Frequent Impact of [18F]Fluorodeoxyglucose Positron Emission Tomography on the Staging and Management of Patients with Indolent Non-Hodgkin's Lymphoma

Imaging in Lymphoma Frequent Impact of [18F]Fluorodeoxyglucose Positron Emission Tomography on the Staging and Management of Patients with Indolent Non-Hodgkin’s Lymphoma Robert H. Blum,1 John F. Seymour,1 Andrew Wirth,2 Michael MacManus,2 Rodney J. Hicks3

Abstract [18F]fluorodeoxyglucose (FDG) positron emission tomography (PET) is useful in staging aggressive non-Hodgkin’s lymphoma (NHL). However, its role in indolent NHL has not been established. This retrospective study assessed the sensitivity and clinical impact of PET findings in patients with indolent NHL. Patients with indolent NHL who underwent FDG-PET scanning between May 1997 and August 2001 were identified. Case records were reviewed for FDG-PET and conventional staging/restaging results and compared for concordance. Forty-seven patients were identified. Twelve staging FDG-PET scans and 37 restaging FDG-PET scans were obtained. The FDGPET case sensitivity rate was 98%. Forty-two percent of staging FDG-PET scans were concordant with conventional staging, with the remaining patients exhibiting more extensive disease on PET. At progression, FDG-PET and conventional assessments were discordant in 46% of cases. Positron emission tomography findings downstaged disease in 30% of these patients and upstaged disease in 16%. Computed tomography (CT) and FDG-PET identified 150 and 146 individual sites of disease, respectively. Among “definite” sites on structural imaging, 74% were also seen on PET. For equivocal lesions, only 19% were seen on both modalities. Clinical management was changed in 34% of patients as a result of FDG-PET findings. Of 22 discordant lesions in which true disease status could be evaluated, the PET findings were confirmed to be correct in 21 (95%; P < 0.0001). These findings demonstrate that FDG-PET has a high sensitivity for indolent NHL and often leads to alteration of disease staging and management. This high accuracy of FDG-PET in assessing discordant lesions suggests a greater diagnostic utility compared with CT.

Clinical Lymphoma, Vol. 4, No. 1, 43-49, 2003 Key words: Computed tomography, Disease progression, Follicular lymphoma, Functional imaging, Structural imaging, Tumor staging

Introduction Indolent non-Hodgkin’s lymphomas (NHLs) are considered incurable when disseminated, with a majority of patients ultimately dying from their disease.1-2 Seventy to eighty percent have stage III/IV disease at presentation, with a median survival approaching 9 years.3 Treatment options for this group are diverse, ranging from observation to high-dose chemotherapy with stem cell transplantation.4 Molecular markers of minimal residual disease such as Bcl-2 assessment by polymerase chain reaction in the blood and bone marrow have been used to guide treatment and predict outcome.5 1Division

of Hematology and Medical Oncology of Radiation Oncology 3Department of Nuclear Medicine and Positron Emission Tomography Peter MacCallum Cancer Institute, Melbourne, Australia 2Division

Submitted: Jan 8, 2003; Revised: Apr 30, 2003; Accepted: May 5, 2003 Address for correspondence: Robert H. Blum, MBBS, CSL Oncology Fellow, Division of Hematology and Medical Oncology, Peter MacCallum Cancer Institute, Locked Bag No 1, A’Beckett St, Melbourne 8006, Australia Fax: 61-3-96561408; e-mail: [email protected]

The remaining 20%-30% of patients present with early-stage disease that is potentially curable.6-8 Treatment of stage I/II indolent NHL with involved-field or regional radiation therapy has been reported to achieve cure rates of 40%-50%.9-10 The additional benefit of chemotherapy to involved-field radiation in this group is still uncertain. However, a prospective phase II trial by Seymour et al demonstrated that 10 courses of cyclophosphamide, vincristine, prednisone, and bleomycin, with doxorubicin added in a risk-adapted manner, in conjunction with 30-40 Gy involved-field radiation therapy, achieved a 10-year disease-free survival rate of 73% in patients with clinical stage I/II indolent NHL.11 The optimal approach to patients with stage III disease remains unclear. In many studies, patients with stage III and stage IV indolent NHL are considered to have “disseminated” disease and are treated in a single group.4,12 However, a number of studies has specifically studied comprehensive lymphatic irradiation in patients with stage III disease, including a large study from Stanford University in which a 15-year survival rate of approximately 30% was achieved.13-15

Clinical Lymphoma June 2003 • 43

PET in Indolent Lymphoma In order to identify patients who are likely to benefit from potentially curative radiation therapy–based treatments, accurate staging at diagnosis is imperative. Traditionally, staging of patients with NHL has consisted of clinical assessment, computed tomography (CT), and bone marrow trephine biopsy. Computed tomography (structural imaging) requires anatomic distortion to detect abnormal pathology. Therefore, small-volume disease may go undetected. Accurate restaging to assess treatment response or progressive disease is also important in order to determine further management. A limitation of conventional radiology after therapy is the inability to distinguish between persistent abnormal anatomy resulting from scar tissue and residual viable disease. Functional imaging in conjunction with structural imaging can improve disease detection. Imaging with the radionuclide gallium citrate Ga 67 is a functional imaging modality traditionally used to stage NHL.16 Although very useful in histologically aggressive NHL, the reported sensitivity in indolent NHL ranges from 40% to 70%.17-19 Thallium scans have also been used in the assessment of indolent NHL and may be helpful in non–gallium-avid disease. However, because of high uptake by normal abdominal organs, it provides relatively poor evaluation of the retroperitoneum, mesentery, and pelvis.20 [18F]fluorodeoxyglucose positron emission tomography (FDG-PET) is also a functional imaging modality, with increasing evidence supporting its role as an important staging investigation in many cancers.21 FDG-PET has a number of advantages over other functional scanning techniques, including less nonspecific intestinal uptake, shorter imaging time, and, most importantly, better imaging resolution. In histologically aggressive NHL, the reported sensitivity and specificity rates of FDG-PET are 84% and 95%, respectively.22,23 However, the diagnostic utility of FDG-PET in indolent NHL has not been established.

Materials and Methods Patients From May 1997 to August 2001, 47 patients with indolent NHL who had undergone FDG-PET imaging at our institution were identified through the central nuclear medicine PET database. Clinical information was retrospectively collected from medical records. Disease histologies classified as indolent NHL for study purposes included follicular center-cell (grades I/II) and marginal zone lymphomas.24 To be included, patients were required to have complete conventional staging (at least history, physical examination, CT and/or other relevant imaging, and marrow examination). Only 1 FDG-PET scan for staging and 1 for progression/surveillance per person were included in the analysis. This was to avoid bias introduced by inclusion of repeatedly scanned patients with known avid disease. Twelve of the 47 patients underwent FDG-PET at initial diagnosis. Thirty-seven patients had FDG-PET performed at definite progression (unequivocal new or enlarging sites on conventional assessment; n = 12) or possible progression (equivocal new or enlarging sites or symptoms; n = 21), or as part of routine clinical surveillance (no indication of recurrence on conventional assessment; n = 4). Two patients underwent FDG-PET for both staging and restaging. This project was approved by the institu-

44 • Clinical Lymphoma June 2003

tional ethics committee. The PET scans were performed as part of routine clinical management. PET Imaging The FDG-PET images were acquired on a GE Quest 300H scanner and processed using iterative reconstruction of both raw and attenuation-corrected data. The FDG-PET images were obtained after a minimum fasting period of 4 hours. Whole-body FDG-PET scans encompassed the neck, thorax, abdomen, pelvis, and proximal thighs approximately 1 hour after administration of radioactive tracer. Images were processed with and without measured transmission attenuation correction. Identical methodology was used for baseline and follow-up FDG-PET scans. The physician performing FDG-PET generally had access to the results of the previous imaging and clinical information; when available, these were directly correlated with the functional imaging. Scans were interpreted qualitatively. All FDG-PET reports were entered prospectively into the central PET database and were not reinterpreted in the light of the subsequent clinical course. Data Collection and Interpretation Scan results and clinical details were obtained from patient records using purpose-designed data forms. Multiple abnormalities within an extranodal site were counted as 1 site (eg, multiple bone lesions, multiple pulmonary nodules). Nodes that were completely excised before imaging and microscopic bone marrow involvement detected at biopsy were considered nonevaluable by imaging and excluded from the analysis of site count, but not from the assessment of stage and treatment impact. Each Ann Arbor classification site was coded as “positive,” “equivocal,” or “negative” for PET and conventional evaluation. Definite sites of disease on conventional radiology were defined as any lesion > 10 mm or described as definite disease in the report summary. Equivocal lesions on structural imaging included lymph nodes < 1 cm or a nondefinite description in the report. Sites of increased radioactive tracer uptake on PET were coded as uninvolved when specifically reported as being caused by intercurrent pathology, reaction to treatment, or physiologic uptake. Increased radioactive tracer uptake in the site of a recent biopsy was coded as equivocal unless the stated findings were unlikely to be caused by postoperative changes. Each patient’s disease was staged according to the Ann Arbor classification by definite sites alone.25 Definition of True Positive and True Negative Sites When functional and structural imaging results were discordant, a “true positive” site was defined by (1) positive biopsy results or (2) detection on functional imaging only, with tumor progression in this site on structural imaging within 6 months in the absence of treatment to that site. A “true negative” site was defined by (1) negative adequate biopsy results or (2) equivocal or negative results on conventional assessment with no progression detected by appropriate evaluation for at least 6 months in the absence of treatment to that site. Sites

Robert H. Blum et al Table 1

Case Sensitivity of PET in Low-Grade NHL CT Positive Disease

Table 2

CT Negative Disease

PET Positive Disease

41

0

PET Negative Disease

1

5

Abbrevations: CT = computed tomography; NHL = non-Hodgkin's lymphoma; PET = positron emission tomography

not meeting these criteria were deemed nonevaluable. In the evaluation of the case sensitivity of PET, true positive cases were those of patients with ≥ 1 positive site. Impact on Stage and Treatment Treatment impact analysis examined the additional information provided by PET over conventional staging and categorized whether there was a change in treatment strategy (ie, radiation therapy alone, chemotherapy alone, or combined-modality therapy) or a change in radiation therapy fields that resulted directly from the PET findings. Statistics All statistical tests were 2-sided and performed using the StatXact statistical package. Ninety-five–percent confidence intervals (CIs) were based on exact binomial distribution. Concordance of stage and individual sites of disease between conventional and PET imaging were performed using the exact marginal homogeneity test.

Results Demographics Forty-seven patients were recruited for this study, with a median age of 55 years, and 49% were men. Follicular lymphoma was detected in 92% of patients, whereas 8% had marginal-zone lymphoma. Positron emission tomography was performed for staging in 12 patients, suspected progression in 21 patients, definite progression in 12 patients, and surveillance in 4 patients. Disease Sensitivity Forty-one of the 47 patients (87%) had definite sites of disease on their index PET scan. Of the remaining 6 patients, only 1 had definite disease on structural imaging. This patient had evaluable disease, revealing that the FDG-PET assessment was correct. Only 2 of the 41 patients with PET-positive disease had low FDG avidity. The remaining patients had moderately to highly FDG-avid disease. Disease histology was not predictive of FDG avidity, with both marginal-zone and follicular cases well visualized (P = 0.37). The overall case sensitivity was 98% (95% CI, 87.4%-99.9 %; Table 1). Stage Impact by PET Twelve patients underwent FDG-PET imaging as part of their initial staging. In 42% of these cases (5 of 12; 95% CI, 15%-72%), FDG-PET found more extensive disease compared with conventional imaging (Figure 1). The remaining 58% (7 of

Conventional and PET Results of 12 Patients with Disease Staged at Initial Presentation

Patient Conventional Number Stage

PET Stage

Treatment Impact

1

I

III

Radiation therapy fields increased; additional chemotherapy given

2

IV

IV

No impact

3

I

I

More extensive but equivocal disease sites on conventional staging; only definite sites on CT confirmed by PET; radiation therapy fields reduced

4

IV

IV

No impact

5

IV

IV

No impact

6

II

III

Radiation therapy fields increased

7

II

III

Radiation therapy fields increased plus addition of systemic chemotherapy

8

III

III

No impact

9

IV

IV

No impact

10

I

III

Changed from radiation therapy to systemic chemotherapy

11

II

IIE

Changed radiation therapy fields

12

IV

IV

No impact

All staging was based on definite sites alone. Abbreviations: CT = computed tomography; PET = positron emission tomography

12) were concordantly staged (Table 2). Thirty-seven patients underwent FDG-PET at suspected progression or as part of routine surveillance. Forty-six percent of patients (17 of 37; 95% CI, 29%-63%) had discordant results. Of those with discordant results, 30% (11 of 37) had their disease downstaged by FDG-PET (Figure 2) and the remaining 16% (6 of 37) had their disease upstaged. Three of the cases downstaged by FDG-PET had no disease evident on functional imaging. All 3 cases had follicular histology. The remaining 54% were concordantly staged. Site-Specific Correlation The total number of definite and equivocal disease sites detected on conventional and functional imaging was also analyzed to establish the degree of concordance between the 2 imaging modalities (Table 3). Of the total of 202 definite and equivocal disease sites seen on either modality, 150 and 146 were detected

Table 3

Concordance Between Conventional Staging and PET of Individual Sites of Detected Disease

Definite CT Results

Definite

PET Results Equivocal

Negative

88

0

30

Equivocal

5

1

26

Negative

32

20

0

Abbreviations: CT = computed tomography; PET = positron emission tomography

Clinical Lymphoma June 2003 • 45

PET in Indolent Lymphoma Figure 1 Coronal FDG-PET Scans of Patient with Follicular Lymphoma

Figure 2 FDG-PET Scans of Patient with Follicular Lymphoma After Radiation Therapy Coronal

Transaxial

Representative coronal FDG-PET images from a patient with newly diagnosed stage II follicular lymphoma based on excised inguinal nodes and known residual right iliac lymphadenopathy based on CT. On FDG-PET, abnormal uptake was confirmed in the known iliac mass (red arrow) but was also apparent in the left supraclavicular region (yellow arrow) and the spleen (blue arrow), making the PET results indicate stage IIIS disease. Based on these findings, management was changed from local radiation therapy to involved-field radiation therapy plus chemotherapy. Abbreviations: CT = computed tomography; FDG-PET = [18F]fluorodeoxyglucose positron emission tomography

on CT and FDG-PET, respectively. Among these, 94 sites were concordantly detected by both structural and functional imaging, whereas 52 sites (36%) were seen on FDG-PET alone and 56 sites (37%) were seen on CT alone. The degree of concordance varied according to the certainty of disease detection by structural imaging. For “definite” sites on structural imaging, there was a 75% concordance with FDG-PET. Conversely, for “equivocal” sites on conventional radiology, the concordance rate was only 19% (P < 0.0001). However, when all lesions detected on either modality were included in the comparison, the correlation was 44% (95% CI, 37%-51%; P = 0.91). Evaluable Discordant Lesions Twenty-two discordant disease sites were evaluable, including lesions that were considered definite or equivocal on 1 modality but negative on the other. Sixteen lesions were defined as definite on either CT or FDG-PET and the remaining 6 were equivocal. Five of these sites underwent biopsy. Fourteen of the evaluable discordant lesions were negative on FDG-PET whereas the remaining 8 were positive. The FDG-PET assessment of disease status was confirmed correct in 21 of the 22 cases (95%, P < 0.0001), including all 5 sites that underwent biopsy. In 1 case, FDG-PET indicated metabolically active disease within paraaortic lymph nodes. Computed tomography did not reveal any abnormality within this region during the following 8 months of observation. Repeat PET was performed 4 months later and showed persisting increased FDG activity at this site. Computed tomography performed 8 months after the initial FDG-PET

46 • Clinical Lymphoma June 2003

Reference coronal and transaxial FDG-PET images from a patient with follicular non-Hodgkin’s lymphoma after radiation therapy. There was no uptake at previously irradiated sites of nodal disease in the abdomen and pelvis but persistent focal abnormality was seen in the spleen (arrows). Subsequent laparotomy and splenectomy confirmed disease confined to the spleen. Abbreviation: FDG-PET = [18F]fluorodeoxyglucose positron emission tomography

showed subtle mesenteric streaking but no definite lymphadenopathy. Treatment Impact Six of the 12 patients (50%; 95% CI, 21%-79%) with disease staged with FDG-PET had their treatment altered by the result. Five patients had their radiation therapy fields modified to include new sites of disease documented by FDG-PET (Table 2; Figure 1), whereas the treatment plan of the remaining patient was changed from radiation therapy to systemic chemotherapy alone. Ten of the 37 patients (27%; 95% CI, 12%-44%) who underwent restaging FDG-PET scans also had their management influenced by the results. Three patients (8%) had their radiation therapy fields modified. One patient with splenic disease associated with a residual mesenteric mass on structural imaging was believed to have only splenic disease on FDG-PET. The patient went on to undergo laparotomy and splenectomy, which confirmed localized disease (Figure 2). One patient with lung and mediastinal disease on structural imaging suggestive of recurrent lymphoma had a solitary apical lesion on FDG-PET. The interpretation of the FDG-PET scan suggested a primary lung tumor rather than recurrent lymphoma. Biopsy revealed an adenocarcinoma. In another patient, pulmonary infiltrates were thought to be caused by recurrent lymphoma on CT but were thought to be caused by an inflammatory process on PET. Biopsy revealed an organizing pneumonia consistent with the functional imaging findings. Four patients with suspected recurrence had their treatment changed from systemic therapy to observation alone as a result of less-extensive disease seen on PET and the absence of symptoms.

Robert H. Blum et al Discussion This study retrospectively examined patients with indolent NHL who had undergone PET scanning at our institution and compared the results of the functional and conventional imaging studies. The results demonstrate that indolent NHL is FDG-avid in 98% of patients with documented disease and improves the accuracy of staging when combined with structural imaging. This is in contrast to some of the available literature that suggests that PET is not a sensitive imaging modality for low-grade NHL.26-27 Accurate staging in indolent NHL is critical in patients with stage I/II disease because cure may be achieved in these patients with radiation therapy alone or in combination with chemotherapy.14-19 There is some evidence to suggest that patients with stage III disease may also experience long-term disease-free survival with comprehensive lymphatic irradiation with or without chemotherapy.13,14,28 In order to truly establish the impact of therapeutic intervention on the outcome of stage III disease, improved staging with combined conventional imaging and FDG-PET is required. In this way, the surreptitious inclusion of stage IV disease, which might in part explain the reported lack of impact of treatment on survival, may be avoided. In this series, 42% of patients who had PET imaging before initial therapy had more extensive disease documented on PET than was documented by conventional radiology. An example of this is presented in Figure 1. This is in keeping with published FDG-PET staging studies in other malignancies, including aggressive NHL and non–small-cell lung cancer.22,23,29,30 The implications of such findings are twofold. First, a proportion of patients with disease upstaged by functional imaging may not be optimally managed by radiation therapy as part of their initial treatment. Second, improved accuracy of disease site identification by FDG-PET will better define radiation therapy fields, which may improve locoregional control and, ultimately, longterm survival. Forty-six percent of patients who underwent functional imaging at suspected progression or during surveillance also had their apparent disease stage altered by FDG-PET. In comparison with the patients who underwent staging at initial presentation, in whom all discordant FDG-PET scans documented moreextensive disease, only 16% of patients in the latter group had their disease upstaged by functional imaging. The remaining patients had less-extensive disease than previously suspected. An example of this presented in Figure 2. The impact of FDGPET on staging is partly affected by the timing of imaging in relation to treatment. This is caused in part by the inability of structural imaging to distinguish between tumor and nonviable scar tissue at sites of earlier disease. In 50% of patients with downstaged disease, persistent abnormalities on structural imaging in previously treated regions were negative on FDGPET. An alternate explanation for the significant proportion of patients with disease downstaged by PET after therapy may be related to therapeutic intervention temporarily suppressing the metabolic activity of the disease, decreasing the FDG avidity. However, this hypothesis is not supported by the follow-up data in this series.

Determination of true disease status of discordant lesions was limited for a number of reasons. The overall concordance between FDG-PET and CT on individual lesions was not statically significant. This is not surprising given the degree of discordance between FDG-PET and CT for equivocal and negative lesions. The other limiting factor was that a subset of only 22 patients had discordant lesions that were evaluable. However, FDG-PET correctly assessed 95% of these evaluable discordant lesions (73% true-negative results and 23% true-positive results) and was incorrect in only 1 case (an apparent false-positive result on the basis of imaging follow-up but unproven by biopsy). Importantly, 20 of the 22 evaluable lesions were considered definite on FDG-PET, with only 2 considered equivocal. The results suggest that FDG-PET is more accurate then conventional radiology when assessing discordant lesions. However, further study is required to confirm these findings because the numbers in our study were small, particularly in disease histologies other than follicular NHL. In this series, the FDG-PET results impacted the management of 34% of cases. Treatment decisions were based on the consensus of FDG-PET and conventional radiology. Changes to management included (1) modification of radiation fields to include new sites of disease, (2) substitution of chemotherapy for radiation therapy because of increased documented disease, and (3) omission of further treatment because of an absence of definite disease. There were also 2 confirmed examples in which FDG-PET findings suggested alternative diagnoses to lymphomatous pathology, which affected management. Although the results from this study support the hypothesis that FDG-PET is a useful tool in the staging of indolent NHL, the conclusions drawn are limited by the retrospective nature of the analysis and the potential pretest referral bias introduced by these patients being referred for FDG-PET scans for clinical rather than research purposes. There is also the potential problem of reporting bias because the nuclear medicine physicians had access to patients’ previous scan results. Nevertheless, our data suggest that residual structural imaging abnormalities or the absence of structural imaging abnormality did not strongly influence PET reporting because disease was both upstaged and downstaged by functional imaging and, when evaluable, the PET result was overwhelmingly found to be correct. Additionally, no attempt was made to blind the reporting radiologist to the result of PET scans performed before the index CT. The issue of histologic bias also needs to be considered when reviewing the results of the series. Although most patients had FDG-avid disease, the majority of patients had follicular lymphoma. Therefore, it is possible that FDG-PET may not be as useful in histologies not represented in the study. There is also the potential for interpretation bias in determining sites of disease based on the reports of the staging investigations. In most reports, formal recording of lymph node size was not performed. Criticism of the criteria used to determine true disease involvement of discordant sites could also be made, specifically the use of 6 months without progression in an untreated site to signify that an area was free of disease. Because indolent NHL by definition progresses slowly, this 6-month

Clinical Lymphoma June 2003 • 47

PET in Indolent Lymphoma cutoff is likely to bias against PET if it is truly a sensitive test. On analysis, the median follow-up of evaluable discordant PETnegative sites that did not undergo biopsy was 18 months, supporting the accuracy of the functional results. There are also intrinsic limitations of PET as an investigation, which may impact its accuracy. First, the reproducibility of the test is dependent on the experience of the reporting physician. There are a number of nonmalignant inflammatory processes that can mimic malignancy, including granulomatous processes (tuberculosis and sarcoidosis), infection, and postradiation therapy changes.31 The sensitivity of FDG-PET is also affected by the intrinsic characteristics of the malignancy studied, including features such as FDG avidity and tumor size. Positron emission tomography may fail to detect low-avidity disease or small-volume disease. Most of the patients in this series had disease that was at least moderately avid for FDG, with only 2 patients’ scans indicating low FDG uptake. There may also be a problem with detection of intestinal infiltration by malignancy because of the mild nonspecific uptake of FDG by the colon.27,31 Structural imaging also has limitations in imaging lymphomatous involvement of the gastrointestinal tract, and therefore endoscopy and biopsy is the investigation of choice for such disease. A final factor that can affect the reliability of FDG-PET is the presence of uncontrolled diabetes, which can interfere with FDG uptake with high circulating levels of glucose or altered uptake in normal tissues by the effects of insulin.32,33 There have been other ancillary investigations used in the staging of low-grade lymphoma in attempts to improve the accuracy of disease detection. Magnetic resonance imaging (MRI) has been used to characterize sites of suspected disease, particularly in regions such as bone, bone marrow, and the central nervous system.34-36 However, the same limitations of structural imaging also apply to MRI. Lymphangiography was once commonly used; however, it has fallen out of favor because of the technical difficulties in performing the test and interpreting the results.37-40 Staging laparotomy is currently performed rarely. The interest in FDG-PET as an investigational staging tool in NHL continues to increase. Many of the studies assessing the accuracy of FDG-PET as a staging tool have included a mixture of histologic subgroups. The numbers of indolent lymphomas in individual series were generally limited. An early study by Leskinen-Kallio et al suggested that histologically aggressive lymphomas were very FDG-avid and therefore easily detected, but that low-grade lymphomas were not always visible.26 However, the findings of the present study are consistent with those of Newman et al41 and Kostakoglu et al,42 who found that indolent lymphomas were reliably detected with FDG-PET imaging. In fact, the series of Kostakoglu et al had 18 patients with low-grade lymphoma in whom FDG-PET detected all disease sites documented by CT. Further study, ideally prospective trials, are needed to better establish the true accuracy of PET in indolent NHL. The implication of this study performed in routine clinical practice is that PET can improve the accuracy of staging. For many years, patients presenting to our institution with clinical

48 • Clinical Lymphoma June 2003

stage I, II, or III NHL and who were being considered for curative radiation-based therapies routinely had functional imaging as part of their initial workup. In almost all cases, FDG-PET has replaced the combination of thallous chloride Tl 201 and gallium citrate Ga 67 single proton emission CT. The improved disease assessment achieved by the addition of FDG-PET to CTbased staging has been shown to alter management and thereby potentially improve patient outcomes. More accurate disease characterization may also improve the ability to define and compare the efficacy of emerging regional and systemic treatment approaches.

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