- The combination of blood microRNA (miRNA) assay and low-dose computed tomography (LDCT) allows optimal screening intensity and reduces unnecessary LDCT repeats in lung cancer (LC) screening.
Why this matters
- Screening by LDCT can reduce LC-specific mortality.
- Adequate risk stratification is needed to choose the optimal screening interval.
- The bioMILD trial prospectively enrolled 4119 volunteers; inclusion criteria were: aged 50-75, ≥30 pack-years, smoking stop ≤10 years.
- At baseline, participants received LDCT and miRNA profiling.
- LDCT threshold cut-off was set at 113 mm3.
- The 24-miRNA signature classifier predicts 3 risk levels; subjects were defined miRNA-negative if classified at low risk or miRNA-positive if classified at intermediate/high risk.
- LDCT and miRNA were tested independently with blind evaluation.
- Participants were grouped into 3 categories: double positive (2-pos: LDCT-positive and miRNA-positive), single positive (1pos: LDCT-positive or miRNA-positive), double negative (2neg: LDCT-negative and miRNA-negative).
- LDCT screening intervals were: 3-6 months (2pos), 1 year (1pos), 3 years (2neg).
- Median observation period was 4.5 years.
- Participants in the 2neg, 1pos, and 2pos groups were 2384 (58%), 1526 (37%), and 209 (5%), respectively.
- After four screening runs, 115 LCs were diagnosed (2.8%).
- Cumulative LC incidence was significantly different in the three groups: 0.6% for 2neg subjects, 3.8% for 1pos and 20.1% for 2pos (P
- LC incidence within 3 years in the three groups was 0.1%, 2.5%, and 19.1%, respectively (P
- LC risk was significantly higher in 1-pos and 2-pos subjects (HR 6.0 and 36.6, respectively).
- LC mortality in the three groups was 0.1%, 0.6% and 3.8%, respectively (P
- LC mortality was significantly higher in 1-pos and 2-pos subjects (HR 5.7 and 32.2, respectively).
- Interval cancer incidence, proportion of stage I, and resected LC were not statistically different among groups.
- Italian Association for Cancer Research (AIRC), Italian Ministry of Health, National Cancer Institute of Milan, US National Institutes of Health, Gensignia.
“Reducing regular follow-up scans based on additional risk information is a way forward, but prospective large randomised clinical trials are needed to confirm safety of these approaches in nationwide programs.” Harry J. de Koning, MD, PhD, Erasmus MC (Rotterdam, Netherlands).