Analysis of radiation-induced liver disease using the Lyman NTCP model. Int J Radiat Oncol Biol Phys

Department of Radiation Oncology, University of Michigan, Ann Arbor, MI 48109-0010, USA.
International Journal of Radiation OncologyBiologyPhysics (Impact Factor: 4.26). 07/2002; 53(4):810-21. DOI: 10.1016/S0360-3016(02)02846-8
Source: PubMed


To describe the dose-volume tolerance for radiation-induced liver disease (RILD) using the Lyman-Kutcher-Burman (LKB) normal tissue complication probability (NTCP) model.
A total of 203 patients treated with conformal liver radiotherapy and concurrent hepatic arterial chemotherapy were prospectively followed for RILD. Normal liver dose-volume histograms and RILD status for these patients were used as input data for determination of LKB model parameters. A complication was defined as Radiation Therapy Oncology Group Grade 3 or higher RILD < o r =4 months after completion of radiotherapy. A maximal likelihood analysis yielded best estimates for the LKB NTCP model parameters for the liver for the entire patient population. A multivariate analysis of the potential factors associated with RILD was also completed, and refined LKB model parameters were obtained for patient subgroups with different risks of RILD.
Of 203 patients treated with focal liver irradiation, 19 developed RILD. The LKB NTCP model fit the complication data for the entire group. The "n" parameter was larger than previously described, suggesting a strong volume effect for RILD and a correlation of NTCP with the mean liver dose. No cases of RILD were observed when the mean liver dose was <31 Gy. Multivariate analysis demonstrated that in addition to NTCP and the mean liver dose, a primary hepatobiliary cancer diagnosis (vs. liver metastases), bromodeoxyuridine hepatic artery chemotherapy (vs. fluorodeoxyuridine chemotherapy), and male gender were associated with RILD. For 169 patients treated with fluorodeoxyuridine, the refined LKB model parameters were n = 0.97, m = 0.12, tolerance dose for 50% complication risk for whole organ irradiated uniformly [TD50(1)] = 45.8 Gy for patients with liver metastases, and TD50(1) = 39.8 Gy for patients with primary hepatobiliary cancer.
These data demonstrate that the liver exhibits a large volume effect for RILD, suggesting that the mean liver dose may be useful in ranking radiation plans. The inclusion of clinical factors, especially the diagnosis of primary hepatobiliary cancer vs. liver metastases, improves the estimation of NTCP over that obtained solely by the use of dose-volume data. These findings should facilitate the application of focal liver irradiation in future clinical trials.

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    • "However, more structured analyses and especially clinical trials are needed to further elucidate a potential benefit of MSC therapies for patients. Liver Liver damage due to radiation is a serious complication, with radiation-induced liver disease (RILD) occurring in up to 10% of patients after average liver doses between 30 and 35 Gy [48]. RILD is characterized by occlusion of the small liver veins and can result in hepatomegaly, ascites, elevated liver enzymes and even liver failure and death without a causative treatment available. "
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    Cancer letters 07/2015; 366(2). DOI:10.1016/j.canlet.2015.06.012 · 5.62 Impact Factor
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    • "With the liver being a parallel functioning organ that can sustain focal damage without failure, partial liver irradiation is more tolerable with a TD 5/5 of 50 Gy and 35 Gy to one-third and two-thirds of the liver, respectively [15]. Radiobiological studies using normal tissue complication probability models have shown doses of >100 Gy in 2 Gy/fraction could theoretically be delivered to small liver volumes for a radiation-induced liver disease (RILD) risk under 5% [16]. However, with the proximity of critical organs adjacent to the liver and the potential for large geometric variations, there is a challenge in delivering dose-escalated radiotherapy to the liver safely. "
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    • "The incidence of RILD is significantly associated with mean dose to normal liver (MDTNL) which may be a predictor of RILD. In a study that investigated the dose-volume tolerance for RILD using the Lyman-Kutcher-Burman normal tissue complication probability model, it was found that no cases of RILD were identified when the mean liver dose was <31 Gy (25). Each 1 Gy increase in MDTNL exhibited a 4% increase in the incidence of RILD. "
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