Clinical Tool Accurately Classifies Benign and Malignant Nodules on Lung Scans of Smokers

Reducing the number of needless tests and increasing rapid, intensive diagnostic workups in individuals with high-risk nodules are major goals of model

A Terry Fox Research Institute (TFRI) -led study has developed a new clinical risk calculator software that accurately classifies, nine out of ten times, which nodules are benign and malignant on an initial lung computed tomography (CT) scan among individuals at high risk for lung cancer. The findings are expected to have immediate clinical impact worldwide among health professionals who currently diagnose and treat individuals at risk for or who are diagnosed with lung cancer, and provide new evidence for developing and improving lung-cancer screening programs.

A total of 12,029 lung cancer nodules observed on CTs of 2,961 current and former smokers were examined in the population-based study. The results published in the September 5th issue of the New England Journal of Medicine (NEJM), will have an immediate impact on clinical practice, according to co-principal investigator Dr. Stephen Lam, chair of BC's Provincial Lung Tumour Group at the BC Cancer Agency and a professor of medicine at the University of British Columbia.

New model and risk calculator can accurately predict which abnormalities that show up on a first CT require further follow up, such as a repeat CT scan, a biopsy, or surgery, and which ones do not.

In countries where guidelines do exist, they largely relate to nodule size. The pan-Canadian team's prediction model, developed by Brock University epidemiologist Dr. Martin Tammemägi, includes a risk calculator that considers several factors in addition to size: older age, female sex, family history of lung cancer, emphysema, location of the nodule in the upper lobe, part-solid nodule type, lower nodule count and spiculation.

The TFRI team used two sets of data to determine their findings, studying a total of 12,029 nodules from 2,961 persons – current and former smokers, aged 50-75, who had undergone low-dose CT screening. One set involved participants in the TFRI Pan-Canadian Early Detection of Lung Cancer Study from 2008 to 2010, where 1,871 persons with a total of 7,008 nodules (102 of which were malignant) were screened and followed. The other set involved 1,090 persons with 5,021 nodules (of which 42 were malignant) who took part in several lung cancer prevention trials conducted by the BC Cancer Agency during 2000-2010 and were funded through the USA National Cancer Institute (NCI). In the former study, participants were followed for an average of three years; in the latter, for an average of eight-and-a-half years.

While nodule size is one predictor of lung cancer, the largest nodule appearing on the CT was not necessarily cancerous. The pan-Canadian study team found that nodules located in the upper lobes of the lung carry an increased probability of cancer. In both data sets studied, researchers found that where cancer was present, fewer nodules were found. This model will simplify the work involved, especially for radiologists, in evaluating and assessing nodules on scans, as well as pulmonologists and thoracic surgeons who must make decisions about tests and treatment for their patients.

"An accurate and practical model that can predict the probability that a lung nodule is malignant and that can be used to guide clinical decision making will reduce costs and the risk of morbidity and mortality in screening programs," wrote Dr. Lam and study colleagues in the article entitled: Probability of Cancer in Pulmonary Nodules Detected on First Screening Computed Tomography."

The USA National Lung Screening Trial (2011) found a 20% reduction in lung cancer mortality with the use of low-dose thoracic CT. According to Dr. Christine Berg, co-principal investigator of the National Lung Screening Trial and former chief, Early Detection Research Group, division of cancer prevention, for the National Cancer Institute in the United States, Dr. Lam and colleagues provide a tool to grapple with the problem of the high rate of positive low-dose computed tomography scans. Fewer follow-up scans with their attendant cost and fewer biopsies with their complications will need to be performed while continuing to diagnosis lung cancer at an early stage to lower mortality. Coupled with continued public health efforts to lower cigarette smoking, this work will have international impact on the leading cause of cancer death worldwide.

The Pan-Canadian study is funded by the TFRI, the research arm of the Terry Fox Foundation, and the Canadian Partnership Against Cancer. The BCCA study was supported by the United States Public Health Service National Cancer Institute.