March 16, 2017
Maryland Proton Treatment Center Medical Director Charles B. Simone, II, MD, is the senior author of a new study that shows a promising biomarker may facilitate earlier detection and targeted treatment of recurrent disease.
The study shows that a blood test to measure levels of circulating tumor cells can detect recurrence of lung cancer an average of six months before it is visible on conventional CT or PET/CT scans. With early detection, patients with locally advanced non-small cell lung cancer (NSCLC) whose cancer returns may be able to receive earlier, targeted treatments that could help improve outcomes.
“Right now, the standard of care after treatment with chemoradiation is to follow patients serially with imaging, either CT or PET/CT scans. Unfortunately, by the time the tumor is big enough to be detected on imaging, the treatment options may be very limited,” says Dr. Simone, associate professor of radiation oncology at the University of Maryland School of Medicine.
“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,” says Dr. Simone. “If additional multi-center studies confirm our findings, this new biomarker could change the way we diagnose recurrences and ultimately treat and tailor treatments to individual patients, giving us critical extra time to combat a potentially deadly recurrence.”
The study of 48 patients is the largest prospective clinical trial to analyze circulating tumor cells in patients with locally advanced NSCLC. The results will be presented today at a plenary session at the 2017 Multidisciplinary Thoracic Cancers Symposium in San Francisco. The meeting is co-sponsored by the American Society for Radiation Oncology (ASTRO), the American Society of Clinical Oncology (ASCO) and The Society of Thoracic Surgeons (STS).
NSCLC accounts for over 85 percent of all lung cancers. Locally advanced cancers (Stage II-III) are cancers in the lung that generally have metastasized tonearby lymph nodes but that have not spread to both lungs or outside of the chest. Circulating tumor cells, or CTCs, are shed from a primary tumor into the bloodstream or lymphatics system and carried throughout the body, where they may seed other tumors if not destroyed by the immune system.
The research was conducted at the University of Pennsylvania, where Dr. Simone was on the faculty until he came to the University of Maryland to become medical director of the Maryland Proton Treatment Center in 2016. Chimbu Chinniah, a research fellow in radiation oncology at the University of Pennsylvania’s Perelman Center for Advanced Medicine, is the lead author.
Patients in the study were treated with concurrent chemotherapy and radiation for locally advanced NSCLC, including squamous cell carcinoma and adenocarcinoma. The median age was 66 years old, and the group was predominately male, Caucasian and comprised of former and current smokers.
The researchers tracked rising levels of CTCs in the patients’ blood after their treatment and monitored them with CT and PET/CT scans every three months. They identified CTCs by using an adenoviral probe that detects elevated levels of telomerase, an enzyme present in nearly all lung cancer cells but not in normal cells.
At a median follow-up of 10.9 months, 22 of the 48 patients (46 percent) experienced a recurrence of their cancer, with the median time to recurrence of 7.6 months. The researchers analyzed blood samples at serial time points from 20 of these recurrent patients, and 15 of them experienced rising levels of CTCs after completing therapy. Of these, 10 had a rise in CTC counts an average of six months before CT and PET/CT scans detected that their cancer had returned.
One patient, who experienced an early recurrence, had persistent elevated CTC levels during and after treatment. And in four cases, patients’ CTC levels did not rise before imaging detected the recurrence. “Not all patients have detectable levels of circulating tumor cells in their blood,” Dr. Simone says.
The researchers concluded that monitoring CTCs in advanced NSCLC patients is feasible and that CTC elevations in many patients “meaningfully” precede radiologic evidence of disease recurrence.
“Together, these findings suggest that CTCs may be a promising biomarker of progressive or recurrent disease and may help guide early salvage therapeutic strategies,” they concluded. Salvage therapies are treatments used after patients have failed to respond to other therapies.
Traditionally, doctors have treated recurrences with systemic therapy, such as chemotherapy, but an isolated recurrence in the chest might be treated with a newer option such as proton therapy to target only the tumor, Dr. Simone says. Proton therapy is a very precise form of radiation therapy that uses protons, instead of photons, to destroy cancer cells. Proton therapy might be the safest option in the recurrent setting and potentially allow for a new chance of cure in selected patients. New types of immunotherapy to prod the patient’s immune system to attack the cancer may also be an option.
“This clinical study led by Dr. Simone breaks significant new ground in demonstrating how circulating tumor cells can help to identify lung cancer patients likely to experience a recurrence well before the cancer can be detected by conventional imaging,” says E. Albert Reece, MD, PhD, MBA, vice president for medical affairs at the University of Maryland and the John Z. and Akiko K. Bowers Distinguished Professor and dean of the University of Maryland School of Medicine. “With early detection, we will be better able to offer patients more effective, personalized treatment options.”
The University of Maryland School of Medicine was chartered in 1807 and is the first public medical school in the United States. It continues today as an innovative leader in accelerating innovation and discovery in medicine. The School of Medicine is the founding school of the University of Maryland and is an integral part of the 11-campus University System of Maryland. Located on the University of Maryland’s Baltimore campus, the School of Medicine works closely with the University of Maryland Medical Center and Medical System to provide a research-intensive, academic and clinically based education. With 43 academic departments, centers and institutes and a faculty of more than 3,000 physicians and research scientists plus more than $400 million in extramural funding, the School is regarded as one of the leading biomedical research institutions in the U.S. with top-tier faculty and programs in cancer, brain science, surgery and transplantation, trauma and emergency medicine, vaccine development and human genomics, among other centers of excellence. The School is not only concerned with the health of the citizens of Maryland and the nation, but also has a global presence, with research and treatment facilities in more than 35 countries around the world. www.medschool.umaryland.edu.
Abstract #3: Prospective Trial of Circulating Tumor Cells as a Biomarker for Early Detection of Recurrence in Patients with Locally Advanced Non-small Cell Lung Cancer Treated with Chemoradiation
C. Chinniah, L. Aguarin, P. Cheng, C. DeCesaris, A. Cutillo, A. T. Berman, M. Frick, W. P. Levin, K. A. Cengel, S. M. Hahn, J. F. Dorsey, G. D. Kao, and C. B. Simone II