The Future of Lung Cancer Diagnosis and Treatment
Kathleen Raven | May 31, 2016
The management of lung cancer, which in many cases is a deadly disease, is likely to change in the near future as the field adopts new strategies for diagnosis and treatment. A more fine-grained and stepwise approach to screening, and pharmaceutical and surgical innovations could help to fight the disease.
The Challenge of False Positive Screening Results
Low dose CT (LDCT) screening could, via earlier detection, provide an advantage over traditional chest X-rays and thus help reduce mortality. One drawback, however, concerns false positive results. These occur when “suspicious” nodules are detected in a patient’s lung, but he or she does not have lung cancer and instead the nodule is benign. In the National Lung Screening Trial (NLST), which enrolled about 53,000 heavy smokers in the U.S., over 96 percent of the positive LDCT screening results were actually false positives. These types of results require subsequent workup, for example through further CT or PET scans and biopsies. This causes additional costs and can be a substantial psychological burden for patients.
New criteria for interpreting screening results, however, might alleviate the problem. Since the NLST, U.S. organizations like the American College of Radiology (ACR) have explained in great detail how to determine if a nodule should be considered positive and thus in need of further investigation.1 “Previously, a nodule had to be 4 mm in diameter, but other studies suggest we can safely raise the threshold size without compromising the sensitivity of LDCT screening,” explains Denise Aberle of UCLA Medical Center in Los Angeles, who was one of the principle investigators on the NLST. A higher nodule threshold size would likely decrease false positives and might result in fewer downstream costs.
The National Lung Screening Trial – Key Facts
The National Lung Screening Trial (NLST) was launched in 2002 and randomly assigned around 53,000 current or former heavy smokers to receive either low-dose computed tomography or chest X-rays for three annual screens. Eligible male and female participants were aged between 55 and 74, had a history of at least 30 pack-years (i.e., 30 years of smoking one pack per day) and, if former smokers, had quit within the past 15 years. Patients were enrolled at 33 medical centers across the U.S. All of the multi-detector CT scanners deployed were at least four-slice systems.
Screening exams were labeled as “positive” if a lung nodule 4 mm in diameter or larger was observed on CT scans, or if a “suspicious” nodule or mass was detected on radiographs. The rate of adherence to screening was over 90 percent, although a number of lung cancer cases were only diagnosed in the post-screening phase. About 6 years after the first enrollment, patients in the LDCT group showed 20 percent lower mortality from lung cancer compared with the radiography arm – likely due to earlier treatment – and a 6.7 percent relative decrease in death from other causes.7
Breath Tests for Cancer
In addition, new screening tools such as genetic sequencing and breath tests for cancer metabolites are on the horizon and could further improve screening accuracy in individual patients. For example, advances in sensor technologies and breath collection methods are paving the way for breath tests that could separate patients with lung cancer from those without. The metabolism of people with lung cancer is different to that of healthy people and this is reflected in the chemical signature of their breath. Thus, the tests could become one of the first steps taken to identify patients at risk.2 Several breath-test prototypes are being developed by companies around the world.
Another future method for detecting lung cancer might be blood tests for genetic sequencing. While much remains to be elucidated within the area of genomic profiling and disease, researchers have recently identified the most common genetic mutations associated with lung cancer subtypes.3 CT scans could be used to verify positive results from such tests in individual patients. Conversely, these tests could be used to reduce false positive rates from screening CT scans. Other diagnostic tools, such as detecting lung cancer using biomarkers circulating in the blood, are at earlier stages of research and development.4
New Surgical Techniques
Meanwhile, treatment possibilities are also improving. Positive results from immunotherapy clinical trials were reported earlier this year.5 As the field of personalized medicine expands, it may be possible to better match patients to targeted therapies designed for subgroups of cancer. Surgical techniques are developing, too. For example, there are ongoing endeavors to establish improved image-guided minimally invasive procedures for removing cancerous tissue through small chest incisions in the early stages of lung cancer.6 Such innovative approaches may be what is needed to increase patients’ survival and improve their quality of life.
About the Author
Kathleen Raven has covered lung cancer clinical trials for Biopharm Insight, consumer health for Reuters Health and biomedical news for Nature Medicine. She is a freelance writer based in New Haven, Connecticut, USA.
1Lung CT Screening Reporting and Data System (Lung-RADS™), http://www.acr.org/Quality-Safety/Resources/LungRADS (Accessed 7 July 2015)
2Dent AG, Sutedja TG, Zimmerman PV (2013) Exhaled breath analysis for lung cancer. J Thorac Dis. 5:S540-50
3Collisson EA, Campbell JD, Brooks AN, et al. (2014) Comprehensive molecular profiling of lung adenocarcinoma. Nature. 511:543-50
4Wozniak MB, Scelo G, Muller DC, et al. (2015) Circulating MicroRNAs as Non-Invasive Biomarkers for Early Detection of Non-Small-Cell Lung Cancer. PLoS ONE 10:e0125026
5http://www.asco.org/press-center/new-immunotherapies-multiple-hard-treat-cancers (Accessed 7 July 2015)
6Percutaneous Image Guided Video-Assisted Thoracic Surgery (VATS) Resection of Lung Lesions, https://clinicaltrials.gov/ct2/show/NCT01847209 (Accessed 7 July 2015)
7The National Lung Screening Trial Research Team (2011) Reduced Lung-Cancer Mortality with Low-Dose Computed Tomographic Screening. N Engl J Med 365:395-409
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