2-[ 18 F]Fluoro-2-deoxyglucose positron emission tomography (FDG-PET) assesses a fundamentalpropertyof neoplasia, theWarburgeffect.This molecularimaging technique offers acomplementary approach to anatomic imaging that is more sensitive and specific in certain cancers. FDG-PET has been widely applied in oncology primarily as a staging and restaging tool that can guide patient care. However, because it accurately detects recurrent or residual disease, FDG-PETalso has significant potential for assessing therapy response. In this regard, it canimprove patient management by identifying responders early, before tumor size is reduced; nonresponders could discontinue futile therapy. Moreover, a reductioninthe FDG-PETsignal withindays or weeks of initiating therapy (e.g., in lymphoma, non^small cell lung, and esophageal cancer) significantly correlates with prolonged survival and other clinical end points now usedin drug approvals.These findings suggest that FDGPETcould facilitate drug development as an early surrogate of clinicalbenefit.This article reviews the scientificbasis ofFDG-PETandits development andapplicationasavaluableoncologyimagingtool. Its potential to facilitate drug development in seven oncologic settings (lung, lymphoma, breast, prostate, sarcoma, colorectal, and ovary) is addressed. Recommendations include initial validation against approved therapies, retrospective analyses to define the magnitude of change indicative of response, further prospective validation as a surrogate of clinical benefit, and application as a phase II/III trial end point to accelerate evaluation and approval of novel regimens and therapies.
FDG-PET (2-[18 F]Fluoro-2-deoxyglucose positron emission tomography) is an accepted and widely used clinical imaging tool in oncology. U.S. Medicare reimbursement of FDG-PET recently expanded to encompass all cancer patients participating in certain prospective studies or registries in addition to more general coverage in 10 defined oncologic settings. Primarily covered are disease diagnosis, staging, and restaging, but FDG-PET is also approved for monitoring response to therapy in locally advanced and metastatic breast cancers when a change in therapy is anticipated. Clinical trials in breast cancer and other settings [e.g., non -small cell lung cancer (NSCLC) and esophageal cancer] have shown that FDG-PET imaging can provide an early indication of therapeutic response that is well correlated with clinical outcome. FDG-PET thus has the potential to improve patient management, particularly by signaling the need for early therapeutic changes in nonresponders, thereby obviating the side effects and costs of ineffective treatment. As an early surrogate for clinical benefit, the modality also has the potential to facilitate oncologic drug development by shortening phase II trials and detecting clinical benefit earlier in phase III investigations. Studies to further explore and validate these approaches are needed and can be conducted in parallel with those employing end points now use...