- Early stage lung cancers are very small lesions and generally treated by surgical removal of the tumor
- These patients may however be shedding tumor cells into the bloodstream resulting in distant spread and relapse of cancer sooner than later
- Detection of such tumor cells in the blood may indicate an unfavorable outcome in persons with early stage lung cancer
Presence of tumor cell groups in the blood may be associated with a bad prognosis in early lung cancer according to a study conducted at the University of Michigan. This finding could be used to initiate additional treatments such as chemotherapy
to control the spread of disease.
The study team was led by Sunitha Nagrath, University of Michigan (U-M) professor of chemical engineering (who designs devices capable of capturing tumor cells within the blood) and included cancer specialists and surgeons. The study titled "Poor prognosis indicated by venous circulating tumor cell (CTC) clusters in early stage lung cancers"
will be published in Cancer Research
in August 2017.
‘Blood test (liquid biopsy) to detect cancer cells may soon be able to identify patients who need further treatment such as chemotherapy in early lung cancer to improve prognosis.’
Looking For CTC Clusters In The Blood - The Findings Of The Study
The study included a small sample of 36 patients with early stage lung cancer
. They underwent surgery to remove the tumor and were followed up for a period of 26 months.
The team collected blood samples before, during and following surgery to remove the tumor. At every stage, the surgeons sampled blood from a vein in the patient's arm, far from the tumor. During surgery, before disturbing the tumor, the surgeons withdrew blood from the lung vein that emerged from the tumor, where tumor cells would be expected to be highly concentrated.
The samples were analyzed by Vasudha Murlidhar, then a doctoral student in the Nagrath lab, using a microfluidic chip that she designed herself.
- Tumor cells from the arm vein showed a median count of around 1.3 per 3 ml, while the vein closer to the lung tumor showed 7.5 per 3 ml of blood.
The team believes that the fall in tumor cell concentration in the arm vein could mean that the tumor cell clusters were getting stuck in capillaries before reaching the arm. These clusters could potentially develop into larger tumors and disseminate. Another theory was that the tumor cells could be destroyed in the bloodstream.
- Clumps of two or more tumor cells indicated shorter duration of survival. Six of the nine patients who suffered a relapse of their cancer during the two to 26 months of follow-up showed tumor cell groups in their blood.
According to Rishindra Reddy, U-M associate professor of surgery who designed the study with Nagrath and Nithya Ramnath, an associate professor of medical oncology at the U-M Medical School, this technique can be used to detect as well as find potential markers of cancer as well as metastatic disease.
Circulating Tumor Cells (CTCs) In Blood - Key In Cancer Treatment And Prognosis
Although a person may be clinically diagnosed to have early stage lung cancer, there may be cancer cells in his bloodstream which might lead to tumor dissemination within the body and relapse of cancer in spite of removing the primary lung lesion.
"Even though you removed the tumor, you left behind these hundreds and hundreds of cells," Nagrath said. "If you know this patient walking out of the clinic is going to relapse after less than a year because of these cells, why don't we treat them now?"
Unique Features Of Circulating Tumor Cell Clusters
Tumor cell clusters have been found on genetic analysis to show an increased expression of genes encoding aggressive characteristics. They were able to travel better, dodge the immune system, and recruit immune cells to help them develop resistance to therapy. In short, tumor cell clusters were better adapted for cancer spread to distant sites.
"These are drivers of tumor progression and resistance, and they are more important to target with therapy," Nagrath said.
Scope Of Current Study
- Finding tumor clumps in the blood helps to identify patients who may benefit from additional treatments as well as targeted therapy utilizing the unique features of these cells.
Dr. Nagrath has created a new service arm within the University of Michigan termed Single Cell Analysis Core which will identify and isolate tumor cells in the blood using microfluidic chips developed by herself and members of her team.
"With a simple blood draw, we can tell the dynamic state of the disease during the treatment and after the treatment, monitoring it closely. If something has to show up on a CT scan, it may already be too late," Nagrath said.
In conclusion, the study shows that a simple blood test may be able to predict outcome in patients with early stage lung cancer, much before radiological findings become evident.
- Vasudha Murlidhar, Rishindra M Reddy, Shamileh Fouladdel, Lili Zhao, Martin K. Ishikawa, Svetlana Grabauskiene, Zhuo Zhang, Jules Lin, Andrew C. Chang, Philip W Carrott, William R Lynch, Mark B. Orringer, Chandan Kumar-Sinha, Nallasivam Palanisamy, David G. Beer, Max S. Wicha, Nithya Ramnath, Ebrahim Azizi, Sunitha Nagrath. Poor Prognosis Indicated by Venous Circulating Tumor Cell Clusters in Early Stage Lung Cancers. Cancer Research, 2017; canres.2072.2016 DOI: 10.1158/0008-5472.CAN-16-2072