For patients with inoperable huge hepatocellular carcinoma (H-HCC, tumor size ≥10 cm), treatment options are limited. This study aimed to evaluate the characteristics and outcomes of patients with H-HCC who use Chinese herbal medicine (CHM). Multi-institutional cohort data were obtained from the Chang Gung Research Database (CGRD) between 1 January 2002 and 31 December 2018. All patients were followed up for 3 years or until the occurrence of death. Characteristics of CHM users and risk of all-cause mortality were assessed, and core CHMs with potential pharmacologic pathways were explored. Among 1618 patients, clinical features of CHM users (88) and nonusers (1530) were similar except for lower serum α-fetoprotein (AFP) and higher serum albumin levels in CHM users. CHM users had significantly higher 3 year overall survival rates (15.0% vs. 9.7%) and 3 year liver-specific survival rates (13.4% vs. 10.7%), about 3 months longer median survival time, and lower risk of all-cause mortality. Core CHMs were discovered from the prescriptions, including Hedyotis diffusa Willd combined with Scutellaria barbata D.Don, Salvia miltiorrhiza Bunge., Curcuma longa L., Rheum palmatum L., and Astragalus mongholicus Bunge. CHM use appears safe and is possibly beneficial for inoperable H-HCC patients; however, further clinical trials are still required.

Esophageal cancer (EC) remains a leading cause of death worldwide and in Taiwan. The prognosis of advanced-stage EC is notably poor, and the treatment options are limited. Chinese herbal medicine (CHM) has been widely used as a complementary treatment for cancer, yet the long-term effect of CHM in stage IV EC remains unclear.The multi-institutional cohort obtained from the Chang Gung research database (CGRD) was used to study the long-term outcome of CHM use among incident stage IV EC patients from 1 January 2002, to 31 December 2018. All patients were followed up to 5 years or the occurrence of death. The overall survival (OS) and disease-specific survival rates were conducted using Kaplan-Meier estimation. Overlap weighing and landmark analysis were used to eliminate confounding and immortal time biases. Furthermore, we demonstrated the core CHMs for stage IV EC by using the Chinese herbal medicine network (CMN) analysis on prescriptions.Nine hundred eighty-five stage IV EC patients were analyzed, including 74 CHM users and 911 non-CHM users. We found the use of CHM was associated with a higher 5-year overall survival rate than CHM nonusers (the cumulative probability: 19.52% versus 6.04%, log-rank test: p < 0.001, and the p < 0.001 with overlap weighting). In addition, the overall median survival time was about 7 months longer among CHM users. Moreover, the lower 1-, 3-, 5-year disease-specific survival rates were higher among CHM users. Additionally, the risk of all-cause mortality was lower among CHM users when considering accessible demographic covariates (adjusted hazard ratio: 0.59, 95%CI: 0.39, 0.89, p = 0.011). Furthermore, the CMN analysis revealed that CHMs improved health while relieving tumor burden. For example, Hedyotis diffusa Willd. was the core CHM with an anti-cancer effect, while Fritillaria thunbergii Miq and Sevilla maindronide Rochebrune were used together to relieve cancer-related gastrointestinal discomfort.The use of CHM seems safe and possibly beneficial among stage IV EC patients with a higher 5-year OS. Further clinical trials on CHM were guaranteed to explore the role of CHM in managing stage IV EC patients.