Gastrointestinal Cancer

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SU_16_2157 - Uncertainties of Normal Tissue Complication Probability (NTCP) and NTCP difference between radiation treatment modalities for radiation-induced liver toxicity in Child-Pugh A primary liver cancer patients

Sunday, October 21
1:15 PM - 2:45 PM
Location: Innovation Hub, Exhibit Hall 3

Uncertainties of Normal Tissue Complication Probability (NTCP) and NTCP difference between radiation treatment modalities for radiation-induced liver toxicity in Child-Pugh A primary liver cancer patients
A. Prayongrat1, K. Kobashi2, Y. Ito3, N. Katoh4, Y. Dekura1, N. Amornwichet5, S. Shimizu6,7, and H. Shirato7,8; 1Department of Radiation Oncology, Graduate School of Medicine, Hokkaido University, Sapporo, Japan, 2Department of Medical Physics, Faculty of Medicine, Hokkaido University, Sapporo, Japan, 3Department of Biostatistics, Faculty of Medicine, Hokkaido University, Sapporo, Japan, 4Department of Radiation Oncology, Hokkaido University Hospital, Sapporo, Japan, 5Division of Radiation Oncology, Department of Radiology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand, 6Department of Radiation Oncology, Faculty of Medicine, Hokkaido University, Sapporo, Japan, 7Global Station for Quantum Medical Science and Engineering, Global Institution for Collaborative Research and Education (GI-CoRE), Hokkaido University, Sapporo, Japan, 8Department of Radiation Medicine, Faculty of Medicine, Hokkaido University, Sapporo, Japan

Purpose/Objective(s): Model-based approach using normal tissue complication probability (NTCP) model has been proposed to select patient for new treatment techniques, such as proton beam therapy (PBT), based on a certain NTCP difference (∆NTCP) threshold. The goal of this study is to make a reliable dose-response curve to predict the probability of radiation-induced liver toxicity (RILT) as well as the ∆NTCP with confidence interval (CI) between treatment modalities for Child-Pugh A (CP-A) primary liver cancer patients.

Materials/Methods: A total of 180 patients (105 hepatocellular carcinoma and 75 intrahepatic cholangiocarcinoma) were treated with 3D conformal radiotherapy (N=87), intensity modulated radiotherapy (IMRT, N=67), or stereotactic radiotherapy (N=26) between June 2007 and February 2017. Hepatitis B or C virus infection was found in 64 patients. Common toxicity criteria for adverse events (CTCAE) grade≥2 RILT was scored. The mean fraction size equivalent dose of normal liver (mean FED), corrected using reference fraction size=2 Gy/fraction, an α/β ratio=2 Gy, was used as a proxy of generalized uniform equivalent dose for the Lyman-Kutcher-Burman (LKB) NTCP model with fixed volume effect parameter (n) to be 1.0. The estimates of LKB NTCP parameters were estimated by the maximum likelihood method. The variance of ∆NTCP of certain combinations of FEDs was evaluated by Delta method for estimating a CI of ∆NTCP.

Results: CTCAE grade≥2 RILT occurred in 83 patients. The median of mean FED was 19.7 Gy in RILT vs 15.9 Gy in non-RILT groups (p=0.006). The identified NTCP parameters were TD50(1)= 20.6 Gy and m=1.35. There were RILT in 33/64 patients with hepatitis infection compared with 50/116 patients without infection. The TD50(1) and m specifically estimated in hepatitis infection subgroup were 16.2 Gy and 0.68, respectively, and 27.9 Gy and 1.97 in non-infection subgroup. Table showed the estimated NTCP and ∆NTCP with 68%CI of an example patient who received mean FED 33 Gy from IMRT plan and 20 Gy from PBT plan assuming different hepatitis infection status.

Conclusion: Viral hepatitis infection status had substantial effect on the prediction curve in CP-A primary liver cancer patients, suggesting the use of specific NTCP curve in subgroups. The uncertainties of NTCP and ∆NTCP curve improve the reliability of NTCP model-based approach which could be useful to guide patient selection for new treatment techniques such as PBT.
NTCPIMRT (68%CI) NTCPPBT (68%CI) NTCP (68%CI)
Child-Pugh A with hepatitis virus infection (derived from 64 patients’ data) 93.5% (87.5%-99.5%) 63.3% (56.2%-70.5%) 30.2% (25.5%-34.9%)
Child-Pugh A without hepatitis virus infection (derived from 116 patients’ data) 53.7% (43.5%-63.9%) 44.3% (39.5%-49.0%) 9.4% (1.3%-17.5%)

Author Disclosure: A. Prayongrat: None. K. Kobashi: None. Y. Ito: None. N. Katoh: None. Y. Dekura: None. N. Amornwichet: None. S. Shimizu: Research Grant; Hitachi Ltd. Patent/License Fees/Copyright; Radiotherapy control apparatus and radiotherapy control program, US9616249 B2, Charged particle beam system, US 14/524,495. H. Shirato: Research Grant; Shimadzu Corporation, Hitachi Ltd. Patent/License Fees/Copyright; Charged particle beam system, US 14/524,495, Moving body pursuit irradiating device and positioning method using this device.

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SU_16_2157 - Uncertainties of Normal Tissue Complication Probability (NTCP) and NTCP difference between radiation treatment modalities for radiation-induced liver toxicity in Child-Pugh A primary liver cancer patients



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