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Circulating tumor cell test can detect lung cancer recurrence before CT
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Blood tests that used circulating tumor cells as biomarkers detected recurrences of locally advanced non–small cell lung cancer months earlier than conventional CT imaging methods, according to a prospective clinical trial presented at the Multidisciplinary Thoracic Cancers Symposium.
“Utilizing [circulating tumor cells (CTCs)] hasn’t really been explored in that much detail for locally advanced non–small cell lung cancer,” Chimbu Chinniah, research fellow in radiation oncology at Perelman School of Medicine of University of Pennsylvania, said during a press conference. “This is the largest prospective trial looking specifically for biomarkers in CTCs. What’s different about this trial is that it’s probing live cells, and we’re looking at something inside the cells themselves and not a cell surface marker.”
Under standard treatment, patients receive surveillance CT or PET/CT scans to monitor for cancer recurrence. However, blood tests can track CTC counts — which often re-enter the bloodstream after treatment — more often and less invasively than follow-up biopsies. Researchers sought to show CTC biomarkers could help find locally advanced NSCLC recurrence earlier than with imaging scans alone.
In the trial, 48 patients (median age, 66 years; range, 31-84; 54% men; 69% white, 21% black) with stage II to stage III locally advanced NSCLC (48% squamous cell carcinoma; 46% adenocarcinoma) and no prior active malignancies were treated with concurrent chemoradiation. Overall, 77% of patients were former smokers and 21% were current smokers. Median primary tumor size was 3.7 centimeters (range, 1.5-10).
Researchers collected blood samples before treatment; at 2, 4 and 6 weeks during treatment; and at 1, 3, 6, 12, 18 and 24 months after treatment. CTCs were identified with adenoviral probes that detect elevated telomerase activity, which is produced when cancer cells replicate. Patients underwent CT or PET/CT imaging at 3-month intervals.
“The reason we used adenoviral probes is because they detect high levels of telomerase, which is found in almost all cancer cells but in almost no normal cells, with the exception of rare stem cells,” Chinniah said. “Consequently, it is a highly specific marker of live cancer cells.”
At a median follow-up of 10.9 months following treatment, 22 patients (46%) experienced recurrence or regression as detected by conventional surveillance scans and biopsies. Median time to recurrence was 7.6 months (range, 1.3-32).
Blood samples were drawn following chemoradiation from 20 of the patients with recurrent disease.
Fifteen of those patients had elevated CTC counts, 10 of whom demonstrated a rise in CTC counts an average of 6 months before PET/CT scans detected the same recurrence. The median lead time between CTC rise and radiographic evidence of recurrence was 4.7 months (range, 1.2-12). For four of these patients, recurrent disease was detected with imaging before CTC tests.
Chinniah and colleagues reported that for many patients, CTC levels were negative immediately following treatment but rose substantially in the months following treatment.
“Something we’re definitely looking at is to see how we can utilize this and improve outcomes,” Chinniah said. “CTC doesn’t delay the progression, but identifies it ahead of time. When patients have less of a disease burden [at earlier recurrence], we can perhaps treat it then for better outcomes. In terms of actually implementing it, we could use the values we get from these blood samples ... to determine if we want to be more aggressive with treatment earlier on.”
The use of precision medicine for lung cancer can follow in the footsteps of advances made in breast cancer, Ravi Salgia, MD, PhD, professor and chair in the department of medical oncology and therapeutics research at City of Hope, who was not involved with the study, said during the press conference.
“Breast cancer has been way ahead of us in the past, but we are really catching up fast and even moving ahead to be able to say circulating tumor cells in lung cancers are here to stay and we have to look at that as a biomarker,” Salgia said.
Future research is needed to test whether early detection of disease recurrence by CTC analysis translates to improved outcomes, Chinniah said.
“Perhaps we can treat these patients earlier on and improve their quality of life down the road,” he said. “In the future, we can evaluate the use of CTCs as a diagnostic tool for stage I patients, so they don’t unnecessarily get biopsies or surgeries.”– by Chuck Gormley
Reference:
Chinniah C, et al. Abstract 3. Presented at: Multidisciplinary Thoracic Cancers Symposium; March 16-18, San Francisco.
Disclosure: Chinniah and Salgia report no relevant financial disclosures. Please see the abstract for a list of all other researchers’ relevant financial disclosures.
Perspective
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Jeffrey D. Bradley, MD
Research on circulating tumor DNA or circulating tumor cells is in its infancy. There are some considerations for these tests.
Usually having a test come back positive is highly dependent on the bulk of tumor in the patient.
A stage IV population with lots of metastasis has a higher chance of picking up those markers than in a patient with a smaller tumor burden. Most of the studies have been done in patients with metastatic disease, but as biopsies are moved earlier in disease, tumor burden is not as high, and their yield is not as high.
Many think now that circulating tumor DNA can be collected at the same time of a biopsy with a faster result within a few days. We might do both, but I do not know that they have replaced biopsies, because they are not that reliable yet.
Right now, circulating tumor DNA or circulating tumor cells should not be used in place of scans unless you have a patient for whom you know that assay is working. In general, these biopies have not replaced the scans, and there is more work that needs to be done. For example, cobas EGFR Mutation Test (Roche Molecular Diagnositics) is approved just for EGFR mutations. What about ROS mutations and ALK translocations? There’s more work to be done on these blood tests before they become the headline test.
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