Efficacy and safety of atezolizumab plus bevacizumab in patients with portal hypertension for unresectable hepatocellular carcinoma.

AIM: Atezolizumab plus bevacizumab combination therapy (Atezo + Beva) is used as the first-line therapy for unresectable hepatocellular carcinoma (u-HCC). Serious adverse events (AEs), including rupture of esophagogastric varices, have been seen during treatment. Therefore, the relationships of efficacy, safety, and portal hypertension (PH) were analyzed. METHODS: A total of 146 patients with u-HCC and Child-Pugh Scores of 5-7 received Atezo + Beva. Prophylactic treatment for varices was performed for patients with the risk of rupture of varices before the start of Atezo + Beva. A propensity score-matched cohort was created to minimize the risk of potential confounders. Efficacy was assessed in 41 propensity score-matched pairs. AEs were assessed between patients without PH (n = 80) and with PH (n = 66). RESULTS: In patients without PH and with PH, median overall survival was 18.4 months and 18.8 months (p = 0.71), and median progression-free survival was 8.6 months and 5.8 months (p = 0.92), respectively. On the best radiological response evaluation for Response Evaluation Criteria in Solid Tumors, the objective response rate was 31.7% and 26.8% (p = 0.81), respectively. Variceal rupture occurred in three patients with PH, but there were no significant differences in the occurrence of variceal rupture (p = 0.090) and Grade 3-4 AEs between patients without and with PH. CONCLUSIONS: No significant differences in efficacy and safety were observed with PH. Prophylactic treatment for varices before the start of Atezo + Beva would allow treatment to continue relatively safely.

Outcomes of Patients with Child-Pugh B and Unresectable Hepatocellular Carcinoma Undergoing First-Line Systemic Treatment with Sorafenib, Lenvatinib, or Atezolizumab Plus Bevacizumab.

INTRODUCTION: Systemic therapy is recommended for patients with Child-Pugh A in hepatocellular carcinoma (HCC). We analyzed the outcomes of a cohort of patients with HCC who received either sorafenib (Sor), lenvatinib (Len) or atezolizumab plus bevacizumab (Atezo + Bev) as first-line systemic therapy for HCC, with the aim of identifying prognostic factors for survival. METHODS: A total of 825 patients with advanced HCC and Child-Pugh A or B received either Sor, Len or Atezo + Bev as first-line systemic therapy. Liver function was assessed according to the Child-Pugh score and the modified albumin-bilirubin (mALBI) grade. RESULTS: Prognosis was analyzed according to liver function such as Child-Pugh classifications, scores, and mALBI grades that worsened with a decline in liver function (p <0.001 for all). A Child-Pugh score of 7 was a factor significantly associated with OS. In patients with a Child-Pugh score of 7, an mALBI grade of 3 was an independent predictor of OS. In Child-Pugh B patients with HCC, receiving Atezo + Bev was identified as a factor associated with PFS. CONCLUSION: Determining the hepatic reserve of patients with unresectable HCC might be useful for identifying patents suitable for systemic treatment for HCC. Atezo + Bev might prolong the PFS of patients with a Child-Pugh score of 7.

Clinical Outcomes of Switching from Zoledronic Acid to Denosumab for the Management of Severe Bone Metastasis from Hepatocellular Carcinoma: A Single-Center, Open-Label, Prospective Intervention Trial.

Background: Zoledronic acid reduces the risk of bone metastasis, but denosumab is a better option for treating bone metastases. However, few studies have evaluated the use of denosumab to treat bone metastasis originating from hepatocellular carcinoma. This study aimed to assess the clinical outcomes of switching from zoledronic acid to denosumab for treating bone metastasis in patients with hepatocellular carcinoma. Methods: This prospective study enrolled 10 patients with HCC and bone metastases. The levels of type 1 collagen cross-linked N-telopeptide (NTx) and tumor growth remained abnormal in these patients despite administration of zoledronic acid for over 3 months. We switched from zoledronic acid to 120 mg denosumab every 4 weeks and evaluated the clinical outcomes, including changes in the NTx level, pain level, and activities of daily living, as well as adverse events, after each administration. Results: Urinary NTx clearance was normal in all patients. The average urinary NTx clearance increased from 13.2 to 21.2 nmol BCE/nmol ·â€†Cre (P = 0.54) after the switch to denosumab. Serum NTx levels were abnormal in all cases. The serum NTx level decreased from 142 nmol BCE/L to 126 nmol BCE/L (P = 0.56). The answers to questionnaires on pain and activities of daily living did not change significantly. Some patients showed elevated transaminase levels, but this was not due to the drug switch. Conclusion: Switching to denosumab did not show a significant change of the pain and activity of daily living for the patients with severe bone metastasis from hepatocellular carcinoma, in whom the efficacy of zoledronic acid was limited.

Therapeutic Efficacy and Safety of Lenvatinib after Atezolizumab Plus Bevacizumab for Unresectable Hepatocellular Carcinoma.

A total of 137 HCC patients treated with atezolizumab plus bevacizumab from October 2020 to September 2022 were enrolled. The median overall survival (OS) and progression-free survival (PFS) from the beginning of atezolizumab plus bevacizumab were 21.1 months (range, 18.8 months-not reached) and 10.5 months (range, 8.2-12.1 months), respectively. Fifty patients were diagnosed with progressive disease after atezolizumab plus bevacizumab. Of this group, 24 patients were administered lenvatinib, and the median OS and PFS from the beginning of lenvatinib were 15.3 months (range, 10.5 months-not reached) and 4.0 months (range, 2.5-6.4 months), respectively. The objective response rates based on the response evaluation criteria in solid tumors (RECISTs) criteria version 1.1 and modified RECISTs were 33.3% and 54.2%, respectively. There was no significant difference in the median serum alpha-fetoprotein level between before and after lenvatinib. In the multivariate analysis, Child-Pugh class A (hazard ratio 0.02, 95% confidence interval (CI) 0.02-0.76, p = 0.02) and intrahepatic tumor occupancy rate < 50% (hazard ratio < 0.01, 95% CI 0.003-0.35, p < 0.01) were the significant factors for OS. There were some frequent adverse events (AEs) in patients treated with lenvatinib such as hypertension, fatigue, anorexia, proteinuria, and so on, but none directly caused death. In conclusion, lenvatinib after atezolizumab plus bevacizumab for unresectable HCC should be considered an effective treatment option.

Risk Factors for Early Onset of Proteinuria in Patients Receiving Atezolizumab Plus Bevacizumab for Unresectable Hepatocellular Carcinoma.

Introduction: Proteinuria is one of the adverse events of atezolizumab plus bevacizumab combination therapy (Atezo + Bev) and can cause interruption in the use of Bev. However, the risk factors for proteinuria in patients with hepatocellular carcinoma (HCC) who are receiving Atezo + Bev have not yet been investigated. The aim of this study was to identify the risk factors for early onset of proteinuria in Atezo + Bev for patients with unresectable HCC. Methods: Sixty-four patients with Child-Pugh scores of 5-7, an Eastern Cooperative Oncology Group performance status of 0 or 1, and low level of proteinuria (1+ or less on a dipstick test and urine protein-to-creatinine ratio (UPCR) less than 2.0 g/g Cr) at the initiation of therapy were analyzed. The level of proteinuria was evaluated based on the Common Terminology Criteria for Adverse Events version 5.0. We adopted the UPCR for the quantitative test instead of a 24-h urine collection. The incidence of proteinuria and changes in liver function were retrospectively investigated. Results: The cumulative incidence of proteinuria over a 24-week period was 34.4%. Multivariate analysis showed that a low estimated glomerular filtration rate (hazard ratio [HR], 3.807; 95% confidence interval [CI], 1.579-9.180; p = 0.003), treatment for hypertension (HR, 6.224; 95% CI, 1.614-24.010; p = 0.008), and high systolic blood pressure (SBP) (HR, 2.649; 95% CI, 1.133-6.194; p = 0.025) were risk factors for proteinuria. Serum albumin levels and albumin-bilirubin scores in patients with proteinuria worsened. In addition, a mean SBP ≥135 mm Hg during treatment was the only risk factor for the development of severe proteinuria (UPCR >2 g/g Cr). Conclusion: Our study found that controlling blood pressure is extremely important for the management of proteinuria in patients with HCC who are receiving Atezo + Bev.

The Analysis of Muscle Volume Measured by Bioelectrical Impedance in Patients with Hepatocellular Carcinoma Treated with First-Line Atezolizumab plus Bevacizumab Combination Therapy or First-Line Lenvatinib.

INTRODUCTION: Measurements of body composition, such as the skeletal muscle index (SMI), are useful for predicting prognosis in hepatocellular carcinoma (HCC). This study aimed to analyze the relationship between skeletal muscle changes during therapy with atezolizumab plus bevacizumab (Atezo + Beva) or lenvatinib (Len) and the association between SMI and prognosis. METHODS: Patients with advanced HCC and Child-Pugh A status received Atezo + Beva or Len as first-line systemic chemotherapy. We assessed prognosis and body composition obtained by bioelectrical impedance analysis. RESULTS: A total of 109 patients received treatment (Atezo + Beva, n = 47; Len, n = 62). During treatment, the arm SMI was reduced in the Len group and maintained in the Atezo + Beva group. The extracellular water to total body water ratio (ECW/TBW) increased significantly in both groups during treatment. In the Atezo + Beva group, no factor was associated with prognosis. Multivariate analysis showed that in the Len group, the arm SMI (hazard ratio [HR], 0.5; 95% CI: 0.26-0.89; p = 0.02), ECW/TBW (HR: 2.7; 95% CI: 1.21-6.01; p = 0.01), and Child-Pugh score (HR: 2.3; 95% CI: 1.31-6.13; p = 0.004) were associated with progression-free survival. CONCLUSION: Assessing body composition with BIA before Atezo + Beva and Len treatment may be useful.

Impact and usefulness of the transition to the new MAFLD classification for non-B, non-C HCC: a retrospective cohort study.

BACKGROUND: Metabolic dysfunction-associated fatty liver disease (MAFLD) represents a new classification system for fatty liver disease. In this study, we investigated the clinical characteristics of patients with MAFLD-hepatocellular carcinoma (HCC) in comparison with those with nonalcoholic fatty liver disease (NAFLD) and considered the validity and challenges of the new criteria. METHODS: This study included 237 untreated non-B, non-C HCC patients with hepatic steatosis. We examined the profile and laboratory findings of patients with MAFLD-HCC and NAFLD-HCC. We also classified MAFLD-HCC patients according to the factors on which the diagnosis was based and compared their clinical characteristics. RESULTS: A total of 222 (94%) and 101 (43%) patients were diagnosed with MAFLD and NAFLD, respectively. MAFLD-HCC patients were more likely to be male than NAFLD-HCC, but there were no significant differences in metabolic indices, noninvasive liver fibrosis score or HCC status. In a study of MAFLD-HCC patients by diagnostic factor, those with overweight only were younger and had advanced liver fibrosis histologically, and when limited to patients younger than 70 years, the majority were overweight. Redefinition of overweight as BMI ≥ 25 reduced the number of MAFLD-HCC patients by only 5, from 222 to 217. CONCLUSIONS: MAFLD accounted for the majority of non-B, non-C HCC cases with hepatic steatosis. Examination of additional cases and revision of the detailed criteria is needed so that it can be used to efficiently select patients with fatty liver who are at high risk of developing HCC.

Evaluation of Response to Atezolizumab Plus Bevacizumab in Patients with Advanced Hepatocellular Carcinoma Using the Combination of Response Evaluation Criteria in Solid Tumors and Alpha-Fetoprotein.

Atezolizumab plus bevacizumab combination therapy (Atezo + Beva) is currently positioned as the first-line therapy for unresectable hepatocellular carcinoma (u-HCC). It may be difficult to decide whether to continue this treatment if radiological response is assessed as stable disease (SD). Therefore, the relationship between radiological response and prognosis was analyzed. A total of 109 patients with u-HCC and Child-Pugh Score of 5-7 received this treatment. Radiological response was assessed using Response Evaluation Criteria in Solid Tumors (RECIST) and modified RECIST at the first and second evaluations. Of SD patients (n = 71) at the first RECIST evaluation, partial response, SD, and progressive disease (PD) were seen in 10, 55, and 6 patients, respectively, at the second evaluation. On multivariate analysis, in patients with SD at the first RECIST evaluation, a 25% or greater increase in the alpha-fetoprotein (AFP) value from initiation of treatment (odds ratio, 7.38; p = 0.037) was the independent factor for PD at the second evaluation. In patients with SD (n = 59) at the second RECIST evaluation, decreased AFP from initiation of treatment (hazard ratio, 0.46; p = 0.022) was the independent factor related to progression-free survival on multivariate analysis. AFP trends could help decide the Atezo + Beva treatment strategy.

Effectiveness of Repeated Stereotactic Body Radiation Therapy for Hepatocellular Carcinoma-Consideration of the Locations of Target Lesions.

The present study retrospectively evaluated the efficacy of stereotactic body radiation therapy (SBRT), including repeated SBRT, for hepatocellular carcinoma. Participants comprised 220 HCC patients treated with SBRT in Hiroshima University Hospital between December 2008 and December 2021. Median overall survival (OS) and disease-free survival were 52 months (range, 45-64 months) and 17 months (range, 14-23 months), respectively. The 5-year local tumor recurrence rate was 3.4% (95% confidence interval (CI), 1.3-6.9%). Fifty-three patients underwent repeated SBRT (twice, 53 cases; three times, 10 cases; four times, 4 cases; five times, 1 case). Median interval between first and second SBRT was 20 months. Median OS from first SBRT was 76 months (95% CI, 50-102 months). Among patients with repeated SBRT, only one case showed local recurrence after second SBRT. Albumin-bilirubin score increased significantly from 6 to 12 months after repeated SBRT, both in the same segment and in remote segments, but the increase was not significant in the same segment. Only one case of grade 3 bile duct stricture was observed in patients who were treated with repeated SBRT. In conclusion, repeated SBRT provides good local control and a low risk of side effects.

Successful Lenvatinib Re-challenge following Atezolizumab Plus Bevacizumab Combination Therapy Failure for Unresectable Hepatocellular Carcinoma.

To our knowledge, there have been no reports of first-line lenvatinib (LEN) and LEN re-challenge following atezolizumab/bevacizumab (Atezo-Bev) failure in the same patient. We herein report a patient with advanced hepatocellular carcinoma who failed either 1st line LEN and 2nd line Atezo-Bev, and successfully achieved complete response to LEN rechallenge with sequencial transcatheter arterial chemoembolization (TACE). This patient had a poor response to TACE before immunotherapy and introduction of molecular-targeted drugs but showed a good response to selective TACE after LEN rechallenge. Our findings suggest the need to reconsider the use of molecular-targeted drugs and TACE with advances in immunotherapy.

Hepatic venous pressure gradient after balloon-occluded retrograde transvenous obliteration and liver stiffness measurement predict the prognosis of patients with gastric varices.

BACKGROUND: Balloon-occluded retrograde transvenous obliteration (BRTO) is a treatment option for patients with gastric varices (GVs). This study aimed to clarify the clinical significance of portal hypertension estimated by the hepatic venous pressure gradient (HVPG), subsequent exacerbation of esophageal varices (EVs), and prognosis of patients who underwent BRTO for GVs. METHODS: Thirty-six patients with GVs treated with BRTO were enrolled in this study, and their HVPG was measured before (pre-HVPG) and on the day after BRTO (post-HVPG). After BRTO, patients were followed-up for a median interval of 24.5 (3-140) months. Clinical factors related to EVs exacerbation and prognosis after BRTO were retrospectively analyzed. RESULTS: Post-HVPG increased compared to pre-HVPG in 21 out of 36 patients (58%), and post-HVPG was overall significantly higher compared to pre-HVPG (P = 0.009). During the observation period, 19 patients (53%) developed EVs exacerbation, and the cumulative EVs exacerbation rates at 1, 3 and 5 years after BRTO were 27%, 67%, and 73%, respectively. Pre-HVPG was not related to EVs exacerbation, although elevation of post-HVPG to ≥ 13 mmHg (P < 0.01) and high level of serum aspartate aminotransferase (P < 0.05) were significant independent risk factors for EVs exacerbation after BRTO. Fourteen patients (38.9%) died during the observation period. An elevated value of liver stiffness measurement (LSM) of ≥ 21 kPa was a significant independent risk factor for poor prognosis after BRTO (P < 0.05). CONCLUSIONS: HVPG increases after BRTO. HVPG after BRTO has greater predictive ability for subsequent EVs exacerbation than HVPG before BRTO. LSM is a potential prognostic parameter in patients who undergo BRTO.

Analysis of Lenvatinib's Efficacy against Intermediate-Stage Unresectable Hepatocellular Carcinoma.

Transarterial chemoembolization (TACE) has been the standard treatment for intermediate-stage, unresectable hepatocellular carcinoma (u-HCC). However, with recent advances in systemic therapy and the emergence of the concept of TACE-refractory or -unsuitable, the effectiveness of systemic therapy, as well as TACE, has been demonstrated for patients judged to be TACE-refractory or -unsuitable. In this study, the efficacy of lenvatinib and its combination with TACE after lenvatinib was investigated in 140 patients with intermediate-stage u-HCC treated with lenvatinib mainly because of being judged to be TACE-refractory or -unsuitable. Median overall survival (OS) and progression-free survival (PFS) were 24.4 and 9.0 months, respectively, indicating a good response rate. In multivariate analysis, modified albumin-bilirubin (mALBI) grade and up to seven criteria were identified as independent factors for OS, and mALBI grade and tumor morphology were identified as independent factors for PFS. While 95% of all patients were TACE-refractory or -unsuitable, the further prognosis was prolonged by the combination with TACE after lenvatinib initiation. These findings suggest that systemic therapy should be considered for intermediate-stage u-HCC, even in patients judged to be TACE-refractory or -unsuitable. The use of TACE after the start of systemic therapy may further improve prognosis.

Calcium channel blockers improve the prognosis of patients with intrahepatic cholangiocarcinoma after resection.

BACKGROUND: Intrahepatic cholangiocarcinoma is the second most common primary cancer of the liver. It is highly malignant and its prognosis is very poor. Although there have been various reports on the effects of calcium channel blockers on cancer, the effects of calcium channel blockers on intrahepatic cholangiocarcinoma have not been reported so far. METHODS: Seventy-nine patients diagnosed with intrahepatic cholangiocarcinoma by hepatectomy between January 2002 and May 2019 were retrospectively evaluated. We compared prognosis and time to recurrence between patients treated with calcium channel blockers (CCBs) (n = 29) and those not treated with CCBs (n = 50). Propensity score matching reduced confounding biases and yielded 25 matched patient pairs. Survival between groups was compared using Kaplan-Meier analyses, logrank tests, and Cox proportional hazard regression models. RESULTS: Overall survival and recurrence-free survival of the CCBs group were significantly longer than those of the non-CCBs group OS in the original cohort and matched cohort (98 months vs 45 months, p = 0.010; 96 months vs 22 months, p = 0.020, respectively). Multivariate analyses showed that CCBs treatment was independently associated with overall survival (HR, 0.37; 95% CI 0.16-0.85; p = 0.019) and recurrence-free survival (HR, 0.39; 95% CI 0.17-0.90; p = 0.020) in the original cohort and matched cohort, respectively. CONCLUSION: CCBs treatment might improve prognosis of patients with intrahepatic cholangiocarcinoma.

Benign Recurrent Intrahepatic Cholestasis Type 1 with Novel Nonsense Mutations in the ATP8B1 Gene.

Benign recurrent intrahepatic cholestasis (BRIC) is a group of genetically heterogeneous autosomal recessive liver disorders characterized by recurrent episodes of jaundice and pruritus. BRIC is divided into two groups, BRIC type 1 (BRIC1) and BRIC type 2 (BRIC2), caused by mutations in the ATP8B1 and ABCB11 genes. We show that novel nonsense mutations in ATP8B1 (c.2989G>A, c.1547T>A) are the cause of BRIC1. A 16-year-old girl presented with severe jaundice. Acute and chronic liver diseases with infectious (hepatitis virus), metabolic, and autoimmune etiologies were excluded. Imaging revealed normal intra- and extra-hepatic bile ducts. Liver biopsy revealed severe intrahepatic bile stasis with bile plugs. She had similar symptoms at the age of 0 years. The BRIC criteria were satisfied, and ATP8B1 and ABCB11 gene analyses performed. Surprisingly, novel nonsense variants of the ATP8B1 gene (c.2989G>A and c.1547T>A) in heterozygosis were found, which were identified in each of her parents. Therefore, the compound heterozygote was thought to cause BRIC1 in these patients. Genetic mutations that differ from those already known may help diagnose patients with BRIC.

Analysis of Survival and Response to Lenvatinib in Unresectable Hepatocellular Carcinoma.

The association between radiological response and overall survival (OS) was retrospectively evaluated in patients treated with lenvatinib as a first-line systemic treatment for unresectable hepatocellular carcinoma. A total of 182 patients with Child-Pugh class A liver function and an Eastern Cooperative Oncology Group performance status of zero or one were enrolled. Radiological evaluation was performed using Response Evaluation Criteria in Solid Tumors (RECIST) and modified Response Evaluation Criteria in Solid Tumors (mRECIST). Initial radiological evaluation confirmed significant stratification of OS by efficacy judgment with both RECIST and mRECIST, and that initial radiological response was an independent prognostic factor for OS on multivariate analysis. Furthermore, in patients with stable disease (SD) at initial evaluation, macrovascular invasion at the initial evaluation on RECIST and modified albumin-bilirubin grade at initial evaluation on mRECIST were independent predictors of OS on multivariate analysis. In conclusion, if objective response is obtained at the initial evaluation, continuation of treatment appears desirable because prolonged OS can be expected; but, if SD is obtained at the initial evaluation, one should determine whether to continue or switch to the next treatment, with careful consideration of factors related to the tumor and hepatic reserve at the initial evaluation.

The importance of body composition assessment for patients with advanced hepatocellular carcinoma by bioelectrical impedance analysis in lenvatinib treatment.

BACKGROUND AND AIMS: The aim of this study was to investigate the relationship between body composition before lenvatinib treatment and prognosis in patients with hepatocellular carcinoma (HCC). We also assessed the relationship between the rate of change in body composition after lenvatinib treatment and prognosis. METHODS: Eighty-one patients with advanced HCC who were treated with lenvatinib were enrolled. We assessed prognosis, various clinical data, body composition parameters obtained by bioelectrical impedance analysis (BIA), and handgrip strength. RESULTS: Multivariate analysis showed that an extracellular water to total body water ratio (ECW/TBW) ≤ 0.400 at treatment initiation was associated with longer overall survival (OS), progression-free survival (PFS), and post-progression survival (PPS) (OS: hazard ratio [H0R], 4.72; 95% CI, 12.03-11.00; P < 0.001; PFS: HR, 2.66; 95% CI, 1.33-5.34; P = 0.0057; PPS: HR, 3.08; 95% CI, 1.32-7.18; P = 0.0093). Multivariate analysis also showed that the skeletal muscle mass index (SMI) of the arm at treatment initiation was associated with a longer PFS (HR, 2.12; 95% CI, 1.23-3.64; P = 0.0069). In the group with an ECW/TBW ≤ 0.400 before lenvatinib treatment, univariate analysis showed that the rate of change in only the arm SMI was associated with a longer OS and PFS. CONCLUSION: Body composition assessment by BIA before and after lenvatinib treatment is useful in predicting prognosis in lenvatinib-treated patients with HCC.

Advanced hepatocellular carcinoma with response to lenvatinib after atezolizumab plus bevacizumab.

RATIONALE: Various treatments are available for treating hepatocellular carcinoma (HCC). The immune checkpoint inhibitor combination of atezolizumab plus bevacizumab was recently approved for the treatment of unresectable HCC, but there are few reports on the failure of the combination treatment. Here, we present a case of unresectable HCC with adrenal metastasis that was eventually operated on after lenvatinib (LEN) treatment that followed failed treatment with atezolizumab plus bevacizumab. PATIENT CONCERNS: A 68-year-old man was diagnosed with non-alcoholic steatohepatitis-based HCC with adrenal metastasis. DIAGNOSIS: Cirrhosis was classified as Child-Pugh score of 5. HCC was diagnosed as Barcelona Clinic Liver Cancer stage C. INTERVENTIONS: We initiated treatment with atezolizumab plus bevacizumab. Liver dysfunction appeared 2 days after the first administration but was improved by intravenous rehydration and did not appear after the second course. The HCC shrank, but the adrenal metastasis grew bigger after the fourth course, so we changed the therapy to LEN. After HCC and adrenal metastasis were necrotic by LEN, conversion surgery was performed. OUTCOMES: After successful conversion therapy, the general condition of the patient was good, and has been carefully followed for 4 months to date without any evidence of further recurrences. LESSONS: This case showed that even if atezolizumab plus bevacizumab is not effective, multidisciplinary treatment such as LEN and conversion surgery is possible. Given the efficacy of LEN after atezolizumab plus bevacizumab, it is important to consider that there is a possibility of cure even when first-line treatment is not effective for a patient with unresectable HCC.

Early Tumor Response and Safety of Atezolizumab Plus Bevacizumab for Patients with Unresectable Hepatocellular Carcinoma in Real-World Practice.

The aim of this study was to investigate the early tumor response and safety of atezolizumab plus bevacizumab for patients with unresectable hepatocellular carcinoma in real-world practice. Forty patients with Child-Pugh class A liver function and eastern cooperative oncology group performance status 0 or 1 were enrolled. The objective response rate (ORR) at six weeks after the start of treatment, changes in α-fetoprotein (AFP) and des-γ-carboxyprothrombin, incidence of adverse events (AEs), and changes in albumin-bilirubin (ALBI) score and serum ammonia level, were evaluated. Among 40 patients, 24 had histories of prior molecular targeted agents (MTAs). The ORR was 22.5% based on mRECIST. Multivariate analysis showed that an AFP ratio <1.0 at three weeks (odds ratio 39.2, 95% confidence interval CI 2.37-649.0, p = 0.0103) was the only significant factor for predicting early response. There was no significant difference in the frequency of AEs between patients receiving first-line treatments and others. Fatigue, proteinuria, and ascites were more frequent in patients who experienced prior treatment. No decrease in ALBI score or increase in serum ammonia level was observed. Our study demonstrated that AFP may be useful in assessing early response and that this treatment is safe, including in patients with prior MTA treatments.

Pathological Features and Imaging Findings in Pancreatic Carcinoma In Situ.

OBJECTIVES: This study aimed to evaluate the pathological features and imaging findings of pancreatic carcinoma in situ (PCIS). METHODS: Twenty patients with PCIS were categorized as flat (F) (n = 6) and low papillary (LP) (n = 14) types. RESULTS: None of F type and 8 (57%) of 14 with LP type lesions showed intraductal infiltrations of the main pancreatic duct (MPD) greater than 10 mm. None of F type and 3 (21%) of 14 with LP type lesions showed skip lesions in the MPD. Magnetic resonance cholangiopancreatography showed irregular MPD stenoses in 5 (83%) of 6 with F and 13 (100%) of 13 with LP type lesions. Magnetic resonance cholangiopancreatography determined that the median lengths of the irregular MPD stenoses were 3.6 mm for F, and 11.6 mm for LP type lesions. Endoscopic retrograde cholangiopancreatography determined that the median lengths of the irregular MPD stenoses were 2.8 mm for F, and 14.3 mm for LP type lesions. Pancreatic cancer recurrences limited to the remnant pancreas occurred in 2 patients with LP type lesions. CONCLUSIONS: In LP type PCIS, intraductal infiltration of the MPD occurs frequently. There may be multiple lesions, and lesions may recur in the remnant pancreas. Long-term strict follow-up assessments should be implemented for LP type PCIS.