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

Positron-emission tomography(PET)-computed tomography(CT) has added a new dimensionto the imaging of cancers andcombination PET-CT scanners are becomingincreasingly universal. Theuse of combination scanners has increasedrapidly over the past 2 years-industry estimates are that the majorityof PET units sold throughout the worldwill be combination PET-CT scanners-and the authors have providedtheir own clinical experience and areview of the literature. While there issubstantial literature on the clinicalutility of PET alone, the use of PETCTis relatively new. The authors suggestthere is incremental benefit tothe addition of structural information(ie, CT) obtained at the same time asthe functional PET imaging.Pros and Cons
The combination scanner allowsfaster imaging by precluding the needfor slower transmission images andintegrating the CT images with PETimages. CT images not only providean anatomic map, they are also usedfor attenuation correction. Simultaneousor single-session anatomic andphysiologic imaging allows easier andmore accurate fusion of images andovercomes the drawback of retrospectivefusion through software, which ismore cumbersome and time consuming,and may not be possible for avariety of reasons including differentimaging protocols for the two studies(eg, arms raised or down) as well aslimitations of downloading digitalimages onto one platform.There are associated concerns, too.The combination machine is moreexpensive; CT scans used for fusionare usually not of diagnostic quality.Potential artifacts-for example, respiratorymotion and motion betweenacquisitions, truncation artifacts, andartifacts from contrast-can also significantlyaffect interpretation.The use of intravenous (IV) andoral contrast in PET-CT has beenshown in phantom studies to lead toCT attenuation artifacts. The use ofhigh-density oral contrast causes overattenuationfrom CT images, obviatedby the use of low-density contrast.[1]Similarly, nonionic IV high-densitycontrast in the arterial phase may alsocause alterations in quantitation; delayedIV contrast administration maymitigate that. Therefore, contrast mustbe used cautiously and with knowledgeof potential visual and quantitativeartifacts. Some groups acquirethe noncontrast CT for attenuation andthen carry out a limited CT assessmentafter IV or negative oral contrast.Every center must properlyoptimize the technique and take intoconsideration potential effects on imageand quantitation.Incremental Benefit?
While it is imperative to ask if thedata show that PET-CT is superior toPET alone, it is also important to ascertainthe incremental benefit of thePET-CT combination scanner. Howmuch benefit does PET-CT provide?What kind of patients are likely tobenefit most, and how often does thecombined technology change patientmanagement? It appears self-evidentthat concomitant evaluation of thePET and CT scan helps establish thelesion characteristic and location withmore certainty than PET alone. Amore important question is to assessobjectively whether simultaneousimaging and fusion using combinationscanners has incremental utilitycompared to visual side-by-side orretrospective fusion using softwareprograms.The published experience with 18Ffluorodeoxyglucose(FDG) PET incancer has been growing exponentiallyover the past several years. Itssignificance and importance in the diagnosis,staging, and follow-up ofmany cancers is established. FDG PEThas better sensitivity, specificity, andpredictive values compared to CTscan, ranging as high as 85% to 100%in certain cancers.[2] The overwhelmingevidence in support of its clinicalutility led to approval of PET by theCenters for Medicare and MedicaidServices (CMS) for a growing numberof indications.Limitations in anatomic localizationof abnormal FDG PET foci canbe only partially resolved by retrospectivefusion techniques, which aretime-consuming and suffer from theinaccuracies inherent in fusing disparateimage data sets. Simultaneousacquisition of anatomic and functionaldata by PET-CT has resulted inbetter diagnosis, staging, and restagingin a variety of cancers.[3] Thepublished literature is still in its infancyand consists largely of abstractsand preliminary data. Moreover, manystudies have compared PET-CT withPET alone rather than PET and CT. Afew studies have compared PET-CTwith "side-by-side PET and CT" orsoftware-fused images.[4-6]Does PET-CT have a greater impacton patient management than PETalone? The jury may still be out. Reinhartzand colleagues, in an analysis of328 patients, found that in 6.7% ofpatients, integrated PET-CT wouldhave gained additional advantage overcombined viewing of PET and CT.[4]Similar results in 260 patients werereported by Antoch et al, who foundthat PET-CT proved significantlymore accurate in assessing tumor.However, combined PET-CT had animpact on the treatment plan in only16 patients (6.1%) when comparedwith PET plus CT.[5]In another study in 204 patients,PET-CT had an impact on the managementof 14% patients, which includedexclusion of cancer in 2%,guiding invasive procedures/biopsiesin 3%, and referral to surgery, radiotherapy,or chemotherapy in 7%.[6]Finally, in patients evaluated for occultrecurrence, there was a statisticallysignificant difference betweenPET-CT and PET plus CT in the specificityand accuracy for site-basedanalysis of the characterization oflesions. However, no significant differencewas seen in sensitivity or predictivevalues. For the patient-basedanalysis, no significant difference wasseen.[7] The clinical significance ofthe additional lesions detected alsoneeds to be systematically addressedfor each cancer type.Optimal Use
The use of fused functional andanatomic imaging is expected to bemost useful in head and neck and abdominopelvicmalignancies, as theanatomy is complex, often complicatedby postoperative or postirradiationchanges, and interference fromphysiologic uptake of tracer may causedifficulties in interpretation. Apreliminary analysis of 68 patientsshowed that PET-CT decreased equivocalfindings in head and neck andabdominopelvic malignancies by 57%and 80%, respectively, and helped inthe delineation of chest findings by25%.[8] Again, the comparison wasmade between PET (not PET plus CT)and PET-CT. FDG PET has lowerspecificity in these regions, andperhaps the greatest impact with combinedimaging will be on specificity.Similar analysis in 45 patients withcolorectal cancer also showed bettercharacterization of lesions withPET-CT, which changed staging by11%.[9]PET-CT will probably prove moreadvantageous in gynecologic cancers,where peritoneal and mesenteric diseaseis frequent, and in evaluating organssuch as the adrenal glands andpancreas. Radioactivity in the kidneys,ureters, and bladder pose a diagnostichurdle in the absence of CT fusion.PET-CT can also help establish withcertainty a lack of uptake in lesionsseen on CT; precise localization forsuch evaluation is of huge value. PETCThas been shown to be superior indetecting malignant bone lesions byincreasing interpretation confidence.[10] Thus, for every cancer, specificclinical indications need to beidentified where the use of PET-CTwill prove incrementally advantageous.Another clinical application forwhich PET-CT appears very promisingand is expected to have a greatimpact on management is radiationtherapy planning. Studies in lung cancer,head and neck cancer, lymphoma,and esophageal cancer using PETscanning have shown its potential inidentifying the viable extent of tumors.The importance of simultaneousstructural and functionalimaging is of paramount importancein the definition of gross and treatmenttarget volumes for radiationtherapy planning. The functional informationprovided by PET oftenleads to alterations in treatment planning,changing the size and/or directionof radiation portals. In a numberof studies, the use of PET-CT wasshown to alter treatment volumes,thereby changing the managementplan. Overall, FDG PET helps achievebetter targets by inclusion of lesionsotherwise missed by other imaging.[11-13] In head and neck cancers,it was shown to alter the plannedradiation therapy volumes in five ofsix patients.[14]Conclusions
While there are many centers thathave made PET-CT scans part of standardpractice, and most studies suggestbetter results with the combination, itis important to remember the experience,although favorable, is still preliminary.Larger studies are needed toestablish the incremental value ofPET-CT compared to PET and CT inindividual cancers. Concern regardingwhether treatment alterations areof significant clinical value with respectto magnitude of improvementof outcome or quality of life needs tobe addressed, perhaps in a rigorouslydesigned and conducted multicentertrial.The advantages of using a combinationPET-CT scanner appear veryobvious. It is a convenient, easy, andaccurate method of combined imagingand is very likely to be used dueto its practical utility. Combined imagingcan have an impact on managementnot only in radiation planningbut also by guiding invasive diagnosticand therapeutic procedures.Has PET-CT rendered PET obsolete?Probably not. PET has shown itsusefulness and ability to help in clinicalmanagement. Each imaging facilitywill need to evaluate its need: Mostclinical questions can be answered byPET alone or with retrospective fusion,and the incremental value of adual-modality scanner needs to becarefully evaluated. Much of the mandatefor the use of PET-CT in specificclinical scenarios should depend uponmore studies with direct comparisonsof PET-CT with PET plus CT.

Disclosures:

The authors have nosignificant financial interest or other relationshipwith the manufacturers of any productsor providers of any service mentioned in thisarticle.

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