Non-resectable and metastatic tumours present a difficult challenge for veterinarians and pet owners. The relatively limited efficacy of intravenous chemotherapy for macroscopic disease, and the cost and morbidity associated with radiation therapy have stimulated the search for additional therapeutic options. Similar difficulties in human oncology have inspired various creative, image-guided, regional tumour therapies in the continuously developing subspeciality of interventional radiology (IR). IR involves the use of contemporary imaging techniques such as fluoroscopy and ultrasonography to selectively access vessels and other structures in order to deliver different materials for therapeutic reasons. In the past two decades, IR techniques have expanded considerably with both vascular and nonvascular procedures being performed routinely in humans. Specifically, IR techniques are being increasingly utilised to help palliate humans with cancer in which traditional therapies have failed or have been demonstrated to provide little benefit. These techniques are particularly useful in cases of regional disease in order to maximise local therapy and minimise systemic toxicity. While results have been variable, regional techniques such as percutaneous tumour ablation, intra-arterial chemotherapy, transcatheter arterial embolisation/chemoembolisation and/or palliative stenting have been demonstrated to improve survival times, disease-free intervals, recurrence rates or completeness of tumour necrosis.

Traditional Therapies

Traditional treatment modalities still remain an important part of managing patients with metastatic or non-resectable cancers. Systemic chemotherapy typically demonstrates poor response rates for most bulky tumours or metastatic disease; however, can occasionally shrink excessively large tumours enabling subsequent resection. Radiation therapy is routinely used for palliation of pain associated with bony tumours and is useful for carcinomas and oral tumours but internal tumours and sarcomas are more difficult to treat. Surgery can still play a major role in animals with advanced malignancies, even when tumour excision is not possible. Debulking non-resectable tumours or closing ulcerated masses may occasionally be indicated, but is typically avoided as the patient's quality of life is often not substantially improved in these situations, and surgical complications are not uncommon.

Palliative Stenting for Malignant Obstructions

Animals are routinely euthanased for local effects of a tumour rather than the systemic effects associated with a large cancer burden. For example, malignant obstructions of the urinary tract associated with transitional cell carcinomas or prostatic tumours can result in life-threatening signs associated with complete urinary tract obstruction. IR techniques involving the placement of intraluminal stents to palliate similar malignant obstructions in humans have been described. Palliative stenting procedures in the urinary tract (Figure 1), respiratory tract and upper and lower gastrointestinal tracts to relieve luminal obstructions due to neoplasia in animals as small as a ferret have recently been performed under fluoroscopic guidance. These IR techniques were rapid, safe, minimally invasive and effective, and complications were minor and uncommon.

Figure 1. Urethral transitional cell carcinoma stent.

Intra-Arterial Chemotherapy Delivery

Current therapies for bulky tumours not amenable to complete surgical resection include chemotherapy, radiation therapy and surgical debulking, but none are able to consistently produce durable remissions. Research suggests that some of these tumours can respond more favourably to higher concentrations of chemotherapy; however, significant deleterious side effects often result when dose escalations are attempted. Recent advancements in interventional radiology techniques now enable veterinarians to administer different drugs into the arteries feeding the actual tumours via minimally invasive approaches in order to achieve very high regional drug concentrations within the tumour without the systemic side effects that would occur had these levels been administered intravenously. This basically provides a local dose escalation without the increased systemic toxicities. Studies confirm both higher achieved levels of chemotherapy within the targeted tissues as well as improved tumour remissions in laboratory animals. It is possible that we can demonstrate similar effects in our canine patients with naturally occurring tumours not amenable to currently available standard-of-care treatments.

Arterial Embolisation / Chemoembolisation

'Embolotherapy' involves the use of fluoroscopy to selectively access specific vascular structures in order to deliver particulate material to control haemorrhage, occlude vascular malformations or reduce tumour growth. Arterial embolisation techniques using polyvinyl alcohol particles or other materials have been performed in veterinary patients to control intractable epistaxis associated with nasal tumours, to reduce haemorrhage associated with non-resectable tumours, or to control pain and slow tumour growth of metastatic cancer. In some cases, subsequent surgical resection was possible following embolisation-induced tumour shrinkage.

Chemoembolisation involves super-selective intraarterial chemotherapy delivery in conjunction with subsequent particle embolisation. Intra-arterial chemotherapy has been shown to result in a 10- to 50-fold increase in intratumoural drug concentrations when compared to systemic intravenous chemotherapy administration. Subsequent particle embolisation results in tumour cell necrosis and paralyses tumour cell excretion of chemotherapy resulting in minimised systemic toxicity. This procedure is most commonly used in the treatment of diffuse hepatocellular carcinoma or metastatic liver disease in humans. Most hepatic tumours depend upon hepatic arterial blood supply (up to 95%) for growth in contrast to the normal liver parenchyma, which receives the majority of its blood supply via the portal vein (only ~20% from the hepatic artery). Hepatic artery embolisation should theoretically cause more ischaemia to the liver tumour while the remaining normal hepatic parenchyma obtains sufficient oxygenation from the portal venous system. In addition, when used within the liver, the chemotherapy is often typically mixed with a carrier agent, Ethiodol. This oily substance supplies radiographic contrast to the chemotherapy as well as acting as a tumour localiser and embolic agent. Hepatic tumours lack Kupffer's cells which are important for metabolising oily substances (lipid) in normal hepatic parenchyma. Therefore, the Ethiodol and accompanying chemotherapy are concentrated within the liver tumour rather than the surrounding healthy hepatic parenchyma. More recently, chemotherapy-eluting beads are being evaluated in veterinary patients with non-resectable liver tumours (Figure 2).

Reported complications in the human literature include haemorrhage at the vascular access site, non-target embolisation complications (skin necrosis, damage to normal parenchyma), hepatic infarction/abscessation, acute renal failure (for liver tumours), and postembolisation syndrome, a collection of clinical signs characterised by malaise, fever and pain.

Figure 2. Hepatic artery chemoembolisation (dog).

Figure 3. 3D CT reconstruction of dog with maxillary fibrosarcoma and cryoprobes in place.

Percutaneous Tumour Ablation

Percutaneous tumour ablation techniques (radiofrequency ablation as well as microwave ablation, laser thermal ablation, cryoablation and percutaneous ethanol injection) tend to be most effective with a few (less than three), small (< 4 cm diameter) lesions. These circumstances are fairly uncommon in the author's clinical experience; however, with the routine use of more advanced imaging techniques in veterinary medicine, lesions of this size and number may become increasingly apparent during tumour restaging procedures, making tumour ablation techniques a reasonable option in the future. More recently, advances in local ablation technology have provided the ability to more closely monitor the areas of ablation as well as to provide larger ablation areas. We are currently evaluating the use of some of these techniques for head and neck tumours, and other soft tissue tumours in areas not easily amenable to aggressive surgical excision.

References

References are available upon request.