Scientists at the Francis Crick Institute, the UCL Cancer Institute, and UCLH have shown that ORACLE, a new predictive test, can better assess lung cancer survival rates compared to existing clinical risk factors. This new development, shared in Nature Cancer, may greatly enhance treatment choices for stage 1 lung cancer patients, lowering the chances of cancer coming back or spreading. 

In a study involving 158 lung cancer patients funded by Cancer Research UK, ORACLE showed better results than traditional methods like tumour staging in predicting how long patients would survive. ORACLE was created in 2019 because there weren't enough reliable biological markers for predicting the outcome of lung cancer. It finds high and low gene expressions across the whole tumour instead of relying on standard biopsy samples, which only show less than 1% of a tumor's genetic diversity.

This advancement is particularly important for stage 1 lung cancer patients, who usually have surgery without chemotherapy. About 25% of these patients face cancer returning. ORACLE helps by finding those who may need extra chemotherapy or closer monitoring. The test effectively identified patients with a lower chance of survival, something that current clinical standards do not offer for stage 1 cases. Furthermore, we linked high ORACLE risk scores to tumour areas that are more prone to metastasis. 

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Oracle also affects personalised treatment, in addition to risk assessment. Researchers found that tumours with high ORACLE scores respond well to platinum-based chemotherapy, like cisplatin. They looked at 359 existing and potential lung cancer drugs. This is due to their association with chromosomal instability, rendering cancer cells more vulnerable to DNA-damaging treatments. A new study from the same lab discovered that the FAT1 gene leads to chromosomal instability. This shows how important ORACLE's genetic markers are for picking treatments. 

The next stage of research will look at the results for high ORACLE score patients who get standard care compared to those who receive extra chemotherapy or increased monitoring. The aim is to find out if ORACLE-guided treatment choices can enhance survival rates, even for patients diagnosed at the earliest stage. 

Dhruva Biswas, Translation Fellow at the Crick and co-first author, highlighted ORACLE’s potential: “ORACLE can now predict survival rates in patients diagnosed at the earliest stage.” If proven effective in larger groups, doctors might use ORACLE to guide treatment choices, applying insights from cancer evolution in clinical settings. 

The co-first author, Yun-Hsin Liu, emphasised the test’s valuable insights: "We’ve demonstrated that ORACLE can identify patients who would benefit from certain chemotherapy drugs and evaluate the chances of cancer spreading, providing a complete view of disease progression and response." 

Charles Swanton, Deputy Clinical Director at the Crick and co-senior author, highlighted the need to move ORACLE into clinical use quickly: Lung cancer is the top cause of cancer deaths worldwide. We need improved markers to categorise tumours and pinpoint high-risk patients. We are collaborating with the translation team at the Crick and industry partners to implement ORACLE in clinical practice quickly. 

Paul Mercer, Head of Industry Partnerships at the Crick, highlighted its importance: “This is a key step in turning our knowledge of lung cancer mutations into a diagnostic tool that can help prioritise patients for the best therapies.” We are excited to work with partners to enhance ORACLE’s impact. 

Dani Edmunds, Science Engagement Manager at Cancer Research UK, explained the findings in relation to overall cancer survival trends: “In the last 50 years, cancer survival rates in the UK have doubled, but lung cancer is still one of the hardest to treat.” Oracle can predict how tumours behave, which may help customise treatments and improve patients' chances of success. More extensive trials are necessary, but these early results show potential for improving personalised lung cancer treatments.