Impact of radiological response and pattern of progression in patients with HCC treated by atezolizumab-bevacizumab.

BACKGROUND AND AIMS: We aim to assess the role of radiological response to atezolizumab-bevacizumab in patients with HCC to predict overall survival. APPROACH AND RESULTS: We retrospectively included patients with HCC treated by atezolizumab-bevacizumab in 2 tertiary centers. A retrospective blinded analysis was performed by 2 radiologists to assess Response Evaluation Criteria in Solid Tumor (RECIST 1.1) and modified RECIST (mRECIST) criteria at 12 weeks. Imaging response and treatment decisions in the multidisciplinary tumor board at 12 weeks were registered. Among 125 patients, 9.6% and 20.8% had a response, 39.2% and 35.2% had stable disease, and 51.2% and 44% had progression, according to RECIST 1.1 and mRECIST, respectively, with a substantial interobserver agreement (k coefficient=0.79). Metastasis was independently associated with a higher risk of progression. Patients classified as responders did not reach median survival, which was 16.2 and 15.9 months for patients classified as stable and 9.1 and 9.0 months for patients classified as progressors, in RECIST 1.1 and mRECIST criteria, respectively. We observed a wide variability in the identification of progression in the multidisciplinary tumor board in clinical practice compared with the blind evaluation by radiologists mainly due to discrepancy in the evaluation of the increase in size of intrahepatic lesions. The appearance of new extrahepatic lesions or vascular invasion lesions was associated with a worse overall survival ( p =0.032). CONCLUSIONS: RECIST 1.1 and mRECIST criteria predict overall survival with more responders identified by mRECIST and the appearance of new extrahepatic lesion or vascular invasion was associated with a poor prognosis. A noticeable discrepancy was observed between patients classified as progressors at reviewing and the decision reached during the multidisciplinary tumor board.

Baseline ALBI score and early variation of serum AFP predicts outcomes in patients with HCC treated by atezolizumab-bevacizumab.

BACKGROUND: The combination of atezolizumab and bevacizumab (AtezoBev) is the current first-line treatment for patients with hepatocellular carcinoma (HCC). Our aim was to evaluate the prognostic role of alpha-foetoprotein (AFP) early response and its combination with albumin-bilirubin (ALBI) in these patients. METHODS: Patients with HCC under AtezoBev with AFP > 20 ng/ml were included in three centres. The optimal threshold of AFP variation after 3 weeks of treatment was identified for overall survival (OS) and radiological response (RR) using RECIST 1.1 and mRECIST and its ability to predict progression-free survival (PFS) and OS was tested using univariate and multivariate analysis in derivation and validation cohorts. RESULTS: Seventy-five patients with AFP values >20 ng/ml were included. Fifty-eight patients were male with a median age of 63.5 years; 73% had cirrhosis and HCC stage was classified as BCLC B (18.7%) or C (81.3%). In the derivation cohort (n = 38), a decline in AFP ≥ 20% at 3 weeks (AFP early response) was associated with RR using mRECIST criteria (OR: 13.09 95% CI: 1.44-19.34 p = .02), PFS (HR: 0.42; 95% CI: 0.19-0.93, p = .03) and OS (HR: 0.35; 95% CI: 0.15-0.83, p = .01). AFP early response was confirmed as predictor of RR (p = .02 for mRECIST) and OS (p = .03) in the validation cohort (n= 37). In the whole cohort, the combination of ALBI and AFP early response was significantly associated with OS (p = .046) and PFS (p = .012) with a poor prognosis in patients belonging to the ALBI2-AFP non-responders class. CONCLUSION: AFP early response at 3 weeks predicts oncological outcomes in HCC patients treated with AtezoBev and combination with ALBI grade refines prognostic discrimination.

Long-Term Middle Meningeal Artery Caliber Reduction Following Trisacryl Gelatine Microsphere Embolization for the Treatment of Chronic Subdural Hematoma.

PURPOSE: Middle meningeal artery (MMA) particle embolization is a promising treatment of chronic subdural hematomas (CSDH). The main purpose of this study is to measure MMA proximal caliber and assess the visibility of the two main MMA branches as a surrogate for long-term distal arterial patency following MMA CSDH embolization with trisacryl gelatine microspheres (TAGM). METHODS: This is a single-center retrospective study. All patients having undergone MMA TAGM only embolization for CSDH treatment between 15 March 2018 and 6 June 2020 with an interpretable follow-up magnetic resonance imaging (MRI) examination and no confounding factors were included. Patients were compared with controls matched for age, sex and MRI machine. Two independent readers analyzed the MRI images. RESULTS: In this study, 30 patients having undergone embolization procedures using TAGM of 36 MMAs were included. The follow-up MRI scans were performed after a mean delay of 14.8 ± 7.1 months (range 4.9-29.4 months). The mean diameter of TAGM embolized MMAs (1 mm; 95% confidence interval, CI 0.9-1.1) was significantly smaller than the mean diameter of paired control MMAs (1.3 mm; 95% CI 1.3-1.4) (p < 0.001). The mean proximal diameter of the embolized MMAs (0.9 mm; 95% CI 0.7-1.1) was significantly smaller than the mean diameter of the contralateral MMAs in the same patients (1.4 mm; 95% CI 1.3-1.6)(p < 0.001). CONCLUSION: Long-term follow-up MRI demonstrated a significant impact of TAGM embolization on MMA proximal caliber as well as on the visibility of the two main MMA branches. All comparisons indicated that there was a probable lasting impact of embolization on the patency of distal branches.

Bifurcation geometry remodelling of vessels in de novo and growing intracranial aneurysms: a multicenter study.

BACKGROUND: Geometrical parameters, including arterial bifurcation angle, tortuosity, and arterial diameters, have been associated with the pathophysiology of intracranial aneurysm (IA) formation. The aim of this study was to investigate whether these parameters were present before or if they resulted from IA formation and growth. METHODS: Patients from nine academic centers were retrospectively identified if they presented with a de novo IA or a significant IA growth on subsequent imaging. For each patient, geometrical parameters were extracted using a semi-automated algorithm and compared between bifurcations with IA formation or growth (aneurysmal group), and their contralateral side without IA (control group). These parameters were compared at two different times using univariable models, multivariable models, and a sensitivity analysis with paired comparison. RESULTS: 46 patients were included with 21 de novo IAs (46%) and 25 significant IA growths (54%). The initial angle was not different between the aneurysmal and control groups (129.7±42.1 vs 119.8±34.3; p=0.264) but was significantly wider at the final stage (140.4±40.9 vs 121.5±34.1; p=0.032), with a more important widening of the aneurysmal angle (10.8±15.8 vs 1.78±7.38; p=0.001). Variations in other parameters were not significant. These results were confirmed by paired comparisons. CONCLUSION: Our study suggests that wider bifurcation angles that have long been deemed causal factors for IA formation or growth may be secondary to IA formation at pathologic bifurcation sites. This finding has implications for our understanding of IA formation pathophysiology.