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 V16–53 (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), V16, V17, 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 (V16–18) and high-dose (V35,36 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 V16–18, V35, 36, and V47. Hence, avoiding radiation hot spots on the PBM could reduce the incidence of severe HT.