Simple blood test could avoid the need for chemotherapy
Australian cancer patients are being invited to participate in groundbreaking research into whether a simple blood test could determine the need for adjuvant chemotherapy.
Researchers are currently recruiting bowel and ovarian cancer patients to trials examining the potential to predict disease recurrence based on circulating tumour DNA – the mutated DNA fragments that float freely in the bloodstream when cancer cells naturally rupture and die.
Advances in sequencing technology mean mutated DNA fragments are now detectable through an inexpensive blood test, even if they are outnumbered by normal healthy cell DNA by a factor of 10,000:1. Researchers hope the technique may reveal previously undetectable micrometastatic disease and help oncologists pinpoint the patients who need, or don’t need, adjuvant chemotherapy.
There are also hopes the test could be used for real-time testing of the benefit of adjuvant chemotherapy, as ctDNA has a short half-life (around 2 hours).
The ctDNA clinical studies – nicknamed the DYNAMIC trials – are being conducted at 40 hospitals across Australia and New Zealand, with researchers hoping to recruit 2000 patients.
Proof of concept studies ‘very compelling’
Associate Professor Sumitra Ananda, clinician-researcher at the Walter and Eliza Hall Institute in Melbourne, said the trials build upon “very compelling” results from proof-of-concept studies in bowel cancer patients.
For instance, a 2016 study of 230 patients with resected stage II colon cancer found that in the subset not receiving adjuvant chemotherapy, recurrence occurred in 79% of those with positive ctDNA, compared with just 9.8% of those with negative ctDNA.
Professor Ananda commented: “The pilot studies have raised hopes that we may be able to escalate or de-escalate chemotherapy dose based on circulating DNA, although the findings need to be validated in large randomized controlled trials as we are now seeking to do.”
Hope for ovarian cancer
Professor Ananda, who is leading the proof-of-concept ovarian cancer arm of the DYNAMIC trial, said it remained to be seen whether ctDNA had sensitivity in ovarian cancer as had been shown in bowel cancer.
“We know that ovarian cancer often spreads intra-abdominally, so it’s possible that it might not be picked up with ctDNA in the same way as has been shown with microscopic disease in the blood stream of bowel cancer patients,” she said.
If proved effective, the test could relieve many future patients of the burden of unnecessary chemotherapy, Professor Ananda said.
“We suspect that a subset of women with early stage ovarian cancer can be treated with surgery alone, but we currently treat all these patients as though their cancer may recur, with high dose chemotherapy,” she said.
“Undergoing chemotherapy is a huge imposition on a patient’s life, both because of the side effects patients have to endure as well as the time the treatment takes.”
There are four studies now recruiting for DYNAMIC: Professor Ananda’s pilot study in ovarian cancer patients; and three randomised controlled trials in patients with stage 2 colon cancer, stage 3 colon cancer, and rectal cancer.
The ovarian cancer study is observational, looking for an association between ctDNA and recurrence. The bowel cancer studies are interventional, with patients randomized to either ctDNA-guided care (only receiving chemotherapy if ctDNA is detected) or to usual care at their clinician’s discretion (blinded to their ctDNA result). The trials are expected to run until 2019 for ovarian cancer and 2021 for bowel cancer.
The ctDNA blood test was developed through a collaboration between the Walter and Eliza Hall Institute and Johns Hopkins Kimmel Cancer Centre, US. Its potential use in population cancer screening is also being explored.