TRACERx data trove helps refine use of blood markers for lung cancer

By Emily Hayes, LabPulse.com editor in chief

October 9, 2019 -- Circulating tumor cells in the blood might be helpful for predicting survival and relapse rates in early-stage non-small cell lung cancer, according to a study of patients enrolled in a Cancer Research UK project. Results were reported in Nature Medicine on October 7.

The multi-institutional Tracking Non-Small Cell Lung Cancer Evolution Through Therapy (TRACERx) translational research program is studying the genetics of 750 lung cancer patients from the time of diagnosis through surgery and either disease relapse or cure. After surgery, the five-year relapse rate in lung cancer ranges from about 20% in patients with stage I disease to 50% at stage III, the investigators noted.

Caroline Dive, PhD, deputy director of the Cancer Research UK Manchester Institute, and colleagues examined circulating tumor cells in a TRACERx cohort of 100 patients (Nat Med, October 7, 2019, Vol. 25, pp. 1534-1539). Specifically, the researchers evaluated the association between pulmonary venous circulating tumor cells (PV-CTCs) at the time of surgery with the CellSearch test (Menarini) and relapse rates/the development of metastases.

The investigators sought to follow up on a pilot study showing an association between peripheral blood circulating tumor cells on CellSearch, which measures the expression of epithelial cell adhesion molecule (EpCAM) and cytokeratin proteins, and survival in patients with early-stage lung cancer.

In the 100 TRACERx patients with stage I-III lung cancer assessed, PV-CTCs were present in almost half (48%). The researchers initially used a threshold for high PV-CTC count of 18 PV-CTCs per 7.5 mL of blood. But while this level was significantly associated with poorer disease-free survival, the sensitivity was only 31.7%.

In an exploratory analysis, they tested a threshold of at least seven PV-CTCs per 7.5 mL of blood and its association with disease relapse. They found a significant association with lung cancer-specific relapse; however, the sensitivity was modest, at 45.2%.

The researchers also noted that each doubling of the PV-CTC count was significantly associated with lung cancer-specific relapse.

"Collectively, these data raise the possibility that patients with a 'high' CellSearch PV-CTC count at resection may benefit from increased minimal residual disease (MRD) monitoring [postsurgery]," Dive and colleagues wrote.

"We have shown that increasing PV-CTC count as a continuous variable is associated with poor prognosis. To use PV-CTCs in a clinical setting, a [predefined] cutpoint will be required to prospectively stratify patients," they added.

Two other studies from TRACERx that provide insight into the evolution of non-small cell lung cancer were also just published. Benny Chain, PhD, a professor of cell and molecular biology at University College London, and colleagues, published their experience with tumor-infiltrating lymphocytes (TILs) in tumor biopsies for assessing immune response in lung cancer (Nat Med, October 7, 2019, Vol. 25, pp. 1549-1559).

In addition, Dhruva Biswas, a doctoral student at the Francis Crick Institute, and colleagues reviewed the use of a genetic profiling technique called Outcome Risk Associated Clonal Lung Expression (ORACLE), in combination with a machine-learning algorithm, for gauging the aggressiveness of lung tumors (Nat Med, October 7, 2019, Vol. 25, pp. 1540-1548). In contrast with other methods, ORACLE homes in on stable genetic features, which the researchers think can overcome a key limitation of tissue biopsies.

"These features could be spotted no matter which part of the [tumor] is sampled for testing meaning they could be a more accurate guide for predicting the future clinical outcome for patients," Biswas said in a statement.


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