Gerard Walls: ctDNA, a future tool for radiation therapy personalization in lung cancer?

Gerard Walls, Lung Cancer Clinical Fellow at The Christie NHS Foundation Trust, shared a thread on X:

“Think ctDNA is only useful in Non-Small Cell Lung Cancer for assessing response to systemic therapy?

Think again! ctDNA has multiple potential applications in patients receiving radiotherapy.

Aadel Chaudhuri, Bruna Pellini and myself explore this in a new International Society of Liquid Biopsy article Mini-tweetorial.

While localised or oligometastatic disease sheds relatively lower levels of ctDNA in comparison with advanced disease, the ultra-deep sequencing methods that are increasingly available are sufficiently sensitive to detect ctDNA in these low tumour volume scenarios.

The best data for ctDNA in Non Small Cell Lung Cancer Radiation Therapy relates to detection of minimum residual disease (MRD) after definitive treatment – PMID 28899864.

ctDNA MRD could guide decisions on post-Radiation Therapy consolidation eg PACIFIC or LAURA… Potentially sparing/deferring treatments for patients who don’t need it.

Emerging evidence suggests ctDNA may have utility in further characterising disease burden patients with radiological oligometastatic disease – PMID 37783809.

In the future ctDNA will likely be able to guide which patientts are selected for Stereotactic Ablative Radiotherapy (SABR) (as opposed to systemic therapy). There are also signals from small proof-of-concept studies that ctDNA kinetics change acutely during Radiation Therapy for some patients – including a spike for 1/3 patients within hours to a small number of days.

The mechanism and clinical implications of ctDNA dynamic changes during RT are unknown. Advancing ctDNA in Radiational Oncology will require collaboration between trialists and biomedical engineers as we seek to iron out the technical challenges in clinically relevant prospective samples – hopefully funders will support these projects & clinician scientist training positions!

The VIGILANCE study at The Christie NHS Foundation Trust run by Ash Grove and Corinne Faivre-Finn is building on this data with more patients, more timepoints and more advanced interrogation of the data – watch this space!”

Source: Gerard Walls/X