Pulmonary Toxicity after Total Body Irradiation—An Underrated Complication? Estimation of Risk via Normal Tissue Complication Probability Calculations and Correlation with Clinical Data

SIMPLE SUMMARY: Total body irradiation is an integral part of many conditioning regimens prior to allogeneic stem cell transplantation. It is a large-field technique affecting all organs at risk, of which the lungs are critical for patient survival. However, the precise rates of long-term pulmonary toxicities are unknown. This analysis provides a large patient cohort with long-term follow-up investigating TBI sequelae. Additionally, we present normal tissue complication probability calculations for acute and chronic lung toxicities to enable comparison between biophysical and real-world data. To our knowledge, this is the first adaption of this model to a total-body irradiation patient cohort, which will help to evaluate the feasibility and appropriateness of this approach. ABSTRACT: Total body irradiation (TBI) is an essential part of various conditioning regimens prior to allogeneic stem cell transplantation, but is accompanied by relevant (long-term) toxicities. In the lungs, a complex mechanism induces initial inflammation (pneumonitis) followed by chronic fibrosis. The hereby presented analysis investigates the occurrence of pulmonary toxicity in a large patient collective and correlates it with data derived from normal tissue complication probability (NTCP) calculations. The clinical data of 335 hemato-oncological patients undergoing TBI were analyzed with a follow-up of 85 months. Overall, 24.8% of all patients displayed lung toxicities, predominantly pneumonia and pulmonary obstructions (13.4% and 6.0%, respectively). NTCP calculations estimated median risks to be 20.3%, 0.6% and 20.4% for overall pneumonitis (both radiological and clinical), symptomatic pneumonitis and lung fibrosis, respectively. These numbers are consistent with real-world data from the literature and further specify radiological and clinical apparent toxicity rates. Overall, the estimated risk for clinical apparent pneumonitis is very low, corresponding to the probability of non-infectious acute respiratory distress syndrome, although the underlying pathophysiology is not identical. Radiological pneumonitis and lung fibrosis are expected to be more common but require a more precise documentation by the transplantation team, radiologists and radiation oncologists.