NEW YORK (GenomeWeb) – Members of the research and lab community believe liquid biopsy is poised to become a widely used tool for assessing cancer mutations within the next one to four years, according to a recent survey of readers conducted by Frost & Sullivan in conjunction with GenomeWeb and analyzed by Divyaa Ravishankar, a senior industry analyst at Frost & Sullivan.
Asked about what technologies they currently use — or plan to use — to analyze either circulating tumor cells or circulating tumor DNA, respondents also overwhelmingly embraced next-generation sequencing, with quantitative PCR and digital droplet-based PCR coming in second and third.
Though only a subset of respondents answered the question, when asked when they plan to implement liquid biopsy in their own labs or facilities, more than 40 percent said they would in the next six months while another 50 percent expect to in the next one to two years.
The online survey was emailed to a subset of GenomeWeb subscribers during July 2015, with 101 respondents completing it in whole or in part. Of these respondents, 35 percent said they represent a reference or independent lab, 31 percent a pharmaceutical or diagnostics company, 22 percent a hospital lab, and 16 percent some other type of research facility.
Participants also represented a wide range of positions, including lab directors, scientists, managers, oncologists, clinicians, and pathologists.
Adoption
When analyzed by their professional affiliation, survey respondents presented some different attitudes toward the adoption of liquid biopsy. A majority of those who reported that they neither currently use nor plan to use liquid biopsy in the future were predominantly from pharma and diagnostic companies. In contrast, almost half of those who said they planned to implement liquid biopsy in the future were from reference labs, followed by hospital labs, then research institutes, then pharma/dx companies.
Respondents who said they are already using liquid biopsy were more evenly split between reference labs, pharma and diagnostics firms, and hospital labs.
Asked for their timeline for employing liquid biopsy methods, a majority of those surveyed skipped the question. But among 25 who responded, close to half said they plan to perform some form of liquid biopsy within six months, and another half expect to in the next one to two years.
As to the field in general, respondents overwhelmingly predicted that liquid biopsy will become a widely used tool — either alongside tissue biopsy or in cases where tissue samples are not available — within one to four years.
Only 10 percent of those surveyed said the technology will be ready for widespread use in less than a year, despite a growing presence of commercial liquid biopsy companies offering everything from simple single-mutation tests performed on ctDNA or CTCs to large next-generation sequencing panels covering tens or even close to 100 genes.
Meanwhile, 20 percent of respondents said they didn't see liquid biopsy becoming a standard practice before at least four years are out. However, none reported that they thought this would never happen.
Bottlenecks for adoption reported by the survey group included a lack of clinical evidence and evidence of utility of liquid biopsy technologies, as well as the challenges of reimbursement and physician awareness.
Technology
When asked about preferred technologies for current or future liquid biopsy activities using either CTCs or ctDNA, respondents most frequently chose next-generation sequencing, followed by quantitative PCR and digital droplet-based PCR technologies. More than 70 percent of respondents reported using or planning to use NGS for CTC analysis, and more than 80 percent said the same for ctDNA. In contrast, only 50 percent reported interest in quantitative PCR and about 30 percent to 40 percent in droplet-based PCR for CTCs or ctDNA.
A relatively small fraction of respondents also chose a variety of other analysis tools including immunohistochemistry or FISH.
In response to a separate question about methodology for liquid biopsy, a majority of those surveyed favored cancer specific panels followed by single-marker tests over broader approaches like pan-cancer sequencing panels or whole-exome or whole-genome sequencing.
Applications
As interest in liquid biopsy has grown rapidly in the last few years, so have the current and potential applications of technologies to analyze circulating tumor cells or cell-free DNA. Currently, companies market tests with the potential not only for general genomic assessment of patients'' cancers, but also to monitor the efficacy of therapy and the emergency of drug resistance, or to detect mutations that make patients eligible for particular molecularly targeted treatments.
Asked about the most promising applications for liquid biopsy, the greatest number of respondents, 59, chose therapy monitoring, followed by 55 who selected diagnosis of recurrence, and 49 who cited the detection of acquired drug resistance.
Interestingly, the fourth most commonly selected application (beating out companion diagnostics, assessment of tumor heterogeneity or clonality, and assessing prognosis) was cancer screening and early detection, something at least some leaders in the field consider a more distant goal for the liquid biopsy community, requiring significant additional research to bring to the clinic.
The issue of the readiness of liquid biopsy technologies for the task of early cancer detection or screening was recently spotlighted by Pathway Genomics' launch this September of an NGS-based ctDNA test for early cancer detection in individuals with an elevated risk.
A few weeks later, the company received a letter from the US Food and Drug Administration saying that it had examined published literature, but could not find any published evidence that Pathway's test or any similar test has been adequately clinically validated as a screening tool for early detection of cancer in high-risk individuals.