Table2_The association between mortality and use of Chinese herbal medicine among incident stage IV esophageal cancer patients: A retrospective cohort study with core herbs exploration.XLSX

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 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.</p

Table4_The association between mortality and use of Chinese herbal medicine among incident stage IV esophageal cancer patients: A retrospective cohort study with core herbs exploration.XLSX

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 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.</p

Table3_The association between mortality and use of Chinese herbal medicine among incident stage IV esophageal cancer patients: A retrospective cohort study with core herbs exploration.XLSX

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 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.</p

Table1_The association between mortality and use of Chinese herbal medicine among incident stage IV esophageal cancer patients: A retrospective cohort study with core herbs exploration.DOCX

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 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.</p

Outcomes and percentage changes in parameters from baseline to 12 weeks.

Outcomes and percentage changes in parameters from baseline to 12 weeks.</p

Adverse events in the YH1 and placebo groups.

Adverse events in the YH1 and placebo groups.</p

The composition and botanical origin of YH1.

The composition and botanical origin of YH1.</p

3D-HPLC fingerprint of YH1.

The chemical composition of YH1 was analyzed using high-performance liquid chromatography (HPLC) with a photodiode array (PDA). Fourteen components, including allantoin, atractylenolide III, berberine, coptisine, ginsenoside Rb1, ginsenoside Re, ginsenoside Rg1, glycyrrhizin, liquiritin, pachymic acid, palmatine, platycodin D, magnoflorin and quercitrin, were detected.</p

Baseline characteristics of participants (per-protocol analysis).

Baseline characteristics of participants (per-protocol analysis).</p

CONSORT flow diagram of enrollment, randomization, and treatment.

Two patients in the YH1 group and three patients in the placebo group were excluded from the study for the various reasons listed.</p