Immortal Time Bias-Corrected Effectiveness of Traditional Chinese Medicine in Non-Small Cell Lung Cancer (C-EVID): A Prospective Cohort Study.

Background: Relatively little is known about the effect of traditional Chinese medicine (TCM) on prognosis of non-small cell lung cancer (NSCLC). Methods: In this nationwide, multicenter, prospective, cohort study, eligible patients aged 18-75 years with radical resection, and histologically confirmed stage II-IIIA NSCLC were enrolled. All patients received 4 cycles of standard adjuvant chemotherapy. Patients who received Chinese herbal decoction and (or) oral Chinese patent medicine for a cumulative period of not less than 6 months were defined as TCM group, otherwise they were considered as control group. The primary endpoint was DFS calculated using the Kaplan-Meier method. A time-dependent Cox proportional hazards model was used to correct immortal time bias. The secondary endpoints included DFS in patients of different characteristics, and safety analyses. This study was registered with the Chinese Clinical Trial Registry (ChiCTR1800015776). Results: A total of 507 patients were included (230 patients in the TCM group; 277 patients in the control group). The median follow-up was 32.1 months. 101 (44%) in the TCM group and 186 (67%) in the control group had disease relapse. The median DFS was not reached in the TCM group and was 19.4 months (95% CI, 14.2 to 24.6) in the control group. The adjusted time-dependent HR was 0.61 (95% CI, 0.47 to 0.78), equalling to a 39% reduction in the risk of disease recurrence with TCM. the number needed to treat to prevent one patient from relapsing was 4.29 (95% CI, 3.15 to 6.73) at 5 years. Similar results were observed in most of subgroups. Patients had a significant improvement in white blood cell decrease, nausea, decreased appetite, diarrhea, pain, and fatigue in the TCM group. Conclusion: TCM may improves DFS and has a better tolerability profile in patients with stage II-IIIA NSCLC receiving standard chemotherapy after complete resection compared with those receiving standard chemotherapy alone. Further studies are warranted.

Association between Chinese Medicine Therapy and Survival Outcomes in Postoperative Patients with NSCLC: A Multicenter, Prospective, Cohort Study.

OBJECTIVE: To evaluate the association between Chinese medicine (CM) therapy and disease-free survival (DFS) outcomes in postoperative patients with non-small cell lung cancer (NSCLC). METHODS: This multiple-center prospective cohort study was conducted in 13 medical centers in China. Patients with stage I, II, or IIIA NSCLC who had undergone radical resection and received conventional postoperative treatment according to the National Comprehensive Cancer Network (NCCN) guidelines were recruited. The recruited patients were divided into a CM treatment group and a control group according to their wishes. Patients in the CM treatment group received continuous CM therapy for more than 6 months or until disease progression. Patients in the control group received CM therapy for less than 1 month. Follow-up was conducted over 3 years. The primary outcome was DFS, with recurrence/metastasis rates as a secondary outcome. RESULTS: Between May 2013 and August 2016, 503 patients were enrolled into the cohort; 266 were classified in the CM treatment group and 237 in the control group. Adjusting for covariates, high exposure to CM was associated with better DFS [hazard ratio (HR) = 0.417, 95% confidential interval (CI): 0.307-0.567)]. A longer duration of CM therapy (6-12 months, 12-18 months, >24 months) was associated with lower recurrence and metastasis rates (HR = 0.225, 0.119 and 0.083, respectively). In a subgroup exploratory analysis, CM therapy was also a protective factor of cancer recurrence and metastasis in both stage I-IIIA (HR=0.50, 95% CI: 0.37-0.67) and stage IIIA NSCLC postoperative patients (HR = 0.48, 95% CI: 0.33-0.71), DFS was even longer among CM treatment group patients. CONCLUSIONS: Longer duration of CM therapy could be considered a protective factor of cancer recurrence and metastasis. CM treatment is associated with improving survival outcomes of postoperative NSCLC patients in China. (Registration No. ChiCTR-OOC-14005398).

Comprehensive treatment with Chinese medicine in patients with advanced non-small cell lung cancer: A multicenter, prospective, cohort study.

OBJECTIVE: To determine whether additional Chinese medicine (CM) could prolong survival and improve the quality of life (QOL) in patients with advanced non-small cell lung cancer (NSCLC) compared with Western medicine (WM) alone. METHODS: This was a multicenter, prospective cohort study. A total of 474 hospitalized patients with stage III-IV NSCLC were recruited and divided into 2 groups. Patients in the WM group received radiotherapy, chemotherapy, and optimal supportive therapy according to the National Comprehensive Cancer Network (NCCN) guidelines. In the integrative medicine (IM) group, individualized CM (Chinese patent medicines and injections) and WM were administered. The primary end point was overall survival, and the secondary end points were time to disease progression, adverse events, and QOL. Follow-up clinical examinations and chest radiography were performed every 2 months. RESULTS: The median survival was 16.60 months in the IM group and 13.13 months in the WM group (P<0.01). The incidences of loss of appetite, nausea, and vomiting in the IM group were significantly lower than those in the WM group (P<0.05). The QOL based on Functional Assessment of Cancer Therapy-Lung in the IM group was markedly higher than that in the WM group at the fourth course (P<0.05). CONCLUSIONS: Additional CM may prolong survival and improve the QOL patients with NSCLC. The adverse effects of radio- and chemotherapy may be attenuated as CM is used in combination with conventional treatments.