figure 33.5. Transverse (C), coronal (A), sagittal (B), and maximum image projection (MIP) (D) (projection) PET images that demonstrate intense uptake of FDG in primary lung cancer (small cell). A previously unsuspected primary breast carcinoma is seen in the left breast.

pattern162 (nodular versus diffuse), and S phase.164,165 A weaker correlation with FDG has been reported for microvessel density, a surrogate of angiogenesis,166,167 and tumor cell density.162,167

No correlation was found between FDG uptake and tumor size,162,163,168 axillary node status,161,162,163 steroid receptor status,162,163,168,169 the presence of inflammatory cells,162 percentage of necrotic, fibrotic, and cystic components,162 or the thymidine labeling index (LI).168

Oshida et al.166 and Mankoff et al.171 found that FDG uptake in the primary tumor is predictive of response to treatment and patient outcome, even when they are treated with a variety of different protocols.

Eubank et al.170 assumed that FDG uptake may be a marker of tumor cell resistance to apoptosis, and this was supported by other studies.172,173 Intermediates in the glu-colytic pathway are key factors in initiating apoptosis, and alterations in these pathways limit apoptosis. Overexpression of some genes is associated with high glucolytic rates and resistance to apoptosis. An example is the P13K/Akt pathway.

Lymph Node Staging

The single most important prognostic factor in early stage breast cancer is the status of the axillary lymph nodes. The 10-year survival rate of patients with histologically negative axillary nodes (65% to 80%) is significantly higher than that of those with involvement of one to three nodes (38% to 63%) or more than three axillary nodes (13% to 27%).174 The extent of axillary disease influences the choice of the therapeutic regimen for individual patients. Many studies using FDG-PET for axillary staging showed a sensitivity of 40% to 94% and a specificity of 80% to 100%.154,175-180

Because neither physical examination nor conventional imaging can detect axillary nodal metastases, lymph node dissection (either conventional or limited with the use of sentinel node localization) is routinely performed to assess axillary nodal status in all patients with invasive cancers of 20 mm or less (80% or more of these patients have negative axillary lymph nodes). The risk of axillary nodal metastases is reported to be less than 5% in patients with tubular carcinoma less than 1 cm in diameter, grade I tumors less than 5 mm in diameter, or tumors with a single focus of microinvasion.

With the introduction of step sectioning and immunohis-tochemical staining, micrometastases can be detected in up to 45% of cases.181 Microscopic nodal involvement may be important for prognosis and treatment planning, and FDG-PET will miss this.182

Avril et al.180 found that the sensitivity of FDG-PET for detecting axillary disease in patients with T1 tumors (33%) was significantly less than for patients with tumors larger than 2 cm (94%). The specificity (100%) was the same for both subgroups. It has also been shown that the number of nodes involved with tumor at dissection influenced the sensitivity of PET (Table 33.9).

In preclinical studies of several types of tumors, including rat mammary tumors, Wahl et al.183 showed that FDG uptake in lymph nodes involved by metastatic tumor is greater than FDG uptake in normal lymph nodes. In a recent multicenter study involving 308 axilla sites, the same investigators reported a moderate accuracy of FDG-PET and a

TABLE 33.9. FDG-PET results for detection of axillary lymph node metastases.



No. of patients



Wahl et al.175

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