A prospective single-arm study on the relationship between dose-volume parameters of pelvic functional bone marrow and acute hematological toxicities during intensity-modulated radiotherapy with or without concurrent chemotherapy for uterine cervical/endometrial cancer

Abstract

Background: FLT-PET/CT can accurately identify and locate functional bone marrow (FBM) with hematopoietic capability, the FBM were divided into two levels as FBM₁ (strongest hemopoietic ability region)and FBM₂ (moderate hemopoietic ability region) via FLT-PET/CT. The purpose of this study was to explore the relationship between dose-volume parameters of pelvic FBM and hematologic toxicity (HT) during radiotherapy with or without concurrent chemotherapy for uterine cervical/endometrial cancer.

Methods: From December 2016 to September 2021, ninety-seven uterine cervical/endometrial cancer patients received intensity-modulated radiation therapy were prospectively recruited in this single-arm, prospective, phase II trial. Blood counts were reviewed weekly during radiotherapy. Single- and multifactor regression methods were used to analyze the relationships between dose-volume parameters of FBM_1/2 and grade ≥ 2 HT. ROC curves were used to determine the cutoff values for the dose-volume parameters of FBM_1/2.

Results: The incidence of grade ≥ 2 leukopenia, neutropenia, thrombocytopenia and anemia in patients during radiotherapy was 63.9%, 45.4%, 19.6% and 38.8% respectively, and the median occurrence time was the 29th, 42th, 35th and 31th day, respectively. Multivariate regression analysis showed that the D_max of FBM₁ was significantly related to grade ≥ 2 leukopenia (OR = 1.277 95% CI 1.067-1.528, P = 0.008), D_mean of FBM₂ was significantly related to grade ≥ 2 thrombocytopenia (OR = 1.262 95% CI 1.066-1.494, P = 0.007), and V₁₀ of FBM₁ was significantly related to grade ≥ 2 anemia (OR = 1.198 95% CI 1.003-1.431, P = 0.046). The incidence of grade ≥ 2 leukopenia for patients with FBM₁ D_max < 53 Gy was lower than that for patients with FBM₁ D_max ≥ 53 Gy (53.4% vs. 95.8%, P < 0.001). The incidence of grade ≥ 2 thrombocytopenia in patients with FBM₂ D_mean < 33 Gy was lower than that in patients with FBM₂ D_mean ≥ 33 Gy (0 vs. 28.4%, P < 0.001). The incidence of grade ≥ 2 anemia for patients with FBM₁ V₁₀ < 95% was lower than that in patients with FBM₁ V₁₀ ≥ 95% (24.4% vs. 57.1%, P = 0.003).

Conclusions: Grade ≥ 2 HT usually occurs in the 4th week of radiotherapy for patients with uterine cervical/endometrial cancer. The D_max and V₁₀ of FBM₁ and the D_mean of FBM₂ were significantly associated with the occurrence of grade ≥ 2 HT. The recommended optimal dose constraints were FBM₁ D_max < 53 Gy, V₁₀ < 95%, and FBM₂ D_mean <33 Gy.

Keywords: Chemoradiotherapy; Endometrial cancer; Functional bone marrow; Hematologic toxicity; Uterine cervical cancer.