Abstract Background & Aims: Clinical responses to atezolizumab plus bevacizumab (AB) therapy can vary across hepatocellular carcinoma (HCC) nodules among individual patients. This study aimed to derive and externally validate a non-invasive radiomics signature (ABRad) translated from a transcriptome signature for nodule-level prediction of AB response (ABS). Methods: We originally derived and validated ABS using 209 and 44 pre-treatment HCC samples from the IMbrave150 and GO30140 trials, respectively. ABS was then translated into ABRad using a machine-learning approach on 59 patients with paired genome-wide transcriptome and pre-resection computed tomography imaging from surgically resected HCC. Subsequently, ABRad was externally validated using 178 HCC nodules from 55 patients treated with AB therapy. Results: The 148-gene ABS predicted therapeutic response and progression-free survival (PFS) in the clinical trial cohorts. The final ABRad model, constructed using a random forest algorithm, was heavily weighted toward contrast-enhanced features. In the external validation cohort, ABRad demonstrated a significant positive association with the degree of therapeutic response (p <0.001). The areas under receiver operating characteristics curve for predicting complete response (CR), objective response (OR), and disease control (DC) were 0.71 (95% confidence interval [CI], 0.61-0.80), 0.65 (95% CI, 0.56-0.73), and 0.69 (95% CI, 0.59-0.78), respectively. Nodule-level ABRad was independently associated with therapeutic response with adjusted odds ratios of 3.39 (95% CI, 1.40-8.21) for CR, 2.55 (95% CI, 1.19-5.67) for OR, and 2.60 (95% CI, 1.03-6.56) for DC. Patient-level ABRad was significantly associated with prolonged PFS (p = 0.005). Conclusions: ABRad successfully predicted nodule-level response to AB therapy in HCC.
Abstract Image-guided ablation has emerged as a potentially curative treatment for colorectal cancer liver metastases (CRLM), yet substantial heterogeneity persists in patient selection, technical execution, and perioperative management. To establish standardized, evidence-based guidance, a multidisciplinary panel of 68 experts including image-guided interventionalists, surgeons, and oncologists conducted a systematic review of literature from 2000 to 2025 and developed consensus recommendations through a modified two-round Delphi process. Evidence was graded using the Oxford Centre for Evidence-Based Medicine framework, achieving at least conditional consensus (≥75% agreement) for all statements. Finally, twenty consensus recommendations were established addressing patient selection, imaging evaluation, image-guided techniques, ablation strategies, complication management, surveillance protocols, and combination therapies. This expert consensus provides a comprehensive framework for optimizing image-guided ablation as an integral component of multidisciplinary, personalized CRLM management.
Abstract Introduction Despite the availability of several approved therapies, continued investigation of novel treatment options is needed to further improve outcomes in advanced hepatocellular carcinoma (HCC). The phase 2 KEYSTEP-004 study evaluated the safety and efficacy of quavonlimab coformulated with pembrolizumab (quavonlimab/pembrolizumab) plus lenvatinib as first-line therapy for advanced HCC. Methods Adults with confirmed advanced HCC and no prior systemic therapy were enrolled. In the safety lead-in phase, participants received intravenous quavonlimab 25 mg coformulated with pembrolizumab 400 mg every 6 weeks plus oral lenvatinib 12 mg (body weight ≥60 kg) or 8 mg (body weight <60 kg) once daily (dose level 0 [DL0]). Allocation to the efficacy expansion phase was permitted if lenvatinib DL0 plus quavonlimab 25 mg coformulated with pembrolizumab 400 mg every 6 weeks was determined to be tolerable. Primary endpoints were objective response rate (ORR) per RECIST v1.1 by blinded independent central review (BICR) and safety. Secondary endpoints included duration of response (DOR) and progression-free survival (PFS) per RECIST v1.1 by BICR, and overall survival (OS). Results As of June 22, 2023, 116 participants were enrolled, and 115 were treated. No dose-limiting toxicities were observed in the safety lead-in phase. Lenvatinib DL0 in combination with quavonlimab 25 mg coformulated with pembrolizumab 400 mg every 6 weeks was determined to be tolerable. Median study follow-up was 18.0 months (range, 12.0–26.6). Confirmed ORR was 37.4% (95% CI: 28.5–46.9). Median DOR was 10.6 months (range, 1.2+ to 23.1+), median PFS was 8.2 months (95% CI: 6.2–10.2), and median OS was 22.1 months (95% CI: 15.5-not reached). Grade 3–5 treatment-related adverse events (AEs) occurred in 66 participants (57.4%); 14 (12.8%) required high-dose steroids for management of a treatment-related AE. Conclusion Quavonlimab coformulated with pembrolizumab plus lenvatinib is an active combination and has a manageable safety profile in advanced HCC.
