Liquid Biopsy Predicts Resistance to Neoadjuvant Therapy in Esophageal Cancer

By Reuters Staff

May 18, 2022

NEW YORK (Reuters Health) - Researchers have developed and validated a liquid biopsy assay that can predict response to neoadjuvant therapy (NAT) in patients with esophageal squamous-cell carcinoma (ESCC), which may lead to more-personalized treatment decisions.

ESCC is one of the most aggressive and lethal subtypes of esophageal cancer and response to NAT is mixed. Predicting NAT resistance is of "great significance for the selection of treatment options in ESCC patients," Dr. Ajay Goel of the Beckman Research Institute of City of Hope, in Monrovia, California, and colleagues note in Annals of Surgery.

The liquid-biopsy-based risk-prediction model for NAT in ESCC they developed provides a "simple, facile and non-invasive pretreatment selection approach in patients suffering from this malignancy," they say.

They developed it using 186 clinical ESCC samples, including 128 formalin-fixed paraffin-embedded specimens and a matched subset of 58 pretreatment serum samples, from two different centers.

When combined, a panel of four microRNA and three messenger RNA expression biomarkers robustly predicted resistance to NAT, with an area under the curve (AUC) of 0.85. Adding tumor size to this model increased the predictive power of this combination signature (AUC, 0.92).

The researchers successfully validated this combination signature in an independent cohort (AUC, 0.78). They further demonstrated that the predictive power was enhanced when combining the model with three clinicopathological predictors of tumor size and location and lymphatic invasion (AUC, 0.81).

In subgroup analyses, this NAT resistance risk (NATRR) model yielded "remarkable accuracy" for discriminating NAT non-responders from responders for each stage category, with an AUC of 0.80 in ESCC stage I & II patients and 0.79 in stage III & IV patients.

The model also showed "impressive" predictive potential in each patient who received either neoadjuvant chemoradiotherapy or neoadjuvant chemotherapy (AUC, 0.88 and 0.77, respectively).

The team successfully translated the NATRR model into a liquid biopsy assay, with an AUC of 0.78. Multivariate regression analysis pegged the model as an independent predictor for response to NAT, with an odds ratio of 6.10 (P<0.01).

"As we usher into the era of precision oncology, it is imperative that patients are offered treatment that have higher likelihood of benefit and minimal toxicity," Dr. Goel and colleagues write.

"Our study provides a proof-of-concept precision-medicine assay, for its further validation in future prospective clinical trials," they say.

Funding for this research was provided by National Cancer Institute. The authors have declared no conflicts of interest.

SOURCE: Annals of Surgery, online May 13, 2022.