Knapen DJ, Kwee TC, Meijne EIM, Fehrmann RSN, de Vries EGE
Immune checkpoint inhibitors (ICI) have improved outcomes for patients with advanced cancers, and results in increasing numbers of long-term survivors. For registration studies, progression-free survival and disease-free survival often serve as primary endpoints. This requires repeated computed tomography (CT) scans for tumour imaging which might lead to major radiation exposure. To determine this, all immune checkpoint inhibitors trials that led to FDA approval were retrieved up to July 29, 2019. From the available protocols, imaging modalities and schedules used in each trial were identified. The anticipated cumulative number of scans made after 1, 3, 5, and 10 years study participation were calculated. The percentage of lifetime attributable cancer risk was calculated using the Biological Effects of Ionizing Radiation VII report. Fifty-one trials were identified, from which 39 protocols were retrieved. Four were adjuvant trials. All protocols required repeated chest-abdomen imaging and specified CT scans as preferred imaging modality. Median calculated cumulative numbers of chest-abdomen CT scans after 1, 3, 5, and 10 years study participation were 7, 16, 24 and 46, respectively. For ages 20-70 years at study entry, the average lifetime attributable cancer risk after 1 year of study participation ranged from 1.11%-0.40% for men and from 1.87%-0.46% for women. At 10 years study participation, this risk increased to a range of 5.91%-1.96% for men and 9.64% -2.32% for women. Given high imaging radiation exposure for long-term survivors in current ICI trials an adaptive imaging interval and imaging termination rules should be considered for long-term survivors.