The Impact of Fluorodeoxyglucose–Positron Emission Tomography in Primary Staging and Patient Management in Lymphoma Patients

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Fully diagnostic positron emission tomography (PET)/CT scans acquired during oral and intravenous contrast can be provided to patients and referring physicians in a single imaging session. Although FDG uptake varies, most low-grade lymphomas exhibit sufficient FDG avidity to also be staged reliably with FDG PET/CT. PET/CT imaging is more accurate for lymphoma staging than PET or CT alone and has substantial impact on patient management. This accurate whole-body glucose metabolic survey should serve as the baseline for subsequent treatment response evaluations. PET/CT has evolved to become the modality of choice for staging of nodal and extranodal lymphoma, for assessing therapeutic response, and for establishing patient prognosis.

Section snippets

Imaging with fluorodeoxyglucose-6-phosphate

Increased glucose metabolic activity as a hallmark of malignant degeneration initially was described in 1924 by Warburg.10 This increase in glycolytic activity takes place even in the presence of oxygen. The increased glycolytic activity of tumors has been exploited for imaging cancer with PET and the glucose analog FDG.11, 12

Competing with serum glucose FDG targets membrane-bound glucose transporters (Glut-1 and Glut-3) that shuttle FDG into tumor cells and hexokinases (HK-1 and HK-2), which

Standardized uptake values

PET images can be analyzed visually, semiquantitatively by means of SUV,16 or quantitatively using appropriate tracer kinetic models.17 Because of their simplicity, PET scans most frequently are analyzed visually or by means of SUV that is defined as:decay-corrected activity [kBq]/tissue volume[mL]injected-FDG activity[kBq]/body weight[g]

The reproducibility of SUVs and that of more sophisticated model-based quantitative approaches that for instance measure tumor glucose use in units of

Fluorodeoxyglucose–positron emission tomography/CT cost and availability

More than 1800 PET/CT and PET scanners are distributed throughout the United States.19 With the emergence of commercial radio-pharmacies that produce FDG in small self-shielded cyclotrons, more than 95% of all cancer patients now have access to PET/CT imaging. Thus, there are essentially no limitations to the use of PET and the old argument, that PET imaging is only available in selected centers, can be put to rest. Another outdated argument is that whole-body FDG PET imaging is expensive while

Technical considerations

Most PET examinations in lymphoma and other cancers are performed as part of PET/CT studies that can be performed in less than 10 minutes in some patients.20, 21 PET/CT also increases patient comfort by reducing the need for multiple visits in clinics. PET image interpretation is facilitated by complementary anatomic information from CT, resulting in fewer equivocal findings, increased reader confidence22, 23, and more accurate assessments of the extent of disease.24, 25 PET/CT interpretations

Artifacts, pitfalls, and potentially false-positive studies

Nonmalignant conditions such as inflammation, infection, and granulomatous eg, sarcoidosis37, 38 and physiologic FDG uptake such as in brown adipose tissue,39 activated muscle (Fig. 5), or hyperplasia of the thymus40 can cause focally increased FDG uptake, and potentially lead to false-positive studies. Similarly, abnormal FDG uptake has been associated with hyperplasia in the bone marrow and spleen after chemotherapy or in patients receiving granulocyte colony-stimulating factor after

Glucose metabolic activity varies among different types of non-Hodgkin lymphoma

Lymphomas differ with regard to their glucose metabolic activity. Systematic studies have shown that indolent lymphomas exhibit lower glucose metabolic activity and hence FDG uptake than the more aggressive ones.42 For instance, diffuse large B-cell, and high-grade follicular lymphoma had, on average, threefold higher FDG SUVs than indolent lymphomas such as low grade follicular, lymphocytic–plasmocytic, mantle cell, marginal zone, or small cell lymphoma.43

These differences in glucose metabolic

Fluorodeoxyglucose uptake in Hodgkin lymphoma

Since the cytologic and immunochemical atypical cells (Reed-Sternberg cells and variants) may represent 1% to 3% of the tumor bulk, PET activity in classical HL almost exclusively reflects the reactive microenvironment (lymphoid hyperplasia) within which the malignant cells are found, rather than the neoplastic population itself. This is in contrast to NHLs, where, with few exceptions, most of the tumor bulk consists of neoplastic cells.

Few studies have examined differences among glucose

The role of positron emission tomography and positron emission tomography/CT imaging in staging of lymphoma

Lymphoma is a tissue biopsy-based diagnosis. Once established, the assumption that most (if not all) enlarged lymph nodes and most (if not all) extranodal lesions are lymphoma involved is reasonable. Therefore, CT-based initial staging has remained the mainstay of the noninvasive diagnostic workup. On the other hand, because all lymphoma patients who have potentially curable disease undergo chemotherapy or chemo/radiation treatment, and FDG PET is far superior to CT for treatment monitoring and

Evaluation of bone marrow involvement

One important aspect of staging is the evaluation of bone marrow involvement.68 In a prospective study the accuracy of PET/CT, bone marrow biopsy and MRI for detecting marrow involvement was compared in 47 patients with aggressive, most frequently diffuse large B-cell lymphoma. Both MRI and PET/CT identified 9 patients with bone marrow involvement while bone marrow aspiration identified only two patients. It seems likely that the noninvasively identified lesions truly represented areas of

Impact of fluorodeoxyglucose positron emission tomography on disease management

Patient prognosis depends upon histopathology and clinical parameters that are used to calculate disease-specific prognostic indices (international prognostic index, Follicular Lymphoma International Prognostic Index71). Because stage usually depends upon the location and number of disease sites, it is not a true measure of tumor burden. Staging is an important prognostic determinant in NHL, and it affects the overall therapeutic strategy. It is performed to identify the small number of

Treatment response assessment

Many studies have reported the prognostic significance of changes in glucose metabolic activity in response to treatment.83, 84, 85, 86, 87, 88 The value of PET for monitoring of treatment is reflected in the recently published guidelines of the International Harmonization Project.9, 89 Please refer to the articles by Schoeder and Cheson in this issue, which discuss this topic in detail.

Summary

Fully diagnostic PET/CT scans acquired during oral and intravenous contrast can be provided to patients and referring physicians in a single imaging session. Although FDG uptake varies, most low-grade lymphomas exhibit sufficient FDG avidity to also be staged reliably with FDG PET/CT.

PET/CT imaging is more accurate for lymphoma staging than PET or CT alone and has substantial impact on patient management. This accurate whole-body glucose metabolic survey should serve as the baseline for

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