Role of FDG-PET scans in staging, response assessment, and follow-up care for non-small cell lung cancer

Abstract

The integral role of positron-emission tomography (PET) using the glucose analog tracer fluorine-18 fluorodeoxyglucose (FDG) in the staging of non-small cell lung cancer (NSCLC) is well established. Evidence is emerging for the role of PET in response assessment to neoadjuvant therapy, combined-modality therapy, and early detection of recurrence. Here, we review the current literature on these aspects of PET in the management of NSCLC. FDG-PET, particularly integrated (18)F-FDG-PET/CT, scans have become a standard test in the staging of local tumor extent, mediastinal lymph node involvement, and distant metastatic disease in NSCLC. (18)F-FDG-PET sensitivity is generally superior to computed tomography (CT) scans alone. Local tumor extent and T stage can be more accurately determined with FDG-PET in certain cases, especially in areas of post-obstructive atelectasis or low CT density variation. FDG-PET sensitivity is decreased in tumors <1 cm, at least in part due to respiratory motion. False-negative results can occur in areas of low tumor burden, e.g., small lymph nodes or ground-glass opacities. (18)F-FDG-PET-CT nodal staging is more accurate than CT alone, as hilar and mediastinal involvement is often detected first on (18)F-FDG-PET scan when CT criteria for malignant involvement are not met. (18)F-FDG-PET scans have widely replaced bone scintography for assessing distant metastases, except for the brain, which still warrants dedicated brain imaging. (18)F-FDG uptake has also been shown to vary between histologies, with adenocarcinomas generally being less FDG avid than squamous cell carcinomas. (18)F-FDG-PET scans are useful to detect recurrences, but are currently not recommended for routine follow-up. Typically, patients are followed with chest CT scans every 3-6 months, using (18)F-FDG-PET to evaluate equivocal CT findings. As high (18)F-FDG uptake can occur in infectious, inflammatory, and other non-neoplastic conditions, (18)F-FDG-PET-positive findings require pathological confirmation in most cases. There is increased interest in the prognostic and predictive role of FDG-PET scans. Studies show that absence of metabolic response to neoadjuvant therapy correlates with poor pathologic response, and a favorable (18)F-FDG-PET response appears to be associated with improved survival. Further work is underway to identify subsets of patients that might benefit individualized management based on FDG-PET.

Keywords: PET; follow-up; non-small cell lung cancer; response assessment; staging.

FIGURE 1

Lung cancer patient with multiple right lung nodules. Shown are corresponding PET (left), CT (right), and fusion (middle) images of a single coronal plane through the right lung. In the upper lobe, where respiratory motion is least, a punctate nodule (white arrowheads) demonstrates intense FDG uptake with a distinctly focal appearance (black arrowhead). In the lower region of the lung, where respiratory motion is greater, the FDG uptake of larger nodules (white arrows) appears relatively less-intense – probably due to “spreading” of the activity over a spatial volume during each breathing cycle, a kind of respiratory artifact. This “spreading” is most visually evident closest to the diaphragm (black arrow).

FIGURE 2

Eighty-two-year-old female with growing right lung nodule. Prior lung CT scans over a 1-year period had demonstrated increasing size of a spiculated-appearing right lung nodule (white arrow). FDG-PET/CT was performed for nodule characterization. Images show corresponding transaxial planes through the chest from the CT and FDG PET (upper right); and a 3D maximum intensity projection imaged centered on the chest region (center image). PET showed detectable, albeit minimal, activity in the right lung nodule (black arrows; SUV_max 2.1) and focal activity in the right pulmonary hilum (arrowhead) thought to represent lymph node FDG uptake. Wedge resection was performed; pathology found focal bronchopneumonia/granuloma.

FIGURE 3

Sixty-seven-year-old male with stage IV non-small cell lung cancer. Top row: 3D maximum intensity projection (MIP) FDG-PET images obtained at baseline (left); after 4 months treatment with pemetrexed and bevacizumab (middle); and 9 months after the baseline scan, switched to second-line docetaxel therapy due to progression on interim scans (right). Arrowheadspoint to an FDG-avid osseous metastasis in the left ilium that initially disappears in response to treatment but then recurs. Middle row: corresponding CT (left) and PET (right) images of a single transaxial plane through the pelvis, showing the lesion of the left ilium on CT that showed no FDG-avidity after 4 months treatment with pemetrexed and bevacizumab, suggesting a treated disease (arrowheads). Bottom row: the subsequent scan, 9 months after baseline, showed no change in the CT appearance of the left iliac bone lesion, but the lesion now demonstrates intense FDG uptake, consistent with a viable/recurrent metastasis.