NEOADJUVANT

Neoadjuvant chemotherapy was initially applied to locally advanced breast cancer but has more recently been used in patients presenting with smaller, resectable breast cancers.¹ Studies identifying the amount of breast and axillary tumor after neoadjuvant chemotherapy have demonstrated prognostic value in predicting disease-free and overall survival.^2–5 In a study using fluorodeoxyglucose (FDG) PET, Bellon and coworkers found that internal mammary nodal involvement in patients with locally advanced breast cancer was predictive of regional or systemic failure.⁶ Modalities with exquisite anatomic and localization capabilities, such as CT and MRI, rely on a change in lesion size to assess efficacy. It is well recognized that a change in size may lag for weeks or months. CT scans are not routinely used to monitor the efficacy of chemotherapy in the neoadjuvant setting, although they may be very helpful to investigate a new finding during this time period. MRI has shown promise, but early results require larger, confirmatory studies. Dynamic contrast-enhanced MRI allows analysis of both tumor size and contrast enhancement pattern. Although these parameters may ultimately prove to be of great value in separating responders from nonresponders, underestimation of residual tumor size, comparing baseline and follow-up studies, could produce false-negative results, especially in larger tumors.^7,8 In the neoadjuvant setting, imaging is used primarily to assess local response.

Metabolic imaging, specifically FDG PET, has shown encouraging results in the neoadjuvant setting.^9–12 PET can be assessed visually or semiquantitatively. The most widely used quantitative method is measurement of the standardized uptake value (SUV) (Figure 1). This measures the amount of FDG uptake in a region of interest (i.e., tumor), divided by the injected dose corrected for patient weight. Many factors can affect this measurement, including lesion size, time interval between injection of FDG and time of imaging, and serum glucose level. Despite these and other variables, the SUV has proved useful for sequential assessment. Changes in SUV may be detected as early as after one cycle of chemotherapy. A significant fall in SUV separates responders from nonresponders and is also used prognostically. These data have been validated against histopathology.^11,13

FIGURE 1 These images demonstrate the use of SUV measurements to assess response to therapy in an 83-year-old woman with nodal metastatic breast cancer. The image on the left shows metastatic foci in bilateral supraclavicular and left paratracheal regions. Note SUV of 7.4 (arrow). Four months later, following therapy, the repeat study shows a decline in SUV to 4.2 (arrow), without resolution of the uptake.

METASTATIC

Monitoring response to chemotherapy in the metastatic setting is also an evolving challenge for imaging. Supporting data from large, wellcontrolled, prospective studies are lacking for both soft tissue and bone metastases. Interest in this particular aspect of breast cancer treatment has been sparked by the continued development of new chemotherapeutic agents, as well as the significant potential toxicity of these drugs. As in the neoadjuvant setting, CT and MRI reliably provide data on lesion size changes. However, changes in size may not occur for months in patients who are responding to treatment. Additionally, various cytostatic agents may never result in a decrease in size, even if efficacious in prolonging survival. Preliminary data on the use of FDG PET are encouraging, with some authors relying on a change in SUV to separate responders from nonresponders.^13–15 Significant differences have been shown between responders and nonresponders, with responders showing declining FDG uptake, as compared with minimal to no change in nonresponders. These changes have been demonstrated as early as after one cycle of chemotherapy. In the area of bone metastases, FDG PET appears to offer an advantage over conventional imaging (CI), including bone scintigraphy. Both CI and scintigraphy have difficulty assessing change in size of bone metastases; however, demonstration of significantly decreased or resolution of hypermetabolic activity on FDG PET provides valuable information.¹⁶

A possible caveat in the use of FDG PET to monitor response to therapy may be in patients treated with hormonal therapy. Initial studies have shown a transient increase in glucose use in responding patients, resulting in a “metabolic flare.” This may be due to an initial agonist effect rather than an antagonist effect of therapy. In two reports, responders showed this early increase in FDG uptake, whereas nonresponders did not.^17,18

Skeletal scintigraphy is covered in Chapter 8. Although whole-body bone scanning is a sensitive test for the identification of osteoblastic metastases, inherent problems with the physiologic basis for a positive study limit its utility for assessing efficacy of chemotherapy. As discussed previously, bone-seeking radiopharmaceuticals concentrate in large part owing to localized osteoblastic activity. Even relatively small increases in osteoblastic activity result in focal hot spots, often weeks to months before these lesions become visible on plain radiography or CT. However, the healing response alone, even in the absence of viable tumor, typically elicits increased radiopharmaceutical uptake, indistinguishable from active metastases. The added issue of suboptimal specificity (i.e., inability to separate benign from malignant disease) limits the role of bone scintigraphy as a modality to assess chemotherapy response. Two exceptions would be the disappearance of previously identified bony metastases on scintiscan and the development of new sites while receiving treatment. Under these circumstances, more definitive statements can be made.