Honing in on Lung Cancer

PET/CT—since its introduction in 2001—has emerged as the primary diagnostic tool in the staging of lung cancer when compared to PET and CT alone. The shift from CT to PET/CT will continue with technological advances in respiratory gating and molecular imaging.

PET/CT vs. CT

FDG PET/CT has emerged as the imaging tool of choice for staging and restaging lung cancer and also assessing patient response to therapy. “PET/CT combined gives you more sensitivity and areas of most metabolic reaction—sites of disease that you otherwise wouldn’t,” says John M. Buatti, MD, professor and head, radiation oncology at the University of Iowa hospitals and clinics in Iowa City.

“The improvement in staging over CT relates not just to the detection of disease outside the thorax, but also for the local extent of the disease in the thorax—regional lymph nodes at the pulmonary hilar regions, in the mediastinum and at base of the neck,” says Michael Fulham, MD, director, department of PET and nuclear medicine at Royal Prince Alfred Hospital in Sydney, Australia. “PET/CT has improved the ability to detect disease in non-enlarged lymph nodes, which is extremely problematic
for conventional CT imaging.” 

PET/CT helps in effective staging and avoiding futile thoracotomies in lung cancer patients, too. “In a study, conducted by Canadian academic institutions, PET/CT correctly upstaged disease to unresectable stage IIIB and IV in 13.8% of patients; conventional staging correctly upstaged disease in only 6.8%,” Mitchell L. Margolis, MD, from the Philadelphia Veterans Affairs Medical Center and University of Pennsylvania in Philadelphia, wrote in an editorial on the study in the Aug. 18, 2009, issue of the Annals of Internal Medicine.

“PET/CT gives more information on the effectiveness of therapy than the CT alone because the tumor may have metabolic changes which do not change in CT,” says Peter S. Conti, MD, PhD, professor of radiology, pharmacy and biomedical engineering
at the University of Southern California’s (USC) Keck School of Medicine. “ If you want early assessment of the effectiveness of therapy, you have to really use the PET/CT; if you want to approach it from the traditional protocol-driven standard follow up period, you still want PET/CT, but you will miss out the full value of what PET brings in which is on the early side”.

“At Royal Prince Alfred Hospital in Sydney, Australia, we have performed over 10,100 FDG PET scans [3,200 PET only and 6,900 PET/CT scans] for patients with suspected or proven non-small cell lung cancer (NSCLC),” says Fulham. “These studies have been performed predominantly in the pre-surgical staging of lung cancer but we also perform studies prior to radiotherapy planning, after the completion of induction chemotherapy and when there is suspected recurrent disease or a new primary tumor.”

However, there are limitations. PET/CT is not useful in screening for lung cancer and, unfortunately, there is no efficient screening test for lung cancer. “Screening tools have to be very sensitive and low cost by definition,” Conti notes. PET/CT is not accurate in detecting sub-centimeter lesions.

Interpretation of data is important in terms of arriving for the proper care for the patient in terms of biopsy and treatment. “A lot of inflammatory lesions also can have a very strikingly high uptake on PET,” says Margolis. “In gross cases, it is easy to determine if the tumor is a T4 tumor and there is extension into the mediastinum—but the problem arises where the abnormal metabolism abuts the mediastinal pleura,” Fulham adds.

Overcoming respiratory motion

Fulham says respiratory gating, which improves the ability to localize and accurately quantify focal areas of abnormal metabolism in the lung fields, offers an advantage. “This is particularly important for the small lesions towards the base of the lungs which are most affected by respiratory motion.”

One approach in treatment is to deliver the radiation beam at a specific point in the respiratory cycle of the patient. “The difficulty with this approach is it requires the patient to breathe exactly the same way throughout the entire treatment—obviously that may or may not be the case” says Ramesh Rengan, MD, PhD, assistant professor, department of radiation oncology at University of Pennsylvania in Philadelphia. “The other approach is to gate the patient—who takes a deep breath and holds the breath during the CT scan. The advantage is a lot of normal tissue can be pulled away from the radiation field when the lung expands and only one spot has to be treated.” While theoretically this approach works well, there are limitations. “Lung cancer patients have poor pulmonary function and taking a deep breath and holding it is very difficult—only 30 percent of the patients can follow the instructions,” Rengan says.

Conti believes that technological advances in respiratory gating are going to improve. “Right now, we still have the capability of doing breath-hold CT on a PET/CT scanner, but it has to be independent of the PET acquisition.

“The challenge is also to see what you treat,” says Rengan. “The challenge is not only to accurately identify where the tumor is, but to see what you are treating. Right now, we do not have a way of visualizing the tumor when the radiation beam is on.”

Shift to PET/CT

Optimism reigns in the future of PET/CT, particularly in light of this technology’s ability to use different molecular markers such as 11C-Acetate or 18-F-Fluorothymidine, Buatti notes. “FDG may not be as quite sensitive [since] 11C-Acetate and 18-F-Fluorothymidine may be able to give index response based on proliferation and distinguish inflammatory vs. cancer,” shares Buatti.

Fulham sees PET/CT as the primary diagnostic tool in the accurate staging of NSCLC outside the brain and predicts that advances in instrumentation, reconstruction algorithms and time-of-flight technology will allow us to pick smaller amounts of disease and improve staging and monitoring response to therapy.

“We see a shift from CT to PET/CT in not just lung cancer but in several cancers—lymphomas no longer get the dedicated CTs; they get PET/CTs,” sums Conti. “There is just no need to do the extra test. [Physicians] want the PET scan because they want the metabolic information and they get the CT anyway so they don’t need to get the extra CT scan. If we need to use more PET/CT and use the CT more effectively in terms of its diagnostic capabilities, then you see more efficient use of resources in the medical community and save costs. Unfortunately, a lot of PET/CT centers are still doing non-diagnostic quality CT for attenuation correction purposes and to me that seems to be a missed opportunity.”