A phase II study of prophylactic thrombopoietin combined with magnetic resonance guided hematopoietical bone marrow-sparing intensity-modulated radiotherapy and concurrent chemotherapy for thoracic esophageal cancer.

Abstract

e16116 Background: Previous large phase III trials of preoperative concurrent chemoradiotherapy and definitive chemoradiotherapy (Dt 40-60Gy) in esophageal cancer have shown rates of platelet inhibition (grade 1-4) of 25-54%. The aim of the trial is to reduce acute thrombocytopenia in patients in thoracic esophageal cancer (EC) patients treated with concurrent chemoradiotherapy (CRT) by sparing the hematopoietical active bone marrow (BM) indentified by magnetic resonance (MR) and prophylactic recombinant human thrombopoietin (rhTPO). (registered in Clinical Trials.gov as NCT05944809). Methods: Thoracic EC patients staged I-IVa (AJCC 7 th ) were prospectively enrolled. The MR images of thoracic vertebra were fused with the simulating CT images. Active BM indentified by MR was contoured as an organ at risk in the treatment plan. The treatment regimen consisted of BM-sparing intensity modulated radiotherapy (BMS-IMRT) (≥45Gy) and concurrent chemotherapy (five cycles of weekly intravenous paclitaxel [50 mg/m²] and cisplatin/nedaplatin [25 mg/m²], or two cycles of intravenous paclitaxel [135-175 mg/m²] and cisplatin [80 mg/m²]), and rhTPO (15000U ih. qw during the radiotherapy). The dose limits for active BM are: volume received more than 5 Gy (V5) < 95%,V10 < 85%,V20 < 60%，V30 < 40%. The primary endpoint is any grade of thrombocytopenia during the radiotherapy and 1 month after the radiotherapy. In order to lower the incidence of thrombocytopenia to ≤ 15% by BMS-IMRT plus prophylactic rhTPO, 23 patients are needed with 80% power to declare 25% absolute reduction compared with that of historical report at a 1-sided significance level of 0.05. Results: From July 20 2023 to June 30 2024, a total of 32 patients met the inclusion criteria for this study. One patient failed to finish MR, three patients had grade 1(G1) thrombocytopenia and one patient had disease progressed during screening phase. Finally, 27 patients were enrolled. Our patient population was predominantly male (92.6% men vs. 7.4% women), with a median age of 59 years (range, 38–75 years). A majority of patients presented with stage II-IVa (70.4%). Before concurrent CRT, seven patients received inductive chemotherapy combined with or without immunotherapy. All patients finished the treatment plan with median radiation dose of 49.45Gy (range 42.8 - 66.66Gy). Concurrent chemotherapy was administered with a median cycle of 5 cycles (range 1-5 cycles). Four patients (14.8%) developed thrombocytopenia (1 pts with G1 and 3 pts with G3). 11 patients experienced leukopenia (2 pts with G1, 7 pts with G2 and 2 pts with G3). Only one patient happened anemia (G2). Conclusions: Techniques to limit low dose radiation to active BM and prophylactic rhTPO could reduce thrombocytopenia in thoracic EC patients treated with CRT. Clinical trial information: NCT05944809 .