A randomized controlled trial of low-dose computed tomography versus ultra-low dose computed tomography for lung cancer screening in high-risk individuals.

Background: Lung cancer (LC) is the leading cause of cancer-related mortality globally. LC is associated with a poor 5-year survival rate, especially when diagnosed at an advanced stage. Lung cancer screening (LCS) with low-dose computed tomography (LDCT) of the thorax reduces lung cancer-specific mortality by 20-25%. Despite endorsement by several organizations, LCS is not routinely performed in many developing countries for various clinical and operational reasons. However, emerging evidence indicates that false positive results with LDCT in developing countries may not be as unacceptably high as previously believed. Concurrently, advances in technology have led to the development of ultra-low dose computed tomography (ULDCT) with improved image quality and diagnostic accuracy even with radiation doses of less than 1mSv (sub millisievert dose). Several observational studies noted comparable diagnostic sensitivity of ULDCT and LDCT. LCS by ULDCT seems to be a feasible approach, however, the lack of randomised trials restricts its wider use.

 Hypothesis: We hypothesize that ULDCT is non-inferior to LDCT in detecting lung cancer, concurrently with significantly reduced radiation dose.

 **Novelty:**A randomized study on ULDCT versus LDCT is not available to date in the literature, and only one study of LDCT for LCS is done in India. So, we intend to do a randomized controlled trial of LDCT versus ULDCT for LCS in high-risk individuals and assess whether ULDCT (with lower radiation dose) is non-inferior to LDCT or not.

**Objectives:**To compare the diagnostic performance of LDCT and ULDCT for LCS in high risk individuals.

Primary

1.   Screen positivity rate with LDCT and ULDCT screening

Secondary

1.   Mean radiation dose with LDCT and ULDCT

2.   Lung cancer detection rate with LDCT and ULDCT

3.   Proportion of patients requiring additional procedures (imaging/invasive procedures) in both groups

4.   Proportion of patients developing complications due to additional procedures in both groups

5.   Proportion of patients who quit/re-initiated smoking after inclusion in study

**Methods:**This will be a randomized, parallel group, double blinded, non-inferior study conducted in the out-patient department of Pulmonary Medicine, AIIMS, Mangalagiri. High risk individuals for lung cancer (aged Â³50 years with Â³20 pack-year history of smoking [or smoking index ≥400]) will be included in the study. Individuals with a clinical suspicion of lung cancer, structural lung disease other than COPD, severe comorbidities limiting survival, recent pulmonary infection in the last 3 months, recent CT thorax in one year, treatment for any cancer in last 5 years will be excluded. Individuals will be randomized in 1:1 ratio to undergo either LDCT or ULDCT. Evaluation and follow-up of positive nodules detected on LDCT/ULDCT will be performed as per standard protocols consistent with the NCCN 2023 guidelines for LCS.

 The outcomes from this study will provide additional data to the previous observational study from India and can serve as a benchmark for policy makers and program managers in the context of feasibility and yield of LCS using LDCT or ULDCT in developing countries like India.