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Open research questions in Hepatocellular Carcinoma Treatment and Prognosis

314 unresolved questions extracted from the limitations and future-work sections of 693 Hepatocellular Carcinoma Treatment and Prognosis papers in our library. Each links back to the study that raised it.

What the literature leaves open

  • The low prevalence of metachronous liver metastasis, which makes it challenging to detect high-risk patients. The need to integrate multiple modalities, including imaging, pathological, clinical, and laboratory information. The challenge of developing a model that can predict metachronous liver metastasis in a clinically useful timeframe.

    From predictive model to clinical application: interpretable prediction of metachronous liver metastasis in colorectal cancer · 2026 · DOI

  • further investigation of the relationship between imaging-derived features and tumor metastasis in CRC, - development of more accurate prediction models for metachronous liver metastasis, - exploration of the clinical utility of the proposed framework in different patient populations

    From predictive model to clinical application: interpretable prediction of metachronous liver metastasis in colorectal cancer · 2026 · DOI

  • The high mortality rate of HCC due to late diagnosis, high recurrence rate, ease of metastasis, and treatment resistance. The complexity of tumor microenvironment and immunotherapy response in HCC. The need to identify and validate prognostic genes for HCC using integrated bulk and single cell RNA sequencing.

    Identification of prognostic genes for hepatocellular carcinoma based on hepatocyte and ketone body metabolism using integrated bulk and single cell RNA sequencing · 2026 · DOI

  • The proposed molecular imaging signatures remain hypothesis-generating and require prospective translational and clinical validation, - The simultaneous application of all molecular tracers discussed is not currently feasible in clinical practice, - Regulatory constraints limit the use of multiple tracers

    Noninvasive molecular imaging signatures of histopathological growth patterns in colorectal cancer liver metastases · 2026 · DOI

  • Prospective translational and clinical validation of the proposed molecular imaging signatures, - Evaluation of one-day protocols combining a limited number of complementary tracers, - Development of dual-target PET tracers to assess multiple biological hallmarks within a single scan

    Noninvasive molecular imaging signatures of histopathological growth patterns in colorectal cancer liver metastases · 2026 · DOI

  • No source data validation was carried out, - No imputation for missing data was done, - The study was limited to patients with ≤9 local treatment-naïve CRLM measuring ≤3 cm, - The study did not capture the method and timing of the initial margins assessment for procedures without confirmation software

    Results from the Pan-European CIEMAR study: Local Tumour Control After Microwave Ablation of Colorectal Liver Metastases and Exploratory Associations with Ablation Margins and Confirmation Software · 2026 · DOI

  • Further studies are needed to confirm the findings and explore the use of MWA in different patient populations, - Research on the optimal margin size and the use of confirmation software is needed, - Studies on the cost-effectiveness of MWA compared to other treatment options are necessary

    Results from the Pan-European CIEMAR study: Local Tumour Control After Microwave Ablation of Colorectal Liver Metastases and Exploratory Associations with Ablation Margins and Confirmation Software · 2026 · DOI

  • Biomarkers that predict survival and therapeutic response to atezolizumab plus bevacizumab in unresectable hepatocellular carcinoma have yet to be established. The role of serum full-length glypican-3 concentration in predicting treatment outcomes is unknown.

    Clinical relevance of serum full-length glypican-3 in unresectable hepatocellular carcinoma treated with atezolizumab and bevacizumab · 2026 · DOI

  • Nevertheless, its pathophysiological significance remains incompletely understood. Although the prognostic value of GPC3 expression in HCC remains inconclusive, its overexpression in the tissues of patients with HCC has been associated with poorer prognosis16.

    Clinical relevance of serum full-length glypican-3 in unresectable hepatocellular carcinoma treated with atezolizumab and bevacizumab · 2026 · DOI

  • Technical challenges of delivering SBRT to the spleen due to its location and motion. Risk of hematological toxicity, including lymphopenia. Need for careful treatment planning to minimize dose to adjacent bowel structures.

    Case Report: MR-guided adaptive stereotactic body radiotherapy for splenic metastases: a case series of technical feasibility and early clinical outcomes · 2026 · DOI

  • Small sample size of four patients, - Rarity of splenic SBRT, - Limited data on long-term outcomes, - Potential risk of hematological toxicity

    Case Report: MR-guided adaptive stereotactic body radiotherapy for splenic metastases: a case series of technical feasibility and early clinical outcomes · 2026 · DOI

  • the study is retrospective, - the sample size is limited to 257 patients, - the study only includes patients who underwent curative-intent hepatectomy after conversion therapy, - the study does not provide a direct comparison with a control group

    Optimal timing of surgery after conversion therapy for initially unresectable hepatocellular carcinoma: a multicenter study integrating major pathological response and treatment duration · 2026 · DOI

  • further studies are needed to confirm the optimal timing of surgery after conversion therapy, - research on the underlying mechanisms of MPR and its relationship with treatment duration is warranted, - studies investigating the role of different conversion therapy regimens in achieving MPR are necessary

    Optimal timing of surgery after conversion therapy for initially unresectable hepatocellular carcinoma: a multicenter study integrating major pathological response and treatment duration · 2026 · DOI

  • However, few studies have compared the perioperative outcomes of open (OLR), laparoscopic (LLR), and robotic liver resections (RLR) together at once for lesions located in the superior parts of the right anterior and posterior segments, S7 and S8.

    Better outcomes of robotic liver resection in segment VII/VIII compared to open and laparoscopic approach · 2026 · DOI

  • BACKGROUND For patients with intermediate-advanced hepatocellular carcinoma (HCC) who have contraindications to immune checkpoint inhibitors, effective alternative therapies are scarce.

    Efficacy of transcatheter arterial embolization plus targeted chemotherapy for advanced hepatocellular carcinoma: A case report and literature review · 2026 · DOI

  • Vacuum-assisted FNAB (v-FNAB) provides controlled negative pressure using 20–25G needles; however, comparative clinical data remain limited.

    Multimodal planning of vacuum-assisted fine-needle aspiration biopsy for focal liver lesions: A single-center comparative diagnostic study · 2026 · DOI

  • The extent to which the tumor transcriptome reflects the underlying liver disease remains incompletely defined.

    Comparative transcriptomic analysis of hepatocellular carcinoma according to primary liver disease using TCGA-LIHC data · 2026 · DOI

  • However, it is susceptible to complications, and safety data on liver biopsies remain scarce.

    Complications of image-guided liver biopsies: Results of a nationwide database analysis · 2025 · DOI

  • The expanding repertoire of chemotherapeutic regiments suitable for patients with HCC should be further investigated.

    Evolving Indications for Liver Transplantation for Hepatocellular Carcinoma Following the Milan Criteria · 2025 · DOI

  • Hispanic/Latino (H/L) patients tend to be diagnosed at younger ages and more advanced stages than Non-Hispanic White (NHW) patients, yet the molecular mechanisms underlying these disparities remain poorly understood.

    Comparative Genomic Analysis of Key Oncogenic Pathways in Hepatocellular Carcinoma Among Diverse Populations · 2025 · DOI

  • The findings suggest that RTK/RAS (FGFR4, IGF1R), PI3K (INPP4B), and TGF-beta (TGFBR2) pathway alterations may play a distinct role in HCC among H/L patients, while their prognostic significance in NHW patients remains unclear.

    Comparative Genomic Analysis of Key Oncogenic Pathways in Hepatocellular Carcinoma Among Diverse Populations · 2025 · DOI

  • Biological features of complete responders were also distinct, and further evaluation of immune cell PD-L1 protein expression and circulating tumor DNA as potential biomarkers is warranted.

    Complete Response to Immunotherapy in Patients With Hepatocellular Carcinoma · 2025 · DOI

  • Robotic-assisted hepatectomy has gained traction in hepatobiliary surgery, but its cost-effectiveness compared to traditional surgical approaches remains unclear.

    Cost-effectiveness and clinical impact of robotic-assisted hepatectomy · 2025 · DOI

  • The treatment efficiency and predictors of atezolizumab plus bevacizumab therapy for unresectable hepatocellular carcinoma in real-world practice have not been established.

    Clinical factors associated with the therapeutic efficacy of atezolizumab plus bevacizumab in patients with unresectable hepatocellular carcinoma: A multicenter prospective observational study · 2024 · DOI

  • Future research should focus on integrating emerging technologies and biomarkers to improve early detection and overall patient outcomes.

    Hepatocellular Carcinoma Surveillance Strategies: Major Guidelines and Screening Advances · 2024 · DOI

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314 open questions have been extracted from the limitations and future-work passages of 693 Hepatocellular Carcinoma Treatment and Prognosis papers in our library. Each one below links back to the study that raised it, so you can read the original claim in context.

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