TY - JOUR
T1 - Normal tissue complication probability modeling of acute hematologic toxicity in patients treated with intensity-modulated radiation therapy for squamous cell carcinoma of the anal canal
AU - Bazan, Jose G.
AU - Luxton, Gary
AU - Mok, Edward C.
AU - Koong, Albert C.
AU - Chang, Daniel T.
PY - 2012/11/1
Y1 - 2012/11/1
N2 - Purpose: To identify dosimetric parameters that correlate with acute hematologic toxicity (HT) in patients with squamous cell carcinoma of the anal canal treated with definitive chemoradiotherapy (CRT). Methods and Materials: We analyzed 33 patients receiving CRT. Pelvic bone (PBM) was contoured for each patient and divided into subsites: ilium, lower pelvis (LP), and lumbosacral spine (LSS). The volume of each region receiving at least 5, 10, 15, 20, 30, and 40 Gy was calculated. Endpoints included grade ≥3 HT (HT3+) and hematologic event (HE), defined as any grade ≥2 HT with a modification in chemotherapy dose. Normal tissue complication probability (NTCP) was evaluated with the Lyman-Kutcher-Burman (LKB) model. Logistic regression was used to test associations between HT and dosimetric/clinical parameters. Results: Nine patients experienced HT3+ and 15 patients experienced HE. Constrained optimization of the LKB model for HT3+ yielded the parameters m = 0.175, n = 1, and TD50 = 32 Gy. With this model, mean PBM doses of 25 Gy, 27.5 Gy, and 31 Gy result in a 10%, 20%, and 40% risk of HT3+, respectively. Compared with patients with mean PBM dose of <30 Gy, patients with mean PBM dose ≥30 Gy had a 14-fold increase in the odds of developing HT3+ (p = 0.005). Several low-dose radiation parameters (i.e., PBM-V10) were associated with the development of HT3+ and HE. No association was found with the ilium, LP, or clinical factors. Conclusions: LKB modeling confirms the expectation that PBM acts like a parallel organ, implying that the mean dose to the organ is a useful predictor for toxicity. Low-dose radiation to the PBM was also associated with clinically significant HT. Keeping the mean PBM dose <22.5 Gy and <25 Gy is associated with a 5% and 10% risk of HT, respectively.
AB - Purpose: To identify dosimetric parameters that correlate with acute hematologic toxicity (HT) in patients with squamous cell carcinoma of the anal canal treated with definitive chemoradiotherapy (CRT). Methods and Materials: We analyzed 33 patients receiving CRT. Pelvic bone (PBM) was contoured for each patient and divided into subsites: ilium, lower pelvis (LP), and lumbosacral spine (LSS). The volume of each region receiving at least 5, 10, 15, 20, 30, and 40 Gy was calculated. Endpoints included grade ≥3 HT (HT3+) and hematologic event (HE), defined as any grade ≥2 HT with a modification in chemotherapy dose. Normal tissue complication probability (NTCP) was evaluated with the Lyman-Kutcher-Burman (LKB) model. Logistic regression was used to test associations between HT and dosimetric/clinical parameters. Results: Nine patients experienced HT3+ and 15 patients experienced HE. Constrained optimization of the LKB model for HT3+ yielded the parameters m = 0.175, n = 1, and TD50 = 32 Gy. With this model, mean PBM doses of 25 Gy, 27.5 Gy, and 31 Gy result in a 10%, 20%, and 40% risk of HT3+, respectively. Compared with patients with mean PBM dose of <30 Gy, patients with mean PBM dose ≥30 Gy had a 14-fold increase in the odds of developing HT3+ (p = 0.005). Several low-dose radiation parameters (i.e., PBM-V10) were associated with the development of HT3+ and HE. No association was found with the ilium, LP, or clinical factors. Conclusions: LKB modeling confirms the expectation that PBM acts like a parallel organ, implying that the mean dose to the organ is a useful predictor for toxicity. Low-dose radiation to the PBM was also associated with clinically significant HT. Keeping the mean PBM dose <22.5 Gy and <25 Gy is associated with a 5% and 10% risk of HT, respectively.
KW - Anal cancer
KW - Bone marrow toxicity
KW - Intensity-modulated radiation therapy
KW - Normal tissue complication probability
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U2 - 10.1016/j.ijrobp.2011.12.072
DO - 10.1016/j.ijrobp.2011.12.072
M3 - Article
C2 - 22414279
AN - SCOPUS:84866734154
SN - 0360-3016
VL - 84
SP - 700
EP - 706
JO - International Journal of Radiation Oncology Biology Physics
JF - International Journal of Radiation Oncology Biology Physics
IS - 3
ER -