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

Positron-emission tomography (PET)-computed tomography (CT) has added a new dimension to the imaging of cancers and combination PET-CT scanners are becoming increasingly universal. The use of combination scanners has increased rapidly over the past 2 years- industry estimates are that the majority of PET units sold throughout the world will be combination PET-CT scanners- and the authors have provided their own clinical experience and a review of the literature. While there is substantial literature on the clinical utility of PET alone, the use of PETCT is relatively new. The authors suggest there is incremental benefit to the addition of structural information (ie, CT) obtained at the same time as the functional PET imaging. Pros and Cons
The combination scanner allows faster imaging by precluding the need for slower transmission images and integrating the CT images with PET images. CT images not only provide an anatomic map, they are also used for attenuation correction. Simultaneous or single-session anatomic and physiologic imaging allows easier and more accurate fusion of images and overcomes the drawback of retrospective fusion through software, which is more cumbersome and time consuming, and may not be possible for a variety of reasons including different imaging protocols for the two studies (eg, arms raised or down) as well as limitations of downloading digital images onto one platform. There are associated concerns, too. The combination machine is more expensive; CT scans used for fusion are usually not of diagnostic quality. Potential artifacts-for example, respiratory motion and motion between acquisitions, truncation artifacts, and artifacts from contrast-can also significantly affect interpretation. The use of intravenous (IV) and oral contrast in PET-CT has been shown in phantom studies to lead to CT attenuation artifacts. The use of high-density oral contrast causes overattenuation from CT images, obviated by the use of low-density contrast.[1] Similarly, nonionic IV high-density contrast in the arterial phase may also cause alterations in quantitation; delayed IV contrast administration may mitigate that. Therefore, contrast must be used cautiously and with knowledge of potential visual and quantitative artifacts. Some groups acquire the noncontrast CT for attenuation and then carry out a limited CT assessment after IV or negative oral contrast. Every center must properly optimize the technique and take into consideration potential effects on image and quantitation. Incremental Benefit?
While it is imperative to ask if the data show that PET-CT is superior to PET alone, it is also important to ascertain the incremental benefit of the PET-CT combination scanner. How much benefit does PET-CT provide? What kind of patients are likely to benefit most, and how often does the combined technology change patient management? It appears self-evident that concomitant evaluation of the PET and CT scan helps establish the lesion characteristic and location with more certainty than PET alone. A more important question is to assess objectively whether simultaneous imaging and fusion using combination scanners has incremental utility compared to visual side-by-side or retrospective fusion using software programs. The published experience with 18Ffluorodeoxyglucose (FDG) PET in cancer has been growing exponentially over the past several years. Its significance and importance in the diagnosis, staging, and follow-up of many cancers is established. FDG PET has better sensitivity, specificity, and predictive values compared to CT scan, ranging as high as 85% to 100% in certain cancers.[2] The overwhelming evidence in support of its clinical utility led to approval of PET by the Centers for Medicare and Medicaid Services (CMS) for a growing number of indications. Limitations in anatomic localization of abnormal FDG PET foci can be only partially resolved by retrospective fusion techniques, which are time-consuming and suffer from the inaccuracies inherent in fusing disparate image data sets. Simultaneous acquisition of anatomic and functional data by PET-CT has resulted in better diagnosis, staging, and restaging in a variety of cancers.[3] The published literature is still in its infancy and consists largely of abstracts and preliminary data. Moreover, many studies have compared PET-CT with PET alone rather than PET and CT. A few studies have compared PET-CT with "side-by-side PET and CT" or software-fused images.[4-6] Does PET-CT have a greater impact on patient management than PET alone? The jury may still be out. Reinhartz and colleagues, in an analysis of 328 patients, found that in 6.7% of patients, integrated PET-CT would have gained additional advantage over combined viewing of PET and CT.[4] Similar results in 260 patients were reported by Antoch et al, who found that PET-CT proved significantly more accurate in assessing tumor. However, combined PET-CT had an impact on the treatment plan in only 16 patients (6.1%) when compared with PET plus CT.[5] In another study in 204 patients, PET-CT had an impact on the management of 14% patients, which included exclusion of cancer in 2%, guiding invasive procedures/biopsies in 3%, and referral to surgery, radiotherapy, or chemotherapy in 7%.[6] Finally, in patients evaluated for occult recurrence, there was a statistically significant difference between PET-CT and PET plus CT in the specificity and accuracy for site-based analysis of the characterization of lesions. However, no significant difference was seen in sensitivity or predictive values. For the patient-based analysis, no significant difference was seen.[7] The clinical significance of the additional lesions detected also needs to be systematically addressed for each cancer type. Optimal Use
The use of fused functional and anatomic imaging is expected to be most useful in head and neck and abdominopelvic malignancies, as the anatomy is complex, often complicated by postoperative or postirradiation changes, and interference from physiologic uptake of tracer may cause difficulties in interpretation. A preliminary analysis of 68 patients showed that PET-CT decreased equivocal findings in head and neck and abdominopelvic malignancies by 57% and 80%, respectively, and helped in the delineation of chest findings by 25%.[8] Again, the comparison was made between PET (not PET plus CT) and PET-CT. FDG PET has lower specificity in these regions, and perhaps the greatest impact with combined imaging will be on specificity. Similar analysis in 45 patients with colorectal cancer also showed better characterization of lesions with PET-CT, which changed staging by 11%.[9] PET-CT will probably prove more advantageous in gynecologic cancers, where peritoneal and mesenteric disease is frequent, and in evaluating organs such as the adrenal glands and pancreas. Radioactivity in the kidneys, ureters, and bladder pose a diagnostic hurdle in the absence of CT fusion. PET-CT can also help establish with certainty a lack of uptake in lesions seen on CT; precise localization for such evaluation is of huge value. PETCT has been shown to be superior in detecting malignant bone lesions by increasing interpretation confidence.[ 10] Thus, for every cancer, specific clinical indications need to be identified where the use of PET-CT will prove incrementally advantageous. Another clinical application for which PET-CT appears very promising and is expected to have a great impact on management is radiation therapy planning. Studies in lung cancer, head and neck cancer, lymphoma, and esophageal cancer using PET scanning have shown its potential in identifying the viable extent of tumors. The importance of simultaneous structural and functional imaging is of paramount importance in the definition of gross and treatment target volumes for radiation therapy planning. The functional information provided by PET often leads to alterations in treatment planning, changing the size and/or direction of radiation portals. In a number of studies, the use of PET-CT was shown to alter treatment volumes, thereby changing the management plan. Overall, FDG PET helps achieve better targets by inclusion of lesions otherwise missed by other imaging.[ 11-13] In head and neck cancers, it was shown to alter the planned radiation therapy volumes in five of six patients.[14] Conclusions
While there are many centers that have made PET-CT scans part of standard practice, and most studies suggest better results with the combination, it is important to remember the experience, although favorable, is still preliminary. Larger studies are needed to establish the incremental value of PET-CT compared to PET and CT in individual cancers. Concern regarding whether treatment alterations are of significant clinical value with respect to magnitude of improvement of outcome or quality of life needs to be addressed, perhaps in a rigorously designed and conducted multicenter trial. The advantages of using a combination PET-CT scanner appear very obvious. It is a convenient, easy, and accurate method of combined imaging and is very likely to be used due to its practical utility. Combined imaging can have an impact on management not only in radiation planning but also by guiding invasive diagnostic and therapeutic procedures. Has PET-CT rendered PET obsolete? Probably not. PET has shown its usefulness and ability to help in clinical management. Each imaging facility will need to evaluate its need: Most clinical questions can be answered by PET alone or with retrospective fusion, and the incremental value of a dual-modality scanner needs to be carefully evaluated. Much of the mandate for the use of PET-CT in specific clinical scenarios should depend upon more studies with direct comparisons of PET-CT with PET plus CT.