Often-discarded lymphatic fluid may guide precision treatment for head and neck cancer
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Lymphatic fluid from surgical drains could offer important insights to guide treatment for certain patients with head and neck cancer, according to study results.
Lymphatic fluid typically is put in the trash; however, HPV DNA from fluid collected postoperatively may be a potentially powerful biomarker that may predict recurrence risk among patients with HPV-positive disease, findings published in Clinical Cancer Research showed.
“This waste fluid, which is usually discarded, could potentially help us objectively measure what the surgeon left behind,” study author José P. Zevallos, MD, MPH, FACS, professor and Eugene N. Myers chair of the department of otolaryngology at the University of Pittsburgh School of Medicine and UPMC Hillman Cancer Center, told Healio. “This not only has the potential to be prognostic but, in some future iteration, it can help define adjuvant therapy. It could help define whether the patient needs radiation alone, chemoradiation, immunotherapy or nothing.”
Healio spoke with Zevallos about the findings and their potential implications.
Healio: What motivated you to evaluate lymphatic fluid as a potential biomarker?
Zevallos: The liquid biopsy field in cancer has taken off in the past decade. Most of this work involves using plasma or blood-based biomarkers for detection of recurrent cancer. One of the frustrations is that this approach hasn’t taken off in head and neck cancer. By the time head and neck cancer recurs, there is not much clinicians can do. We wanted to understand whether we could somehow employ the liquid biopsy/cell-free DNA approach within the curative pathway for these patients to inform treatment decisions.
I began to wonder if there would be value in looking at this fluid, which — for a hundred years of modern surgery — has been overlooked. Surgeons are used to dealing with this fluid that collects in surgical drains postoperatively; someone has to measure it and discard it. The idea was to investigate whether it might contain useful data.
I am a clinician-scientist — I’m a surgeon in the morning and I’m a researcher in the afternoon — so it was a classic surgeon-scientist story. The fact we have people who are working in both of these roles allows these types of insights to develop.
Healio: How does the process work?
Zevallos: When a patient undergoes surgery for head and neck cancer, we remove the tumor and lymph nodes from the neck. We put a drain in and, 24 hours after surgery, we collect fluid from the surgical drain and run a series of tests on it. Specifically, we run a polymerase chain reaction (PCR)-based assay for detection of HPV DNA. After measuring HPV DNA, we correlated that with cancer recurrence outcomes.
Importantly, our study compared this approach with gold-standard pathology. We wanted to know whether it adds prognostic information compared with or in addition to what is provided by traditional pathologic staging. It turned out it does. It provides more and better predictive information.
In a subset of patients, we not only ran the HPV PCR assay but also ran next-generation sequencing analysis of the DNA in the fluid to confirm the mutations we were seeing were the same as those seen in the primary tumor. They were, and this confirmed we are actually measuring residual tumor DNA. As this is further developed, it will enable us to make adjuvant therapy decisions in a more objective and personalized way than with pathology.
Healio: What are the next steps in research?
Zevallos: My lab is working on this every day — not just in HPV-positive head and neck cancer, but also those with HPV-negative disease. We’re also looking at this in pancreatic cancer and breast cancer. We’re studying multiple proximal postoperative biofluids to see if we can learn about minimal residual disease left behind after surgery. We’re also looking at the immune response that we can detect in the fluid.
Droplet Biosciences, a company I founded, is working on this commercially and developing the first liquid biopsy lymphatic fluid assay for commercial use. We expect this assay — which will be for HPV-negative head and neck cancer — to be available within a year. Droplet also has partnerships with nine different academic institutions to evaluate this technology in head and neck cancer, lung cancer and bladder cancer. So, we’re building the commercial side of the assay, and our hope is to extend this to all solid tumors.
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For more information:
José P. Zevallos, MD, MPH, FACS, can be reached at University of Pittsburgh Medical Center, Department of Otolaryngology, Eye & Ear Institute, 203 Lothrop St., Suite 500, Pittsburgh, PA 15213; email: zevallosjp@upmc.edu.
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