Dataset Information

Dosimetric Analysis and Normal-Tissue Complication Probability Modeling of Child-Pugh Score and Albumin-Bilirubin Grade Increase After Hepatic Irradiation.

ABSTRACT:

Purpose

This study aimed to develop robust normal-tissue complication probability (NTCP) models for patients with hepatocellular carcinoma treated with radiation therapy (RT) using Child-Pugh (CP) score and albumin-bilirubin (ALBI) grade increase as endpoints for hepatic toxicity.

Methods and materials

Data from 108 patients with hepatocellular carcinoma treated with RT between 2008 and 2017 were evaluated, of which 47 patients (44%) were treated with proton RT. Of these patients, 29 received stereotactic body RT and 79 moderately hypofractionated RT to median physical tumor doses of 43 Gy in 5 fractions and 59 Gy in 15 fractions, respectively. A generalized Lyman-Kutcher-Berman (LKB) model was used to model the NTCP using 2 clinical endpoints, both evaluated at 3 months after RT: CP score increase of ≥2 and ALBI grade increase of ≥1 from the pre-RT baseline. Confidence intervals on LKB fit parameters were determined using bootstrap resampling.

Results

Compared with previous NTCP models, this study found a stronger correlation between normal liver volume receiving low doses of radiation (5-10 Gy) and a CP score or ALBI grade increase. A CP score increase exhibited a stronger correlation to normal liver volumes irradiated than an ALBI grade increase. LKB models for CP increase found values for the volume-effect parameter of a = 0.06 for all patients, and a = 0.02/0.09 when fit to photon/proton patients separately. Subset analyses for patients with superior initial liver functions showed consistent dose-volume effects (a = 0.1) and consistent dose-response relationships.

Conclusions

This study presents an update of liver NTCP models in the era of modern RT techniques using relevant endpoints of hepatic toxicity, CP score and ALBI grade increase. The results show a stronger influence of low-dose bath on hepatic toxicity than those found in previous studies, indicating that RT techniques that minimize the low-dose bath may be beneficial for patients.

SUBMITTER: Pursley J

PROVIDER: S-EPMC7381375 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundsThe Child-Pugh score is a scoring system used to measure liver function and predict postoperative outcomes in patients with hepatocellular carcinoma (HCC). Recently, the Albumin-Bilirubin (ALBI) grade has been proposed for the evaluation of hepatic reserve function in HCC. This study aimed to assess and compare the capability of ALBI grade and Child-Pugh score in predicting overall survival (OS).MethodsA total of 196 consecutive HCC patients who treated with hepatectomy were enrolled in this retrospective study. The prognostic values of ALBI grade and Child-Pugh score in predicting postoperative OS were respectively estimated using the Kaplan-Meier method and time-dependent receiver operating curves (ROC). Univariate and multivariate Cox regression analyses were performed to investigate the prognostic factors for OS.ResultsStratified by the Albumin-Bilirubin (ALBI) system, there were 81 (41.3%) patients with grade 1 and 115 (58.7%) patients with grade 2. The cumulative 1-, 3-, 5-year OS rates in patients with ALBI-1 were 82.7%, 51.5% and 35.5%, respectively. For patients with ALBI-2, the cumulative 1-, 3-, 5-year OS rates were 57.6%, 19.4% and 0%, respectively. Based on the Child-Pugh classification, 136 (69.4%) patients had a score of 5, and 60 (30.6%) patients had a score of 6. Patients with Child-Pugh-A5 showed a better OS than those with Child-Pugh-A6, with respective OS at 1, 3 and 5 years (72.7%, 29.2%, 20.3% vs. 53.9%, 21.1%, 0%, Log-rank P<0.001). Besides, the ALBI grade revealed two prognostic groups within Child-Pugh-A5 (P<0.001), while the Child-Pugh score did not distinguish ALBI-2 in different prognostic groups (P=0.705). The multivariate analysis indicated that both ALBI grade and Child-Pugh score could significantly stratify the patients with different OS [hazard ratio (HR), 3.088 and 1.783; 95% confidence interval (CI), 1.985 to 4.805 and 1.272 to 2.731; P<0.001 and P=0.032 for ALBI grade and Child-Pugh score, respectively]. Additionally, time-dependent ROC analysis in the entire cohort proved that the ALBI grade had a better discriminatory ability than the Child-Pugh score in predicting survival, especially for long-term outcomes. According to the subgroup analyses, the ALBI grade had a better discriminatory ability and survival prediction accuracy in overall subsets than the Child-Pugh score for the prediction of OS.ConclusionsALBI grade supplied better prognostic performance and distribution of liver function than Child-Pugh score in stratifying prognosis for HCC patients treated by hepatectomy. These results declared that ALBI grade could be an alternative liver function grading system for stratification in patients with HCC.

Project description:BackgroundThe Child-Pugh score has been used extensively to assess hepatic function and predict post-treatment outcomes in patients with hepatocellular carcinoma (HCC). Recently, the albumin-bilirubin (ALBI) grade has been put forward as an objective method of evaluating liver function and predicting overall survival (OS) in HCC patients. Transarterial chemoembolization (TACE) is considered to be effective in prolonging OS among intermediate-stage HCC patients. This study aimed to explore and compare the performance of ALBI grade and Child-Pugh score in predicting outcomes for HCC patients who underwent TACE.MethodsThere were a total of 221 consecutive HCC patients enrolled in this study, all of whom received TACE and were enrolled retrospectively. The Kaplan-Meier method and time-dependent receiver operating curves (ROC) were used to estimate the discriminatory ability and survival prediction accuracy of ALBI grade and Child-Pugh score in predicting postoperative OS. Univariate and multivariate Cox regression analyses were performed to evaluate the prognostic factors for OS.ResultsOf the patients enrolled in the study, 106 (48.0%) were ALBI grade 1 and 115 (52.0%) were ALBI grade 2. Overall survival differed significantly between patients with ALBI-1 and ALBI-2 [hazard ratio (HR), 3.032; 95% CI, 2.019-4.555, P<0.001]. With regard to Child-Pugh scores, 160 (72.4%) patients had a score of A5 and 61 (27.6%) had a score of A6. There was also a difference in overall survival between patients with Child-Pugh-A5 and Child-Pugh-A6 (HR, 1.548; 95% CI, 1.066-2.247, P=0.022). In multivariate analyses, both ALBI grade and Child-Pugh score could significantly stratify the patients with different OS (HR, 2.994 and 1.545, P<0.001 and P=0.026 for ALBI grade and Child-Pugh score, respectively). Furthermore, time-dependent ROC analysis and its subgroup analyses demonstrated that the ALBI grade had a better discriminatory ability than Child-Pugh score in predicting survival.ConclusionsIn stratifying prognosis for HCC patients who had received TACE therapy, the ALBI grade provided better prognostic performance and discrimination of liver function than Child-Pugh score. These results suggest that ALBI grade could provide an alternative liver function grading system for stratification of patients with HCC.

Project description:PurposeTo identify dosimetric parameters associated with acute hematological toxicity (HT) and identify the corresponding normal tissue complication probability (NTCP) model in cervical cancer patients receiving helical tomotherapy (Tomo) or fixed-field intensity-modulated radiation therapy (ff-IMRT) in combination with chemotherapy, that is, concurrent chemoradiotherapy (CCRT) using the Lyman-Kutcher-Burman normal tissue complication probability (LKB-NTCP) model.MethodsData were collected from 232 cervical cancer patients who received Tomo or ff-IMRT from 2015 to 2018. The pelvic bone marrow (PBM) (including the ilium, pubes, ischia, acetabula, proximal femora, and lumbosacral spine) was contoured from the superior boundary (usually the lumbar 5 vertebra) of the planning target volume (PTV) to the proximal end of the femoral head (the lower edge of the ischial tubercle). The parameters of the LKB model predicting ≥grade 2 hematological toxicity (Radiation Therapy Oncology Group [RTOG] grading criteria) (TD50 (1), m, and n) were determined using maximum likelihood analyses. Univariate and multivariate logistic regression analyses were used to identify correlations between dose-volume parameters and the clinical factors of HT.ResultsIn total, 212 (91.37%) patients experienced ≥grade 2 hematological toxicity. The fitted normal tissue complication probability model parameters were TD50 (1) = 38.90 Gy (95%CI, [36.94, 40.96]), m = 0.13 (95%CI [0.12, 0.16]), and n = 0.04 (95%CI [0.02, 0.05]). Per the univariate analysis, the NTCP (the use of LKB-NTCP with the set of model parameters found, p = 0.023), maximal PBM dose (p = 0.01), mean PBM dose (p = 0.021), radiation dose (p = 0.001), and V16-53 (p < 0. 05) were associated with ≥grade 2 HT. The NTCP (the use of LKB-NTCP with the set of model parameters found, p = 0.023; AUC = 0.87), V16, V17, and V18 ≥ 79.65%, 75.68%, and 72.65%, respectively (p < 0.01, AUC = 0.66∼0.68), V35 and V36 ≥ 30.35% and 28.56%, respectively (p < 0.05; AUC = 0.71), and V47 ≥ 13.43% (p = 0.045; AUC = 0.80) were significant predictors of ≥grade 2 hematological toxicity from the multivariate logistic regression analysis.ConclusionsThe volume of the PBM of patients treated with concurrent chemoradiotherapy and subjected to both low-dose (V16-18 ) and high-dose (V35,36 and V47 ) irradiation was associated with hematological toxicity, depending on the fractional volumes receiving the variable degree of dosage. The NTCP were stronger predictors of toxicity than V16-18 , V35, 36 , and V47 . Hence, avoiding radiation hot spots on the PBM could reduce the incidence of severe HT.