28 Primary and secondary liver malignancies

Primary and secondary liver malignancies

6

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

6. INDICATIONS, CONTRA-INDICATIONS

(European Society for Medical Oncology [ESMO] or European Association for the Study of the Liver [EASL] Guidelines) should be followed. This also includes a critical assessment of patient fitness for surgery and brachytherapy. Frequently used indices to assess the patient’s performance are ECOG status and the Karnofsky index. Furthermore, laboratorymeasurements of GGT, GOT/GPT, albumin, bilirubin, creatinine, INR, partial thromboplastin time (PTT) and platelets should be made and the (creatinine modified) Child Pugh score should be calculated in order to estimate liver function. There is, to the best of our knowledge, no published limit for either ECOGor Child Pugh-Scores for liver malignancy ablation usingHDR brachytherapy, but it should be usedwith caution inCPS class >B8. However, in a smaller cohort of 24 patients with HCC (and Child-Pugh A or B cirrhosis) undergoing either yttrium-90 selective internal radiation therapy (SIRT) or brachytherapy, only mild changes in liver function parameters compared to baseline, with recovery within 6-12 weeks were detected [22]. Nonetheless, critical discussion on a case by case basis should be undertaken, especially when brachytherapy ablation of lesions with >5 cm largest diameter are planned. The goal of brachytherapy should be clarified and documented in the interdisciplinary tumour-board discussion and should be known to the patient (Palliative or curative approach? Down-staging before liver transplantation?). The patient’s blood count must be adequate to perform interventional procedures (e.g. INR 1.5, platelet count >50×10 9 /l, PTT <50 sec) with results not older than one week. Potential anticoagulation should be interrupted or bridged according to contemporary guidelines with pausing of low molecular weight heparin or oral heparin-analogues for at least 48 hours before the intervention, whenever possible (e.g. consensus guidelines of the Society of interventional radiology [SIR] / Cardiovascular and Interventional Radiological Society of Europe [CIRSE]) [23,24]. In contrast, intake of acetylsalicylic acidmay be continued in patients receiving secondary prophylaxis. Medical history assessment should reflect if there is a potential insufficiency of the sphincter of Oddi or presence of a hepatojejunostomy, as this leads to an increased risk of infection, abscess formation and potential sepsis after brachytherapy. Additional risk factors for infection are cirrhosis and diabetes. In these high-risk cases, periprocedural antibiotic prophylaxis is now recommended in the updated standard operating procedure (SOP) as published by SIR and supported by CIRSE [25]. While these recommendations focus primarily on thermal ablations, they may be used as guide for brachytherapy of liver malignancies as well. To date there are no published randomised controlled trials that investigate antibiotic prophylaxis in low-risk patients undergoing hepatic tumour brachytherapy. In these patients “the use of a single agent targeted to skin flora (i.e. cefazolin) may be reasonable”, according to the updated consensus guideline [25]. Preprocedural allergy assessment is needed regarding contrast- agents, local anaesthetics, systemic pain-medications as well as sedatives. Depending on the severity of the known allergic reaction potential modifications to the ablation plan should be discussed (modality switch or avoidance possible? Premedication and anaesthesia stand-by?). General best practice recommendations concerning contrast-agent application as issued by the European society of urogenital radiology (ESUR) should be followed – including for example assessment of thyroid function to exclude or manage hyperthyroidism.

Patients with primary liver malignancies or with oligometastatic disease of the liver can be considered suitable for liver brachytherapy if surgical options or other locally ablative treatments are not feasible or desired by patients. All patients should be discussed in an interdisciplinary tumour board before treatment and deemed amenable for local ablative treatment using brachytherapy. Relative contraindications include liver cirrhosis, Child-Pugh-stage B or higher, more because of a considerably higher risk of severe bleeding and catheter dislocation events than concerns regarding the post-interventional liver function [26,27]. Ascites is a technical contraindication, and even though it may be drained before application, it indicates either advanced liver cirrhosis, peritoneal carcinomatosis or cardiac comorbidity, questioning the value of local ablation with respect to the impact on overall survival in the context of possible adverse events. Serious attention should be paid to oral or s.c. anticoagulation due to the increased risk of severe bleeding events and subsequently increased mortality [26]. A biliodigestive anastomosis appears to increase the risk of post-interventional infection and abscess formation [28]. Hepatocellular carcinoma Optimal treatment of primary liver cancer is highly dependent on a multidisciplinary approach due to the complexity of diagnosis, staging, medical comorbidities (especially underlying cirrhosis), and the myriad treatment options.The contribution and collaboration of the disciplines of diagnostic radiology, pathology, hepatology, transplant surgery, surgical oncology, medical oncology, radiation oncology, and interventional radiology are critical to achieve individualised and evidence-based patient care. Multiple treatment modalities are used for the definitive treatment of primary liver cancer. For HCC, orthotopic liver transplantation (OLT), surgery, and thermal ablation (radiofrequency [RFA] or microwave) are standard treatment modalities with curative intent. Catheter-based therapies (e.g. transarterial embolisation [TAE], transarterial chemoembolisation [TACE], and transarterial radioembolisation [TARE]) are considered acceptable treatment options for locoregional tumour control. According to the Barcelona Clinic Liver Cancer (BCLC) staging system, patients with "very early" and "early" stage HCC benefit especially from local ablation [29]. RFA is the most commonly used ablative technique and, because of its high efficacy in small HCCs (≤3 cm largest diameter) it has been recommended as a first-line curative treatment option for small HCCs [30]. However, despite its high efficacy in small tumours, RFA remains limited by a number of tumour factors such as size (>3 cm), tumour location in close proximity to a large vessel that may result in a heat sink or proximity to organs at risk (e.g. bowel), multiple lesions and vascularization [31]. HDR brachytherapy is an alternative, minimally invasive, radioablative technique. The published data support the use of brachytherapy as a safe and effective treatment strategy in the management of primary and secondary liver tumours (see table 3 and 4). Compared with SBRT, HDR brachytherapy is less affected by respiratory motion because the implanted catheters move with the tumour and liver [4]. In addition, the radiation dose to nearby OARs can be significantly lower with HDR brachytherapy because the dose gradient is generally steeper compared to SBRT [1]. For patients with liver cirrhosis and unresectable early-stage HCC (BCLCA), Orthotopic liver transplantation (OLT) is another option that provides curative treatment of the underlying liver disease in