Liquid biopsies can rapidly detect residual disease following cervical chemoradiation, study finds

Two liquid biopsy exams that search for the presence of human papillomavirus (HPV) within the blood precisely recognized sufferers with a excessive threat of cervical most cancers recurrence after the completion of chemoradiation, a brand new examine confirms. Findings will likely be introduced in the present day on the American Society for Radiation Oncology (ASTRO) Annual Meeting.

The examine in contrast two novel exams—a digital polymerase chain response (dPCR) test and a sequencing take a look at for genetic materials from HPV, the primary reason for cervical cancer—and located they had been equally efficient at figuring out residual disease within the blood of sufferers who just lately accomplished radiation and chemotherapy for cervical cancer. Earlier detection permits for earlier remedy of residual illness and doubtlessly higher survival charges.

“These non-invasive exams can detect residual illness following chemoradiation remedy sooner than imaging or a scientific examination,” stated lead examine writer Kathy Han, MD, a radiation oncologist on the Princess Margaret Most cancers Heart on the College of Toronto. “We are able to detect very minimal illness, earlier than it grows greater, which doubtlessly will allow us to intervene earlier and enhance outcomes for individuals with cervical most cancers.”

Roughly 11,500 new cases of cervical most cancers are identified yearly within the U.S., and an estimated 4,000 People die from the illness annually. Roughly 30-40% of sufferers with cervical most cancers develop tumor recurrence following chemoradiation, and at the moment, residual illness is usually detected too late to enhance survival charges.

Tissue biopsy has lengthy been considered the gold commonplace for figuring out tumors, however it requires an invasive process to pattern sufficient tumor tissue to be visualized on imaging, and it supplies a snapshot solely of a selected tumor area. Liquid biopsies can detect microscopic parts of tumors in bodily fluids comparable to blood or urine, offering a much less invasive choice to assess malignancy. Blood exams are probably the most broadly used kind of liquid biopsy and might establish circulating tumor DNA (ctDNA), circulating RNA and different markers that sign the presence of most cancers, together with HPV.

As a result of these exams can detect fragments of the HPV virus that stay within the blood following chemoradiation however earlier than tumors recur, “liquid biopsies present perception earlier than tissue biopsy turns into attainable,” stated Dr. Han. “If we are able to predict who could be at larger threat of recurrence, it might be a sign to clinicians to ensure these sufferers are adopted extra intently.”

In a earlier, pilot examine, Dr. Han and her staff collected blood samples from 20 sufferers with cervical most cancers earlier than and after chemoradiation remedy. Utilizing digital polymerase chain response (dPCR) exams, they discovered individuals with detectable HPV ctDNA on the finish of chemoradiation had worse outcomes than these with no detectable HPV ctDNA.

This new examine sought to validate these findings in a bigger pattern of sufferers, utilizing each dPCR and extra refined HPV sequencing exams. To take action, researchers prospectively enrolled 70 sufferers from 4 Canadian facilities; all members had been identified with HPV-positive cervical most cancers and handled with chemoradiation. Sufferers had been adopted for a median of two.2 years.

Sufferers gave blood samples earlier than remedy; additionally they obtained blood exams instantly after remedy, between 4 to 6 weeks post-treatment and 12 weeks post-treatment. Sufferers with detectable HPV ctDNA of their blood at every of those three timepoints had considerably worse progression-free survival charges than these with no detectable HPV of their blood.

Particularly, 53% of sufferers with detectable HPV ctDNA instantly following chemoradiation had been progression-free two years later, in comparison with 87% of sufferers with out detectable HPV ctDNA instantly after remedy. The distinction was much more pronounced on the 12-week mark; sufferers with detectable HPV ctDNA three months following chemoradiation had a 26% two-year progression-free survival fee, in comparison with 85% for these with out.

“We had been comfortable to see that we might validate our preliminary outcomes,” stated Dr. Han. “We had been shocked, nonetheless, to search out no important variations between the digital PCR take a look at and the HPV sequencing take a look at. Though HPV sequencing was extra delicate than digital PCR, each approaches returned comparable outcomes after remedy.”

Lately, advances in know-how have accelerated using liquid biopsies, that are believed to carry nice potential for non-invasive most cancers screening in high-risk populations. Nonetheless, the exams are usually not but broadly accessible.

One of many challenges with making HPV ctDNA testing broadly accessible for individuals with cervical most cancers is the number of HPV varieties that trigger the illness, stated Dr. Han, noting that 11 distinct HPV varieties had been detected of their evaluation. But Dr. Han stated the HPV sequencing take a look at was able to detecting all 11 varieties with excessive accuracy and steered that it might grow to be a generalizable method for HPV-positive cervical most cancers.

Increasing entry to liquid biopsies can be needed, stated Dr. Han, and will likely be essential for future analysis utilizing liquid biopsies to establish sufferers at high-risk of recurrence and randomizing them to intensive versus commonplace remedy.