RF ablation targets extrahepatic tumors

The impressive results attained with radio-frequency ablation in the treatment of unresectable liver primary cancer and liver metastases have encouraged researchers to use the technique for other types of cancer. Several experimental studies have demonstrated that RF ablation can completely destroy healthy lung or renal parenchyma and tumor models in animals.^1-4 Small and medium-sized clinical series have also treated kidney, lung, bone, adrenal, pelvic, thyroid, breast, and nodal metastases.

Renal cell carcinomas were among the first extrahepatic tumors to be targeted with RF ablation. RF treatment is similar to that of the liver, although CT guidance is used far more often in kidney ablation. Existing reports of renal RF ablation have been marred by a relatively short follow-up time despite the fact that tumor growth is characteristically slow. Evaluation of treatment efficacy has also been based exclusively on imaging without histological proof. Imaging assessment fails to meet World Health Organization or RECIST (response evaluation criteria in solid tumors) standards because the postablation scar is at least as large as the tumor and decreases in size extremely slowly.^5,6

Whatever the studies' limitations, however, the results appear promising. The largest reported series describes 34 patients with 42 renal cell carcinomas.6 Treatment resulted in complete ablation of all peripheral or exophytic tumors measuring less than 3 cm. Just 10% of these small tumors required an additional RF treatment session to achieve 100% ablation, while 30% of tumors measuring between 3 and 5 cm needed two sessions. Our own investigation found that all peripheral tumors measuring less than 5 cm could be fully ablated in a single session, but Gervais and colleagues demonstrated that tumors with diameters larger than 5.3 cm were unlikely to undergo complete destruction, whatever their location.⁵

Gervais and colleagues achieved successful ablation of tumors with a central component in just five of 11 tumors. Their difficulties were probably due to the heat sink effect caused by large neighboring vessels. Centrally located tumors are also more prone to postablative complications. Two complications arose among the 11 central tumors they treated, compared with two complications out of 31 peripheral or exophytic tumors.⁶

Experimental work suggests that combining RF treatment with selective embolization or temporary balloon occlusion of the renal artery may increase the ablated volume and improve the uniformity and reproducibility when treating large areas or centrally located tumors.⁷ Selective embolization has been used once in clinical practice.⁸ But temporary occlusion is a double-edged sword; suppressing the heat sink effect actually increases the risk of vessel wall damage and vascular thrombosis. Furthermore, in the experimental setting, hilar occlusion combined with RF has been reported to induce chronic pyelonephritis of the whole renal unit,⁹ although Kariya et al did not experience this complication.7 Practitioners should also be alert to increased complications in the urinary tract. Adverse effects in the biliary tract appear to occur more frequently when inflow is stopped during RF ablation.¹⁰

Most authors believe that a halt in lesion growth and the disappearance of tumor contrast enhancement demonstrate successful ablation, as is the case for liver tumors.11 Ablated tumors are often peripheral, and perirenal fat stranding is a common feature (Figure 1). This stranding is roughly parallel to the ablation area and evolves into a more organized rim of hyperattenuating tissue around the ablated area on follow-up CT scans.^5,6 Wedge-shaped unenhancing areas adjacent to the ablated lesion are seen on more than half the follow-up CT images after two months. These are probably due to peripheral renal infarcts after coagulation of small arterial feeding branches. A small amount of perirenal or pararenal blood is seen in 10% to 40% of ablated renal lesions, but this disappears after one or two months.

The incidence of renal carcinoma continues to increase. Over 30,000 new kidney cancer cases were discovered in 2001 in the U.S.¹² Most of these tumors are incidental findings: The frequency of tumors measuring less than 4 cm in diameter is five times greater in asymptomatic patients than in patients showing symptoms of disease.¹³

Nephron-sparing surgery has been used to preserve renal function in patients with a single functioning kidney. The high tumor-free survival rates in such patients suggest that nephron-sparing surgery might be useful for managing small unilateral tumors. This raises the possibility that a local ablative technique could be used in kidney cancer. The efficacy of this technique must first be demonstrated in a nonsurgical subgroup of patients, however. Little is known about the long-term efficacy of RF ablation on renal cell carcinoma, and long-term follow-up studies will be needed to draw firm conclusions. In one study, histologic analysis of nephrectomy specimens that had been ablated seven days earlier found remnant tumor, and this also requires further investigation.14

LUNG TUMORS

Radio-frequency energy deposition varies substantially among various organs. Treatment protocols should be tailored to the target organ to obtain a predictable and reproducible volume of destruction. Electrical conductivity and heat diffusion values differ considerably between the lung, which is full of air, and the liver. RF ablation of lung tumors requires lower power and less energy than is required to treat a liver tumor of the same size. A tumor's pleural contact should be taken into account because it modifies electric conductivity of tissue.

The technique for ablating lung tumors is similar to that used for lung biopsies, although the procedure involves a larger caliber (14-gauge) needle. The needle tract is inserted as perpendicular as possible to the pleura and should traverse the shortest length of aerated lung parenchyma, avoiding scissurae. The number of passes via the pleural cavity should be minimized to reduce the likelihood of pneumothoraces. Lungs are treated one at a time to avoid the possibility of life-threatening complications from bilateral adverse events, such as massive hemorrhage or pneumothorax.¹⁵ Several tumors can be treated on one side during the same session.

Expandable needles will be more stable when open and will not slip out of position if a massive pneumothorax moves the target tumor away from the needle. We found pneumothoraces occurring in 50% of treatment sessions, but 29% were small enough that they did not require treatment. The remaining 21% were expelled manually after inserting a small-bore needle catheter with sideholes while the patient was still lying on the CT table, immediately after or during RF ablation. We used CT guidance to insert the needle and to verify that the pneumothorax had been drained completely. Larger caliber chest tubes were subsequently required in just 2.5% of treatment sessions.

CT images obtained within a few minutes after the end of RF energy delivery show the lung tumor surrounded by ground-glass opacity, which in our experience enlarges the diameter of the hyperattenuating area by an average of 68% (Figure 2). Enlargement is even greater on images acquired after 24 and 48 hours, although opacity eventually decreases during follow-up.

We have verified treatment efficacy in 104 of the 110 lung tumors we targeted. The successfully ablated tumors were found in 49 of 55 patients. We assessed efficacy according to an imaging follow-up protocol performed two to 12 months after ablation, based on a decrease in size and the absence of contrast uptake in the treated tumor. These results are consistent with reports presented at international conferences during the past 12 months. In our experience, local tumor regrowth was seen more than six months after treatment. These late discoveries of recurrence emphasize the importance of a preliminary report that was presented at this year's European Congress of Radiology, suggesting that PET scanning could be used for follow-up, allowing early detection of incomplete treatment.¹⁶

BROADENING SCOPE

RF can be used either to ablate small bone tumors completely or to ease pain caused by large bone metastases that cannot be successfully managed with medication and radiation therapy. Osteoid osteoma was one of the first bone lesions to be treated with thermal ablation (laser and RF). Most publications reported efficacy rates exceeding 90%.¹⁷ This benign tumor is usually small and requires accurate targeting. Treatment is often performed under CT guidance after drilling the cortical bone. Insertion of a single bare laser fiber or individual RF needle in the right location can be followed by a short thermal ablation session. Small malignant tumors have been ablated successfully with RF, but only a few cases have been reported, again with a limited follow-up period.

Expandable multiple-array needles produce a larger volume of ablated tissue. Preliminary reports indicate that these tools yield excellent results for palliative treatment of pain caused by large osteolytic bone tumors that cannot be successfully managed by standard pain management with analgesics and radiation therapy.¹⁸ Complete tumor ablation is not necessary when RF energy is used in pain management; instead, practitioners seek to destroy nerve endings in the endosteum that are partially responsible for the pain from destroyed bone. Physicians should try to preferentially target the margin of bone metastases with a view to treating the soft-tissue/ bone interface.

Nerves, especially the spinal cord, are highly sensitive to heat. Temperatures above 45 degrees C have been shown to be toxic to the spinal cord. Extreme caution should be exercised when treating the vertebral body with RF energy as a pain management tool. Cortical bone can act as an insulator, providing a shield when vertebral body tumors are treated with RF.¹⁹ RF treatment may not be possible if posterior wall cortical bone is not present in a vertebral body tumor less than 1 cm from the spine.

Post-therapy changes may take a long time to become visible on CT. Postablation healing of an osteoid osteoma, for example, can take a year to be visualized on imaging. Early pain relief, which usually occurs in less than a week, is the best sign that therapy has been successful. Malignant bone tumors exhibit a similar healing pattern. Tumor shrinkage and recalcification appear a long time after pain relief. The periablation rim of inflammation is seen as hyperintense on T2-weighted MR imaging, with a highly enhanced rim (Figure 3).

Reasonable success for RF treatment of adrenal lesions has been reported at international conferences, but results are limited to small groups of patients²⁰. An animal experiment has also been used to demonstrate the use of RF, via an endoscopic ultrasound system, to destroy small tissue volumes in the pancreas.^21,22 This option could be developed to treat small pancreatic tumors such as neuroendocrine lesions, which are sometimes discovered at an early stage.

Only one study has been published on the clinical application of RF ablation in the pancreas. The researchers used RF to treat unresectable pancreatic tumors in 20 patients. They encountered two major complications and achieved a biological response rate of 75%, but the paper has no details of follow-up studies.

We have recently used preoperative RF to treat metastases from renal cancer in the pancreatic tail. CT scans showed satisfactory ablation on day seven (Figure 4), but pancreatitis induced false aneurysms of the splenic artery after two weeks. The patient then underwent surgical splenectomy and caudal pancreatectomy.

Pelvic tumors pose a treatment challenge, due to rectal carcinoma recurrence in the presacral space. The proximity of other organs such as nerve roots, which are highly sensitive to heat damage, limits the use of RF ablation in this location. We encountered a neurogenic bladder after attempting RF treatment (Figure 5), and anecdotal evidence indicates that other groups have encountered the same problem.

RF ablation offers great potential as a minimally invasive therapy for local cancer. But many steps are needed before the techniques described above can be used in routine clinical practice. These include, at the very least:

optimizing RF ablation in each organ by tailoring treatment to specific morphology, vascularization, electrical conductivity, and heat diffusion;

exercising caution to avoid collateral damage in the targeted organ and in neighboring organs;

validating procedure and imaging parameters that correlate with tumor destruction, thereby rapidly establishing the technique's efficacy and avoiding recurrences many months after treatment;

determining the local efficacy of RF ablation in a larger series of patients and with longer follow-up; and

comparing results of RF ablation with other techniques, such as surgery, to determine their respective place in the therapeutic regime.

It is not yet possible to define the exact role of extrahepatic RF in the treatment of cancer, but it seems likely that the option will be reserved for nonsurgical candidates.

DR. DE BAERE is an interventional radiologist at the Institut Gustave Roussy in Villejuif, France.

References

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