Abstract
It was recently reported that hepatocellular carcinoma (HCC) patients with non-alcoholic steatohepatitis (NASH) are not responsive to immune-checkpoint inhibitor (ICI) treatment. The present ...study aimed to evaluate the therapeutic efficacy of lenvatinib in patients with non-alcoholic fatty liver disease (NAFLD)/NASH-related unresectable-HCC (u-HCC). Five hundred thirty u-HCC patients with Child–Pugh A were enrolled, and divided into the NAFLD/NASH (n = 103) and Viral/Alcohol (n = 427) groups. Clinical features were compared in a retrospective manner. Progression-free survival (PFS) was better in the NAFLD/NASH than the Viral/Alcohol group (median 9.3 vs. 7.5 months, P = 0.012), while there was no significant difference in overall survival (OS) (20.5 vs. 16.9 months, P = 0.057). In Cox-hazard analysis of prognostic factors for PFS, elevated ALT (≥ 30 U/L) (HR 1.247, P = 0.029), modified ALBI grade 2b (HR 1.236, P = 0.047), elevated AFP (≥ 400 ng/mL) (HR 1.294, P = 0.014), and NAFLD/NASH etiology (HR 0.763, P = 0.036) were significant prognostic factors. NAFLD/NASH etiology was not a significant prognostic factor in Cox-hazard analysis for OS (HR0.758, P = 0.092), whereas AFP (≥ 400 ng/mL) (HR 1.402, P = 0.009), BCLC C stage (HR 1.297, P = 0.035), later line use (HR 0.737, P = 0.014), and modified ALBI grade 2b (HR 1.875, P < 0.001) were significant. Lenvatinib can improve the prognosis of patients affected by u-HCC irrespective of HCC etiology or its line of treatment.
Background/Aim
Although systemic therapy is recommended for patients with multiple intermediate stage unresectable hepatocellular carcinoma (u‐HCC) classified as beyond the up‐to‐7 criteria (UT‐7 ...out/multiple) as a transcatheter arterial chemoembolization (TACE) unsuitable condition, few reports have examined the therapeutic efficacy of atezolizumab plus bevacizumab combination therapy (Atez/Bev) in such cases. This study aimed to elucidate the therapeutic response of Atez/Bev in u‐HCC patients classified as UT‐7 out/multiple.
Material/Methods
From September 2020 to September 2021, 95 u‐HCC Japanese patients classified as UT‐7 out/multiple/Child‐Pugh A were enrolled from 21 institutions (median age 76 years, males 73, Child‐Pugh 5:6 = 68:27, TNM stage II:III = 17:78). Therapeutic response was retrospectively evaluated using Response Evaluation Criteria in Solid Tumors (RECIST), ver. 1.1 and modified RECIST (mRECIST).
Results
Atez/Bev was given as first‐line treatment to 52 (54.7%). Objective response rate (ORR)/disease control rate (DCR) at six weeks of RECIST and mRECIST were 17.7%/84.7% and 42.5%/86.2%, respectively. Median PFS was 8.0 months (median observation period: 6.0 months). Child‐Pugh A/modified Albumin‐bilirubin grade (mALBI) 1 and 2a at baseline, 3, 6, and 9 weeks, were 100%/69.4%, 89.8%/57.3%, 94.8%/65.3%, and 91.4%/60.0%, respectively. Among adverse events (any‐grade, >10%) during the present observation period, general fatigue was most frequent (23.2%), followed by urine protein (21.1%), appetite loss (20.0%), and hypertension (13.7%).
Conclusion
Atez/Bev treatment showed favorable therapeutic response with less influence on hepatic function, suggesting it as a useful therapeutic option for patients with such condition.
Abstract
We investigated the impact on survival of modified albumin–bilirubin (mALBI) grade versus Child–Pugh classification in patients with hepatocellular carcinoma (HCC) who received lenvatinib. A ...total of 524 patients with HCC who received lenvatinib were included. Univariate analysis showed that mALBI grade 2b/3 and Child–Pugh class B/C were significantly associated with survival hazard ratio (HR), 2.471; 95% confidence interval (CI), 1.944–3.141 and HR, 2.178; 95%CI, 1.591–2.982. In patients with a Child–Pugh score of 5, multivariate analysis showed that mALBI grade 2b/3 was independently associated with survival (HR, 1.814; 95%CI, 1.083–3.037). Conversely, among patients with mALBI grade 1/2a, there was no difference in survival between those with a Child–Pugh class of 5 or 6 (
p
= 0.735). Time-dependent receiver operating characteristic analysis showed that the ALBI score predicted survival better than the Child–Pugh score. The optimal cut-off value of the ALBI score for predicting survival was nearly the same as the value separating mALBI grades 2a and 2b. In conclusion, the mALBI grade was a better predictor of survival than the Child–Pugh classification in patients with unresectable HCC who received lenvatinib therapy.
Aim
Tyrosine kinase inhibitor (TKI) therapy resulted in better prognosis for patients with hepatocellular carcinoma (HCC). However, some cases with Barcelona Clinic Liver Cancer (BCLC) stage C ...disease still had poor prognosis. This study aimed to investigate prognosis and characteristics of patients with HCC treated with TKI based on liver function and the extent of portal vein tumor thrombosis (PVTT).
Methods
Patients receiving TKI therapy (n = 345) were recruited retrospectively. Child–Pugh score and albumin–bilirubin (ALBI) score were used for assessment of liver function. The extent of PVTT was classified from Vp0 to Vp4. Radiotherapy or hepatic arterial infusion chemotherapy were carried out as additional therapy to TKI. The end‐point for this analysis was overall survival (OS).
Results
A total of 291 and 54 patients received sorafenib and lenvatinib as first‐line TKI therapy, respectively. The median OS of patients treated with TKI were significantly stratified by ALBI grade (grade 1, 20.1 months; grade 2a, 16.3 months; grades 2b and 3, 9.8 months; P = 0.0003). The classification of PVTT significantly stratified the prognosis of patients treated with TKI (median OS: Vp0, 18.5 months; Vp1/2, 14.4 months; Vp3/4, 5.5 months; P < 0.0001). In the ALBI 2b/3 and Vp3/4 groups, the median OS of patients treated with TKI and additional therapies was significantly longer than those treated with TKI only (9.2 months vs.. 3.6 months; P = 0.0129).
Conclusion
Liver function and PVTT are useful for stratifying prognosis of HCC patients treated with TKI. The applicative classification could lead to appropriate therapy and better prognosis.
Aim
Multiple molecular agents have been developed for treating unresectable hepatocellular carcinoma. This study aimed to elucidate the clinical efficacy of sequential treatment with lenvatinib after ...regorafenib failure.
Methods
From June 2017 to October 2020, 63 patients with Child–Pugh A and treated with regorafenib followed by sorafenib were enrolled (median age 71 years, 52 men, Barcelona Clinic Liver Cancer B:C = 23:40). They were divided into two groups, those treated with lenvatinib after regorafenib treatment (R‐L group, n = 47) and those who did not receive lenvatinib after regorafenib (non‐R‐L group, n = 16). Prognostic factors were retrospectively analyzed after adjustment with inverse probability weighting.
Results
Serum albumin level at the start of regorafenib and reasons for discontinuation of regorafenib were significantly different between the R‐L and non‐R‐L groups, whereas the albumin‐bilirubin score, Child–Pugh class, and tumor burden were not. Progression‐free survival was also not significantly different (median 4.1 vs. 3.8 months, p = 0.586). As for overall survival, the R‐L group showed better prognosis after introducing regorafenib and after introducing sorafenib, following inverse probability weighting adjustment (MST 19.7 vs. 10.3 months, 33.8 vs. 15.3 months, p < 0.001 and p = 0.022, respectively). Modified albumin‐bilirubin grade 2b (score >−2.27) at the start of regorafenib (HR 2.074, p = 0.041) and the presence of lenvatinib treatment after regorafenib failure (HR 0.355, p = 0.004) were found to be significant prognostic factors in Cox proportional hazards multivariate analysis, after inverse probability weighting adjustment.
Conclusion
These results show that lenvatinib is a good sequential treatment option after progression under regorafenib therapy in unresectable hepatocellular carcinoma patients with better hepatic reserve function.
We investigated the impact of C-reactive protein to albumin ratio (CAR) on predicting outcomes in 522 patients with unresectable hepatocellular carcinoma (HCC) treated with lenvatinib. We determined ...the optimal CAR cutoff value with time-dependent receiver operating characteristic curve analysis. Additionally, we clarified the relationship between CAR and liver function or HCC progression. Median overall survival was 20.0 (95% confidence interval (CI), 17.2-22.6) months. The optimal CAR cutoff value was determined to be 0.108. Multivariate analysis showed that high CAR (≥ 0.108) (hazard ratio (HR), 1.915; 95% CI, 1.495-2.452), Eastern Cooperative Oncology Group performance status ≥ 1 (HR, 1.429), and α-fetoprotein ≥ 400 ng/mL (HR, 1.604) were independently associated with overall survival. Cumulative overall survival differed significantly between patients with low versus high CAR (p < 0.001). Median progression-free survival was 7.5 (95% CI, 6.7-8.1) months. Multivariate analysis showed that age, CAR ≥ 0.108 (HR, 1.644; 95% CI, 1.324-2.043), and non-hepatitis B, non-hepatitis C etiology (HR, 0.726) were independently associated with progression-free survival. Cumulative progression-free survival differed significantly between patients with low versus high CAR (p < 0.001). CAR values were significantly higher as Japan Integrated Staging score increased (p < 0.001). In conclusion, CAR can predict outcomes in patients with unresectable HCC treated with lenvatinib.
Background/aim
We assessed suitable factors indicating newly developed lenvatinib (LEN) treatment for unresectable hepatocellular carcinoma (u‐HCC) by investigating real‐world clinical features of ...patients.
Materials/methods
One hundred fifty two u‐HCC patients, who receive LEN treatment from March to December 2018, were enrolled. (Child‐Pugh score CPS 5/6/7/8 = 76/61/13/2, modified albumin‐bilirubin grade mALBI 1/2a/2b/3 = 53/35/60/4). Clinical features were evaluated retrospectively.
Results
Overall‐response rate (ORR)/disease control rate (DCR) at 1 month after starting LEN were 38.7%/86.0%, respectively. Estimated median time to progression (TTP) was 7.0 months, while median survival time was not reached within the observation period. CPS (≥7) and past history of tyrosine‐kinase inhibitor (TKI) were not significant prognostic factors. mALBI ≥2b was an only significant prognostic factor (HR 4.632, 95%CI 1.649‐13.02, P = 0.004) in Cox‐hazard multivariate analysis. In patients with Child‐Pugh A, c‐index/Akaike's information criterion (AIC) of prognostic predictive value of mALBI were superior to CPS (0.682/135.6 vs 0.652/138.7), while those of stopping LEN also showed that mALBI was better (0.575/447.3 vs 0.562/447.8). Additional analysis of patients with good mALBI (1/2a) revealed that time to stopping LEN was significantly shorter in those with the adverse event (AE) of appetite loss (any grade) than those without (P = 0.006) and body mass index (BMI) was also lower in patients with that AE (20.3 ± 3.0 vs 23.6 ± 4.0kg/m2, P < 0.001), while patients with a hand‐foot skin reaction (any grade) showed good ORR/DCR (59.1%/86.4%) and longer TTP as compared to patients without (P = 0.007).
Conclusion
Good hepatic function (mALBI 1/2a) is the best indication for LEN, while potential appetite loss in association with low BMI should be kept in mind in such cases.
Child‐Pugh score was not enough for evaluation of hepatic function in unresectable patients treated with lenvatinib. Good hepatic function (modified Albumin‐bilirubin grade 1/2a) is the best indication for lenvatinib. When lenvatinib is given to patients with lower BMI (<21.0 kg/m2), close attention is needed for decline of appetite, while a dose adjustment may be required soon in accordance with the condition in order to avoid a long period of interruption or stopping the drug, which can reduce therapeutic efficacy.
Background/Aim
Atezolizumab plus bevacizumab (Atez/Bev) treatment is recommended for unresechepatocellular carcinoma (u‐HCC) patients classified as Child‐Pugh A (CP‐A). This study aimed to elucidate ...the prognosis of patients treated with Atez/Bev, especially CP‐A and ‐B cases.
Materials/methods
From September 2020 to March 2022, 457 u‐HCC patients treated with Atez/Bev were enrolled (median age 74 years, male:female = 368:89, CP‐A:CP‐B = 427:30, Child‐Pugh score CPS 5:6:7:8:9 = 271:156:21:8:1). Therapeutic response was evaluated using RECIST ver.1.1. Clinical features and prognosis were retrospectively evaluated.
Results
There were no significant differences between CP‐A and ‐B patients in regard to best response (CR:PR:SD:PD = 16:91:194:81 vs. 0:7:13:8, p = 0.739; objective response rate/disease control rate = 28.0%/78.8% vs. 25.0%/71.4%). Analysis performed using inverse probability weighting adjustments of clinical factors other than those related to hepatic reserve function with a p value < 0.10 for comparisons between patients with CP‐A and ‐B showed that the progression‐free survival (PFS) rate for CP‐A cases was better (6‐/12‐/18‐month: 58.2%/36.1%/27.8% vs. 49.6%/8.7%/non‐estimable NE, p < 0.001), as was overall survival (OS) rate (6‐/12‐/18‐month: 89.9%/71.7%/51.4% versus 63.6%/18.4%/NE; p < 0.001). Median PFS (mPFS) and median OS (mOS) for the CPS‐5 were 9.5 months/NE, and 5.1/14.0 months for the CPS‐6 (both p < 0.001). Furthermore, for modified albumin‐bilirubin grade (mALBI)‐1/2a/2b, mPFS was 9.4/8.5/5.3 months (p < 0.001) and mOS was NE/17.8/13.4 months (p < 0.001).
Conclusion
Better hepatic function, such as mALBI grade 1 or 2a are thought to indicate a better condition for obtaining sufficient prognosis with Atez/Bev treatment for u‐HCC patients, whereas for CP‐B patients, who mainly shown an mALBI grade of 2b or 3, Atez/Bev might have less therapeutic efficacy.
Abstract
External auditory canal cancer (EACC) is a rare malignant tumor. In the present study, we retrospectively evaluated the treatment results in patients with advanced EACC who were treated ...using external-beam radiotherapy (EBRT) combined with chemotherapy or radical surgery. Overall, 21 patients with Stage III (n = 8) or Stage IV (n = 13) EACC who underwent initial treatment at our hospital between 2003 and 2016 were enrolled in this study. The 2-year overall survival (OS) and locoregional control (LRC) rates of all patients were 62% and 71%, respectively. The 2-year OS and LRC rates in patients who had received EBRT and concurrent chemotherapy with docetaxel, cisplatin and 5-fluorouracil (TPF, n = 6) were 100%. These results were higher than the 2-year OS and LRC rates of 62% and 69%, respectively, in patients who had received radical surgery and EBRT (n = 13). The rates were 0% in those who had neither received TPF nor undergone surgery in addition to EBRT (n = 2). Grade 3 bone or soft tissue necrosis was observed in 2 patients who had undergone surgery and postoperative EBRT. Our data suggest that the combination therapy of EBRT and surgery and/or chemotherapy may be the most effective treatment options for advanced EACC, and EBRT with concurrent chemotherapy with TPF is potentially the most acceptable.
Aim
This study aimed to investigate the utility of C-reactive protein (CRP) and alpha-fetoprotein (AFP) in immunotherapy (CRAFITY) score in hepatocellular carcinoma (HCC) patients receiving ...atezolizumab and bevacizumab (Atez/Bev).
Methods
This retrospective cohort study included a total of 297 patients receiving Atez/Bev from September 2020 to November 2021 at 21 different institutions and hospital groups in Japan. Patients with AFP ≥ 100 ng/mL and those with CRP ≥ 1 mg/dL were assigned a CRAFITY score of 1 point.
Results
The patients were assigned CRAFITY scores of 0 points (
n
= 147 49.5%), 1 point (
n
= 111 37.4%), and 2 points (
n
= 39 13.1%). AFP ≥ 100 ng/mL and CRP ≥ 1.0 mg/dL were significantly associated with progression-free survival (PFS) and overall survival (OS). The median PFS in the CRAFITY score 0, 1, and 2 groups was 11.8 months (95% confidence interval CI 6.4-not applicable NA), 6.5 months (95% CI 4.6–8.0), and 3.2 months (95% CI 1.9–5.0), respectively (
p
< 0.001). The median OS in patients with CRAFITY score 0, 1 and 2 was not reached, 14.3 months (95% CI 10.5-NA), and 11.6 months (95% CI 4.9-NA), respectively. The percentage of patients with grade ≥ 3 liver injury, any grade of decreased appetite, any grade of proteinuria, any grade of fever, and any grade of fatigue was lowest in patients with a CRAFITY score of 0, followed by patients with CRAFITY scores of 1 and 2.
Conclusions
The CRAFITY score is simple and could be useful for predicting therapeutic outcomes and treatment-related adverse events.
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