Impact of Blood Parameters and Normal Tissue Dose on Treatment Outcome in Esophageal Cancer Patients Undergoing Neoadjuvant Radiochemotherapy

SIMPLE SUMMARY: Prognosis of patients with locally advanced esophageal tumors remains poor despite ongoing efforts to improve treatment options. Nevertheless, neoadjuvant radiochemotherapy (RCTx) followed by surgery has resulted in increased survival rates. One critical point for irradiation of esophageal cancer is the optimal sparing of surrounding normal tissue, especially for the lungs, heart and bone marrow, in the immediate neighborhood of the target volume, since corresponding toxicity could impact the outcome of treated patients. Therefore, the aim of our study was to assess the potential influence of normal tissue radiation dose and blood parameters on survival in this patient cohort. Furthermore, functional imaging parameters of these organs at risk, extracted from 18F-FDG-PET/CT before and during neoadjuvant RCTx, have been correlated with the radiation dose to normal tissues and the blood parameters of interest. We found a significant association of higher radiation doses to the lungs and heart with overall survival. In contrast, neither functional imaging parameters nor blood values were prognostic in this neoadjuvant patient cohort. ABSTRACT: Despite technological advances, normal tissue sparing in photon beam irradiation is still challenging. Since in esophageal cancer this may inflict damage on the lungs, heart and bone marrow, possibly impacting on outcome, the aim of this study was to investigate the association of normal tissue dose and blood parameters on the survival of patients having undergone neoadjuvant radiochemotherapy (RCTx) followed by surgery. This retrospective study included 125 patients irradiated to 40–41.4 Gy with photons or protons combined with concurrent chemotherapy. On initial and restaging 18F-FDG-PET/CT, the lungs and heart were contoured as organs at risk for which standardized uptake values (SUV) were evaluated. The mean radiation dose (D(mean)) to the lungs and heart, the volume of the lungs receiving at least 20 Gy (V(20Gy_lung)) and various pre- and per-treatment blood parameters were included in the Cox regression analyses. Results: The median follow-up time was 19.8 months and median overall survival 37 months (95% confidence interval: 16–58.9 months). In multivariate analysis, higher radiation doses to the lungs and heart were statistically significantly associated with decreased overall survival (D(mean_lung): p < 0.001; V(20Gy_lung): p < 0.002; D(mean_heart): p = 0.005). Neither the 18F-FDG-PET nor blood parameters were predictive for overall survival. In patients with locally advanced esophageal cancer treated with RCTx, the radiation dose to the heart and lungs was significantly associated with overall survival.