Imaging Hepatocellular Carcinoma:

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1 Imaging Hepatocellular Carcinoma: The Role of Radiology in Diagnosis & Treatment Rachel Jimenez Gillian Lieberman, MD March 2008

2 Clinical Presentation 50 year old man with chronic Hepatitis C & cirrhosis, awaiting transplant What is the role of imaging in the pre-transplant patient? Monitoring of a liver transplant candidate includes: Blood tests to determine liver & kidney function EKG, Echocardiogram, & Cardiac stress test to assess heart function Chest X-ray (CXR) and pulmonary function test to assess lung health Abdominal ultrasound (US) to view the liver & evaluate vessel patency Computed Tomography (CT) to assess liver size and anatomy Magnetic Resonance Imaging (MRI) to evaluate for lesions

3 Ultrasound (US) Best FIRST test in pre-transplant surveillance Performed every 3-6 months to look for new lesions or changes to vessel patency Advantages: High availability Low cost Non-invasive High Specificity Limitations: Operator experience Obese patients Low sensitivity) Limited differentiation of soft tissue Bialecki, E. & Di Bisceglie, HPB, 2005.

4 Our Patient: Screening Liver Ultrasound Sagittal View PACS, BIDMC Isoechoic mass in Segment VIII

5 Our Patient: Screening Liver Ultrasound Transverse View PACS, BIDMC A hypoechoic rim is visible around the mass

6 Our Patient: Screening Liver Ultrasound Doppler PACS, BIDMC Portal vein & major vessels are patent

7 Anatomy: Couinaud Classification

8 Differential diagnosis: Solitary liver mass in US Benign: Adenoma Hemangioma Hamartoma Fatty Infiltration Focal Nodular Hyperplasia Regenerative nodular hyperplasia Malignant: Hepatocellular carcinoma Hepatoblastoma Hemangiosarcoma Cholangiocarcinoma Leiomyosarcoma Hemangiopericytoma Metastases M. M. Reeder and B Felson, Gamuts in Radiology, Springer-Verlag Telos, 3 rd edition, 1993.

9 Differential diagnosis: Solitary liver mass in US Isoechoic Benign: Adenoma Hemangioma Hamartoma Fatty Infiltration Focal Nodular Hyperplasia Regenerative nodular hyperplasia Malignant: Hepatocellular carcinoma Hepatoblastoma Hemangiosarcoma Cholangiocarcinoma Leiomyosarcoma Hemangiopericytoma Metastases M. M. Reeder and B Felson, Gamuts in Radiology, Springer-Verlag Telos, 3 rd edition, 1993.

10 Differential diagnosis: Solitary liver mass in US Isoechoic Hypoechoic rim Benign: Adenoma Hemangioma Hamartoma Fatty Infiltration Focal Nodular Hyperplasia Regenerative nodular hyperplasia Malignant: Hepatocellular carcinoma Hepatoblastoma Hemangiosarcoma Cholangiocarcinoma Leiomyosarcoma Hemangiopericytoma Metastases Herbay, A., Frieling, T., Niederau, C., & Hussinger, D. (1997) AJR, 169(9): M. M. Reeder and B Felson, Gamuts in Radiology, Springer-Verlag Telos, 3 rd edition, 1993.

11 Magnetic Resonance Imaging (MRI) BEST test for evaluating abnormal ultrasound in patients with known liver disease Useful in distinguishing benign from malignant masses using T2 non-contrast & T1 phase-contrast sequences Advantages: High sensitivity (82-96)% High resolution Limitations: Expensive Time Intensive Patient Dependent Bialecki, E. & Di Bisceglie, HPB, 2005.

12 Our Patient: Liver Mass on T1 Abdominal MRI Non-contrast T1 PACS, BIDMC A cirrhotic liver, enlarged spleen, and ascites

13 Our Patient: Liver Mass on T2 Abdominal MRI Non-contrast T2 PACS, BIDMC Ill-defined round 5cm lesion with increased signal

14 Our Patient: 3 Phase Contrast Enhanced T1 MRI Arterial Phase Portal Venous Phase Delayed Phase PACS, BIDMC Lesion demonstrates enhancement during the arterial phase and washout during the venous phase

15 Comparison Patient: Focal Nodular Hyperplasia on MRI Contrast our patient s MRI with this patient s. MRI demonstrating the typical appearance of FNH on C+ MRI Non-contrast T2 Hyperintense Enhancement of stellate scar Delayed phase T1 Hypointense Enhancement of stellate scar

16 MRI Summary 5 cm mass in segment VIII of liver No lymphadenopathy or vessel involvement Increased signal intensity during arterial phase Decreased signal intensity during venous phase No evidence of stellate scar Patient history Diagnosis: Hepatocellular Carcinoma* * Pathology confirmed diagnosis of HCC

17 Hepatocellular Carcinoma Hepatocellular carcinoma (HCC) is a primary tumor of hepatocytes that develops in the setting of chronic liver disease. Median age group is & predominates in men HBV & HCV cause > 90% of HCC's worldwide Patients with HCC usually have no physical symptoms Common sites of metastasis include lung & bone Median survival is 5% at 5 years Hagop et al., MD Anderson Manual of Medical Oncology, 2006.

18 Staging of HCC American Joint Committee on Cancer-TNM System Stage TNM Scheme I T1N0M0 Single tumor <2cm II T2N0M0 >2cm or single tumor <2cm + vascular invasion IIIA T3N0M0 Single tumor >5cm or >2cm + vascular invasion IIIB T1-3N1M0 Positive Regional Lymph Node IVA T4N0-1M0 Multiple tumors involving major vessels/multiple lobes IVB T1-4N0-1M1 Remote Metastasis Vauthey et al., J Clin Oncol, 2002.

19 Our Patient: Normal CXR The lungs are clear. PACS, BIDMC AP view of the thorax Left lateral view of the thorax

20 Our Patient: Normal RN Bone Scan No evidence of MDP avid osseous metastases. Anterior Posterior PACS, BIDMC Bone Scintigraphy: Technetium, 99 Tc m

21 Staging of HCC American Joint Committee on Cancer-TNM System Stage TNM Scheme I T1N0M0 Single tumor <2cm II T2N0M0 >2cm or single tumor <2cm + vascular invasion IIIA T3N0M0 Single tumor >5cm or >2cm + vascular invasion IIIB T1-3N1M0 Positive Regional Lymph Node IVA T4N0-1M0 Multiple tumors involving major vessels/multiple lobes IVB T1-4N0-1M1 Remote Metastasis Vauthey et al., J Clin Oncol, 2002.

22 Treatment Liver transplantation 5 year survival 60-70%, limited to Stage I & II HCC Surgical resection 5 year survival 40-50%, limited to single, welldemarcated, and anatomically accessible lesions Percutaneous destruction e.g. Radiofrequency ablation 5 year survival ~40%, limited to lesions measuring <3cm Transcatheter Arterial Chemoembolization (TACE) OUR PATIENT Modest survival benefit, Treatment of choice for single intrahepatic lesions >5cm Hagop et al., MD Anderson Manual of Medical Oncology, 2006.

23 Our Patient: Transcatheter Arterial Chemoembolization PACS, BIDMC A catheter is inserted into the hepatic artery via the femoral artery

24 Our Patient: Transcatheter Arterial Chemoembolization PACS, BIDMC Contrast is injected to confirm proper placement of catheter

25 Our Patient: Transcatheter Arterial Chemoembolization PACS, BIDMC Chemotherapy & embolic agents are mixed & injected together.

26 Our Patient: CT Post-procedure Imaging Used within 24 hours of procedure to assess for effective delivery of chemotherapy to mass PACS, BIDMC successful chemoembolization of the hypervascular mass Bialecki, E. & Di Bisceglie, HPB, 2005.

27 Our Patient: CT at 3 Month Follow-up BEST test for evaluation of known hepatic malignancy & for detecting extra- hepatic metastases PACS, BIDMC Interval decrease in mass size no new liver lesions. Oliva & Saini, Cancer Imaging, 2004.

28 Summary Radiology vital in the medical management, diagnosis, & therapy of Hepatocellular Carcinoma Ultrasound - Assessing for lesion & vessel patency Magnetic resonance imaging - Characterizing known lesion Nuclear Scintigraphy/Plain Film - Tumor staging Hepatic Angiography - Visualization for interventional therapy Computed tomography (CT) - Evaluation of tumor progression post-therapy

29 Acknowledgments Gillian Lieberman, MD Maria Levantakis Andrew Hines-Peralta, MD Diana Ferris, MD Alice Lee, MD

30 References M. M. Reeder and B Felson, Gamuts in Radiology, 3 rd edition, Springer-Verlag Telos, Bialecki, E. & Di Bisceglie, A. Diagnosis of hepatocellular carcinoma. HPB (Oxford). 2005; 7(1): Bruix J, Sherman M, Lloret JM, Beaugrand M, Lencioni R, Burroughs AK, et al. Clinical management of hepatocellular carcinoma. Conclusions of the Barcelona-2000 EASL conference. European Association for the Study of the Liver. J Hepatol. 2001;35:421 Hagop M. Kantarjian, Robert A. Wolff, Charles A. Koller (Eds.) The MD Anderson Manual of Medical Oncology. Chapter 15, Pancreatic Cancer and Hepatobiliary Malignancies. New York, McGraw- Hill, Herbay, A., Frieling, T., Niederau, C., & Hussinger, D. (1997) Solitary Hepatic Lesions with a Hypoechoic Rim: Value of Color Doppler Sonography. AJR, 169(9): Maria Raquel Oliva, M. & Saini, S. Liver cancer imaging: role of CT, MRI, US and PET. Cancer Imaging. 2004; 4. S42-S46. M. M. Reeder and B Felson, Gamuts in Radiology, 3 rd edition, Springer-Verlag Telos, Vauthey JN, Lauwers GY, Esnaola NF. Simplified staging for hepatocellular carcinoma. J Clin Oncol 2002;20:

Hepatocellular Carcinoma: A Guide to Screening and Diagnosis

February 2012 Hepatocellular Carcinoma: A Guide to Screening and Diagnosis Reid Merryman, Harvard Medical School Year III Agenda Hepatocellular carcinoma (HCC) introduction Index patient: clinical presentation