Anussara Prayongrat1, Keiji Kobashi2, Yoichi M Ito3, Norio Katoh4, Masaya Tamura5, Yasuhiro Dekura1, Chie Toramatsu6, Chonlakiet Khorprasert7, Napapat Amornwichet7, Petch Alisanant7, Hiroki Shirato8, Shinichi Shimizu9. 1. Department of Radiation Oncology, Graduate School of Medicine, Hokkaido University, Sapporo, Japan. 2. Department of Medical Physics, Faculty of Medicine, Hokkaido University, Sapporo, Japan. 3. Department of Statistical Data Science, The Institute of Statistical Mathematics, Tokyo, Japan. 4. Department of Radiation Oncology, Hokkaido University Hospital, Sapporo, Japan. 5. Department of Medical Physics, Hokkaido University Hospital, Sapporo, Japan. 6. Department of Radiation Oncology, Tokyo Women's Medical University, Japan. 7. Division of Radiation Oncology, Department of Radiology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand. 8. Department of Radiation Medicine, Faculty of Medicine, Hokkaido University, Sapporo, Japan; Global Station for Quantum Biomedical Science and Engineering, Global Institute for Cooperative Research and Education, Hokkaido University, Sapporo, Japan. 9. Global Station for Quantum Biomedical Science and Engineering, Global Institute for Cooperative Research and Education, Hokkaido University, Sapporo, Japan; Department of Radiation Oncology, Faculty of Medicine, Hokkaido University, Sapporo, Japan. Electronic address: sshing@med.hokudai.ac.jp.
Abstract
PURPOSE: To predict the probability of radiation-induced liver toxicity (RILT) and implement the normal tissue complication probability (NTCP) model-based approach considering confidence intervals (CIs) to select patients for new treatment techniques, such as proton beam therapy, based on a certain NTCP reduction (ΔNTCP) threshold for primary liver cancer patients. METHODS AND MATERIALS: Common Toxicity Criteria for Adverse Events (CTCAE) grade ≥2 RILT was scored. The Lyman NTCP models predicting the probability of CTCAE grade ≥2 RILT as a function of the fraction-size adjusted mean liver dose (MLD), using reference fraction size = 2 Gy/fraction and α/β ratio = 2 Gy, were fitted using the maximum likelihood method. At certain combinations of MLDs, ΔNTCP with a CI was evaluated by the delta method. RESULTS: Of the 239 patients, the incidence of CTCAE grade ≥2 RILT was 55% (46% in the Child-Pugh (CP)-A vs. 81% in the CP-B/C, p < 0.001). Among 180 CP-A patients, 40% who had viral hepatitis infections experienced toxicity vs. 32% in the nonhepatitis subgroup. The MLD was 18 Gy in the toxicity group vs. 16.1 Gy in the nontoxicity group (p = 0.002). The estimated NTCP model parameters specific to the patient subgroups and the ΔNTCP with CI assuming a particular CP classification and viral hepatitis infection status were considerably different which possible changed treatment decision. CONCLUSIONS: Patients with CP-A and viral hepatitis infection or CP-B/C cirrhosis had greater susceptibility to CTCAE grade ≥2 RILT. The estimated NTCP and ΔNTCP for individual patients along with a consideration of uncertainties improve the reliability of the NTCP model-based approach.
PURPOSE: To predict the probability of radiation-induced liver toxicity (RILT) and implement the normal tissue complication probability (NTCP) model-based approach considering confidence intervals (CIs) to select patients for new treatment techniques, such as proton beam therapy, based on a certain NTCP reduction (ΔNTCP) threshold for primary liver cancerpatients. METHODS AND MATERIALS: Common Toxicity Criteria for Adverse Events (CTCAE) grade ≥2 RILT was scored. The Lyman NTCP models predicting the probability of CTCAE grade ≥2 RILT as a function of the fraction-size adjusted mean liver dose (MLD), using reference fraction size = 2 Gy/fraction and α/β ratio = 2 Gy, were fitted using the maximum likelihood method. At certain combinations of MLDs, ΔNTCP with a CI was evaluated by the delta method. RESULTS: Of the 239 patients, the incidence of CTCAE grade ≥2 RILT was 55% (46% in the Child-Pugh (CP)-A vs. 81% in the CP-B/C, p < 0.001). Among 180 CP-Apatients, 40% who had viral hepatitis infections experienced toxicity vs. 32% in the nonhepatitis subgroup. The MLD was 18 Gy in the toxicity group vs. 16.1 Gy in the nontoxicity group (p = 0.002). The estimated NTCP model parameters specific to the patient subgroups and the ΔNTCP with CI assuming a particular CP classification and viral hepatitis infection status were considerably different which possible changed treatment decision. CONCLUSIONS:Patients with CP-A and viral hepatitis infection or CP-B/Ccirrhosis had greater susceptibility to CTCAE grade ≥2 RILT. The estimated NTCP and ΔNTCP for individual patients along with a consideration of uncertainties improve the reliability of the NTCP model-based approach.