# Impact of Bone Metastases and Actionable Genetic Alterations in Biliary Tract Cancer

## TL;DR

This study found that bone metastases in biliary tract cancer do not affect survival, and targeted treatments for genetic changes significantly improve outcomes.

## Contribution

The study is the first to show that bone metastases in biliary tract cancer do not impact survival and that targeted therapies for genetic alterations significantly improve survival.

## Key findings

- Bone metastases in biliary tract cancer do not influence overall survival.
- Patients with actionable genetic alterations and matched targeted treatments had a median survival of 29.9 months.
- Actionable genetic alterations were equally common in patients with and without bone metastases.

## Abstract

We know little about how common bone metastases (cancer spreading to bones from its original site) are in biliary tract cancers (BTC), or if they are more common in some BTC types compared to others. To learn more, we reviewed the medical notes of 197 patients with BTC treated in a large UK cancer centre. We studied details of patients’ BTCs, if they had bone metastases, and how they responded to treatment. In patients with incurable BTC, we found no difference in survival for patients with bone metastases compared to those without. Patients with special cancer-related genetic alterations (called ‘actionable alterations’) were just as likely to have bone metastases than those without, and with similar survival rates. When targeting these alterations with matched anti-cancer treatments, over 50% of patients had a survival of over 29.9 months since their cancer diagnosis, which is longer than that reported in many other studies.

Background: Bone metastasis (BM) prevalence is underreported in biliary tract cancers (BTC). This study aimed to assess BM prevalence in a real-world BTC population, alongside examining its relationship to prognosis and genomic alterations. Methods: Patients with histology-proven BTC as reviewed at a university cancer centre between January 2019 and August 2022 were assessed. Data extracted from records included BTC subtype, molecular profiling and systemic anti-cancer therapy (SACT) use. Stratification by BTC subtype and metastasis sites occurred. Median overall survival (mOS) was defined as time from relapse or metastases to death. Survival analysis was conducted using the Cox Proportional Hazard model. Results: Of 197 patients, 74 (37.6%) had intrahepatic and 67 (34%) had extrahepatic cholangiocarcinoma. Thirty-four patients had BM (17.3%), with 14 identified at initial diagnosis. OS was not influenced by bone (HR 1.15; p = 0.48) or liver metastases (HR 1.09; p = 0.6). Stratifying for age and gender, no significant difference in OS was observed. Actionable alterations were equally likely in patients with (52.4%) and without BM (58.5%). Age of BTC onset (<65 or ≥65) did not significantly influence prevalence of actionable alterations. Patients receiving matched, targeted SACT had a mOS of 29.9 months, compared to 13.3 months in those with actionable alterations but no SACT matching (HR 0.35; p < 0.005). Conclusions: In advanced BTC, BM do not affect OS. Across all cohorts, actionable alterations improved OS when treated with matched SACT.