To assess the relationship between survival outcomes and subtypes of radiological progressive disease (PD) in patients with hepatocellular carcinoma (HCC) treated with atezolizumab and bevacizumab (Atezo/Bev).

A total of 462 patients with Atezo/Bev-treated HCC diagnosed with radiological PD during follow-up were enrolled. PD was classified into three categories: progression or emergence of intrahepatic lesions (PD-IH), macroscopic vascular invasion (PD-MVI), and extrahepatic spread lesions (PD-EHS). We defined PD-multiple as the presence of two or more PD categories. Subsequent analysis was categorized into the "PD-IH or PD-EHS" and "PD-MVI or PD-multiple" groups.

The median progression-free survival (PFS) durations for patients with PD-IH, PD-MVI, PD-EHS, and PD-multiple were 5.3, 3.2, 3.9, and 3.5 months (p = 0.003). Patients with "PD-IH or PD-EHS" and "PD-MVI or PD-multiple" had median PFS of 5.2 and 3.5 months (p < 0.001). Median overall survival (OS) for PD-IH, PD-MVI, PD-EHS, and PD-multiple was 22.3, 15.1, 19.4, and 14.2 months (p = 0.002). The OS for patients with "PD-IH or PD-EHS" and "PD-MVI or PD-multiple" was 21.4 and 14.5 months (p < 0.001). Multivariate analysis demonstrated that ECOG-PS ≥ 1 (hazard ratio (HR), 1.508), α-fetoprotein levels ≥ 100 ng/mL (HR, 1.293), albumin-bilirubin grade ≥ 2 (HR, 1.573), liver cirrhosis (HR, 1.361), and PD subtypes PD-MVI or PD-multiple (HR, 1.735) were independently associated with OS.

Patients with HCC undergoing Atezo/Bev treatment, diagnosed with PD-multiple (not solely based on IH or EHS) or PD-MVI, experienced poor prognosis, specifically in terms of OS.

Liver cancer, primarily HCC, exhibits highly heterogeneous histological and molecular aberrations across tumors and within individual tumor nodules. Such intertumor and intratumor heterogeneities may lead to diversity in the natural history of disease progression and various clinical disparities across the patients. Recently developed multimodality, single-cell, and spatial omics profiling technologies have enabled interrogation of the intertumor/intratumor heterogeneity in the cancer cells and the tumor immune microenvironment. These features may influence the natural history and efficacy of emerging therapies targeting novel molecular and immune pathways, some of which had been deemed undruggable. Thus, comprehensive characterization of the heterogeneities at various levels may facilitate the discovery of biomarkers that enable personalized and rational treatment decisions, and optimize treatment efficacy while minimizing the risk of adverse effects. Such companion biomarkers will also refine HCC treatment algorithms across disease stages for cost-effective patient management by optimizing the allocation of limited medical resources. Despite this promise, the complexity of the intertumor/intratumor heterogeneity and ever-expanding inventory of therapeutic agents and regimens have made clinical evaluation and translation of biomarkers increasingly challenging. To address this issue, novel clinical trial designs have been proposed and incorporated into recent studies. In this review, we discuss the latest findings in the molecular and immune landscape of HCC for their potential and utility as biomarkers, the framework of evaluation and clinical application of predictive/prognostic biomarkers, and ongoing biomarker-guided therapeutic clinical trials. These new developments may revolutionize patient care and substantially impact the still dismal HCC mortality.

Treatment outcomes are predicted by analyzing peripheral blood markers such as serum lactate dehydrogenase (LDH). We conducted this study to investigate whether serum LDH levels can predict the prognosis of patients treated with atezolizumab plus bevacizumab (ATZ/BEV) therapy for hepatocellular carcinoma (HCC) and whether LDH levels correlate with metabolic changes.

We enrolled 66 HCC patients treated with ATZ/BEV. Based on the change in serum LDH levels before and after treatment, the patients were divided into two groups, and the prognosis of each group was examined. Moreover, the association of LDH levels with tumor metabolism was analyzed by fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT).

There were 32 patients categorized as the LDH-decrease group. Kaplan-Meier survival analysis indicated worse progression-free survival (PFS) in the LDH-increase group than in the LDH-decrease group (p = 0.0029). Multivariate analysis showed that an increase in the LDH level was an independent risk factor for worse PFS (p = 0.0045). The baseline LDH level correlated significantly with a high maximum standardized uptake value of 18F-FDG, according to the PET/CT findings. Transcriptomic analyses of specimens resected after ATZ/BEV therapy showed downregulated mitochondria-related pathways.

Serum LDH levels are a potential prognostic marker and an indicator of tumor metabolism.

Although atezolizumab plus bevacizumab (Atezo/Bev) therapy has been used as the preferred first-line treatment for advanced hepatocellular carcinoma (HCC), up to 26% of patients do not achieve disease control, suggesting alternative treatments might be more beneficial for such patients. We investigated key predictors for refractoriness to Atezo/Bev therapy, particularly in the first-line setting.

We retrospectively analyzed 302 patients with HCC who received Atezo/Bev therapy between October 2020 and September 2022 across nine hospitals in Japan. Refractoriness was defined as best overall response (BOR) of progressive disease or stable disease and a progression-free survival (PFS) of < 180 days (RECIST v1.1). Clinical benefit was defined as BOR of partial/complete response or stable disease with PFS of ≥ 180 days. Baseline characteristics and potential predictors, identified through literature review, were compared between these groups. Stratifications of overall survival (OS), and PFS were also assessed.

Refractoriness was observed in 126 (41.7%) patients, while 154 (51.0%) achieved clinical benefit. Due to a significant association between the treatment line and refractory rate, the subsequent analysis focused on the first-line cohort (n = 214; 72 [33.6%] patients showed refractoriness). Among 13 potential predictors, the CRP and AFP in immunotherapy (CRAFITY) score had the best predictive performance, with refractory rates of 24.6%, 44.6%, and 57.9% in CRAFITY-0, 1, and 2 patients, respectively (p < 0.001). OS and PFS were also well-stratified by this scoring system.

Approximately one-third of patients were refractory to first-line Atezo/Bev therapy. The CRAFITY score demonstrated superior performance in predicting refractoriness.

There are few reports on conversion surgery (CS) after chemotherapy plus nivolumab as a first-line treatment in patients with unresectable advanced or recurrent gastric cancer (GC). This multicenter study was conducted to analyze real-world data on CS after chemotherapy plus nivolumab as a first-line treatment and to identify predictive biomarkers.

This multicenter study included 104 patients who received chemotherapy plus nivolumab as primary treatment for unresectable advanced recurrent GC from 12 institutes. We investigated and analyzed patient characteristics and blood test data in the presence or absence of CS, the relationship between the Gustave Roussy Immune Score (GRIm-s) and CS, and the characteristics of CS cases.

CS was performed in 12 patients (11.5%). Eastern Cooperative Oncology Group Performance Status (ECOG-PS) was significantly better in patients who underwent CS (p < 0.0001). There were no CS cases with high-risk GRIm-s (0%), however there were 22 non-CS cases (23.9%). No high-risk GRIm-s cases were converted to CS. Minimally invasive surgery was performed in 50.0% of the cases, with R0 resection in all cases and only one case of urinary retention (Grade II) as a postoperative complication, indicating a good postoperative short-term outcome. There were two cases of postoperative recurrence (16.7%), both of which were grade 1b.

The short-term postoperative results of CS after chemotherapy plus nivolumab as the first-line treatment for GC were acceptable in this study. There were no high-risk GRIm-s cases among those who underwent CS, suggesting that the GRIm-s may be a predictor of CS.

Background and objective: The aim of this research is to investigate whether the GRIm score serves as a novel prognostic tool for predicting the survival rates among early breast cancer patients undergoing surgical treatment. Methods: This retrospective study included 313 cases of breast cancer patients hospitalized in our hospital from January 2015 to November 2015. All enrolled patients received surgery and had no metastasis. The GRIm score was based on five objective markers: (1) albumin level (<3.5 g/L = 1 point), (2) LDH level (≥245 U/L = 1 point); (3) AST-to-ALT ratio (≥1.44 = 1 point); (4) total bilirubin level (≥21 μmol/ml = 1 point); (5) NLR (≥1.51 = 1 point). The best critical value was 1.51 for NLR by ROC. Patients were categorized into two groups based on GRIm scores: low-score group (0 point) and high-score group (1 to 5 points). Kaplan-Meier method and log rank test were utilized to estimate disease free survival (DFS) and overall survival (OS). Both univariate analysis and multivariate Cox analysis were used to analyze the relationship among the enrolled parameters. Nomograms were formulated reliant on the outcomes of multivariate Cox analysis. Results: Based on the GRIm score, the cohort was divided into two groups: a low-score group with 81 cases and a high-score group with 232 cases. The mean DFS and OS were significantly prolonged in low-score group compared to high-score group (DFS: 74.39 vs. 66.20 months, χ2=8.729, P=0.0031; OS: 83.71 vs. 76.40 months, χ2=8.729, P=0.0031). According to multivariable analysis, GRIm score was notably correlated with DFS (HR: 2.789, 95% CI: 1.304-5.965, P= 0.004) and OS (HR: 3.015, 95% CI: 1.409-10.087, P=0.004). Nomograms exhibited excellent predictive performance for DFS (C-index: 0.823) and OS (C-index: 0.807). Conclusions: GRIm score serves as a predictive tool for assessing the prognosis of early breast cancer patients. Nomograms based on GRIm score show good prediction ability.

It is highly important to be able to predict the therapeutic efficacy of chemotherapy on patients with unresectable advanced or recurrent gastric cancer (GC). The Gustave Roussy Immune Score (GRIm-s) is a predictor of therapeutic sensitivity to chemotherapy and immune checkpoint inhibitors (ICIs) in other cancers. The present study aimed to analyze the association of the GRIm-s with the therapeutic sensitivity of first-line chemotherapy in GC patients.

We included 156 patients receiving primary chemotherapy treatment for unresectable or advanced recurrent GC between January 2012 and December 2021 at our institution. We evaluated the correlation between the GRIm-s and therapeutic sensitivities to chemotherapy. The GRIm-s was assessed before the start of first-line chemotherapy.

Among the 156 patients, 138 (88.5%) and 18 (11.5%) were classified in the low- and high-risk groups, respectively. The GRIm-s high-risk group was significantly older (p = 0.013), had more advanced unresectable cancer (p = 0.0098), and was significantly less likely to progress to second-line chemotherapy (p = 0.014). The overall survival rate (OS) (p = 0.039) and the progression free survival rate (PFS) (p = 0.017) were significantly worse in the GRIm-s high-risk group. The high GRIm-s was an independent prognostic factor for poor survival in multivariate analysis (p = 0.0094).

Focusing on the GRIm-s before first-line chemotherapy initiation for unresectable advanced or postoperative recurrent GC was useful in predicting the therapeutic resistance to chemotherapy, transition to second-line chemotherapy, and poor prognosis.

Atezolizumab plus bevacizumab (Atezo/Bev) is frequently selected as the primary systemic therapy for hepatocellular carcinoma (HCC).

To investigate the outcomes of patients with HCC treated with Atezo/Bev in a real-world setting based on whether they met the inclusion criteria for the phase 3 IMbrave150 trial.

A total of 936 patients were enrolled. There were 404 patients who met the inclusion criteria of the phase 3 IMbrave150 trial (IMbrave150 group) and 532 who did not (non-IMbrave150 group).

Median progression-free survival (PFS) in the IMbrave150 and non-IMbrave150 groups was 7.4 months and 5.6 months (p = 0.002). Multivariable analysis revealed that non-B, non-C HCC aetiology (hazard ratio [HR], 1.173), α-fetoprotein ≥100 ng/mL (HR, 1.472), Barcelona Clinic Liver Cancer stage ≥ C (HR, 1.318), and modified albumin-bilirubin (mALBI) grade 2b or 3 (HR, 1.476) are independently associated with PFS. Median overall survival (OS) in the IMbrave150 and non-Imbrave150 groups was 26.5 and 18.8 months (p < 0.001). Multivariable analysis revealed that Eastern Cooperative Oncology Group performance status ≥2 (HR, 1.986), α-fetoprotein ≥100 ng/mL (HR, 1.481), and mALBI grade 2b or 3 (HR, 2.037) are independently associated with OS. In subgroup analysis, there were no significant differences in PFS or OS between these groups among patients with mALBI grade 1 or 2a.

Patients who are treated with Atezo/Bev and meet the inclusion criteria for the phase 3 IMbrave150 trial, as well as those who do not meet the inclusion criteria but have good liver function, have a good prognosis for survival.

The Gustave Roussy Immune (GRIm) score predicts survival outcomes in several cancers. However, the prognostic significance of the GRIm score in patients with malignant ascites has not yet been investigated.

Clinical samples were collected from a cohort of patients with malignant ascites secondary to hepatocellular carcinoma (HCC). We calculated serum GRIm (sGRIm) and ascites GRIm (aGRIm) scores and divided the samples into low and high GRIm score groups. Survival analysis was used to compare the prognostic significance of the sGRIm and aGRIm scores. 16S rRNA sequencing was performed to determine the profiles of the intratumoral microbiota in the groups. A fluorescent multiplex immunohistochemistry (mIHC) assay was used to detect the expression of different immune cells by labeling seven markers of malignant ascites.

155 patients with HCC and malignant ascites were enrolled in this study. Survival analysis revealed that the aGRIm score showed a superior prognostic significance compared to the sGRIm score. Microbial analysis demonstrated that the bacterial richness and diversity were higher in the low aGRIm score group than in the high aGRIm score group. LefSe analysis revealed that certain bacteria were correlated with high aGRIm scores. Fluorescent mIHC displayed the tumor microenvironment of malignant ascites and found that the density of CD8 + T cells was significantly higher in the low aGRIm score group than in the high aGRIm score group.

Our present study identified a novel scoring system (aGRIm score) that can predict the survival outcome of patients with malignant ascites secondary to HCC.

The treatment of hepatocellular carcinoma (HCC), particularly advanced HCC, has been a serious challenge. Immune checkpoint inhibitors (ICIs) are landmark drugs in the field of cancer therapy in recent years, which have changed the landscape of cancer treatment. In the field of HCC treatment, this class of drugs has shown good therapeutic prospects. For example, atezolizumab in combination with bevacizumab has been approved as first-line treatment for advanced HCC due to significant efficacy. However, sensitivity to ICI therapy varies widely among HCC patients. Therefore, there is an urgent need to search for determinants of resistance/sensitivity to ICIs and to screen biomarkers that can predict the efficacy of ICIs. This manuscript reviews the research progress of prognostic biomarkers associated with ICIs in HCC in order to provide a scientific basis for the development of clinically individualised precision medication regimens.

This study aimed to conduct a comprehensive analysis, evaluating the prognostic significance of the baseline Advanced Lung Cancer Inflammation Index (ALI) and Gustave Roussy Immune (GRIm) Score in patients undergoing immune checkpoint inhibitor (ICI) therapy.

A comprehensive search was performed across various databases, including PubMed, the Cochrane Library, EMBASE, and Google Scholar, until October 21, 2023, to compile relevant articles for analysis. The investigation encompassed diverse clinical outcomes, including overall survival (OS) and progression-free survival (PFS).

This analysis included a total of 15 articles, comprising 19 studies involving 3335 patients. Among the 19 studies, nine studies focused on NSCLC, and six studies were conducted on HCC. Pooled results revealed that patients with elevated ALI levels experienced prolonged OS (HR: 0.51, 95% CI: 0.37-0.70, p < 0.001) and extended PFS (HR: 0.61, 95% CI: 0.52-0.72, p < 0.001). Furthermore, a GRIm score > 1 was associated with reduced OS (HR: 2.07, 95% CI: 1.47-2.92, p < 0.001) and diminished PFS (HR: 1.78, 95% CI: 1.35-2.34, p < 0.001) in cancer patients receiving ICIs. Subgroup analysis indicated that ALI cutoff values of 18 exhibited enhanced predictive potential. Additionally, for HCC patients, those with HCC-GRIm score > 2 showed a substantially decreased risk of mortality compared to individuals with HCC-GRIm score ≤ 2 (HR: 2.63, 95% CI: 1.89-3.65, p < 0.001).

The ALI and GRIm score served as dependable prognostic indicators for patients undergoing ICI therapy in the context of cancer treatment.

This study was designed to investigate the relationship between the Gustave-Roussy immune score (GRIm-score) and platinum resistance in patients with advanced high-grade serous ovarian cancer (HGSOC).

We conducted a retrospective study of patients diagnosed with advanced HGSOC between January 2017 and December 2020. A nomogram was developed to predict the risk of platinum resistance. Receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis (DCA) were used to validate the nomogram. Bootstrap analysis was utilized for internal validation. Additionally, we analyzed the risk factors for platinum resistance in patients who received neoadjuvant chemotherapy (NACT).

A total of 232 patients with advanced HGSOC were included, 52 (22.4 %) of whom experienced relapse with platinum resistance. Multivariate logistic regression analysis revealed that high GRIm-score (OR = 4.174, P < 0.001), NACT (OR = 2.706, P = 0.017), PLT > 260 (OR = 2.233, P = 0.037) and non-R0 (OR = 2.526, P = 0.012) were independent risk factors for platinum resistance. The area under the curve (AUC) of the model was 0.802 (95 % CI 0.736-0.868), and the internally validated AUC of 1000 bootstrap samples was 0.798 (95 % CI 0.725-0.862). In NACT-treated patients, univariate and multivariate logistic regression analyses revealed that a low KELIM score (OR = 10.405, P = 0.001) and PLT > 260 (OR = 4.611, P = 0.014) were independent risk factors for platinum resistance.

The GRIm-score and PLT count are important prognostic factors in patients with HGSOC. For precision treatment, the status of partially platinum-sensitive patients should also be considered.

To construct a nomogram for hepatocellular carcinoma (HCC) patients base on HCC-GRIm score.

Clinical cases of HCC patients diagnosed at Hunan Integrated Traditional Chinese and Western Medicine Hospital were included, and these were randomly divided into the training cohort (n = 219) and the validation cohort (n = 94), and those patients were divided into low GRIm-Score group (scores 0, 1, and 2) and high GRIm-Score group (scores 3, 4, and 5). In the training cohort, independent risk factors were determined by Cox regression analysis, and a nomogram was constructed by independent risk factors. The efficiency and the clinical applicability of nomograms were evaluated using ROC curves, calibration plot, and the decision curve (DCA), and the patients were divided into high-risk, middle-risk, and low-risk groups according to total score of nomogram.

Compared to low HCC-GRIm score group, high HCC-GRIm score group with BCLC stage is more advanced (P < 0.001), and fewer patients received TACE (P = 0.005) and surgical treatment (P = 0.001). There was higher rate of the presence of vascular invasion (P < 0.001) and distant metastasis (P < 0.001). Multivariate Cox regression analysis screened 4 independent risk factors to construct a nomogram of HCC patients, including HCC-GRIm score, BCLC stage, albumin-to-globulin ratio (AGR), and glutamyl trans-peptidase (GGT). The consistency index (C-index) of the nomogram of the training was 0.843 (0.832-0.854) and the validation was 0.870 (0.856-0.885). The time-dependent parameter showed the AUC values of the training cohort at 1, 3, and 5 years were 0.954 (95% CI 0.929-0.980), 0.952 (95% CI 0.919-0.985), and 925 (95% CI 0.871-0.979), while the AUC values of validation cohort at 1, 3, and 5 years were 0.974 (95% CI 0.950-0.998), 0.965 (95% CI 0.931-0.999), and 0.959 (95% CI 0.898-1.021). The calibration plot showed the nomogram fits well onto perfect curves, and the DCA curve showed the net benefit of the nomogram at a certain probability threshold is significantly higher than the net benefit of the BCLC stage at the same threshold probability. Finally, all patients were divided into high-risk, middle-risk, and low-risk groups based on the total score of nomogram, and it showed effectively to identify high-risk patients.

The nomogram constructed by the independent risk factors can predict the prognosis of HCC patients, providing an effective tool with clinical workers to evaluate the prognosis and survival time of HCC patients.

The study goal was to compare the outcomes of patients with unresectable hepatocellular carcinoma (HCC) who received atezolizumab plus bevacizumab (Atezo/Bev) as either first- or later-line systemic therapy.

A total of 430 patients with HCC treated with Atezo/Bev at 22 institutions in Japan were included. Patients treated with Atezo/Bev as first-line therapy for HCC were defined as the first-line group (n = 268) while those treated with Atezo/Bev as second- or later-line therapy were defined as the later-line group (n = 162).

The median progression-free survival times in the first- and later-line groups were 7.7 months (95% confidence interval [CI], 6.7-9.2) and 6.2 months (95% CI, 5.0-7.7) (P = 0.021). Regarding treatment-related adverse events, hypertension of any grade was more common in the first-line group than in the later-line group (P = 0.025). Analysis adjusted by inverse probability weighting, including patient and HCC characteristics, showed that the later-line group (hazard ratio, 1.304; 95% CI, 1.006-1.690; P = 0.045) was significantly associated with progression-free survival. In patients with Barcelona Clinic Liver Cancer stage B, the median progression-free survival times in the first- and later-line groups were 10.5 months (95% CI, 6.8-13.8) and 6.8 months (95% CI, 5.0-9.4) (P = 0.021). Among patients with a history of lenvatinib therapy, the median progression-free survival times in the first- and later-line groups were 7.7 months (95% CI, 6.3-9.2) and 6.2 months (95% CI, 5.0-7.7) (P = 0.022).

The use of Atezo/Bev as first-line systemic therapy in patients with HCC is expected to prolong survival.

To identify the risk factors associated with prognosis in patients with hepatocellular carcinoma (HCC) treated with immune checkpoint inhibitors (ICI) via meta-analysis. And to construct prediction models to aid in the prediction and improvement of prognosis.

We searched PubMed, Embase, Web of Science and Cochrane Library for relevant studies from inception to March 29, 2023. After completing literature screening and data extraction, we performed meta-analysis, sensitivity analysis, and subgroup analysis to identify risk factors associated with OS and PFS. Using the pooled hazard ratio value for each risk factor, we constructed prediction models, which were then validated using datasets from 19 centers in Japan and two centers in China, comprising a total of 204 patients.

A total of 47 studies, involving a total of 7649 ICI-treated HCC patients, were included in the meta-analysis. After analyzing 18 risk factors, we identified AFP, ALBI, NLR, ECOG performance status, Child-Pugh stage, BCLC stage, tumor number, vascular invasion and combination therapy as predictors for OS prediction model, while AFP, ALBI, NLR, ECOG performance status, Child-Pugh stage, BCLC stage, tumor number and vascular invasion were selected as predictors for PFS model. To validate the models, we scored two independent cohorts of patients using both prediction models. Our models demonstrated good performance in these cohorts. In addition, in the pooled cohort of 204 patients, Our models also showed good performance with area under the curve (AUC) values of 0.712, 0.753, and 0.822 for the OS prediction model at 1-year, 2-year, and 3-year follow-up points, respectively, and AUC values of 0.575, 0.749 and 0.691 for the PFS prediction model Additionally, the calibration curve, decision curve analysis, and Kaplan-Meier curves in the pooled cohort all supported the validity of both models.

Based on the meta-analysis, we successfully constructed the OS and PFS prediction models for ICI-treated HCC patients. We also validated the models externally and observed good discrimination and calibration. The model's selected indicators are easily obtainable, making them suitable for further application in clinical practice.