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. 2023 Apr 14;15(4):e37574. doi: 10.7759/cureus.37574

Table 1. Summary table of the nine articles included in the review .

PSK: polysaccharide-K; UFT/LV: oral adjuvant uracil and tegafur plus leucovorin; DFS: disease-free survival

Study Purpose   Sample Methods / Study Design  Type of Mushroom Major Findings
GASTRIC CANCER
Hsu et al. 2016 (28) Elucidate long-term outcomes obtained in gastric cancer patients treated by adjuvant immunochemotherapy and how this is influenced by PD-L1 (a protein that helps keep the body’s immune responses under control) expression based on a large-scale surgical series. 918 patients with stages II and III gastric cancer undergoing curative gastrectomy and receiving adjuvant chemotherapy. Retrospective review of patient charts classified into four cohorts stratified by PD-L1 expression and PSK administration, namely PD-L1, PSK. In addition, another independent cohort of 20 patients undergoing radical gastrectomy was prospectively recruited to check their immunological cells of sera before and 2 months after PSK administration. Meta-analysis performed. PSK (from Trametes versicolor, also known as Coriolus versicolor and Turkey Tail mushroom).   The results collectively suggested that PSK serves as an immune modulator to enhance effectiveness of adjuvant chemotherapy in gastric cancer patients, providing survival benefits for patients with stage IIIA/IIIB disease, especially in PDL negative group.
Ito et al. 2012 (29) Evaluate the expression of major histocompatibility complex (MHC) class I in gastric cancer patients who received PSK postoperative adjuvant immunochemotherapy and investigate the correlation between MHC class I expression and clinical outcomes. The trial consisted of 349 stage II/III gastric cancer patients receiving  adjuvant therapy after curative resection. Controlled trial with patients in 2 treatment groups. The first group was given oral chemotherapy only; the second group was given chemotherapy in addition to PSK. Out of 349 patients, 225 patients with adjuvant chemotherapy were given only an oral fluoropyrimidine formulation; the other 124 patients were given oral fluoropyrimidine plus PSK as immunotherapy .   PSK (from Trametes versicolor, also known as Coriolus versicolor and Turkey Tail mushroom).   Survival‑prolonging effects from PSK when included in gastric cancer therapy in patients who have had curative resection, at high risk of recurrence (presence of lymph node metastasis and the absence of MHC class I expression).  It was thought that PSK effects residual cancer cells that have eluded antitumor immune functions;  potential to prevent lymph node metastasis.
Tanaka et al. 2012 (30) Evaluate the effect of Protein-bound PSK on the overall survival of patients with gastric cancer. 254 patients with gastric carcinoma.  Inclusion was limited to patients to whom curative surgery with postoperative adjuvant treatment with clinical stage II/III was offered.  Retrospective study of patients with gastric carcino split into a study group of PSK plus Fluoropyrimidine and control group of just Flouropurimidine therapy for approximately 16 months. PSK (from Trametes versicolor, also known as Coriolus versicolor and Turkey Tail mushroom).   In the analysis of all patients, no significant differences were found in relapse-free or overall survival. Although, survival was improved in patients with multiple lymph node metastases following administration of PSK.
Wang et al. 2022 (31) Evaluate the efficacy of PSK as an adjuvant therapy alongside chemotherapy in patients outside of Japan with gastric cancers who have already had a gastrectomy. 10,617 newly diagnosed gastric cancer patients who had a gastrectomy and were receiving adjuvant chemotherapy. Retrospective historical study cohort with a control group. PSK (from Trametes versicolor, also known as Coriolus versicolor and Turkey Tail mushroom).   The PSK group had a significantly longer survival than the control group. After adjusting for age, sex, urbanization, income, comorbidities and chemotherapy regimen, the use of PSK was still significantly associated with a reduction in the risk of death.
Qi et al. 2020 (10) Determine the antitumor role of Huaier granules and the potential antitumor mechanism of Huaier polysaccharides in gastric cancer. 136 Stage IIb gastric patients were enrolled, with 54 in the Huaier+Tegafur Gimeracil Oteracil Potassium group, and 72 in the Tegafur Gimeracil Oteracil Potassium only group. Retrospective cohort design. Dosage for patients that got oral Tegafur Gimeracil Oteracil Potas-sium was 60 mg. twice daily (capsule form) for the first 14 days, 3 weeks of a cycle within 1 year, with or without Huaier granule 20 mg. 3 times per day for 1 year. Trametes robiniophila Murr (also known as Huaier, a sandy beige mushroom that grows on hard wood trees. Patients in the study group showed to have greater DFS compared to the control group. Overall, Huaier polysaccharides promote anti-tumor and gastric cell apoptosis effectively.
BREAST CANCER
Hangai et al. 2013 (32) Explore the beneficial effects of active hexose-correlated compound (AHCC) on adverse events in patients receiving adjuvant chemotherapy for breast cancer. Study consisted of 41 female patients treated with anthracyclines and taxanes for breast cancer (aged 31-61 years)   This was a retrospective cohort study (with control group) that surveyed medical records of women with breast cancer on adjuvant chemotherapy for which the treatment group received AHCC therapy; Patients who had taken AHCC during chemotherapy (1.0 g) by mouth post each meal. The placebo group did not receive AHCC. Active hexose-correlated compound (AHCC), an extract of Lentinula edodes (Shiitake), which contains a polysaccharide called lentinan. The AHCC group had significantly fewer neutrophil related events and less use of granulocyte colony-stimulating factor. The treatment group also experienced a higher (non-significant) rate of adverse events associated with c-glutamyl transpeptidase. AHCC may be able to lower the severity of neutropenia stemming from chemotherapy (including granulocyte-colony stimulating factor use during chemotherapy; AHCC also showed promise in lowering the toxicity of chemotherapy, allowing for increase in dosage breast cancer patients receiving chemotherapy.   
Nagashima et al. 2017 (34) Evaluate the effectiveness of Lentinula edodes mycelia extract (LEM) derived from the Shiitake mushroom which is an oral biological response modifier (BRM) medicine for cancer patients as an adjuvant.  47 breast cancer patients who were female, aged ≥ 20 years, were diagnosed with breast cancer, and were scheduled for anthracycline-based adjuvant chemotherapy as postoperative adjuvant therapy. The patients had a life expectancy of > 3 months. Placebo-controlled randomized double-blind study that evaluated the effectiveness of Lentinula edodes mycelia extract (LEM). Lentinula edodes mycelia extract (LEM), a dried powder extracted from the shiitake mushroom.  Coadministration of LEM may ameliorate anthracycline-based chemotherapy induced decreases in QOL and immune function in postoperative breast cancer patients. Oral LEM may prove to be a useful supportive care option for such postoperative breast cancer patients.
Valadares et al. 2013 (35) Evaluate the effects of dietary supplementation of Agaricus Sylvaticus on clinical and nutritional parameters in breast cancer patients undergoing chemotherapy. 46 female patients with breast cancer, Stage II and III. A randomized, placebo-controlled, double-blind, clinical trial (random assignment to either  nutritional supplement with Agaricus Sylvaticus group or placebo group.    Agaricus Sylvaticus, also known as Blushing wood mushroom, Scaly wood mushroom, and Pinewood mushroom  Patients who were in the Agaricus Sylvaticus gooup showed improvement in gastrointestinal activities. Decreased appetite showed a 20% decrease, with no alterations in bowel functions. Vomiting and nausea also decreased in the treatment group.
COLORECTAL CANCER
Miyake et al. 2017 (36) Compare oral adjuvant immunochemotherapy with uracil and tegafur plus PSK (UFT/PSK) to oral adjuvant chemotherapy with uracil and tegafur plus leucovorin (UFT/LV) in stage IIB and III colorectal cancer patients to ascertain if the clinical response of UFT/PSK was “not inferior” to UFT/LV.   In this study, 351 colorectal cancer patients who also had Japanese D2/D3 lymphadenectomy. The median age was 65 years, colon/rectum stage IIB/IIIA/IIIB/IIIC.  Prospective randomized, open-label, phase III trial, with. Positive end results would indicate the patient was disease-free for 3 years. The randomized non-inferiority study compared UFT/LV to UFT/PSK. In addition to overall survival, the researchers investigated adverse events, compliance, and quality of life. PSK (from Trametes versicolor, also known as Coriolus versicolor and Turkey Tail mushroom).   Findings could not conclude that (UFT/LV)/UFT/PSK adjuvant therapy was “non-inferior" to UFT/LV therapy.  The 3-year overall disease-free survival, but secondary endpoints (adverse effects, compliance, and quality of life) showed better results with UFT/PSK than UFT/LV.