Researchers have discovered that a test named ORACLE can more accurately predict survival rates for lung cancer patients at the time of diagnosis, outperforming existing clinical risk assessments. This advancement may enable doctors to make better-informed treatment choices for individuals with stage 1 lung cancer, which could lessen the likelihood of cancer recurrence or metastasis.
A team from the Francis Crick Institute, UCL Cancer Institute, and UCLH has demonstrated that ORACLE can more effectively predict survival outcomes for lung cancer patients at diagnosis compared to traditional clinical risk factors. This improvement could assist healthcare providers in offering more tailored treatment options for those with stage 1 lung cancer, thereby potentially lowering the risk of cancer returning or spreading.
Published in Nature Cancer, this research involved testing ORACLE on 158 lung cancer patients as part of the Cancer Research UK-funded TRACERx study. The findings indicated that ORACLE is capable of more accurately forecasting patient survival than current clinical benchmarks such as tumor stage.
Introduced in 2019, ORACLE was designed to address the absence of biological indicators in lung cancer, which can help doctors identify patients at a higher risk of recurrence or progression of the disease1.
This is especially crucial for stage 1 lung cancer patients, who typically undergo surgery without accompanying chemotherapy. Unfortunately, 25% of these patients experience a recurrence, suggesting they might have benefited from closer monitoring or chemotherapy treatments.
When physicians obtain a tumor sample, they generally capture less than 1% of the tumor, which can possess significant genetic variation among different areas. ORACLE addresses this challenge by analyzing genes that are either highly or minimally expressed throughout the entire tumor.
The latest research indicates that ORACLE can identify stage 1 lung cancer patients with a reduced chance of survival, suggesting that they may require chemotherapy alongside surgery—information that current clinical standards fail to provide for this patient group.
Additionally, the study revealed that high ORACLE risk scores correlated with tumor regions that are more likely to spread to other body parts.
Moreover, when examining 359 available and candidate drugs for lung cancer, researchers found that elevated ORACLE risk scores were associated with better responses to certain chemotherapy agents, especially platinum-based drugs like cisplatin.
This is attributed to the fact that areas of tumors exhibiting high ORACLE scores are linked to chromosomal instability, which is specifically targeted by these platinum therapies. Recent findings from the same research team have identified alterations in a significant gene known as FAT1 that lead to chromosomal instability—one of the genetic factors that ORACLE monitors.
The researchers plan to compare the outcomes of patients with high ORACLE scores receiving standard treatment against those undergoing increased surveillance or chemotherapy, in order to ascertain whether the test contributes to improved survival rates, even in cases diagnosed at the earliest stages.
Dhruva Biswas, a Translation Fellow at the Crick and a Postdoctoral Fellow at the UCL Cancer Institute, along with co-first author, stated: “ORACLE is now capable of predicting survival rates for patients diagnosed at the most initial stages. If validated in larger patient populations, it could help physicians make well-informed treatment choices, integrating insights from cancer evolution into clinical practice.”
Yun-Hsin Liu, Research Assistant at the UCL Cancer Institute and co-first author, mentioned: “Our goal was to expand on previous work with ORACLE and demonstrate its ability to predict survival rates at the point of lung cancer diagnosis. We have also shown its capacity to identify patients likely to benefit from specific chemotherapy types, as well as assess the potential for cancer spread, thereby providing a comprehensive evaluation of a patient’s cancer trajectory and response.”
Charles Swanton, Deputy Clinical Director and Head of the Cancer Evolution and Genome Instability Laboratory at the Crick, who is also a medical oncologist with University College London Hospitals and Chief Investigator for TRACERx, remarked: “Lung cancer remains the leading cause of cancer-related fatalities globally, highlighting the urgent need for improved markers to accurately categorize tumors and identify high-risk patients. We are collaborating with the Translation team at the Crick and industry partners to advance ORACLE into a tool that may be utilized in clinical settings as soon as possible.”
Paul Mercer, Head of Industry Partnerships in the Crick Translation team, added: “This represents a significant advancement in transforming our understanding of the complexities of lung cancer mutations into a diagnostic instrument that prioritizes patients for the most effective treatments. We anticipate collaborating with partners to further develop this research for maximal patient benefit through ORACLE.”
Dani Edmunds, Science Engagement Manager at Cancer Research UK, commented: “Over the past 50 years, cancer survival rates have doubled in the UK. Nonetheless, progress has not been uniform across all cancer types. While survival rates for lung cancer have improved since the 1970s, it continues to pose considerable treatment challenges.
“Innovative tests to forecast lung cancer behavior could empower doctors to customize treatment plans for individual patients, thereby enhancing chances of successful outcomes.
“This research underlines Cancer Research UK’s dedication to addressing this difficult-to-treat cancer. Although ORACLE requires testing in larger clinical trials, these initial findings indicate it could help pave the way for more personalized lung cancer treatment approaches, ultimately allowing more individuals to live longer, healthier lives.”
This study is backed by the National Institute for Health and Care Research UCLH Biomedical Research Centre.
