Consultants at Cromwell Hospital have contributed to a significant new international research paper published in iScience (opens in a new window >), exploring how cancer-related DNA found in body fluids could help identify treatment options for patients with advanced cancer.

The study, circulating tumour DNA in body fluids for molecular characterisation of cancers beyond tissue and blood, included contributions from Dr Andrew Gaya, Consultant Clinical Oncologist, and Professor Tim Crook, Consultant Clinical Oncologist at Cromwell Hospital. The research was conducted in collaboration with an international group of experts and partners including Datar Cancer Genetics, whose Cancertrack liquid biopsy platform was used in the study.

Looking beyond traditional biopsies

Precision oncology increasingly relies on molecular profiling to identify genetic alterations that can inform treatment decisions. Traditionally, this information is obtained through tissue biopsy or blood-based liquid biopsies. However, these approaches do not always capture the full genetic complexity of a patient’s cancer.

The researchers investigated whether analysing circulating tumour DNA (ctDNA) from body fluids already collected during routine care, including cerebrospinal fluid (CSF), pleural fluid, ascitic fluid and pericardial fluid, could provide additional clinically meaningful information.

The study evaluated 45 patients with advanced cancers and found that ctDNA was detected in 87% of body fluid samples, including 96% of ascitic fluid samples.

Finding answers that may otherwise be missed

One of the most important findings was that body fluid analysis revealed potentially targetable genetic alterations that had not been identified through blood or tissue testing alone.

In 13% of patients, the body fluid sample identified a clinically relevant alteration that had been missed by blood and/or tissue testing. Examples included:

  • HER2 amplification in breast cancer ascites
  • ESR1 D538G mutation in breast cancer cerebrospinal fluid
  • KIT alterations identified in pleural fluid from patients with gastrointestinal stromal tumours (GIST)

These findings demonstrate how body fluid testing can provide complementary information that may help guide targeted treatment decisions.

Potentially actionable treatment opportunities

The research also found that 31% of patients carried ESCAT Tier IA alterations, representing genetic changes associated with standard-of-care targeted therapies and recognised as highly actionable within precision oncology.

The most commonly identified mutations involved genes including TP53, EGFR and KRAS, which play important roles across multiple cancer types.

More than a diagnostic test

The study highlighted another potentially important role for body fluid ctDNA analysis.

In four out of five samples where conventional cytology testing did not detect cancer cells, ctDNA analysis was positive. This suggests that molecular analysis of body fluids may help identify malignant involvement even when standard cytology results are negative, potentially influencing staging, prognosis and treatment planning.

A practical approach for patients

For oncologists and patients, one of the advantages of this approach is that these body fluids are often already being collected to relieve symptoms such as breathlessness or abdominal discomfort.

This means valuable molecular information may be obtained without requiring an additional invasive biopsy, particularly in situations where tumour tissue is unavailable or blood-based testing does not reveal an actionable result.

Rather than replacing existing approaches, the researchers propose that body fluid ctDNA analysis should be viewed as complementary to tissue testing, plasma liquid biopsies and cytology, helping clinicians build a more complete picture of a patient’s disease.

Advancing precision oncology through collaboration

The contributions of Dr Andrew Gaya and Professor Tim Crook helped support research into innovative approaches that could expand access to precision oncology and potentially improve treatment selection for patients with advanced cancers.

As liquid biopsy technologies continue to evolve, studies such as this help demonstrate how new sources of tumour DNA may unlock additional opportunities for personalised cancer care and support more informed treatment decisions.