# ctDNA guided management of POLE mutant GI malignancies promotes exceptional responses and prolonged survival to immunotherapy

## TL;DR

Using ctDNA to identify rare POLE mutations in GI cancers helps select patients who respond well to immunotherapy, leading to improved survival.

## Contribution

Demonstrates the clinical utility of ctDNA-guided selection for immunotherapy in POLE-mutant GI malignancies.

## Key findings

- ctDNA-guided management led to complete metabolic and radiologic responses in POLE-mutant GI cancer patients.
- All three patients treated with immunotherapy based on ctDNA results showed extended survival.
- The study supports using liquid biopsies and multidisciplinary teams to personalize treatment for GI cancers.

## Abstract

Patients with unresectable Gastrointestinal cancers (GI) including advanced colorectal cancer (CRC) and gall bladder cancer (GBC) have limited treatment options. Treatment with chemotherapy is associated with limited success resulting from therapeutic resistance. Immune checkpoint inhibitors are effective for a subset of metastatic CRC (5% with MSI-H status) and up to 30% of patients with GBC. Therefore, there is an urgent unmet need to discover new predictive biomarkers to aid patient selection for ICIs with a demonstrated clinical value in a challenging patient population. We highlight the utility of a liquid biopsy approach to aid selection of GI cancer patients harbouring rare POLE mutations for immunotherapy, leading to complete metabolic response in addition to radiologic responses and extended survival in all three patients. This study advocates for specialised multi-disciplinary teams performing shared clinical decision making to advance personalised care and improve outcomes of a subset of GI cancer patients with a poor prognosis.