PET assessment could facilitate NSCLC response-adapted therapy
Although expensive compared with CT, serial 18F-FDG PET could have practical value by facilitating response-adapted therapy and could actually reduce overall healthcare costs by leading to more cures and diminishing the use of and complications associated with ineffective treatment, according to a review of PET assessment of non-small cell lung cancer (NSCLC) in the May supplement issue of the Journal of Nuclear Medicine.

Rodney J. Hicks, MD, from the University of Melbourne and the Centre for Molecular Imaging, Peter MacCallum Cancer Centre, in Melbourne, Australia, discussed the current evidence supporting the role of 18F-FDG PET in evaluating the response of lung cancer to both chemotherapy and radiotherapy.

"Despite recognized limitations, structural imaging with CT remains the standard technique for evaluating the response of lung cancer to both chemotherapy and radiotherapy," wrote Hicks. "At present, an assessment of the therapeutic response in
NSCLC is primarily based on changes in the measured dimensions of lesions identified on CT."

Volume rendering of staging 18F-FDG PET demonstrates difficulties posed in defining primary lesion dimensions on CT in presence of atelectasis. Extensive loss of aerated lung was apparent in relationship to right lower lobe primary tumor that partially obstructed bronchus. Non-enlarged lymph nodes (arrows) with high 18F-FDG uptake, indicating likely involvement, were not amenable to response assessment by RECIST but could be monitored on serial 18F-FDG PET scans. High right paratracheal and aortopulmonary nodal involvement significantly increased radiation volume required to achieve coverage of macroscopic disease. Image and caption courtesy of SNM.
However, the advent of PET and, in particular, the widespread implementation of PET/CT with 18F-FDG, have allowed more accurate detection of both nodal and distant forms of metastatic disease. The imaging of changes in glucose metabolism, as reflected by cellular uptake and trapping of the glucose analog 18F-FDG, can provide a response assessment that is both more timely and more accurate than that provided by standard structural imaging, Hicks noted.

"The assumption that changes in tumor dimensions, as measured with CT or any other anatomic imaging modality, are a true marker of therapeutic efficacy is fraught with difficulty because tumors comprise variable proportions of malignant cells, stroma, and inflammatory cells," he wrote.

From a disease management and healthcare allocation perspective, the consequences of more sensitive detection of metastatic disease are that fewer NSCLC patients are likely to undergo futile thoracotomy and that more patients will be identified as requiring aggressive locoregional or systemic treatment, Hicks observed.

"As a corollary of more sensitive detection of metastatic disease, more patients are deemed not to be candidates for curative treatment with a single modality but nevertheless to have a relatively good performance status and therefore to be candidates for more aggressive palliative regimens," he wrote.

Although there have been many studies that have demonstrated the higher accuracy and prognostic stratification capabilities of 18F-FDG PET imaging for NSCLC, these have been focused on the response in either the primary tumor alone or the most metabolically active mediastinal node. Hicks argues that for a systemic disease, some method for providing an aggregate response to therapy is required.

"The aggregated data on the use of 18F-FDG PET and PET/CT in therapeutic response assessment strongly indicate that a reduction in tissue 18F-FDG retention, however it is measured and at whatever time after treatment it is recorded, is more likely to be associated with both a pathologic response and improved survival than is a lack of change," he wrote.

Hicks noted that there are no hard and fast rules of metabolic response of 18F-FDG as a biomarker.

"Accordingly, outside clinical trials, a metabolic response should be evaluated in the context of all available information, including the type and duration of treatment, the time elapsed between the last treatment and the PET evaluation, clinical evidence of toxicity and response, and the expected likelihood of a cure on the basis of risk factors and published response rates," he advised.

The timing of a PET scan to evaluate serial changes in tumor standardized uptake value (SUV) during therapy relates to the treatment regimen of the patient.

Hicks cited a recent 18F-FDG PET study evaluating serial changes in the SUV during chemotherapy for NSCLC in 16 patients demonstrated that a 50 percent or greater reduction in the SUV maximum between studies performed after 1 and 3 weeks of therapy was predictive of the survival of patients for more than 6 months, whereas patients with a less marked SUV reduction died within 6 months.

"From this information it should be clear that the percentage reduction that predicts a response may relate to the timing of the follow-up scan," he wrote.

However, for patients undergoing radiotherapy, the 18F-FDG assessment may need to occur a few months after treatment cessation. Hicks noted that a similar study of 15 patients receiving radiotherapy demonstrated that the peak residual 18F-FDG activity and qualitative response obtained during treatment correlated with the overall response obtained 3 months after treatment, which was previously shown to predict outcome.

"The optimal timing of therapeutic response assessment is theoretically that which provides the most robust assessment of a response and the greatest opportunity to alter treatment in non-responders," he wrote. "More robust response assessment will reduce the cost and morbidity associated with ineffective treatment and increase the opportunity for the institution of effective salvage treatment."