Antibiotics Significantly Decrease the Survival of Head and Neck Carcinoma Patients with Immunotherapy: A Real-World Analysis of More Than 3000 Cases
Objective: The human gut microbiome is strongly influenced by the administration of drugs, namely antibiotics. We hypothesized that the effectiveness of immunotherapy with pembrolizumab in oral squamous cell carcinoma patients is decreased by the administration of antibiotics three months before and...
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MDPI AG
2023-04-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/15/8/2342 |
| _version_ | 1811153801278652416 |
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| author | Saskia Preissner Max Heiland Robert Preissner Markus Wirth Barbara Wollenberg |
| author_facet | Saskia Preissner Max Heiland Robert Preissner Markus Wirth Barbara Wollenberg |
| author_sort | Saskia Preissner |
| collection | DOAJ |
| description | Objective: The human gut microbiome is strongly influenced by the administration of drugs, namely antibiotics. We hypothesized that the effectiveness of immunotherapy with pembrolizumab in oral squamous cell carcinoma patients is decreased by the administration of antibiotics three months before and after immunotherapy. Methods: We retrieved data from patients diagnosed with head and neck squamous cell carcinoma (HNSCC) (International Classification of Diseases [ICD]-10 codes C00-C14) and receiving immunotherapy with pembrolizumab from the TriNetX network. Two cohorts were built: patients in cohort I did not receive any antibiotics within three months before or up to three months after immunotherapy, while patients in cohort II were administered antibiotics at least once within three months before or after immunotherapy. To exclude confounders, we matched cohorts 1:1 for age, sex, secondary lymph node metastases, nicotine dependence, the insertion of feeding devices, body mass index (BMI) and severe sepsis. After defining the primary outcome as “death”, a Kaplan–Meier analysis was performed, and the risk ratio (RR), odds ratio (OR) and hazard ratio (HR) were calculated. Results: A total of 3651 patients were enrolled, and after matching, each cohort consisted of 1362 patients. Among cohorts I and II, 346 and 511 patients were deceased within one year (risk of death = 25.5 and 38.3%, respectively), whereby the risk difference was significant (<i>p</i> = 0.000; log-rank test). The RR was 0.68 (95% confidence interval: 0.60–0.76), OR was 0.57 (0.48–0.67) and HR was 0.58 (0.51–0.67). Conclusions: Our hypothesis was confirmed: administering antibiotics significantly decreases the drug effectiveness of immunotherapy. We hypothesize that this finding is associated with antibiotic-related changes in the gut microbiome. Prospective clinical studies on the gut microbiome in cancer patients are necessary to understand the complex ecosystem of microbiota during immunotherapy. Trial Registration: Due to the retrospective nature of the study, no registration was necessary. |
| first_indexed | 2024-03-11T05:10:13Z |
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| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-11T05:10:13Z |
| publishDate | 2023-04-01 |
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| series | Cancers |
| spelling | doaj.art-8b4d1ecf82344df6b4bd670cdfd75a5f2023-11-17T18:39:39ZengMDPI AGCancers2072-66942023-04-01158234210.3390/cancers15082342Antibiotics Significantly Decrease the Survival of Head and Neck Carcinoma Patients with Immunotherapy: A Real-World Analysis of More Than 3000 CasesSaskia Preissner0Max Heiland1Robert Preissner2Markus Wirth3Barbara Wollenberg4Department of Oral and Maxillofacial Surgery, Charité—Universitätsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, GermanyDepartment of Oral and Maxillofacial Surgery, Charité—Universitätsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, GermanyInstitute of Physiology and Science-IT, Charité—Universitätsmedizin Berlin, Philippstr. 12, 10115 Berlin, GermanyClinic for Otorhinolaryngology, Head and Neck Surgery, Klinikum Rechts der Isar der Technischen Universität München (MRI TUM), Ismaningerstr. 22, 81675 Munich, GermanyClinic for Otorhinolaryngology, Head and Neck Surgery, Klinikum Rechts der Isar der Technischen Universität München (MRI TUM), Ismaningerstr. 22, 81675 Munich, GermanyObjective: The human gut microbiome is strongly influenced by the administration of drugs, namely antibiotics. We hypothesized that the effectiveness of immunotherapy with pembrolizumab in oral squamous cell carcinoma patients is decreased by the administration of antibiotics three months before and after immunotherapy. Methods: We retrieved data from patients diagnosed with head and neck squamous cell carcinoma (HNSCC) (International Classification of Diseases [ICD]-10 codes C00-C14) and receiving immunotherapy with pembrolizumab from the TriNetX network. Two cohorts were built: patients in cohort I did not receive any antibiotics within three months before or up to three months after immunotherapy, while patients in cohort II were administered antibiotics at least once within three months before or after immunotherapy. To exclude confounders, we matched cohorts 1:1 for age, sex, secondary lymph node metastases, nicotine dependence, the insertion of feeding devices, body mass index (BMI) and severe sepsis. After defining the primary outcome as “death”, a Kaplan–Meier analysis was performed, and the risk ratio (RR), odds ratio (OR) and hazard ratio (HR) were calculated. Results: A total of 3651 patients were enrolled, and after matching, each cohort consisted of 1362 patients. Among cohorts I and II, 346 and 511 patients were deceased within one year (risk of death = 25.5 and 38.3%, respectively), whereby the risk difference was significant (<i>p</i> = 0.000; log-rank test). The RR was 0.68 (95% confidence interval: 0.60–0.76), OR was 0.57 (0.48–0.67) and HR was 0.58 (0.51–0.67). Conclusions: Our hypothesis was confirmed: administering antibiotics significantly decreases the drug effectiveness of immunotherapy. We hypothesize that this finding is associated with antibiotic-related changes in the gut microbiome. Prospective clinical studies on the gut microbiome in cancer patients are necessary to understand the complex ecosystem of microbiota during immunotherapy. Trial Registration: Due to the retrospective nature of the study, no registration was necessary.https://www.mdpi.com/2072-6694/15/8/2342oral squamous cell carcinomaoral cancerimmunotherapypembrolizumabantibioticsgut microbiome |
| spellingShingle | Saskia Preissner Max Heiland Robert Preissner Markus Wirth Barbara Wollenberg Antibiotics Significantly Decrease the Survival of Head and Neck Carcinoma Patients with Immunotherapy: A Real-World Analysis of More Than 3000 Cases Cancers oral squamous cell carcinoma oral cancer immunotherapy pembrolizumab antibiotics gut microbiome |
| title | Antibiotics Significantly Decrease the Survival of Head and Neck Carcinoma Patients with Immunotherapy: A Real-World Analysis of More Than 3000 Cases |
| title_full | Antibiotics Significantly Decrease the Survival of Head and Neck Carcinoma Patients with Immunotherapy: A Real-World Analysis of More Than 3000 Cases |
| title_fullStr | Antibiotics Significantly Decrease the Survival of Head and Neck Carcinoma Patients with Immunotherapy: A Real-World Analysis of More Than 3000 Cases |
| title_full_unstemmed | Antibiotics Significantly Decrease the Survival of Head and Neck Carcinoma Patients with Immunotherapy: A Real-World Analysis of More Than 3000 Cases |
| title_short | Antibiotics Significantly Decrease the Survival of Head and Neck Carcinoma Patients with Immunotherapy: A Real-World Analysis of More Than 3000 Cases |
| title_sort | antibiotics significantly decrease the survival of head and neck carcinoma patients with immunotherapy a real world analysis of more than 3000 cases |
| topic | oral squamous cell carcinoma oral cancer immunotherapy pembrolizumab antibiotics gut microbiome |
| url | https://www.mdpi.com/2072-6694/15/8/2342 |
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