Evaluating the Effects of Bone Marrow Sparing Radiotherapy on Acute Hematologic Toxicity for Patients with Locoregionally Advanced Cervical Cancer: A Prospective Phase II Randomized Controlled Trial

Abstract

Bone marrow sparing intensity modulated radiotherapy (BMS-IMRT) can reduce the incidence of acute hematologic toxicity (HT) for locoregionally advanced cervical cancer (LACC) patients receiving concurrent chemoradiotherapy (CCRT), but the norm has been controversial. The purpose of the study was to evaluate the effects of bone marrow (BM) V40 <25% on decreasing the incidence of acute HT in a prospective clinical trial. A total of 242 LACC patients were recruited from May 2021 to May 2022, who were evenly randomized into BMS-IMRT group and standard IMRT group according to a computer-generated random number list. All patients received pelvic irradiation with concurrent cisplatin (40 mg/m2 weekly), followed by brachytherapy. For patients in BMS-IMRT group, the outer contour of pelvic bone, lumbar spine and left and right femur heads were additionally delineated as a surrogate for BM, and V40 <25% was prescribed. Blood counts were tested weekly, of which nadirs during external beam radiotherapy (EBRT) were graded to assess acute HT as primary observation index. Second observation index were dosimetric parameters of EBRT plan from the dose volume histograms (DVHs). Binary logistic regression model and receiver operating characteristic (ROC) curve were used for predictive value analysis. Baseline demographic, disease and treatment characteristics were all balanced between BMS-IMRT group and standard IMRT group. BMS-IMRT was associated with a lower incidence of grade ≥2 and grade ≥3 acute HT, leukopenia and neutropenia (72.70% vs 90.90%, P <0.001*; 16.50% vs 65.30%, P <0.001*; 66.10% vs 85.10%, P = 0.001*; 13.20% vs 54.50%, P <0.001*; 37.20% vs 66.10%, P <0.001*; 10.70% vs 43.80%, P <0.001*). Plan target volume (PTV) for all patients satisfied the clinical requirement of V(100%) ≥95%, and conformity and homogeneity were both comparable between 2 groups. BMS also decreased dose delivered to the organs at risk (OARs) including rectum, bladder and left and right femur head. Univariate and multivariate analyses showed that BM V40 was an independent risk factor for grade ≥3 acute HT (odds ratio [OR] = 2.734, 95% confidence interval [CI] = 1.959-3.815, P <0.001*). Cutoff value was 25.036% and area under the curve (AUC) was 0.786. The nomogram was constructed, which was rigorously evaluated and internally cross-validated, showing good predictive performance. BM V40 <25% can reduce the risks of acute HT for LACC patients receiving CCRT while the dose delivery of target volume and other normal tissues were not compromised. With great practicality and applicability, BM V40 <25% is a promising strategy, making BMS-IMRT widespread especially in the area where application of image guided radiotherapy (IGRT) such as 18F-fluorodeoxyglucose positron emission tomography (18FDG-PET)/CT is not popularized. Chinese clinical trial registry (ChiCTR2200066485).