Title: Risk of radiation-induced cancers in patients treated with contemporary radiation therapy for early-stage lung cancer
Description: Purpose: In the contemporary management of early-stage lung cancer with RadiationTherapy (RT), there is increased imaging utilization for the diagnosis and treatment and follow-up after completion of treatment. We evaluated whether this increased radiation exposure to patients with early-stage lung cancer that receive stereotactic body radiotherapy (SBRT) significantly increases the risk of radiation-induced carcinogenesis (RIC). Methods: Following IRB approval, one hundred and ninety-six consecutively treated lung cancer patients treated with SBRT were selected for analysis. Information collected included demographics and all ionizing imaging scans one year before SBRT treatment and one year following treatment. These included chest X-rays (CXR), computerized tomography scan (CT scan), positron emission tomography scan (PET-CT scan), bone scan, ventilation-perfusion scan (VQ scan), cone-beam CT scans. In addition to the lung cancer patients, comparative data on ten prostate and breast cancer patients each was collected to get an estimate of the radiation-induced risk (RIC) in other common malignancies.

For each patient, the total effective dose (mSv) was calculated by the sum of all effective doses for all scans (1 year before SBRT to 1-year post-SBRT). After calculating the total effective dose, the summed dose was used to calculate the RIC using the RadRat tool. For the study, we decided that a 1% increase in the baseline risk of radiation-induced lung cancer will be considered a significant increase. Results: Among lung cancer patients, there were 87 males (44.4%) and 109 females (55.6%). The median number of Pre-SBRT CXRs (PA/lateral) was 2 (Range: 1-22), the median number of pre-SBRT CT scans was 2 (Range: 1-6), the median number of pre-SBRT PET-CT scans was 1 (Range: 1-4), the median number of Bone Scans or VQ scans pre-SBRT was 1. The median effective exposure dose from all scans was 72mSv (Range: 24-140.36mSv). The median excess lifetime risk (ELR) of developing lung cancer (a chance in 100,000) with a 90% uncertainty range was 57.15. The Excess Future risk (EFR), the risk from 2019 to the end of the expected lifetime of developing cancer (a chance in 100,000), showed a median of EFR mean of 73.75 (Range: 8.45- 416).

The total future risk (TFR, a sum of baseline and excess risk) of developing cancer, from 2019 to end of an expected lifetime was 2732.5 (Range: 808-8290), the median of TFR upper bound was 2785.5 (Range: 856-8400) and median of TFR lower bound was 2679.5 (Range: 761- 8183). At 6 months, survival was 94.7% (144/152), at 1 year, 79% (94/119), at 3 years 32.5% (27/83). At five years, with survival data on 77 patients available, 9 (11.6%) were alive. Regarding the comparison of RIC from imaging before RT for patients with prostate cancer, the median total effective radiation dose from all pre-SBRT and post-SBRT scans was 20mSv (Range: 20-30mSv), and the median of mean ELR for development of RIC prostate cancer was 4.24 (per 100,000). Regarding early-stage breast cancer, the median total effective radiation dose from all pre-RT and post-RT scans was 16.56mSv (Range: 10.52-31.48mSv), and the median of mean ELR for development of RIC was 35.95 (per 100,000). Conclusion: The median excess cancer lifetime radiation-induced cancer risk for the lung cancer cohort was 0.05%, which is significantly less than the 1% risk that was determined to be clinically significant as per our study objective.

The survival in this cohort of patients was poor. Enhanced imaging to enhance staging accuracy, safety during SBRT treatment, and adequate follow-up outweigh the RIC risk.