Caroll C. Overton, MD (left), and Andrew S. Kennedy, MD, prepare to deliver microspheres to a patient via the left femoral artery. The Plexiglas apparatus contains the radioactive microspheres.

Four years ago, this magazine profiled Wake Radiology in Cary, NC, and its innovative practice model, which includes radiologists and oncologists, as well as its state-of-the-art freestanding imaging and oncology center. In returning there, Decisions in Axis Imaging News looked at how this unique, collaborative community practice is delivering state-of-the-art diagnostics and treatment for patients with cancer by focusing on one of the body’s most complex and delicate organs: the liver.

Through collaboration between oncology and interventional radiology, Wake is using transarterial chemoembolization (TACE), radiofrequency ablation (RFA), and yttrium microspheres to provide the most current care available anywhere in the United States. The care for such patients at Wake is such that the practice receives four to five queries a week from institutions throughout the country for consultations. This is a story about a practice that is bringing state-of-the-art care into the community, giving hope and answers to people who previously had to go to a research center. Significantly, this is being done profitably, through educating payors and tenaciously seeking reimbursement for the newest, most appropriate care.


From 1984 to 1999, 4,000 to 6,000 new cases of hepatocellular carcinoma (HCC) were discovered each year in the United States, with an annual increase of 4.5%. 1 For 2003, the American Cancer Society reported an anticipated 17,300 new cases of cancers in the liver and intrahepatic bile duct. The explanation for the sharp increase lies in the fact that 60% to 80% of these cancers develop in cirrhotic livers, 2 and cirrhosis is becoming more prevalent with the increase in chronic hepatitis B and hepatitis C infections.

In the United States, a far more common cause of malignant hepatic lesions is metastases, particularly from colorectal cancer. Of the estimated 155,000 new cases of colorectal cancer identified here each year, 10% to 15% are initially accompanied by hepatic metastases, and 50% to 60% of patients eventually have such lesions. Other common cancers, including those of the lung, breast, and prostate, and less common cancers, such as those of the stomach and pancreas and melanoma and neuroendocrine tumors, also have a propensity to metastasize to the liver.


Although surgery may be curative, only about 30% of HCCs are resectable. 2 Resection of liver metastases can likewise be curative, but the outlook is even more dire, with fewer than 10% of patients having disease that is both technically and physiologically resectable. 3 The result is a large number of candidates for liver-directed measures: regional chemotherapy, 4 portal venous or transarterial chemoembolization, or interstitial ablation with radiofrequency energy or the laser. 5,6 The goal of all of these techniques depends on the individual situation. Thus, it may be to make lesions resectable, 7-9 to reduce the local recurrence rate, 10,11 or to obtain palliation. 8,9

A new option is selective internal radiation therapy (also called brachytherapy) with beta-emitting radioactive 90 Y microspheres administered via the hepatic artery. Tumor doses in excess of 400 Gy can be delivered, while subjecting the healthy liver to just over 100 Gy, 12 permitting outpatient administration with few or no complications. In an early trial at the Wakefield Gastroenterology Centre in Wellington, New Zealand, enrolling 50 patients with nonresectable hepatic metastases of colorectal cancer, a single dose of 90 Y microspheres followed at 4-week intervals by regional 5-fluorouracil produced survival for as long as 30 months (median 17.5 months). 13 The microsphere technique also is being applied in unresectable HCC. Interventional radiologists at William Beaumont Hospital in Royal Oak, Mich, describe median survival rates of 23 months and 11 months, respectively, for patients with Okuda stage I and stage II disease. 14

Venous phase axial CT images of a patient with colon cancer liver metastases. The left image is prior to treatment and the right image obtained post treatment with 90Y-microspheres. Tumor clearance in the liver was complete, with stable scar formation in the liver that was unchanged for > 6 months.

One of the few sites in the United States offering yttrium brachytherapy is Wake Radiology, where it is supervised by Andrew S. Kennedy, MD, a radiation oncologist and one of the leading practitioners of the technique. The tumor is staged by CT scan and perhaps positron emission tomography, and an angiogram (sometimes a CT angiogram with or without three-dimensional reconstruction) is obtained to determine if the patient is or can be converted into a candidate.

(Left image) Pretreatment PET scan of a patient with colon cancer metastasized to the liver and refractory to chemotherapy. It is not resectable surgically, but was destroyed by an application of radioactive 90Y-microspheres (right image confirms lack of activity in post-treatment PET scan).

“If a vascular shunt allows the microspheres to pass from the liver to the lung, they could kill the patient,” according to Carroll C. Overton, MD, an interventional radiologist who works closely with Kennedy at Wake Radiology. “A shunt therefore is a contraindication to brachytherapy. However, in many patients, we can use TACE to close shunting vessels. Thankfully, shunts occur in fewer than 5% of cases, usually in association with less common tumors such as metastases from breast carcinoma, although we found a shunt in one HCC patient. Also, we have had a few patients in whom the hepatic lesion gobbled up some vasculature from a nearby organ such as the stomach, pancreas, or duodenum. We embolize those parasitic vessels with a coil or Gelfoam so that when we infuse the microspheres, they will not go to that other organ and cause complications.”

Microsphere delivery requires a catheter to be advanced well out into the arterial system. “Formerly, many patients could not be given brachytherapy because the catheters were too big to reach an appropriate vessel,” Overton recalls. “Today’s microcatheters, which aren’t much bigger than fishing line, can go anywhere in the body from the brain to toe, although it sometimes takes a fair amount of work to get them there.”


Yttrium brachytherapy obviously requires the coordinated activity of diagnostic, therapeutic, and interventional radiologists, along with experts in medical physics and radiation safety.

“As a radiation oncologist, I do not read films, but I use them extensively,” reports Kennedy. “We try to keep a central file on each patient so that even if we cannot fuse the data from two studies, we can look at them on the same screen. With our equipment, I can call the interventionist at the same time I am talking to the nuclear medicine practitioner. In each case, we try to have everyone look at the same images at the same time, with everyone focusing on the technique he or she does best, so we can select the best treatment plan for a given patient.”

The most likely patients to benefit from microspheres are ones with liver-predominant disease, and nearly normal liver function as measured by blood tests, according to Kennedy. “Vascular access is the essential delivery route, but even in patients that have had multiple TACE and/or RFA procedures, we are usually able to treat them,” Kennedy explains. “The key is that many patients are not candidates for TACE or RFA, or it would become an open surgery to use RFA, but almost all candidates, regardless of the amount or location of tumor in the liver, can receive microspheres.”

According to Kennedy, the most common patients treated at Wake are (in order of frequency) colorectal, carcinoid, breast, sarcoma, and pancreas/biliary cancer patients. Wake receives referrals from Duke and University of North Carolina-Chapel Hill gastrointestinal oncology teams as well as other university teams around the country and several countries in Europe for patients for whom microspheres are the preferred treatment.

“We have the capacity to treat six patients a week without causing significant changes in our oncology practice; however, we average one or two per week,” notes Kennedy. Oncologists at Wake have performed more than 400 microsphere infusions, with referrals increasing weekly for the practice’s liver-cancer services.

At Wake, the microsphere procedure is performed by the oncologists and the TACE and RFA procedures are performed by the interventional radiologists. “In general, we have reserved the majority of yttrium candidates to those with colorectal and carcinoid cancer,” Overton explains, “though some candidates with terminal disease from other primaries, for example breast and angiosarcoma, have been considered, as they have been given no other options or have exhausted all other treatment options. RFA can be used to further debulk tumor burden, but, in general, our brachytherapy patients are responding so well that RFA has not been needed here.”

Facilitating this cooperation between interventional radiology and radiation oncology is the design of the building. “When we built in 1998, we knew that three-dimensional treatment planning was the wave of the future, so we built one large combined imaging and therapy center,” explains Robert E. Schaaf, MD, president of Wake Radiology.


One of the reasons state-of-the-art care is confined to research centers is the issue of reimbursement. If a procedure is not properly reimbursed, it needs to be subsidized by research dollars, typically in a university setting.

When Kennedy left his position at the University of Maryland to join the Wake Radiology practice in August 2002, a stipulation of that agreement was that he be able to continue to work with yttrium microspheres as well as other new and innovative therapies. Kennedy agreed to continue to work with payors for reimbursement.

Initially, Kennedy’s was a lone voice attempting to educate insurance payors on a case-by-case basis. In time, he was able to arrange to meet directly with the larger payor technology committees and convince them it was the best and often most cost-effective medical option for selected patients. “Until this year, all cases were being reimbursed, but lately several payors have started questioning payment, especially for off-label use (non-colorectal),” Kennedy notes. “I am scheduled to meet with the technology committees again, this time with support from all interested organizations, including the ASTRO, ACRO, and American Brachytherapy Society, and industry.”

The microsphere dose itself is only reimbursable via the C-codes of hospitals and must be ordered and billed for by a hospital. CMS recently approved an increase from about $8,000/dose to the fully billed $14,000/dose the vendor has always charged.

According to Schaaf, it was not necessary to add any full-time equivalents or additional resources when Wake began offering the microsphere treatment. “All payors have been very cooperative, and we have not had any denials for either the imaging or therapy portions of the procedure,” he notes.


Wake Radiology has taken many other steps to facilitate the care process for patients and referring physicians and their staffs as well as its radiologists. Of particular importance is a full-time marketing staff of three former radiologic technologists who make regular visits to referring physicians’ offices to explain what is new, what new procedures are being done, and, just as important, which are no longer in use. (They also provide CPR training for nurses and secretaries on request.)

Left image is a PET scan of a patient with metastatic colon cancer in the liver prior to receiving 90Y-microspheres. The center drawing describes the procedure illustrating the catheter placed into the right hepatic artery for delivery of microspheres. The right image is a follow-up PET scan of the same patient 6 weeks after delivery of microspheres into the right lobe of liver only. There is significant clearing of tumor on PET in the treated right lobe, and persistent tumor in the untreated left lobe of liver.

“These marketing people educate the referring physicians, scheduling personnel, and nurses,” Schaaf stresses. “The intent is to ensure that they order the correct examination the first time. Also, we see to it that the patients are educated by the referring physicians, printed literature, and our Web site so that when they arrive, they are prepared medically, emotionally, and physically for the examination or treatment. If the patient has a 9 AM appointment, the procedure should be done at 9 AM, and then the patient can leave. This preappointment education minimizes reschedules, and our no-show rate is virtually zero.”

The radiation oncologists help with marketing activities by giving talks to lay audiences such as cancer survivors and to the medical community, both family practitioners and specialists such as medical oncology nurses.

“Our specialty is changing so fast that it is all the radiology community can do to keep up, and people in other fields can’t hope to,” Schaaf remarks.

Another facet of Wake Radiology’s plan to make the lives of its users easier is getting results quickly to those who need them. “Our preferred turnaround time for a report is about 20 minutes,” Schaaf says. “Secretaries and nurses are busy. They want procedures scheduled promptly, and they do not want to make a lot of phone calls to get the results. If you impose that burden on them, they will send their patients somewhere else.”

Another important marketing element is asking for complaints. “We want to know about problems so we can fix them, but if you don’t ask, often you are not told. The practice will simply decide to use someone else,” Schaaf points out.


“The importance of imaging in today’s radiation oncology is bringing diagnostic and therapeutic radiology back together after 20 years of separation,” according to Schaaf. The arrangements at Wake Radiology may well become the norm.


Intensity-modulated radiation therapy (IMRT) is an advanced form of three-dimensional (3D) conformal radiotherapy. The goal is to shape the treatment field precisely, tiny volume by tiny volume, and to alter the dose throughout the field in order to ensure exposure of the entire tumor to a cytotoxic radiation dose while minimizing damage to the normal organs at risk (OARs), especially critical ones. For example, in treating a prostate cancer, the field is designed to minimize the dose to the rectum, bladder, and femoral heads, whereas for head and neck cancers, particular efforts are made to protect the spinal cord and parotid gland. IMRT is possible because of specialized equipment that can modify the radiation beam. Thus, whereas standard radiation beams result in a uniform dose throughout the field, with the multileaf collimators commonly used for IMRT, the dose within a field can be whatever intensity is dictated by the clinical situation. A prominent benefit is the ability to create fields with a concave edge, which is appropriate for about 30% of cancers and not possible with other radiation planning techniques. The term sometimes used to describe the precise shaping and dose modulation is “dose painting.”

Various IMRT techniques are in use, but they have several features in common. The first is the requirement for 3D multimodality imaging to determine precisely the extent and geometry of the tumor volume. The second is the need for extensive patient-specific inverse planning beginning with the desired dose distribution and working backward. The patient is immobilized and marked, and 3D CT images are acquired. The cancer and critical nearby structures are outlined on the images, and the radiation oncologist specifies the desired tumor dose and the dose limit for the normal organs. The dosimetrist and the physicist then design the treatment plan on the basis of parameters supplied by the radiation oncologist. Once the physician is satisfied with the dose distribution, plan implementation is confirmed with a phantom.

IMRT planning is highly time and labor intensive. “An IMRT treatment can easily take 5, 6, or even 8 hours of planning,” explains Scott L. Sailer, MD, of Wake Radiology in Cary, NC. “The technique entails the use of five to seven radiation beams, each of which has its dose intensity varied over the beam so as to deliver isodoses that will wrap around structures and avoid normal tissue. As experience with IMRT increases, the time required for planning usually decreases, although the planning will almost always take longer than that for standard 3D treatment.” Extensive equipment quality assurance procedures consume more of the experts’ time.

The third common feature of the various types of IMRT is the greater amount of time required for delivery. The treatment probably takes at least two schedule slots in Sailer’s experience. “Each radiation beam stays on for several minutes while the intensity is modulated,” he explains. “There may be 15 or 20 segments in each beam, so if you have seven beams, you may have 120 separate segments of treatment that are delivered. In contrast, standard radiotherapy generally uses two to four beams that are open the whole time. That may take several minutes, whereas IMRT may take 15 or 20 minutes.”

Not surprisingly, IMRT is considerably more expensive to deliver than traditional radiation therapy. In the past, any center wishing to make IMRT available had to absorb the extra cost. Although insurers resisted the extra cost, Medicare recently approved codes for IMRT planning (77301) and delivery (77418) for some cancers, making it more appealing to health care provider. Reimbursement is adequate, although with time, it is likely to decline.

At present, IMRT is applied primarily to prostate, head and neck, breast, and esophageal cancers and to those brain tumors close to sensitive structures such as the eye. Its availability is expanding rapidly: whereas in 1998, only 4% of radiation oncology facilities provided IMRT, in 2003, 38% did. 15 Also, considerable work is being devoted to make IMRT usable in other cancers such as those in the lung and abdomen, where motion is a problem. Although third-party payors are likely to continue to be skeptical, Webb has pointed out that “a failed treatment is a wasted high cost” and “[m]ore expensive successful therapy is better than cheaper unsuccessful therapy.” 16 As these facts are taken into account and more cancer patients demand reduction in treatment side effects, the indications for IMRT and the need to convince third-party payors of its appropriatenessare likely to increase. 17

Judith Gunn Bronson, MS, is a contributing writer for Decisions in Axis Imaging News.


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