Radiography
Volume 18, Issue 1 , Pages 15-20, February 2012

Interventional oncology

  • Tze Wah

      Affiliations

    • Leeds Teaching Hospitals, NHS Trust, UK
    • ,
  • David Breen

      Affiliations

    • Southampton General Hospital, UK
    • ,
  • Jai Patel

      Affiliations

    • Leeds Teaching Hospitals, NHS Trust, UK
    • ,
  • Tony Nicholson

      Affiliations

    • Leeds Teaching Hospitals, NHS Trust, UK
    • Corresponding Author InformationCorresponding author. Radiology Department, Leeds General Infirmary, Leeds LS13EX, UK. Tel.: +44 (0) 1133922860.

published online 12 December 2011.

Article Outline

Abstract 

Interventional Oncology is a relatively new term that has been used to describe the practice of minimally invasive percutaneous cancer treatment. It has been used for palliative and adjuvant treatments to improve quality of life for some forty years. Curative interventions or interventions which extend life significantly, require ablative techniques i.e. techniques that destroy tumour mass either completely or sufficiently to reduce the tumour load. This review describes the state of the art in liver and renal ablation and liver chemotherapy and isotope embolisation. Such ablative techniques are increasingly being used in other cancer treatments such as the lung, prostate and perhaps in future the breast.

Keywords: Interventional, Oncology, Ablation, Renal cancer, Liver cancer

 

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Introduction 

The increasing importance of percutaneous ablative techniques was the driver behind the term interventional oncology but, in truth, interventional radiologists had been treating cancers since the earliest days of the subspecialty. The occlusion of blood supply to tumour, embolisation or embolotherapy, was well described by numerous authors by 1975,1 usually to treat tumour haemorrhage, as was the direct intra-arterial administration of chemotherapy.2 The introduction of stents in the late 1980’s saw the development of percutaneous palliative cancer treatments for pancreatic and biliary cancer3 and later for oesophageal and rectal cancers.4 The devastating symptoms of cancer induced superior and inferior vena cava obstruction can be almost instantaneously relieved by vena cava stenting5 and preoperative embolisation of tumour blood supply is used extensively to negate the serious mortality and morbidity caused by intra-operative bleeding.6

However these are mainly palliative or adjuvant treatments that improve the quality of fading lives, like the majority of chemotherapeutic and some radiation treatments. Curative interventions or interventions which extend life significantly, require ablative techniques i.e. techniques that destroy tumour mass either completely or sufficiently to reduce the tumour load. This review will therefore concentrate on ablative techniques, describing the state of the art in liver and renal ablation and liver chemo and isotope embolisation. Such ablative techniques are increasingly being used in other cancer treatments such as the lung, prostate and perhaps in future the breast.

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Liver tumour ablation 

Improvements in cross-sectional imaging in recent years have driven the increasing detection of small volume, ‘subclinical’ disease, and nowhere is this more evident than in the liver. The multidisciplinary team (MDT) is increasingly faced with the older patient under follow-up for colorectal cancer with small volume metastatic disease or the cirrhotic patient under surveillance with a new small hepatocellular carcinoma. Image guided tumour ablation was first performed in the liver in the early 1990’s, an acknowledgment of the fact that major liver resection – in particular for small volume disease – is a major undertaking for patient and surgeon alike. Effective liver tumour ablation requires an understanding of the devices currently on the market, effective image-guidance and an appreciation of the pathophysiology of the disease and the background organ environment.

Thermal ablation began with monopolar radiofrequency ablation (RFA) in the early 1990’s. In essence this is an open ‘circuit’ operating a ‘radiofrequency’ with grounding pads attached to the patient and the resulting current flux centred around the exposed monopolar tip of the probe which causes lethal tissue heating. Unfortunately, early reports yielded small and poorly predictable volumes of tissue destruction. The manufacturers set about improving probe effectiveness by creating expandable, ‘multi-tined’ and even multipolar probes. These now yield reliable 4 + cm diameter spheres of tissue destruction. More recently microwave (MWA) probes have been developed which appear to produce much faster and more robust zones of tissue destruction in approximately a third of the time of RFA. Cryoablation (CRA) has been utilised in the liver and is attractive as an interventional tool as the lethal ‘iceball’ can be very reliably visualised at CT/MR. There are however still anxieties about CRA in the liver due to reports of earlier devices causing iceball cracking and poorly predictable systemic patient reactions to larger volumes of freezing in the liver.

These devices must be deployed with care in the liver in particular so as to avoid central, perihilar biliary injury or thermal injury to the bowel in the setting of more peripheral treatments. In this respect combined guidance with both ultrasound and CT are of critical importance to both safety and optimised outcomes (Fig. 1).

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  • Figure 1 

    Typical CT Interventional suite set up with MDCT, ultrasound, the ablation equipment plus instruments nursing and radiographic staff. Often anaesthetic staff are present also.

Hepatocellular carcinoma 

Image-Guided ablation (IGA) – largely RFA and MWA – is commonly used in the treatment of smaller volume (<4 cm), discrete hepatocellular carcinoma and in particular where the underlying cirrhosis can add significantly to the morbidity and mortality of more traditional resective surgical techniques. There is increasing evidence that IGA is in oncologic equipoise with resection yielding ∼60% 5-year overall survival for sub-5 cm hepatocellular carcinoma.7 It has been shown that RFA and surgical resection of sub-5 cm hepatocellular carcinoma demonstrated no difference in overall survival or recurrence-free survival rates. All this with considerably reduced costs, hospital stay and patient morbidity.

To further extend the effectiveness of IGA it is increasingly being combined with drug-eluting chemoembolisation techniques to yield oncologically effective outcomes in patients with intermediate and even advanced hepatocellular carcinoma by means of minimally invasive interventional radiology techniques.

Metastatic colorectal carcinoma 

In recent decades major steps forward have been taken in the management of patients with metastatic colorectal disease. Currently liver resection can achieve 40–50% 5-year survival in selected cases with low mortality but morbidity remains high at ∼30–35% in the older age group.8 Likewise modern combination chemotherapy is achieving median survivals of 16–24 months but again at great cost and significant morbidity. Can ablation add something to these significant achievements either as a replacement for surgery in small volume metastatic disease or as an adjunct to systemic chemotherapy?

Initially IGA struggled with high local recurrence rates but with improvements in devices and image-guidance along with better case selection sound results are being achieved. Gillams9 recently reported a 33% 5-year overall survival in patients with sub-35 mm colorectal metastatic disease, obviously achieved in patients rejected for surgery and often chemotherapy. This result alone significantly exceeds the survival currently gained by modern combination chemotherapy. Similarly interim analysis of the CLOCC study of combination chemotherapy +/− additive RFA has shown an improvement in the median progression free survival from 10 to 17 months in the RFA arm. We must be cautious but careful and effective. IGA appears set to make a significant contribution both as an adjunct to chemotherapy and as a less invasive option for patients with small volume, paucimetastatic disease.

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Percutaneous ablation of renal cell carcinoma 

The incidence of renal cell carcinoma (RCC) is rising with over 6000 new cases per year in the UK and around 30,000 new cases per year in the United States.10, 11 This is partly due to greater use of imaging resulting in the detection of smaller incidental RCCs but there may also be an increased incidence in the aging population. Open radical nephrectomy is the gold standard for treating renal cell carcinoma.12 However it is now widely accepted that small RCC (<4 cm) should be treated with minimally invasive and nephron sparing techniques such as image-guided energy ablative therapy and laparoscopic partial nephrectomy.

The energy ablative technologies use either heat based ablative energy such as radiofrequency ablation (RFA), microwaves or cold-based ablative energy, cryoablation.13, 14, 15, 16, 17, 18, 19 Up to now RFA has enjoyed greater popularity because of the smaller RFA needle electrode size that allowed interventional radiologists to perform image-guided treatment with ease. However, percutaneous cryoablation is rapidly gaining popularity as there is now a comparable needle electrode (around 17G) available. Also the ability to visualise a post ablative ice ball in entirety during treatment is a significant advantage. Microwave therapy is a new technology and may offer another option in the treatment of RCC.

Regardless of the type of energy we may use in the future, most published series agree that image-guided treatment of the small RCCs has great promise and the preliminary results show that treatment is safe and effective, with good outcomes for both RFA and cryoablation therapy of small renal cell cancers.4, 5, 6, 7, 8, 9, 13, 14, 15, 16, 17, 18, 20, 21, 22

Technique 

Energy ablative therapy may be delivered via open surgery, laparoscopy or image guidance under ultrasound (US), computed tomography (CT) or magnetic resonance imaging (MRI).

Nowadays, most interventional radiologists perform this treatment in the CT interventional suite. This is because CT is more widely available and cost effective than open MRI for guidance. CT has many advantages such as accurate targeting of the tumour and good visualisation of all the electrode tips especially with the multi-tined expandable electrodes in renal RFA. Precise visualisation of the tips of the tines is crucial in order to avoid ablative injury to surrounding intra-abdominal viscera such as colon or retroperitoneal structures during the ablative treatment. CT also allows operators to inject saline to move viscera away, so called hydro-dissection technique.23 In addition, in CT the ice ball formed during percutaneous cryoablation can be sculpted to fit the exact treatment margin. Monitoring of the treatment response during and after the energy ablative is performed with contrast enhanced CT in patients without contrast allergy or impaired renal function. However, there is a small number of operators who prefer to use ultrasound guidance to insert the initial needle electrodes then use CT to assess the position in relation to the adjacent intra-abdominal structures.

Radiofrequency ablation of renal cell carcinoma 

Radiofrequency ablation destroys tumour by using the frictional heat generated by the radiofrequency waves. When the temperature rises above 60° C, cell death by destruction of the cellular membrane and denaturing of proteins occurs. Such energy can be delivered via either impedance or temperature controlled systems.

For US guided treatment, the RFA needle electrode could be inserted directly under US guidance. An echogenic cloud is formed during treatment (Fig. 2), and this obscures the needle electrode which makes subsequent needle readjustment difficult with US guidance alone. Therefore, nowadays most established centre use CT to check the needle electrode position during treatment (Fig. 3A–C).

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  • Figure 3 

    (A) Contrast enhanced CT shows a small renal cell carcinoma at the upper pole of the left kidney. (B & C) Coronal and sagittal CT reformat shows the overall coverage of the multi-tines RFA needle electrode after insertion into the tumour under CT guidance.

When tumours are centrally located or closely related to the ureter, cold pyeloperfusion (retrograde injection of cold dextrose into the ureter) can be used to minimize the risk of thermal injury to the collecting system which will cause subsequent ureteric stricture.24, 25 More usually percutaneous cryoablation is used.

NICE recommends that patient selection and referral should be via the cancer network. Indications have expanded from candidates unsuitable for surgery to patients with a solitary kidney, Von Hippel Lindau patients with RCC and increasingly patients with none of these things but given the choice of two successful treatments. Patients with metastatic disease undergoing immunotherapy may also be considered for this therapy to debulk the primary tumour.

Pre and post procedural evaluation and outcome 

Prior to treatment patients attend the tumour ablation clinic for staging and counselling. Laboratory investigations such as clotting and baseline renal function, biopsy of the tumour either before/just prior to therapy are also undertaken. Pre-RFA imaging often consists of a combination of US, CT and MRI. They are for staging, planning of therapy and as a baseline for post-RFA changes. After RFA, imaging follow up is variable depending on the operator’s experience. Most institutions have patient follow-up at 1, 3, 6 and 12 m post treatment and annually thereafter.27

The main factors that influence the outcome of therapy are size and location. For tumours smaller than 3 cm in diameter, complete ablation can be achieved in 90% of the cases treated with a single treatment session. Tumour locations can be divided into: exophytic, parenchymal, central/mixed location. The exophytic tumours typically have the best treatment outcome from oven heat effect-due to the surrounding pararenal fat acting as heat insulator to maximise the ablation effect. For tumours between 3 and 5.5 cm, 100% successful ablation is achievable with exophytic tumours and 70% of the cases are treated in a single session.26

Immediately post procedure, the patient is monitored for gross haematuria and must be able to pass urine before discharge. If there is concern regarding complications then early imaging is advised. Minor complications are more common. They are microscopic haematuria in up to 2/3 of cases, perirenal haematoma and post-RFA syndrome.28 Major complications are rare and include haemorrhage that requires blood transfusion, renal failure from acute tubular necrosis, urinoma/calyceal cutaneous fistula and ureteric injury.15, 29, 30

Successful programs require co-operative work within a cancer network, adequate resources and a multi-disciplinary team approach. Good interventional radiology training and diagnostic imaging skills are important for those performing this procedure as the technical success and complication rate is directly related to the operator’s experience.31

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Transarterial chemoembolisation (TACE) 

TACE is a loco-regional therapy for hepatocellular carcinoma (HCC). The basic concept of TACE is to deliver chemotherapy directly into the hepatic artery in order to achieve a high dose in the tumour and reduce the systemic dose and hence side effects of the drug. It takes advantage of the preferential supply to liver tumours from the hepatic artery (90%:10% ratio of hepatic artery (HA):portal vein (PV) supply to tumours; this compares to 75%:25% HA:PV supply to normal liver parenchyma). The procedure is performed under local anaesthesia via a femoral artery puncture. Initial angiography of the celiac axis is performed to provide a roadmap of the hepatic artery tumour supply. The angiographic run is continued into the portal phase to ensure PV flow is in the normal direction. A coaxial microcatheter system is then used to select the tumour supply and deliver the treatment.

The drugs used in TACE are doxorubicin and/or cisplatin. Both drugs are effective agents for TACE, although doxorubicin is the preferred agent in many centres. The drug is mixed with lipiodol to form an emulsion. The lipiodol acts as a carrier, taking the drug into the tumour and releasing it as the two compounds separate out. This is then followed by injection of a particulate embolic agent to slow down the blood flow to the tumour and reduce washout of the chemotherapy (Fig. 4A–D). Recent years have seen the development of drug-eluting beads (DEB) as an alternative drug delivery device. Compared to lipiodol, DEB provide sustained release of the drug resulting in a more prolonged high drug concentration in the tumour (several days as opposed to several hours) and markedly reduced systemic concentrations.

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  • Figure 4 

    TACE of HCC in segments 2/3. Initial angiogram in the (A) arterial and (B) parenchymal phase shows an abnormal blush corresponding to the tumour. (C) Post chemoembolisation angiogram confirms absence of residual tumour enhancement. (D) Follow-up CT scan demonstrates dense lipiodol staining within the tumour.

Patients should have adequate analgesia during and after the procedure as pain from post embolisation syndrome is common. Other complications include infection or liver abscess formation and deterioration in liver function, the latter generally recovering over a period of 2–3 weeks. However, it can occasionally progress to acute liver failure and death.

TACE is a palliative treatment and is, therefore, offered to patients who are not suitable for potentially curative treatments such as liver resection, transplantation and ablation. It has been shown to significantly improve survival at 2 years in selected patients with intermediate stage HCC when compared to supportive treatment.32, 33, 34, 35

The vast majority of patients with HCC have underlying liver cirrhosis and this is an important factor to consider in patients being considered for TACE as their survival is not only determined by the tumour but also by the severity of the cirrhosis. The ischaemic insult resulting from TACE can push the patient with advanced cirrhosis into liver failure. Hence TACE is limited to patients with Child-Pugh class A and early B liver failure. Other contraindications are patients with macroscopic vascular invasion by the tumour (although this remains under debate with some units excluding any form of vascular invasion whilst others will treat patients with segmental vascular invasion), main PV thrombosis, >50% liver involvement by the tumour and the presence of extrahepatic disease. The decision to offer TACE should be taken following discussion at a hepatobiliary cancer MDT.

The advent of DEB TACE has seen an increase in its use in treating non-surgical patients with liver metastases from colorectal cancer (mCRC). DEB loaded with Irinotecan are delivered in a relatively non-selective lobar fashion. At present this treatment has been largely limited to patients with progressive disease despite having 2 or 3 different regimens of systemic chemotherapy. Current data suggests there may be an improvement in survival of patients with mCRC with DEB TACE but is limited to a few cohort studies.36 Larger randomised studies are required before more widespread use of TACE in mCRC can be advocated.

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Selective internal radiation therapy (SIRT) 

SIRT (also known as radioembolisation) is a form of brachytherapy used to treat both primary and secondary liver tumours. It involves the intra-arterial delivery of beta radiation in the form of Y-90 microspheres (half life 64 h). As with TACE, the microspheres are preferentially delivered to the tumours due to their predominant HA tumour supply, resulting in high doses of radiation within the tumours but much lower doses in the normal liver. The Y-90 microspheres are delivered non-selectively to the whole liver via a femoral artery catheter placed in the hepatic artery.

In order to prevent non-target embolisation outside the liver (GI tract, pancreas, lungs) a work-up study is performed, in advance of the treatment procedure, to embolise any branch vessels arising from the HA (most commonly the gastroduodenal artery and right gastric artery). This ensures all the radiation administered during treatment is delivered solely to the liver. Given the small size of the microspheres (32 microns) there is potential for the beads to pass through intra-tumoural shunts resulting in radiation being delivered to the pulmonary circulation. Excessive shunting of the Y-90 microspheres can result in radiation pneumonitis, a condition which can be fatal. The amount of shunting through the tumour is therefore assessed during the work-up by administering Tc-99m labelled macro aggregated albumin (MAA) (which is of a similar size to the Y-90 microspheres and mimics the therapeutic injection). It not only allows assessment of the degree of shunting but also confirms successful embolisation of all extrahepatic branches by demonstrating absence of extrahepatic tracer on the MAA scan. If there is a greater than 20% shunt, treatment is contraindicated. The patient then returns for the therapeutic procedure 2–3 weeks following the workup.

Complications of SIRT include post embolisation syndrome, non-target embolisation (resulting in gastric/duodenal ulcers, pancreatitis, cholecystitis) and radiation hepatitis leading to liver failure.

SIRT has been predominantly used in patients with mCRC. Treatment of other primary and secondary liver tumours has also been reported in smaller cohort series. Encouraging results seen in cohort series in patients with advanced mCRC who have undergone numerous lines of systemic chemotherapy,37 has led to a renewed enthusiasm to investigate its efficacy at an earlier stage in the disease. This is currently being investigated in a randomised trial of first line chemotherapy with or without SIRT.38

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Conclusion 

Percutaneous image guided cancer treatments require a multi-disciplinary approach. They offer relatively safe and effective palliative, and in many cases curative, treatments that improve the quality of life and the length of survival. As the evidence for these new treatments becomes irresistible new agents will be developed and new technologies for the delivery of energy ablation will appear, along with nanotechnologies for the delivery of drugs and radiation directly to the tumour mass. It is important to recognise the new direction that cancer treatment is taking so that all patients have access to well trained expert interventional radiologists and imaging experts working in proper environments with the right equipment.

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PII: S1078-8174(11)00094-0

doi:10.1016/j.radi.2011.10.001

Radiography
Volume 18, Issue 1 , Pages 15-20, February 2012

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