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

addition to potentially curative treatment for HCC.The prognosis of patients undergoing OLT due to HCC has greatly improved after the introduction of the Milan criteria [32], which determine eligibility for OLT based on the maximal number and size of HCC lesions. Specifically, a patient is suitable for transplantation if a single tumour is present and does not exceed 5 cm in size (largest diameter), or if up to three nodules with a diameter ≤ 3 cm are present [33]. While patients within theMilan criteria are considered eligible for primary OLT, patients outside theMilan Criteria may be considered for OLT based on an individual evaluation that includes the response to local ablative treatment [34]. A limitation is the shortage of liver grafts resulting in a considerable delay in treatment for many patients while waiting for donor organs. In HCC patients, bridging therapies are frequently applied to avoid tumour progression which could result in delisting. Moreover, it was shown that successful local ablative therapy before liver transplantation is an independent statistically significant factor for long-term tumour-related survival for patients with HCC in cirrhosis [35]. Several local ablative treatments are available as treatment options for either downstaging or bridging before OLT. Most commonly, TACE or RFA are used as bridging- therapies with good results [36]. However, for a subset of patients, these treatment options are not ideal for reasons such as tumour size, localisation or proximity to adjacent structures. In these cases, brachytherapy may be an alternative bridging approach until liver transplantation with good local control rates [2,37–40]. Cholangiocellular carcinoma In patients with intrahepatic cholangiocarcinoma, surgery is the only potentially curative treatment option. However, in patients with unresectable disease, historical median overall survival (OS) and intrahepatic progression free survival (PFS) rates after chemotherapy alone remain poor [41]. Therefore, after induction chemotherapy, consolidative local treatment should be considered for unresectable intrahepatic cholangiocarcinoma to improve local control and intrahepatic PFS and mitigate tumour-related liver failure. Liver failure results from obstruction of the portal or hepatic veins and/or bile ducts due to tumour progression [42]. Therefore, local ablative or locoregional image-guided procedures with different therapeutic goals have gained importance in the treatment of intrahepatic cholangiocarcinoma. Although local ablative procedures, such as microwave ablation or RFA, interstitial HDR brachytherapy or SBRT aim at complete local control in the sense of full remission, these locoregional procedures usually achieve only partial remission. They are therefore mostly used in palliation or, less frequently, neoadjuvantly. Examples include both TACE and SIRT. In patients in whom surgery is not an option due to tumour size, location, multifocal disease or restricted performance status, local ablative procedures are an alternative local treatment option and interstitial HDR brachytherapy could increase OS. Retrospective studies support the efficacy of brachytherapy as consolidation therapy with excellent local control rates. Brachytherapy is able to achieve adequate local control rates independent of the tumour diameter, even in larger tumours (> 4 cm), as long as a good coverage with a therapeutic dose could be achieved [43]. Another option is the use of HDR brachytherapy as a salvage option in case of recurrences after surgical therapy [44]. An important component of multidisciplinary discussion is the choice, timing and sequencing of planned systemic therapy in combination with brachytherapy. Oligometastastic disease The concept of OMD is today supported by a growing number of high-quality trials. Three randomized trials reported an

improvement in PFS [45] or OS [46,47] by the addition of local metastases-directed therapy to standard-of-care systemic therapy. Based on these positive studies, the concept of radical local treatment with curative intent in OMD has been rapidly implemented by the oncology community. While the exact definition of oligometastatic disease remains controversial, there is general agreement that more aggressive local treatments are desirable in patients with low metastatic burden. Moreover, the development of highly potent systemic therapies has contributed to a paradigm shift from the exclusive palliative status of metastasized disease to a potentially curable condition in an increasing number of patients with solid tumours. This has renewed interest in locally ablative treatment options for patients with limitedmetastatic burden in combination with systemic treatments. For unresectable liver metastases, a variety of other locally ablative treatments, the so-called "toolbox of locally ablative treatments," can be used [48]. A phase II study reported longer survival for patients who underwent thermal ablation of unresectable liver metastases compared with systemic treatment alone [47]. Two established radiotherapy methods are currently available for the treatment of liver metastases: either external beam SBRT or minimally invasive HDR interstitial brachytherapy [2]. While SBRT is a widely used technique that is frequently employed in the treatment of various anatomical regions, including brainmetastases, lung metastases, liver metastases, or bone metastases - interstitial HDR brachytherapy of the liver is generally underutilized, although it is a well-established radiation technique. Brachytherapy is an excellent tool to deliver very high doses directly to liver lesions with low morbidity [49].

7. TUMOUR AND TARGET VOLUMES

Target delineation includes gross tumour volume (GTV) with an additional margin of 3 – 5 mm for the clinical target volume (CTV), depending on visualization quality of the GTV. The GTV is contoured using additional pre-treatment diagnostic imaging (CTwith i.v. contrast or liver specificMRI with hepatocyte specific contrast). In individual cases, image fusion with diagnostic PET or MRI images may be necessary for proper target definition.

Figure 3: Exemplar target definition and OAR contouring. Red: PTV, dark red: liver, grey: portal vein, blue: truncus coeliacus