PET/CT drives changes in art and geometry of oncology

Radiologists and radiation oncologists approach cancer from different vantage points. For radiologists, the goal is to define the shape and nature of malignancy. For radiation oncologists, it's to plot the trajectories for delivering radiation to tumor sites.

Now that advanced imaging techniques are providing exquisite information about the location and bioactivity of tumors and metastases, the perspectives of the two specialties are converging. Radiation oncologists are paying greater attention to manifestations of focal and systemic malignancies, and nuclear medicine physicians are narrowing their identification of malignancies to the smallest volumes that may be targeted with high-dose boost radiotherapy.

Until recently, the use of PET imaging to assess patients with cancer was confined to distinguishing benign from malignant disease and staging malignant neoplasms. But when used with CT, PET has been critical in increasing the accuracy of cancer staging. It has improved the sensitivity and specificity of staging patients with non-small cell lung cancer, for instance, from 60% to 85% and has significantly strengthened prognostic stratification.

A role for PET in planning radiotherapy is steadily emerging. According to a paper reviewing efforts to implement biologic target volumes in radiotherapy planning for patients with non-small cell lung cancer, PET in combination with CT has changed the shape of radiation portals and volumes, improved the demarcation of tumors in the presence of atelectasis, and enlarged portions of the radiation beam aperture.

On the one hand, PET has significantly increased target volumes for radiotherapy by identifying occult areas of tumor involvement or additional regional nodal disease, wrote the paper's principal author, Dr. Jeffrey Bradley, an assistant professor of radiation oncology at Washington University School of Medicine in St. Louis. On the other hand, it has substantially decreased target volumes by identifying areas of lung consolidation or enlarged lymph nodes with little radioactive uptake.

In reviewing studies from 1996 through 2003, Bradley found that PET altered radiation treatment planning in 5% to 45% of patients. In his own experience with 24 lung cancer patients who had 3D conformal radiotherapy, Bradley concluded that PET significantly altered treatment volume for 14 patients by finding previously unsuspected nodal disease in 10 patients, locating a separate tumor focus in the same lung lobe in one patient, and distinguishing tumor from atelectasis in three patients.

"In about 10% to 20% of patients, we find metastatic disease, and PET significantly changes the treatment program for a patient with metastasis. In patients with no metastatic disease, PET changes tumor volumes for radiation therapy 30% to 50% of the time. When you add those two percentages up, there's a significant change based on PET imaging," he said.

In a paper presented at the 2004 RSNA meeting, investigators from Johns Hopkins University reported that PET/CT changed the calculation of gross tumor volume for six patients. Tumor volumes derived from PET/CT were 17% larger than those obtained from CT alone and 14% larger than those based on PET alone.

However, there is no standardized way of interpreting functional imaging data from one clinical setting to another. As a result, calculations of radiation planning target volumes have varied from 24% to 76% in different studies. Normal structures and metabolic processes have often been confused with abnormal ones.

Interpretations of PET images have been complicated by false positives, such as inflammatory plaques within the aorta, fulminating tuberculosis, pleural reactions, scarring after radio- or chemotherapy, and motion effects. Tumors have been known to move by as much as 3 cm in one dimension and along the x, y, and z trajectories, according to Bradley.

Hardware and software are helping to correct these problems. At the American Association of Physicists in Medicine meeting in July, investigators from Washington University and M.D. Anderson Cancer Center reported on PET/CT 4D scanning, which can correct for image blurring and other distortions caused by lung and heart motion. A research team from Massachusetts General Hospital is testing software that adjusts radiation dose by tracking tumor motion on 4D scans.

But advancements in PET/CT imaging are not turning radiation treatment planning into a paint-by-number exercise that can be adopted by rote. On the contrary, the technology demands the focus and expertise of two specialties to take full advantage of its potential.

PET FOR TREATMENT PLANNING

Although radiation oncologists are accustomed to computing treatment plans with CT data, they are largely unfamiliar with PET information. Bradley acknowledged that he is fairly adept at reading a CT scan of the chest but not at reviewing PET data that look for malignancies everywhere else. Abdominal images are especially difficult to interpret because of normal uptake in the bladder, bowel, kidney, and stomach, he said.

In the case of lung cancer, it is not uncommon for a tumor to lie adjacent to a collapsed area of the lung, and the two are almost indistinguishable, said Dr. William Regine, chief of radiation oncology at the University of Maryland.

Consequently, nuclear medicine physicians and radiation oncologists are working closely to coordinate the reading of scans. At Cedars Sinai Medical Center in Los Angeles, nuclear medicine physicians take radiation oncologists step by step through PET scans to differentiate true malignancies from normal variations in metabolic activity and hypermetabolic conditions that are not related to cancer.

Nuclear medicine physicians also counsel about the pitfalls and limitations of functional imaging, said Dr. Alan D. Waxman, cochair of the Mark Taper Foundation Imaging Center at Cedars Sinai. Among questions that arise: What constitutes areas of increased FDG uptake that are due to secondary infection or inflammation? Why does the heart appear in various forms in many of the fields that may be targeted for irradiation and what should be done about it? And why are inflammatory plaques in the aorta sometimes mistaken for involved lymph nodes?

Radiation oncologists are guided by the principle that the smaller the volume targeted for therapy, the higher the dose of radiation that can be delivered to kill the greatest number of cancer cells while preserving as many normal cells as possible. Helping radiation oncologists drill down to the smallest treatment volume requires that nuclear medicine physicians pay close attention to margins of error: whether an area of increased metabolic activity lies too close to the spinal cord to take the chance that it will be included in the irradiation field, whether the motion of the heart is too variable to clearly demarcate the edge of a tumor near the left ventricle, whether there is an 80% chance that a malignancy has metastasized to the mediastinum or the percentage is high that a lymph node is most likely normal. Compromising these decisions is the lack of understanding of the meaning of functional images.

"PET has changed our radiation treatment targets, but we haven't established a way to threshold the PET so the images appear the same. We haven't addressed the fact that PET gives you much more information than just volumes; it can give you the degree of FDG uptake or the standard uptake value. We're just starting to learn what that information may mean in terms of prognosis," Bradley said.

FINE-TUNING DELIVERY

Radiation oncologists and nuclear medicine physicians also are at the beginning stages of using yttrium-impregnated glass or ceramic beads to deliver high doses of radiation to hepatic tumors and limit toxicity to normal liver tissue. To be sure the radioactive beads lodge only in liver tumors, nuclear medicine physicians have been conducting full-body surveys of the deposition of macroaggregates of albumin, verifying that the albumin is collecting in the capillary vessels of the liver and not in collateral vessels feeding the gut, stomach, or lung through collateral circulation.

PET/CT is central to the process, as it assesses the 3D distribution of a test dose of a tracer so it can be incorporated in treatment planning algorithms, said Dr. Bruce R. Line, director of nuclear medicine at the University of Maryland.

As technology moves radiation therapy beyond the external beam, the two specialties are intensifying efforts to learn from each other. Radiation oncologists are becoming schooled in molecularly based imaging and molecularly guided therapeutic techniques, and radiologists are becoming more practiced in applying molecular imaging to calculate radiation doses.

"These are two huge specialties that have a lot to learn from each other," Line said. "The reason it's happening more now is that the technology is moving in such a way that it is becoming possible for radiologists and radiation oncologists to use each other's tool sets to solve problems in a more sophisticated way."

Ms. Sandrick is a contributing editor for Diagnostic Imaging.