US scientists have found that by examining both blood tests and tumour tissue from patients who have non-small-cell lung cancer, they can find markers which reveal the stage of the cancer and help to distinguish between major subtypes of the disease. The study was published in Scientific Reports under a Creative Commons Open Access licence which means the study is available to read in full, online. The institutions working together, included Massachusetts General Hospital, Harvard Medical School, Boston, Division of X-Ray imaging and Computed Tomography, German Cancer Research Centre, Heidelberg, Germany, Department of Urology in Berlin, among others.
Lung cancer accounts for around 26% of all cancer deaths in the US for both men and women. It is usually diagnosed in the late stages, with over 70% of patients dying. There is a lack of universal early screening for the disease and most patients are seeking medical help too late. Scientists are looking for a blood test which can detect molecules from cancer early enough for more effective treatment.
The tissue and blood samples were taken from 42 patients, who had been diagnosed with squamous cell carcinomas of the lung, and 51 patients who had adenocarcinomas of the lung. The scientists deliberately chose to include more patients at the early stage, as the aim of the study was to diagnose the disease earlier. Blood samples were also included from 29 healthy volunteers, to be a control. Fifty-eight of the patients had early or Stage I lung cancer and 35 were more advanced (Stages II, III or IV).
Current practice in the US suggests that middle-aged and older people, who have a history of being heavy smokers, should be screened annually for the disease, using low-dose CT. This scan is good at detecting small tumours, but it is an expensive test, and offers risks related to repeated radiation exposure. A blood test would offer a minimally invasive method to identify people who may need a CT scan. It is also important to catch the disease in the early stages to offer the best chance of successful treatment.
The scientists used high-resolution magnetic resonance spectroscopy or MRS to help characterise the chemical components of the tissue. This method has been used previously to help identify possible biomarkers of lung cancer in serum, but this is the first time, to the scientists’ knowledge that it has been used on paired samples from patients. They were looking for common features in both tissue and blood samples to help identify whether this could be used to diagnose lung cancer, the subtype and confirm the blood test results. They looked at the specific profiles of metabolites, which were found in both samples. These were able to indicate which type of lung cancer a patient had. The different types require different treatment. The profiles could also be used to identify which stages the disease had reached. Early stage disease is treatable while some of the later stages are not.
The profiles were also able to identify whether a patient was more or less likely to live for an average of 41 months following surgery. This discovery needs to be validated through further study, but it it were to be replicated, then patients could be identified who were at high risk for early death. These patients could be made high priority for clinical trials of new drugs. The study aimed to develop a blood test which could be part of a standard physical examination to enable suspicious signs relating to lung cancer to be found. Patients who were identified by the blood tests could then be referred for CT.
Limitations of the study, included the small sample of patients from a lung tumour bank, which enrolled patients who had already shown symptoms or whose disease had been found incidentally - so the results may not apply to a larger, more random section of patients. Also the scientists only looked for evidence of two types of non-small-cell lung cancer, so their conclusions can not be applied to other types of the disease without further study. However the scientists did feel that their exploratory study had provided a good basis for proof-of-concept and that their results showed that further study was needed.
Christiani, D.C., Cheng, L.L., et al., Magnetic Resonance Spectroscopy-based Metabolomic Biomarkers for Typing, Staging and Survival Estimation of Early-Stage Human Lung Cancer, Scientific Reports 9, July 2019, Article No: 10319