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For: Zocco MA, Garcovich M, Lupascu A, Di Stasio E, Roccarina D, Annicchiarico BE, Riccardi L, Ainora ME, Ponziani F, Caracciolo G, Rapaccini GL, Landolfi R, Siciliano M, Pompili M, Gasbarrini A. Early prediction of response to sorafenib in patients with advanced hepatocellular carcinoma: the role of dynamic contrast enhanced ultrasound. J Hepatol 2013;59:1014-1021. [PMID: 23811306 DOI: 10.1016/j.jhep.2013.06.011] [Citation(s) in RCA: 68] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [What about the content of this article? (0)] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/12/2013] [Revised: 06/10/2013] [Accepted: 06/17/2013] [Indexed: 02/06/2023]

For:	Zocco MA, Garcovich M, Lupascu A, Di Stasio E, Roccarina D, Annicchiarico BE, Riccardi L, Ainora ME, Ponziani F, Caracciolo G, Rapaccini GL, Landolfi R, Siciliano M, Pompili M, Gasbarrini A. Early prediction of response to sorafenib in patients with advanced hepatocellular carcinoma: the role of dynamic contrast enhanced ultrasound. J Hepatol 2013;59:1014-1021. [PMID: 23811306 DOI: 10.1016/j.jhep.2013.06.011] [Citation(s) in RCA: 68] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [What about the content of this article? (0)] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/12/2013] [Revised: 06/10/2013] [Accepted: 06/17/2013] [Indexed: 02/06/2023]

Number

Cited by Other Article(s)

Scolozzi V, Nicoletti A, Capotosti A, Ponziani FR, Taralli S, Genco E, Leccisotti L, Moretti R, Indovina L, Pompili M, Calcagni ML. ¹³N-Ammonia PET-CT for Evaluating Response to Antiangiogenic Therapy and Prognosis in Patients with Advanced Hepatocellular Carcinoma: A Pilot Study. Cancers (Basel) 2025;17:656. [PMID: 40002251 PMCID: PMC11853641 DOI: 10.3390/cancers17040656] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/24/2024] [Revised: 02/11/2025] [Accepted: 02/14/2025] [Indexed: 02/27/2025] Open

Abstract

PURPOSE

To prospectively investigate dynamic 13N-ammonia PET-CT for evaluating early treatment response and predicting prognosis in advanced hepatocellular carcinoma (HCC) patients who have undergone antiangiogenic therapy.

METHODS

Dynamic 13N-ammonia PET-CT was performed in 23 advanced HCC patients before antiangiogenic therapy (baseline) and in 18/23 patients after 8-10 weeks of treatment (post-therapy). At kinetic PET-CT analysis, mean, maximum, and peak values of K1 (mL/cm3/min) and k2 (min-1) were estimated in HCC lesions and non-neoplastic liver using cardiologic 13N-ammonia PET-CT in 15 patients without any liver diseases as normal controls. Outcome endpoints were treatment response after 8-10 weeks assessed by contrast-enhanced CT, progression-free survival (PFS), and overall survival (OS).

RESULTS

At both baseline and post-therapy PET-CT, all kinetic PET parameters were significantly higher (p < 0.05) in HCC lesions than in non-neoplastic and healthy liver of HCC patients and controls. According to mRECIST criteria, 13/18 patients (72.2%) were responders (1 CR, 1 PR, and 11 SD), and 5/18 patients (27.8%) were non-responders (PD), with no significant differences in baseline and post-therapy PET parameters between the two groups. At follow-up (median: 14.2 months), 15/18 patients (83.3%) experienced radiological progression, and 14/18 (77.8%) died (7/14 within 12 months from treatment). The nine earlier-progression patients (within 6 months from treatment) showed significantly lower baseline K1mean in HCC lesions than all nine patients with later or no-progression (p = 0.03). Patients still alive 12 months after treatment (n = 11) showed significantly lower post-therapy K1mean (p = 0.05), K1max (p = 0.05), and K1peak (p = 0.03) in non-neoplastic liver than patients with shorter OS (n = 7).

CONCLUSIONS

In advanced HCC patients treated with antiangiogenic agents, kinetic parameters from baseline and post-therapy 13N-ammonia PET-CT may predict early disease progression and survival. PET-CT seems not able to discriminate responders and non-responders after 8-10 weeks of treatment, suggesting the need for future and larger studies after a longer treatment period.

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Affiliation(s)

Valentina Scolozzi Unità di Medicina Nucleare, Dipartimento di Diagnostica per Immagini e Radioterapia Oncologica, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy
Alberto Nicoletti Liver Unit, CEMAD-Centro Malattie dell’Apparato Digerente, Medicina Interna e Gastroenterologia, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy
Amedeo Capotosti Dipartimento di Diagnostica per Immagini e Radioterapia Oncologica, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy
Francesca Romana Ponziani Liver Unit, CEMAD-Centro Malattie dell’Apparato Digerente, Medicina Interna e Gastroenterologia, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy Dipartimento di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, 00168 Rome, Italy
Silvia Taralli Unità di Medicina Nucleare, Dipartimento di Diagnostica per Immagini e Radioterapia Oncologica, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy
Enza Genco Radiologia Addomino-Pelvica, Dipartimento di Diagnostica per Immagini e Radioterapia Oncologica, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy
Lucia Leccisotti Unità di Medicina Nucleare, Dipartimento di Diagnostica per Immagini e Radioterapia Oncologica, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy Istituto di Medicina Nucleare, Dipartimento Universitario di Scienze Radiologiche ed Ematologiche, Università Cattolica del Sacro Cuore, 00168 Rome, Italy
Roberto Moretti Dipartimento di Diagnostica per Immagini e Radioterapia Oncologica, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy
Luca Indovina Dipartimento di Diagnostica per Immagini e Radioterapia Oncologica, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy
Maurizio Pompili Liver Unit, CEMAD-Centro Malattie dell’Apparato Digerente, Medicina Interna e Gastroenterologia, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy Dipartimento di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, 00168 Rome, Italy
Maria Lucia Calcagni Unità di Medicina Nucleare, Dipartimento di Diagnostica per Immagini e Radioterapia Oncologica, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy Istituto di Medicina Nucleare, Dipartimento Universitario di Scienze Radiologiche ed Ematologiche, Università Cattolica del Sacro Cuore, 00168 Rome, Italy

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Hu H, Zhao Y, He C, Qian L, Huang P. Ultrasonography of Hepatocellular Carcinoma: From Diagnosis to Prognosis. J Clin Transl Hepatol 2024;12:516-524. [PMID: 38779517 PMCID: PMC11106354 DOI: 10.14218/jcth.2024.00018] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/12/2024] [Revised: 03/15/2024] [Accepted: 04/07/2024] [Indexed: 05/25/2024] Open

Sun D, Zhang X, Sun Y, Mu Z, Wang H, Zhang Y, Liang J, Lin Y. Early Structural, Biochemical, and Metabolic Responses to Anlotinib in Patients With Progressive Radioactive Iodine Refractory Differentiated Thyroid Cancer. Endocr Pract 2024;30:456-464. [PMID: 38447630 DOI: 10.1016/j.eprac.2024.02.005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/15/2023] [Revised: 02/22/2024] [Accepted: 02/28/2024] [Indexed: 03/08/2024]

Abstract

OBJECTIVE

We aimed to assess the early efficacy of anlotinib in patients with progressive radioactive iodine refractory differentiated thyroid cancer at the structural, biochemical, and metabolic levels.

METHODS

Ten eligible patients were prospectively enrolled to receive anlotinib. Their responses were assessed at 6 weeks. Apart from the structural response according to Response Evaluation Criteria in Solid Tumors version 1.1, the biochemical response was assessed by serum thyroglobulin (Tg), and the metabolic response was assessed by 2-deoxy-2-[18F] fluoro-D-glucose positron emission tomography/computed tomography (18F-FDG PET/CT) according to the European Organization for Research and Treatment of Cancer criteria. A safety profile was recorded.

RESULTS

Structurally controlled disease (20% partial response + 80% stable disease) was observed in all patients. The median longest diameter of target lesions shrank from 20.8 mm (IQR, 14.9-27.5) to 17.0 mm (IQR, 14.1-23.7) (P < .001), and the average shrinkage rate was -15.1 ± 14.1%. Sharp serum Tg reduction by 72.8 ± 16.4% was observed in 8 measurable patients. The 18F-FDG PET/CT-mapped glucose metabolic response was not quite comparable to the structural response, with 90% of the patients having controlled disease (30% partial metabolic response + 60% stable metabolic disease), whereas 10% presented progressive metabolic disease. The most common treatment-emergent adverse events (AEs) were hypertension (100%) and proteinuria (70%). Most AEs were grade 1 or 2, whereas grade 3 AEs occurred only in hypertension.

CONCLUSION

Anlotinib is generally well tolerated and can bring early disease control within the initial 6 weeks of treatment. The sharp biochemical response suggests Tg to be an early sensitive biomarker to anlotinib, whereas the heterogeneous metabolic response might play a complementary role.

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Affiliation(s)

Di Sun Department of Nuclear Medicine, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College (PUMC) Hospital, Chinese Academy of Medical Sciences & PUMC, Beijing 100730, China; Beijing Key Laboratory of Molecular Targeted Diagnosis and Therapy in Nuclear Medicine, Beijing 100730, China
Xin Zhang Department of Nuclear Medicine, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College (PUMC) Hospital, Chinese Academy of Medical Sciences & PUMC, Beijing 100730, China; Beijing Key Laboratory of Molecular Targeted Diagnosis and Therapy in Nuclear Medicine, Beijing 100730, China
Yuqing Sun Department of Nuclear Medicine, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College (PUMC) Hospital, Chinese Academy of Medical Sciences & PUMC, Beijing 100730, China; Beijing Key Laboratory of Molecular Targeted Diagnosis and Therapy in Nuclear Medicine, Beijing 100730, China
Zhuanzhuan Mu Department of Nuclear Medicine, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College (PUMC) Hospital, Chinese Academy of Medical Sciences & PUMC, Beijing 100730, China; Beijing Key Laboratory of Molecular Targeted Diagnosis and Therapy in Nuclear Medicine, Beijing 100730, China
Hao Wang Department of Oncology, Qingdao Hospital, University of Health and Rehabilitation Sciences (Qingdao Municipal Hospital), Qingdao 266012, China
Yingqiang Zhang Department of Nuclear Medicine, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College (PUMC) Hospital, Chinese Academy of Medical Sciences & PUMC, Beijing 100730, China; Beijing Key Laboratory of Molecular Targeted Diagnosis and Therapy in Nuclear Medicine, Beijing 100730, China
Jun Liang Department of Oncology, Peking University International Hospital, Peking University, Beijing 102206, China; Department of Medical Oncology, Key Laboratory of Carcinogenesis & Translational Research (Ministry of Education/Beijing), Peking University Cancer Hospital and Institute, Beijing 100142, China.
Yansong Lin Department of Nuclear Medicine, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College (PUMC) Hospital, Chinese Academy of Medical Sciences & PUMC, Beijing 100730, China; Beijing Key Laboratory of Molecular Targeted Diagnosis and Therapy in Nuclear Medicine, Beijing 100730, China.

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Zhang Y, Zheng R, Liu M, Zhang X, Sun Y, Shen H, Chen S, Cai H, Guo W, Xie X, Liu B, Huang G. Quantitative Parameters of Contrast-Enhanced Ultrasound Predicting the Response to Combined Immune Checkpoint Inhibitor and Anti-angiogenesis Therapies for Unresectable Hepatocellular Carcinoma. ULTRASOUND IN MEDICINE & BIOLOGY 2024;50:352-357. [PMID: 38072718 DOI: 10.1016/j.ultrasmedbio.2023.11.005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/01/2023] [Revised: 11/07/2023] [Accepted: 11/09/2023] [Indexed: 01/23/2024]

Affiliation(s)

Yi Zhang Division of Interventional Ultrasound, Department of Medical Ultrasonics, Institute of Diagnostic and Interventional Ultrasound, First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
Ruiying Zheng Division of Interventional Ultrasound, Department of Medical Ultrasonics, Institute of Diagnostic and Interventional Ultrasound, First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
Ming Liu Division of Interventional Ultrasound, Department of Medical Ultrasonics, Institute of Diagnostic and Interventional Ultrasound, First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
Xiaoer Zhang Division of Interventional Ultrasound, Department of Medical Ultrasonics, Institute of Diagnostic and Interventional Ultrasound, First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
Yueting Sun Division of Interventional Ultrasound, Department of Medical Ultrasonics, Institute of Diagnostic and Interventional Ultrasound, First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
Hui Shen Division of Interventional Ultrasound, Department of Medical Ultrasonics, Institute of Diagnostic and Interventional Ultrasound, First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
Song Chen Department of Interventional Radiology, First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
Hongjie Cai Department of Interventional Radiology, First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
Wenbo Guo Department of Interventional Radiology, First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
Xiaoyan Xie Division of Interventional Ultrasound, Department of Medical Ultrasonics, Institute of Diagnostic and Interventional Ultrasound, First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
Baoxian Liu Division of Interventional Ultrasound, Department of Medical Ultrasonics, Institute of Diagnostic and Interventional Ultrasound, First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
Guangliang Huang Division of Interventional Ultrasound, Department of Medical Ultrasonics, Institute of Diagnostic and Interventional Ultrasound, First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China; Department of Medical Ultrasonics, Guangxi Hospital Division of the First Affiliated Hospital, Sun Yat-Sen University, Guangxi, China.

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Cerrito L, Ainora ME, Cuccia G, Galasso L, Mignini I, Esposto G, Garcovich M, Riccardi L, Gasbarrini A, Zocco MA. Dynamic Contrast-Enhanced Ultrasound in the Prediction of Advanced Hepatocellular Carcinoma Response to Systemic and Locoregional Therapies. Cancers (Basel) 2024;16:551. [PMID: 38339302 PMCID: PMC10854581 DOI: 10.3390/cancers16030551] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2023] [Revised: 01/19/2024] [Accepted: 01/24/2024] [Indexed: 02/12/2024] Open

Affiliation(s)

Lucia Cerrito Department of Internal Medicine and Gastroenterology, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Catholic University of Rome, 00168 Rome, Italy (M.E.A.); (G.C.); (G.E.); (M.G.); (L.R.); (A.G.) CEMAD Digestive Disease Center, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Catholic University of Rome, 00168 Rome, Italy; (L.G.); (I.M.)
Maria Elena Ainora Department of Internal Medicine and Gastroenterology, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Catholic University of Rome, 00168 Rome, Italy (M.E.A.); (G.C.); (G.E.); (M.G.); (L.R.); (A.G.) CEMAD Digestive Disease Center, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Catholic University of Rome, 00168 Rome, Italy; (L.G.); (I.M.)
Giuseppe Cuccia Department of Internal Medicine and Gastroenterology, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Catholic University of Rome, 00168 Rome, Italy (M.E.A.); (G.C.); (G.E.); (M.G.); (L.R.); (A.G.) CEMAD Digestive Disease Center, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Catholic University of Rome, 00168 Rome, Italy; (L.G.); (I.M.)
Linda Galasso CEMAD Digestive Disease Center, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Catholic University of Rome, 00168 Rome, Italy; (L.G.); (I.M.)
Irene Mignini CEMAD Digestive Disease Center, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Catholic University of Rome, 00168 Rome, Italy; (L.G.); (I.M.)
Giorgio Esposto Department of Internal Medicine and Gastroenterology, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Catholic University of Rome, 00168 Rome, Italy (M.E.A.); (G.C.); (G.E.); (M.G.); (L.R.); (A.G.) CEMAD Digestive Disease Center, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Catholic University of Rome, 00168 Rome, Italy; (L.G.); (I.M.)
Matteo Garcovich Department of Internal Medicine and Gastroenterology, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Catholic University of Rome, 00168 Rome, Italy (M.E.A.); (G.C.); (G.E.); (M.G.); (L.R.); (A.G.) CEMAD Digestive Disease Center, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Catholic University of Rome, 00168 Rome, Italy; (L.G.); (I.M.)
Laura Riccardi Department of Internal Medicine and Gastroenterology, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Catholic University of Rome, 00168 Rome, Italy (M.E.A.); (G.C.); (G.E.); (M.G.); (L.R.); (A.G.) CEMAD Digestive Disease Center, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Catholic University of Rome, 00168 Rome, Italy; (L.G.); (I.M.)
Antonio Gasbarrini Department of Internal Medicine and Gastroenterology, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Catholic University of Rome, 00168 Rome, Italy (M.E.A.); (G.C.); (G.E.); (M.G.); (L.R.); (A.G.) CEMAD Digestive Disease Center, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Catholic University of Rome, 00168 Rome, Italy; (L.G.); (I.M.)
Maria Assunta Zocco Department of Internal Medicine and Gastroenterology, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Catholic University of Rome, 00168 Rome, Italy (M.E.A.); (G.C.); (G.E.); (M.G.); (L.R.); (A.G.) CEMAD Digestive Disease Center, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Catholic University of Rome, 00168 Rome, Italy; (L.G.); (I.M.)

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Zhou F, Sun Y, Hou Y, Liu F, Yu X. Intratumoral perfusion may affect microwave ablation area of hepatocellular carcinoma. Int J Hyperthermia 2023;40:2268892. [PMID: 37927295 DOI: 10.1080/02656736.2023.2268892] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/27/2023] [Accepted: 10/05/2023] [Indexed: 11/07/2023] Open

Gao Y, Zeng X, Liao X. Correlation between microvessel maturity and ISUP grades assessed using contrast-enhanced transrectal ultrasonography in prostate cancer. Open Med (Wars) 2023;18:20230772. [PMID: 37588658 PMCID: PMC10426265 DOI: 10.1515/med-2023-0772] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2022] [Revised: 06/27/2023] [Accepted: 07/19/2023] [Indexed: 08/18/2023] Open

Zocco MA, Cintoni M, Ainora ME, Garcovich M, Lupascu A, Iezzi R, Annichiarico BE, Siciliano M, Riccardi L, Rapaccini GL, Grieco A, Pompili M, Gasbarrini A. Noninvasive Evaluation of Clinically Significant Portal Hypertension in Patients with Liver Cirrhosis: The Role of Contrast-Enhanced Ultrasound Perfusion Imaging and Elastography. ULTRASCHALL IN DER MEDIZIN (STUTTGART, GERMANY : 1980) 2023;44:428-435. [PMID: 36526267 DOI: 10.1055/a-1933-2847] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/17/2023]

Paratore M, Garcovich M, Ainora ME, Riccardi L, Gasbarrini A, Zocco MA. Dynamic contrast enhanced ultrasound in gastrointestinal diseases: A current trend or an indispensable tool? World J Gastroenterol 2023;29:4021-4035. [PMID: 37476588 PMCID: PMC10354578 DOI: 10.3748/wjg.v29.i25.4021] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/26/2023] [Revised: 05/24/2023] [Accepted: 06/05/2023] [Indexed: 06/28/2023] Open

Characterization of spatially mapped volumetric molecular ultrasound signals for predicting response to anti-vascular therapy. Sci Rep 2023;13:1686. [PMID: 36717575 PMCID: PMC9886917 DOI: 10.1038/s41598-022-26273-0] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2022] [Accepted: 12/13/2022] [Indexed: 01/31/2023] Open

Uchikawa S, Kawaoka T, Fujino H, Ono A, Nakahara T, Murakami E, Yamauchi M, Miki D, Imamura M, Aikata H. Evaluation of atezolizumab plus bevacizumab combination therapy for hepatocellular carcinoma using contrast-enhanced ultrasonography. J Med Ultrason (2001) 2023;50:57-62. [PMID: 36169740 PMCID: PMC10912139 DOI: 10.1007/s10396-022-01260-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/27/2022] [Accepted: 08/19/2022] [Indexed: 02/04/2023]

Affiliation(s)

Shinsuke Uchikawa Department of Medicine and Molecular Science, Division of Frontier Medical Science Programs for Biomedical Research Graduate School of Biomedical Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan
Tomokazu Kawaoka Department of Medicine and Molecular Science, Division of Frontier Medical Science Programs for Biomedical Research Graduate School of Biomedical Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan.
Hatsue Fujino Department of Medicine and Molecular Science, Division of Frontier Medical Science Programs for Biomedical Research Graduate School of Biomedical Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan
Atsushi Ono Department of Medicine and Molecular Science, Division of Frontier Medical Science Programs for Biomedical Research Graduate School of Biomedical Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan
Takashi Nakahara Department of Medicine and Molecular Science, Division of Frontier Medical Science Programs for Biomedical Research Graduate School of Biomedical Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan
Eisuke Murakami Department of Medicine and Molecular Science, Division of Frontier Medical Science Programs for Biomedical Research Graduate School of Biomedical Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan
Masami Yamauchi Department of Medicine and Molecular Science, Division of Frontier Medical Science Programs for Biomedical Research Graduate School of Biomedical Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan
Daiki Miki Department of Medicine and Molecular Science, Division of Frontier Medical Science Programs for Biomedical Research Graduate School of Biomedical Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan
Michio Imamura Department of Medicine and Molecular Science, Division of Frontier Medical Science Programs for Biomedical Research Graduate School of Biomedical Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan
Hiroshi Aikata Department of Medicine and Molecular Science, Division of Frontier Medical Science Programs for Biomedical Research Graduate School of Biomedical Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan

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He P, Wan H, Wan J, Jiang H, Yang Y, Xie K, Wu H. Systemic therapies in hepatocellular carcinoma: Existing and emerging biomarkers for treatment response. Front Oncol 2022;12:1015527. [PMID: 36483039 PMCID: PMC9723250 DOI: 10.3389/fonc.2022.1015527] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2022] [Accepted: 10/28/2022] [Indexed: 07/21/2023] Open

Early Assessment of Chemoradiotherapy Response for Locally Advanced Pancreatic Ductal Adenocarcinoma by Dynamic Contrast-Enhanced Ultrasound. Diagnostics (Basel) 2022;12:diagnostics12112662. [PMID: 36359506 PMCID: PMC9689529 DOI: 10.3390/diagnostics12112662] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2022] [Revised: 10/27/2022] [Accepted: 10/28/2022] [Indexed: 11/06/2022] Open

Abstract

Objective: To evaluate the value of dynamic contrast-enhanced ultrasound (DCE-US) and quantitative parameters in early prediction of tumor response to chemoradiotherapy (CRT) in patients with locally advanced pancreatic ductal adenocarcinoma (LAPC). Patients and Methods: In this prospective study, patients with biopsy-proved and histopathologically proved LAPC who underwent regular CRT were recruited. DCE-US evaluations were performed before and four months after CRT. SonoVue-enhanced contrast-enhanced ultrasound (CEUS) was performed by an ultrasound system (ACUSON Sequoia; Siemens Medical Solutions, USA) equipped with a 5C1 MHz convex array transducer. Time−intensity curves were created by VueBox software (Bracco, Italy), and various DCE-US quantitative parameters were obtained. Taking Response Evaluation Criteria in Solid Tumors (RECIST) based on computed tomography (CT) or magnetic resonance imaging (MRI) as the gold standard, DCE-US parameters were compared between the treatment responder group (RG) and non-responder group (NRG). The correlation between the DCE-US parameters and the serum carbohydrate antigen 19-9 (CA 19-9) level was also analyzed. Results: Finally, 21 LAPC patients (mean age 59.3 ± 7.2 years) were included. In comparing the RG (n = 18) and NRG (n = 3), no significant change could be found among the mean size of the lesions (31.2 ± 8.1 mm vs. 27.2 ± 8.3 mm, p = 0.135). In comparing the TICs between the two groups, the LAPC lesions in the RG took a longer time to reach peak enhancement and to wash out. Among all the DCE-US parameters, RT (rise time), WiAUC (wash-in area under the curve), WoAUC (wash-out area under the curve) and WiWoAUC (wash-in and wash-out area under the curve) decreased significantly after CRT in the RG (p < 0.05). The RT ratio, WiAUC ratio, WoAUC ratio and WiWoAUC ratio were closely correlated with the change in serum CA 19-9 level in the RG (p < 0.05). Conclusion: DCE-US might be a potential imaging method for non-invasive follow-up for early response in LAPC patients treated by CRT.

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Cerrito L, Ainora ME, Mosoni C, Borriello R, Gasbarrini A, Zocco MA. Prognostic Role of Molecular and Imaging Biomarkers for Predicting Advanced Hepatocellular Carcinoma Treatment Efficacy. Cancers (Basel) 2022;14:4647. [PMID: 36230569 PMCID: PMC9564154 DOI: 10.3390/cancers14194647] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2022] [Revised: 09/19/2022] [Accepted: 09/20/2022] [Indexed: 11/30/2022] Open

Affiliation(s)

Lucia Cerrito Department of Internal Medicine and Gastroenterology, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Catholic University of Rome, 00168 Rome, Italy CEMAD Digestive Disease Center, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Catholic University of Rome, 00168 Rome, Italy
Maria Elena Ainora Department of Internal Medicine and Gastroenterology, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Catholic University of Rome, 00168 Rome, Italy CEMAD Digestive Disease Center, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Catholic University of Rome, 00168 Rome, Italy
Carolina Mosoni Department of Internal Medicine and Gastroenterology, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Catholic University of Rome, 00168 Rome, Italy CEMAD Digestive Disease Center, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Catholic University of Rome, 00168 Rome, Italy
Raffaele Borriello Department of Internal Medicine and Gastroenterology, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Catholic University of Rome, 00168 Rome, Italy CEMAD Digestive Disease Center, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Catholic University of Rome, 00168 Rome, Italy
Antonio Gasbarrini Department of Internal Medicine and Gastroenterology, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Catholic University of Rome, 00168 Rome, Italy CEMAD Digestive Disease Center, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Catholic University of Rome, 00168 Rome, Italy
Maria Assunta Zocco Department of Internal Medicine and Gastroenterology, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Catholic University of Rome, 00168 Rome, Italy CEMAD Digestive Disease Center, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Catholic University of Rome, 00168 Rome, Italy

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Contrast-enhanced ultrasonography for blood flow detection in hepatocellular carcinoma during lenvatinib therapy. J Med Ultrason (2001) 2022;49:425-432. [PMID: 35355122 DOI: 10.1007/s10396-022-01204-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2022] [Accepted: 02/24/2022] [Indexed: 02/07/2023]

Faccia M, Garcovich M, Ainora ME, Riccardi L, Pompili M, Gasbarrini A, Zocco MA. Contrast-Enhanced Ultrasound for Monitoring Treatment Response in Different Stages of Hepatocellular Carcinoma. Cancers (Basel) 2022;14:481. [PMID: 35158749 PMCID: PMC8833342 DOI: 10.3390/cancers14030481] [Citation(s) in RCA: 21] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2021] [Revised: 01/10/2022] [Accepted: 01/14/2022] [Indexed: 01/01/2023] Open

Delaney LJ, Tantawi M, Wessner CE, Machado P, Forsberg F, Lyshchik A, O'Kane P, Liu JB, Civan J, Tan A, Anton K, Shaw CM, Eisenbrey JR. Predicting Long-Term Hepatocellular Carcinoma Response to Transarterial Radioembolization Using Contrast-Enhanced Ultrasound: Initial Experiences. ULTRASOUND IN MEDICINE & BIOLOGY 2021;47:2523-2531. [PMID: 34130880 PMCID: PMC8355136 DOI: 10.1016/j.ultrasmedbio.2021.05.006] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/21/2020] [Revised: 02/26/2021] [Accepted: 05/06/2021] [Indexed: 05/12/2023]

Laterza L, Ainora ME, Garcovich M, Galasso L, Poscia A, Di Stasio E, Lupascu A, Riccardi L, Scaldaferri F, Armuzzi A, Rapaccini GL, Gasbarrini A, Pompili M, Zocco MA. Bowel contrast-enhanced ultrasound perfusion imaging in the evaluation of Crohn's disease patients undergoing anti-TNFα therapy. Dig Liver Dis 2021;53:729-737. [PMID: 32900648 DOI: 10.1016/j.dld.2020.08.005] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/16/2020] [Revised: 07/01/2020] [Accepted: 08/02/2020] [Indexed: 12/11/2022]

Affiliation(s)

Lucrezia Laterza Department of Internal Medicine and Gastroenterology, Fondazione Policlinico Universitario A. Gemelli IRCCS - Catholic University, Rome, Italy
Maria Elena Ainora Department of Internal Medicine and Gastroenterology, Fondazione Policlinico Universitario A. Gemelli IRCCS - Catholic University, Rome, Italy.
Matteo Garcovich Department of Internal Medicine and Gastroenterology, Fondazione Policlinico Universitario A. Gemelli IRCCS - Catholic University, Rome, Italy
Linda Galasso Department of Internal Medicine and Gastroenterology, Fondazione Policlinico Universitario A. Gemelli IRCCS - Catholic University, Rome, Italy
Andrea Poscia Catholic University, Rome, Italy
Enrico Di Stasio Department of Biochemistry and Clinical Biochemistry, Fondazione PoliclinicoUniversitario A. Gemelli IRCCS, Catholic University of Rome, Italy
Andrea Lupascu Department of Internal Medicine and Gastroenterology, Fondazione Policlinico Universitario A. Gemelli IRCCS - Catholic University, Rome, Italy
Laura Riccardi Department of Internal Medicine and Gastroenterology, Fondazione Policlinico Universitario A. Gemelli IRCCS - Catholic University, Rome, Italy
Franco Scaldaferri Department of Internal Medicine and Gastroenterology, Fondazione Policlinico Universitario A. Gemelli IRCCS - Catholic University, Rome, Italy
Alessandro Armuzzi Department of Internal Medicine and Gastroenterology, Fondazione Policlinico Universitario A. Gemelli IRCCS - Catholic University, Rome, Italy
Gian Ludovico Rapaccini Department of Internal Medicine and Gastroenterology, Fondazione Policlinico Universitario A. Gemelli IRCCS - Catholic University, Rome, Italy
Antonio Gasbarrini Department of Internal Medicine and Gastroenterology, Fondazione Policlinico Universitario A. Gemelli IRCCS - Catholic University, Rome, Italy
Maurizio Pompili Department of Internal Medicine and Gastroenterology, Fondazione Policlinico Universitario A. Gemelli IRCCS - Catholic University, Rome, Italy
Maria Assunta Zocco Department of Internal Medicine and Gastroenterology, Fondazione Policlinico Universitario A. Gemelli IRCCS - Catholic University, Rome, Italy

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Taiji R, Nishiofuku H, Tanaka T, Minamiguchi K, Fukuoka Y, Saito N, Taguchi H, Matsumoto T, Marugami N, Hirai T, Kichikawa K. Useful Parameters in Dynamic Contrast-enhanced Ultrasonography for Identifying Early Response to Chemotherapy in a Rat Liver Tumor Model. J Clin Imaging Sci 2021;11:15. [PMID: 33767907 PMCID: PMC7981939 DOI: 10.25259/jcis_6_2020] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/12/2021] [Accepted: 02/15/2021] [Indexed: 12/24/2022] Open

Colagrande S, Calistri L, Campani C, Dragoni G, Lorini C, Nardi C, Castellani A, Marra F. CT volume of enhancement of disease (VED) can predict the early response to treatment and overall survival in patients with advanced HCC treated with sorafenib. Eur Radiol 2021;31:1608-1619. [PMID: 32827266 PMCID: PMC7880966 DOI: 10.1007/s00330-020-07171-3] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2020] [Revised: 06/22/2020] [Accepted: 08/07/2020] [Indexed: 12/14/2022]

Abstract

OBJECTIVES

To analyse the predictive value of the volume of enhancement of disease (VED), based on the CT arterial enhancement coefficient (ΔArt%), in the evaluation of the sorafenib response in patients with advanced hepatocellular carcinoma (HCC).

METHODS

Patients with sorafenib-treated advanced HCC, who underwent a multiphase contrast-enhanced CT before (T0) and after 60-70 days of starting therapy (T1), were included. The same target lesions utilised for the response evaluation according to modified Response Evaluation Criteria in Solid Tumors criteria were retrospectively used for the ΔArt% calculation ([(HUarterial phase - HUunenhanced phase) / HUunenhanced phase] × 100). ΔArt% was weighted for the lesion volume to obtain the VED. We compared VEDT0 and VEDT1 values in patients with clinical benefit (CB) or progressive disease (PD). The impact of VED, ancillary imaging findings, and blood chemistries on survival probability was evaluated.

RESULTS

Thirty-two patients (25 men, mean age 65.8 years) analysed between 2012 and 2016 were selected. At T1, 8 patients had CB and 24 had PD. VEDT0 was > 70% in 8/8 CB patients compared with 12/24 PD patients (p = 0.011). Patients with VEDT0 > 70% showed a significantly higher median survival than those with lower VEDT0 (451.5 days vs. 209.5 days, p = 0.032). Patients with VEDT0 > 70% and alpha-fetoproteinT0 ≤ 400 ng/ml had significantly longer survival than all other three combinations. In multivariate analysis, VEDT0 > 70% emerged as the only factor independently associated with survival (p = 0.037).

CONCLUSION

In patients with advanced HCC treated with sorafenib, VED is a novel radiologic parameter obtained by contrast-enhanced CT, which could be helpful in selecting patients who are more likely to respond to sorafenib, and with a longer survival.

KEY POINTS

• To achieve the best results of treatment with sorafenib in advanced HCC, a strict selection of patients is needed. • New radiologic parameters predictive of the response to sorafenib would be essential. • Volume of enhancement of disease (VED) is a novel radiologic parameter obtained by contrast-enhanced CT, which could be helpful in selecting patients who are more likely to respond to therapy, and with a longer survival.

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Therapeutic response monitoring after targeted therapy in an orthotopic rat model of hepatocellular carcinoma using contrast-enhanced ultrasound: Focusing on inter-scanner, and inter-operator reproducibility. PLoS One 2020;15:e0244304. [PMID: 33362203 PMCID: PMC7757904 DOI: 10.1371/journal.pone.0244304] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2020] [Accepted: 12/03/2020] [Indexed: 11/30/2022] Open

Liang Q, Kong L, Zhu X, Du Y, Tian J. Noninvasive Imaging for Assessment of the Efficacy of Therapeutic Agents for Hepatocellular Carcinoma. Mol Imaging Biol 2020;22:1455-1468. [PMID: 31834570 DOI: 10.1007/s11307-019-01431-5] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/30/2022]

Affiliation(s)

Qian Liang CAS Key Laboratory of Molecular Imaging, the State Key Laboratory of Management and Control for Complex Systems, Institute of Automation, Chinese Academy of Sciences, Beijing, 100190, China University of Chinese Academy of Sciences, Beijing, 100080, China Beijing Key Laboratory of Molecular Imaging, Beijing, 100190, China
Lingxin Kong CAS Key Laboratory of Molecular Imaging, the State Key Laboratory of Management and Control for Complex Systems, Institute of Automation, Chinese Academy of Sciences, Beijing, 100190, China University of Chinese Academy of Sciences, Beijing, 100080, China Beijing Key Laboratory of Molecular Imaging, Beijing, 100190, China
Xu Zhu Department of Interventional Therapy Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Peking University School of Oncology, No. 52 Fucheng Road, Haidian District, 100142, Beijing, China.
Yang Du CAS Key Laboratory of Molecular Imaging, the State Key Laboratory of Management and Control for Complex Systems, Institute of Automation, Chinese Academy of Sciences, Beijing, 100190, China. University of Chinese Academy of Sciences, Beijing, 100080, China. Beijing Key Laboratory of Molecular Imaging, Beijing, 100190, China.
Jie Tian CAS Key Laboratory of Molecular Imaging, the State Key Laboratory of Management and Control for Complex Systems, Institute of Automation, Chinese Academy of Sciences, Beijing, 100190, China. University of Chinese Academy of Sciences, Beijing, 100080, China. Beijing Key Laboratory of Molecular Imaging, Beijing, 100190, China. Beijing Advanced Innovation Center for Big Data-Based Precision Medicine, School of Medicine, Beihang University, Beijing, 100191, China. Engineering Research Center of Molecular and Neuro Imaging of Ministry of Education, School of Life Science and Technology, Xidian University, Xi'an, 710126, Shaanxi, China.

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Beckmann S, Simanowski JH. Update in Contrast-Enhanced Ultrasound. Visc Med 2020;36:476-486. [PMID: 33447604 PMCID: PMC7768106 DOI: 10.1159/000511352] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2020] [Accepted: 09/03/2020] [Indexed: 12/21/2022] Open

Abstract

BACKGROUND

The aim of modern medicine is to safely classify diseases for successful therapy without invasive measures. Sonography, computed tomography (CT), and magnetic resonance imaging (MRI) are potent imaging techniques. However, without contrast medium, the informative value of the 3 native methods is limited. The advantages of sonography are: no radiation exposure or previously known physically harmful interactions with tissue, proportionate disappearance of a contrast agent risk, no (probably irreversible) contrast agent deposits, and no risk of renal insufficiency. But, is that enough to compete with of even exceed CT and MRI?

SUMMARY

In this review, the state of the art of contrast-enhanced ultrasound (CEUS) in the abdominal cavity is presented. The remarkable diagnostic possibilities can unfortunately only be demonstrated here in a small number of impressive, typical case studies underpinned by the literature, so that, from one's own perspective, the full spectrum of CEUS can be used by oneself or initiated. Within the limits of physics, the real-time dynamics of CEUS enable conclusions to be drawn, so that with the current technology, sonography, including expansion by contrast, can be considered superior to other imaging methods. It is not uncommon for CEUS to have the value of a control and reference method.

KEY MESSAGES

Sonography very often enables reliable diagnostics. The introduction of a contrast agent in sonography has led to a quantum leap similar to that of other imaging techniques. Already natively, the real-time representation of dynamic events leads to a certain superiority, i.e., complete observation of the inflow and outflow phases of the contrast medium and the resulting diagnostic; tissue-specific differentiation options provide a unique selling point. Further advantages of the first-choice imaging diagnostic method are: a lack of radiation exposure, repeatability of the examination at any time, local independence, a negligible allergy rate compared to the contrast agents of other methods, and a lack of kidney and thyroid exposure or excluded deposits.

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da Fonseca LG, Reig M, Bruix J. Tyrosine Kinase Inhibitors and Hepatocellular Carcinoma. Clin Liver Dis 2020;24:719-737. [PMID: 33012455 DOI: 10.1016/j.cld.2020.07.012] [Citation(s) in RCA: 29] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]

Han X, Dong J, Liu Z, Wu B, Tian Y, Tan H, Cheng W. Quantitative dynamic contrast-enhanced ultrasound to predict intrahepatic recurrence of hepatocellular carcinoma after radiofrequency ablation: a cohort study. Int J Hyperthermia 2020;37:1066-1073. [PMID: 32924654 DOI: 10.1080/02656736.2020.1817576] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023] Open

Cruz M, Ferreira AA, Papanikolaou N, Banerjee R, Alves FC. New boundaries of liver imaging: from morphology to function. Eur J Intern Med 2020;79:12-22. [PMID: 32571581 DOI: 10.1016/j.ejim.2020.06.004] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/05/2020] [Revised: 05/20/2020] [Accepted: 06/04/2020] [Indexed: 12/12/2022]

Ultrasound Molecular Imaging With BR55, a Predictive Tool of Antiangiogenic Treatment Efficacy in a Chemo-Induced Mammary Tumor Model. Invest Radiol 2020;55:657-665. [DOI: 10.1097/rli.0000000000000661] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]

Chai W, Xie L, Zhao Q, Cheng C, Tian G, Jiang T, Wu P. Ultrasound and Contrast-enhanced Ultrasound Findings after Percutaneous Irreversible Electroporation of Hepatic Malignant Tumors. ULTRASOUND IN MEDICINE & BIOLOGY 2020;46:620-629. [PMID: 31924420 DOI: 10.1016/j.ultrasmedbio.2019.12.012] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/06/2019] [Revised: 12/06/2019] [Accepted: 12/12/2019] [Indexed: 06/10/2023]

Höner Zu Siederdissen C, Potthoff A. [Sonographic diagnostics of liver tumors]. Internist (Berl) 2020;61:115-122. [PMID: 31925480 DOI: 10.1007/s00108-019-00728-5] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]

Wege H, Li J, Ittrich H. Treatment Lines in Hepatocellular Carcinoma. Visc Med 2019;35:266-272. [PMID: 31602390 DOI: 10.1159/000501749] [Citation(s) in RCA: 28] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/01/2019] [Accepted: 06/25/2019] [Indexed: 12/31/2022] Open

Abstract

Background

Hepatocellular carcinoma (HCC) is the most frequent primary liver cancer and the second most lethal malignancy worldwide. In the Western world, HCC predominantly develops in patients with liver cirrhosis. Therefore, application of locoregional interventions and systemic agents should be based on an interdisciplinary evaluation, most importantly, taking the functional liver reserve into account. This review summarizes current treatment lines and novel strategies in the management of HCC. For the most part, randomized controlled trials and large meta-analyses are reported, with an emphasis on systemic therapies.

Summary

In patients with limited hepatic disease and sufficient liver function, resection and local ablation are the most frequently employed curative locoregional therapies. Due to recurrence rates of up to 70% within 5 years and in patients with compromised liver function not amenable to these local modalities, liver transplantation remains superior in terms of tumor control and long-term survival. However, its applicability is limited because of the increasing gap between available donor organs and patients on the waiting list. Transarterial chemoembolization is commonly employed to bridge patients to transplantation and also serves as standard of care for patients not suitable for other local therapies. Recently, various phase 3 trials have reported a clinical benefit for the tyrosine kinase inhibitors lenvatinib, regorafenib, and cabozantinib in HCC. In addition, ramucirumab, an angiostatic antibody, also improves survival in second-line systemic therapy. This opens new avenues in the sequential application of treatment lines, and thus early response assessment is necessary to fully utilize the clinical impact of locoregional therapies and systemic therapies and to shift patients to further treatment lines before hepatic deterioration.

Key Messages

Clinical decision-making in hepatocellular carcinoma is based on an interdisciplinary evaluation. Liver transplantation should always be considered as long-term curative treatment option, especially in T2 patients. In palliative treatment, early response assessment is required to advance patients to the next treatment line before decompensation.

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Comparison of dynamic contrast-enhanced magnetic resonance imaging and contrast-enhanced ultrasound for evaluation of the effects of sorafenib in a rat model of hepatocellular carcinoma. Magn Reson Imaging 2019;57:156-164. [DOI: 10.1016/j.mri.2018.11.012] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2018] [Revised: 10/25/2018] [Accepted: 11/17/2018] [Indexed: 12/11/2022]

Chen Q, Tang L, Liu N, Han F, Guo L, Guo S, Wang J, Liu H, Ye Y, Zhang L, Liu L, Wang P, Li Y, He Q, Yang X, Tang Q, Li Y, Liang Y, Sun X, Xie C, Mo Y, Guo Y, Sun R, Mo H, Cao K, Guo X, Zeng M, Mai H, Ma J. Famitinib in combination with concurrent chemoradiotherapy in patients with locoregionally advanced nasopharyngeal carcinoma: a phase 1, open-label, dose-escalation Study. Cancer Commun (Lond) 2018;38:66. [PMID: 30382933 PMCID: PMC6235389 DOI: 10.1186/s40880-018-0330-z] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/06/2018] [Accepted: 09/15/2018] [Indexed: 12/20/2022] Open

Abstract

BACKGROUND

Famitinib is a tyrosine kinase inhibitor against multiple targets, including vascular endothelial growth factor receptor 2/3, platelet-derived growth factor receptor, and stem cell factor receptor (c-kit). Previous studies have demonstrated anti-tumour activities of famitinib against a wide variety of advanced-stage solid cancers. We aimed to determine the safety and efficacy of famitinib with concurrent chemoradiotherapy (CCRT) in patients with locoregionally advanced nasopharyngeal carcinoma (NPC). We also evaluated the feasibility of contrast-enhanced ultrasound (D-CEUS) as a predictor of early tumour response to famitinib and to correlate functional parameters with clinical efficacy.

METHODS

The trial was conducted in subjects with stage III or IVa-b NPC using a 3 + 3 design of escalating famitinib doses. Briefly, subjects received 2 weeks of famitinib monotherapy followed by 7 weeks of famitinib plus CCRT. D-CEUS of the neck lymph nodes was performed at day 0, 8 and 15 after famitinib was administered before starting concurrent chemoradiotherapy. End points included safety, tolerability and anti-tumour activity.

RESULTS

Twenty patients were enrolled (six each for 12.5, 16.5 and 20 mg and two for 25 mg). Two patients in the 25 mg cohort developed dose-limiting toxicities, including grade 4 thrombocytopenia and grade 3 hypertension. The most common grade 3/4 adverse events were leukopenia, neutropenia and radiation mucositis. D-CEUS tests showed that more than 60% of patients achieved a perfusion parameter response after 2 weeks taking famitinib alone, and the parameter response was associated with disease improvement. In the famitinib monotherapy stage, three patients (15%) showed partial responses. The complete response rate was 65% at the completion of treatment and 95% 3 months after the treatment ended. After a median follow-up of 44 months, the 3-year progression-free survival (PFS) and distant metastasis-free survival were 70% and 75%, respectively. Subjects with a decrease of perfusion parameter response, such as peak intensity decreased at least 30% after 1 week of famitinib treatment, had higher 3-year PFS (90.9% vs. 44.4%, 95% CI 73.7%-100% vs. 11.9%-76.9%, P < 0.001) than those with an increase or a reduction of less than 30%.

CONCLUSIONS

The recommended famitinib dose for phase II trial is 20 mg with CCRT for patients with local advanced NPC. D-CEUS is a reliable and early measure of efficacy for famitinib therapies. Further investigation is required to confirm the effects of famitinib plus chemoradiotherapy.

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Affiliation(s)

Qiuyan Chen State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Sun Yat-sen University Cancer Center, Guangzhou, 510060, P. R. China.,Department of Nasopharyngeal Carcinoma, Sun Yat-sen University Cancer Center, Guangzhou, 510060, P. R. China
Linquan Tang State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Sun Yat-sen University Cancer Center, Guangzhou, 510060, P. R. China.,Department of Nasopharyngeal Carcinoma, Sun Yat-sen University Cancer Center, Guangzhou, 510060, P. R. China
Na Liu State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Sun Yat-sen University Cancer Center, Guangzhou, 510060, P. R. China
Feng Han State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Sun Yat-sen University Cancer Center, Guangzhou, 510060, P. R. China.,Department of Ultrasound, Sun Yat-sen University Cancer Center, Guangzhou, 510060, P. R. China
Ling Guo State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Sun Yat-sen University Cancer Center, Guangzhou, 510060, P. R. China.,Department of Nasopharyngeal Carcinoma, Sun Yat-sen University Cancer Center, Guangzhou, 510060, P. R. China
Shanshan Guo State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Sun Yat-sen University Cancer Center, Guangzhou, 510060, P. R. China.,Department of Nasopharyngeal Carcinoma, Sun Yat-sen University Cancer Center, Guangzhou, 510060, P. R. China
Jianwei Wang State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Sun Yat-sen University Cancer Center, Guangzhou, 510060, P. R. China.,Department of Ultrasound, Sun Yat-sen University Cancer Center, Guangzhou, 510060, P. R. China
Huai Liu Department of Radiation Oncology, Key Laboratory of Translational Radiation Oncology, Hunan Cancer Hospital and The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, 410013, P. R. China
Yanfang Ye Department of Science and Education, Sun Yat-sen Memorial Hospital, Guangzhou, 510120, P. R. China
Lu Zhang Department of Radiation Oncology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510120, P. R. China
Liting Liu State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Sun Yat-sen University Cancer Center, Guangzhou, 510060, P. R. China.,Department of Nasopharyngeal Carcinoma, Sun Yat-sen University Cancer Center, Guangzhou, 510060, P. R. China
Pan Wang State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Sun Yat-sen University Cancer Center, Guangzhou, 510060, P. R. China.,Department of Nasopharyngeal Carcinoma, Sun Yat-sen University Cancer Center, Guangzhou, 510060, P. R. China
Yingqin Li State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Sun Yat-sen University Cancer Center, Guangzhou, 510060, P. R. China
Qingmei He State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Sun Yat-sen University Cancer Center, Guangzhou, 510060, P. R. China
Xiaoqun Yang State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Sun Yat-sen University Cancer Center, Guangzhou, 510060, P. R. China
Qingnan Tang State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Sun Yat-sen University Cancer Center, Guangzhou, 510060, P. R. China.,Department of Nasopharyngeal Carcinoma, Sun Yat-sen University Cancer Center, Guangzhou, 510060, P. R. China
Yang Li State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Sun Yat-sen University Cancer Center, Guangzhou, 510060, P. R. China.,Department of Nasopharyngeal Carcinoma, Sun Yat-sen University Cancer Center, Guangzhou, 510060, P. R. China
YuJing Liang State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Sun Yat-sen University Cancer Center, Guangzhou, 510060, P. R. China.,Department of Nasopharyngeal Carcinoma, Sun Yat-sen University Cancer Center, Guangzhou, 510060, P. R. China
XueSong Sun State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Sun Yat-sen University Cancer Center, Guangzhou, 510060, P. R. China.,Department of Nasopharyngeal Carcinoma, Sun Yat-sen University Cancer Center, Guangzhou, 510060, P. R. China
Chuanmiao Xie State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Sun Yat-sen University Cancer Center, Guangzhou, 510060, P. R. China.,Department of Imaging, Sun Yat-sen University Cancer Center, Guangzhou, 510060, P. R. China
Yunxian Mo State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Sun Yat-sen University Cancer Center, Guangzhou, 510060, P. R. China.,Department of Imaging, Sun Yat-sen University Cancer Center, Guangzhou, 510060, P. R. China
Ying Guo State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Sun Yat-sen University Cancer Center, Guangzhou, 510060, P. R. China.,Department of Clinical Trial Center, Sun Yat-sen University Cancer Center, Guangzhou, 510060, P. R. China
Rui Sun State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Sun Yat-sen University Cancer Center, Guangzhou, 510060, P. R. China.,Department of Nasopharyngeal Carcinoma, Sun Yat-sen University Cancer Center, Guangzhou, 510060, P. R. China
Haoyuan Mo State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Sun Yat-sen University Cancer Center, Guangzhou, 510060, P. R. China.,Department of Nasopharyngeal Carcinoma, Sun Yat-sen University Cancer Center, Guangzhou, 510060, P. R. China
Kajia Cao State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Sun Yat-sen University Cancer Center, Guangzhou, 510060, P. R. China.,Department of Nasopharyngeal Carcinoma, Sun Yat-sen University Cancer Center, Guangzhou, 510060, P. R. China
Xiang Guo State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Sun Yat-sen University Cancer Center, Guangzhou, 510060, P. R. China.,Department of Nasopharyngeal Carcinoma, Sun Yat-sen University Cancer Center, Guangzhou, 510060, P. R. China
Musheng Zeng State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Sun Yat-sen University Cancer Center, Guangzhou, 510060, P. R. China
Haiqiang Mai State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Sun Yat-sen University Cancer Center, Guangzhou, 510060, P. R. China. .,Department of Nasopharyngeal Carcinoma, Sun Yat-sen University Cancer Center, Guangzhou, 510060, P. R. China.
Jun Ma State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Sun Yat-sen University Cancer Center, Guangzhou, 510060, P. R. China. .,Department of Radiation Oncology, Sun Yat-sen University Cancer Center, Guangzhou, 510060, P. R. China.

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Zhan Y, Zhou F, Yu X, Luo F, Liu F, Liang P, Cheng Z, Han Z, Yu J. Quantitative dynamic contrast-enhanced ultrasound may help predict the outcome of hepatocellular carcinoma after microwave ablation. Int J Hyperthermia 2018;35:105-111. [PMID: 30300039 DOI: 10.1080/02656736.2018.1483533] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022] Open

Marisi G, Cucchetti A, Ulivi P, Canale M, Cabibbo G, Solaini L, Foschi FG, De Matteis S, Ercolani G, Valgiusti M, Frassineti GL, Scartozzi M, Casadei Gardini A. Ten years of sorafenib in hepatocellular carcinoma: Are there any predictive and/or prognostic markers? World J Gastroenterol 2018;24:4152-4163. [PMID: 30271080 PMCID: PMC6158485 DOI: 10.3748/wjg.v24.i36.4152] [Citation(s) in RCA: 133] [Impact Index Per Article: 19.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/03/2018] [Revised: 08/06/2018] [Accepted: 08/24/2018] [Indexed: 02/06/2023] Open

Affiliation(s)

Giorgia Marisi Biosciences Laboratory, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola 47014, Italy
Alessandro Cucchetti Department of Medical and Surgical Sciences, Alma Mater Studiorum, University of Bologna, Bologna 40126, Italy General and Oncologic Surgery, Morgagni-Pierantoni Hospital, Forlì 47121, Italy
Paola Ulivi Biosciences Laboratory, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola 47014, Italy
Matteo Canale Biosciences Laboratory, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola 47014, Italy
Giuseppe Cabibbo Section of Gastroenterology, DI.BI.M.I.S., University of Palermo, Palermo 35628, Italy
Leonardo Solaini Department of Medical and Surgical Sciences, Alma Mater Studiorum, University of Bologna, Bologna 40126, Italy General and Oncologic Surgery, Morgagni-Pierantoni Hospital, Forlì 47121, Italy
Francesco G Foschi Department of Internal Medicine, Degli Infermi Hospital, Faenza 48018, Italy
Serena De Matteis Biosciences Laboratory, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola 47014, Italy
Giorgio Ercolani Department of Medical and Surgical Sciences, Alma Mater Studiorum, University of Bologna, Bologna 40126, Italy General and Oncologic Surgery, Morgagni-Pierantoni Hospital, Forlì 47121, Italy
Martina Valgiusti Department of Medical Oncology, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori IRCCS, Meldola 47014, Italy
Giovanni L Frassineti Department of Medical Oncology, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori IRCCS, Meldola 47014, Italy
Mario Scartozzi Department of Medical Oncology, University of Cagliari, Cagliari 45698, Italy
Andrea Casadei Gardini Department of Medical Oncology, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori IRCCS, Meldola 47014, Italy

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Nam K, Stanczak M, Lyshchik A, Machado P, Kono Y, Forsberg F, Shaw CM, Eisenbrey JR. Evaluation of Hepatocellular Carcinoma Transarterial Chemoembolization using Quantitative Analysis of 2D and 3D Real-time Contrast Enhanced Ultrasound. Biomed Phys Eng Express 2018;4:035039. [PMID: 29887989 DOI: 10.1088/2057-1976/aabb14] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]

Dynamic contrast-enhanced ultrasonography (D-CEUS) for the early prediction of bevacizumab efficacy in patients with metastatic colorectal cancer. Eur Radiol 2018;28:2969-2978. [PMID: 29417252 DOI: 10.1007/s00330-017-5254-5] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2017] [Revised: 11/30/2017] [Accepted: 12/18/2017] [Indexed: 12/16/2022]

Contrast-Enhanced Ultrasound of the Liver: Optimizing Technique and Clinical Applications. AJR Am J Roentgenol 2017;210:320-332. [PMID: 29220210 DOI: 10.2214/ajr.17.17843] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]

Del Prete M, Di Sarno A, Modica R, Lassandro F, Giorgio A, Bianco A, Muto M, Gasperi M, Del Prete F, Colao A, Montesarchio V, Faggiano A. Role of contrast-enhanced ultrasound to define prognosis and predict response to biotherapy in pancreatic neuroendocrine tumors. J Endocrinol Invest 2017;40:1373-1380. [PMID: 28667452 DOI: 10.1007/s40618-017-0723-x] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/22/2017] [Accepted: 06/23/2017] [Indexed: 12/13/2022]

Liver investigations: Updating on US technique and contrast-enhanced ultrasound (CEUS). Eur J Radiol 2017;96:65-73. [PMID: 29103478 DOI: 10.1016/j.ejrad.2017.08.029] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2017] [Revised: 06/15/2017] [Accepted: 08/28/2017] [Indexed: 12/15/2022]

Early prediction of tumor response to bevacizumab treatment in murine colon cancer models using three-dimensional dynamic contrast-enhanced ultrasound imaging. Angiogenesis 2017;20:547-555. [PMID: 28721500 DOI: 10.1007/s10456-017-9566-5] [Citation(s) in RCA: 24] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/09/2017] [Accepted: 07/13/2017] [Indexed: 12/18/2022]

Mogensen MB, Hansen ML, Henriksen BM, Axelsen T, Vainer B, Osterlind K, Nielsen MB. Dynamic Contrast-Enhanced Ultrasound of Colorectal Liver Metastases as an Imaging Modality for Early Response Prediction to Chemotherapy. Diagnostics (Basel) 2017;7:diagnostics7020035. [PMID: 28604623 PMCID: PMC5489955 DOI: 10.3390/diagnostics7020035] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2017] [Revised: 05/21/2017] [Accepted: 06/06/2017] [Indexed: 12/12/2022] Open

Ippolito D, Querques G, Okolicsanyi S, Franzesi CT, Strazzabosco M, Sironi S. Diagnostic value of dynamic contrast-enhanced CT with perfusion imaging in the quantitative assessment of tumor response to sorafenib in patients with advanced hepatocellular carcinoma: A feasibility study. Eur J Radiol 2017;90:34-41. [PMID: 28583645 DOI: 10.1016/j.ejrad.2017.02.027] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/09/2016] [Revised: 02/11/2017] [Accepted: 02/15/2017] [Indexed: 02/05/2023]

Abstract

PURPOSE

To investigate the feasibility of perfusion-CT (p-CT) measurements in quantitative assessment of hemodynamic changes related to sorafenib in patients with advanced hepatocellular carcinoma (HCC).

MATERIALS AND METHODS

Twenty-two patients with advanced HCC underwent p-CT study (256-MDCT scanner) before and 2 months after sorafenib administration. Dedicated perfusion software generated a quantitative map of arterial and portal perfusion and calculated the following perfusion parameters in target liver lesion: hepatic perfusion (HP), time-to-peak (TTP), blood volume (BV), arterial perfusion (AP), and hepatic perfusion index (HPI). After the follow-up scan, patients were categorized as responders and non-responders, according to mRECIST. Perfusion values were analyzed and compared in HCC lesions and in the cirrhotic parenchyma (n=22), such as between baseline and follow-up in progressors and non-progressors.

RESULTS

Before treatment, all mean perfusion values were significantly higher in HCC lesions than in the cirrhotic parenchyma (HP 47.8±17.2 vs 13.3±6.3mL/s per 100g; AP 47.9±18.1 vs 12.9±10.7mL/s; p<0.001). The group that responded to sorafenib (n=17) showed a significant reduction of values in HCC target lesions after therapy (HP 29.2±23.3 vs 48.1±15.1; AP 29.4±24.6 vs 49.2±17.4; p<0.01), in comparison with the non-responder group (n=5) that demonstrated no significant variation before and after treatment of HP (46.9±25.1 vs 46.7±24.1) and AP (43.4±21.7 vs 43.5±24.6). Among the responder group, HP percentage variation (Δ) in target lesions, during treatment, showed a significantly different (p=0.04) ΔHP in the group with complete response (79%) compared to the group with partial response or stable disease (16%).

CONCLUSIONS

p-CT technique can be used for HCC quantitative assessment of changes related to anti-angiogenic therapy. Identification of response predictors might help clinicians in selection of patients who may benefit from targeted-therapy allowing for optimization of individualized treatment.

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Hyvelin JM, Gaud E, Costa M, Helbert A, Bussat P, Bettinger T, Frinking P. Characteristics and Echogenicity of Clinical Ultrasound Contrast Agents: An In Vitro and In Vivo Comparison Study. JOURNAL OF ULTRASOUND IN MEDICINE : OFFICIAL JOURNAL OF THE AMERICAN INSTITUTE OF ULTRASOUND IN MEDICINE 2017;36:941-953. [PMID: 28240842 DOI: 10.7863/ultra.16.04059] [Citation(s) in RCA: 43] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/26/2016] [Accepted: 08/05/2016] [Indexed: 06/06/2023]

Abstract

OBJECTIVES

To compare physicochemical characteristics and in vitro and in vivo contrast-enhanced ultrasound imaging performance of 3 commercially available ultrasound contrast agents: SonoVue (Bracco Imaging SpA, Colleretto Giacosa, Italy; also marketed as Lumason in the USA), Definity (Lantheus Medical Imaging, North Billerica, MA) and Optison (GE Healthcare AS, Oslo, Norway).

METHODS

Physicochemical characteristics were measured with a Multisizer Coulter Counter (Beckman Coulter, Fullerton, CA). Two ultrasound systems (Aplio 500; Toshiba Medical Systems Corp, Tochigi-ken, Japan; and Logiq E9; GE Healthcare, Little Chalfont, England) were used with different transducers. Contrast enhancement was measured in vitro by dose-ranging measurements using a custom-built beaker setup; in vivo imaging performances were compared in pigs (heart and liver) and rabbits (liver). Quantitative analyses were performed with VueBox quantification software (Bracco Suisse SA, Plan-les-Ouates, Switzerland).

RESULTS

Measured physicochemical characteristics were in agreement with those provided by the manufacturers. In vitro data demonstrated that the performance of SonoVue was similar to or better than that of Definity but superior to Optison (normalized scattered power 2- to 10-fold higher with SonoVue). Similar results were obtained in vivo, although the duration of enhancement in the pig heart was longer for SonoVue compared to Definity, and quantitative analysis revealed higher enhancement for SonoVue (1.5-fold increase). For liver imaging, SonoVue and Definity showed similar contrast enhancement and duration of enhancement, but compared to Optison, both peak enhancement and duration of enhancement were superior for SonoVue (up to 2-fold increase).

CONCLUSIONS

Imaging performance of SonoVue was similar to or slightly better than that of Definity, but it was superior to Optison for the conditions used in this study.

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Ye XD, Yuan Z, Zhang J, Yuan Z. Radiological biomarkers for assessing response to locoregional therapies in hepatocellular carcinoma: From morphological to functional imaging (Review). Oncol Rep 2017;37:1337-1346. [PMID: 28184942 DOI: 10.3892/or.2017.5420] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2016] [Accepted: 01/16/2017] [Indexed: 11/05/2022] Open

Eschbach RS, Clevert DA, Hirner-Eppeneder H, Ingrisch M, Moser M, Schuster J, Tadros D, Schneider M, Kazmierczak PM, Reiser M, Cyran CC. Contrast-Enhanced Ultrasound with VEGFR2-Targeted Microbubbles for Monitoring Regorafenib Therapy Effects in Experimental Colorectal Adenocarcinomas in Rats with DCE-MRI and Immunohistochemical Validation. PLoS One 2017;12:e0169323. [PMID: 28060884 PMCID: PMC5217974 DOI: 10.1371/journal.pone.0169323] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2016] [Accepted: 12/15/2016] [Indexed: 12/24/2022] Open

Abstract

OBJECTIVES

To investigate contrast-enhanced ultrasound (CEUS) with VEGFR2-targeted microbubbles for monitoring therapy effects of regorafenib on experimental colon carcinomas in rats with correlation to dynamic contrast-enhanced MRI (DCE-MRI) and immunohistochemistry.

MATERIALS AND METHODS

Human colorectal adenocarcinoma xenografts (HT-29) were implanted subcutaneously in n = 21 (n = 11 therapy group; n = 10 control group) female athymic nude rats (Hsd: RH-Foxn1rnu). Animals were imaged at baseline and after a one-week daily treatment with regorafenib or a placebo (10 mg/kg bodyweight), using CEUS with VEGFR2-targeted microbubbles and DCE-MRI. In CEUS tumor perfusion was assessed during an early vascular phase (wash-in area under the curve = WiAUC) and VEGFR2-specific binding during a late molecular phase (signal intensity after 8 (SI8min) and 10 minutes (SI10min)), using a conventional 15L8 linear transducer (transmit frequency 7 MHz, dynamic range 80 dB, depth 25 mm). In DCE-MRI functional parameters plasma flow (PF) and plasma volume (PV) were quantified. For validation purposes, CEUS parameters were correlated with DCE-MRI parameters and immunohistochemical VEGFR2, CD31, Ki-67 and TUNEL stainings.

RESULTS

CEUS perfusion parameter WiAUC decreased significantly (116,989 ± 77,048 a.u. to 30,076 ± 27,095a.u.; p = 0.005) under therapy with no significant changes (133,932 ± 65,960 a.u. to 84,316 ± 74,144 a.u.; p = 0.093) in the control group. In the therapy group, the amount of bound microbubbles in the late phase was significantly lower in the therapy than in the control group on day 7 (SI8min: 283 ± 191 vs. 802 ± 460 a.u.; p = 0.006); SI10min: 226 ± 149 vs. 645 ± 461 a.u.; p = 0.009). PF and PV decreased significantly (PF: 147 ± 58 mL/100 mL/min to 71 ± 15 mL/100 mL/min; p = 0.003; PV: 13 ± 3% to 9 ± 4%; p = 0.040) in the therapy group. Immunohistochemistry revealed significantly fewer VEGFR2 (7.2 ± 1.8 vs. 17.8 ± 4.6; p < 0.001), CD31 (8.1 ± 3.0 vs. 20.8 ± 5.7; p < 0.001) and Ki-67 (318.7 ± 94.0 vs. 468.0 ± 133.8; p = 0.004) and significantly more TUNEL (672.7 ± 194.0 vs. 357.6 ± 192.0; p = 0.003) positive cells in the therapy group. CEUS parameters showed significant (p < 0.05) correlations to DCE-MRI parameters and immunohistochemistry.

CONCLUSIONS

CEUS with VEGFR2-targeted microbubbles allowed for monitoring regorafenib functional and molecular therapy effects on experimental colorectal adenocarcinomas with a significant decline of CEUS and DCE-MRI perfusion parameters as well as a significant reduction of specifically bound microbubbles under therapy, consistent with a reduced expression of VEGFR2.

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von Felden J, Schulze K, Gil-Ibanez I, Werner T, Wege H. First- and Second-Line Targeted Systemic Therapy in Hepatocellular Carcinoma-An Update on Patient Selection and Response Evaluation. Diagnostics (Basel) 2016;6:E44. [PMID: 27916795 PMCID: PMC5192519 DOI: 10.3390/diagnostics6040044] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2016] [Revised: 11/22/2016] [Accepted: 11/23/2016] [Indexed: 12/30/2022] Open

Amin S, Bathe OF. Response biomarkers: re-envisioning the approach to tailoring drug therapy for cancer. BMC Cancer 2016;16:850. [PMID: 27814715 PMCID: PMC5097425 DOI: 10.1186/s12885-016-2886-9] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2016] [Accepted: 10/25/2016] [Indexed: 12/15/2022] Open

Malone CD, Mattrey RF, Fetzer DT. Contrast-Enhanced Ultrasound (CEUS) for the Diagnosis and Management of Hepatocellular Carcinoma: Current Status and Future Trends. ACTA ACUST UNITED AC 2016. [DOI: 10.1007/s11901-016-0324-8] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]

Wang H, Lutz AM, Hristov D, Tian L, Willmann JK. Intra-Animal Comparison between Three-dimensional Molecularly Targeted US and Three-dimensional Dynamic Contrast-enhanced US for Early Antiangiogenic Treatment Assessment in Colon Cancer. Radiology 2016;282:443-452. [PMID: 27490690 DOI: 10.1148/radiol.2016160032] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]

Abstract

Purpose To perform an intra-animal comparison between (a) three-dimensional (3D) molecularly targeted ultrasonography (US) by using clinical-grade vascular endothelial growth factor receptor 2 (VEGFR2)-targeted microbubbles and (b) 3D dynamic contrast material-enhanced (DCE) US by using nontargeted microbubbles for assessment of antiangiogenic treatment effects in a murine model of human colon cancer. Materials and Methods Twenty-three mice with human colon cancer xenografts were randomized to receive either single-dose antiangiogenic treatment (bevacizumab, n = 14) or control treatment (saline, n = 9). At baseline and 24 hours after treatment, animals were imaged with a clinical US system equipped with a clinical matrix array transducer by using the following techniques: (a) molecularly targeted US with VEGFR2-targeted microbubbles, (b) bolus DCE US with nontargeted microbubbles, and (c) destruction-replenishment DCE US with nontargeted microbubbles. VEGFR2-targeted US signal, peak enhancement, area under the time-intensity curve, time to peak, relative blood volume (rBV), relative blood flow, and blood flow velocity were quantified. VEGFR2 expression and percentage area of blood vessels were assessed ex vivo with quantitative immunofluorescence and correlated with corresponding in vivo US parameters. Statistical analysis was performed with Wilcoxon signed rank tests and rank sum tests, as well as Pearson correlation analysis. Results Molecularly targeted US signal with VEGFR2-targeted microbubbles, peak enhancement, and rBV significantly decreased (P ≤ .03) after a single antiangiogenic treatment compared with those in the control group; similarly, ex vivo VEGFR2 expression (P = .03) and percentage area of blood vessels (P = .03) significantly decreased after antiangiogenic treatment. Three-dimensional molecularly targeted US signal correlated well with VEGFR2 expression (r = 0.86, P = .001), and rBV (r = 0.71, P = .01) and relative blood flow (r = 0.78, P = .005) correlated well with percentage area of blood vessels, while other US perfusion parameters did not. Conclusion Three-dimensional molecularly targeted US and destruction-replenishment 3D DCE US provide complementary molecular and functional in vivo imaging information on antiangiogenic treatment effects in human colon cancer xenografts compared with ex vivo reference standards. ^© RSNA, 2016 Online supplemental material is available for this article.

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Lo GM, Al Zahrani H, Jang HJ, Menezes R, Hudson J, Burns P, McNamara MG, Kandel S, Khalili K, Knox J, Rogalla P, Kim TK. Detection of Early Tumor Response to Axitinib in Advanced Hepatocellular Carcinoma by Dynamic Contrast Enhanced Ultrasound. ULTRASOUND IN MEDICINE & BIOLOGY 2016;42:1303-1311. [PMID: 27033332 DOI: 10.1016/j.ultrasmedbio.2016.01.025] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/04/2015] [Revised: 01/27/2016] [Accepted: 01/30/2016] [Indexed: 06/05/2023]