Integrated PET-CT: Evidence-Based Review of Oncology Indications

Recent technical advances leading to the development of integrated positron-emission tomography (PET)-computed tomography (CT) have been a boon for oncologic imaging. Combining these two imaging modalities into the same imaging unit has greatly simplified visual fusion of function (PET) and anatomic (CT) data. The popularity of this modality has resulted in over 60% of all PET sales currently being PET-CT units. PET-CT Advantages
The "software fusion" alternative has been shown to pose difficulties, especially when dealing with imaging studies from different facilities and vendors, as commonly occurs. On the other hand, PET-CT has greatly benefited by the reduction in scanning time of the patient, limiting patient motion, and therefore maximizing image resolution. Average scan times have been reduced by approximately 50% to 15 to 20 minutes. Using CT data for attenuation correction rather than a transmission radioactive source as used in PET-only units has been the primary source of time reduction. New scanner designs, electronics, and better scintillator materials promise to reduce scan times even more in future-generation units while preserving image quality. Growth in PET has been exponential since initial Medicare reimbursement for a limited number of indications was granted in 1999. Diagnostic accuracy with PET-CT compared to stand-alone PET units has improved by up to 60%.[1] For pleural lesions, PET-CT is very accurate in distinguishing malignant from benign pleural thickening seen on CT, as well as in predicting survival and increasing the accuracy of preoperative staging. PET-CT can also localize sites for biopsy, with the greatest potential for detecting malignant involvement. The intensity of malignant pleural uptake is a good predictor of tumor aggressiveness. PET quantitation has been very helpful, with higher uptake intensity correlating well with poor prognosis. Mapping intensity variations in tumors has been shown to correlate with degree of tumor activity, thereby benefiting radiotherapy planning. Staging and Recurrence
Preoperative PET-CT has affected staging and patient management of malignancies by 20% to 30%.[2] Incidental, unexpected focal abnormalities on PET-CT scans are associated with up to a 70% probability of malignancy or malignant potential and frequently indicate unsuspected subclinical tumors. Asymmetric adrenal uptake on PET in patients with cancer suggests > 85% probability of malignant involvement. PET improves the accuracy of detecting tumor recurrence in postoperative colon cancer patients, who often show significant alterations in normal anatomy. Gastrointestinal stromal tumors (GISTs) have been shown to respond very well to imatinib(Drug information on imatinib) (Gleevec) in about 70% of cases,[3] and PET has been an accurate predictor of imatinib response. PET may have a similarly accurate early-response predictor capability for non-Hodgkin's and Hodgkin's lymphomas after two chemotherapy cycles. Further investigation in these settings is warranted. Finally, PET has improved the detection of splenic involvement with Hodgkin's lymphoma, especially in children. Timing of Studies and Other Considerations
Optimizing the timing of PET-CT studies relative to therapy and surgery is important. In general, we schedule PET-CT scans > 2 months after completion of chemotherapy and > 3 months after surgery (especially for head and neck primaries). Likewise, inflammatory uptake postradiotherapy may remain for up to 6 months. Glucose uptake in the thyroid gland is bothersome, if focal. The Hürthle cell variant of follicular thyroid cancer does not take up radioiodine, but conversely is highly glucose-avid. Therefore, PET-CT should be used to follow these patients after initial radioiodine thyroid gland ablation. The risk of distant metastases is greater with Hürthle cell carcinoma than other thyroid cancer cell types. PET has proven beneficial in identifying recurrent thyroid cancer in patients with negative radioiodine scans. In patients with melanoma for metastatic evaluation, the standard PETCT image area is expanded to "top of head to bottom of feet." Up to 8% of melanoma metastatic lesions have been shown to be outside the standard imaging area of base of skull to midthigh. The value of PET in differentiating postchemotherapy and/or postradiotherapy and/or surgery fibrosis sequelae from recurrent/residual tumor is well documented. One of the earliest clinical indications for PET was in answering this clinical question in patients with high-grade (3/4) cerebral gliomas. PET-CT is also promising for the evaluation of posttherapy seminoma, ovarian cancer, and cervical cancer patients, being the most significant predictor of survival in these populations. Overall tumor-node-metastasis (TNM) staging accuracy is 80% with PET-CT, compared to 52% with magnetic resonance imaging.[4] Therapy Planning and Future Directions
In general, PET-CT results change the therapeutic plan of clinical management in 33% of patients.[5] Standard uptake value quantitation has been shown to be an independent predictor of patient survival in lymphoma, head and neck, pancreas, and non- small-cell lung cancer. PET-CT aids radiation therapy planning and affects the planned treatment volume. In patients with liver metastases from colorectal, breast, and esophageal cancers and lymphoma, PET is an early predictor of eventual response to chemotherapeutic agents. Beyond radioactive glucose, several new positron-emitter agents are showing promise in development. These include ¹¹C-choline for prostate cancer assessment, and ¹⁸F-fluorothymidine as potentially a more specific radiopharmaceutical for malignancy than ¹⁸F-fluorodeoxyglucose.