Details of the Researcher

PHOTO

Yuya Yoshida
Section
Graduate School of Medicine
Job title
Assistant Professor

Awards 2

  1. 第230回東北地方会 指導医賞

    2023/09

  2. 第2回日本腫瘍循環器学会若手奨励賞 優秀賞

    2019/09

Papers 13

  1. A retrospective study of pembrolizumab plus chemotherapy for head and neck cancer patients: influence of response in combination phase on subsequent maintenance phase. International-journal

    Ken Saijo, Hiroo Imai, Yuki Kasahara, Ryunosuke Numakura, Reio Ueta, Keiju Sasaki, Yuya Yoshida, Sho Umegaki, Sakura Taniguchi, Kota Ouchi, Keigo Komine, Hidekazu Shirota, Masanobu Takahashi, Chikashi Ishioka

    Discover oncology 16 (1) 479-479 2025/04/07

    DOI: 10.1007/s12672-025-02256-1  

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    BACKGROUND: Pembrolizumab plus chemotherapy is considered one of the standard treatment regimens for patients with recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC). The regimen comprises up to 6 cycles of pembrolizumab-chemotherapy combination phase and subsequent pembrolizumab maintenance phase. Pembrolizumab-chemotherapy combination confers high response rate, creating favorable conditions for pembrolizumab maintenance phase. This study examined the influence of response in the combination phase on the efficacy in subsequent maintenance phase. METHODS: We retrospectively reviewed the medical records of patients with R/M HNSCC who received pembrolizumab plus chemotherapy as a first-line regimen at Tohoku University Hospital, Sendai, Japan. Progression-free survival (PFS) was analyzed when it was divided into the combination and maintenance phases. RESULTS: A total of 44 patients were enrolled. The best overall response was observed in the combination phase in all patients, and the overall response rate was 46.3%. The median PFS was 5.8 months (95% CI: 4.9-7.1). PFS differed significantly according to the response. When analyzed separately, the PFS only in the maintenance phase differed depending on the response of partial response (PR) or stable disease (SD). There was no difference in the number of chemotherapy cycles between patients with PR and SD. Univariate and multivariate analyses showed that the response in the combination phase was significantly associated with PFS in the maintenance phase. CONCLUSION: In the pembrolizumab plus chemotherapy regimen for patients with R/M HNSCC, the response in the combination phase may be associated with PFS in the maintenance phase.

  2. Impact of genetic mutations on prognosis and chemotherapy efficacy in advanced appendiceal carcinoma: insights from the nationwide Japanese comprehensive genomic profiling test database.

    Sakura Hiraide Taniguchi, Masanobu Takahashi, Shih-Wei Chiu, Keigo Komine, Shonosuke Wakayama, Ryunosuke Numakura, Yuya Yoshida, Yuki Kasahara, Kota Ouchi, Hiroo Imai, Ken Saijo, Hidekazu Shirota, Chikashi Ishioka

    International journal of clinical oncology 2025/02/28

    DOI: 10.1007/s10147-025-02724-2  

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    BACKGROUND: Appendiceal carcinoma (AC) is a rare malignancy and has distinct genomic features, but their impact on prognosis and chemotherapy efficacy requires further investigation. METHODS: This retrospective study analyzed patients with advanced AC from the Japanese nationwide comprehensive genomic profiling test database, the Center for Cancer Genomics and Advanced Therapeutics (C-CAT) database, focusing on genetic alterations and their associations with clinical outcomes. RESULTS: Of the 314 patients, the histological types Queryincluded adenocarcinoma (Ad) (51.9%), mucinous adenocarcinoma (MAd) (30.3%), goblet cell adenocarcinoma (12.4%), and signet-ring cell adenocarcinoma (5.4%). The most common mutations were KRAS (52.5%), TP53 (49.4%), SMAD4 (18.8%), and GNAS (17.2%). KRAS mutations were most frequent in MAd (68.4%) and Ad (58.9%), whereas TP53 mutations were mostly prevalent in Ad (62.6%). We classified patients into molecular subtypes based on the presence of mutations and analyzed differences in overall survival (OS) by molecular subtype. Patients with TP53-mutant (mut) dominant tumors (all TP53-mut) and KRAS-mut focused tumors (TP53-wild-type (wt)/GNAS-wt/KRAS-mut/any SMAD4) showed a poorer median OS compared with those with GNAS-mut focused tumors (TP53-wt/GNAS-mut/any KRAS /any SMAD4) (median 47.4 and 37.5 months vs. not reached; p = 0.01 and p = 0.01, respectively). TP53 mutation was associated with poor time to treatment failure and OS with the oxaliplatin-based regimen for first-line chemotherapy. CONCLUSIONS: This study suggested that the genetic mutations influenced the prognosis and chemotherapy efficacy in AC.

  3. Correlation between Efficacy and Cardiovascular Adverse Events in Patients with Advanced Solid Cancer Who Received VEGF Pathway Inhibitors: Hypertension within the First Eight Weeks Is Associated with Favorable Outcomes of Patients Treated with VEGF Pathway Inhibitors.

    Yuya Yoshida, Masanobu Takahashi, Keigo Komine, Sakura Taniguchi, Hideharu Yamada, Keiju Sasaki, Sho Umegaki, Yoshifumi Kawamura, Yuki Kasahara, Kota Ouchi, Hiroo Imai, Ken Saijo, Hidekazu Shirota, Noriko Takenaga, Chikashi Ishioka

    Internal medicine (Tokyo, Japan) 64 (2) 177-185 2025/01/15

    DOI: 10.2169/internalmedicine.3373-23  

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    Objective Many vascular endothelial growth factor (VEGF) pathway inhibitors are used in the treatment of patients with various advanced cancers; however, treatments induce cardiovascular adverse events (CVAEs), such as hypertension, heart failure, arrhythmia, arterial or venous embolism, and hemorrhage. Some studies have suggested a correlation between efficacy and CVAEs; however, further evidence is required. This study evaluated real-world data concerning the frequency and degree of CVAEs and possible associations between CVAEs and efficacy in such patients. Methods We analyzed CVAEs observed in 294 patients with advanced cancer who were treated with ramucirumab, regorafenib, pazopanib, sunitinib, or sorafenib. Results CVAEs of any grade and proteinuria within 8 weeks after the initiation of VEGF pathway inhibitors (early) or during the treatment period (total period) were observed in 72-85% and 77-92% of the patients, respectively. The progression-free survival (PFS) of patients with a CVAE of grade ≥1 in the early period was favorable compared with the PFS of those who had no CVAE (median, 4.9 vs. 3.5 months, p=0.016, log-rank test). Furthermore, the PFS of patients with a CVAE grade ≥3 in the early period was favorable compared to that of those with CVAEs of grades 0-2. Taken together, a higher degree of CVAE was correlated with favorable patient outcomes. Conclusion This study revealed the frequency and degree of CVAEs in patients with solid cancers who received VEGF pathway inhibitors in a real-world setting and added evidence regarding the correlation between CVAEs and efficacy of VEGF pathway inhibitors.

  4. Pretreatment neutrophil-lymphocyte ratio as a prognostic factor in recurrent/metastatic head and neck cancer treated with pembrolizumab. International-journal

    Yuki Kasahara, Ken Saijo, Reio Ueta, Ryunosuke Numakura, Keiju Sasaki, Yuya Yoshida, Sakura Taniguchi, Kota Ouchi, Keigo Komine, Hiroo Imai, Hidekazu Shirota, Masanobu Takahashi, Chikashi Ishioka

    Scientific reports 14 (1) 28255-28255 2024/11/16

    DOI: 10.1038/s41598-024-79130-7  

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    Pembrolizumab-containing regimens are the standard first-line treatment for recurrent/metastatic squamous cell carcinoma of the head and neck (R/M HNSCC). The neutrophil-to-lymphocyte ratio (NLR) and C-reactive protein-to-albumin ratio (CAR) have been reported to be important prognostic factors in a variety of carcinomas, but none have been investigated in combination with pembrolizumab and chemotherapy or in first-line treatment. Seventy-four patients with R/M HNSCC received pembrolizumab-containing regimens at Tohoku University Hospital, Sendai, Japan, from April 2020 to March 2023. Patient characteristics, tumor response, overall survival (OS), progression-free survival (PFS), and laboratory findings were reviewed. Associations between NLR, CAR, and survival outcomes were analyzed. The 1-year OS and 1-year PFS rates were 60.4% and 18.1%, respectively. The disease control rate was 66.2%. In multivariate analysis, low NLR (< 5) was significantly associated with better OS and PFS. NLR may be a predictive factor for OS and PFS in patients with R/M HNSCC treated with a pembrolizumab-containing regimen.

  5. Tretinoin synergistically enhances the antitumor effect of combined BRAF, MEK, and EGFR inhibition in BRAFV600E colorectal cancer. International-journal

    Yuya Yoshida, Masanobu Takahashi, Sakura Taniguchi, Ryunosuke Numakura, Keigo Komine, Chikashi Ishioka

    Cancer science 115 (11) 3740-3754 2024/11

    DOI: 10.1111/cas.16280  

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    Patients with BRAF-mutated colorectal cancer (BRAFV600E CRC) are currently treated with a combination of BRAF inhibitor and anti-EGFR antibody with or without MEK inhibitor. A fundamental problem in treating patients with BRAFV600E CRC is intrinsic and/or acquired resistance to this combination therapy. By screening 78 compounds, we identified tretinoin, a retinoid, as a compound that synergistically enhances the antiproliferative effect of a combination of BRAF inhibition and MEK inhibition with or without EGFR inhibition on BRAFV600E CRC cells. This synergistic effect was also exerted by other retinoids. Tretinoin, added to BRAF inhibitor and MEK inhibitor, upregulated PARP, BAK, and p-H2AX. When either RARα or RXRα was silenced, the increase in cleaved PARP expression by the addition of TRE to ENC/BIN or ENC/BIN/CET was canceled. Our results suggest that the mechanism of the synergistic antiproliferative effect involves modulation of the Bcl-2 family and the DNA damage response that affects apoptotic pathways, and this synergistic effect is induced by RARα- or RXRα-mediated apoptosis. Tretinoin also enhanced the antitumor effect of a combination of the BRAF inhibitor and anti-EGFR antibody with or without MEK inhibitor in a BRAFV600E CRC xenograft mouse model. Our data provide a rationale for developing retinoids as a new combination agent to overcome resistance to the combination therapy for patients with BRAFV600E CRC.

  6. Nivolumab-induced Thrombotic Thrombocytopenic Purpura in Patients with Gastric Tube Cancer.

    Yuya Yoshida, Sakura Toriyabe, Hiroo Imai, Keiju Sasaki, Yuki Kasahara, Kota Ouchi, Ken Saijo, Koichi Onodera, Chikashi Ishioka

    Internal medicine (Tokyo, Japan) 63 (19) 2667-2671 2024/10/01

    DOI: 10.2169/internalmedicine.2931-23  

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    Recently, immune checkpoint inhibitors (ICIs) have been used to treat several cancer types. ICIs have been reported to cause a wide variety of immune-related adverse events, including endocrine, neurologic, gastrointestinal, and cutaneous disorders. Thrombotic thrombocytopenic purpura (TTP) is an autoimmune hematologic disorder characterized by the presence of autoantibodies against a disintegrin and metalloprotease with thrombospondin-1, member 13. Several previous cases of TTP were thought to have been caused by ICI treatment. We herein report a rare case of TTP that developed after long-term treatment with an ICI (nivolumab) for gastric tube cancer.

  7. Genome-wide DNA methylation status is a predictor of the efficacy of anti-EGFR antibodies in the second-line treatment of metastatic colorectal cancer: Translational research of the EPIC trial. International-journal

    Kota Ouchi, Shin Takahashi, Keiju Sasaki, Yuya Yoshida, Sakura Taniguchi, Yuki Kasahara, Keigo Komine, Hiroo Imai, Ken Saijo, Hidekazu Shirota, Masanobu Takahashi, Chikashi Ishioka

    International journal of colorectal disease 39 (1) 89-89 2024/06/11

    DOI: 10.1007/s00384-024-04659-y  

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    PURPOSE: The genome-wide DNA methylation status (GWMS) predicts of therapeutic response to anti-epidermal growth factor receptor (EGFR) antibodies in treating metastatic colorectal cancer. We verified the significance of GWMS as a predictive factor for the efficacy of anti-EGFR antibodies in the second-line treatment of metastatic colorectal cancer. METHODS: Clinical data were obtained from a prospective trial database, and a genome-wide DNA methylation analysis was performed. GWMS was classified into high-methylated colorectal cancer (HMCC) and low-methylated colorectal cancer (LMCC). The patients were divided into subgroups according to the treatment arm (cetuximab plus irinotecan or irinotecan alone) and GWMS, and the clinical outcomes were compared between the subgroups. RESULTS: Of the 112 patients, 58 (51.8%) were in the cetuximab plus irinotecan arm, and 54 (48.2%) were in the irinotecan arm; 47 (42.0%) were in the HMCC, and 65 (58.0%) were in the LMCC group regarding GWMS. Compared with the LMCC group, the progression-free survival (PFS) was significantly shortened in the HMCC group in the cetuximab plus irinotecan arm (median 1.4 vs. 4.1 months, p = 0.001, hazard ratio = 2.56), whereas no significant differences were observed in the irinotecan arm. A multivariate analysis showed that GWMS was an independent predictor of PFS and overall survival (OS) in the cetuximab plus irinotecan arm (p = 0.002, p = 0.005, respectively), whereas GWMS did not contribute to either PFS or OS in the irinotecan arm. CONCLUSIONS: GWMS was a predictive factor for the efficacy of anti-EGFR antibodies in the second-line treatment of metastatic colorectal cancer.

  8. Chylous Ascites Associated with Advanced Pancreatic Cancer That Improved with Appropriate Treatment: A Case Report. International-journal

    Hiroo Imai, Ken Saijo, Noriko Takenaga, Keigo Komine, Kota Ouchi, Yuki Kasahara, Shiori Ishikawa, Keiju Sasaki, Yuya Yoshida, Hidekazu Shirota, Masanobu Takahashi, Chikashi Ishioka

    Current oncology (Toronto, Ont.) 31 (3) 1477-1482 2024/03/12

    DOI: 10.3390/curroncol31030112  

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    Chylous ascites is a rare form of ascites with high triglyceride content arising from the thoracoabdominal lymph nodes in the peritoneal cavity due to various benign or malignant etiologies, including pancreatic cancer. During cancer chemotherapy, the accumulation of ascites can lead to the deterioration of the patient's general condition, making chemotherapy administration difficult, and resulting in a poor prognosis. We encountered a rare case of chylous ascites complicated by advanced pancreatic cancer. The patient presented with a discrepancy between the shrinkage of the pancreatic cancer and the accumulation of ascites. Therefore, we were able to promptly diagnose chylous ascites by performing biochemical tests. The patient was treated with octreotide, reportedly effective in treating chylous ascites, which rapidly improved the chylous ascites and general condition of the patient, allowing the patient to continue chemotherapy for pancreatic cancer. Therefore, physicians should consider the possibility of chylous ascites when clinically unexplained ascites are observed in patients with advanced cancer. The investigation and treatment of chylous ascites should be initiated as soon as possible.

  9. Antibiotics May Interfere with Nivolumab Efficacy in Patients with Head and Neck Squamous Cell Carcinoma. International-journal

    Reio Ueta, Hiroo Imai, Ken Saijo, Yoshifumi Kawamura, Shuto Kodera, Keigo Komine, Kota Ouchi, Yuki Kasahara, Sakura Taniguchi, Yuya Yoshida, Keiju Sasaki, Hidekazu Shirota, Masanobu Takahashi, Chikashi Ishioka

    Oncology 102 (3) 252-259 2024

    DOI: 10.1159/000533860  

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    INTRODUCTION: Patients with the head and neck squamous cell carcinoma (SCC) are often treated with immune checkpoint inhibitors (ICIs). Recently, antibiotic intake was reported to lower the efficacy of ICIs in patients with several types of cancers. However, it is unclear if antibiotics affect the efficacy of ICIs in patients with head and neck SCC. We retrospectively assessed the influence of antibiotics on the treatment efficacy of nivolumab, an ICI, in patients with head and neck SCC. METHODS: We reviewed the medical records of patients with head and neck SCC treated with nivolumab at the Department of Medical Oncology, Tohoku University Hospital, between 2017 and 2021. Patients who received oral or intravenous antibiotics from a month before the day of nivolumab initiation to the day of the first imaging evaluation of ICI efficacy were assigned to the antibiotic-treated group. The remaining patients were assigned to the antibiotic-untreated group. The response rate (RR), progression-free survival (PFS), and overall survival time (OS) of both groups were compared. RESULTS: Forty-five patients were assigned to the antibiotic-treated group and 19 to the antibiotic-untreated group. The RR, median PFS, and median OS of the antibiotic-treated group were 23.7%, 3.2 months (95% confidential interval [CI]: 2.0-4.1), and 8.4 months (95% CI: 5.3-15.1) and those of the antibiotic-untreated group were 42.1%, 5.8 months (95% CI: 2.3-16.7), and 18.4 months (95% CI: 6.2-23.1), respectively. The PFS of the antibiotic-untreated group was significantly longer than that of the antibiotic-treated group. CONCLUSION: Our findings indicate that antibiotic treatment significantly shortens the PFS with nivolumab therapy in patients with head and neck SCC.

  10. FOLFIRI Chemotherapy for Patients With Metastatic Urachal Carcinoma. International-journal

    Sakura Hiraide Taniguchi, Keigo Komine, Noriko Takenaga, Yuya Yoshida, Keiju Sasaki, Yoshifumi Kawamura, Yuki Kasahara, Kota Ouchi, Hiroo Imai, Ken Saijo, Hidekazu Shirota, Masanobu Takahashi, Chikashi Ishioka

    Anticancer research 43 (12) 5699-5704 2023/12

    DOI: 10.21873/anticanres.16775  

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    BACKGROUND/AIM: Urachal carcinoma is a rare cancer, with limited evidence regarding systemic chemotherapy for metastatic urachal carcinoma. This study aimed to evaluate the efficacy and safety of a combination therapy of 5-fluorouracil and irinotecan (FOLFIRI) in patients with metastatic urachal carcinoma. PATIENTS AND METHODS: Patients with metastatic urachal carcinoma treated with FOLFIRI between March 2008 and April 2023 at the Department of Medical Oncology, Tohoku University Hospital, were retrospectively analyzed using medical records. RESULTS: Six patients with urachal carcinoma received FOLFIRI. The histological type was adenocarcinoma in all patients. The metastatic or recurrent sites were the peritoneum, lungs, lymph nodes, and local relapse sites. Three patients received FOLFIRI as first-line chemotherapy, and the other three received FOLFIRI as second-line chemotherapy. Two patients had only non-measurable lesions as the targets of tumor response. The best response was the stable disease or non-complete response/non-progressive disease in four patients, with a disease control rate of 67%. The median progression-free survival was 7.5 months. In two patients with ascites only as the site of metastasis, the amount of ascites and serum tumor marker levels decreased after FOLFIRI was initiated. Grade 3/4 toxicities included grade 3 neutropenia in one patient and grade 3 diarrhea in one patient. CONCLUSION: FOLFIRI has modest efficacy and good tolerability for the treatment of metastatic urachal carcinoma.

  11. Depth of response may predict clinical outcome in patients with recurrent/metastatic head and neck cancer treated with pembrolizumab-containing regimens. International-journal

    Ken Saijo, Hiroo Imai, Kota Ouchi, Keiju Sasaki, Yuya Yoshida, Yoshifumi Kawamura, Sakura Taniguchi, Yuki Kasahara, Keigo Komine, Hidekazu Shirota, Masanobu Takahashi, Chikashi Ishioka

    Frontiers in oncology 13 1230731-1230731 2023

    DOI: 10.3389/fonc.2023.1230731  

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    BACKGROUND: Pembrolizumab-containing regimens are standards of care for recurrent and metastatic head and neck squamous cell carcinoma (R/M HNSCC). The depth of response (DpR) predicts the survival of patients with several types of solid cancers; however, its association with the survival outcomes of patients with R/M HNSCC treated with pembrolizumab-containing regimens remains unclear. METHODS: This study included 66 patients with R/M HNSCC who received a pemblolizumab-containing regimen as a first-line therapy at Tohoku University Hospital, Sendai, Japan. The patients' characteristics, combined positive score, baseline tumor size, tumor response, DpR, overall survival (OS), progression-free survival (PFS), PFS2, and adverse events were reviewed. The associations between DpR and survival outcomes were analyzed. RESULTS: The 1 year-OS and 1 year-PFS rates of pembrolizumab-containing regimens were 69.4% and 24.4%, respectively. The response rate was 28.8%. The mean and median values of tumor change from baseline were 5.1% and -9.0%. In the correlation analysis, a significant negative correlation was observed between tumor change rate from baseline and survival outcomes (OS: r= -0.41, p=0.0017; PFS: r=-0.49, p<0.001). In the multivariate analysis, DpR with tumor change of ≤-45 was associated with better OS and PFS. CONCLUSION: DpR induced by pembrolizumab-containing regimens may be a predictive factor for OS and PFS in patients with R/M HNSCC.

  12. Tumor suppressor miR-193a-3p enhances efficacy of BRAF/MEK inhibitors in BRAF-mutated colorectal cancer

    Sakura Hiraide, Masanobu Takahashi, Yuya Yoshida, Hideharu Yamada, Keigo Komine, Chikashi Ishioka

    Cancer Science 112 (9) 3856-3870 2021

    DOI: 10.1111/cas.15075  

    ISSN: 1347-9032

    eISSN: 1349-7006

  13. Antibiotics Improve the Treatment Efficacy of Oxaliplatin-Based but Not Irinotecan-Based Therapy in Advanced Colorectal Cancer Patients. International-journal

    Hiroo Imai, Ken Saijo, Keigo Komine, Yuya Yoshida, Keiju Sasaki, Asako Suzuki, Kota Ouchi, Masahiro Takahashi, Shin Takahashi, Hidekazu Shirota, Masanobu Takahashi, Chikashi Ishioka

    Journal of oncology 2020 1701326-1701326 2020

    DOI: 10.1155/2020/1701326  

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    BACKGROUND: Oxaliplatin and irinotecan are generally used to treat advanced colorectal cancer (CRC) patients. Antibiotics improve the cytotoxicity of oxaliplatin but not irinotecan in a colon cancer cell line in vitro. This study retrospectively assessed whether antibiotics improve the treatment efficacy of oxaliplatin- but not irinotecan-based therapy in advanced CRC patients. Patients and Methods. The medical records of 220 advanced CRC patients who underwent oxaliplatin- or irinotecan-based therapy were retrospectively reviewed. The oxaliplatin and irinotecan groups were further divided into antibiotic-treated (group 1) and antibiotic-untreated (group 2) subgroups. RESULTS: In oxaliplatin groups 1 and 2, the response rate (RR) was 58.2% and 30.2%, while the disease control rate (DCR) was 92.5% and 64.2%, respectively; the median progression-free survival (PFS) was 10.5 months (95% confidence interval (CI) = 7.5-12.2) and 7.0 months (95% CI = 17.0-26.0), respectively, and the median overall survival (OS) was 23.8 months (95% CI = 5.1-9.1) and 17.4 months (95% CI = 13.1-24.9), respectively. In irinotecan groups 1 and 2, the RR was 17.8% and 20.0%, while the DCR was 75.6% and 69.1%, respectively; the median PFS was 8.2 months (95% CI = 6.2-12.7) and 7.9 months (95% CI = 12.0-23.0), respectively, and the median OS was 16.8 months (95% CI = 5.9-10.6) and 13.1 months (95% CI = 10.4-23.7), respectively. CONCLUSION: To improve the treatment efficacy of oxaliplatin-based therapy in advanced CRC patients, adding antibiotics is a potential therapeutic option.

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