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

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.

The Burden of Survivorship on Hematological Patients—Long-Term Analysis of Toxicities after Total Body Irradiation and Allogeneic Stem Cell Transplantation

“…Overall, pulmonary toxicities had a prevalence of 23.9% in the current analysis and, thereby, significantly contribute to morbidity and mortality. In the literature, incidence numbers of pulmonary toxicities (often only registered as pneumonitis) differ between 8.3% and 70.5%, depending on the study cohort and the conditioning regimens utilized [6,7,[10][11][12][13][14][15][16][17][19][20][21][22][23][24][25][26]. A comparison of the present study to similar TBI cohorts is provided in Table 4.…”

“…RT induces a multi-step process of local inflammation resulting in subacute pneumonitis and, later, collagen deposition, which causes chronic lung fibrosis [4,27]. Normal tissue-complication probability calculations in a TBI cohort have an estimated rate of 20.3% for overall pneumonitis (both clinical and radiological), 0.6% for clinically symptomatic pneumonitis and 20.4% for lung fibrosis [26]. In contrast, the present analysis only registered infectious pneumonia without accounting for radiation-induced pneumonitis.…”

Strahlentherapeutische Behandlung von Leukämien

“…In der praktischen Durchführung befindet sich der/die Patient*in einer liegenden oder sitzenden Position in großer Entfernung (2–6 m) vom Bestrahlungsgerät und wird in einem einzigen Feld mit 6–15 MV Photonen behandelt, das den gesamten Körper umschließt ([ 18 , 20 , 27 ]; Abb. 1 a,b; Abb.…”

“…2 a). Kritische Organe wie die Lungen können über Bleiblöcke in ihrer Dosis begrenzt werden, sodass ein Anstieg der Toxizitätsrate vermieden wird [ 18 – 20 , 27 ]. Die Dosis einer MA-TBI beträgt bei fraktionierter Durchführung zwischen 8 und 16 Gy in Einzeldosen von 1,2–2 Gy und mindestens 5 Gy bei unfraktionierter Applikation [ 2 , 22 , 27 ].…”

“…1 gibt einen Überblick über die Häufigkeit verschiedener Organtoxizitäten in Kollektiven mit Langzeitnachbeobachtung. Hierbei zeigt sich ein konsistentes Auftreten pulmonaler Toxizitäten, deren Häufigkeit (oftmals nur als Pneumonitis angegeben) zwischen 8 und 70,5 % divergiert [ 1 , 4 , 5 , 7 , 8 , 15 , 18 , 19 , 24 ]. Sie haben relevante Auswirkungen auf Morbidität und Mortalität nach SCT.…”