# Mutational Signature Changes in Patients With Metastatic Squamous Cell Carcinoma of the Anal Canal

## TL;DR

This study shows that mutations in cancer DNA circulating in the blood can change after treatment in anal canal cancer patients, suggesting ctDNA can track tumor evolution.

## Contribution

The study demonstrates temporal mutational heterogeneity in metastatic SCCA and highlights ctDNA's potential for real-time tracking of tumor evolution during therapy.

## Key findings

- 34.5% of posttreatment ctDNA mutations were also found in pretreatment tumor tissue.
- 47.6% of pretreatment tumor tissue mutations were detected in posttreatment ctDNA.
- Seven patients had new mutations in ctDNA not present in pretreatment tissue.

## Abstract

We examined the concordance of genetic mutations between pretreatment tumor tissue and posttreatment circulating tumor DNA (ctDNA) in patients with metastatic squamous cell carcinoma of the anal canal (SCCA) and assessed the impact of therapy on this concordance.

We analyzed next-generation sequencing reports from pretreatment tumor tissue and posttreatment ctDNA in 11 patients with metastatic SCCA treated at Vanderbilt University Medical Center between 2017 and 2021.

Among the mutations identified in posttreatment ctDNA, 34.5% were also found in pretreatment tumor tissue, while 47.6% of pretreatment tumor tissue mutations were found in posttreatment ctDNA. Four patients had preservation of potentially actionable mutations in both pretreatment tissue and posttreatment ctDNA, while 7 patients had newly identified mutations in posttreatment ctDNA that were not present in pretreatment tumor tissue.

Patients with SCCA demonstrate a high degree of temporal mutational heterogeneity. This supports the hypothesis that ctDNA can serve as a real-time tracking mechanism for solid tumors’ molecular evolution in response to therapy. Our findings highlight the potential of ctDNA in identifying emerging actionable mutations, supplementing information from tissue-based genomic assessments. Further research, ideally with larger and multi-institutional cohorts, is needed to validate our findings in this relatively rare tumor type.

This study aimed to describe how tissue-based and ctDNA-based mutational concordance, as identified by next-generation sequencing, is affected by chemoradiation and systemic therapy in the context of patients’ unique clinicodemographic features.