ESTRO 2021 Abstract Book

S195

ESTRO 2021

Materials and Methods Using 150 MeV protons 50% of the total lung volume was irradiated with or without co-irradiation of the heart. As an overall parameter for cardiopulmonary function respiratory rate was measured and means for timespans of 6-12 weeks (early), 18-24 weeks (intermediate) and 36-42 weeks (late) after irradiation were calculated. Echocardiography was performed at 8, 26 and 38 weeks after irradiation and rats were sacrificed for tissue collection. Vascular remodeling was scored in Verhoeff-stained lung sections (Figure 1A). As a correlate of pulmonary vascular resistance, longitudinal right-ventricle contraction was quantified by the tricuspid annular plane systolic excursion (TAPSE). Results After an initial significant increase in the early and intermediate phase, respiratory rate recovered in the late phase if only 50% of the lung is irradiated (Figure 1B). In contrast, after combined irradiation of the heart with 50% of the lung, respiratory rate remained significantly increased during all time spans without showing recovery. Vascular remodeling exhibited a similar pattern of recovery if only the lung was irradiated. In contrast, no recovery was observed if the heart was co-irradiated (Figure 1C). In line with this, right ventricle contraction was reduced 8 weeks after irradiation, but recovered to control level at the later time points. This recovery did not occur if both heart and lung were irradiated (Figure 1D).

Figure 1: Examples for a normal, slight, moderate and severe remodeled vessel (A); respiratory rate at early (8-12 weeks), intermediate (18-24 weeks) and late (36-42 weeks) time span after irradiation (B); scoring of vascular remodeling (C); and analysis of TAPSE (D); all graphs show the mean with SEM and significances compared to corresponding controls; n=4-11 Conclusion Vascular damage plays an important role in radiation-induced respiratory side effects. Although over time recovery of the pulmonary vasculature is possible, co-irradiation of the heart prevents this. Taken together, these results indicate that reducing dose to the heart is not only important to reduce early side effects, but also essential to preserve the potential to recover from these early side effects. OC-0288 Preclinical study of chronic radiation cystitis and cell therapy treatment C. Brossard 1 , A. Lefranc 2 , M. Dos Santos 3 , M. Benadjaoud 4 , C. Demarquay 2 , V. Buard 2 , G. Tarlet 2 , C. Linard 2 , C. Squiban 2 , N. Mathieu 2 , R. Granger 5 , A. Sache 5 , D. Denais Lalieve 5 , J. Simon 6 , M. Benderitter 4 , F. Milliat 2 , A. Chapel 2 1 IRSN, LRMed, Fontenay aux Roses, France; 2 IRSN, LRMed, Fontenay aux roses, France; 3 IRSN, LRAcc, Fontenay aux roses, France; 4 IRSN, SERAMED, Fontenay aux roses, France; 5 IRSN, GSEA, Fontenay aux roses, France; 6 Hôpital universitaire de la Pitié-Salpêtrière, Département de radio-oncologie, Paris, France Purpose or Objective Chronic radiocystitis (CRC) is a consecutive pathology of pelvic irradiation characterized by chronic inflammation occasionally progressing to fibrosis with symptoms such as pain and bleeding. Previous studies on radiation rectitis have shown that Mesenchymal Stem Cells (MSCs) can reverse chronic inflammation and fibrosis after irradiation. In a preclinical model of CRC, we further investigated whether MSC infusion may limit inflammation and fibrosis. Materials and Methods Our study is divided into two parts, the design of a rat model of CRC then the influence of MSC infusion on CRC. CRC was induced by localized irradiation of the whole bladder with two beams, guided by tomography using the Small Radiation Research Platform (SARRP). A dose range of 20 to 80 Gy with a follow-up of 3 to 12 months post-irradiation was performed. Then we retained to use an irradiation of 40 Gy, followed 4 months later by an intravenous injection of 5 million of MSCs, administered every two weeks (3 injections in total). Physiological, histological and molecular monitoring was performed over 12 months after irradiation (figure 1).