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Prepublished online as a Blood First Edition Paper on January 16, 2003; DOI 10.1182/blood-2002-09-2778.
CLINICAL OBSERVATIONS, INTERVENTIONS, AND THERAPEUTIC TRIALS
From the Abramson Family Cancer Research
Institute of the University of Pennsylvania, Philadelphia; and the
Departments of Medicine, Nuclear Medicine, and Laboratory Medicine and
Pathology, University of Pennsylvania Medical Center, Philadelphia.
We retrospectively evaluated 18fluoro-2-deoxyglucose
positron emission tomography (FDG-PET) scans in 172 patients with
lymphoma and correlated results with pathologic diagnosis using the
World Health Organization (WHO) classification system. In total,
FDG-PET detected disease in at least one site in 161 patients (94%)
and failed to detect disease in 11 patients (6%). The most frequent lymphoma diagnoses were diffuse large B-cell lymphoma (LBCL; n = 51),
Hodgkin lymphoma (HL; n = 47), follicular lymphoma (FL; n = 42),
marginal zone lymphoma (MZL; n = 12), mantle cell lymphoma (MCL;
n = 7), and peripheral T-cell lymphoma (PTCL; n = 5). FDG-PET detected disease in 100% of patients with LBCL and MCL and in 98% of
patients with HL and FL. In contrast, FDG-PET detected disease in only
67% of MZL and 40% of PTCL. Comparison with bone marrow biopsies
showed that FDG-PET was not reliable for detection of bone marrow
involvement in any lymphoma subtype.
(Blood. 2003;101:3875-3876) Computed tomography (CT) scanning
and histopathologic examination of bone marrow comprise the current
approach to initial staging and evaluation of response to therapy of
lymphomas. However, the utility of these modalities is limited, because
criteria for disease involvement by CT scan are usually based on the
size of a lesion, and bone marrow examination may be limited by
sampling error. Furthermore, it may be difficult to distinguish
residual disease from nonmalignant "scar" tissue following
treatment or to differentiate inflammatory from malignant lesions
by CT.
Cancer imaging by positron emission tomography (PET) using
18fluoro-2-deoxyglucose (FDG) is based on the observation
that most cancers, including many lymphomas, metabolize glucose at an
abnormally high rate.1 FDG-PET is becoming widely used in
the evaluation of patients with lymphoma.2-4
Although most lymphomas can be imaged by FDG-PET, we and others have
observed cases that lack FDG uptake. Previous studies evaluating the
sensitivity of FDG-PET in lymphomas showed conflicting results,
particularly in indolent lymphomas.5-11
We hypothesized that biologic differences between specific
pathologic subtypes of lymphoma result in different degrees of FDG
uptake and that utility of FDG-PET imaging varies between specific
lymphomas. We retrospectively studied results of FDG-PET scans in
patients with lymphoma using the World Health Organization (WHO)
classification system to identify the specific subtypes reliably
detected by FDG-PET. Furthermore, the ability of FDG-PET to detect bone
marrow involvement by various lymphoma subtypes was evaluated by
comparison with bone marrow biopsy.
Patients
FDG-PET scanning
Bone marrow comparison Comparison of FDG-PET and iliac crest bone marrow biopsy was performed on all patients with large B-cell lymphoma (LBCL), follicular lymphoma (FL), Hodgkin lymphoma (HL), marginal zone lymphoma (MZL), and mantle cell lymphoma (MCL) for whom biopsy material was available for review. PET scans were reviewed as described in "FDG-PET scanning," and bone marrow was considered positive by FDG-PET if any area of bone marrow showed an SUV more than 2.5. Bone marrow biopsies were reviewed along with diagnostic specimens.
A total of 172 patients met criteria for analysis (Table
1). FDG-PET imaging detected disease in
at least one site in 100% of patients with LBCL (n = 51) and MCL
(n = 7) and in 98% of patients with HL (n = 47) and FL (n = 42).
The single HL case not detected by FDG-PET was in early relapse
documented by biopsy of a subcentimeter subpleural pulmonary nodule.
The single case of undetected FL consisted of an ileal tumor detected
only by endoscopic biopsy. These cases suggest that tumor volume may be
a factor in false-negative FDG-PET studies. FDG-PET also detected
disease in patients with ALCL (n = 2), MF (n = 1), BL (n = 1),
SLL (n = 1), and T/NK (n = 1); however, the numbers of
patients with these diagnoses are too small to assess the utility of
FDG-PET. In contrast, only 67% of MZL (n = 12) and 40% of PTCL
(n = 5) were detected by FDG-PET. Two cases of low-grade CBCL were
also not detected by FDG-PET.
FDG-PET imaging was further evaluated for accuracy in detection
of bone marrow involvement by comparing results with iliac crest bone
marrow biopsy in the most common histologic subtypes: LBCL, FL, HL,
MZL, and MCL. Detection of bone marrow involvement by FDG-PET was
suboptimal for all pathologic subtypes of lymphoma examined. Bone
marrow biopsies were available for 105 of 159 patients with these
histologies. As shown in Table 2, PET
rarely detected pathologically identifiable marrow involvement by FL
and did not detect marrow involvement by MCL or MZL in any case. This
situation may be due to relatively low FDG uptake per cell or to
diffuse, low-density marrow involvement by tumor. HL and LBCL,
conversely, showed FDG uptake in bone marrow that was not confirmed by
iliac crest biopsy in several cases. Although these cases may represent false-positives, patients may alternatively have had patchy bone marrow
involvement that was not detected by blind iliac crest biopsy. Whether
FDG-PET may in fact improve sensitivity of disease detection in these
histologies over blind iliac crest biopsy is an important question that
is currently under investigation.
Other groups have reported conflicting results regarding the utility of FDG-PET imaging in indolent lymphomas.12,13 However, lymphoma diagnosis by the WHO classification was not reported in these studies. Our data indicate that WHO classification of lymphomas is crucial in determining the utility of FDG-PET to image lymphomas. We suggest that biologic characteristics intrinsic to specific histologic subtypes determine glucose utilization and, therefore, FDG uptake. The fact that FL almost invariably showed high FDG uptake demonstrates that histologic grade is not the most important predictor of FDG avidity. Similarly, the variability of results within MZL and PTCL suggests that the mechanisms of metabolic deregulation during lymphomagenesis are more complex than simply meeting the cellular needs of growth and proliferation. The identification of lymphomas that are uniformly detected by FDG-PET implies that this imaging modality may be useful in detecting residual active disease for specific lymphomas even in the absence of a baseline scan. Confirmation of our results in prospective studies of larger numbers of patients and in multiple centers is needed before conclusions derived from these results can be adopted into clinical practice.
Submitted September 11, 2002; accepted January 11, 2003.
Prepublished online as Blood First Edition Paper, January 16, 2003; DOI 10.1182/blood-2002-09-2778.
Supported in part by grants from the Anne V. Petchel Foundation and The Leukemia & Lymphoma Society (grant no. 6152-02; S.J.S.).
The publication costs of this article were defrayed in part by page charge payment. Therefore, and solely to indicate this fact, this article is hereby marked "advertisement" in accordance with 18 U.S.C. section 1734.
Reprints: Rebecca L. Elstrom, Division of Hematology/Oncology, University of Pennsylvania, 16 Penn Tower, 3400 Spruce St, Philadelphia, PA 19104; e-mail: relstrom{at}mail.med.upenn.edu.
1. Warburg O. On the origin of cancer cells. Science. 1956;123:309-311. 2. Hustinx R, Benard F, Alavi A. Whole-body FDG-PET imaging in the management of patients with cancer. Semin Nucl Med. 2002;32:35-46[Medline] [Order article via Infotrieve]. 3. Spaepen K, Stroobants S, Dupont P, et al. Can positron emission tomography with [(18)F]-fluorodeoxyglucose after first-line treatment distinguish Hodgkin's disease patients who need additional therapy from others in whom additional therapy would mean avoidable toxicity? Br J Haematol. 2001;115:272-278[CrossRef][Medline] [Order article via Infotrieve]. 4. Naumann R, Vaic A, Beuthien-Baumann B, et al. Prognostic value of positron emission tomography in the evaluation of post-treatment residual mass in patients with Hodgkin's disease and non-Hodgkin's lymphoma. Br J Haematol. 2001;115:793-800[CrossRef][Medline] [Order article via Infotrieve]. 5. Jerusalem G, Beguin Y, Najjar F, et al. Positron emission tomography (PET) with 18F-fluorodeoxyglucose (18F-FDG) for the staging of low-grade non-Hodgkin's lymphoma (NHL). Ann Oncol. 2001;12:825-830[Abstract].
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© 2003 by The American Society of Hematology.
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Abstract
Introduction