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.

The impact of bone marrow irradiation dose on acute haematologic toxicity in cervical cancer patients treated with concurrent chemoradiotherapy

“…The decrease in HGB in this study was associated not only with low-dose radiation but also with high-dose radiation. Wang [ 9 ] reached a similar conclusion that PBM dose irradiation of cervical cancer patients treated with CCRT and a process to both low-dose (V16-18) and high-dose (V35, 36 and V47) irradiation was associated with HT, depending on the fractional volumes receiving the variable degree of dosage.…”

“…Rose [ 5 ] and Albuquerque [ 6 ] reported that the volume of pelvic bone marrow (PBM) receiving low-dose radiation such as 10 Gy or 20 Gy is associated with HT among cervical cancer patients undergoing CCRT, while other studies [ 7 ] showed that the volume of BM receiving 40 Gy and the mean dose to BM correlated with higher rates of grade ≥ 2 HT. In addition, some studies [ 8 , 9 ] have suggested that acute HT in cervical cancer patients receiving CCRT is related to both low-dose and high-dose BM irradiation. Despite controversy, interest in dosimetric predictors of acute HT is still growing due to its clinical significance.…”

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

“…It has been reported that the incidence of grade ≥ 2 HT in uterine cervical cancer during chemoradiotherapy is 23-91.37% [ 5 , 8 , 21 ], and the incidence of grade ≥ 3 HT is 14.7-77% [ 10 , 14 , 21 , 22 ]. In this study, the incidence of grade ≥ 2 leukopenia, neutropenia, thrombocytopenia and anemia for patients with uterine cervical/endometrial cancer during radiotherapy was 63.9%, 45.4%, 19.6%, and 38.8%, respectively.…”

“…Some low dose-volume parameters (such as V 10 and V 20 ) [ 4 – 8 ] and high dose-volume parameters (such as V 40 ) of the pelvic bone marrow have been related to acute HT [ 7 – 10 ]. Intensity-modulated radiation therapy (IMRT) can reduce the irradiated volume of the pelvic bone marrow [ 6 , 11 , 12 ] and reduce the risk of HT [ 4 , 13 , 14 ].…”

Development of a nomogram for predicting grade 2 or higher acute hematologic toxicity of cervical cancer after the pelvic bone marrow sparing radiotherapy

“…At present, personalized prediction models constructed by multiple predictors have been promoted and applied in several fields (13-15). Although many prediction models associated with cervical cancer have been developed, they are rarely used to predict the risk of acute HT (16,17). Many studies reported that the patient's status [age, body mass index (BMI)], tumor status, and treatment strategies (surgery, chemotherapy, radiotherapy) were possible risk factors causing HT, (8,9,16,18) but a comprehensive and convenient risk assessment system has not been established.…”