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Title: Dose-volumetric parameters predicting radiation-induced hepatic toxicity in unresectable hepatocellular carcinoma patients treated with three-dimensional conformal radiotherapy

Abstract

Purpose: To identify the dose-volumetric parameters associated with the risk of radiation-induced hepatic toxicity (RIHT) in hepatocellular carcinoma patients treated with three-dimensional conformal radiotherapy. Methods and Materials: A total of 105 hepatocellular carcinoma patients underwent three-dimensional conformal radiotherapy (total dose range, 44-58.5 Gy; median, 54). RIHT was scored within 4 months of completing three-dimensional conformal radiotherapy. The dose-volume parameters analyzed were the gross tumor volume; normal liver volume; total liver volume; radiation dose; mean dose to the normal liver; percentage of the normal liver volume receiving {>=}20, {>=}25, {>=}30, {>=}35, and {>=}40 Gy; percentage of the total liver volume receiving {>=}20, {>=}25, {>=}30, {>=}35, and {>=}40 Gy; and the normal tissue complication probability. Results: Of the 105 patients, Grade 1 RIHT was observed in 21 (20.0%), Grade 2 in 7 (6.7%), Grade 3 in 5 (4.8%), and Grade 4 in 1 (1.0%) patient. No fatal Grade 5 RIHT developed. On multivariate analysis for predicting Grade 2 or worse RIHT, the total liver volume receiving {>=}30 Gy was the only significant parameter (p < 0.001). Grade 2 or worse RIHT was observed in only 2 (2.4%) of 85 patients with a total liver volume receiving 30 Gy of {<=}60% and inmore » 11 (55.0%) of 20 patients with >60% (p < 0.001). Conclusion: The total liver volume receiving {>=}30 Gy appears to be a useful dose-volumetric parameter for predicting the risk of RIHT. This volume should be limited to {<=}60% whenever possible to minimize the risk of Grade 2 or worse RIHT.« less

Authors:
 [1];  [2];  [1];  [1];  [1];  [1];  [1];  [1];  [1];  [1]
  1. Research Institute and Hospital, National Cancer Center, Goyang (Korea, Republic of)
  2. Research Institute and Hospital, National Cancer Center, Goyang (Korea, Republic of). E-mail: radiopia@ncc.re.kr
Publication Date:
OSTI Identifier:
20850318
Resource Type:
Journal Article
Resource Relation:
Journal Name: International Journal of Radiation Oncology, Biology and Physics; Journal Volume: 67; Journal Issue: 1; Other Information: DOI: 10.1016/j.ijrobp.2006.08.015; PII: S0360-3016(06)02768-4; Copyright (c) 2007 Elsevier Science B.V., Amsterdam, Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
62 RADIOLOGY AND NUCLEAR MEDICINE; HEALTH HAZARDS; HEPATOMAS; LIVER; MULTIVARIATE ANALYSIS; PATIENTS; RADIATION DOSES; RADIOTHERAPY; TOXICITY

Citation Formats

Kim, Tae Hyun, Kim, Dae Yong, Park, Joong-Won, Kim, Seong Hoon, Choi, Joon-Il, Kim, Hyun Beom, Lee, Woo Jin, Park, Sang Jae, Hong, Eun Kyung, and Kim, Chang-Min. Dose-volumetric parameters predicting radiation-induced hepatic toxicity in unresectable hepatocellular carcinoma patients treated with three-dimensional conformal radiotherapy. United States: N. p., 2007. Web. doi:10.1016/j.ijrobp.2006.08.015.
Kim, Tae Hyun, Kim, Dae Yong, Park, Joong-Won, Kim, Seong Hoon, Choi, Joon-Il, Kim, Hyun Beom, Lee, Woo Jin, Park, Sang Jae, Hong, Eun Kyung, & Kim, Chang-Min. Dose-volumetric parameters predicting radiation-induced hepatic toxicity in unresectable hepatocellular carcinoma patients treated with three-dimensional conformal radiotherapy. United States. doi:10.1016/j.ijrobp.2006.08.015.
Kim, Tae Hyun, Kim, Dae Yong, Park, Joong-Won, Kim, Seong Hoon, Choi, Joon-Il, Kim, Hyun Beom, Lee, Woo Jin, Park, Sang Jae, Hong, Eun Kyung, and Kim, Chang-Min. Mon . "Dose-volumetric parameters predicting radiation-induced hepatic toxicity in unresectable hepatocellular carcinoma patients treated with three-dimensional conformal radiotherapy". United States. doi:10.1016/j.ijrobp.2006.08.015.
@article{osti_20850318,
title = {Dose-volumetric parameters predicting radiation-induced hepatic toxicity in unresectable hepatocellular carcinoma patients treated with three-dimensional conformal radiotherapy},
author = {Kim, Tae Hyun and Kim, Dae Yong and Park, Joong-Won and Kim, Seong Hoon and Choi, Joon-Il and Kim, Hyun Beom and Lee, Woo Jin and Park, Sang Jae and Hong, Eun Kyung and Kim, Chang-Min},
abstractNote = {Purpose: To identify the dose-volumetric parameters associated with the risk of radiation-induced hepatic toxicity (RIHT) in hepatocellular carcinoma patients treated with three-dimensional conformal radiotherapy. Methods and Materials: A total of 105 hepatocellular carcinoma patients underwent three-dimensional conformal radiotherapy (total dose range, 44-58.5 Gy; median, 54). RIHT was scored within 4 months of completing three-dimensional conformal radiotherapy. The dose-volume parameters analyzed were the gross tumor volume; normal liver volume; total liver volume; radiation dose; mean dose to the normal liver; percentage of the normal liver volume receiving {>=}20, {>=}25, {>=}30, {>=}35, and {>=}40 Gy; percentage of the total liver volume receiving {>=}20, {>=}25, {>=}30, {>=}35, and {>=}40 Gy; and the normal tissue complication probability. Results: Of the 105 patients, Grade 1 RIHT was observed in 21 (20.0%), Grade 2 in 7 (6.7%), Grade 3 in 5 (4.8%), and Grade 4 in 1 (1.0%) patient. No fatal Grade 5 RIHT developed. On multivariate analysis for predicting Grade 2 or worse RIHT, the total liver volume receiving {>=}30 Gy was the only significant parameter (p < 0.001). Grade 2 or worse RIHT was observed in only 2 (2.4%) of 85 patients with a total liver volume receiving 30 Gy of {<=}60% and in 11 (55.0%) of 20 patients with >60% (p < 0.001). Conclusion: The total liver volume receiving {>=}30 Gy appears to be a useful dose-volumetric parameter for predicting the risk of RIHT. This volume should be limited to {<=}60% whenever possible to minimize the risk of Grade 2 or worse RIHT.},
doi = {10.1016/j.ijrobp.2006.08.015},
journal = {International Journal of Radiation Oncology, Biology and Physics},
number = 1,
volume = 67,
place = {United States},
year = {Mon Jan 01 00:00:00 EST 2007},
month = {Mon Jan 01 00:00:00 EST 2007}
}
  • Purpose: To identify the parameters that predict hepatic toxicity and deterioration of hepatic function. Materials and Methods: A total of 47 patients with small unresectable primary hepatocellular carcinoma received hypofractionated stereotactic body radiotherapy (SBRT) using the CyberKnife. Of those, 36 patients received no other local treatments that could influence hepatic toxicity at least for 3 months after the completion of SBRT. The gross tumor volume (GTV) was 18.3 {+-} 15.9 cm{sup 3} (range, 3.0-81.3 cm{sup 3}), and the total dose administered was 30-39 Gy (median, 36 Gy). To assess the deterioration of hepatic function, we evaluated the presence or absencemore » of the progression of Child-Pugh class (CP class). To identify the parameters of predicting the radiation-induced hepatic toxicity and deterioration of the hepatic function, several clinical and dose-volumetric parameters were evaluated. Results: Of 36 patients, 12 (33%) developed Grade 2 or higher hepatic toxicity and 4 (11%) developed progression of CP class. The multivariate analysis showed that the only significant parameter associated with the progression of CP class was the total liver volume receiving a dose less than 18 Gy (<18 Gy). Conclusions: The progression of CP class after SBRT limits other additional local treatments and also reflects the deterioration of hepatic function. Therefore, it would be important to note that the presence or absence of the progression of CP class is a dose-limiting factor. The total liver volume receiving <18 Gy should be greater than 800 cm{sup 3} to reduce the risk of the deterioration of hepatic function.« less
  • Purpose: To assess the significance of the ratio between standardized uptake values (SUV) of tumor and normal liver tissue obtained from positron emission tomography with fluorine-18-fluorodeoxyglucose (FDG-PET) in predicting the response of hepatocellular carcinoma (HCC) patients treated with external beam radiotherapy (EBRT). Methods and Materials: We retrospectively analyzed 35 HCC patients who were treated with EBRT between January 2004 and June 2007. All patients underwent FDG-PET in which SUV values were obtained from tumor and normal liver tissues and were used to calculate the ratios (SUV{sub Tumor}/SUV{sub Liver}). After FDG-PET, patients received liver treatment including concurrent chemoradiation, transarterial chemoembolization plusmore » RT, or intraarterial chemotherapy plus RT. Using three-dimensional conformal RT, median dose of 45 Gy was delivered in conventional fractions. Patients underwent abdominal/pelvic CT 1 month after RT, and treatment responses were evaluated according to the Response Evaluation Criteria in Solid Tumors criteria. Results: Patients were divided into high-SUV ratio group (n = 20) and low-SUV ratio group (n = 15) according to SUV ratio at a cutoff value of 2.5. Objective responses consisting of either complete response (CR) or partial response (PR) were observed in 16 and 6 patients (46% vs. 17%, p = 0.015), respectively; median survivals after RT were 8 months and 5 months (p = 0.41) for the high-SUV ratio group and the low-SUV ratio group, respectively. Rates of intrahepatic metastases (9% vs. 11%, p = 0.39) and distant metastases (32% vs. 32%, p = 0.27) showed no significant difference between two groups. Conclusions: External beam RT for HCC patients with higher SUV ratios resulted in higher response rates than for patients with lower SUV ratios. Treatment of HCC with higher SUV ratios did not result in increased survival; high rates of intrahepatic and distant metastases in both SUV groups may have affected patient survival. SUV ratios from pre-RT FDG-PET may be beneficial for selecting patients who are likely to respond to EBRT for unresectable HCC.« less
  • Purpose: Hepatocellular carcinoma (HCC) is a poor prognosis tumor, and only 20% of patients will benefit from curative therapies (surgery, liver transplantation, percutaneous ablation). Although conventional radiotherapy has been traditionally regarded as inefficient and toxic for cirrhotic patients, three-dimensional conformal radiotherapy (3DCRT) has provided promising preliminary data for the treatment of HCC. Methods and Materials: Prospective phase II trial including Child-Pugh A/B cirrhotic patients with small-size HCC (1 nodule {<=}5 cm, or 2 nodules {<=}3 cm) nonsuitable for curative treatments, to assess tolerance and efficacy of high-dose (66 Gy, 2 Gy/fraction) 3DCRT. Results: Twenty-seven patients were enrolled. Among the 25more » assessable patients, tumor response was observed for 23 patients (92%), with complete response for 20 patients (80%), and partial response for 3 patients (12%). Stable disease was observed in 2 patients (8%). Grade 4 toxicities occurred in 2 of 11 (22%) Child-Pugh B patients only. Child-Pugh A patients tolerated treatment well, and 3/16 (19%) developed asymptomatic Grade 3 toxicities. Conclusion: High-dose 3DCRT is a noninvasive, well-tolerated modality that is highly suitable for the treatment of small HCCs in cirrhotic patients, with promising results. However, additional trials are needed to optimize this technique and formally compare it with the usual curative approaches.« less
  • Purpose: To identify prognostic factors and evaluate biochemical control rates for patients with localized prostate cancer treated with either high-dose intensity-modulated radiotherapy (IMRT) or conventional-dose three-dimensional conformal radiotherapy 3D-CRT. Methods: Four hundred sixteen patients with a minimum follow-up of 3 years (median, 5 years) were included. Two hundred seventy-one patients received 3D-CRT with a median dose of 68.4 Gy (range, 66-71 Gy). The next 145 patients received IMRT with a median dose of 75.6 Gy (range, 70.2-77.4 Gy). Biochemical control rates were calculated according to both American Society for Therapeutic Radiology and Oncology (ASTRO) consensus definitions. Prognostic factors were identifiedmore » using both univariate and multivariate analyses. Results: The 5-year biochemical control rate was 60.4% for 3D-CRT and 74.1% for IMRT (p < 0.0001, first ASTRO Consensus definition). Using the ASTRO Phoenix definition, the 5-year biochemical control rate was 74.4% and 84.6% with 3D-RT and IMRT, respectively (p = 0.0326). Univariate analyses determined that PSA level, T stage, Gleason score, perineural invasion, and radiation dose were predictive of biochemical control. On multivariate analysis, dose, Gleason score, and perineural invasion remained significant. Conclusion: On the basis of both ASTRO definitions, dose, Gleason score, and perineural invasion were predictive of biochemical control. Intensity-modulated radiotherapy allowed delivery of higher doses of radiation with very low toxicity, resulting in improved biochemical control.« less
  • Purpose: To investigate whether three-dimensional conformal radiotherapy (3D-CRT) influences hepatitis B virus (HBV) reactivation and chronic hepatitis B (CHB) exacerbation in patients with HBV-related hepatocellular carcinoma (HCC). Methods and Materials: Of the 48 HCC patients with HBV who underwent 3D-CRT to the liver, 16 underwent lamivudine therapy before and during 3D-CRT (Group 1) and 32 did not receive antiviral therapy before 3D-CRT (Group 2). To analyze spontaneous HBV reactivation, we included a control group of 43 HCC patients who did not receive any specific treatment for HCC or CHB. Results: The cumulative rate of radiation-induced liver disease for Groups 1more » and 2 was 12.5% (2 of 16) and 21.8% (7 of 32), respectively (p > 0.05). The cumulative rate of HBV reactivation was significantly greater in Group 2 (21.8%, 7 of 32) than in Group 1 (0%, 0/16) or the control group (2.3%, 1 of 43; p < 0.05 each). The cumulative rate of CHB exacerbation, however, did not differ significantly between Groups 2 (12.5%, 4 of 32) and 1 (0%, 0 of 16) or the control group (2.3%, 1 of 43; p > 0.05 each). The CHB exacerbations in the 4 Group 2 patients had radiation-induced liver disease features but were differentiated by serum HBV DNA changes. Two of these patients required antiviral therapy and effectively recovered with lamivudine therapy. Conclusions: In patients with HBV-related HCC undergoing 3D-CRT, HBV reactivation and consequent CHB exacerbation should be considered in the differential diagnosis of radiation-induced liver disease, and antiviral therapy might be considered for the prevention of liver function deterioration after RT.« less