Impact of Chemotherapy on Normal Tissue Complication Probability Models of Acute Hematologic Toxicity in Patients Receiving Pelvic Intensity Modulated Radiation Therapy

Abstract

To determine how chemotherapy agents affect radiation dose parameters that correlate with acute hematologic toxicity (HT) in patients treated with pelvic intensity modulated radiation therapy (P-IMRT) and concurrent chemotherapy. We assessed HT in 141 patients who received P-IMRT for anal, gynecologic, rectal, or prostate cancers, 95 of whom received concurrent chemotherapy. Patients were separated into 4 groups: mitomycin (MMC) + 5-fluorouracil (5FU, 37 of 141), platinum ± 5FU (Cis, 32 of 141), 5FU (26 of 141), and P-IMRT alone (46 of 141). The pelvic bone was contoured as a surrogate for pelvic bone marrow (PBM) and divided into subsites: ilium, lower pelvis, and lumbosacral spine (LSS). The volumes of each region receiving 5-40 Gy were calculated. The endpoint for HT was grade ≥3 (HT3+) leukopenia, neutropenia or thrombocytopenia. Normal tissue complication probability was calculated using the Lyman-Kutcher-Burman model. Logistic regression was used to analyze association between HT3+ and dosimetric parameters. Twenty-six patients experienced HT3+: 10 of 37 (27%) MMC, 14 of 32 (44%) Cis, 2 of 26 (8%) 5FU, and 0 of 46 P-IMRT. PBM dosimetric parameters were correlated with HT3+ in the MMC group but not in the Cis group. LSS dosimetric parameters were well correlated with HT3+ in both the MMC and Cis groups. Constrained optimization (0<n≤ 1) of the Lyman-Kutcher-Burman model resulted in n=1, m = 0.11, TD50 = 31 Gy for LSS in the MMC group and n=1, m = 0.27, TD50 = 35 Gy for LSS in the Cis group. The incidence of HT3+ depends on type of chemotherapy received. Patients receiving P-IMRT ± 5FU have better bone marrow tolerance than those receiving irradiation concurrent with either Cis or MMC. Treatment with MMC has a lower TD50 and more steeply rising normal tissue complication probability curve compared with treatment with Cis. Dose tolerance of PBM and the LSS subsite may be lower for patients treated with MMC compared with Cis.