Interventional procedure overview of image-guided percutaneous laser ablation of primary and secondary liver tumours
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Evidence summary
Population and studies description
This interventional procedures overview is based on about 3,000 people from 4 randomised controlled trials (Di Costanzo 2015, Orlacchio 2014, Ferrari 2007, Zou 2017), 1 quasi-randomised controlled trial (Ferrari 2006), 1 retrospective non-randomised comparative study (Adwan 2022), 1 case-control study (Morisco 2018), 5 cohort studies (Pacella 2009, Francica 2012, Vogl 2004, Vogl 2014, Vogl 2013) and 1 case report (Helmberger 2002). Of these 3,000 people, about 2,500 had the procedure. There is likely to be some population overlap between the studies. This is a rapid review of the literature, and a flow chart of the complete selection process is shown in figure 1. This overview presents 13 studies as the key evidence in table 2 and table 3, and lists 40 other relevant studies in table 5.
Most of the studies were from Italy or Germany, with 1 randomised controlled trial from China. All 4 randomised controlled trials included people with HCC and compared laser ablation with RFA. The non-randomised studies included people with HCC and metastatic liver tumours, and comparators included microwave ablation, TACE, and percutaneous ethanol injection. Most of the studies included people with up to 5 small tumours (maximum diameters ranged from 3 cm to 5 cm) and with Child-Pugh class A or B cirrhosis. An exception was the case control study by Morisco (2018), which compared laser ablation with TACE in a population with a solitary HCC 40 mm or larger. The retrospective cohort study by Francica (2012) aimed to compare outcomes of laser ablation in HCC tumours at high-risk locations compared with those at standard risk locations. Several studies reported follow up beyond 5 years.
In the study by Ferrari (2006), which has been described as quasi-randomised, computer randomisation was used for most treatments but there were some exceptions. Tumours with a difficult percutaneous approach were treated with TACE, and an alternative treatment to laser ablation was used for superficial lesions next to large vessels and cholecysts.
The cohort study by Vogl (2014) specifically stated that 57% (n=337) of people had treatment with a curative intention aiming to eliminate disease from the liver and 43% (n=257) had treatment with a palliative intention.
Table 2 presents study details.
Procedure technique
Of the 13 studies, 7 stated that the laser ablation was done under ultrasound guidance and 4 stated that the ablation was done under MRI guidance, with the needles being placed under CT guidance. Of the 7 using ultrasound, 3 stated that an Echolaser system was used, which consists of an ultrasound device and a diode laser unit (Di Costanzo 2015, Orlacchio 2014, Zou 2017). Other studies stated that a Nd:YAG laser was used. Most studies described using up to 4 fibres for ablation.
Efficacy
Complete tumour ablation
The rates of complete tumour ablation were reported in 9 studies and ranged from 67% to 99%.
In the randomised controlled trial of 140 people with HCC (157 tumours), complete tumour ablation was reported in 96% (67 out of 70; 95% CI 88 to 99) of people who had laser ablation and 97% (68 out of 70; 95% CI 90 to 99) of people who had RFA. More treatment sessions were needed in the laser group to obtain complete tumour ablation (82 compared with 72 in the RFA group, p=0.058; Di Costanzo 2015). In the randomised controlled trial of 30 people with HCC (30 tumours), a complete response at 30 days was reported in 67% (10 out of 15) of those who had laser ablation and 87% (13 out of 15) of those who had RFA. After a second treatment session, the rates were 87% (13 out of 15) in the laser ablation group and 93% (14 out of 15) in the RFA group (p=not significant; Orlacchio 2014). In the randomised controlled trial of 81 people with HCC (95 tumours), complete ablation was reported in 78% (35 out of 45) of tumours in the laser ablation group and 94% (47 out of 50) of tumours in the RFA group (Ferrari 2007). In the randomised controlled trial of 74 people with HCC, a complete response at 3 months was reported for 89% (31 out of 35) of those who had laser ablation and 92% (36 out of 39) of those who had RFA (p=0.583; Zou 2017). In the quasi-randomised controlled trial of 131 people with HCC, complete necrosis after the first treatment session was reported in 92% (46 out of 50) of tumours treated by laser ablation, 70% (14 out of 20) of tumours treated by TACE, 74% (28 out of 38) of tumours treated by PEI and 80% (32 out of 40) of tumours treated by combined TACE and PEI (Ferrari 2006). In the non-randomised comparative study of 303 people with HCC (510 tumours), initial complete ablation was reported for 99% (74 out of 75) of tumours treated by laser ablation and 98% (425 out of 435) of tumours treated by microwave ablation (Adwan 2022). In the case-control study of 82 people with a solitary HCC 40 mm or larger, a complete response was reported in 63% (21 out of 41) of those who had laser ablation and 20% (8 out of 41) of those who had TACE (p<0.001). The response rates for tumours between 51 mm and 60 mm in diameter were 75% after laser ablation and 14% after TACE (p=0.013; Morisco 2018).
In 2 single-arm studies of people with HCC, the complete response after laser ablation was 80% (436 out of 548; Pacella 2009) and 93% (170 out of 182) of tumours (Francica 2012).
Local tumour progression or recurrence
Local tumour progression, progression-free survival or recurrence was reported as an outcome in 10 studies.
In the randomised controlled trial of 140 people with HCC, local tumour progression was reported in 23% (16 out of 70) of people who had laser ablation and 26% (18 out of 70) of people who had RFA (p=0.956). The mean time to local progression was similar between the groups (46 months for laser ablation and 40 months for RFA, p=0.376; Di Costanzo 2015). In the randomised controlled trial of 30 people with HCC, cumulative rates of freedom from local disease progression at 3, 6 and 12 months after treatment were 85%, 62% and 54% in the laser ablation group, and 92%, 86% and 86% respectively in the RFA group (p=0.083; Orlacchio 2014). In the randomised controlled trial of 81 people with HCC, disease recurrence (local tumour progression or new HCC) was reported in 27% (11 out of 41) of those who had laser ablation and 23% (9 out of 40) of those who had RFA. All local tumour progression was observed within 24 months after treatment (Ferrari 2007). In the non-randomised comparative study of 303 people with HCC, local tumour progression was reported in 4% (2 out of 53) of those who had laser ablation and 6% (15 out of 250) of those who had microwave ablation. Local tumour progression-free survival at 1, 3 and 5 years from ablation date was similar between the groups (Adwan 2022). In the case control study of 82 people with a solitary HCC 40 mm or larger, the rate of disease recurrence after initially successfully treatment was 19% (5 out of 26) in the laser ablation group and 75% (6 out of 8) in the TACE group (p<0.0001; Morisco 2018).
In the cohort study of 164 people with HCC (182 tumours), the rate of local tumour progression was 11% (18 out of 170). There was no statistically significant difference in the cumulative incidence of local tumour progression among tumours at high-risk sites compared with elsewhere (p=0.499; Francica 2012). In the cohort study of 432 people with HCC, the rate of recurrence (local and distant) was 20% (67 out of 338). The mean time to recurrence was 24 months (95% CI 20 to 28; Pacella 2009).
In the cohort study of 603 people with CRC liver metastases, local recurrence rate at 6 months was 2% for tumours 0 cm to 2 cm in diameter, 2% for tumours between 2 cm to 3 cm, 1% for tumours between 3 cm and 4 cm and 4% for tumours larger than 4 cm in diameter (Vogl 2004). In the cohort study of 594 people with CRC liver metastases (1,545 tumours), the median progression-free survival was 13 months (95% CI 11 to 15). Progression-free survival was 51% at 1 year, 35% at 2 years, 31% at 3 years, 25% at 4 years and 22% at 5 years (Vogl 2014). In the cohort study of 401 people with liver metastases from primary sites other than CRC (809 tumours), median progression-free survival was 12 months (range 0 to 134). Progression-free survival was 51% at 1 year, 34% at 2 years, 26% at 3 years, 20% at 4 years and 17% at 5 years (Vogl 2013).
Disease-free survival
Disease-free survival was reported in 3 studies. In the non-randomised comparative study of 303 people with HCC, disease-free survival at 1, 3 and 5 years from ablation date was 55%, 30% and 17% in the laser ablation group, compared with 46%, 31% and 25% in the microwave ablation group (p=0.719; Adwan 2022). In the case-control study of 82 people with a solitary HCC 40 mm or larger, mean disease-free survival was 31.5 months (95% CI 24.1 to 38.8) in the laser ablation group and 14.2 months (95% CI 9.7 to 18.7) in the TACE group (p<0.0001; Morisco 2018).
In the cohort study of 432 people with HCC, median disease-free survival time was 26 months (95% CI 22 to 30; Pacella 2009).
Overall survival
Overall survival was reported in 9 studies. In the randomised controlled trial of 140 people with HCC, mean overall survival was 42 months (95% CI 37 to 47) in the laser ablation group and 43 months (95% CI 38 to 47) in the RFA group (p=0.346). The 1-year survival probability was 94% in both groups and the 3-year survival probability was 80% in the laser group and 89% in the RFA group (Di Costanzo 2015). In the randomised controlled trial of 81 people with HCC, the cumulative survival rates at 1 to 5 years were higher in the RFA group than the laser ablation group, but the difference was not statistically significant (Ferrari 2007). In the quasi-randomised controlled trial of 131 people with HCC, cumulative survival at 1, 3 and 5 years was 90%, 53% and 31% for those who had treatment with laser ablation, 67%, 11% and 0% for those who had treatment with TACE, 71%, 29% and 18% for those who had treatment with PEI, and 91%, 41% and 19% for those who had treatment with combined TACE and PEI. Those who had laser ablation or combined therapy survived longer than those who had TACE (p=0.0001 and 0.0096, respectively), and laser ablation was associated with longer survival than PEI (p=0.0274; Ferrari 2006). In the non-randomised comparative study of 303 people with HCC, overall survival at 1, 3 and 5 years from diagnosis was 96%, 55% and 30% in the laser ablation group, compared with 94%, 65% and 49% in the microwave ablation group (p=0.002). Overall survival at 1, 3 and 5 years from ablation date was 85%, 38% and 17% in the laser ablation group, compared with 87%, 53% and 40% in the microwave ablation group (p=0.001; Adwan 2022). In the case control study of 82 people with a solitary HCC 40 mm or larger, mean overall survival was 40 months (95% CI 33 to 46) in the laser ablation group and 37 months (95% CI 31 to 43) in the TACE group (p=0.725). Overall survival probability at 1, 2 and 3 years was 90%, 66% and 55% in the laser group, compared with 85%, 66% and 49% in the TACE group (Morisco 2018).
In the cohort study of 432 people with HCC (548 tumours), median overall survival was 47 months (95% CI 41 to 53), 3-year cumulative survival was 61% and 5-year cumulative survival was 34%. Survival duration was statistically significantly longer in patients with main tumour size of 2.0 cm or less compared with 3.1 cm to 4.0 cm (p=0.003), and in those with main tumour size of 2.1 cm to 3.0 cm compared with 3.1 cm to 4.0 cm (p=0.027; Pacella 2009).
In the cohort study of 603 people with CRC liver metastases, mean survival from date of diagnosis of metastasis was 4.4 years (95% CI 4.0 to 4.8) and median survival was 3.5 years (95% CI 3.0 to 3.9). Survival at 1, 2, 3, and 5 years was 94%, 77%, 56% and 37%, respectively. Mean survival from date of first laser ablation was 3.8 years (95% CI 3.4 to 4.2) and median survival was 2.9 years (95% CI 2.4 to 3.3). Survival at 1, 2, 3, and 5 years was 86%, 64%, 49% and 33%, respectively (Vogl 2004). In the cohort study of 594 people with CRC liver metastases, the median overall survival from first laser ablation was 25 months (95% CI 22.5 to 27.5). Mean survival was 29.3 months (range 0 to 121). Overall survival was 78% at 1 year, 50% at 2 years, 28% at 3 years, 16% at 4 years and 8% at 5 years (Vogl 2014). In the cohort study of 401 people with liver metastases from primary sites other than CRC, median overall survival from first laser ablation was 37.6 months (range 0 to 1,632). Mean overall survival was 62 months (SD 25.9). Overall survival was 87% at 1 year, 67% at 2 years, 52% at 3 years, 40% at 4 years and 33% at 5 years. Statistically significant prognostic factors for long-term survival were the initial number of metastases (p=0.008), mean volume of metastasis (p<0.001), the quotient of the total volumes of necroses and metastases (p<0.001), and the T stage of the primary tumour according to the TNM classification (p<0.001; Vogl 2013).
Patient satisfaction
In the randomised controlled trial of 74 people with HCC, the proportion of people who reported great or general satisfaction 3 days after treatment was 94% in the laser group and 69% in the RFA group (p=0.022; Zou 2017).
Safety
Complications that were described as major or clinically relevant have been summarised below.
Mortality
One treatment-related death was reported in the cohort study of 432 people. Acute liver decompensation associated with severe respiratory failure happened 4 days after the procedure (Pacella 2009). Death within 30 days was reported after less than 1% (2 out of 1,555) of treatment sessions in the cohort study of 603 people. One person died 4 weeks after the procedure from peritonitis and respiratory failure, after developing leakage in the jejunum. The other person died from suspected sepsis, but this was unconfirmed (Vogl 2004).
Cardiac air embolism
A case report of massive cardiac air embolism after laser ablation was published in 2002. The air embolism was identified during the CT scan that was done immediately after the procedure. The right ventricle was percutaneously punctured with a needle and the air was evacuated. After external electrical defibrillation, the patient recovered and remained haemodynamically stable (Helmberger 2002).
Pancreatitis
Pancreatitis within 24 hours of laser ablation, categorised as a major complication, was reported in 1 person in the cohort study of 432 people (Pacella 2009).
Intrahepatic haematoma
Intrahepatic haematoma within 24 hours of laser ablation, categorised as a major complication, was reported in 1 person in the cohort study of 432 people (Pacella 2009).
Bleeding
Major peritoneal bleeding within 24 hours of laser ablation was reported in 1 person in the cohort study of 432 people (Pacella 2009). Clinically relevant intra-abdominal bleeding was reported after less than 1% (2 out of 1,555) of treatment sessions in the cohort study of 603 people (Vogl 2004).
Transient decompensation of liver function
Major transient decompensation of liver function was reported in 1% (4 out of 432) of people within 30 days of laser ablation.
Bile duct injury
Main bile duct injury was reported in 1 person, who had a tumour in a high-risk location, after laser ablation in the cohort study of 164 people (Francica 2012). Injury to the bile duct was reported in 1 person in the cohort study of 603 people (Vogl 2004).
Pleural effusion
Clinically relevant pleural effusion was reported after 1% (17 out of 1,555) of treatment sessions in the cohort study of 603 people (Vogl 2004).
Liver abscess
Liver abscess, described as clinically relevant, was reported after less than 1% (6 out of 1,555) treatment sessions in the cohort study of 603 people (Vogl 2004).
Pneumothorax
Pneumothorax, described as clinically relevant, was reported in 1 person in the cohort study of 603 people (Vogl 2004).
Bronchial-biliary fistula
Bronchial-biliary fistula, described as clinically relevant, was reported in 1 person in the cohort study of 603 people (Vogl 2004).
Tumour seeding
Subcutaneous tumour seeding was reported in 1 person who had laser ablation and 1 who had RFA in the randomised controlled trial of 140 people with HCC. In both people, it was surgically removed (Di Costanzo 2015). Three studies including 690 people who had laser ablation specified that no tumour seeding had been observed (Vogl 2004, Ferrari 2006 and 2007).
Anecdotal and theoretical adverse events
Expert advice was sought from consultants who have been nominated or ratified by their professional society or royal college. They were asked if they knew of any other adverse events for this procedure that they had heard about (anecdotal), which were not reported in the literature. They were also asked if they thought there were other adverse events that might possibly occur, even if they had never happened (theoretical).
They did not describe any additional anecdotal or theoretical adverse events.
Three professional expert questionnaires for this procedure were submitted. Find full details of what the professional experts said about the procedure in the specialist advice questionnaires for this procedure.
Validity and generalisability
Most of the data included in the key evidence is from Europe.
There are several randomised controlled trials comparing laser ablation with RFA for treating HCC. No randomised controlled trials were identified for metastatic liver cancer.
In the non-inferiority randomised controlled trial by Di Costanzo (2015), the 2 treatment groups were not entirely balanced because of the random inclusion of more large and high-risk located tumours in the laser ablation group.
The retrospective case control study by Morisco (2018) used multicentre historical controls treated with TACE to compare with laser ablation at a single centre, which may have introduced some bias.
Different techniques were used to do laser ablation, including different laser systems and different types of imaging.
Some studies included people who had already had treatment for liver cancer, but some excluded those who had previous treatment.
Some studies included people who had refused surgery as well as those for whom surgery was unsuitable. The outcomes may be different in these separate groups.
Most studies included people with up to 5 small tumours (generally up to 50 mm in diameter). One study compared laser ablation with TACE for a solitary large HCC (up to 76 mm; Morisco 2018). The randomised controlled trial by Orlacchio (2014) only included people with a single HCC tumour with maximum diameter 40 mm. It is likely that multifocal HCC has a different biological behaviour compared with unifocal HCC, with worse trends in terms of both survival and recurrence.
Most studies excluded people with Child-Pugh class C liver disease.
Some studies reported response rates after the first treatment session, but others reported the rates after additional sessions.
One author noted that particularly for HCC, disease-free survival time and overall survival may be related to the aetiology and severity of the liver failure associated with cirrhosis and histological type of tumour. Survival rates can be influenced by the onset of other tumours, both primary and secondary, or complications resulting from liver failure. Local disease progression-free survival or recurrence-free survival may be a better outcome measure for local ablation procedures.
Several studies reported follow up of 5 years or longer.
No potential conflicts of interest were declared in the key evidence papers.
No ongoing key trials were identified.
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