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With the help of a new blood test being developed, researchers at the Lineberger Center's Cancer Research Center at Lineberger's Cancer Studies Center have identified features that could be used to personalize the treatment of patients with a type of head and neck cancer badociated with HPV infection.
The researchers believe the findings, published in the journal Clinical research on cancer, could help identify patients with features related to improved treatment responses. They hope to adapt the treatment to these patients in order to reduce their exposure to possible toxic side effects.
"Cancers of the head and neck caused by HPV infection tend to have a better overall outcome than head and neck cancers related to other factors such as smoking and smoking. Alcoholism, "said Gaorav Gupta of UNC Lineberger, an badistant professor at the UNC School of Medicine's Department of Radiation Oncology. "There has been a lot of interest in finding out if we can give these patients less treatment while maintaining the same level of cure, while reducing the toxicities of the treatment." The purpose of this study was to determine whether a Blood test for screening for HPV circulating tumor DNA can potentially be used to monitor a patient's cancer response to chemotherapy and radiation therapy. "
The researchers developed the test to detect DNA levels in the blood from HPV-related oropharyngeal squamous cell carcinoma tumors. Studies are underway to determine if the test can be used to monitor patients' response to radiotherapy and chemotherapy. In addition, the test was licensed for commercial development at Naveris Inc.
In their latest work, the researchers identified features in patients that could be used to stratify and personalize the treatment. They drew their conclusions from a study of blood test results from 103 patients who were undergoing chemotherapy and radiation therapy for HPV-related oropharyngeal squamous cell carcinoma.
"This means that in the future, dynamic and real-time monitoring of tumor HPV DNA circulating in the blood during treatment can help us better customize and choose the treatment – especially the level of radiotherapy and chemotherapy that we give to the patient ". first author of the study, Bhishamjit S. Chera, MD, professor at UNC Lineberger, badociate professor in the department of radiation oncology of the UNC School of Medicine.
One of the features of their study as biomarker of good result was a high level of HPV tumor DNA circulating in the blood before treatment. The results seem counter-intuitive, the researchers plan to explain why a high level of initial viral DNA in the blood would be badociated with a better result.
"It may sound confusing at first, but we think it reflects how dependent the tumor is on the biology of HPV," said Gupta.
In addition, they found that patients who then rapidly removed circulating tumor DNA from their blood were more likely to have better results. Patients who were able to remove more than 95% of their blood DNA at 28 days of treatment were considered to have a favorable clearance rate. For 19 of 67 patients with these two favorable biomarkers, they found that no patient had a persistent or recurrent disease.
"When we brought together these two factors, that is, if any one had a lot of HPV DNA and that this one was eliminated quickly, we did not observe no treatment failure in our cohort, "Gupta said.
Conversely, they found that cancers with low levels of circulating DNA from tumors initially – less than 200 copies of HPV DNA per milliliter – and with an unfavorable elimination of the disease. HPV DNA after treatment had a higher risk of recurrence. This risk was even worse when it was badociated with other risk factors, such as many smoking history.
The researchers at UNC Lineberger plan to open a clinical trial in which patients are stratified to receive different levels of treatment based on real-time monitoring of HPV DNA. tumor in circulation. The planned trial, which will be led by Colette Shen, MD, an badistant professor in the department of radiation oncology at the UNC School of Medicine, will include patients who have previously smoked tobacco and who do not are currently not eligible for reduced intensity treatment. By using HPV DNA monitoring in circulating tumors during treatment, the researchers hope to identify patients likely to be spared from the additional toxicities of a full-intensity treatment.
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Besides Chera and Gupta, other writers include Sunil Kumar, Brian T. Beaty, David Brown, Stuart R. Jeffreys, Rebecca L. Green, Emily C. Goldman, Robert Amdur, Nathan Sheets, King Dagan, D. Neil Hayes, Jared Weiss, Juneko E. Grilley-Olson, Adam M. Zanation, Trevor G. Hackman, Jeffrey M. Blumberg, Samip Patel, Mark Christian Weissler, Tan Xianming, Joel S. Parker, and William M. Mendenhall.
Conflict of interest: Chera and Gupta have a stake in Naveris and are both members of the Scientific Advisory Board. They also filed a patent application for the test.
Funding: The study was funded by the University Cancer Research Fund, the Department of Radiation Oncology of the UNC School of Medicine, UNC Lineberger and the Department of Radiation Oncology of the University of Ottawa. Medical School of the University of Florida.
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