SAN FRANCISCO-A blood test for circulating tumor cells (CTCs) was able to detect lung cancer recurrence months before evidence appeared on PET or CT scans, researchers told attendees at the 2017 Multidisciplinary Thoracic Cancers Symposium (Abstract 3). In the largest prospective clinical trial to date, a CTC assay detected recurrence of localized advanced stage II or III non-small cell lung (NSCLC) up to 6 months before imaging.
"CTC monitoring in patients undergoing chemoradiation for locally advanced NSCLC is feasible," said Chimbu Chinniah, MD, Research Fellow in Radiation Oncology in the Perelman School of Medicine at the University of Pennsylvania in Philadelphia.
"CTC elevations in many of the patients meaningfully preceded radiologic evidence of recurrence and may be a promising biomarker of progressive or recurrent disease to help guide early salvage therapeutic strategies," he noted.
Unlike other biomarkers, a blood test for elevated CTC would allow more frequent and less-invasive testing for recurrence, Chinniah explained.
"The additional lead time afforded by an earlier diagnosis may enable doctors to better tailor alternative and salvage treatments to improve their patients' outcomes and quality of life. Earlier detection of recurrence may even translate into an increased likelihood of curing these patients when their tumor burden is lowest and thus more likely to respond to therapy."
Methods, Results
The trial involved 48 patients with locally advanced NSCLC who were receiving concurrent chemoradiation for either squamous cell carcinoma (48%) or adenocarcinoma (46%). They ranged in age from 31 years to 84 years, with a median age of 66 years, and none had a history of prior malignancy.
The investigators also factored into their analysis patient gender (54% male), race (69% Caucasian, 21% African-American), smoking status (77% former, 21% current), histology (48% squamous cell carcinoma, 46% adenocarcinoma), and primary tumor size (median 3.7 cm).
An adenoviral probe was used to detect elevated telomerase activity as a biomarker of cancer cell replication. Blood samples were collected before, during, and after 1, 3, 6, 12, 18, and 24 weeks after treatment, and CRCs were identified at each examination using the probe and surveillance scans with CT or PET/CT were conducted at 3-month intervals.
Patients had stage IIIA (54%) or IIIB (33%) NSCLC with cN2 (60%) or cN3 (23%) nodal disease. At a median follow-up of 10.9 months, 22 of 48 patients (46%) recurred at a median time of 7.6 months post-RT (range 1.3-32.0). Blood samples were obtained following chemoradiation therapy for 20 of the 22 recurrent patients.
Fifteen of these 20 patients had elevated CTC counts following treatment, with a median lead time of 4.7 months and a range of 1.2 months to 1 year. In 15 patients, two-thirds had elevated CTC counts on average 6 months before recurrence was detected by PET/CT or CT scan.
"For many patients, CTC levels were negative immediately following treatment, but rose subsequently in the months following treatment," noted Chinniah. "While most of these CTC level rises occurred before disease recurrence was identified on imaging, four of the 20 patients experienced recurrences that were detected with imaging before elevated CTC levels indicated the disease had returned."
"The future use of circulating tumor cells as a diagnostic and prognostic tool for localized NSCLC looks promising. Although imaging remains the cornerstone of post-treatment surveillance for patients, blood tests could, and perhaps should, be used in conjunction with imaging scans to better monitor patients during their follow-up period after treatment," noted Charles B. Simone, II, MD, the study's senior author.
"Right now the standard of care after treatment with chemoradiation is to follow patients serially with imaging, either CT or MRI scans. Unfortunately, by the time the tumor is big enough to be detected on imaging, treatment options may be very limited," he continued. "Analyzing tumor cells in the blood may help us diagnose recurrences at an earlier phase when these recurrent cancers may be more amenable to being cured."
Future for Lung Cancer
Lung cancer research is gradually catching up with advances in treating other types of cancers, said briefing moderator Ravi Salgia, MD, PhD, Professor and Chair of Medical Oncology and Therapeutics Research at City of Hope Comprehensive Cancer Center, in Duarte, Calif.
"We've come a long, long way," he said. "In the early days, we focused on early disease, but today we are truly in the age of personalized precision medicine. Breast cancer has been ahead of us, but lung cancer is catching up fast, and as we go forward with individualized therapy we need to be looking out for new biomarkers. We have always been looking for a blood biomarker test, until now no CTC test for lung cancer has come to fruition," he told Oncology Times.
Although the study demonstrates it is possible to measure CTCs in blood and use them as a predictive biomarker for cancer recurrence, much work remains, he noted.
"To me, this is a proof-of-concept study. We have to be very picky about CTCs and their significance in different stages of NSCLC, together with their context when used with radiation, chemotherapy, or both."
Hopefully, a blood test will be developed that will be easy to administer, like testing for PCA in prostate cancer.
"Other types of assays, such as liquid biopsies to test for DNA mutations, also play a role. We already have an approved urine test for T790M mutations. These tests are already here and we are using them in clinical practice, but we have to be savvy in interpreting the results-what's right for each patient," Salgia concluded.
Kurt Samson is a contributing writer.