**4. Nonsurgical therapies**

#### **4.1. Intervention radiology**

#### *4.1.1. Radiofrequency thermoablation and microwave thermoablation*

Percutaneous radiofrequency thermoablation (RFTA) and microwave thermoablation (MWA) are considered the standard care for patients with BCLC 0-A HCC, who are not eligible for surgical treatment.

Percutaneous ablation techniques are indicated for HCC nodules <2 cm, while nodules with diameter between 2 and 3 cm need to be discussed in a multidisciplinary unit in order to determine an appropriate management plan (**Table 3**). In patients with a single HCC nodule less than 2 cm in diameter, a complete necrosis ratio of 97% is expected [34].


**Table 3.** Indications to Radio-Frequency Thermal Ablation.

A modest expansion to Milan criteria was given by "up to seven criteria," which had achieved satisfactory results in patients without extrahepatic metastases and/or macrovascular inva-

An increasing number of older patients with end-stage liver disease (ESLD) are evaluated for liver transplantation (LT). In fact, patients aged ≥65 years represent one of the fastest-growing patient populations in LT [29]. The most extreme of these patients, those aged ≥70 years, are associated with several difficult clinical dilemmas. Firstly, advanced patient age is associated with higher risk and poorer outcomes after complex surgical procedures [30]. LT in advanced age patients is associated with increased risk for infection and cardiovascular impairment, increased resource utilization, and lower patient survival [31]. Since the number of adult candidates on the waiting list continues to rise and organ availability remains unable to fully

Equivalent outcomes can be achieved in elderly recipients and age alone should not be used

Recent data for waitlist registrants on the SRTR registry suggest that <12% of waitlisted patients are aged ≥65 years, but this proportion has steadily increased over the past decade. Continued improvements in care in pre- and posttransplant medicine and surgery suggest that this age group will continue to grow on the waiting list. With this demographic shift in the ESLD, more elderly patients will be considered for LT, and the use of scarce donor livers will need to be addressed because these recipients have a shorter life expectancy compared with younger patients. Despite the shortened lifespan, single-centered reports have shown

Due to physical and psychological impairment, elderly patients are often considered unfit for liver transplantation, since in super-selected groups only satisfying result in LT is achieved,

Percutaneous radiofrequency thermoablation (RFTA) and microwave thermoablation (MWA) are considered the standard care for patients with BCLC 0-A HCC, who are not eligible for

Percutaneous ablation techniques are indicated for HCC nodules <2 cm, while nodules with diameter between 2 and 3 cm need to be discussed in a multidisciplinary unit in order to determine an appropriate management plan (**Table 3**). In patients with a single HCC nodule

less than 2 cm in diameter, a complete necrosis ratio of 97% is expected [34].

surgical resection remains, for elderly, the first-line approach when performable.

meet this demand, proper organ allocation and utilization are critically important.

equivalent posttransplant survival in super-selected patients [32, 33].

*4.1.1. Radiofrequency thermoablation and microwave thermoablation*

sion. A prospective validation is needed [28].

as a barrier to LT.

40 Liver Cancer

**4. Nonsurgical therapies**

**4.1. Intervention radiology**

surgical treatment.

Several randomized studies have documented the superiority of surgical resection over percutaneous ablation techniques in terms of efficacy, while thermoablation has shown lower morbidity, mortality, hospitalization rates, and costs [35].

MWA and RFTA have shown comparable safety and effective results, although MWA seems to have certain theoretical advantages compared to RFTA: shorter procedure, higher ablation temperature, larger area of necrosis, lower probability of biliary duct injury, and reduction in the heat-sink effect through a more uniform heating in the volume of ablation. However, these advantages have not been confirmed in clinical practice. Although EASL guidelines recommend the use of MWA for nodules up to 4 cm, a recent phase II trial, comparing the two techniques in patients with similar mean lesion volumes, showed no significant difference between them in terms of outcome and recurrence ratio [36].

RFTA and MWA can also be safely and effectively performed via a video laparoscopic (VL) approach [37]. VL allows the operator to treat nodules that would normally not be eligible for a percutaneous approach due to nonaccessible locations and allows for hybrid management of patients with multiple nodules (e.g., surgical resection and RFTA on additional nonresectable nodules).

Percutaneous ablation techniques are a precious tool in management of elderly patients with multiple comorbidities.

HCC is often methacronous and new nodules are expected to develop during follow-up after the first tumor. Therefore, it is crucial to perform an appropriate follow-up in patients who have been treated for HCC, in order to detect new nodules at an early stage, so that the least invasive treatment available can be delivered. This is particularly relevant in elderly patients, or those who have already undergone extensive hepatic resection, who might not be eligible for surgery.

Percutaneous ablation is a recommended treatment modality, when indicated, due to its mini-invasive nature, high effectiveness, low rates of adverse events, short hospitalization times, and its relatively few contraindications.

#### *4.1.2. Transarterial chemoembolization*

Transarterial chemoembolization (TACE) is a palliative treatment that is routinely used in patients with HCC that are neither eligible for surgery nor for percutaneous ablation, and in stage BCLC B HCC. TACE is indicated for asymptomatic patients in Child-Pugh class up to B7 and PS ≤ 1 [17] (**Table 4**).

TACE can also be combined with percutaneous ablation, particularly in patients with tumor recurrence within 1 year since the initial treatment, those with tumor diameters of 3.1–5.0 cm, and those with tumor recurrences after initial treatment with thermoablation, where sequen-

HCC in Elderly Patients. Curative Intraoperative Strategies and Management in Recurrences

http://dx.doi.org/10.5772/intechopen.79748

43

The benefit of this sequential approach is due to the occlusion of hepatic arterial flow by means of embolization before ablation. Furthermore, lipiodol and gelatine sponge particles used in TACE reduce the portal flow around the tumor by filling the peripheral portal vein via multiple arterioportal communications. Therefore, the reduced cooling effect of the hepatic blood flow on ablation-induced thermal coagulation allows the achievement of an enlarged

Transarterial radioembolization (TARE) is a palliative brachytherapy for HCC. Radioactive substances (I131-lipidol or Y90-beads) are delivered into the tumor by injecting them selec-

This is a complex technique that requires a high-level specialization and has potentially severe side effects such as hepatic, intestinal, and lung toxicity [17]. Therefore, it should only be performed in specialized centers, with high volume activity and experience with this procedure. Given the fact that TARE has minimal embolizing effects, it can be safely performed even in

It can be used as a first-line treatment when TACE is not recommended, such as in the case of large or multifocal HCC or if there are signs of portal thrombosis. However, liver function

TARE has also been shown to be an appropriate bridge or downstaging treatment in order to

Furthermore, TARE can be used as a second-line treatment in patients who did not respond

Mean survival for Child-Pugh class A or B patients who underwent TARE is, respectively, 17.2 and 7.7 months [48, 49]. Mean survival for patients with portal vein thrombosis is 9 months,

A study has revealed similar results in terms of overall survival (OS) and toxicity between cTACE and TARE in patients with nonresectable HCC [51]; another study has shown a better time-to-progression (TTP) and lower toxicity following TARE compared to TACE [52].

TARE cannot be performed in patients with a pulmonary shunt >20% or if other vascular

Indications for this treatment are often controversial and should only be discussed in dedicated multidisciplinary teams. The difficulty in determining the precise indications of TARE is in part due to the lack of cost-effectiveness studies and the fact that its therapeutical equivalence to TACE has only been proved in selected patients. TARE is usually indicated in patients with stage BCLC C HCC, especially those with portal vein thrombosis and preserved liver function.

anomalies may cause irradiation of visceral organs (stomach and intestine) [17].

tial TACE-thermoablation might be the best treatment option [45].

ablation zone which might reduce recurrence rates.

patients with thrombosis of the portal vein or its branches.

to TACE or who are intolerant to chemotherapy [17, 47].

meet liver transplantation criteria [17, 46].

must be conserved (Child-Pugh ≤7, bilirubin ≤2.0 mg/dl, no ascites) [17].

while for those with intrahepatic portal thrombosis is 17 months [50].

*4.1.3. Transarterial radioembolization*

tively into its feeding arteries.

A study found no significant difference in survival following TACE in patients with Child-Pugh Class 8–9 compared to class 7; however, patients with Child-Pugh 8–9 had a significant worse prognosis and more dangerous side effects [38].

TACE is not indicated for patients with signs of HCC vascular invasion, metastases, untreatable ascites, jaundice, thrombosis of a major portal vessel, and HCC nodules >10 cm. In these cases, due to an already compromised liver function, there is a high risk of liver failure and eventually death.

Drug-eluting beads TACE (DEB-TACE) is a more recent variation of conventional TACE (cTACE) that uses embolizing beads eluted with doxorubicin as a chemotherapeutic agent. It has shown overall similar effectiveness, but less systemic side effects compared to cTACE.

Randomized trials have found superior outcomes with DEB-TACE compared to cTACE in patients with Child-Pugh class B and/or PS ≥ 1 [39, 40].

Although contrast-enhanced CT (CECT) or MRI with hepatospecific contrast agent is recommended for TACE outcome evaluation, contrast-enhanced US (CEUS) could be an appropriate alternative in patients with less than four nodules [41].

If imaging follow-up detects residual or recurrent HCC nodules, TACE can be repeated up to three times per nodule. Treatment failure is considered when there are no signs of lesion response, as assessed using the mRECIST criteria, after two treatments or if there is no complete response after three treatments [42]; in eastern countries, different staging criteria, RECICIL, are actually in use [43].

TACE has been proved safe and effective in elderly as well as in younger patients. In particular, a prospective study found that elderly patients suffered from the same complication rates as nonelderly, while effectiveness rates were similar [44].

More important than age is the liver functional status, and the patient's performance status that mostly affects the safety profile of TACE. Therefore, TACE can be an effective palliative treatment able to give benefits in terms of disease control and improved quality of life in elderly patients with HCC.


**Table 4.** Indications to Trans Arterial Chemo-Embolization.

TACE can also be combined with percutaneous ablation, particularly in patients with tumor recurrence within 1 year since the initial treatment, those with tumor diameters of 3.1–5.0 cm, and those with tumor recurrences after initial treatment with thermoablation, where sequential TACE-thermoablation might be the best treatment option [45].

The benefit of this sequential approach is due to the occlusion of hepatic arterial flow by means of embolization before ablation. Furthermore, lipiodol and gelatine sponge particles used in TACE reduce the portal flow around the tumor by filling the peripheral portal vein via multiple arterioportal communications. Therefore, the reduced cooling effect of the hepatic blood flow on ablation-induced thermal coagulation allows the achievement of an enlarged ablation zone which might reduce recurrence rates.
