28 Primary and secondary liver malignancies

Primary and secondary liver malignancies

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THE GEC ESTROHANDBOOKOF BRACHYTHERAPY | Part II Clinical Practice Version 1 - 15/07/2022

and in Southeast Asia the liver fluke infections [13]. There are significant differences in surgery and locoregional therapy between these tumours. The main approach to curative therapy is complete surgical resection, although this is only possible in 30-50% of patients [14]. Because all bile duct cancers are rare tumours that require complex multidisciplinary therapy, treatment decisions should be made in a specialized multidisciplinary team. Hellman and Weichselbaum first described oligometastatic disease (OMD) in 1995 as a distinct cancer stage between locally confined and systemic metastatic disease [15]. While significant heterogeneity exists in the current OMD definitions in the literature, a recent ESTRO-ASTRO consensus defined OMD as 1–5 metastatic lesions, a controlled primary tumour being optional, but where all metastatic sites must be safely treatable [16]. However, because no biomarker is clinically available to identify patients with true oligometastatic disease, the diagnosis of oligometastatic disease is based solely on imaging findings. A small number of metastases on imaging could represent different clinical scenarios associated with different prognoses and requiring different treatment strategies [17]. The ESTRO-EORTC has made an attempt to classify these different clinical situations of OMD, considering scenarios of induced oligometastatic disease (history of polymetastatic disease) and genuine oligometastatic disease (no history of polymetastatic disease). In addition, oligorecurrence, oligoprogression, and oligopersistence were subdivided, taking into account whether oligometastatic disease was diagnosed during a treatment-free interval or during active systemic therapy and whether or not an oligometastatic lesion had progressed on current imaging. Preprocedural imaging is key in the identification of primary or secondary liver malignancies suitable for brachytherapy. Most commonly, patients with metastatic cancer after previous chemotherapy and/or surgery and either stable or new liver metastasis will be referred for brachytherapy of the liver for consolidation or therapy intensification. MRI of the liver with gadoxetic acid or PET/CT increase sensitivity towards smaller metastasis and thus provide a clearer picture of the total tumour burden in metastatic liver disease [18]. Concerning primary liver malignancies, for instance HCC, MRI with gadoxetic acid and multiphase imaging including late phase imaging allow for tumour burden estimation with high specificity, high accuracy and even the detection of potential precursor lesions, when the European association for the study of the liver (EASL) criteria are applied [19–21]. Routine staging CT, MRI and, depending on availability and suspected tumour type, PET/CT, may be combined to provide information for the key questions before moving forward with brachytherapy: 1. Is there evidence of systemic disease? 2. Are previous malignancies known? 3. Is the nature of the liver lesion proven - visually or histologically and is a biopsy warranted? 4. Are tumour size and lesion number favoring other treatments? 5. Is transplantation an option? The latter questions especially should be discussed in an interdisciplinary tumour board and specific recommendations 5. WORK UP

Figure 2: Liver anatomy and vascular structures. AA: Aorta abdominalis, TC: Truncus coeliacus, AHC: Arteria hepatica communis, AL: Arteria lienalis, AHP: Arteria hepatica propria, AHD: Arteria hepatica dextra, AES: Arteria epigastrica superior, VCI: Vena cava inferior, PV: Vena porta, AG: adrenal gland, CR: Costodiaphragmatic recess, C9-C12: ribs 9-12, L1: lumbar vertebra L1

4. PATHOLOGY

Indications for liver brachytherapy include primary liver malignancies such as HCC or CCC and liver oligometastases from various origins. HCC is the most common primary liver malignancy (>80%) and mostly develops on the background of pre-existing liver cirrhosis or chronic liver disease [7]. It is the sixth most common malignancy and fourthmost common cause of cancer mortality worldwide [8]. The incidence varies geographically with Asia having the highest incidence worldwide (72.5%), followed by Europe (9.8%), Africa (7.7%), North America (5%), Latin America and the Caribbean (4.6%) and Oceania (0.4%) [9]. Risk factors include chronic liver disease leading to cirrhosis, like chronic viral hepatitides (HBV and HCV), heavy alcohol consumption or non-alcoholic fatty liver disease [10]. The treatment of HCC is stage dependent and determined by several variables, including liver function and performance status, in addition to the number and size of lesions. Biliary cancers are a rare and inhomogeneous tumour entity, accounting for less than 3% of all gastrointestinal malignancies [11]. There are significant geographic differences in the overall incidence of biliary cancers. They occur rarely in Europe, Australia and the USA with an incidence of 0.3-3.5/10 5 population. In Asian countries with frequent liver fluke infections, the incidence is much higher [12]. The most common histologic subtype of cholangiocarcinoma in all locations is adenocarcinoma with a biliary differentiation. They are divided according to their location into intrahepatic, perihilar, and distal bile duct cancers. The risk factors differ depending on the location. The main risk factors for intrahepatic carcinoma of the bile ducts correspond to those for hepatocellular carcinoma, i.e. primarily liver cirrhosis and hepatitis B or C infections. For extrahepatic carcinoma of the bile ducts, chronic inflammation of the bile ducts has been identified as a risk factor, especially primary sclerosing cholangitis and other strictures of the bile ducts with biliary cysts and Caroli syndrome,