Summary: The ORACLE test can predict lung cancer survival at diagnosis more accurately than existing clinical methods, offering new hope for tailored treatments in stage 1 patients.

Takeaways

  1. Enhanced Prognostic Accuracy: ORACLE predicts survival rates for stage 1 lung cancer patients better than clinical standards, helping identify those who might benefit from chemotherapy in addition to surgery.
  2. Targeted Chemotherapy: The test links high-risk scores to better responses to platinum-based chemotherapy drugs like cisplatin, which target unstable tumor DNA regions.
  3. Clinical Potential: With further validation, ORACLE could guide personalized treatment plans, improving outcomes for early-stage lung cancer patients by reducing recurrence and spread risks.

Researchers at the Francis Crick Institute, the UCL Cancer Institute and UCLH have shown that a test called ORACLE can predict lung cancer survival at the point of diagnosis better than currently used clinical risk factors. This could help doctors make more informed treatment decisions for people with stage 1 lung cancer, potentially reducing the risk of the cancer returning or spreading.

In research publishedx in Nature Cancer, the team tested ORACLE in 158 people with lung cancer as part of the Cancer Research UK-funded TRACERx study. They found that ORACLE could better predict patient survival than currently used clinical standards like tumor stage.

ORACLE: A Test for Lung Cancer Survival

ORACLE was developed in 2019 to overcome the lack of biological markers in lung cancer, which can indicate to doctors who might be at a greater risk of their cancer coming back or spreading to another part of the body(1).

This is particularly important for people with stage 1 lung cancer, who are normally given surgery without chemotherapy. For a quarter of stage 1 patients, their cancer returns, suggesting they may have benefitted from more frequent monitoring or chemotherapy.

When doctors take a sample from a tumor, they typically only capture less than 1% of the tumou, and the genetics can vary massively from region to region within the same tumor. ORACLE overcomes this by looking at genes expressed at a high or low level in every part in the tumor.

Predicting Survival Rates for Lung Cancer Patients

The new findings show that ORACLE could predict which patients with stage 1 lung cancer had a lower chance of survival, and might benefit from chemotherapy as well as surgery. Currently used clinical standards weren’t able to give this information for stage 1 patients.

“ORACLE can now predict survival rates in patients diagnosed at the earliest stage,” says Dhruva Biswas, translation fellow at the Crick, postdoctoral fellow at the UCL Cancer Institute, associate research scientist at Yale School of Medicine, and co-first author. “If  validated in larger cohorts of patients with lung cancer, doctors could one day use ORACLE to help make informed treatment decisions, bringing lessons from cancer evolution into the clinic.

The researchers also found that high ORACLE risk scores were linked to regions of the tumor that were more likely to spread to another part of the body.

“We wanted to build on the previous work developing ORACLE and show that it can predict survival at the point of a lung cancer diagnosis,” says Yun-Hsin Liu, research assistant at the UCL Cancer Institute, and co-first author. “We’ve also shown that it can predict who would benefit from certain types of chemotherapy drugs or if someone’s cancer is likely to spread, giving a holistic measure of how a patient’s cancer might progress and respond.”

Finally, by looking at 359 current and potential lung cancer drugs, they found that a high ORACLE risk score predicted better response to some types of chemotherapy, particularly platinum drugs like cisplatin

This is because tumor regions with high ORACLE scores are associated with unstable DNA (called ‘chromosomal instability’), which is particularly targeted by platinum drugs. The same lab has recently found that changes in a key gene called FAT1 drive chromosomal instability, which is also one of the genetic variations ORACLE looks for.

The next steps for the researchers are to compare people with high ORACLE scores receiving standard care and those receiving more surveillance or chemotherapy to determine if the test improves survival, even for people diagnosed at the earliest stage.

“In the last 50 years, cancer survival has doubled in the UK. However, progress has not been equal across all types of cancer. Although survival for lung cancer has improved since the 1970s, it’s still one of the most challenging cancers to treat,” says Dani Edmunds, science engagement manager at Cancer Research UK. “New tests to predict lung cancer’s behaviour could help doctors tailor treatment strategies to each person’s condition, giving the best chance of a successful outcome.

The study is supported by the National Institute for Health and Care Research UCLH Biomedical Research Centre.

References:

  1. In research published in Nature Medicine in 2019, the team analyzed genetic information from 156 tumor regions from 46 patients enrolled in TRACERx. They identified genes expressed in cells throughout the whole tumour which increase cancer cell reproduction. They used this information to generate a package of genes to look for in a sample (ORACLE). This research reports the testing of ORACLE in another set of TRACERx samples, to validate its ability to predict patient survival, particularly within the stage 1 group.