C. Zhao1,2, X. Li2, W. Qi3, S. Li3, H. Li3, J. Y. Chen3, and S. Zhao3; 1Department of Oncology, Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou, China, 2Department of Oncology, Affiliated Cancer Hospital of Guizhou Medical University, Guiyang, Guizhou, China, 3Department of Radiation Oncology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
Purpose/Objective(s): To determine the relationships between radiation doses to the thoracic bone marrow/mean cardiopulmonary dose and risks of hematologic toxicities in esophageal squamous cell carcinoma (ESCC) patients during neoadjuvant chemoradiation therapy (nCRT) with or without pembrolizumab. Materials/
Methods: We included 216 patients with ESCC who received nCRT from a prospective database of our institution (NCT04435197, NCT04435197, NCT04513418, NCT03990532), of which 144 received nCRT with pembrolizumab. Weekly blood counts were retrospectively plotted to characterize the time course of cytopenias. Dose-volume histogram (DVH) parameters for the thoracic vertebrae body (TVB), sternum, mCPD including the volumetric sum of heart, lungs, and great vessels, and ribs were assessed for associations with changes in blood counts during the course of nCRT. Linear and logistic regression analyses were performed to identify associations between hematologic nadirs and DVH parameters. Receiver-operating characteristic curves were used to derive optimal dosimetric planning constraints. Vx indicates the total organ volume percentage exceeding a radiation dose of x (Gy). Results: The baseline characteristics of nCRT with or without pembrolizumab were comparable, and there was no significant risk difference of hematologic toxicities between the two cohorts. White blood cells (WBCs) and neutrophils reached nadir at week 2 of nCRT. Grade=2 hematologic toxicity including neutropenia developed in 31.02% (n=67), leukopenia in 77.78% (n=168), anemia in 26.39% (n=57), and thrombocytopenia in 16.67% (n=36) of patients. In univariate analysis, greater RT dose to the thoracic bone marrow was associated with higher risk of Grade=2 neutrophil/neutropenia nadir including TVB V30–40, sternum V20-40(SV20-40), mCPD V30–40, mean rib dose and rib V30-40 (RV30-40). Mean vertebral dose (MVD), TVV5–10 and mean sternum dose were associated with WBCs nadir or leukemia. On multivariate analysis, TVV30-40, SV20-40, and RV40 were associated with the risk of developing neutropenia (grade=2)/neutropenia nadir, while mean rib dose and rib V40 was also associated with risk of developing neutropenia (grade=2). Mean dose of TVB, V5 and V10 of TVB does and mean dose of sternum was independent risk factor for developing WBC nadir/ leukopenia (grade=2). Additionally, the RT dose to thoracic bone marrow/mCPD did not increase the risk of developing grade anemia and thrombocytes. Conclusion: In this large prospective cohort of ESCC treated with nCRT, the addition of pembrolizumab did not increase the risk of developing hematologic toxicities. Greater RT doses to the thoracic bone marrow including TVB, sternum and ribs was associated with increased risk of developing leukopenia and neutropenia, but not for anemia and thrombocytes. The application of advanced radiation techniques to protect the thoracic bone marrow would reduce the hematologic toxicities and improve the tolerance of nCRT.
