Interventionalists offer new choices for cancer therapy

Five years ago, Dr. Michael Soulen, an interventional radiologist at the University of Pennsylvania, used radiofrequency ablation to kill malignant liver tumors in six patients per year. He now treats about the same number of patients with tumors in several organs during a single day, using a host of interventional oncology procedures.

Thermal ablation and other minimally invasive image-guided therapies for the treatment of solid malignancies have seen dramatic increases in utilization. Interventional radiologists view the development of interventional oncology as an opportunity to increase the visibility and clout of their specialty. The Society of Interventional Radiology launched an Interventional Oncology Task Force (IOTF) in 2004 to help shape the budding field (see accompanying article).

Increasing data and public interest have cast image-guided therapies for cancer into the spotlight, with RFA as poster child. Improved imaging modalities allow IRs to target tumors more accurately, with the ability to relieve symptoms of certain types of cancer and the might to destroy others. Alone or in combination with other interventional techniques, image-guided therapies have enabled IRs to make a significant leap.

"For a specialty that has been otherwise making major contributions to oncology-though in palliation, not in cure-being capable of doing what only surgeons were able to do until recently is a big jump," said Dr. Andreas Adam, president of the Cardiovascular and Interventional Radiological Society of Europe.

Adam has worked closely with the IOTF on the development of the interventional oncology strategy.

DRIVING FORCES

Interventional radiology's involvement in the field of oncology started decades ago. First, IRs developed a host of image-guided procedures such as shunting, drainages, and stenting, which became useful adjuncts for several types of cancer patients.

Researchers showed during the early 1980s that peritoneovenous shunting, a procedure to improve blood flow, could benefit patients with malignant ascites from liver cancer. Shortly thereafter, they expanded the procedure to treat patients with malignant ascites from abdominal, breast, genitourinary, and gynecologic cancers. Image-guided catheter drainages have been proven particularly helpful to eliminate fluid collection in patients with cancer of the spleen, kidney, and pancreas. Likewise, percutaneous stenting helps bypass obstructed organs and vessels to facilitate internal drainage.

The new image-guided techniques are aimed more at treating tumors, not just their corollaries. CT- or ultrasound-guided percutaneous thermal ablation allows interventionalists to use different sources of energy to kill tumors by literally cooking or freezing them. The most widely used techniques include radiofrequency, microwave, laser, and, to a lesser extent, focused ultrasound ablation and cryotherapy.

With transarterial chemoembolization, the specialist delivers chemotherapeutic agents directly into the tumor while blocking its blood supply. Most biochemical agents used include polyvinyl alcohol particles, Trisacryl gelatin microspheres, cisplatin, doxorubicin, or mitomycin C.

Intra-arterial radioembolization, a brachytherapy technique developed by IRs, entails the use of radioactive microspheres such as iridium-192 or yttrium-90 to irradiate tumors. These radiotherapeutic agents are meant to mimic the effects of conventional radiotherapy with a twist: They have to be infused into the area of interest with microcatheters so the radiation hits the tumor from the inside out.

Other techniques that help to alleviate the excruciating pain caused by tumors also help patients regain stability or mobility. Osteoplasty and vertebroplasty procedures fill bony structures that have been weakened or fractured by malignancies, frequently in the spine or pelvis, with cement. The cement reaches high temperatures, which may produce an effect similar to thermal ablation.

When IRs incorporated these tools-the byproduct of years of experience in helping to treat cancer patients-into their armamentarium, they gained the necessary edge to become the fourth arm of cancer treatment, said Dr. Daniel B. Brown, an interventional radiologist at Washington University's Mallinckrodt Institute of Radiology.

BREAKTHROUGHS

The ability to curb a tumor's blood supply using drugs is no novelty. Neither is the ability to cauterize living tissues using heat. What's new, in separate or combined procedures, are the use of microcatheters to reach just the right vascular segment of a tumor, the introduction of tiny radioactive seeds or drug-eluting chemotherapeutic agents, and the use of thermal ablative devices to kill tumors, said IOTF cochair Dr. Damian Dupuy, an interventional radiologist at Brown University Medical School.

Most ablative devices remain somewhat basic, but they undergo frequent updates. Until recently, for instance, cryotherapy probes were so large that procedures could be performed only through laparoscopic or open surgery, requiring a long recovery time in the hospital. Improved cryotherapy technology means not only smaller probes for percutaneous ablation but also the possibility of outpatient treatment.

Researchers from the Karmanos Cancer Institute and Wayne State University in Detroit recently treated 11 patients with metastatic ovarian or cervical cancer using cryotherapy. The procedure provided safe tumor control without significant morbidity or mortality, and the patients were sent home four to six hours later. The investigators presented their findings at the 2005 SIR meeting in New Orleans.

Several other studies presented at that meeting showed promising results. Trials proposed single or combined approaches for patients who may not undergo conventional treatments.

Dupuy and colleagues at Brown assessed the safety and efficacy of RFA followed by Ir-192 brachytherapy in 13 inoperable stage I non-small cell lung cancer patients. The procedure was technically successful in all patients, with no treatment-related deaths. The researchers have not seen signs of recurrence after a mean follow-up interval of six months. Findings suggest the combined approach may offer a promising noninvasive alternative.

Interventional radiologists at the Center for Surgical Advancement's Celebration Health/Florida Hospital reported results on 42 patients treated with focal cryoablation to target and destroy prostate cancer. The investigative team, led by Dr. Gary Onik, determined that 95% of the patients have stable prostate-specific antigen tests and no sign of recurrence after eight years of follow-up. They found that focal cryoablation of prostate tumors could destroy malignancy without affecting healthy tissue around the gland, which helps preserve urinary and sexual functions.

While the focus of interventional oncologists is to provide a cure, palliative care remains important. In many cases, patients are diagnosed when it is too late, and the focus of treatment shifts, said Dr. Anthony G. Ryan, an interventional radiologist at Vancouver General Hospital in British Columbia.

"Interventional radiology offers a huge range of treatments to help relieve some of the most distressing symptoms of advanced cancer, which can significantly reduce the quality of remaining life of these patients," he said.

Ryan coauthored another study presented at the SIR meeting that included patients treated with osteoplasty to relieve tumor-induced pain. The Vancouver investigators assessed five patients with malignancies and three with benign tumors. The lesions affected the sacrum, acetabulum, ischium, and pubis, and some presented with significant technical challenges for the injection of bone cement into the tumor. All patients experienced prompt and lasting relief from pain without significant complications.

ORGAN-BASED STRATEGY

Interventional radiologists have been recording encouraging results for a host of organs and applications. But to match their oncology colleagues' clout, they must invest in the areas where they have accumulated the most credible research. Insiders agree that most efforts will concentrate on the liver, kidneys, and lungs.

RFA of the liver has provided the most consistent results in the past. The liver was the initial target organ for treatment, as most patients with liver tumors do not qualify for surgical resection. IR practices will most likely see such patients from two sources:

- hepatocellular carcinoma, a type of primary cancer that until recently had not been prominent among U.S. patients; and

- colon cancer metastases, the most common source of liver tumors in the country.

Percutaneous ablation usually tops the image-guided therapy list for kidney tumors. Surgery can still be considered as a low-risk and effective standard of care, but oncologists refer most nonoperable patients or those with residual renal masses to ablative therapy.

Patients with lung tumors who are not candidates for surgery also qualify for ablation. Some specialists observe that many patients with lung carcinomas who fail radiation therapy end up in the interventional suite as well. Lung RFA could make a considerable contribution to the clinical management of these patients.

Lung cancer is the number one killer of cancer patients in the world. Although it is still a contentious issue, the ability to screen high-risk patients may enable physicians to detect more tumors at an early stage. If interventional radiologists were to prove that RFA can give a curative chance to these patients, the economic implications would be huge, said Dr. Riccardo Lencioni, a researcher and interventional radiologist from the University of Pisa, Italy.

"Lung RFA could have an unbelievable potential. Currently, we calculate the universe of lung cancer patients will border on something like 180,000 for the next year only in the U.S. Although this is only a rough prediction, you can get a sense of what it could mean for IRs," he said.

WORKING WITH ONCOLOGISTS

IRs can offer oncologists a helping hand. Surgery remains the ultimate treatment in local regional therapy, according to Dr. Jeffrey Geschwind, director of interventional radiology at Johns Hopkins University. It is the only method of cure in areas that are off-bounds to ablation, such as the small intestines and colon. But it has shortcomings. Many patients are either too ill or have too many contraindications to undergo surgery, making them prime candidates for image-guided therapy.

Chemotherapy has proven to be an exceptionally successful technique, but it too is imperfect. Chemo-treated malignancies may seem to shrink or even disappear, but then recur. In addition, systemic therapy's potential toxicity remains an issue.

"In order to kill the tumor using systemic therapy, you need to give high doses of chemo that could also destroy a significant amount of healthy tissue, whereas with local regional therapy, you are targeting only the area that needs to be treated. That is a huge advantage," Geschwind said.

As for radiation therapy, some interventionalists assert that it cannot offer the results that minimally invasive image-guided therapies could in certain organs.

However contentious these issues might appear, IRs and oncologists have not become locked in turf battles. They have developed a complementary relationship in which oncology specialists first chose to be neutral observers and then collegial partners as they saw image-guided therapies' results.

"We are not going to replace conventional treatment strategies. Yet we are going to offer a very compelling new arm to the oncologic armamentarium. Our research shows how combining thermal ablation with either chemo- or radiation therapy can potentially be more efficacious than any of those therapies alone. I envision interventional oncology being a robust, important part of the multidisciplinary oncologic practice of the future," said Dr. S. Nahum Goldberg, director of the Tumor Ablation Program at Beth Israel Deaconess Medical Center in Boston.

IRs need to ensure that the indications for image-guided therapies are sound. They bear the burden of proof to show that their interventions are better than surgery or at least as good. Until IRs conduct large-scale trials showing that ablation works as well as surgery, surgery must be the first choice, Adam said.

Interventionalists have to work closely with oncologists to develop the right treatment protocols, according to Lencioni. They need to discuss the trials that they believe are needed, cancer by cancer. And they need to find out from the oncologists if and when they can be the first option for nonsurgical candidates.

"Let's decide on a trial of RFA or another ablation technique versus radiation therapy, which is currently the accepted treatment for nonsurgical lung cancer. By discussing together these kinds of trials, and becoming more and more involved, we will continue to go in the right direction," Lencioni said.

OPPORTUNITY AND CHALLENGE

The push into interventional oncology could open a whole new area of subspecialization. Some IRs foresee an opportunity to perform services that could generate considerable revenue, allowing them to focus on intervention rather than diagnostic work.

In a study presented at the 2005 SIR meeting, a group of University of Pennsylvania researchers led by Dr. Catherine Tuite and Dr. Jeffrey Solomon studied the feasibility of setting up an independently run clinical interventional oncology practice in an academic hospital. Although the clinical practice of interventional oncology represented a large investment of time and resources, they found that it could provide substantial incremental income to the general radiology practice.

The investigative team, including financial and marketing analysts, recorded every possible aspect involved in the workup of interventional oncology patients, from initial consultation to diagnostic imaging to intervention and treatment monitoring. They analyzed the relative value units generated against standard payment rates from the Centers for Medicare and Medicaid Services, and the results were astounding. The total downstream professional revenue to the radiology department was more than $7000 per new ablation patient and about $10,000 per new chemoembolization patient. The average revenue to the radiology practice was above $120,000 annually, said coauthor Soulen.

He and other IRs consider it too early to start talking about a new subspecialty. Large hospitals may tolerate IRs specialized in single organs. But that is unusual, and with a shortage of diagnostic radiologists, let alone general interventionalists, this kind of specialization is premature.

Others see an opportunity to break away from diagnostic radiology altogether. One of them is Dr. Riad Salem, director of interventional oncology at Northwestern Memorial Hospital in Chicago.

While IRs continue to lose turf in endovascular interventions such as carotid stenting to vascular surgeons and cardiologists, oncology offers a particularly attractive partnership avenue, Salem said.

"That's the best marriage, because we really complement one another. Our future is not in vascular disease anymore, but in interventional oncology," he said.

To make their strategy successful, IRs must start thinking of themselves in a completely different way. IRs recognize their most immediate need to be education in clinical oncology. Knowing how to perform the procedures is one thing. Learning to talk oncologists' language is another, Soulen said. Others stress that the key to success in the new field depends on offering good clinical services to their patients.

"The key to success is to be a real clinician and not a technician. A patient is a whole person, not a lump," Adam said.

Together or separate from diagnostic radiology, IRs are moving into interventional oncology anyway. Some, like Salem, predict the break will take place within the next five years. Others, including Soulen, are more cautious.

"Vascular surgeons tried to break away from their board, and it didn't happen. We are looking at that lesson with attention," he said.

Whatever happens, the horizon looks promising for oncologic IRs. A new level of sophistication in imaging will enable them to target tumors much more accurately. The instruments they use to perform image-guided interventions will become more sophisticated. The plateau is still years ahead. Most data show that despite their lack of optimization or customization to specific organs-most IRs use the same equipment to treat varied tumors-these specialists are producing impressive results.

"We are doing a good job, even without the many technical and clinical advances that we will someday achieve," Lencioni said.