A new liquid biopsy assay has demonstrated the ability to predict immunotherapy response in advanced cancer patients months before conventional imaging methods, according to results from the RADIOHEAD study published in Cancer Research Communications. The methylation-based circulating tumor DNA test, Guardant Reveal, successfully identified treatment responders and non-responders across multiple solid tumor types, potentially transforming how oncologists monitor immunotherapy effectiveness.
Study Design and Patient Population
The collaboration between Guardant Health and the Parker Institute for Cancer Immunotherapy analyzed more than 500 patients with advanced solid tumors, including lung, skin, head and neck, breast, gastrointestinal, genitourinary, and gynecologic cancers. The RADIOHEAD program represents a pantumor, prospective cohort study of 1,070 immunotherapy-naive patients receiving standard-of-care immune checkpoint inhibitor regimens across 49 US community oncology clinics.
The comprehensive study collected over 3,700 longitudinal blood samples at pretreatment, early on-treatment, and immune-related adverse event timepoints. Multi-omic profiling, including circulating tumor DNA analysis, whole-exome sequencing, and high-dimensional immune profiling, was paired with detailed clinical and demographic data to enable deep translational insights into mechanisms of response, resistance, and toxicity.
Key Clinical Findings
The study revealed compelling evidence for the clinical utility of blood-based monitoring in immunotherapy management. Patients with any reduction in tumor fraction demonstrated superior outcomes compared to those without reductions. Most significantly, patients with a decrease of 80% or more in circulating tumor DNA showed a 75% lower risk of progression.
The assay's ability to identify disease progression up to 5 months earlier than standard-of-care imaging represents a potential paradigm shift in cancer care. In some cases, non-responders were identified more than three months before disease progression became visible through conventional methods.
"Precise serial monitoring at the molecular level provides real value to oncologists and to patients using immunotherapy," said Craig Eagle, MD, chief medical officer at Guardant Health. "This study shows that Guardant Reveal has the potential to revolutionize how oncologists assess patient response, identifying earlier insights that can empower them to make informed decisions faster and improve patient outcome and quality of care."
Clinical Implications
The findings address a critical need in immunotherapy management, where approximately 30% of patients with advanced-stage cancer receive immunotherapy treatment with varying degrees and duration of response. The ability to detect treatment failure months before imaging changes could enable oncologists to pivot to alternative therapies earlier, potentially sparing patients unnecessary toxicity from ineffective regimens.
The Guardant Reveal assay utilizes methylation-based circulating tumor DNA analysis to provide a tissue-free method for measurable residual disease assessment. This technology expands the clinical utility of liquid biopsies beyond their established use in early-stage cancers like colorectal cancer, offering a new level of precision monitoring for patients with advanced malignancies.
Broader Research Context
The RADIOHEAD study represents one of the largest real-world investigations into immune checkpoint inhibitor regimens, with a focus on major immuno-oncology indications including non-small cell lung cancer and malignant melanoma. The comprehensive dataset provides opportunities to uncover mechanisms of response and resistance while applying machine learning approaches to explore immune and disease pathways.
"Our RADIOHEAD study of Guardant Reveal in advanced stage cancers provides patients with a new caliber of precision monitoring in order to create better patient outcomes," said Tarak Mody, PhD, chief business officer at the Parker Institute for Cancer Immunotherapy. "These findings exemplify PICI's commitment to forging mission-driven partnerships to bring cutting-edge technology into clinical practice, accelerate discoveries, and advance the development of curative immune therapies for patients."
The move toward non-invasive, blood-based monitoring for immunotherapy response represents a promising advancement in precision medicine, potentially optimizing treatment pathways for cancer patients while reducing healthcare costs associated with ineffective therapies.
