TOPLINE:

Among patients with head and neck squamous cell carcinoma (HNSCC) undergoing chemoradiotherapy, higher baseline salivary Lachnoanaerobaculum abundance was associated with substantially improved locoregional recurrence-free and overall survival. 

METHODOLOGY:

• The oral microbiome, consisting of bacteria, viruses, fungi, and archaea, may influence both HNSCC progression and response to chemoradiotherapy. However, no specific oral microbiome biomarkers have been consistently linked to tumor control or survival among patients undergoing treatment.
• To identify microbiome signatures predictive of outcomes, researchers analyzed saliva samples from 92 patients with HNSCC (mean age, 61 years; 83.7% men) enrolled in two prospective biomarker studies. All patients underwent definitive chemoradiotherapy. Baseline oral microbiome composition was analyzed through 16S ribosomal RNA gene sequencing. To explore potential mechanisms, the researchers evaluated tumor-infiltrating lymphocytes in pretreatment biopsy specimens via immunohistochemistry.
• Locoregional recurrence-free survival was the primary outcome and overall survival was a secondary outcome. The findings were further assessed using data from The Cancer Microbiome Atlas and The Cancer Genome Atlas cohorts.
• Overall, 51% of the participants had died and 49% were alive at the last follow-up; locoregional recurrence occurred in 30% (n = 28) of the participants, and 70% (n = 64) remained recurrence-free.

TAKEAWAY:

• Overall, greater abundance of oral Lachnoanaerobaculum bacteria was associated with significantly improved outcomes. Compared with patients with salivary Lachnoanaerobaculum below the median, those with levels above the median had longer locoregional recurrence-free survival (median, 69 months vs 11 months; hazard ratio [HR], 0.50) and overall survival (median, 75 months vs 27 months; HR, 0.54).
• Analysis of tumor-infiltrating lymphocytes showed that high Lachnoanaerobaculum abundance correlated with increased numbers of CD8-positive and CD4-positive lymphocytes — suggesting immunomodulatory effects that may enhance chemoradiotherapy efficacy, the authors wrote. Data from The Cancer Genome Atlas further supported an “immune-activated” tumor microenvironment in the presence of greater of intra-tumor Lachnoanaerobaculum abundance.
• In The Cancer Microbiome Atlas, which included 157 patients with HNSCC, intra-tumor Lachnoanaerobaculum abundance showed a strong correlation with survival: Median overall survival was 71 months among patients with above-median abundance of Lachnoanaerobaculum vs 36 months among patients with below-median abundance (HR, 0.62).
• Salivary Lachnoanaerobaculum levels were not associated with the occurrence, timing, or radiation dose threshold of severe radiation-induced oral mucositis.

IN PRACTICE:

"The association between [Lachnoanaerobaculum]abundance and treatment outcomes lays the groundwork for further research into microbiome-targeted interventions aimed at enhancing chemoradiotherapy responses in HNSCC," the authors wrote. A next step, they noted, is to investigate whether specific species of the bacterium are associated with an immune-stimulated tumor microenvironment.

SOURCE:

The study, led by Alexander Rühle, MD, MHBA, Medical Center-University of Freiburg, Freiburg, Germany, was published online in JAMA Otolaryngology-Head & Neck Surgery.

LIMITATIONS:

The study did not analyze longitudinal changes in the saliva microbiome during treatment, which may offer better prognostic insights. The small cohort size precluded subgroup assessments, including the prognostic value of Lachnoanaerobaculum among patients with p16 ‐ positive oropharyngeal cancer. A low events-per-variable ratio in multivariable models raised concerns of overfitting, potentially affecting the reliability of the estimated hazard ratios.

DISCLOSURES:

This study received funding from the Stiftung Tumorforschung Kopf-Hals. Rühle reported receiving grants from Stiftung Tumorforschung Kopf-Hals during the study period and personal fees from AstraZeneca, Merck, Novocure, Johnson & Johnson, and Need Inc, as well as grants and support from Novocure outside the submitted work. Several authors reported financial ties with various sources. Full disclosures are noted in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.