The Association Between Modified Albumin-Bilirubin (mALBI) and Survival in Advanced Non-small Cell Lung Cancer Patients Treated With Immunotherapy.

OBJECTIVE: This study aimed to assess the clinical value of the modified albumin-bilirubin (mALBI) grade in predicting the survival of patients with advanced non-small cell lung cancer (NSCLC) treated with immunotherapy. METHODS: We conducted a retrospective cohort study of patients with advanced NSCLC who received immune checkpoint inhibitors (ICIs) from January 2020 to May 2022. The primary endpoints were overall survival (OS), treatment response, and the association between different mALBI grades and survival. RESULTS: In these 67 patients, 85.1% (57/67) were male, and the median age was 63 years. The patients with mALBI grades 1 and 2a at baseline had a median OS of 12.83 months (95% CI: 9.4 to 16.27 months), whereas it was 3.2 months (95% CI: NA to 11.59 months) for patients with mALBI grades 2b and 3. The OS for patients with dynamic mALBI grades 1 and 2a was 13.27 months (95% CI: 8.72 to 17.81 months), significantly longer than five months (95% CI: 2.47 to 7.53 months) for dynamic mALBI grades 2b and 3 patients (p<0.01).  Conclusion: In conclusion, mALBI grade may be a potential dynamic biomarker for predicting the prognosis in advanced NSCLC patients treated with immunotherapy.

Development and validation of a modified albumin-bilirubin grade and α-fetoprotein score (mALF score) for hepatocellular carcinoma patients receiving atezolizumab and bevacizumab.

AIM: Predicting the survival of hepatocellular carcinoma (HCC) patients receiving atezolizumab and bevacizumab (Atez/bev) remains a challenge. This study aims to validate the modified albumin-bilirubin grade and α-fetoprotein score (mALF score). METHODS: This retrospective, multicenter study included 426 HCC patients receiving Atez/Bev. Each patient was randomized 3:2 to a training set (n = 255) and a validation set (n = 171). We investigated prognostic factors in the training set and developed an easily applicable mALF score, which was evaluated in the validation set. RESULTS: We built the mALF score using baseline mALBI grade 2b or 3 (HR 2.36, 95% CI 1.37-4.05, p = 0.002) and α-fetoprotein ≥ 100 ng/ml (HR 2.61, 95% CI 1.49-4.55, p < 0.001), which were identified as unfavorable prognostic factors in a multivariate analysis. The 1-year OS rates were 82.7% (95% CI 68.9-90.8) in patients who meet neither of the criteria (mALF 0 points, n = 101), 61.7% (95% CI 44.5-74.9) in patients who meet either of the two criteria (mALF 1 point, n = 109), and 24.6% (95% CI 9.0-44.3) in patients who meet both criteria (mALF 2 points, n = 45); the difference was statistically significant (p < 0.001). The median PFS in patients with mALF 0, 1, and 2 points was 9.5 months (95% CI 4.3-NA), 6.6 months (95% CI 6.0-8.0), and 3.8 months (95% CI 3.0-5.2), respectively, which amounted to a significant difference (p < 0.001). These results were confirmed in the validation set (1-year OS rates, 0/1/2 points = 94.2%/62.1%/46.3%, p < 0.001; median PFS, 0/1/2 points = 9.3/6.7/4.7 months, p = 0.018). CONCLUSION: The mALF score can reliably predict the prognosis of HCC patients receiving Atez/Bev.

Long-term Outcomes and Prognostic Factors of Stereotactic Body Radiotherapy for Hepatocellular Carcinoma.

BACKGROUND/AIM: This study was conducted to determine the prognosis and risk factors for survival in patients treated with stereotactic body radiotherapy (SBRT) for hepatocellular carcinoma (HCC). PATIENTS AND METHODS: This retrospective study analyzed 73 patients who underwent SBRT for HCC at Nagasaki University Hospital from December 2012 to July 2019 and examined the relationship between baseline information and prognosis. The Kaplan-Meier analysis and log-rank test were used to estimate the survival rate. Cox regression analysis was performed to determine the factors associated with overall survival (OS) after SBRT. RESULTS: The 1- and 2-year local control rates were 98.6% and 89.9%, respectively. Survival rates at 1, 3, and 5 years were 94.5%, 63.9%, and 45.5%, respectively. In the univariate analysis, baseline modified albumin-bilirubin grade (mALBI grade) [2b/3, hazard ratio (HR)=2.762, p=0.001], tumor size (≥2 cm, HR=2.479, p=0.003), and Barcelona Clinic Liver Cancer stage (BCLC) (B/C, HR=3.284, p<0.001) were significantly associated with poor prognosis. In multivariate analysis, baseline mALBI grade (2b/3, HR=2.283, p=0.009) and BCLC stage (B/C, HR=2.330, p=0.013) were significantly associated with poor prognosis. Only three patients (4.1%) developed grade 3 adverse events related to SBRT. CONCLUSION: SBRT is effective and safe in patients with HCC. The baseline mALBI grade is useful for predicting patient prognosis after SBRT. Patients with an mALBI grade of 1/2a are expected to have a better prognosis than patients with an mALBI grade of 2b/3.

A detailed assessment of liver function in patients with hepatocellular carcinoma via the modified albumin-bilirubin (mALBI) grade.

Recently, the albumin-bilirubin (ALBI) score, a continuous index consisting of only albumin and bilirubin, has been developed for objectively assessing liver function in patients with hepatocellular carcinoma (HCC). However, the ALBI score was arbitrarily categorized into three ALBI grades based on two artificially predetermined cutoff points with no explanation and statistical grounds, causing a considerable loss of discriminatory ability. This study aims to propose a modified ALBI (mALBI) grade for offering a detailed evaluation of hepatic reserve and specify its role during clinical practice in the HCC setting. The study population comprised 3540 HCC patients treated with mainstream therapies including hepatectomy (n=2056), thermal ablation (n=550), and transcatheter arterial chemoembolization (n=934) from 2002 to 2017. The ALBI score was stratified into four mALBI grades through a recently proposed statistical method aiming to select the optimal cutoff points of a continuous predictive variable by maximizing the discriminative ability in a multivariable Cox regression model. The mALBI grade had an overall better discriminatory ability than the ALBI grade in predicting overall survival through Harrell's C-index (0.614 vs. 0.598, P<0.001). Both visual inspections of Kaplan-Meier curves and calculation of hazard ratios displayed a more subtle evaluation of liver function using the mALBI grade. Moreover, the newly identified cut-point (ALBI score = -2.29) between the mALBI grade 2a and 2b was much closer to a 30% retention rate of indocyanine green at 15 minutes, an indicator for the performance of a subsegmentectomy. The newly proposed mALBI grade provides a more subtle assessment of liver function to guide clinical decision-making and predicts the prognosis of HCC patients more accurately than the original ALBI grade.

Sequential therapy including regorafenib for unresectable hepatocellular carcinoma: Effect of early relative changes in hepatic functional reserve after regorafenib administration on prognosis.

AIM: Regorafenib is a second-line treatment for unresectable hepatocellular carcinoma after sorafenib-refractory treatment. This study examined the effects of regorafenib administration on hepatic functional reserve and the treatment course after regorafenib discontinuation. METHODS: This retrospective, multicenter study involved 51 patients treated with regorafenib after sorafenib-refractory treatment for u-HCC at seven institutions before March 2021. RESULTS: Fourteen, 13, and 24 patients were classified based on modified albumin-bilirubin (mALBI) grade 1, 2a, and 2b, respectively. The median survival time and progression-free survival were 16.7 and 3.3 months, respectively. Only mALBI grade 2b or 3 was significantly associated with survival rate (hazard ratio, 2.13; 95% confidence interval, 1.01-4.49; p = 0.047). A comparison of median ALBI scores at the initiation of regorafenib (-2.35) with those at 4 weeks (-1.93) revealed a significant relative change (p = 0.0001). After 4 weeks, grade 1 or 2a persisted in 15 patients (Group 1); grade 1 or 2a deteriorated to 2b in 12 patients (Group 2); grade 2b or 3 before regorafenib administration was present in 22 patients (Group 3); and MST was 33.3, 12.8, and 11.3 months in the three groups, respectively (p = 0.05). Patients treated with lenvatinib (LEN) (n = 27, MST = 23.4 months) after regorafenib had a significantly longer survival time from regorafenib initiation than those not treated with LEN (n = 24, 11.8 months; p = 0.043). CONCLUSIONS: Hepatic functional reserve significantly declined after regorafenib administration. During regorafenib treatment, favorable hepatic functional reserve before administration and maintenance of favorable hepatic reserve after administration lead to prolonged prognosis.

Changes in Background Liver Function in Patients with Hepatocellular Carcinoma over 30 Years: Comparison of Child-Pugh Classification and Albumin Bilirubin Grade.

BACKGROUND: Background liver function in patients with hepatocellular carcinoma (HCC) has improved remarkably with advances in various treatments. Recently, the Child-Pugh classification (CPC) system has been recognized as limited in its ability to assess patients with good hepatic reserve. We compared the albumin-bilirubin (ALBI) grade, which is suitable for a more detailed evaluation of patients with good liver function, with CPC over a 30-year period. METHODS: A total of 2,347 patients were analyzed. Patients were stratified by year of diagnosis into 6 groups: Group A (1990-1994, n = 376), Group B (1995-1999, n = 434), Group C (2000-2004, n = 438), Group D (2005-2009, n = 444), Group E (2010-2014, n = 392), and Group F (2015-2018, n = 263). We compared ALBI grade and CPC across the groups. RESULTS: The prevalence of patients with CPC A at diagnosis increased throughout the study period, reaching nearly 80% in Groups E and F (p < 0.001). By contrast, the percentage of patients with ALBI grade 1 disease remained approximately 50% in Groups E and F (p < 0.001). Modified ALBI (mALBI) grade 2a corresponds to patients with CPC A who have poor hepatic function. There were significant survival differences between patients with mALBI grade 1 versus 2a, 1 versus 2b, and 2a versus 2b disease, respectively (p < 0.0001), in patients with CPC A. CONCLUSIONS: CPC is not suitable for assessing patients with recently diagnosed HCC and good remnant hepatic function. In such patients with HCC, the prognosis can be stratified by ALBI grade rather than CPC.

Validation of Modified ALBI Grade for More Detailed Assessment of Hepatic Function in Hepatocellular Carcinoma Patients: A Multicenter Analysis.

BACKGROUND/AIM: The frequency of hepatocellular carcinoma (HCC) in patients with good hepatic reserve function has been increasing in Japan along with the progression of antiviral therapies and aging of the society. We evaluated the usefulness of modified albumin-bilirubin (ALBI) grade as a tool for assessment of hepatic reserve function. MATERIALS/METHODS: We enrolled 6,649 naïve HCC patients treated from 2000 to 2017 and divided them into training (Ehime Prefecture group: E group, n = 2,357) and validation (validation group: V group, n = 4,292) cohorts. Child-Pugh classification and ALBI and modified ALBI (mALBI) grading were compared using with Japan Integrated Staging (JIS), ALBI-TNM (ALBI-T), and mALBI-T scores, which were calculated based on TNM stage and each assessment tool, retrospectively. RESULTS: In the E group, Akaike's Information Criterion (AIC) and c-index values for mALBI-T (13,725.2/0.744) were better as compared to those of ALBI-T (13,772.6/0.733) and JIS score (13,874.7/0.720), with similar results observed in the V group (mALBI-T: 27,727.4/0.760; ALBI-T: 27,817.8/0.750; JIS: 27,807.5/0.748). Although there were some significant differences between the groups with regard to clinical background factors (age, etiology, tumor size, tumor number, treatment modalities), for all patients the AIC and c-index values of mALBI-T (45,327.1/0.755) were also better than those of ALBI-T (45,467.7/0.744) and JIS scores (45,555.8/0.739), indicating its superior stratification ability and prognostic predictive value in patients with HCC. CONCLUSION: The detailed stratification ability of mALBI grade for hepatic reserve function is suitable for the recent trend of HCC patients, while mALBI-T may provide a more accurate predictive value than existing total staging scoring systems.