Treating cancer

Understanding ablative techniques

The objectives of tumour ablation are to increase patient survival and sometimes to palliate local symptoms and painful tumours. There are several techniques which cause either tissue heating (radiofrequency [RF], microwave, laser, focused ultrasound) or freezing (cryotherapy). Advantages over surgical tumour resection are due to the minimally invasive nature of these therapies, which allows a wider spectrum of patients to be treated and reduces morbidity and mortality. Some treatments are performed on an outpatient/day-case basis, with potential to decrease costs.

Imaging guidance for ablation

Fluoroscopy, ultrasound, computed tomography (CT) and magnetic resonance imaging (MRI) are the modalities used, with ultrasound and CT being the most useful and practical.

Imaging has five distinct purposes:

• Planning: ultrasound, CT, MRI and more recently, positron emission tomography (PET) are used for planning/assessing suitability.

• Targeting: ideal qualities of a targeting technique include clear delineation of the tumour(s), treatment electrodes and the surrounding anatomy, coupled with real-time imaging and multiplanar and interactive capabilities ( Fig. 44.1 ).

  

• Monitoring: important aspects of monitoring include how well the tumour and/or target is being covered by the ablation zone and whether any adjacent normal structures are being affected at the same time.

• Controlling: MRI is currently the only modality with real-time temperature monitoring. When using cryotherapy, CT clearly delineates formation of the iceball.

• Assessing treatment response: post-procedural imaging.

Size of lesion:

Increase in size is normal during the first 1–4 weeks due to reactive changes after ablation. At 3 months, the lesion should be equal to or smaller than the pre-procedural size. Considerable involution is expected by 6 months and thereafter.

Contrast enhancement:

A lack of enhancement suggests adequate tumour ablation.

Another important follow-up tool is tumour markers – elevation in organ-specific tumour markers points to recurrence or new lesions.

Tip

If using ultrasound guidance, start with the deeper portions of the tumour to prevent microbubbles produced during ablation of the superficial parts blocking your view!

When using CT, utilize the multiplanar images and reconstructions for better evaluation of probe and electrode tips – this is especially important when using expandable multi-tined probes.

Radiofrequency ablation

RF ablation (RFA) is the most widely used minimally invasive image-guided tumour ablation technique and is used for treating a wide variety of focal primary or secondary tumours in many organs, particularly the liver, lung, bone and kidneys.

General principles of RFA

• Tumour size should be <4 cm if a complete cure is the aim, regardless of the site of origin.

• Curative tumour ablation treatment must include an 0.5–1-cm margin of healthy tissue around the target lesion in order to treat any microscopic satellite foci and avoid early local recurrence.

• Multiple overlapping spheres ( Fig. 44.2 ) or cylinders of necrosis may be needed to achieve adequate ablation of tumour, and systems that are based on coaxial guidance can be advantageous for larger lesions.

  

• For tumours >5 cm, the main role of RFA is to debulk the lesion prior to chemotherapy or for pain relief.

There is a variety of different systems available for RFA, but the core principles and science behind RFA remain the same. In essence, RFA applicators are introduced percutaneously into the target tumour using CT or ultrasound guidance. The applicators have straight or expandable electrodes ( Figs. 44.1 b and c , 44.3 ). A high-frequency alternating current (460–500 kHz) is delivered through the lesion, which causes agitation of ionic molecules producing localized frictional heating within the tissue. The electrical current exits the body through grounding pads attached to the thighs ( Fig. 44.4 ). Local tissue temperatures between 60°C and 100°C produce protein denaturation, immediate cell death and coagulative necrosis of the tumour.

Tip

The endpoint of ablation is assessed either by a change in electrical impedance or by measurement of the temperature at the electrode tip. Check that you are familiar with the parameters of the equipment you are using.

Contemporary systems vary in power, size of needles, electrical parameters, and, most importantly, the electrode technique to maximize treatment volumes. Temperature and impedance changes during RFA reflect tissue cooking or overcooking. Although temperature and impedance are measured in several of the systems, each one uses one parameter to maximize treatment diameter. There are system-specific treatment algorithms which require varying degrees of operator input. Temperature information at the periphery of the thermal lesion (from thermocouples on the RFA probes or external thermocouples) may help to assess skip areas next to vessels from the heat sink.

Microwave ablation

Microwave ablation relies on agitation of water molecules around the probe to heat the surrounding tissue. The technique can be used percutaneously, laparoscopically or with open surgery. Optimal tumour size for treatment is <3 cm. Microwave typically produces higher intra-lesional temperatures than RFA and is less prone to heat sink effect.

There are several different device modifications available. Many needles need active cooling with saline to reduce the risk of heating non-target tissue proximal to the antenna tip. Several devices types allow placement of multiple antenna to permit treatment of a larger volume of tissue. Active monitoring of treatment is possible with placement of intra-tumoral thermocouples.

Cryotherapy

Cryotherapy uses related freeze/thaw cycles to cause cell death. The nature of the effect is complex and depends on the temperature reached, the speed of cooling, the rate of thawing and the number of freeze/thaw cycles. In simple terms, at temperatures from 0 to −20°C extracellular ice crystal formation causes cell death by osmotic dehydration (solution effect injury). At lower temperatures, e.g. −20° to −40°C, intracellular ice crystal formation leads directly to cell death. In addition, damage to capillary endothelium leads to coagulation and tissue hypoxia.

The cryoprobe is inserted into the tumour under image guidance and rapid expansion of argon induces cooling (Joule Kelvin effect) with subsequent helium flushing controlling the thaw cycle ( Fig. 44.5 ). The technique can be used percutaneously, laparoscopically or at open surgery. The best results are achieved in tumours <4 cm, however in patients unsuitable for other treatment modalities using multiple probes, it is possible to treat much larger tumours with cryotherapy. The main advantage of cryotherapy is that the iceball produced is readily visualized on CT, MR or ultrasound (US) scanning with immediate demonstration of target tumour destruction. Cryotherapy is not for the faint-hearted; multiple probes are required but it is very controllable as a technique. The control of the iceball makes cryo particularly suitable for central renal lesions. Typically cryotherapy treatment sessions take 1.5–2 h and usually it is kinder to have the patient under general anaesthesia.

Alarm

Patients with cirrhosis and liver tumours can develop ‘cryoshock’, which has a poor prognosis and, although technically tempting, the pendulum is swinging away from treating this group with cryotherapy.

There are limited numbers of cryotherapy systems available but all use the same technology. Multiple probes are required, typically 4–6 probes will be used to treat a lesion that is 5 cm. Argon and helium are relatively expensive and coordinating delivery of gases can be a hassle.

Irreversible electroporation

Irreversible electropolation (IRE) is a relatively new form of ablation that utilizes microsecond pulses of direct current to induce cell membrane damage and cell death by apoptosis. Unlike other ablation techniques based on thermal techniques, IRE offers a degree of tissue selectivity; structures formed predominately of protein are not affected by IRE and therefore collagen-based structures such as vessels and ductal systems can be preserved. The transition zone between ablated and non-ablated tissue is narrow, in theory, only a few cell layers, and complex treatment fields can be configured by placement of multiple electrodes. Finally, IRE is not sensitive to thermal sink effects and allows effective treatment closer to vascular structures. It may sound as though IRE is the perfect ablation technique but it does have its own complexities; strong muscle contractions mandate deep muscle relaxation, ECG synchronization of pulses is required to minimize the risk of cardiac arrhythmia and differences in local electrical conductivity can impair treatment volumes. Although experience is limited, this technique has particular promise in treatment of tumours that are challenging to thermal techniques due to vascular proximity such as pancreatic lesions.

Procedure

Ablation: key procedural steps

The key to complete and successful ablation is the precise placement of the electrode relative to the tumour.

• Review all pertinent cross-sectional images, including MPR.

• Note the size and number of tumours, and the anatomical relationship of the tumour to vital structures.

• Plan the point of entry, a safe trajectory, and the end position of the needle; understanding image guidance is essential. (See Chapter 26 for intervention for useful tips.)

• If using RFA, ensure ground pads are secure and be familiar with the electrode/generator and regimen for heating.

• Ensure adequate analgesia and sedation for during and after the procedure; some treatments will require general anaesthesia.

• Inject local anaesthetic from the skin to the surface of the target organ (except for lung lesions).

• Advance the electrode towards the tumour along anaesthetized tract and deploy.

• At the end of the procedure, perform scan to check for any immediate complications.

Complications

New techniques bring new complications and essentially the potential complications can be divided into three categories.

Complications of electrode placement

• Bleeding: depends on tumour location and character of the underlying parenchyma.

• Infection: strict sterility; risk factors are diabetes and biliary enteric communication (for liver RFA).

• Tumour seeding: commoner in superficially located, poorly differentiated hepatocellular carcinoma. Meticulous technique is required for initial placement of the electrode, with care taken to ensure optimal positioning on the first pass. Use coaxial needle, with the advancement of the inner electrode only through the tumour. ‘Hot withdrawal’ technique to coagulate tract site may reduce tumour seeding and also reduce bleeding rate.

• Pneumothorax: similar to lung biopsy; traversing fissures or long transpleural tracts increases the risk.

Complications of thermal therapy

• Post-ablation syndrome: this presents with constitutional symptoms such as fever (low-grade) and arthralgia. Seen more commonly when large tumour volume is treated. Supportive treatment with pain medication and rest is all that is required. Strict adherence to aseptic technique and eradication of pre-existing infection prior to the procedure help avoid post-ablation syndrome.

Alarm

Persistent fever after 2–3 weeks should raise suspicion for infection.

• Non-target damage: bile duct strictures, cholecystitis and perforated bowel have all been recorded. Colon is at higher risk than small bowel (more mobile) or stomach (thicker wall and fewer adhesions).

• Grounding pad burns: The grounding pads heat up during RFA; if you are in any doubt if you feel the leading edge of the pad during treatment. Grounding pad burns are well recognized and largely avoidable by checking of the pads prior to use for blemishes and periprocedural checks to monitor any temperature increases.

Organ-specific complications

• These are covered in the sections on specific applications.

Primary hepatocellular tumours

Primary hepatic tumours are increasing in incidence. Transplantation offers the best chance of a cure. Patients unsuitable for surgery are considered for ablation, chemo or radio embolization or chemotherapy with sorafenib. The choice between these agents is dependent upon number of tumours, volume of disease, location of disease and background liver function. For patients with suitable disease, ablation offers the best chance of local control and in patients with tumours <5 cm in size delivers comparable results with hepatic resection but with better preservation of hepatic function.

Hepatic metastases

The optimum treatment remains hepatic resection for secondary liver tumours. Small-volume (<4 cm in diameter) colorectal metastases have been treated with ablation but, as there are likely to be micrometastases, recurrence rates are higher than for hepatocellular carcinoma. Chemoembolization has generally produced disappointing results for colorectal metastases however radioembolization has shown some promising results in patients who have previously had chemotherapy. At present, radioembolization remains a complex treatment and its use is restricted to specialist centres and a small patient cohort.

Bland embolization

Embolization with standard particulate agents is used to treat carcinoid tumours to provide symptomatic relief. In hepatoma, particulate agents and coils can be useful in the treatment of acute bleeding but anti-tumoral effects are better with trans-arterial chemoembolization (TACE) and radioembolization.

Transarterial chemoembolization

TACE is a treatment used for irresectable hepatoma. The treatment delivers high doses of chemotherapy directly to the tumour and combines this effect with hypoxia to induce tumour regression. Selection criteria will vary between units but generally TACE is considered for patients with a single tumour >5 cm (tumours below this are usually suitable for resection or ablation) or multifocal disease.

TACE is possible due to the dual blood supply to the liver from the hepatic artery and portal vein. Occlusion of a segmental hepatic artery produces tissue hypoxia but the residual portal vein supply prevents hepatic infarction. Hence, determination of portal vein patency is a key component of pre-intervention assessment. Patients with segmental portal vein occlusion can be treated but the risk of complications increases significantly. Inevitably, there is a loss of hepatic function with TACE and patients with severely impaired hepatic function (e.g. Child's C, bilirubin >50 mmol) are at a high risk of hepatic failure. Finally, there is risk of hepatic abscess post-treatment, which increases markedly if there is a biliary enteric fistula (25%).