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PET/CT Is Fast Reshaping Cancer Management,Drawing Two Specialties Together

PET/CT Is Fast Reshaping Cancer Management,Drawing Two Specialties Together

CHICAGO-Now that advanced imaging techniques are providing exquisitely detailed information about the location and bioactivity of tumors and metastases, the perspectives of radiologists and radiation oncologists are converging, as evident in interviews with and reports from presenters at the 90th Scientific Assembly and Annual Meeting of the Radiological Society of North America (RSNA). 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. PET in RT Planning Until recently, use of positron emission tomography (PET) imaging to assess patients with cancer was confined to distinguishing benign from malignant disease and staging malignant neoplasms. When used with CT, however, 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 (NSCLC), 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 review article by Jeffrey Bradley, MD, an assistant professor of radiation oncology at Washington University School of Medicine, St. Louis, Missouri, and colleagues, describing efforts to implement biologic target volumes in radiotherapy planning for patients with NSCLC, use of PET in combination with CT has led to changes in the shape of radiation portals and volumes, improved demarcation of tumors in the presence of atelectasis, and enlargement of portions of the radiation beam aperture (Bradley JD, Perez CA, et al: J Nucl Med 45(Supp 1):965-1015, 2004). While PET has significantly increased target volumes for radiotherapy by identifying occult areas of tumor involvement or additional regional nodal disease, Dr. Bradley and his associates stated, 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, the investigators found that PET altered radiation treatment planning in up to 45% of patients. In his own experience with 24 lung cancer patients who had 3D conformal radiotherapy, Dr. 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," he said. "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 together, there is a significant change based on PET imaging," he said. For example, at the 2004 RSNA meeting, radiologist William Lavely, MD, from Johns Hopkins University, Baltimore, Maryland, reported that PT/CT changed the calculation of gross tumor volume for six patients (abstract SSK26-05). Tumor volumes derived from PET/CT were 17% larger than those obtained from CT alone and 14% larger than those based on PET. Limitations of PET 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, Dr. Bradley said. Hardware and software are helping to correct these problems. At the 46th annual meeting of the American Association of Physicists in Medicine, in Pittsburgh, Pennsylvania, investigators from Washington University, St. Louis, Missouri, and The University of Texas M.D. Anderson Cancer Center, Houston, reported on PET/ CT 4D scanning, which can correct for image blurring and other distortions caused by lung and heart motion. Further, a research team from Massachusetts General Hospital is testing software that adjusts radiation dose by tracking tumor motion on 4D scans. (See the report on gated 4D PET/CT on page 10). Despite recent advancements in PET/CT imaging, presenters emphasized, the technology demands the focus and expertise of two specialties to take full advantage of its potential. Interpreting PET Scans for Treatment Planning In the case of lung cancer, it is not uncommon for a tumor to lie adjacent to a collapsed area of the lung, and these two features are almost indistinguishable, noted William F. Regine,MD, professor and chair of the department of radiation oncology at the University of Maryland, Baltimore. 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 scan review, to help them differentiate true malignancies from normal variations in metabolic activity and hypermetabolic conditions that are not related to cancer. Nuclear medicine physicians also provide counsel about the pitfalls and limitations of functional imaging, said Alan D. Waxman, MD, co-chair of the Mark Taper Foundation Imaging Center at Cedars Sinai. Questions that arise, he said, include that of what constitutes areas of increased FDG uptake caused by secondary infection or inflammation rather than malignancy; why the heart appears in various forms in many of the fields that may be targeted for irradiation and what should be done about it; and why inflammatory plaques in the aorta are 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 sparing as many normal cells as possible. Helping these specialists 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, and whether there is an 80% chance that a malignancy has metastasized to the mediastinum or the probability is high that a lymph node is most likely normal. Compromising these decisions is a lack of understanding about the meaning of functional images. "PET has changed our radiation treatment targets, but we have not established a way to threshold the PET so the images appear the same. We have not really 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. But we are just starting to learn what that information may mean in terms of patients' prognosis," Dr. Bradley said. Fine-Tuning Radiation Delivery Radiation oncologists and nuclear medicine physicians also are at the beginning stages of using yttriumimpregnated 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 and therefore can be incorporated in treatment planning algorithms, commented Bruce R. Line, MD, professor of diagnostic radiology and director of the division of nuclear medicine at the University of Maryland, Baltimore. As technology moves radiation therapy beyond the external beam, the two specialties are intensifying efforts to educate 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 two specialties have a lot to learn from each other," Dr. Line said. The reason information exchange is increasing between these groups, he added, is that "the technology is moving in a direction that makes it possible for radiologists and radiation oncologists to use each other's tool sets to solve problems in a more sophisticated way."

 
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