Risk of infections following spleen irradiation–FCCSS study

Abstract

<h3>Objectives</h3> Infection-related outcomes associated with asplenia or impaired splenic function in childhood cancer survivors (CCS) remain understudied. Splenectomy and splenic radiation have been previously found to be risk factors regarding late infection-related mortality but few data exist concerning overall infections. <h3>Methods</h3> Late infection-related morbidity and mortality was evaluated in the FCCSS cohort including 7670 5-year CCS diagnosed before the age of 21 treated before 2001 using data registered in the national medical database. Using a radiotherapy treatment planning system the dose distribution on different organs had been calculated on CT-based phantom. <h3>Results</h3> 4259 CCS had received radiotherapy, 5762 chemotherapy, and 87 splenectomy. Between 2006-2018: 580 patients were hospitalized at least once for bacterial infection, and 110 patients had severe sepsis or septic shock. 1493 late death are recorded, with an infectious cause in 3.8%(n=57). In a multivariate analysis, spleen irradiation was found to be a risk factor for infection (RR1.8-2.0[CI95%1.2-2.9]), non-significantly modified by radiotherapy, if considered as a binary variable, (RR1.7[CI95%1.4-2.0]) nor lung irradiation (RR1.7-2.1[CI95%1.3-3.2]) nor pituitary irradiation (RR1.5-1.9[CI95%1.1-3.2]).The risk was not related to the dose received to the spleen nor to the volume of spleen involved. Gender, age at diagnosis and chemotherapy were not found to play a significant role in the risk of infection. These results were not altered when considering any regular antibiotic prophylaxis nor vaccine therapy. When analyzing the risk of death by infection, the average dose to the spleen was a risk factor, from doses < 5 Gy, with an increased risk depending on the dose received, as well as a dose > 30 Gy on the pituitary gland. <h3>Conclusion</h3> Splenic radiation was found to significantly increase the risk of late infection-related mortality but not of late severe infection. Nevertheless these data should be taken with caution as 45.6% of the deaths with an infectious cause were patients with a second progressive cancer. The dose to the pituitary gland was also a risk factor that may suggest a link with a hormonal deficit, possibly adrenal, that may increase the risk of decompensation during an infection. This hypothesis must be explored secondarily.