Dosimetric predictors and Lyman normal tissue complication probability model of hematological toxicity in cervical cancer patients with treated with pelvic irradiation

Abstract

Purpose: To identify dosimetric parameters associated with acute hematological toxicity (HT) and identify the corresponding normal tissue complication probability (NTCP) model in cervical cancer patients receiving helical tomotherapy (Tomo) or fixed-field intensity-modulated radiation therapy (ff-IMRT) in combination with chemotherapy, that is, concurrent chemoradiotherapy (CCRT) using the Lyman-Kutcher-Burman normal tissue complication probability (LKB-NTCP) model.

Methods: Data were collected from 232 cervical cancer patients who received Tomo or ff-IMRT from 2015 to 2018. The pelvic bone marrow (PBM) (including the ilium, pubes, ischia, acetabula, proximal femora, and lumbosacral spine) was contoured from the superior boundary (usually the lumbar 5 vertebra) of the planning target volume (PTV) to the proximal end of the femoral head (the lower edge of the ischial tubercle). The parameters of the LKB model predicting ≥grade 2 hematological toxicity (Radiation Therapy Oncology Group [RTOG] grading criteria) (TD₅₀ (1), m, and n) were determined using maximum likelihood analyses. Univariate and multivariate logistic regression analyses were used to identify correlations between dose-volume parameters and the clinical factors of HT.

Results: In total, 212 (91.37%) patients experienced ≥grade 2 hematological toxicity. The fitted normal tissue complication probability model parameters were TD₅₀ (1) = 38.90 Gy (95%CI, [36.94, 40.96]), m = 0.13 (95%CI [0.12, 0.16]), and n = 0.04 (95%CI [0.02, 0.05]). Per the univariate analysis, the NTCP (the use of LKB-NTCP with the set of model parameters found, p = 0.023), maximal PBM dose (p = 0.01), mean PBM dose (p = 0.021), radiation dose (p = 0.001), and V_16-53 (p < 0. 05) were associated with ≥grade 2 HT. The NTCP (the use of LKB-NTCP with the set of model parameters found, p = 0.023; AUC = 0.87), V_16, V_17, and V₁₈ ≥ 79.65%, 75.68%, and 72.65%, respectively (p < 0.01, AUC = 0.66∼0.68), V₃₅ and V₃₆ ≥ 30.35% and 28.56%, respectively (p < 0.05; AUC = 0.71), and V₄₇ ≥ 13.43% (p = 0.045; AUC = 0.80) were significant predictors of ≥grade 2 hematological toxicity from the multivariate logistic regression analysis.

Conclusions: The volume of the PBM of patients treated with concurrent chemoradiotherapy and subjected to both low-dose (V_16-18 ) and high-dose (V_35,36 and V₄₇ ) irradiation was associated with hematological toxicity, depending on the fractional volumes receiving the variable degree of dosage. The NTCP were stronger predictors of toxicity than V_16-18 , V_{35, 36} , and V₄₇ . Hence, avoiding radiation hot spots on the PBM could reduce the incidence of severe HT.

Keywords: acute hematologic toxicity; bone marrow; cervical cancer; dose-volume parameter; normal tissue complication probability model.