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The so-called liquid biopsy is very promising for the more accurate detection of a variety of cancers, for the direction of individualized treatment and for the improvement of monitoring during treatment. New data suggest that analysis of human papillomavirus (ctHPVDNA) DNA in circulating plasma tumors may be an effective method of surveillance in patients p16Oropharyngeal Squamous Cell Carcinoma (OPSCC).
The performance of a multianalyte blood test optimized for detecting the recurrence of ctHPVDNA cancer was "exceptional," the researchers said. The test had a negative predictive value (NPV) of 100%.
"We have developed a test that is very effective at detecting the risk of recurrence of cancer," explained lead author Bhisham Chera, MD, of the Lineberger Comprehensive Cancer Center of North Carlina University in Chapel Hill. (A C). "Of all patients who had undetectable rates at follow-up, all are without cancer."
At an average follow-up of 19.8 months, none of the 70 patients with undetectable cDNA-htVP at any time of post-treatment surveillance experienced recurrence of the disease.
Chera presented her findings to the American Society of Radiation Oncology (ASTRO) 2018.
Liquid biopsies have been of great interest to both pathologists and oncologists because they can potentially be used in a wide variety of settings. CDNA monitoring should provide clinicians with faster, less expensive and less invasive ways to evaluate the clinical status of cancer patients and their response to treatment.
However, a panel of experts recently said that these tests "are not yet ready for a prime time in the diagnosis or management of solid tumors at an early or advanced stage."
The journal, which was prepared jointly by the American Society of Clinical Oncology and the College of American Pathologists, also indicated that these tests are not useful, apart from clinical trials, to monitor patients for residual disease. minimal after definitive treatment of cancer or for cancer. screening.
But ready or not, liquid biopsies make their way into the clinical context. For example, cell-free DNA released from the tumor and collected serum is increasingly used to guide the treatment of lung cancer, both as an adjunct to tumor tissue biopsy after drug resistance and, in some cases as an alternative to tissue biopsy. .
In cervicofacial oncology, Chera of the UNC noted that there is data indicating that circulating HPV DNA is detectable and may constitute a biomarker. In the studies he's conducted, as well as in those of other researchers, the results show that "the majority of patients with HPV-related tumors have detectable circulating tumor HPV DNA".
But the question, he said, is whether plasma ctHPVDNA can be used to detect cancer recurrence.
Study details to 89 patients
In the current study, Chera and her team have developed a highly sensitive and sensitive liquid biopsy blood test for patients with HPV-associated CPSPO. The test, which used a standardized multi-step analytical protocol to optimize specificity and sensitivity, could distinguish between ctHPVDNA and native viral genomes. The current test also detected strains 16, 18, 31, 33 and 35 of CtHPV, and Chera noted that "more high-risk strains are being prepared".
This prospective biomarker trial included 89 patients with an HPV-associated CPSPO whose cancer had initially metastasized. All patients were treated with definitive chemotherapy (TRC); 78 patients received a detuned cathode ray tube up to a total radiation dose of 60 gray (Gy) and 11 patients received a standard catheter tube of 70 Gy.
Blood samples were collected initially (58 of 89 patients) each week during treatment (30 of 89) and at each follow-up visit (89) for the extraction of nucleic acid circulating in the plasma. Clinical surveillance was performed every 2 to 4 months during years 1 and 2, then every 6 months between 3 and 5 years. Thoracic imaging was also performed every 6 months. Additional imaging was obtained if the ctHPVDNA became detectable.
In this cohort, 53 of 58 evaluable patients had undetectable ctHPV-DNA within 3 months of CRT; 70 of the 89 patients in the surveillance cohort had undetectable ctHPV-DNA at all times beyond 3 months after TRC. All 70 of these patients remained free from the disease for a 100% NPV.
For the other patients, 16 out of 89 patients received a positive result on the ctHPVDN test 16 years after 16.7 months of TRC (median value: 75 copies / mL). In this group, eight patients were diagnosed with recurrence (no local, one regional, seven distant). Currently, eight patients have detectable ctHPVV DNA (23-28,369 copies / mL), but no evidence of recurrence and are followed up.
In addition, 11 patients had detectable ctHPVD DNA, but no evidence of recurrent disease was detected during imaging. For four patients, the signal of ctHPVDNA was spontaneously cleared. The remaining seven patients continue to be closely monitored, Chera said.
The sensitivity of the ctHPVV-DNA assay was 100%, the specificity was 90%, the NPV was 100% and the positive predictive value was 50%.
"In the future, I think this can help make our surveillance more effective in identifying cancer, and for those with undetectable levels, we can omit imaging," he said. Chera. "It can help us to use diagnostic tests more appropriately."
In the future, this could help make our monitoring more efficient.
He added that this could also help detect cancer faster and would be more cost effective because the use of expensive imaging could be reduced.
In addition, the ctHPVDN test may have applications for other HPV-related malignancies, such as cervical cancer and anus cancer.
Validation required
Commenting on the study, Richard Bakst, MD, associate professor of radiation oncology at the Icahn School of Medicine at Mount Sinai in New York City, explained that "we know that cancer is the only cause of cancer. HPV-related oropharynx behaves very differently from the negative HPV disease.
"While we regularly survey patients with scans to see if there is any disease after treatment and / or that we are monitoring recurrences, the results of this study suggest that we could have a more sensitive test using the 39, DNA from a tumor in circulation, "he said. Medscape Medical News. "Recurrences can potentially be detected earlier using such a test, but it needs to be validated on a larger cohort to avoid false positive or negative results.Today, imaging tests remain the standard of care for monitoring patients with an HPV-related disease. "
Dr. Chera has relationships with Naveris, the Burroughs Wellcome Fund, the US Department of Defense, the Susan G. Komen Foundation, and the UNC Linberger University Cancer Research Fund. Dr. Bakst did not reveal any relevant financial relationship.
American Radiation Oncology Society (ASTRO) 2018. LBA 6, presented on October 23, 2018.
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