Investigators Review ELCAP’s Goals and Screening Protocols

NEW YORK—Leaders of the Early Lung Cancer Action Project (ELCAP) outlined their goals and the screening protocol that has evolved over the past 2 years at the 4^th International Conference on Screening for Lung Cancer.

Claudia Henschke, MD, PhD, chief, Division of Chest Imaging, and professor of radiology, Weill Medical College, Cornell University, said that the primary ELCAP goal is to determine tumor distribution at baseline and on repeat screenings. "You really want to know how early you can find these cancers by stage, by size, and perhaps in the future by other criteria, and how significant they are by cell type," she said.

Prognosis by subtypes of lung cancer, with and without early intervention, will also be assessed. Some patients, she noted, are willing to be screened and have diagnostic workups but will not consent to resection. "Those are very valuable individuals," she said. "Follow-up on them will give us information on the natural history of lung cancer and help us answer the question of overdiagnosis—if it exists and to what extent."

Another ELCAP goal is to find the frequency of newly diagnosed cancers by indications for screening, Dr. Henschke said. Participants are to provide data on smoking history, environmental background, age, and biomarkers to permit correlation with diagnoses. Persons screened in the ELCAP protocol, she added, should be asymptomatic.

Protocol Variations

While institutions participating in ELCAP are to follow its protocol, "the validity of the study is not threatened by variations in certain aspects of that program," Dr. Henschke said. "Participating institutions do not need to commit to more than one repeat scan. You do have to do a baseline and at least one repeat. We ideally want you to continue screening, but it is not an absolute requirement."

Eligibility criteria for registry in the screening may differ by institution, she added, and so may equipment.

"The flexibility that you have," Dr. Henschke said, "is permitted because the distribution of lung cancers is presumably invariant over successive repetitions of screenings as well as over various levels of risk for lung cancer. In other words, while the overall frequency of lung cancer increases with, for example, age, it should not determine the relative frequencies of the diagnostic subtypes."

All individuals enrolled at participating institutions must be registered with the ELCAP coordinating center and all data collected on them transmitted to enable analysis. All interim diagnoses of lung cancer, Dr. Henschke stressed, must be documented. Although interventions may vary in different institutions, the timing and nature of treatment must be documented for the coordinating center.

"The first thing you have to specify is what equipment you will use to obtain the images," Dr. Henschke said. The protocol, she reported, recommends using a multislice helical scanner at low-dose settings, 401cVp, 40 mA, with a fast pitch of 6.1 and a 1.25-mm slice thickness. Such scans, she noted, provide the best imaging now possible in a single breath-hold with contiguous slices from the thoracic inlet to the adrenal glands and do not require contrast materials.

Institutions that do not yet have multislice equipment, she said, may use a single-slice helical CT at low-dose settings. Any positive scans detected with such equipment, she noted, must be followed by a standard-dose CT to get high-resolution images of the nodule.

The reader should view the scans on a monitor that has preset lung and mediastinal windows, Dr. Henschke said, and document the location and size of all noncalcified nodules, noting whether they are solid or ground glass opacities. The documentation is entered into the web-based ELCAP management system.

The test at baseline is considered negative, she said, if no noncalcified nodules are seen or if there are 1 to 6 noncalcified nodules all less than 5 mm in size. The test is classified as positive if the scan shows more than 6 noncalcified nodules or 1 to 6 such nodules with the largest being larger than 5 mm.

If the baseline scan is negative, the first repeat screening is scheduled for 12 months after the baseline scan. The scans are repeated annually as long as no suspicious lesions are detected.

Workup for Positive Scans

David Yankelevitz, MD, professor of radiology, Weill Medical College, Cornell University, presented the protocol for patients with positive CT scans.

The baseline protocol, he said, is highly dependent on nodule size. For nodules of less than 5 mm, a high-resolution CT scan, limited to the nodule of record, is performed 6 months after the initial screening test. This is a change from the initial ELCAP protocol, which called for the first repeat CT scan in such circumstances to be at 3 months.

If no growth is seen on the repeat scan, the workup stops and the patient is asked to return for another test 6 months later, or 1 year after the baseline scan. If the nodule has grown, a biopsy is performed immediately.

For 5- to 9-mm nodules, a high-resolution CT scan limited to the nodule of record is obtained 3 months after the baseline screen, Dr. Yankelevitz said. Nodule growth prompts immediate biopsy. If no growth is seen, another scan is obtained 3 months later. If that too is negative, the patient is scheduled to come back 6 months later, or 1 year after the initial screen, and scans are obtained annually thereafter.

Nodules Larger Than 10 mm

Three options are permitted under the protocol for nodules larger than 10 mm: immediate biopsy, antibiotics followed by high-resolution CT scan 1 month after the screening test, or contrast-enhanced CT scan or PET scan. Inclusion of the antibiotic option, with the drug being given for 2 weeks, Dr. Yankelevitz said, sometimes results in complete or partial resolution of the nodule.

With complete resolution, he said, "we’re done." With partial resolution, the test is repeated at 3 months. "If we see no change at 3 months, we then have them come back again at 6 months," he said. If no further improvement is seen, a biopsy is performed. If the antibiotic course produces no change in the nodule, it is biopsied.

Contrast-enhanced CT and PET are currently limited to nodules 1 cm and larger, Dr. Yankelevitz said. "We’ve found that their usefulness in the 5- to 9-mm range is limited," he said, "and you’re often not sure whether your result is influenced strictly by the size of the lesion vs its actual activity or vascularity."

Positive tests with these methods, he indicated, give the clinician a choice of either immediate biopsy or trying an antibiotic course. Negative results, he said, should prompt a high-resolution CT scan at 3 months; the nodule should then be followed in the same manner as a 5- to 9-mm nodule.

If multiple nodules are associated with a nodule of 10 mm, Dr. Yankelevitz said, the protocols for the smaller ones are the same as if they were isolated. "Occasionally, you’ll see one large nodule that potentially is benign, but one of the small ones may be malignant," he said, "so we treat each of them according to its size."

Any new nodule detected on repeat scans, Dr. Yankelevitz said, "is almost by definition a growing nodule. It wasn’t there previously." Such a finding, he indicated, should lead to an immediate 2-week course of antibiotics followed by high-resolution CT at 1 month. "Further workup," he said, "depends on the high-resolution CT results."

CT-guided fine-needle biopsies are preferred in the workups, Dr. Yankelevitz said. If this method is not feasible, he noted, "then video-assisted thoracoscopy is to be performed."

Several members of the audience asked whether the protocol and its underlying rationale could be posted on the ELCAP website.

"At the moment, it’s a protocol subject to change," Dr. Henschke responded. It will not be posted, she indicated, until "we feel comfortable enough to make [it] into guidelines."