An NHMRC-funded investigator-initiated trial has commenced in Victoria with around 100 patients recruited from across VCCC Alliance hospitals. The study is evaluating novel assays to detect circulating tumour DNA (ctDNA) before and after lung cancer surgery. There are currently no sensitive or specific blood-based biomarkers in clinical use for lung cancer, so the study aims to develop and validate molecular predictive and prognostic markers to improve outcomes for patients with the disease.
The study, DURATION (Droplet digital PCR – Using chromosome Rearrangements As Tumour-specific markers In disease mONitoring for lung cancer) is led by Associate Professor Gavin Wright, VCCC Alliance Research & Education Lead (R&E Lead) Lung Cancer with principal investigator, Associate Professor Alexander Dobrovic, who heads the Translational Genomics and Epigenomics Laboratory at the Olivia Newton-John Cancer Research Institute.
Blood-based ctDNA detection offers a non-invasive and easily accessible way for cancer diagnosis and potential for patient monitoring. Dr Wright said that there are currently no evidence-based guidelines for the clinical follow-up of non-small cell lung cancer (NSCLC) patients after surgery.
“This study will enable us to assess the presence of ctDNA pre- and post-surgical resection as a predictor of relapse or disease-free survival in surgically treated lung cancer patients,” he said.
“Currently CT scanning is the only widely available method to monitor for relapse. While scans provide a method of surveillance, they are expensive. They also expose patients to radiation and add time and cost demands on people forced to travel to major centres for treatment.”
Dr Wright said his VCCC Alliance appointment enables him to run a hub-and-spoke system of trial sites and sub-sites and provides scope to develop multidisciplinary and multi-centre collaborations.
As a specialist thoracic surgeon, he has appointments at St Vincent’s Hospital Melbourne, Peter MacCallum Cancer Centre and The Royal Melbourne Hospital. The DURATION study involves investigators from Peter Mac, St Vincent’s public and private, Olivia Newton-John Cancer Wellness and Research Centre and WEHI.
Dr Wright said the concept of using rearrangements for monitoring disease goes back to the use of recurrent chromosome rearrangements in haematological malignancies. “In addition to the comparatively rare recurrent mutations such as EML4-ALK, each epithelial tumour harbours a “personal” set of chromosomal rearrangements, that can be identified by whole genome sequencing.
“These personal rearrangements can be used as markers to identify the presence of tumour DNA. The advantage of this approach relies on the nature of chromosomal rearrangements. As rearrangements are tumour specific, only DNA containing the specific rearrangements will be amplified using PCR assays flanking the rearrangement junction,” he said.
Harnessing technological and bioinformatic advances are key improvements in the DURATION study.
“Most established scientists would have laughed at the prospect of sequencing a whole human genome in a day, but that technology exists for us now.
“Once we have sequenced the cancer DNA in Brisbane, we use the bioinformatic method developed in Prof Tony Papenfuss’ laboratory - GRIDSS, to identify a patient’s unique genomic rearrangements and combine this with an extremely sensitive detection method developed by Prof Dobrovic’s team utilising digital droplet PCR (ddPCR) of chromosome rearrangements. This allows us to accurately quantify ctDNA levels in patients’ blood to monitor the effectiveness of the cancer treatment."
Dr Wright maintains that their approach to enrolling patients is centred on the ethos of collaboration. “We are equal partners in this journey of discovery,” he said.
“My team includes very professional and passionate clinical trial staff with an enthusiastic ‘can do’ attitude.
I realise how lucky I am to have this.
“We share a balanced and mutually respectful relationship, and our lung cancer multidisciplinary teams share a thirst for scientific truth. I am fortunate and grateful,” he said.
For more information on the VCCC Alliance R&E Lead, Lung Cancer program, contact
Dr Jasper De Boer or to discuss the DURATION trial, contact Associate Professor Gavin Wright.
