomes: CD8 %, liver dysfunction, renal dysfunction, oral mucositis, dry skin, poor appetite, and interstitial lung disease. Fig. 3 illustrates the evidence map of TCM interventions to outcomes when combined with targeted therapy.
Fig. 3.
Evidence Map of TCM Interventions to outcomes when combined with TKIs. X-axis: outcomes divided into three sections (ORR to 2-year survival: survival; CD4/CD8 to liver dysfunction: Laboratory tests; Nausea and vomiting to interstitial lung disease: symptoms. Y-axis: TCM interventions ranked by alphabetical order. Color: green part of the bubbles indicates that the systematic reviews showed a beneficial or probably beneficial effect on corresponding outcomes; on the contrary, red part of the bubbles indicate a harmful effect or no effect. Bubble size: number of systematic reviews on the topic.
3.5.3. Radiotherapy
Nine of the 196 systematic reviews assessed the effect of TCM combined with radiotherapy. Consistent beneficial results were observed in all reviews for 10 outcomes: objective response rate, 1-year survival, 2-year survival, 3-year survival, leukopenia, bone marrow suppression, quality of life, radiation pneumonia, radiation esophagitis, and improvement of clinical symptoms. Conversely, in the single review that assessed the following six outcomes, negative results were reported for all: anemia, thrombocytopenia, CD4/CD8 ratio, CD4 %, CD8 %, and natural killer cells. Supplement 7 shows the evidence map of TCM interventions to outcomes when combined with radiotherapy.
3.5.4. Immunotherapy
Only one review in the year of 2025 assessed the effect of TCM combined with immunotherapy. In this single review, positive results were reported for 13 outcomes, including objective response rate, disease control rate, leukopenia, anemia, thrombocytopenia, CD4/CD8 ratio, CD3 %, CD4 %, tumor markers, nausea and vomiting, quality of life, diarrhea, and fatigue. Conversely, the review found ineffective results for three outcomes: liver dysfunction, renal dysfunction, and rash. Supplement 8 shows the evidence map of TCM interventions to outcomes when combined with immunotherapy.
3.5.5. Best supportive care
Best supportive care serves to reinforce the effectiveness after 4–6 cycles of first-line therapy with the intent to maximize QoL. Five of the 196 included systematic reviews assessed the effect of TCM combined with BSC. The results were beneficial in all reviews for 8 outcomes: objective response rate, disease control rate, progression-free survival, 2-year survival, leukopenia, nausea and vomiting, QoL, and cough. However, more than half of the reviews reported ineffective results for two outcomes: 1-year survival and overall survival. Supplement 9 shows the evidence map of TCM interventions to outcomes when combined with BSC.
3.6. Recent reviews for chemotherapy
Given the extensive number of reviews on TCM combined with chemotherapy, we conducted further investigation into ORR, leukopenia, and QoL to avoid potential overlap of patients across reviews and to provide the most current evidence. During this process, we retained only the most recently published systematic review for each specific TCM intervention to develop the following evidence maps. Detailed evidence maps of each outcome are provided in Supplement 10.
3.6.1. Objective response rate
A total of 40 types of TCM were evaluated for their effect on ORR in the included systematic reviews. For the TCM type with the most systematic reviews available, 33 of these reviews showed that TCM combined with chemotherapy significantly improved ORR. The quality of these systematic reviews varied, with 10 rated as low quality and 23 as critically low quality according to the AMSTAR-2 assessment. The analyses revealed that several TCMs, including Ginseng and its components, Shenqi Fuzheng Injection, Kangai Injection, and Compound Kushen Injection, were associated with beneficial effects on ORR. On the other hand, 7 systematic reviews of critically low quality reported that some TCMs (like Lentinan Injection and Cinobufacin Injection) were associated with improvements in ORR that were not statistically significant. None of the systematic reviews found a reduction in ORR. The details of each TCM intervention mapping to AMSTAR-2 results are displayed in Fig. 4.
Fig. 4.
Evidence map of the most recent systematic review for each type of TCM that reported ORR. X-axis: effectiveness of each TCM intervention; Y-axis: Overall confidence assessed by AMSTAR-2.
3.6.2. Effect on leukopenia
In the analysis of leukopenia, 35 types of TCM were evaluated. Based on the most recent systematic review available for each type, 34 systematic reviews indicated that TCM combined with chemotherapy significantly reduced the incidence of leukopenia. Among these, 7 were rated as low quality and 27 as critically low quality according to the AMSTAR-2 criteria. The results suggested that several TCM interventions—such as Aidi Injection, Compound Kushen Injection, Ginseng and its active components, and Shenqi Fuzheng Injection—were associated with a beneficial effect on leukopenia. In contrast, one systematic review of critically low quality found that Ruanjian Sanjie did not show a statistically significant difference in reducing leukopenia. None of the reviews reported an increase in leukopenia incidence with TCM treatment. The details of each TCM intervention mapping to AMSTAR-2 results are displayed in Fig. 5.
Fig. 5.
Evidence Map of the most recent systematic review for each type of TCM that reported leukopenia. X-axis: effectiveness of each TCM intervention; Y-axis: Overall confidence assessed by AMSTAR-2.
3.6.3. Quality of life
In the analysis of QoL, 36 types of TCM were evaluated. Based on the most recent systematic review for each type, 34 reported that TCM combined with chemotherapy significantly improved QoL. According to the AMSTAR-2 criteria, the quality of these reviews varied, with 10 rated as low quality and 24 as critically low quality. The results indicated that several TCMs, including Aidi Injection, Astragalus-containing TCM, Kang Ai Injection, Compound Kushen Injection, Shenqi Fuzheng Injection, and other herbal injections, were associated with beneficial effects on QoL. In contrast, two systematic reviews of critically low quality showed that Shenfu Injection and Delisheng Injection did not lead to statistically significant improvements in QoL. The details of each TCM intervention mapping to AMSTAR-2 results are displayed in Fig. 6.
Fig. 6.
Evidence Map of the most recent systematic review for each type of TCM that reported QoL. X-axis: effectiveness of each TCM intervention; Y-axis: Overall confidence assessed by AMSTAR-2.
4. Discussion
4.1. Summary of key findings
In this study, we synthesized and visualized the evidence by collecting data on TCM interventions and outcomes, along with AMSTAR-2 assessments for 196 systematic reviews. We categorized them by combined therapies including chemotherapy, targeted therapy, radiotherapy, and best supportive care to clearly present the evidence through evidence mapping.
Broadly, the evidence map indicates consistent benefits of TCM across different distinct treatment modalities. In combination with chemotherapy, TCM consistently showed benefits in mean survival time, bone marrow suppression, and immunological markers. For targeted therapy, the addition of TCM was associated with improved PFS and QoL, although it did not significantly reduce specific toxicities like liver dysfunction. In the context of radiotherapy, the mapping revealed positive outcomes in mitigating radiation pneumonitis and esophagitis. Finally, for patients receiving best supportive care, TCM appeared to transition from an adjuvant to a primary option, offering benefits in performance status and symptom management without the treatment-stopping toxicity often seen in conventional therapies.
By synthesizing the volume of positive findings reported across systematic reviews, several TCM interventions demonstrate distinct profiles aligned with specific clinical needs. For patients experiencing chemotherapy-induced bone marrow suppression, Shenqi Fuzheng Injection (with 13 reviews reporting positive effects on leukopenia) and Aidi Injection (12 reviews) were the most frequently supported interventions for mitigating hematological toxicity. Regarding the improvement of quality of life, a critical patient-centered outcome, Kanglaite Injection (positively reported in 20 reviews), Aidi Injection (20 reviews), and Compound Kushen Injection (14 reviews) emerged as the interventions with the most substantial supportive evidence. In terms of enhancing antitumor efficacy, particularly objective response rate when combined with chemotherapy, Aidi Injection (supported by 22 reviews), Kanglaite Injection (22 reviews), and Brucea Javanica Oil Injection (10 reviews) were the most prominently reported effective interventions.
In regard to the safety of the application of TCM, none of the included reviews reported any harmful effects compared to chemotherapy, targeted therapy, radiotherapy or BSC. This suggests that TCM may offer a safer alternative or complement to these conventional treatments. Further research is needed to solidify these findings and explore the safety and efficacy mechanisms of TCM. This will require more rigorous and larger RCTs and thorough assessments of patient-reported outcomes and QoL, which are crucial for understanding TCM's holistic impact on NSCLC patients.
4.2. Comparison with previous studies
Our application of evidence mapping offers several strategic advantages, particularly in the complex landscape of TCM research. This approach is particularly beneficial in areas like TCM, where there are many modalities and clinical effects can vary widely between them.24 Although no standard definition of evidence mapping has emerged,25 reviews that use this technique share some common characteristics: (a) they are appropriate for addressing broad topics that are often too expansive for an individual systematic review; (b) they involve experts in the area of study to set the inclusion and exclusion criteria; (c) they are based on a systematic search; and (d) they include user-friendly summaries of results. In our study, evidence mapping provides a comprehensive framework for the visualization of a broad spectrum of data across diverse outcomes and therapeutic interventions. Some authors consider using highly specific search strategies for evidence mapping,26 but, for the purposes of this project, we preferred to make a sensitive and adapted search strategy in order to obtain the largest number of documents. Evidence maps are one of many tools and information sources to support evidence, and like systematic reviews, they should use methods that are reproducible and transparent.27 However, while systematic reviews target specific research questions, evidence mapping focuses on the nature, volume, and characteristics of the research to identify, describe and summarize what is known. The creation and publication of evidence maps allows a graphical representing of the best evidence to facilitate access to information.
4.3. Clinical and scientific implications
Our mapping reveals a fundamental limitation in the current assessment of TCM safety. The vast majority of included systematic reviews were designed with a primary focus on evaluating TCM's efficacy in mitigating adverse effects induced by conventional therapies (such as chemotherapy-induced myelosuppression or targeted therapy-related rash). Consequently, the "safety" outcomes reported predominantly reflect a reduction in the burden of conventional toxicities, which is a measure of TCM's protective benefit. This paradigm has inadvertently led to a significant evidence gap concerning the intrinsic adverse drug reaction profile of the TCM interventions themselves. The reporting of TCM-specific adverse events (e.g., allergic reactions to injections or gastrointestinal discomfort from oral formulations) has been sporadic and unsystematic. This lack of dedicated safety assessment prevents a comprehensive risk-benefit analysis and underscores an urgent need for future trials and reviews to explicitly monitor and report the independent safety profile of TCM.
Another central finding of this evidence mapping is the high proportion of systematic reviews with low methodological quality. According to the AMSTAR-2 criteria, 179 (91.3 %) of the included reviews were rated as "critically low." This situation requires a careful interpretation of our results. Common methodological weaknesses, such as not registering a study protocol in advance, conducting incomplete literature searches, and failing to adequately explain heterogeneity, significantly reduce the reliability of the conclusions drawn from these reviews. Therefore, although the large number of studies and their generally positive results are notable, they should not be considered as strong, conclusive evidence for guiding clinical practice. More appropriately, this body of evidence should be regarded as hypothesis-generating. It identifies specific TCM interventions (e.g., Aidi Injection or Astragalus-based formulations) as promising options that now need to be verified through well-designed, large-scale randomized controlled trials and future high-quality systematic reviews. This fact further highlights the critical need to improve methodological standards in this research area.
The AMSTAR-2 assessment reveals that the "Critically Low" ratings predominantly stem from a few critical, recurring flaws. The most common issues were the failure to register a protocol, inadequate search strategies that likely missed unpublished studies, and a lack of consideration for the risk of bias in primary studies when interpreting results.28 Therefore, the most pressing need identified by this mapping is not for more systematic reviews, but for better, methodologically rigorous ones, along with better-designed and better-reported RCTs and trial protocols.29,30 The future credibility and clinical relevance of TCM evidence synthesis depend on a committed adherence to established guidelines.
4.4. Strengths and limitations
This is the first evidence mapping study that we know of which assesses systematic reviews of TCM for NSCLC. We have found that published systematic reviews have shown that various TCM in combination with chemotherapy can improve efficacy (e.g., objective response rate, quality of life, immune function) and reduce adverse reactions (e.g., leukopenia, thrombocytopenia, nausea and vomiting). There are also several limitations of the current study. Firstly, most included reviews, and the RCTs that they included, did not provide data on patients’ sensitizing genetic mutation and PD-L1 expression, which might fail to filter people who might benefit from those who may not. Secondly, our study includes only one review comparing TCM with immunotherapy, because of the lack of relevant RCTs and systematic reviews, which restricts the consideration of the application of TCM as an add-on to immunotherapy. Results of phase III RCTs have established the role for pembrolizumab as first-line treatment in patients with untreated, advanced NSCLC and tumor characterised by PD-L1 expression>50 %.31 Thus, it is urgent to further explore TCM application in immunotherapy. The generalizability of our findings is also limited by the standardization issues inherent in many TCM preparations. For complex formulations and injections, variations in manufacturing processes and quality control among different manufacturers can result in inconsistent chemical profiles and bioactivity.32 This lack of standardization challenges the reproducibility of the reported clinical outcomes. Therefore, advancing future research and clinical application requires a concerted effort towards establishing and adhering to unified quality standards for TCM products. Finally, although the conclusions of the included systematic reviews showed that TCM had certain advantages in the treatment of NSCLC, most reviews were rated as “critically low” methodological quality, reducing the credibility of their conclusion. These limitations might have resulted in inaccurate evaluation of the outcomes and improvements in the quality of evidence and an objective assessment of the efficacy of oral CHM in treating NSCLC will require future systematic reviews that meet the relevant quality and reporting standards.
4.5. Conclusions and suggestions for future research
In conclusion, we have provided a visual overview of the evidence for TCM for treating NSCLC, and suggested that the integration of TCM in NSCLC treatment shows promise, particularly for enhancing the efficacy of conventional therapies and mitigating adverse effects. Interventions such as Aidi and Kanglaite injections stand out as particularly promising. However, the methodological shortcomings in the current body of evidence, including poorly conducted and reported systematic reviews, limit confidence in these findings. To ensure that TCM can be effectively and safely incorporated into NSCLC treatment, future research must focus on producing high-quality, rigorously conducted RCTs and systematic reviews of these. These efforts are crucial to substantiate the potential therapeutic benefits of TCM and establish clear guidelines for its application in clinical practice.
Author contributions
LL, LC, YZ: Supervision; LL, NL, YZ: Conceptualization; ZD, XC, CT, YW, RZ, KL: Data curation; LL, YZ: Methodology; ZD: Software; ZD, CT, YW: Writing original draft; LL, XC, NL, YZ, MC: Writing, review and editing. ZD and XC contributed equally to this work.
Ethics statement
This study involves publicly available data, and no new human participants were involved in its conduct. Therefore, the Consent to Participate requirement does not apply, and no approval from an Institutional Review Board (IRB) or Ethics Committee was required.
Funding
This study was supported by Sichuan Science and Technology Program (2023NSFSC1556, 2023YFQ0071, 2025YFHZ0216), National Natural Science Foundation of China Grant Numbers(82004213, 82174227), “Qimingxing” Research Fund for Young Talents (HXQMX0002); Medical Quality Evidence-based Management Research Project of the Hospital Management Institute of the National Health Commission in China (YLZLXZ23K009, YLZLXZ23G042).
Declaration of competing interest
YZ is an editorial board member of the journal but his member status had no bearing on the editorial decision. There is no conflict of interest.
Footnotes
Supplementary material associated with this article can be found, in the online version, at doi:10.1016/j.imr.2025.101281.
Supplement 1. Search strategies.
Supplement 2. Characteristics of included systematic reviews and meta-analyses.
Supplement 3. AMSTAR-2 scores and its overall assessment.
Supplement 4. Trends in the year of publication of the included reviews.
Supplement 5. Stacked bar plot on the distribution of AMSTAR-2 ratings.
Supplement 6. Overall methodological quality assessment summaries (“Half-donut” plot).
Supplement 7. Evidence map combined with radiotherapy.
Supplement 8. Evidence map combined with immunotherapy.
Supplement 9. Evidence map combined with BSCs.
Supplement 10. Evidence map combined with chemotherapy.
Contributor Information
Lei Liu, Email: liuleihx@wchscu.cn.
Lingmin Chen, Email: chenlingmin@wchscu.cn.
Appendix. Supplementary materials
Data availability
The datasets generated or analyzed during the current study, as well as any custom code and data collection tables, are available from the corresponding author upon reasonable request for the purpose of further research.
References
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Supplementary Materials
Data Availability Statement
The datasets generated or analyzed during the current study, as well as any custom code and data collection tables, are available from the corresponding author upon reasonable request for the purpose of further research.