Integrating genomic testing into Biliary Tract Cancer management (BTC) pathway

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This project aims to steer uptake of genomic testing, monitoring and driving targeted chemotherapy informed by genomic testing in the Biliary Tract Cancer management (BTC) pathway at Nottingham University Hospitals (NUH) NHS Trust.

What have we done?

A team at Nottingham University Hospitals (NUH) NHS Trust, on behalf of the East Midlands region, have:

collected/audited the past 2-3 years of genomic data on BTC patients who received palliative chemotherapy,
established a standard regional BTC pathway to drive widespread adoption and acceptance of genomic testing among hepato-bilary (HPB) MDTs
disseminated information through organising a regional teaching event.

Why did we undertake this project?

Biliary Tract Cancer, a rare cancer of unmet need with limited treatment options and poor prognosis, poses significant challenges, and the NHS mission is to leverage cutting-edge genomics to tailor treatment strategies.

NICE recommends Larotrectinib for treating NTRK fusion-positive solid tumours (27 May 2020), Pemigatinib for relapsed or refractory advanced cholangiocarcinoma with FGFR2 fusion or rearrangement (25 Aug 2021), Pembrolizumab for previously treated biliary cancer with high microsatellite instability or mismatch repair deficiency (20th Sep 2023) and Ivosidenib as an option for treating locally advanced/ metastatic cholangiocarcinoma with an IDH1 R132 mutation in adults after 1 or more systemic treatments (14 Dec 2023).

Targeted therapies optimise efficacy and minimise side-effects. These tests are now done in-house at NUH.

This project will be a transformative step towards precision medicine in BTC care, improving patient outcomes by integration of genomics into BTC management pathway.

Who have we worked with?

Our goal was to ensure regional HPB teams are committed to advancing cancer care and recognise the transformative potential of genomic testing in personalised medicine.

The NUH-based team that delivered this project included:

Project Lead, Arvind Arora,
East GMSA Medical Lead, Guru Aithal
HPB MDT Lead, Suresh Venkatachalapathy
Pathology GLH lead, Tom Mcculloch
Data collectors/analysts (Oncology SpR)
Regional HPB Oncologists, Sean Dulloo and Catherine Shankland
Senior Pharmacist, Emma Dring

Project outputs

Production of a new BTC Pathway for the East Midlands
Analysis of retrospective BTC data completed
Held a Regional Educational Event to share project findings and outputs

Conclusions on integrating Genomic Testing into BTC management

The project highlights significant gaps in the current genomic testing practices for BTC patients and provides a roadmap for integrating these tests into standard care.

Through educational initiatives, standardized pathways, and ongoing audits, the adoption of genomic testing can be improved, leading to more personalized and effective treatments for BTC patients.

Suboptimal uptake in the past 3 years may be due to reasons including:

drugs were only approved recently (e.g. Ivosidenib was approved in December 2023 for IDH1 mutated BTC and Pembrolizumab in September 2023 for MSI-H BTC)
drugs indicated only in second line setting
insufficient tissue available for testing in some cases; and
deterioration in Performance status of patients post first line therapy making them unsuitable for any further treatment.

We should now aim to significantly improve this uptake as drugs are NICE approved and upfront testing means patients would be able to access drugs straightway after progression on first line therapy improving their experience and outcomes.

Please expand the headings below to read more about the main project conclusions.

Patient Demographics and disease characteristics

Our audit covered 188 BTC patients (from Nottingham, Leicester and Mansfield), with a median age of 67.9 years.

The majority were over 65 years old (65.4%) and female (52.7%). Ethnically, the patient population was predominantly White-British (84.6%). The most common type of BTC observed was intrahepatic cholangiocarcinoma (IH CCA), accounting for 51.1% of cases, followed by extrahepatic cholangiocarcinoma (EH CCA) at 19.7%.

Genomic Testing uptake and results

Genomic testing uptake was suboptimal, with a significant proportion of patients not being tested for key genetic alterations:

MMR status: 88.8% not tested
IDH1 mutation: 87.2% not tested
FGFR2 fusion: 78.2% not tested
NTRK fusion: 81.4% not tested

Among those tested, IDH1 mutations were present in 16.6% of patients, FGFR2 fusions in 7.3%, and no NTRK fusions were detected. Only 4.8% of the tested patients had positive MMR status.

Survival Data and Treatment Outcomes

For patients with metastatic disease, the median progression-free survival (PFS) was 8.35 months, and the median overall survival (OS) was 11.1 months.

Recommendations for Future Practice

Increase Genomic Testing: The project underscores the need for widespread adoption of genomic testing in BTC patients. This would enable more personalized treatment approaches and potentially improve outcomes.
Educational Initiatives: Continued education and awareness campaigns for MDTs are essential to ensure genomic testing becomes a routine part of BTC management.
Re-audit and Continuous Improvement: Re-auditing the genomic testing practices in 2 years is crucial to measure the impact of the implemented pathway and make necessary adjustments.
Enhanced Data Collection: Comprehensive documentation of genomic testing results will support more robust analysis and better-informed clinical decisions.

Impact on Clinical Practice

The integration of genomic testing into the BTC management pathway has the potential to:

Enhance early detection of actionable alterations
Enable personalized treatment plans that target specific genetic alterations
Improve patient outcomes through more effective and tailored therapeutic strategies

Meet our team

Dr Arvind Arora, Project Lead ( Lead HPB Oncologist & Honorary Professor of Medical Oncology, Nottingham University Hospitals NHS Trust) (Arvind.Arora@nuh.nhs.uk)
Col Spencer, PMO Support, EGMSA (colin.spencer@nuh.nhs.uk)

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