901P - Gut microbiome metagenomics and toxicity outcomes from chemoradiation therapy in head and neck squamous cell carcinoma

Background

Chemoradiation (CRT) in patients (pts) with locally advanced head and neck squamous cell cancer (HNSCC) is associated with significant toxicities, including oral mucositis (OM). The gut microbiome (GM) is an emerging biomarker of treatment outcomes and adverse events. This study aimed to investigate the role of GM composition to predict CRT toxicities in HNSCC pts, including development of severe OM.

Methods

We prospectively collected fecal samples of 52 pts with HNSCC undergoing CRT. Using shotgun metagenomic sequencing and MetaPhlAn4 pipeline, LefSe differences in GM composition at baseline were assessed according to CTCAE v4.0 toxicity grading including OM and enteral feeding tube requirement. Overall survival (OS) and progression-free survival (PFS) were estimated using the Kaplan-Meier method.

Results

Most tumors (n=40) were p16-positive, including oropharyngeal (n=35) and unknown primaries (n=4). TNM staging was III-IV in 54% (n=28). After a median follow-up of 27 mo, the 12-mo OS and PFS were 96% and 84%, respectively. In terms of toxicity, OM was seen in all pts, and 22 pts (42%) developed grade ≥3 OM. Thirteen pts (25%) required enteral feeding. Grade ≥3 OM was associated with a significant decrease in OS (p=0.02) even when accounting for staging and p16 status in multivariate analysis (MVA; p<0.05), as well as a numerically shorter PFS (p=0.09). No baseline characteristic correlated with increased risk of severe OM in MVA. However, GM beta-diversity differed between grade 1-2 and grade 3 OM (PERMANOVA p=0.04) but there was no difference in alpha-diversity. Pts with severe OM had distinct GM enriched with Mediterraneibacter (Ruminococcus gnavus) and members of the Clostridiaceae family, including Hungatella hathewayi. In pts with mild OM, Eubacterium rectale, Alistipes putredinis and members of the Ruminococcaceae family were overrepresented. We observed similar microbiome differences in pts requiring enteral feeding.

Conclusions

Severe OM was associated with decreased OS and PFS in pts with HNSCC undergoing CRT. Pts who developed severe OM or required enteral feeding had a distinct GM enriched with deleterious bacteria that have been associated with resistance to immune checkpoint inhibitors.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Oncobiome grant #825410.

Disclosure

All authors have declared no conflicts of interest.