Non-invasive liquid biopsy tracks cancer treatment success in real time

A non-invasive, blood-based biopsy for kidney cancer can tell doctors how a patient’s disease is responding to treatment.

Known as liquid biopsies, these blood tests could help physicians better treat their patients by allowing them to see which treatments are working in real time without the need for repeated, invasive biopsies of solid tumors.

A clinical study published May 26 in the Journal of Clinical Oncology and led by University of Wisconsin–Madison scientists followed more than 100 patients undergoing treatment for renal cell carcinoma. Researchers isolated and measured circulating tumor cells, which tumors release into the blood. These cells can act as a signal of disease burden in a patient.

Changes in both the number of circulating tumor cells and their molecular profiles were able to predict how long a patient would survive while undergoing either new immune system-based treatments or receiving more traditional kidney cancer drugs.

“Cancer is not a static disease. As the disease progresses, molecular characteristics change over time, and these changes are important to understand how the disease responds to treatment as well as how resistance develops,” says Matthew Bootsma, a researcher in the UW School of Medicine and Public Health and one of the lead authors of the report. “That makes it really important for a clinician to have real-time access to these metrics.”

The research team also included UW–Madison Professor of Human Oncology Shuang Zhao, Professor of Medicine Joshua Lang, and the researchers leading cell measurement and the patient treatment trials. Patients came from one of two treatment cohorts.

In one, the OMNIVORE trial led by authors Rana McKay and Toni Choueiri, patients all received immune therapies. The immunotherapy drug stimulates the immune system to help it identify and kill cancer cells.

The other cohort, led by Hamid Emamekhoo at UW Health, involved patients whose physicians prescribed the treatment they thought best, including immune therapies, but also drugs known as tyrosine kinase inhibitors. Researchers gathered a total of 457 blood samples from 104 patients.

The team was able to automatically count and analyze the circulating tumor cells thanks to specialized equipment at the Circulating Biomarker Core in the UW–Madison Carbone Cancer Center managed by author Jennifer Schehr.

Patients with increasing levels of circulating tumor cells lived four months shorter on average than patients with a lower rate of change in their blood.

“I think these results make a lot of sense,” says Zhao. “Circulating tumor cells are a surrogate for tumor burden. If they are going up, that’s likely a bad sign. If they’re dropping, that’s promising that treatment is working.”

The equipment also measured the levels of two important proteins: HLA 1 and PD-L1. These two proteins provide opposite information about tumor cells. High levels of HLA 1 can make cells more sensitive to attack by the immune system, while high levels of PD-L1 helps tumor cells hide from the immune system.

The team combined that information into a single data point per patient, the ratio of HLA 1 to PD-L1. As patients underwent treatment, that ratio changed. The lower it went, the better treatments like immunotherapy were working — as the most vulnerable cancer cells were killed first by the immune response. If the ratio didn’t change or became higher, it might be a sign that the tumors were becoming resistant to treatment.

“We hope to use this information to react faster going forward and get patients on a more appropriate therapy,” says Bootsma. “That’s where the value of these real-time liquid biopsies comes into play.”

With more research trials, such real-time information could become the standard of care for physicians treating patients with kidney cancer and potentially other cancers as well.

“These trials are on the way, with the National Cancer Institute recently approving one of these trials that will integrate these blood studies for patients with metastatic kidney cancer that will open in early 2023,” says Lang.

This work was supported in part by the National Institutes of Health (grants DP2 OD030734-0 and P30 CA014520).