Pneumonitis after normofractionated radioimmunotherapy: a method for dosimetric evaluation

Abstract Background Post-Therapy-Pneumonitis (PTP) is a critical side effect of both, thoracic radio(chemo)therapy (R(C)T) and immune checkpoint inhibition (ICI). However, disease characteristics and patient-specific risk factors of PTP after combined R(C)T + ICI are less understood. Given that RT-triggered PTP is strongly dependent on the volume and dose of RT [1], driven by inflammatory mechanisms, we hypothesize that combination therapy of R(C)T with ICI influences the dose-volume-effect correlation for PTP. This study focuses on the development of a method for evaluation of alterations of dosimetric parameters for PTP after R(C)T with and without ICI. Methods and materials PTP volumes were delineated on the follow-up diagnostic Computed Tomography (CT) and deformably matched to the planning CT for patients with PTP after thoracic R(C)T + ICI or R(C)T. Dose data was converted to 2-Gy equivalent doses (EQD2) and dosimetrically analyzed. Dosimetric and volumetric parameters of the segmented PTP volumes were analyzed. The method was exemplarily tested on an internal patient cohort including 90 patients having received thoracic R(C)T + ICI (39) and R(C)T (51). Thirtytwo patients with PTP were identified for further analysis. Additional data on previous chemotherapy, RT, smoking status and pulmonary co-morbidity were conducted. A matched pair analysis with regard to planning target volumes (PTV) was conducted for curative intended (definitive) and palliative patient cohorts individually. Results The presented method was able to quantify and compare the dosimetric parameters of PTP for the different therapies. For our study group, no significant differences between R(C)T + ICI and R(C)T only was observed. However, the dosimetric analysis revealed large volumetric fractions (55%) of the PTP volumes to be located outside of high dose (EQD2