NEW BLOOD TEST FOR LUNG CANCER DETECTION

September 20, 2010 — A new blood test to aid in the detection of lung cancer has been available in the United States for a year now, and is expected to be launched in Europe soon.

The test is targeted at high-risk populations, such as heavy smokers. The manufacturer claims that the blood test offers a way of detecting lung cancer at an early stage, when it is still treatable. However, experts approached by Medscape Medical News were not overly impressed with the data accumulated so far.

Detects Small and Early Tumors

One of the biggest problems with lung cancer is late diagnosis — by the time it is usually detected, it has already progressed to a stage where treatment has little impact; hence, it remains the leading cause of cancer death.

Efforts to detect lung cancer at an earlier stage have focused on the use of computed tomography (CT) scanning, as previously reported by Medscape Medical News, but this has proved controversial because many of the lesions that are detected turn out not to be lung cancer.

The new blood test, EarlyCDT-Lung (Oncoimmune), tests for autoantibodies to 6 cancer-associated antigens (p53, NY-ESO-1, CAGE, Gbu4-5, Annexin 1, and SOX2). According to the company, it is less sensitive than CT, but it can detect smaller and less advanced cancers and has greater specificity.

In an interview with Medscape Medical News, chief scientific officer of the company, John Robertson MD, illustrated how the 2 approaches compare. A series from the Mayo Clinic found that a first CT screening picked up nodules in 51% of individuals in a high-risk population, but subsequent tests found that only 1 of the 37 were lung cancer, he said. In comparison, EarlyCDT-Lung found nodules in 10% of a high-risk population, and subsequent tests found that 1 of 11 was cancer.

The blood test is not a replacement for CT scanning, Dr. Robertson emphasized — the 2 approaches should be used in conjunction with one another.

Clinical Validation in Patients

Clinical validation of the blood test in 3 cohorts of patients with newly diagnosed lung cancer was reported in a paper by Dr. Roberson and colleagues published online July 30 in the Annals of Oncology. "Even with the most conservative estimate of occult lung cancer, the panel of autoantibodies can identify 40% of primary lung cancer, including early stage of diseases, with a specificity of 90% against age-matched, gender-matched, and smoking-history matched controls," the researchers, some of whom are company employees, report.

The sensitivity of 40% and specificity of 90% are similar to that seen in mammography in high-risk young women, they say. However, the incidence of lung cancer in heavy smokers is at least 3 times the incidence of breast cancer in high-risk young women, and the mortality rate for lung cancer is between 85% and 95%, they point out.

An expert approached for independent comment was not impressed. "Although it has some interesting data, I am not convinced of the solidity of the conclusions," Michael Unger, MD, FACP, FCCP, director of the pulmonary cancer detection and prevention program at Fox Chase Cancer Center in Philadelphia, Pennsylvania, told Medscape Medical News. The study mixes different stages of lung cancer in small numbers of patients, and the large confidence limits make the analysis "more questionable," he said. In addition, the "evaluation of the results is somewhat hampered by conflict of interest."

"Biological evaluations will be crucial in defining risk groups and in guiding the treatment and potential prognosis in the future," he said, adding that "we are not there yet."

Technology Developed in UK

The technology behind the new test was developed by Dr. Robertson and colleagues at the University of Nottingham in the United Kingdom. Dr. Robertson is a named inventor on the patent and is a founder of Oncoimmune. He now splits his time between the company and the university, where he heads the Division of Breast Surgery.

The same technology is being used to develop a test for detecting breast cancer, which could be launched next year. Further down the pipeline are tests aimed at detecting hepatocellular, ovarian, and esophageal cancers.

All of the tests have a different combination of antigens — some of the proteins are produced by all or many cancers, some are fairly specific for individual cancers but are not "absolutely specific," Dr. Robertson explained. However, the chances of finding cancer are narrowed by limiting the population that is screened to those who are at high risk for the disease, he added.

For the EarlyCDT-Lung test, high-risk individuals include long-term smokers and those with exposure to environmental carcinogens such as radon and asbestos.

Use in Clinical Practice

One physician who has been using the test since its launch last year is Chris Ottinger, MD, who is in a private practice in Overland Park, Kansas, and has about 1800 patients. He has been so impressed with the test that he volunteered to speak to other physicians about it; for this, he receives a small honorarium from the company.

In an interview with Medscape Medical News, Dr. Ottinger said that he has offered the test to patients who have been heavy smokers for at least 15 years, and over the past year or so has tested nearly 50 patients. Of those, 6 tests have returned positive, of which 1 turned out to be "significant," he said.

In that case, subsequent CT scans showed 2 small masses (<1 cm), and this patient is now being monitored with CT scans every 6 months. This patient is in his early 50s, and since the test has gone through classic symptoms of denial, anger, and acceptance, Dr. Ottinger said. Currently, he is very compliant with the monitoring and he has stopped smoking, even though he had ignored previous attempts to help him to quit. "I don't know if this is cancer, it could be granuloma or a walled of area of tissue, so we will follow it to see if it grows," he said.

In the other 5 cases in which the blood tests came back positive, subsequent CT scans did not find any lesions, Dr. Ottinger said. These patients have been also been offered regular monitoring; some have accepted but others have declined for various reasons, including the costs involved in copayment for the scans.

One unexpected benefit has been that some patients have stopped smoking.

"This was so neat . . . . I never expected this," he said. The delay between having the blood test taken and receiving the results is about 10 days, and was obviously a worrying time for the patients. One patient, upon hearing that the test was negative, "hugged me and thanked me for a second chance of life . . . and said he was never going to smoke again," Dr. Ottinger said.

Pulmonologist in a Farming Community

Another physician who has been using the test since it was launched last year is Richard Kucera MD, a pulmonologist and critical care physician in private practice in Greensburg, Pennsylvania. He receives no honoraria from the company, but is happy to talk about his experience with the test. He describes a case report in a video on the company's Web site.

In an interview with Medscape Medical News, Dr. Kucera said he found the test useful for risk assessment and stratification. His practice is based in a farming community, and many older people (50 to 80 years of age) were exposed to histoplasmosis in their youth through contact with chickens. Many also have a history of heavy smoking. As a result of both of these factors, many now have granulomas and pulmonary nodules visible on CT scans. "The big question is: Is this lung cancer?" he said.

"You don't want to do too much and you want to make sure you cause the least amount of harm, but at the same time you don't want to miss a cancer," he said.

So far, of the 30 to 40 patients who have had the blood test, 5 have been positive. One of these turned out to be a stage Ia nonsmall-cell lung cancer, which was "very resectable," he said. "This is the stage at which we want to find lung cancer, because we can fix these people."

The other 4 patients are being monitored with CT scans every 3 months. These patients have also had positron emission tomography (PET) scans, but "at this stage, the PET scans haven't really helped," he said, adding, "I don't know how this is going to turn out." He intends to continue monitoring, and any pulmonary nodules that show changes will be biopsied. One benefit from having had the blood test is that patients are now "a lot more compliant" with coming in for scans, Dr. Kucera said, which "surprised me and has helped me with the scanning."

However, Dr. Kucera cautioned that "a negative result does not mean there is no cancer." One of his patients who tested negative was subsequently found to have a cancer in the lung, although it turned out not to be lung cancer; it was a metastasis from a primary tumor in the abdomen, he said.

Questions About Clinical Value

Approached for comment, Howard (Jack) West, MD, from the Swedish Cancer Institute in Seattle, Washington, who writes the oncology blog Blowing Smoke on Medscape Medical News, said that the new blood test appears to be "promising, perhaps especially in combination with an ambiguous screening CT scan . . . [but] it has yet to have demonstrated a survival benefit as a screening technique."

He was also unimpressed by the clinical experiences described by the 2 clinicians interviewed. They show that the test "identified people who are probably very anxious, don't have anything to treat right now, and are getting a bunch of scans that wouldn't otherwise be done and that aren't clearly recommended. While it's possible that a higher-risk result triggers a few patients to quit smoking, it's also completely possible that a lower-risk result emboldens some patients to feel more comfortable continuing to smoke."

"There is a very real concern that a long-time smoker who gets a result that is not high risk will feel exonerated and comfortable continuing to smoke," he added.

Dr. Robertson is employed by Oncoimmune, and is a named inventor on patents for the technology. Dr. Ottinger receives an honorarium from Oncoimmune. Dr. Kucera has disclosed no relevant financial relationships, and has not received any honoraria from Oncoimmune. Dr. Unger and Dr. West have disclosed no relevant financial relationships.