Real-World Evidence of Traditional Chinese Medicine (TCM) Treatment on Cancer: A Literature-Based Review

Peng, Linjia; Zhang, Ke; Li, Yujie; Chen, Lianyu; Gao, Huifeng; Chen, Hao

doi:https://doi.org/10.1155/2022/7770380

Evidence-Based Complementary and Alternative Medicine

On this page

Abstract Discussion Data Availability Conflicts of Interest Acknowledgments References Copyright Related Articles

Review Article | Open Access

Volume 2022 | Article ID 7770380 | https://doi.org/10.1155/2022/7770380

Real-World Evidence of Traditional Chinese Medicine (TCM) Treatment on Cancer: A Literature-Based Review

Linjia Peng,¹Ke Zhang,¹Yujie Li,¹Lianyu Chen,¹Huifeng Gao,¹and Hao Chen¹

Academic Editor: Isac Medeiros

Received14 Apr 2022

Revised12 May 2022

Accepted16 Jun 2022

Published29 Jun 2022

Abstract

While randomized controlled trials (RCTs) are the gold standard for evidence-based medicine, they do not always reflect the real condition of patients in the real-world setting, which limits their generalizability and external validity. Real-world evidence (RWE), generated during routine clinical practice, is increasingly important in determining external effectiveness of the tightly controlled conditions of RCTs and is well recognized as a valuable complement to RCTs by regulatory bodies currently. Since it could provide new ideas and methods for clinical efficacy and safety evaluation of traditional Chinese medicine (TCM) and high-quality evidence support, real-world study (RWS) has received great attention in the field of medicine, especially in the field of TCM. RWS has shown desirable adaptability in the clinical diagnosis and treatment practice of traditional Chinese medicine. Consequently, it is increasingly essential for physicians and researchers to understand how RWE can be used alongside clinical trial data on TCM. Here, we discuss what real-world study is and outline the benefits and limitations of real-world study. Furthermore, using examples from TCM treatment on cancer, including Chinese herbal medicine, acupuncture, moxibustion, integrated TCM and Western medicine treatment, and other treatments, we elaborate how RWE can be used to help inform treatment decisions when doctoring patients with cancer in the clinic.

1. Real-World Study (RWS)

1.1. What Is Real-World Study (RWS) and Real-World Evidence (RWE)?

Real-world study refers to the process of the collection of data (real-world data) related to the health of research subjects in a real-world setting or aggregated data derived from preset clinical questions and through analysis, to obtain medication utilization, potential benefits, and benefit-risk clinical evidence. Real-world data refer to diverse data collected on a routine basis related to physical conditions of patients besides diagnosis, treatment, and care. Not all real-world data can become real-world evidence after analysis, and only real-world data that satisfy applicability can generate real-world evidence. Real-world evidence refers to clinical evidence on the use and potential benefit-risk of a drug obtained through appropriate and adequate analysis of applicable real-world data, including evidence from retrospective or prospective observational studies or interventional studies such as pragmatic randomized controlled studies [1]. RWS is characterized by the use of large-scale sample data, relaxation of inclusion and exclusion criteria, long-term follow-up, attention to the real clinical setting, and selection of different interventions according to the patient’s actual condition and willingness, as well as the selection of broadly clinically significant indicators to evaluate outcomes [2, 3]. RWS has been widely used in the research of long-term outcome evaluation of postmarketing drugs, patient compliance, disease characteristics, rare subtypes of cancer, and special populations [4–8].

1.2. Benefits and Limitations of Real-World Study

For a long time, it has been firmly convinced that RCT is the most effective research mean to verify causality and the gold standard for testing treatment effects which drive the high internal authenticity and accuracy conclusions of research studies [4, 9, 10]. However, with the poor extrapolation of RCT and the sample size limited by different diseases, RCT requires a lot of financial, materials, labor, and time cost investment which cause both operability and economic benefits difficult to attain [9, 10]. Cohort studies and case-control studies are also widely used in TCM clinical research, but they also have different benefits and limitations. Case-control studies are easy to organize and carry out and can simultaneously study the association between multiple factors and a disease. They are especially suitable for exploratory etiological studies and do no harm to the study subjects. On the other hand, it is difficult to avoid selectivity and recall bias when selecting subjects and obtaining previous information. The authenticity of information is difficult to guarantee, the sequence of exposures is often difficult to determine, and the confounding effects are difficult to control. When it comes to cohort studies, the benefits are as follows: first, subjects were grouped according to their exposure and followed up before the occurrence of disease, and the data obtained were complete and reliable without recall bias. Second, the time sequence of exposure factors and diseases is clear, so the ability to demonstrate the causal relationship is strong. Third, it can directly estimate the strength of the association between exposure and disease as well as help understand the natural history of disease. Moreover, the limitations are as follows: first, the organization and implementation are difficult, time-consuming, laborious, and costly. Second, it is not suitable to study diseases with a very low incidence. Third, because of the long follow-up time, it is prone to loss of follow-up bias. Fourth, it requires high design requirements and complicated data collection and analysis.

Traditional clinical trials play a very vital role in promoting the modernization and standardization of traditional Chinese medicine, but traditional Chinese medicine emphasizes the integration of heaven and earth, respects individual differences, and follows the characteristics of syndrome differentiation for treatment, which determines that the types of studies mentioned above are difficult to reflect the curative effect and characteristic advantages. Based on real-world settings, which generalizes the conclusions, the emergence of RWS compensates for the insufficiency of RCT [7]. Therefore, in the evaluation of TCM efficacy, both scientific rigor and flexibility should be given to reflect the objective reality. RWS can fully reflect these characteristics, providing a new path and mean for TCM efficacy evaluation and evidence accumulation. In addition, RWS can also be used for paradigm and program optimization of complementary advantages of integrated traditional Chinese and Western medicine to establish evidence for clinical efficacy improvement. Finally, it can provide the basis for early clinical research to develop new treatment methods. Although RWS has many advantages, this open, nonrandom research method also has some limitations: First, because of the lack of randomization and low internal authenticity, the reliability of the results will be questioned. Second, observer bias affects the quality of the research results, especially the differentiation of TCM syndrome and personal experience, autonomy, and randomness. Third, patients’ compliance may not be high due to long follow-up time. Fourth, there are many confounding factors, so it is not only difficult to distinguish the effectiveness of a single component in the overall intervention but also the results of the study may be close to meaningless. Fifth, to a certain extent, because it is an observational study and no intervention measures are taken, its research effectiveness has a certain lag [11]. In addition, it requires a large number of research samples and even multicenter events and has high difficulty in data collection, huge workload, strong data heterogeneity, and higher requirements on statistical methods than traditional research, and most of them are retrospective analysis or post hoc analysis, so how to ensure the effectiveness of research evidence is a challenge. Nevertheless, RWS can complement other types of research to further supplementing evidence of efficacy [1, 4, 12].

Table 1 summarizes the distinction between real-world studies and randomized controlled trials, cohort studies, and case reports.

2. Real-World Evidence from Traditional Chinese Medicine on Cancer

Clinical efficacy and safety have always been the core content of research in the field of traditional Chinese medicine. However, with the continuous deepening of research as well as its limitations, RCTs have been unable to meet the clinical demand of traditional Chinese medicine which is considered with unique diagnostic advantages. In recent years, how to scientifically and objectively evaluate the validity of traditional Chinese medicine in a real-world setting has become a hot topic in clinical research. As an important supplement to randomized controlled trials, real-world study is one of the approaches in line with the scientific research paradigm of TCM clinical research. Based on the characteristics of clinical diagnosis and treatment of traditional Chinese medicine, it collects a large amount of real-world data, as well as incorporates clinically meaningful outcomes, so as to mine and evaluate the efficacy and safety of traditional Chinese medicine in the real world.

Traditional Chinese medicine has remarkable effects on cancers in the clinical practice, either directly inhibiting the occurrence and development of tumors, or reducing the side effects caused by chemotherapy and radiotherapy, or reducing the dosage of other therapies. Kuo conducted a real-world analysis of 582,799 adult cancer patients in Taiwan based on whether they used traditional Chinese medicine. The main analysis was the use of traditional Chinese medicine, as well as specific medical visits. After the adjustment of age, gender, urbanization of residence, occupation, annual medical center visit, and annual nonmedical center visit, adjusted hazard ratios (aHR) for mortality were significantly lower among TCM users than those who do not get TCM. This study indicates that more attention should be paid to the use of traditional Chinese medicine in the clinical diagnosis and treatment of cancer patients [13].

Since acupuncture, moxibustion, and other treatments of TCM are rarely used in the treatment of tumors alone, they are mainly used to treat the adverse reactions and tumor-related complications. Therefore, this paper mainly focuses on the discussion of Chinese herbal medicine. Table 2 summarizes the contents related to the treatment of tumors by acupuncture and other therapies. In addition, the integrated TCM and Western medicine treatment in the real-world clinical practice is summarized in Table 3. Next, we will conduct literature mining for common clinical tumors and sort out the antitumor effects of Chinese herbal medicine under real-world conditions. The results are summarized in Table 4. Moreover, Table 5 demonstrates the types of syndrome differentiation of common tumors.

2.1. Respiratory System Cancer

Lung cancer is the most common malignant tumor of the respiratory system, accounting for most of the tumors of the respiratory tract [14]. Buzhong Yiqi Decoction, Xiangsha Liujunzi Decoction, Baihe Gujing Decoction, Bei-Mu (BM), Xing-Ren (XR), and Ge-Gen (GG) are the most commonly used Chinese herbal formulas and Chinese medicines for the treatment of lung cancer, respectively [15]. A real-world study led by Li included 1988 patients with newly diagnosed locally advanced metastatic lung adenocarcinoma between 2006 and 2012 who received first-line therapy gefitinib or erlotinib as well as the Chinese herbal medicine as an adjuvant treatment. Compared with patients who did not receive Chinese herbal medicine, the mortality rate of patients who used Chinese herbal medicine for ≥180 days was significantly reduced, which means that in patients with advanced lung adenocarcinoma treated with first-line TKIs, adjuvant Chinese herbal medicine treatment could improve the overall survival rate and progression-free survival rate [16]. Additionally, another study showed that Qingzao Jiufei Decoction was an effective decoction in reducing lung cancer mortality in a real-world setting [17].

2.2. Digestive System Cancer

The most common tumors of the digestive system are colorectal cancer, pancreatic cancer, liver cancer, intrahepatic bile duct cancer, and gastric cancer [14]. A total of 13,943 pancreatic cancer patients were divided into two groups according to whether they took Chinese herbal medicine (mainly Chinese medicine Hedyotis diffusa and Chinese herbal formula Xiangsha Liujunzi Decoction) in a real-world setting. The results showed that pancreatic cancer patients who had used complementary Chinese herbal medicine had a better prognosis and those who received CHM for more than 90 days had a significantly lower hazard ratio for mortality than non-CHM users [18]. In addition, a real-world study of traditional Chinese medicine in the treatment of liver cancer analyzed the commonly used Chinese herbal medicine treatments in liver cancer patients and their impact on the survival of liver cancer patients. It turns out that Jiawei Xiaoyao San and Chaihu Shugan Decoction were the most effective Chinese herbal formula to improve the overall survival, as well as significantly improve the survival rate of patients with liver cancer [19]. By observing the clinical efficacy and adverse reactions of patients with advanced colorectal cancer treated with Jianpi Jiedu Tongluo formula combined with tegafur maintenance under real-world conditions, the results indicated that this scheme can improve the quality of life of patients and prolong the disease-free survival of the disease [20]. Regarding the study of gastric cancer, the results of the study proved that complementary traditional Chinese medicine (mainly Chinese herbal medicine Herba Hedyotidis Diffusae and Xiangsha Liujunzi Decoction) can significantly improve the survival rate of gastric cancer patients [21]. As for metastatic gastric cancer, a study on the effect of traditional Chinese medicine, especially Fuzheng Jiedu therapy, on the overall survival rate and progression-free survival rate of patients was conducted in a real-world setting, thus exhibiting that the most commonly utilized medicine in this therapy are Chinese herbal formula Shenmai and compound Kushen injections which can significantly improve the survival rate of patients with metastatic gastric cancer [22].

2.3. Breast Cancer

Breast cancer (BC) is the second most commonly diagnosed cancer in women in the United States and a prime reason for death in women globally [14]. A real-world study from Taiwan included 79,335 breast cancer patients who were divided into two groups based on whether they took more than 80 grams of Danshen within 28 days after diagnosis. The findings suggest that higher doses or longer use of Danshen has a protective effect in breast cancer patients [23]. Besides, according to whether they used traditional Chinese medicine while receiving hormone therapy, estrogen receptor (+) breast cancer patients were divided into two groups. The use of TCM did support the potential advantage of TCM in breast cancer-related mortality, while did not show significant impact on adherence to HT [24]. Tamoxifen is a common drug for patients with estrogen receptor-positive breast cancer [25–27], but it is easy to induce endometrial cancer and various adverse reactions [26]. Jia-Wei-Xiao-Yao-San and Shu-Jing-Huo-Xue-Tang significantly improved the overall survival rate of estrogen receptor-positive breast cancer patients and reduced the risk of tamoxifen-induced endometrial cancer [28].

2.4. Other Cancers

Chinese herbal medicine also plays a significant role in treating other cancers. As for cervical cancer, Bai-Hua-She-She-Cao (Herba Oldenlandiae, synonym: Herba Hedyotis diffusae) and Jia-Wei-Xiao-Yao-San were the most commonly used single-flavor Chinese medicine and Chinese herbal formula, respectively. After treatment, compared with cervical cancer patients who did not use Chinese herbal medicine, the survival rate of cervical cancer patients who took Chinese herbal medicine was significantly improved [29]. One study performed a real-world retrospective cohort study of head and neck cancer (HNC) patients between 2001 and 2011 using the Taiwan National Health Insurance Research Database. The Cox regression model was used to determine the correlation between Chinese herbal medicine use and survival outcomes. The results demonstrated that the application of Chinese herbal medicine was significantly associated with a 32% reduction in all-cause mortality. Patients who took Chinese herbal medicine for a long time had lower mortality [30]. By taking whether or not to take Chinese herbal medicine as an exposure factor, Xu collected 595 patients with stage III-IV esophageal cancer and divided them into two groups based on taking or not taking Chinese herbal medicine. Analyzing the follow-up survival time and prognostic factors of the patients, the results showed that Chinese herbal medicine could prolong the survival time of patients with stage IV esophageal cancer and taking Chinese herbal medicine was an independent factor for the survival time of patients with stage IV esophageal cancer [31].

3. Discussion

In China, more than 4 million people are diagnosed with cancer every year, and with its morbidity and mortality, it ranks first in the world and has become a major public health problem that seriously endangers human health [32]. Conventional treatment options include surgical resection [33], chemotherapy [33], and radiotherapy [34], and new treatment options including immunotherapy [34–37] and targeted therapy [38–42] are continuously generating and developing. Despite present diverse desirable effects, they also bring different degrees of recurrence and side effects. As the birthplace and most widely used country of traditional Chinese medicine, in fact, more than 80% of cancer patients in China have received traditional Chinese medicine treatment more or less, indicating that traditional Chinese medicine has an irreplaceable position and importance in the treatment of malignant tumors. Traditional Chinese medicine has abundant experience in the treatment of cancers and has definite curative effect on a variety of common tumors in the clinic. In addition, traditional Chinese medicine also exhibit a certain alleviation effect on the side effects caused by surgery, chemotherapy, and other treatments and some precancerous lesions [43, 44]. A large number of studies have also proved that traditional Chinese medicine including Chinese herbal medicine, acupuncture, and moxibustion as well as other treatments exert their antitumor effects from multiple perspectives and multiple targets [44–52]. The antitumor mechanism of Chinese herbal medicine is shown in Figure 1.

Real-world study has received global attention since its inception due to its consistency to clinical practice [53]. China, the United States, and European countries have successively passed a series of policy bills to support the development of RWS [53–56]. Undoubtedly, the concept of the real world is extensively accepted by clinical researchers and RWS has set off a global research boom [57]. RWS is closely linked with human life and health in the field of medicine which is clinical problem-oriented research that involved all stages of the diagnosis and treatment process such as disease etiology, diagnosis, treatment, prognosis, and clinical prediction models, which will overwhelmingly improve the quality of life and health of patients.

Despite there are already reviews on the clinical efficacy and mechanism of TCM in the treatment of cancer, the clinical efficacy of TCM in the real world remains to be studied [58]. In the field of traditional Chinese medicine, RWS is mostly used to evaluate the effectiveness and safety of prescriptions that combine traditional Chinese and Western medicine or to analyze the relationship between “drug-drug,” “drug-syndrome,” and “disease-syndrome.” In terms of research methods, the most widely applied one is observational study. The statistical analysis method is essentially the same as that of traditional clinical research, but the needs to be focused on the control of bias and confounding factors. From the perspective of research needs, RWS is a new research method that is not a substitute for existing types of studies but a supplement [1, 57]. However, it is expected to look for more evidence and clues to solve clinical problems in the real-world setting outside the nonrigorous RCT conditions. Because the diagnosis, treatment, and prognosis of different tumors are quite different, real-world research has a wonderful match with traditional Chinese medicine on clinical research and treatment on tumors. On the one hand, it can restore the clinical efficacy of traditional Chinese medicine in the treatment of tumors, and on the other hand, it can reduce the medical burden of patients to varying degrees.

All in all, the application of RWS in the field of traditional Chinese medicine has great potential in the future and will dispose of more problems closely related to clinical practice. We expect that better design and analysis methods can be discovered, adjusted, and applied, and the limitations and problems of the application of RWS can be better solved.

Data Availability

Data are openly available in a public repository.

Conflicts of Interest

The authors declare no conflicts of interest.

Acknowledgments

This study was supported by the National Natural Science Foundation of China (81973616).

References

J. M. Franklin and S. Schneeweiss, “When and how can real world data analyses substitute for randomized controlled trials?” Clinical Pharmacology and Therapeutics, vol. 102, no. 6, pp. 924–933, 2017.
View at: Publisher Site | Google Scholar
N. A. Dreyer, “Advancing a framework for regulatory use of real-world evidence: when real is reliable,” Therapeutics Innovation and Regulatory Sciences, vol. 52, no. 3, pp. 362–368, 2018.
View at: Publisher Site | Google Scholar
P. M. Welsing, K. Oude Rengerink, S. Collier et al., “Series: pragmatic trials and real world evidence: paper 6. Outcome measures in the real world,” Journal of Clinical Epidemiology, vol. 90, pp. 99–107, 2017.
View at: Publisher Site | Google Scholar
H. G. Eichler, F. Pignatti, B. Schwarzer‐Daum et al., “Randomized controlled trials versus real world evidence: neither magic nor myth,” Clinical Pharmacology and Therapeutics, vol. 109, no. 5, pp. 1212–1218, 2021.
View at: Publisher Site | Google Scholar
R. Collins, L. Bowman, M. Landray, and R. Peto, “The magic of randomization versus the myth of real-world evidence,” New England Journal of Medicine, vol. 382, no. 7, pp. 674–678, 2020.
View at: Publisher Site | Google Scholar
National Academies of Sciences, “The national academies collection: reports funded by national institutes of health,” Examining the Impact of Real-World Evidence on Medical Product Development: Proceedings of a Workshop Series, National Academies Press, Washington, DC, USA, 2019.
View at: Google Scholar
J. Corrigan-Curay, L. Sacks, and J. Woodcock, “Real-world evidence and real-world data for evaluating drug safety and effectiveness,” JAMA, vol. 320, no. 9, p. 867, 2018.
View at: Publisher Site | Google Scholar
C. L. Ventola, “Big data and pharmacovigilance: data mining for adverse drug events and interactions,” P T, vol. 43, no. 6, pp. 340–351, 2018.
View at: Google Scholar
P. Glasziou, I. Chalmers, M. Rawlins, and P. McCulloch, “When are randomised trials unnecessary? picking signal from noise,” BMJ, vol. 334, no. 7589, pp. 349–351, 2007.
View at: Publisher Site | Google Scholar
I. Shrier and S. D. Stovitz, “Randomization versus real-world evidence,” New England Journal of Medicine, vol. 383, no. 4, p. e21, 2020.
View at: Publisher Site | Google Scholar
S. H. Giordano, Y. F. Kuo, Z. Duan, G. N. Hortobagyi, J. Freeman, and J. S. Goodwin, “Limits of observational data in determining outcomes from cancer therapy,” Cancer, vol. 112, no. 11, pp. 2456–2466, 2008.
View at: Publisher Site | Google Scholar
N. A. Dreyer, M. Hall, and J. B. Christian, “Modernizing regulatory evidence with trials and real-world studies,” Therapeutics Innovation Regulatory Sciences, vol. 54, no. 5, pp. 1112–1115, 2020.
View at: Publisher Site | Google Scholar
Y. T. Kuo, T. T. Chang, C. H. Muo et al., “Use of complementary traditional Chinese medicines by adult cancer patients in taiwan: a nationwide population-based study,” Integrative Cancer Therapies, vol. 17, no. 2, pp. 531–541, 2018.
View at: Publisher Site | Google Scholar
R. L. Siegel, K. D. Miller, H. E. Fuchs, and A. Jemal, “Cancer statistics, 2021,” CA: A Cancer Journal for Clinicians, vol. 71, no. 1, pp. 7–33, 2021.
View at: Publisher Site | Google Scholar
T. M. Li, Y. H. Yu, F. J. Tsai et al., “Characteristics of Chinese herbal medicine usage and its effect on survival of lung cancer patients in Taiwan,” Journal of Ethnopharmacology, vol. 213, pp. 92–100, 2018.
View at: Publisher Site | Google Scholar
C. L. Li, T. C. Hsia, C. H. Li, K. J. Chen, Y. H. Yang, and S. T. Yang, “Adjunctive traditional Chinese medicine improves survival in patients with advanced lung adenocarcinoma treated with first-line epidermal growth factor receptor (egfr) tyrosine kinase inhibitors (TKIs): a nationwide, population-based cohort study,” Integrative Cancer Therapies, vol. 18, Article ID 153473541982707, 2019.
View at: Publisher Site | Google Scholar
Y. H. Liao, C. I. Li, C. C. Lin, J. G. Lin, J. H. Chiang, and T. C. Li, “Traditional Chinese medicine as adjunctive therapy improves the long-term survival of lung cancer patients,” Journal of Cancer Research and Clinical Oncology, vol. 143, no. 12, pp. 2425–2435, 2017.
View at: Publisher Site | Google Scholar
Y. T. Kuo, H. H. Liao, J. H. Chiang et al., “Complementary Chinese herbal medicine therapy improves survival of patients with pancreatic cancer in taiwan: a nationwide population-based cohort study,” Integrative Cancer Therapies, vol. 17, no. 2, pp. 411–422, 2018.
View at: Publisher Site | Google Scholar
Y. H. Liao, C. C. Lin, H. C. Lai, J. H. Chiang, J. G. Lin, and T. C. Li, “Adjunctive traditional Chinese medicine therapy improves survival of liver cancer patients,” Liver International, vol. 35, no. 12, pp. 2595–2602, 2015.
View at: Publisher Site | Google Scholar
L. Wang, Clincal Observation on the Combination of Spleen Detoxification and Tongluo Formula with Tegafur in the Maintenance Treatment of Middle and Advanced Colorectal Cancer in the Real World, Anhui University of Traditional Chinese Medicine, Hefei, China, 2021.
K. F. Hung, C. P. Hsu, J. H. Chiang et al., “Complementary Chinese herbal medicine therapy improves survival of patients with gastric cancer in Taiwan: a nationwide retrospective matched-cohort study,” Journal of Ethnopharmacology, vol. 199, pp. 168–174, 2017.
View at: Publisher Site | Google Scholar
C. Hou, D. Yang, Y. Zhang et al., “Effect of fuzheng qingdu therapy for metastatic gastric cancer is associated with improved survival: a multicenter propensity-matched study,” Integrative Cancer Therapies, vol. 20, Article ID 153473542110584, 2021.
View at: Publisher Site | Google Scholar
Y. S. Lin, Y. C. Shen, C. Y. Wu et al., “Danshen improves survival of patients with breast cancer and dihydroisotanshinone I induces ferroptosis and apoptosis of breast cancer cells,” Frontiers of Pharmacology, vol. 10, p. 1226, 2019.
View at: Publisher Site | Google Scholar
P. W. Chan, J. H. Chiu, N. Huang et al., “Influence of traditional Chinese medicine on medical adherence and outcome in estrogen receptor (+) breast cancer patients in taiwan: a real-world population-based cohort study,” Phytomedicine, vol. 80, Article ID 153365, 2021.
View at: Publisher Site | Google Scholar
Early Breast Cancer Trialists’ Collaborative Group EBCTCG, “Aromatase inhibitors versus tamoxifen in premenopausal women with oestrogen receptor-positive early-stage breast cancer treated with ovarian suppression: a patient-level meta-analysis of 7030 women from four randomised trials,” Lancet Oncology, vol. 23, no. 3, pp. 382–392, 2022.
View at: Publisher Site | Google Scholar
G. Emons, A. Mustea, and C. Tempfer, “Tamoxifen and endometrial cancer: a janus-headed drug,” Cancers (Basel), vol. 12, no. 9, p. 2535, 2020.
View at: Publisher Site | Google Scholar
S. Jayaraman, J. M. Reid, J. R. Hawse, and M. P. Goetz, “Endoxifen, an estrogen receptor targeted therapy: from bench to bedside,” Endocrinology, vol. 162, no. 12, Article ID bqab191, 2021.
View at: Publisher Site | Google Scholar
Y. T. Tsai, J. N. Lai, and C. T. Wu, “The use of Chinese herbal products and its influence on tamoxifen induced endometrial cancer risk among female breast cancer patients: a population-based study,” Journal of Ethnopharmacology, vol. 155, no. 2, pp. 1256–1262, 2014.
View at: Publisher Site | Google Scholar
C. Wang, K. Y. H. Lin, M. Y. Wu et al., “Adjunctive Chinese herbal medicine treatment is associated with an improved survival rate in patients with cervical cancer in taiwan: a matched cohort study,” Integrative Cancer Therapies, vol. 20, Article ID 153473542110617, 2021.
View at: Publisher Site | Google Scholar
H. C. Lin, C. L. Lin, W. Y. Huang et al., “The use of adjunctive traditional Chinese medicine therapy and survival outcome in patients with head and neck cancer: a nationwide population-based cohort study,” Qjm, vol. 108, no. 12, pp. 959–965, 2015.
View at: Publisher Site | Google Scholar
Y. Xu, The Real-World Study of the Clinical Efficacy of Traditional Chinese Medicine in the Treatment of III-IV Stages Esophageal, Henan University of Chinese Medicine, Zhengzhou, China, 2021.
M. Cao and W. Chen, “Epidemiology of cancer in China and the current status of prevention and control,” Chinese Journal of Clinical Oncology, vol. 46, no. 03, pp. 145–149, 2019.
View at: Google Scholar
E. Versteijne, J. L. van Dam, M. Suker et al., “Neoadjuvant chemoradiotherapy versus upfront surgery for resectable and borderline resectable pancreatic cancer: long-term results of the Dutch randomized PREOPANC trial,” Journal of Clinical Oncology, vol. 40, no. 11, pp. 1220–1230, 2022.
View at: Publisher Site | Google Scholar
J. Mahmood, H. Shukla, S. Soman et al., “Immunotherapy, radiotherapy, and hyperthermia: a combined therapeutic approach in pancreatic cancer treatment,” Cancers (Basel), vol. 10, no. 12, p. 469, 2018.
View at: Publisher Site | Google Scholar
S. Han and J. Wu, “Three-dimensional (3D) scaffolds as powerful weapons for tumor immunotherapy,” Bioactive Materials, vol. 17, pp. 300–319, 2022.
View at: Publisher Site | Google Scholar
C. M. Laumont, A. C. Banville, M. Gilardi, D. P. Hollern, and B. H. Nelson, “Tumour-infiltrating B Cells: immunological mechanisms, clinical impact and therapeutic opportunities,” Nature Review Cancer, 2022.
View at: Google Scholar
Y. Tian, D. Xie, and L. Yang, “Engineering strategies to enhance oncolytic viruses in cancer immunotherapy,” Signal Transduction and Targeted Therapy, vol. 7, no. 1, p. 117, 2022.
View at: Publisher Site | Google Scholar
Z. Fu, S. Li, S. Han, C. Shi, and Y. Zhang, “Antibody drug conjugate: the “biological missile” for targeted cancer therapy,” Signal Transduction and Targeted Therapy, vol. 7, no. 1, p. 93, 2022.
View at: Publisher Site | Google Scholar
F. Fontana, M. Anselmi, and P. Limonta, “Molecular mechanisms and genetic alterations in prostate cancer: from diagnosis to targeted therapy,” Cancer Letters, vol. 534, Article ID 215619, 2022.
View at: Publisher Site | Google Scholar
M. Galanopoulos, A. Doukatas, F. Gkeros, N. Viazis, and C. Liatsos, “Room for improvement in the treatment of pancreatic cancer: novel opportunities from gene targeted therapy,” World Journal of Gastroenterology, vol. 27, no. 24, pp. 3568–3580, 2021.
View at: Publisher Site | Google Scholar
J. J. Xu, W. C. Zhang, Y. W. Guo, X. Y. Chen, and Y. N. Zhang, “Metal nanoparticles as a promising technology in targeted cancer treatment,” Drug Delivery, vol. 29, no. 1, pp. 664–678, 2022.
View at: Publisher Site | Google Scholar
Z. Ma, X. Xiang, S. Li et al., “Targeting hypoxia-inducible factor-1, for cancer treatment: recent advances in developing small-molecule inhibitors from natural compounds,” Seminars in Cancer Biology, vol. 80, pp. 379–390, 2022.
View at: Publisher Site | Google Scholar
Y. Z. Zhao, Y. Z. Dai, and K. Nie, “Research progress on the antiemetic effect of traditional Chinese medicine against chemotherapy-induced nausea and vomiting: a review,” Frontiers Pharmacology, vol. 12, Article ID 790784, 2021.
View at: Publisher Site | Google Scholar
W. Xu, B. Li, M. Xu, T. Yang, and X. Hao, “Traditional Chinese medicine for precancerous lesions of gastric cancer: a review,” Biomedicine & Pharmacotherapy, vol. 146, Article ID 112542, 2022.
View at: Publisher Site | Google Scholar
H. Ge, C. Xu, H. Chen et al., “Traditional Chinese medicines as effective reversals of epithelial-mesenchymal transition induced-metastasis of colorectal cancer: molecular targets and mechanisms,” Frontiers Pharmacology, vol. 13, Article ID 842295, 2022.
View at: Publisher Site | Google Scholar
H. Jiang, M. Li, K. Du et al., “Traditional Chinese medicine for adjuvant treatment of breast cancer: taohong siwu decoction,” Chinese Medicine, vol. 16, no. 1, p. 129, 2021.
View at: Publisher Site | Google Scholar
Y. Zheng, W. Zhang, L. Xu, H. Zhou, M. Yuan, and H. Xu, “Recent progress in understanding the action of natural compounds at novel therapeutic drug targets for the treatment of liver cancer,” Frontiers Oncology, vol. 11, Article ID 795548, 2021.
View at: Publisher Site | Google Scholar
C. Xinyi, D. Qing, T. Shaodan, H. Li, J. Mei, and L. Xiao, “Comment on the clinical value of traditional Chinese medicine in the maintenance treatment of tumor,” Journal of Beijing University of Traditional Chinese Medicine, vol. 44, no. 09, pp. 777–783, 2021.
View at: Google Scholar
S. Si, S. Shan, X. J. Yan, and H. N. Liu, “Research progress on traditional Chinese medicine in treatment of cancer,” China Journal of Traditional Chinese Medicine and Pharmacy, vol. 33, no. 10, pp. 4539–4541, 2018.
View at: Google Scholar
W. C. S. Cho and K. N. Leung, “In vitro and in vivo immunomodulating and immunorestorative effects of Astragalus membranaceus,” Journal of Ethnopharmacology, vol. 113, no. 1, pp. 132–141, 2007.
View at: Publisher Site | Google Scholar
J. Qu, Q. Liu, G. You et al., “Advances in ameliorating inflammatory diseases and cancers by andrographolide: pharmacokinetics, pharmacodynamics, and perspective,” Medicinal Research Reviews, vol. 42, no. 3, pp. 1147–1178, 2022.
View at: Publisher Site | Google Scholar
Y. Xu, X. Wang, L. Liu, J. Wang, J. Wu, and C. Sun, “Role of macrophages in tumor progression and therapy (Review),” International Journal of Oncology, vol. 60, no. 5, p. 57, 2022.
View at: Publisher Site | Google Scholar
L. Burns, N. L. Roux, R. Kalesnik-Orszulak et al., “Real-world evidence for regulatory decision-making: guidance from around the world,” Clinical Therapeutics, vol. 44, no. 3, pp. 420–437, 2022.
View at: Publisher Site | Google Scholar
H. Zhang, Y. Geng, Y. Z. Sun, Q. Li, and Z. M. Yang, “Background and key elements of guidance of real-world research to support drug development and evaluation in children,” Chinese Journal of Clinical Pharmacology, vol. 37, no. 02, 2021.
View at: Google Scholar
The formulation group of technical specifications for real world research of traditional Chinese medicine, “Technical specifications for real world research in traditional chinese medicine—evidence quality evaluation,” Reporting Journal of Traditional Chinese Medicine, vol. 63, no. 03, pp. 293–300, 2022.
View at: Google Scholar
U. Fda, “Real-world data: assessing registries to support regulatory decision-making for drug and biological products guidance for industry,” 2016, https://www.fda.gov/regulatory-information/selected-amendmentsfdc-act/21st-century-cures-act.
View at: Google Scholar
S. Khosla, R. White, J. Medina et al., “Real world evidence (RWE) - a disruptive innovation or the quiet evolution of medical evidence generation?” F1000Research, vol. 7, p. 111, 2018.
View at: Publisher Site | Google Scholar
X. Q. Hu, Y. Sun, E. Lau, M. Zhao, and S. B. Su, “Advances in synergistic combinations of Chinese herbal medicine for the treatment of cancer,” Current Cancer Drug Targets, vol. 16, no. 4, pp. 346–356, 2016.
View at: Publisher Site | Google Scholar
Q. Zhao, S. Zheng, G. P. Delaney et al., “Acupuncture for cancer related pain: protocol for a pragmatic randomised wait-list controlled trial,” Integrative Cancer Therapies, vol. 19, Article ID 153473542097657, 2020.
View at: Publisher Site | Google Scholar
J. Zayas, K. J. Ruddy, J. E. Olson et al., “Real-world experiences with acupuncture among breast cancer survivors: a cross-sectional survey study,” Support Care Cancer, vol. 28, no. 12, pp. 5833–5838, 2020.
View at: Publisher Site | Google Scholar
B. de Valois, T. Young, P. Thorpe, T. Degun, and K. Corbishley, “Acupuncture in the real world: evaluating a 15-year NADA auricular acupuncture service for breast cancer survivors experiencing hot flushes and night sweats as a consequence of adjuvant hormonal therapies,” Support Care Cancer, vol. 30, no. 6, pp. 5063–5074, 2022.
View at: Publisher Site | Google Scholar
Y. He, H. Zhang, Y. Li et al., “Acupuncture combined with opioids for cancer pain: a pilot pragmatic randomized controlled trial,” Acupuncture in Medicine, vol. 40, no. 2, pp. 133–141, 2022.
View at: Publisher Site | Google Scholar
B. Lee, B. K. Kim, M. Kim et al., “Electroacupuncture for treating cancer-related insomnia: a multicenter, assessor-blinded, randomized controlled, pilot clinical trial,” BMC Complementary Medicine and Therapies, vol. 22, no. 1, p. 77, 2022.
View at: Publisher Site | Google Scholar
X. Chen, P. Wang, M. Yang et al., “Therapeutic effect of Jianpi Liqi Fang combined with transcatheter arterial chemoembolization in patients with hepatocellular carcinoma and spleen deficiency syndrome,” Journal of Tradititional Chinese Medicine, vol. 41, no. 1, pp. 157–166, 2021.
View at: Publisher Site | Google Scholar
M. D. Yang, W. J. Zhou, X. L. Chen et al., “Therapeutic effect and mechanism of bushen-jianpi-jiedu decoction combined with chemotherapeutic drugs on postoperative colorectal cancer,” Frontiers Pharmacology, vol. 12, Article ID 524663, 2021.
View at: Publisher Site | Google Scholar
Y. J. Cai, H. B. Deng, Z. Q. Wang et al., “Effect of Kangliu Jiandu Formula combined with chemotherapy on short-term effect and quality-of-life in patients with non-small cell lung cancer: based on real world study,” Hebei Journal of Tradititional Chinese Medicine, vol. 43, no. 09, 2021.
View at: Google Scholar
Y. C. Lee, Y. H. Chen, Y. C. Huang, Y. F. Lee, and M. Y. Tsai, “Effectiveness of combined treatment with traditional Chinese medicine and western medicine on the prognosis of patients with breast cancer,” The Journal of Alternative and Complementary Medicine, vol. 26, no. 9, pp. 835–842, 2020.
View at: Publisher Site | Google Scholar
Y. Zhang, B. H. Lei, Q. Zou, Q. Y. Zhu, Z. J. Lu, and Y. Wang, “Clinical efficacy of integrated traditional Chinese and Western medicine for castration-resistant prostate cancer,” Zhonghua Nan Ke Xue, vol. 23, no. 10, pp. 922–927, 2017.
View at: Google Scholar
H. Wen, A Real-World Study Predict 90-day Risk in Patients with Primary Lung Cancer Chinese Medicine Treatment, Jiangxi University of Chinese Medicine, Nanchang, China, 2021.
R. Huang, P. T. Zhang, and R. Miao, “Characteristics of traditional Chinese medicine syndromes in 223 pancreatic cancer cases based on syndrome hierarchical diagnosis mode,” Journal of Traditional Chinese Medicine, vol. 63, no. 06, pp. 551–556, 2022.
View at: Google Scholar
J. Chen, “Neuromodulation and neurostimulation for the treatment of functional gastrointestinal disorders,” Gastroenterology & Hepatology, vol. 18, no. 1, pp. 47–49, 2022.
View at: Google Scholar
T. Wu, S. Zhang, S. Guo et al., “Correspondence analysis between traditional Chinese medicine (TCM) syndrome differentiation and histopathology in colorectal cancer,” European Journal of Integrative Medicine, vol. 7, no. 4, pp. 342–347, 2015.
View at: Publisher Site | Google Scholar
S. F. Zhai and H. N. Wu, “The relationship between typing of gastric carcinoma according to TCM theories and clinical pathological classification,” Chinese Journal of Integrated Traditional and Western Medicine, vol. 9, no. 01, 1989.
View at: Google Scholar
M. J. Piao, “Correlation between microvessel growth and differentiation of traditional Chinese medicine in breast cancer,” Journal of Basic Chinese Medicine, vol. 22, no. 07, pp. 927-928, 2016.
View at: Google Scholar
P. Xue, X. Y. Ren, Q. Yan, and Q. Lu, “Distribution of TCM syndrome types and its influencing factors in senile patients with advanced cervical cancer,” Chinese Journal of Gerontology, vol. 41, no. 24, pp. 5538–5541, 2021.
View at: Google Scholar

Copyright

Copyright © 2022 Linjia Peng et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

PDF Download Citation

Download other formats

Order printed copies

Views

882

Downloads

706

Citations