Preoperative CT-guided Localisation of Lung Nodules

A paper published in Radiology reported on a series of 198 preoperative CT-guided fiducial marker placement procedures that were performed on 190 patients to localise 205 nodules.  The technical success rate was 98.5%.  There were no major complications.  A total of 202 nodules were resected.  Of the resected nodules, 146 were lung cancers, 26 nodules were metastases, 2 were carcinoid tumors, and 28 were benign.

The authors concluded that CT-guided marker placement was an effective and resulted in a low localisation failure rate. 

USPSTF Updated Lung Cancer Screening

 The U.S. Preventive Services Task Force (USPSTF) issued updated recommendations that were published in JAMA regarding screening of lung cancer.  Lung cancer is the leading cause of cancer deaths in the U.S., and the goal of expanded screening is to detect it early enough to cure it in more individuals at high risk as those who smoke.  Large studies have concluded that among people at high risk, annual CT scans can reduce the risk of death from cancer by up to 25%.  The expert panel recommended that individuals with a long history of smoking should begin receiving low-dose CT scans at age 50, five years earlier than the group recommended in 2013. 

AI Matches Radiologists in Diagnosing Lung Cancer.

 A study published in Radiology found that deep learning artificial intelligence (AI) algorithm diagnosed lung cancer from chest radiographs at a rate similar to radiologists.  The researchers tested it on 10,285 radiographs form 10,202 individuals with 10 radiographs with visible cancer.  The algorithm showed comparable sensitivity 90% to 60% for the radiologists.  In a screening cohort of 100,525 chest x-rays from 50,070 individuals with 47 radiographs with lung cancer, the algorithm's sensitivity was 83% and false positive rate was 3%.  The investigators suggested the algorithm could prove useful especially for clinicians treating healthy persons with lower prevalence of lung cancer.

CT Screenings Can Reduce Lung Cancer Mortality

A study published in the New England Journal of Medicine, focused on data from 13,195 men and 2,594 women aged 50 to 74 years old who were heavy smokers, found that participants had a lower mortality if they were screened with computed tomography (CT).

All individuals were followed for a minimum of 10 years and each was randomly assigned to get either low-dose CT scans at baseline, a year, three years and 5.5 years, or no screenings at all. Participants who were screened had lower death rates than the control group: 24% lower for men and 33% lower for women.  The overall referral rate for suspicious nodules was 2.1%.

A U.S. trial of nearly 54,000 heavy smokers in 2011 also found a 20% drop in lung cancer deaths via screenings with CT in comparison to chest X-rays. 

Following the U.S. study, the U.S. Preventive Services Task Force recommended low-dose CT screening for people aged 55 to 80 who had a history of smoking equal to a pack a day for 30 years and were either still smoking or had quit within the past 15 years. 

The American Cancer Society states that lung cancer is responsible for 25% of all cancer deaths and estimates that 72,500 men and 63,220 women in the U.S. are expected to die of lung cancer in 2020

Low Dose CT Lung Cancer Screening

Research by Kinsinger et al published in JAMA Internal Medicine revealed that “low dose CT scans” frequently produce false positives and demand considerable effort by both patients and requesting physicians.

The US Preventive Services Task Force recommends annual lung cancer screening (LCS) with low-dose computed tomography for current and former heavy smokers aged 55 to 80 years.

This clinical demonstration study was conducted at 8 academic VHA hospitals among 93 033 who met the criteria for LCS, 2106 agreed to undergo screening (2028 were men and 78 women; mean [SD] age, 64.9 [5.1] years).

Wide variation in processes and patient experiences occurred among the 8 sites. Of the 2106 patients screened, 1257 (59.7%) had nodules; 1184 of these patients (56.2%) required tracking, 42 (2.0%) required further evaluation but the findings were not cancer, and 31 (1.5%) had lung cancer. A variety of incidental findings, such as emphysema, other pulmonary abnormalities, and coronary artery calcification, were noted on the scans of 857 patients (40.7%).

In conclusion the research, conducted in more than 2000 high-risk VHA patients aged 55 to 80 years found lung cancer in 1.5% of patients, but around 60% of individuals who were screened had 1 or more nodules that required follow up. In addition, incidental findings were reported in around 40% of patients. It is estimated that implementation of LCS in the VHA 6.7 million patients will lead to approximately 900000 patients being eligible for LCS and will require substantial clinical effort for both patients and staff.

Liquid biopsy shows promise

The study by Sacher et al published in JAMA Oncology reported on “a blood test” that detects EGFR and KRAS mutations with rapid plasma genotyping of cell free DNA.

The objective of their study was to prospectively validate plasma droplet digital PCR (ddPCR) for the rapid detection of common epidermal growth factor receptor (EGFR) and KRAS mutations, as well as the EGFR T790M acquired resistance mutation.

Patients with advanced non-squamous non–small-cell lung cancer (NSCLC) who either had a new diagnosis and were planning period for initial therapy or had developed acquired resistance to an EGFR kinase inhibitor and were planned for rebiopsy underwent initial blood sampling and immediate plasma ddPCR for EGFR exon 19 del, L858R, T790M, and/or KRAS G12X between July 3, 2014, and June 30, 2015, at a National Cancer Institute–designated comprehensive cancer center. All patients underwent biopsy for tissue genotyping, which was used as the reference standard for comparison; rebiopsy was required for patients with acquired resistance to EGFR kinase inhibitors. Test turnaround time (TAT) was measured in business days from blood sampling until test reporting.

Of 180 patients with advanced NSCLC (62% female; median [range] age, 62 [37-93] years), 120 cases were newly diagnosed; 60 had acquired resistance. Tumor genotype included 80 EGFR exon 19/L858R mutants, 35 EGFR T790M, and 25 KRAS G12X mutants. Median (range) TAT for plasma ddPCR was 3 (1-7) days. Tissue genotyping median (range) TAT was 12 (1-54) days for patients with newly diagnosed NSCLC and 27 (1-146) days for patients with acquired resistance. Plasma ddPCR exhibited a positive predictive value of 100% for EGFR 19 del, 100% for L858R, and 100% for KRAS, but lower for T790M at 79%.  The sensitivity of plasma ddPCR was 82 for EGFR 19 del, 74% for L858R, and 77% for T790M, but lower for KRAS at 64%. Sensitivity for EGFR or KRAS was higher in patients with multiple metastatic sites and those with hepatic or bone metastases, specifically.

In conclusion, plasma ddPCR detected EGFR and KRAS mutations rapidly with the high specificity needed to select therapy and avoid unnecessary biopsies. The test accurately provided the information whether a patient with NSCLC lung cancer had a mutation that makes the disease treatable. It could also tell if less-fortunate patients had a different mutation, saving them weeks or months of treatment that would ultimately failed.  Finally, the noninvasive genotyping provides physicians with all the information they need thus the inherent risks of tissue genotyping due to repeated biopsies are avoided.

CMS approves CT Lung Cancer Screening

The Centers for Medicare and MedicaidServices on February 6, 2015 issued its final decision approving Medicare coverage for lung cancer screening by low-dose CT.  Medicare will cover annual screenings for beneficiaries aged 55-77 who are current smokers or who quit in the last 15 years, and who have a history of at least 30 “pack years.”   According to the American Cancer Society, lung cancer kills nearly 158,000 patients a year.

CT Screening for Lung Cancer may be Cost-Effective

Black et al in their article published by the NEJM report that findings from the National Lung Screening Trial, that was funded by the NCI, showed that screening with low-dose computed tomography as compared with chest radiography reduced lung-cancer mortality.

Their research team estimated mean life-years, quality-adjusted life-years (QALYs), costs per person, and incremental cost-effectiveness ratios (ICERs) for three alternative strategies: screening with low-dose CT, screening with radiography, and no screening. Estimations of life-years were based on the number of observed deaths that occurred during the trial and the projected survival of persons who were alive at the end of the trial. Quality adjustments were derived from a subgroup of participants who were selected to complete quality-of-life surveys. Costs were based on utilization rates and Medicare reimbursements. They also performed analyses of subgroups defined according to age, sex, smoking history, and risk of lung cancer and performed sensitivity analyses based on several assumptions.

As compared with no screening, screening with low-dose CT costs an additional $1,631 per person and provided an additional 0.0316 life-years per person and 0.0201 QALYs per person. The corresponding ICERs were $52,000 per life-year gained and $81,000 per QALY gained. However, the ICERs varied widely in subgroup and sensitivity analyses.

They concluded that screening for lung cancer with low-dose CT would cost $81,000 per QALY gained.  They also determined that modest changes in their assumptions would greatly alter this figure. The determination of whether screening outside the trial will be cost-effective will depend on how screening is implemented.

References

1.  Updating Cost-Effectiveness — The Curious Resilience of the $50,000-per-QALY Threshold.  Peter J. Neumann, Sc.D., et al N Engl J Med 2014; 371:796-797August 28, 2014  http://www.nejm.org/doi/full/10.1056/NEJMp1405158
2.  On November 11, 2014 the U.S. Centers for Medicare and Medicaid Services (CMS) approved CT lung cancer screening for Medicare recipients, saying the evidence is sufficient to justify screening high-risk individuals until the age of 74 years.

C-Arm Cone-Beam CT-guided Transthoracic Needle Biopsy.

According to a study published in Radiology, by Lee SM et al from Seoul, South Korea they report on a retrospective analysis of percutaneous biopsies of lung lesions performed on 1108 patients in the period between January 2009 and December 2011.  The gender distribution in this study was 633 males and 475 females  with a mean age of 62.4 years.  

The diagnostic performance, complication rate, influencing factors and patient radiation exposure, of the 1116 lesions (mean size 2.7 cm) that were biopsied with an 18-gauge co-axial needle were evaluated.    Of the nodules biopsied 766 were malignant (66.4%), 323 were benign (28%) and 59 were indeterminate (5.1%).  The sensitivity, specificity and accuracy for the diagnosis of malignancy were 95.7%, 100% and 97% respectively.  There were five technical failures and 33 biopsies were false negative.  Lesions in the lower lobes, multiple passages and emphysema were risk factors.  Pneumothorax occurred in in 196 (17%) and hemoptysis in 80 (7%) patients.  Mean estimated radiation dose during the procedure was 7.3 mSv +/- 4.1.   

The authors conclude that Cone-beam CT-guided biopsy is an accurate and safe means to diagnose lung lesions. 

Lee SM, Park CM, Lee KH, Young E: Transthoracic Needle Biopsy of Lung Nodules: Clinical Experience in 1108 Patients.  Radiology, Vol 271(1), April 2014: 291-300

DOI: http://dx.doi.org/10.1148/radiol.13131265