Cited by 4,319Hepatocellular Carcinoma Treatment and PrognosisColorectal Cancer Treatments and StudiesRenal cell carcinoma treatment

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BCLC strategy for prognosis prediction and treatment recommendation: The 2022 update

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Reig, Maria, Forner, Alejandro, Rimola, Jordi, Ferrer-Fàbrega, Joana, Burrel, Marta, Garcia-Criado, Ángeles, Kelley, Robin K., Galle, Peter R., Mazzaferro, Vincenzo, Salem, Riad, Sangro, Bruno, Singal, Amit G., Vogel, Arndt, Fuster, Josep, Ayuso, Carmen, Bruix, Jordi·2022·Journal of Hepatology

DOI 10.1016/j.jhep.2021.11.018PMC PMC8866082

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Abstract

There have been major advances in the armamentarium for hepatocellular carcinoma (HCC) since the last official update of the Barcelona Clinic Liver Cancer prognosis and treatment strategy published in 2018. Whilst there have been advances in all areas, we will focus on those that have led to a change in strategy and we will discuss why, despite being encouraging, data for select interventions are still too immature for them to be incorporated into an evidence-based model for clinicians and researchers. Finally, we describe the critical insight and expert knowledge that are required to make clinical decisions for individual patients, considering all of the parameters that must be considered to deliver personalised clinical management.

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BackgroundMethodInfluential
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Method
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Method
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“Additionally, it is believed that medicinal chemotherapy is still the primary method of tumor treatment, in accordance with a range of different criteria and consensus both domestically and internationally (Chen et al., 2022; Reig et al., 2022; Strazzabosco et al., 2022).”
Background
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Method
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“…liver disease (MELD) [32], presence of clinically significant portal hypertension (CSPH) [33], Barcelona Clinic Liver Cancer (BCLC) stage [34], meeting Milan criteria [35], number of lesions, size of the largest lesion (cms), presence of portal thrombosis [36], metastasis, and lymphadenopathy.”
Background
The Current and Prospective Adjuvant Therapies for Hepatocellular Carcinoma
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Hepatocellular carcinoma: Advances in systemic therapies
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Hepatocellular carcinoma
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Hepatocellular Carcinoma and the Multifaceted Relationship with Its Microenvironment: Attacking the Hepatocellular Carcinoma Defensive Fortress
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“The multikinase inhibitors family also encompasses regorafenib, ramucirumab and cabozatinib, drugs that are currently approved as second-line treatments, after progression in patients treated with sorafenib (cabozantinib may also be prescribed as a third-line treatment) [17].”
Background
Multimodal multiphasic preoperative image-based deep-learning predicts HCC outcomes after curative surgery
Hui, R. W., Chiu, K. W.-H., Lee, I., Wang, C., Cheng, H. M., Lu, J., Mao, X., Yu, S. N., Lam, L.-K., Mak, L., et al. (2024) · Hepatology · doi:10.1097/hep.0000000000001180 · Cited by 17
Vision transformer-based model can optimize curative-intent treatment for patients with recurrent hepatocellular carcinoma
Zhang, K., Ru, J., Wang, W., Ma, Q., Gao, F., Wu, J., Dai, Z., Xie, Q., Mu, L., Zhang, H., et al. (2025) · Nature Communications · doi:10.1038/s41467-025-59197-0 · Cited by 17
“According to the Barcelona Clinic Liver Cancer (BCLC) staging classi ﬁ cation system, patients with very early (BCLC 0 stage) or early (BCLC A stage) HCC are recommended curative modalities, including local ablation, hepatic resection, and liver transplantation 3 .”
The present and the future of immunotherapy in hepatocellular carcinoma and biliary tract cancers
Cabibbo, G., Rimassa, L., Lamarca, Á., Masi, G., Daniele, B., Pinato, D. J., & Gardini, A. C. (2025) · Cancer Treatment Reviews · doi:10.1016/j.ctrv.2025.102955 · Cited by 18
Temporal evolution of the LI-RADS radiation treatment response assessment on multiphase CT/MRI in patients undergoing selective internal radiation therapy for hepatocellular carcinoma
Wei, H., Jiang, H., Yoo, J., Kim, J. H., Kang, H., Wu, Y., Liu, R., Kim, H., & Lee, J. M. (2025) · European Radiology · doi:10.1007/s00330-025-11659-1 · Cited by 17
The genomic and epigenomic abnormalities of plasma cfDNA as liquid biopsy biomarkers to detect hepatocellular carcinoma: a multicenter cohort study
Guo, D., Huang, A., Sun, J., Zhang, S., Cheng, J., Jiang, R., Wang, Y., 陈慧豪, Zhang, F., Peng, J., et al. (2025) · Journal of Hematology & Oncology · doi:10.1186/s13045-025-01747-6 · Cited by 19
“The lack of an effective means of early diagnosis leads to dismal patient outcomes [2–4].”
Lenvatinib plus transarterial chemoembolization and PD-1 inhibitors as conversion therapies for unresectable intermediate-advanced hepatocellular carcinoma: a phase 2 trial and exploratory biomolecular study
Zhang, X., Cai, H., Peng, W., Wang, H., Wu, J., Zhu, X., Weixin, G. U. O., Xie, F., Zhang, Y., Wang, M., et al. (2026) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-025-02498-z · Cited by 19
Point of care molecular cancer diagnostics
Bhaskar, S., Umrao, S., Lee, H., Tibbs, J., Bacon, A. K., Shepherd, S., Ayupova, T., Ciloglu, F. U., Liu, L., Tan, A., et al. (2026) · Lab on a Chip · doi:10.1039/d5lc01014d · Cited by 18
An Analysis of Microwave Ablation Parameters for Treatment of Liver Tumors from the 3D-IRCADb-01 Database
Radmilović-Radjenović, M., Boskovic, N. M., Sabo, M., & Radjenović, B. (2022) · Biomedicines · doi:10.3390/biomedicines10071569 · Cited by 17
Baseline Splenic Volume Outweighs Immuno-Modulated Size Changes with Regard to Survival Outcome in Patients with Hepatocellular Carcinoma under Immunotherapy
Müller, L., Gairing, S. J., Kloeckner, R., Foerster, F., Weinmann, A., Mittler, J., Stoehr, F., Emrich, T., Düber, C., Galle, P. R., et al. (2022) · Cancers · doi:10.3390/cancers14153574 · Cited by 17
Self-citation
Comparison of the Efficacy and Safety of Transarterial Chemoembolization with or without Lenvatinib for Unresectable Hepatocellular Carcinoma: A Retrospective Propensity Score–Matched Analysis
Chen, Y.-X., Zhang, J.-X., Zhou, C., Liu, J., Liu, S., Shi, H., & Zu, Q. (2022) · Journal of Hepatocellular Carcinoma · doi:10.2147/jhc.s373250 · Cited by 17
Systematic review of adjuvant external beam radiotherapy for hepatocellular carcinoma following radical hepatectomy
Wang, L., Qiu, L., Ke, Q., Ji, H., & Wu, J. (2022) · Radiotherapy and Oncology · doi:10.1016/j.radonc.2022.08.019 · Cited by 17
Surgical Resection Is Superior to TACE in the Treatment of HCC in a Well Selected Cohort of BCLC-B Elderly Patients—A Retrospective Observational Study
Brozzetti, S., D’Alterio, C., Bini, S., Antimi, J., Rocco, B., Fassari, A., Lucatelli, P., Nardis, P., Martino, M. D., Sanctis, G. M. D., et al. (2022) · Cancers · doi:10.3390/cancers14184422 · Cited by 17
Efficacy and safety of transarterial chemoembolization plus antiangiogenic- targeted therapy and immune checkpoint inhibitors for unresectable hepatocellular carcinoma with portal vein tumor thrombus in the real world
Feng, J.-K., Liu, Z., Fu, Z., Chai, Z., Sun, J., Wang, K., Cheng, Y., Zhu, H., Xiang, Y., Zhou, L.-P., et al. (2022) · Frontiers in Oncology · doi:10.3389/fonc.2022.954203 · Cited by 17
The value of the Advanced Lung Cancer Inflammation Index (ALI) in assessing the prognosis of patients with hepatocellular carcinoma treated with camrelizumab: a retrospective cohort study
Li, Q., Ma, F., Tsilimigras, D. I., Åberg, F. O., & Wang, J. F. (2022) · Annals of Translational Medicine · doi:10.21037/atm-22-5099 · Cited by 17
Selecting the Best Approach for the Treatment of Multiple Non-Metastatic Hepatocellular Carcinoma
Cassese, G., Han, H., Cho, J. Y., Lee, H.-W., Lee, B., & TROISI, R. I. (2022) · Cancers · doi:10.3390/cancers14235997 · Cited by 17
“If the number or the size of the lesions overwhelms the Milan criteria or the liver function is not well preserved, such patients are classified as intermediate stage according to BCLC, with western guidelines actually contraindicating surgery in the light of worsened outcomes [5,6,16].”
BackgroundMethodInfluential
Hepatocellular Carcinoma with Bile Duct Tumor Thrombus: A Case Report and Literature Review of 890 Patients Affected by Uncommon Primary Liver Tumor Presentation
Conticchio, M., Maggialetti, N., Rescigno, M., Brunese, M. C., Vaschetti, R., Inchingolo, R., Calbi, R., Ferraro, V., Tedeschi, M., Fantozzi, M. R., et al. (2023) · Journal of Clinical Medicine · doi:10.3390/jcm12020423 · Cited by 17
Impact of adjuvant sorafenib treatment after local ablation for HCC in the phase II SORAMIC trial
Seidensticker, M., Öcal, O., Schütte, K., Malfertheiner, P., Berg, T., Loewe, C., Klümpen, H., van Delden, O. M., Ümütlü, M. R., Khaled, N. B., et al. (2023) · JHEP Reports · doi:10.1016/j.jhepr.2023.100699 · Cited by 18
Self-citation
Transcatheter Arterial Chemoembolization for Treatment-Naive Hepatocellular Carcinoma Has Different Treatment Effects Depending on Central or Peripheral Tumor Location
Asano, K., Kageyama, K., Yamamoto, A., Jogo, A., Uchida‐Kobayashi, S., Sohgawa, E., Murai, K., Kawada, N., & Miki, Y. (2023) · Liver Cancer · doi:10.1159/000530441 · Cited by 17
Image-guided percutaneous locoregional therapies for hepatocellular carcinoma
Chevallier, O., Zhao, K., Marinelli, B. S., & Yarmohammadi, H. (2023) · Chinese Clinical Oncology · doi:10.21037/cco-22-119 · Cited by 17
Methylated SEPT9 assay-based liquid biopsy as a biomarker in molecular targeted agent-treated hepatocellular carcinoma
Saeki, I., Suehiro, Y., Yamauchi, Y., Hoshida, T., Tanabe, N., Oono, T., Kawamoto, D., Nishimura, T., Matsumoto, T., Ishikawa, T., et al. (2023) · Hepatology International · doi:10.1007/s12072-023-10488-y · Cited by 17
“These combined immunotherapies are recommended as the first-line therapy for advanced HCC, and all other MTAs (SORA, lenvatinib [LEN], regorafenib, ramucirumab, and cabozantinib) have shifted to later-line therapies [1].”
BackgroundInfluential
Synergistic Nanomedicine: Photodynamic, Photothermal and Photoimmune Therapy in Hepatocellular Carcinoma: Fulfilling the Myth of Prometheus?
Ailioaie, L. M., Ailioaie, C., & Litscher, G. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24098308 · Cited by 17
Development and validation of the OSASH score to predict overall survival of hepatocellular carcinoma after surgical resection: a dual-institutional study
Wei, H., Fu, F., Jiang, H., Wu, Y., Qin, Y., Wei, H., Yang, T., Wang, M., & Song, B. (2023) · European Radiology · doi:10.1007/s00330-023-09725-7 · Cited by 17
Clinical Outcomes of Cabozantinib in Patients Previously Treated with Atezolizumab/Bevacizumab for Advanced Hepatocellular Carcinoma—Importance of Good Liver Function and Good Performance Status
Kuzuya, T., Kawabe, N., Ariga, M., Ohno, E., Funasaka, K., Nagasaka, M., Nakagawa, Y., Miyahara, R., Shibata, T., Takahara, T., et al. (2023) · Cancers · doi:10.3390/cancers15112952 · Cited by 17
“In the future, MTA will likely be administered sequentially after ICI treatment [11].”
Background
Neoadjuvant intensity modulated radiotherapy for a single and small (≤5 cm) hepatitis B virus-related hepatocellular carcinoma predicted to have high risks of microvascular invasion: a randomized clinical trial
Wei, X., Jiang, Y., Feng, S., Lu, C., Huo, L., Zhou, B., Meng, Y., Lau, W. Y., Zheng, Y., & Cheng, S. (2023) · International Journal of Surgery · doi:10.1097/js9.0000000000000574 · Cited by 17
Indolent cancer and pattern of progression: Two missing parameters in trial design for hepatology
Iavarone, M. A., Nault, J., Cabibbo, G., Torres, F., & Reig, M. (2023) · Hepatology · doi:10.1097/hep.0000000000000527 · Cited by 17
Self-citation
Synergistic effect of OK-432 in combination with an anti-PD-1 antibody for residual tumors after radiofrequency ablation of hepatocellular carcinoma
Sun, T., Sun, B., Cao, Y., Liu, J., Chen, J., Liang, B., Zheng, C., & Kan, X. (2023) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2023.115351 · Cited by 18
Current Therapeutic Strategies for Hepatocellular Carcinoma in Japan
Kudo, M. (2023) · Liver Cancer · doi:10.1159/000534304 · Cited by 17
Incidence and Predictors of Esophagogastric Varices Bleeding in Patients with Hepatocellular Carcinoma in Lenvatinib
Iavarone, M. A., Alimenti, E., Tada, T., Shimose, S., Suda, G., Yoo, C., Soldà, C., Piscaglia, F., Tosetti, G., Marra, F., et al. (2023) · Liver Cancer · doi:10.1159/000534127 · Cited by 17
Pretreatment Neutrophil-to-Lymphocyte Ratio as Prognostic Biomarkers in Patients with Unresectable Hepatocellular Carcinoma Treated with Hepatic Arterial Infusion Chemotherapy Combined with Lenvatinib and Camrelizumab
Xiao, Y., Zhu, G., Xie, J., Luo, L., Deng, W., Lin, L., Tao, J., Hu, Z., & Shan, R. (2023) · Journal of Hepatocellular Carcinoma · doi:10.2147/jhc.s432134 · Cited by 17
“33 The Barcelona Clinic Liver Cancer (BCLC) categorization system was used to determine the stage of HCC. 34”
MethodInfluential
Indication of Liver Transplant for HCC: Current Status and Future Directions
Horwitz, J. K., & Agopian, V. G. (2024) · Current Hepatology Reports · doi:10.1007/s11901-024-00641-y · Cited by 17
Locoregional Therapies for Hepatobiliary Tumors: Contemporary Strategies and Novel Applications
Jipa, A. M., & Makary, M. S. (2024) · Cancers · doi:10.3390/cancers16071271 · Cited by 17
“Systemic therapy may be considered as an option if patients are not candidates for resection or locoregional therapy. lesions in the absence of PVT or bi-lobar disease (Figure 2) [2].”
BackgroundInfluential
Transarterial Chemoembolization Combined with Tyrosine Kinase Inhibitors Plus Immune Checkpoint Inhibitors Versus Tyrosine Kinase Inhibitors Plus Immune Checkpoint Inhibitors in Unresectable Hepatocellular Carcinoma with First- or Lower-Order Portal Vein Tumor Thrombosis
Zhang, J.-X., Cheng, Y., Wei, J., Fan, W.-L., Liu, J., Zhou, C., Liu, S., Shi, H., Chu, X., Zheng, W., et al. (2024) · CardioVascular and Interventional Radiology · doi:10.1007/s00270-024-03724-x · Cited by 17
“According to the current Barcelona Clinic Liver Cancer (BCLC) staging system, HCC with PVTT is regarded as advanced-stage disease (BCLC stage C) [5].”
Targeted degradation of NDUFS1 by agrimol B promotes mitochondrial ROS accumulation and cytotoxic autophagy arrest in hepatocellular carcinoma
Dong, L., Luo, L., Wang, Z., Lian, S., Wang, M., Wu, X., Fan, J., Zeng, Y., Li, S., Lv, S., et al. (2024) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2024.04.242 · Cited by 19
Clinical Utility of the Novel Oncological Criteria of Resectability for Advanced Hepatocellular Carcinoma
Shindoh, J., Kawamura, Y., Akahoshi, K., Matsumura, M., Okubo, S., Akuta, N., Tanabe, M., Kokudo, N., Suzuki, Y., & Hashimoto, M. (2024) · Liver Cancer · doi:10.1159/000539381 · Cited by 17
Effectiveness of mailed outreach and patient navigation to promote HCC screening process completion: a multicentre pragmatic randomised clinical trial
Singal, A. G., Narasimman, M., Daher, D., Yekkaluri, S., Liu, Y., Lee, M., Cerda, V., Khan, A., Dahan, K. S. E., Kramer, J. R., et al. (2024) · Gut · doi:10.1136/gutjnl-2024-332508 · Cited by 17
Self-citation
Advancements in Immunotherapeutic Treatments for Hepatocellular Carcinoma: Potential of Combination Therapies
Zarlashat, Y., Mushtaq, H., Pham, L., Abbas, W., & Sato, K. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25136830 · Cited by 19
“Intermediate-stage HCC involves larger tumors and relatively preserved or compromised liver function [63].”
Background
Predicting liver ablation volumes with real-time MRI thermometry
Öcal, O., Dietrich, O., Lentini, S., Bour, P., Faller, T. L., Ozenne, V., Maier, F. C., Fabritius, M. P., Puhr‐Westerheide, D., Schmidt, V. F., et al. (2024) · JHEP Reports · doi:10.1016/j.jhepr.2024.101199 · Cited by 17
Predictive factors and survival outcome of conversion therapy for unresectable hepatocellular carcinoma patients receiving atezolizumab and bevacizumab: Comparative analysis of conversion, partial response and complete response patients
Hatanaka, T., Kakizaki, S., Hiraoka, A., Tada, T., Hirooka, M., Kariyama, K., Tani, J., Atsukawa, M., Takaguchi, K., Itobayashi, E., et al. (2024) · Alimentary Pharmacology & Therapeutics · doi:10.1111/apt.18237 · Cited by 17
Streamlining Radioembolization without Lung Shunt Estimation versus Regular Radioembolization in Patients with Hepatocellular Carcinoma within the Milan Criteria
Kim, H., Suh, M., Paeng, J. C., Lee, J. H., Lee, M., Chung, J. W., & Choi, J. W. (2024) · Journal of Vascular and Interventional Radiology · doi:10.1016/j.jvir.2024.10.007 · Cited by 17
Hepatic Resection for Hepatocellular Carcinoma
Tabrizian, P., Pero, A., & Schwartz, M. (2024) · Clinics in Liver Disease · doi:10.1016/j.cld.2024.08.008 · Cited by 17
Resistance to Tyrosine Kinase Inhibitors in Hepatocellular Carcinoma (HCC): Clinical Implications and Potential Strategies to Overcome the Resistance
Ermi, A. G., & Sarkar, D. (2024) · Cancers · doi:10.3390/cancers16233944 · Cited by 21
“In terminal cases of In terminal cases of HCC, who are not eligible for curative treatments, supportive care focuses on relieving symptoms and improving the quality of life for patients [13].”
Influential
Next‐Generation Flexible Embolic Systems: Targeted Transarterial Chemoembolization Strategies for Hepatocellular Carcinoma
Wu, H., Lv, S.-D., Zhang, R., Gu, L., Xu, J., Li, C., Zhang, L., Shen, F., Kow, A. W. C., Wang, M.-D., et al. (2025) · Advanced Materials · doi:10.1002/adma.202503971 · Cited by 17
Artificial intelligence-assisted platform performs high detection ability of hepatocellular carcinoma in CT images: an external clinical validation study
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“In clinical practice, such patients with a relatively lower detection rate account for a high proportion [24–26].”
Predicting treatment response and prognosis of immune checkpoint inhibitors-based combination therapy in advanced hepatocellular carcinoma using a longitudinal CT-based radiomics model: a multicenter study
Xu, J., Li, J., Wang, T., Luo, X., Zhu, Z., Wang, Y., Wang, Y., Zhang, Z., Song, R., Yang, L., et al. (2025) · BMC Cancer · doi:10.1186/s12885-025-13978-4 · Cited by 18
“The diagnosis of HCC is based on established guidelines or criteria [24–26].”

Authors: Reig, M., Forner, A., Rimola, J., Ferrer-Fàbrega, J., Burrel, M., Garcia-Criado, Á., Kelley, R. K., Galle, P. R., Mazzaferro, V., Salem, R., Sangro, B., Singal, A. G., Vogel, A., Fuster, J., Ayuso, C., & Bruix, J.
Affiliations: Hospital Clínic de Barcelona (ES)
University of California, San Francisco (US)
University Medical Center of the Johannes Gutenberg University Mainz (DE)
University of Milan (IT)
Northwestern University (US)
Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (ES)
The University of Texas Southwestern Medical Center (US)
Medizinische Hochschule Hannover (DE)
Corresponding author: Bruix, Jordi
ORCID: Reig, Maria
Forner, Alejandro
Rimola, Jordi
Burrel, Marta
Garcia-Criado, Ángeles
Kelley, Robin K.
Galle, Peter R.
Mazzaferro, Vincenzo
Salem, Riad
Sangro, Bruno
Singal, Amit G.
Vogel, Arndt
Fuster, Josep
Ayuso, Carmen
Bruix, Jordi
Venue: Journal of Hepatology
Publisher: Elsevier BV
Published: 2022-03
Volume: 76
Issue: 3
Pages: 681-693
ISSN: 0168-8278 (ISSN-L)
DOI: 10.1016/j.jhep.2021.11.018
PMC: PMC8866082
OpenAlex: W3213277274
Cited by: 4,319
References: 136
Citations by year: 2026: 684 · 2025: 1071 · 2024: 1166 · 2023: 962 · 2022: 424
FWCI: 83.72
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
Locations: Journal of Hepatology (publishedVersion)
PubMed (publishedVersion)
PubMed Central (acceptedVersion)
Archivio Istituzionale della Ricerca (Universita Degli Studi Di Milano) (submittedVersion, other-oa)
eScholarship (California Digital Library) (submittedVersion)
Funders: Fundación Científica de la Asociación Española Contra el Cáncer (PI044031)
National Institutes of Health (R01 R01 MD012565, PI18/00768)
Horizon 2020 Framework Programme (952103)
Instituto de Salud Carlos III (AC16/00065, PI18/0358, PI15/00145, PI18/00542, PI19/00742, PI18/00768)
European Association for the Study of the Liver
Horizon 2020
Topics: Health Sciences › Medicine › Hepatology › Hepatocellular Carcinoma Treatment and Prognosis
Health Sciences › Medicine › Oncology › Colorectal Cancer Treatments and Studies
Health Sciences › Medicine › Oncology › Renal cell carcinoma treatment
Keywords: hepatocellular carcinoma, Barcelona Clinic Liver Cancer staging, outcome prediction, treatment guidelines, evidence-based clinical decision-making
MeSH terms: Female, Carcinoma, Hepatocellular, Humans, Liver Neoplasms, Male, Middle Aged, Neoplasm Staging, Prognosis, Severity of Illness Index

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BCLC strategy for prognosis prediction and treatment recommendation: The 2022 update

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