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Liquid biopsy test confirms remission in HPV-associated oral cancer

A novel liquid biopsy test showed compelling specificity and sensitivity in detecting HPV DNA among patients who underwent chemoradiotherapy for HPV-associated oropharyngeal squamous cell carcinoma, according to findings presented at the American Society for Radiation Oncology Annual Meeting.

“This blood test has exceptional performance in monitoring patients for cancer recurrence after radiation therapy,” Bhisham Chera, MD, an associate professor of radiation oncology at The University of North Carolina at Chapel Hill and a member of the UNC Lineberger Comprehensive Cancer Center, said in a press release.

Recent studies have shown that most patients with HPV-related oropharyngeal squamous cell carcinoma have detectable circulating tumor HPV DNA, according to Chera. “The data is very interesting in that it correlates as a biomarker for tumor burden and possibly also response kinetics of treatment,” he said.

Liquid biopsy tests have generated great interest recently, but it can be difficult to differentiate DNA from normal cells from that of tumor cells, the researchers said.

The test developed by Chera and colleagues is a multistep digital polymerase chain reaction assay that can detect as few as six molecules of HPV DNA in blood samples. It does not cross-detect other types of cellular DNA, according to Chera.

The researchers conducted a prospective, multinational biomarker study to evaluate the ability of circulating tumor HPV DNA to detect cancer recurrence after treatment.

The analysis included 89 patients with, all of whom underwent chemoradiation treatment.

“We analyzed about 1,000 blood samples for this study,” Chera said.

The cohort included 78 patients who underwent a de-intensified chemoradiation regimen of 60 Gy and 11 patients treated with standard-of-care 70 Gy.

Beginning 3 months after treatment, clinicians monitored patients with a combined approach of PET/CT scans, CT scans and chest X-rays at 6-month intervals. Clinicians also examined participants every 2 to 4 months for a 2-year period, and then at 6-month intervals for 3 more years. Blood samples taken during each visit were tested for ctHPV DNA.

“If a patient developed HPV DNA detectability in the blood during follow-up, throughout the course of the study, we started doing subsequent imaging because our results were very promising,” Chera said.

Patients were followed for an average of 19.8 months (range, 3.7-44.7). During the follow-up period, 70 of the 89 patients had undetectable HPV DNA levels. No cancer recurrence was observed among these patients. “We estimate that the negative predictive value of this blood test is 100%,” Chera said.

The other 19 patients tested positive for ctHPV DNA at a median duration of 16.7 months (range, 7.8-3.04) following the end of chemoradiation therapy. Clinicians detected a median of 75 copies/mL (range, 9-28,369) among these patients.

Eight of the 19 patients with detectable ctHPV DNA experienced a recurrence of cancer. None of these cases was local; one was regional and seven were distant.

“We estimate that the positive predictive value of the test is around 42%,” Chera said.

Among the remaining 11 patients, clinicians observed broad range of ctHPV DNA levels (range, 23-28,369 copies/ml), but no evidence of cancer recurrence. “That means their physical exams are negative, we’ve done CT or PET scans, and there is no evidence,” Chera said. “Interestingly, in four of these patients, they developed a detectable level at some point post-treatment, but then cleared. Possibly the immune system is eradicating cancer.”

Chera said the test could reduce the need for costly radiological studies.

“This can help make our surveillance more effective, and make us more effective at using radiographic imaging,” he said. “Those who have undetectable levels, we will eliminate imaging. For those who develop positive ctDNA levels, we will use imaging. It will help us appropriately use what could be considered expensive diagnostic radiographic tests for the right patients. Ultimately, it will help us detect cancer earlier than we do now.” – by Rob Volansky

 

Reference:

Chera B, et al. Abstract LBA-6. Presented at: American Society for Radiation Oncology Annual Meeting; Oct. 21-24, 2018; San Antonio.

 

Disclosure: Intellectual property related to the liquid biopsy test and held by the University of North Carolina at Chapel Hill has been licensed to Naveris, a company in which Chera holds an equity stake. HemOnc Today could not confirm other relevant financial disclosures at the time of reporting.

A novel liquid biopsy test showed compelling specificity and sensitivity in detecting HPV DNA among patients who underwent chemoradiotherapy for HPV-associated oropharyngeal squamous cell carcinoma, according to findings presented at the American Society for Radiation Oncology Annual Meeting.

“This blood test has exceptional performance in monitoring patients for cancer recurrence after radiation therapy,” Bhisham Chera, MD, an associate professor of radiation oncology at The University of North Carolina at Chapel Hill and a member of the UNC Lineberger Comprehensive Cancer Center, said in a press release.

Recent studies have shown that most patients with HPV-related oropharyngeal squamous cell carcinoma have detectable circulating tumor HPV DNA, according to Chera. “The data is very interesting in that it correlates as a biomarker for tumor burden and possibly also response kinetics of treatment,” he said.

Liquid biopsy tests have generated great interest recently, but it can be difficult to differentiate DNA from normal cells from that of tumor cells, the researchers said.

The test developed by Chera and colleagues is a multistep digital polymerase chain reaction assay that can detect as few as six molecules of HPV DNA in blood samples. It does not cross-detect other types of cellular DNA, according to Chera.

The researchers conducted a prospective, multinational biomarker study to evaluate the ability of circulating tumor HPV DNA to detect cancer recurrence after treatment.

The analysis included 89 patients with, all of whom underwent chemoradiation treatment.

“We analyzed about 1,000 blood samples for this study,” Chera said.

The cohort included 78 patients who underwent a de-intensified chemoradiation regimen of 60 Gy and 11 patients treated with standard-of-care 70 Gy.

Beginning 3 months after treatment, clinicians monitored patients with a combined approach of PET/CT scans, CT scans and chest X-rays at 6-month intervals. Clinicians also examined participants every 2 to 4 months for a 2-year period, and then at 6-month intervals for 3 more years. Blood samples taken during each visit were tested for ctHPV DNA.

“If a patient developed HPV DNA detectability in the blood during follow-up, throughout the course of the study, we started doing subsequent imaging because our results were very promising,” Chera said.

Patients were followed for an average of 19.8 months (range, 3.7-44.7). During the follow-up period, 70 of the 89 patients had undetectable HPV DNA levels. No cancer recurrence was observed among these patients. “We estimate that the negative predictive value of this blood test is 100%,” Chera said.

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The other 19 patients tested positive for ctHPV DNA at a median duration of 16.7 months (range, 7.8-3.04) following the end of chemoradiation therapy. Clinicians detected a median of 75 copies/mL (range, 9-28,369) among these patients.

Eight of the 19 patients with detectable ctHPV DNA experienced a recurrence of cancer. None of these cases was local; one was regional and seven were distant.

“We estimate that the positive predictive value of the test is around 42%,” Chera said.

Among the remaining 11 patients, clinicians observed broad range of ctHPV DNA levels (range, 23-28,369 copies/ml), but no evidence of cancer recurrence. “That means their physical exams are negative, we’ve done CT or PET scans, and there is no evidence,” Chera said. “Interestingly, in four of these patients, they developed a detectable level at some point post-treatment, but then cleared. Possibly the immune system is eradicating cancer.”

Chera said the test could reduce the need for costly radiological studies.

“This can help make our surveillance more effective, and make us more effective at using radiographic imaging,” he said. “Those who have undetectable levels, we will eliminate imaging. For those who develop positive ctDNA levels, we will use imaging. It will help us appropriately use what could be considered expensive diagnostic radiographic tests for the right patients. Ultimately, it will help us detect cancer earlier than we do now.” – by Rob Volansky

 

Reference:

Chera B, et al. Abstract LBA-6. Presented at: American Society for Radiation Oncology Annual Meeting; Oct. 21-24, 2018; San Antonio.

 

Disclosure: Intellectual property related to the liquid biopsy test and held by the University of North Carolina at Chapel Hill has been licensed to Naveris, a company in which Chera holds an equity stake. HemOnc Today could not confirm other relevant financial disclosures at the time of reporting.

    Perspective

    This is not a trial that changes practice today. It has enormous power to change practice in the future. Liquid biopsy technology is continuing to advance and generate new data for all sorts of solid tumors. It has shown the capacity to monitor and surveil post-treatment for recurrence, and the ability to detect emergence of new cancers. In this HPV head and neck cohort, the negative predictive value of 100% showing that those patients whose HPV DNA is nondetectable post-treatment, at least with the follow-up on the order of 20 months, is very compelling. This may offer a new opportunity to diminish the expense of complex imaging and utilize this blood to identify patients that may manifest recurrence.

    • Paul Harrari, MD
    • University of Wisconsin School of Medicine and Public Health

    Disclosures: HemOnc Today could not confirm Harrari’s relevant financial disclosures at the time of reporting.

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