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

12. RESULTS

anastomosis or following endoscopic papillectomy. Usually they arise with a latency of weeks to months after the intervention and can be clinically silent [26]. Detection of an abscess is obtained by imaging, preferably by contrast-enhanced CT, and the treatment of choice is percutaneous drainage with aspiration for culture and appropriate antibiotic treatment. In high-risk cases, application of prophylactic antibiosis might be a treatment option to prevent infection. Radiation toxicity Regarding radiation toxicity, adjacent liver parenchyma will be exposed to a significant radiation dose and will suffer focal radiation induced damage following brachytherapy. According to literature, the tolerance dose of the liver parenchyma for a focal loss of liver function is around 10 Gy, with hepatocytes showing dysfunction above this threshold at 6 weeks after single fraction brachytherapy. However, this volume decreases over time due to repair mechanisms for a time period of up to 6 months post brachytherapy, indicating that the radiation induced liver parenchymal damage around the ablated tumour remains rather small [86,87]. However, in patients with multiple ablations (sequential or multiple lesions at the same time) and patients with a small functional reserve of the liver, this radiation induced liver injury can lead to radiation induced liver disease (RILD; i.e. liver decompensation) [88]. The frequency of RILD after brachytherapy is very rare and about 0.5% [27]. In order to avoid a RILD after HDR brachytherapy a minimum of one third of the liver should not be exposed with more than 5 Gy (see Table 2) [86]. In cases of high dose exposure of healthy liver tissue, prophylactic medication to ameliorate radiation induced liver parenchymal damage is recommended and consists of low molecular weight heparin, ursodesoxycholic acid and pentoxifylline [89]. For large, centrally located liver tumours, clinically relevant biliary duct complications are rare and have not been associated with a reduction in overall survival in available studies [90].The excellent treatability of central liver tumours is a unique feature of interstitial brachytherapy as compared to other local-therapeutic procedures, including surgical resection.

Oncologic outcome In primary liver malignancies, HDR brachytherapy has high local control rates for both unresectable bilary tract cancer [43,61,62] as well as hepatocellular carcinoma [40,63–65]. An overview of the published literature is given in table 3 and 4. Evidence for the treatment of secondary liver malignancies withHDR brachytherapy includes oligometastases of a wide range of histologies, including anal squamous cell carcinoma [66], breast cancer [67–69], colorectal cancer [48,70–72], gastric adenocarcinoma [73,74], gastrointestinal stroma tumours [75], neuroendocrine tumours [76], pancreatic cancer [28,77] and renal cell carcinoma [77,78]. In patients with oligometastatic colorectal cancer and unresectable liver metastases, the European Society for Medical Oncology (ESMO) recommends HDR brachytherapy as an ablative treatment option in the current consensus guideline [48]. Procedural complications and toxicity Overall, procedural complications that may arise from theminimally invasive intervention should be distinguished from the toxicity of the radiation itself. Severe complications are rare and reported for less than 1.5% of all interventions and include bleedings, infection and pain [3,63]. There is evidence of a strong correlation between major bleeding events and the secondary diagnosis of an advanced liver cirrhosis (usually in patients with HCC), or the peri-interventional administration of low-molecular-weight heparin [26,27]. If there are signs of a hypovolemic shock, internal bleeding must be ruled out by CT, and if active arterial bleeding is detected, immediate intervention is required. The treatment of choice is angiographic embolization with particles or coils, and surgical intervention is rarely needed. Liver abscesses (~2%) may occur more frequently in patients with a history of biliodigestive 13. ADVERSE SIDE EFFECTS

14. KEYMESSAGES

• Interstitial HDR liver brachytherapy provides excellent local control rates of >90% at 12 months for primary or secondary liver tumours such as hepatocellular carcinoma (HCC) or cholangiocellular carcinoma (CCC), as well as for secondary liver malignancies in oligometastatic disease.

• The prescription dose depends on histology and varies from 15-25 Gy (D100%) in a single session.

• Interstitial HDR liver brachytherapy is particularly beneficial in the treatment of large liver tumours, multiple lesions, or tumours in central location and can be used as an alternative to other local ablative treatment options. • Severe radiation related toxicity rates and serious procedural complications (major bleeding or infection after the procedure) are very low (1.5%).