Abstract: The methodological quality of primary studies was generally unsatisfying and the results were reported inadequately in many aspects. Additional information was not available from primary trialists. The meta-analysis results showed that patients who had been given G. lucidum alongside with chemo/radiotherapy were more likely to respond positively compared to chemo/radiotherapy alone (RR 1.50; 95% CI 0.90 to 2.51, P = 0.02). G. lucidum treatment alone did not demonstrate the same regression rate as that seen in combined therapy. The results for host immune function indicators suggested that G. lucidum simultaneously increases the percentage of CD3, CD4 and CD8 by 3.91% (95% CI 1.92% to 5.90%, P < 0.01), 3.05% (95% CI 1.00% to 5.11%, P < 0.01) and 2.02% (95% CI 0.21% to 3.84%, P = 0.03), respectively. In addition, leukocyte, NK-cell activity and CD4/CD8 ratio were marginally elevated. Four studies showed that patients in the G. lucidum group had relatively improved quality of life in comparison to controls. One study recorded minimal side effects, including nausea and insomnia. No significant haematological or hepatological toxicity was reported. Our review did not find sufficient evidence to justify the use of G. lucidum as a first-line treatment for cancer. It remains uncertain whether G. lucidum helps prolong long-term cancer survival. However, G. lucidum could be administered as an alternative adjunct to conventional treatment in consideration of its potential of enhancing tumour response and stimulating host immunity. G. lucidum was generally well tolerated by most participants with only a scattered number of minor adverse events. No major toxicity was observed across the studies. Although there were few reports of harmful effect of G. lucidum, the use of its extract should be judicious, especially after thorough consideration of cost-benefit and patient preference. Future studies should put emphasis on the improvement in methodological quality and further clinical research on the effect of G. lucidum on cancer long-term survival are needed. An update to this review will be performed every two years.

Plain-language summary: Our review identified and subsequently included five relevant randomised controlled trials. A total of 373 subjects were analysed. A meta-analysis was performed to pool available data from individual trials. Our results found that patients with G. lucidum extract in their anticancer regimen were 1.27 times more likely to respond to chemotherapy or radiotherapy than those without. However, the data failed to demonstrate significant effect on tumour shrinkage when it was used alone. In addition, G. lucidum could stimulate host immune functions by considerably increasing CD3, CD4 and CD8 lymphocyte percentages. Nevertheless, natural killer (NK)-cell activity, which has been suggested to be an indicator of self-defence against tumour cell, was marginally elevated. Patients in the G. lucidum group were found to have a relatively better quality of life after treatment than those in the control group. A few cases of minor side effect associated with G. lucidum treatment including nausea and insomnia were reported. There are limitations of the results from this systematic review. First, most included studies were small and there were concerns on the methodological quality of individual trials. Second, all participants in the individual trials were recruited from the Chinese population. Together, the robustness and applicability of the results were largely affected.