Joint Program in Nuclear Medicine

Whole Body FDG PET in the Evaluation of Lymphoma

Kavitha Vadde, MD
Alan J. Fischman, MD, PhD

March 7, 2000

Presentation

A 44-year-old male with lymphoma, histology indeterminate between Hodgkin's Disease and non-Hodgkin's lymphoma presented for restaging. Pre-treatment the lymphoma was gallium avid.

Imaging Findings

CT Chest:

A CT scan of the chest showed ground glass opacity in the right upper lobe (shown by arrows), stable compared with a study 6 months prior and consistent with scarring or post-radiation changes.

CT Abdomen/Pelvis:

A CT scan of the abdomen and pelvis showed multiple hypodense lesions (several shown by arrows) in the spleen consistent with residual lymphoma. No pathologic lymphadenopathy by size criteria was appreciated.

Gallium Scintigraphy:

On gallium scintigraphy there was no evidence of gallium avid lymphoma.

Whole Body 18F-fluorodeoxyglucose PET:

FDG PET showed abnormal tracer uptake in the right upper lung (see on MIP reprojection images) and multiple abnormal foci within the spleen (shown by arrow) correlating to the abnormalities present on CT. An intense focus of tracer uptake is seen in the peri-portal region (shown by arrow). Findings are consistent with residual lymphoma.

Re-evaluation of the CT:

Upon re-evaluation of the CT of the abdomen / pelvis a 3.8 cm by 1.5 cm portacaval node (shown by arrow) is detected that is new with respect to a CT approximately 1 year prior.

Discussion

Malignant Lymphoma

Malignant lymphomas arise form neoplastic transformation of lymphoid cells in lymph nodes, spleen or thymus gland. About 45, 000 cases of non-Hodgkin's lymphoma and 7,500 cases of Hodgkin's disease are diagnosed each year in the United States. The incidence of non-Hodgkin's lymphoma increases linearly with age. In contrast, Hodgkin's disease has a bimodal age incidence with the first peak seen in young adults (15 -35 years) and the second peak in the over 50 age group. In both age groups males predominate unlike non-Hodgkin's lymphoma in which there is no sex predilection.

Non-Hodgkin's lymphoma (NHL) is categorized according to the cell of origin and clinically indolent or aggressive behavior. 90% are of B cell origin and 10% are of T cell origin. Multifocal, hematogenously disseminated disease with abdominal lymph node and bone marrow involvement is common. Systemic symptoms, fever and weight loss, are seen in less than 20% and are associated with more aggressive subtypes.

In Hodgkin's disease (HD) the cell of origin is unclear. The presence of Reed-Sternberg cells is required for diagnosis. Four histologic subtypes, nodular sclerosing (most common), lymphocyte predominant, mixed cellularity and lymphocyte depleted are recognized. Localized nodal disease characterized by contiguous spread to lymphoid tissues is common. Mediastinal lymph node involvement and systemic symptoms are also common.

Lymphoma is one of the most curable forms of cancer. Approximately 80% of Hodgkin's and 35% non-Hodgkin's lymphoma are curable. Treatment and prognosis depends on histologic subtype / grade and stage.

Ann Arbor Staging System

The Ann Arbor Staging System is used for both Hodgkin's and non-Hodgkin's lymphoma. The number of tumor sites (nodal and extranodal), location and the presence or absence of systemic symptoms determines stage.

Stage I is defined as involvement of a single lymph node region or single extralymphatic site.
Stage II is involvement of two or more lymph node regions on the same side of the diaphragm, or localized contiguous involvement of only one extralymphatic site and lymph node region.
Stage III is defined as disease in lymph node regions on both sides of the diaphragm and includes splenic involvement.
Stage IV disease is disseminated involvement of one or more extralymphatic organs with or without lymph node involvement.

Each stage is further subdivided into "A" or "B" based on the absence or presence of systemic symptoms (fevers, weight loss and night sweats) (1).

Essential components of the staging evaluation are physical and laboratory evaluation, chest radiography, computed tomography and bone marrow biopsy. Computed tomography is the conventional imaging modality to determine the extent of disease. Pathologic lymphadenopathy is determined by size criteria.

Whole Body 18F-FDG PET Imaging:

FDG PET imaging allows the detection of viable tumor cells independent of morphology. Deoxyglucose labeled with the positron emitter fluorine -18 (FDG) is a glucose analogue that is transported into cells like glucose. Unlike glucose it its trapped in cells in a phosphorylted form after uptake and further metabolism does not occur. Since cancer cells have a higher glycolytic rate than normal cells, the tracer concentrates in neoplastic tissues allowing their detection.

FDG uptake is seen in Hodgkin's and in non-Hodgkin's lymphoma. Tracer uptake declines with therapy. Areas in which the utility of FDG PET imaging is being evaluated include the initial staging of disease, treatment monitoring, and detection of recurrence (2).

In the few studies to date that have compared CT and FDG PET staging of lymphoma, the sensitivities of the two modalities have been comparable. However, FDG-PET appears superior in treatment monitoring, particularly in distinguishing between residual viable tumor and fibrosis (3). Identification of patients with viable tumor post-treatment allows early intensification of treatment (salvage chemotherapy or bone marrow transplantation) in order to induce complete remission.

Hoh et al (4) compared whole body FDG PET and conventional staging in 7 patients with Hodgkin's disease and 11 patients with NHL. Acknowledging the limitations of a small patient population, the accuracy of PET was comparable to conventional staging. 17/18 patients were accurately staged with FDG PET compared with 15/18 with conventional methods as determined by follow up and biopsy.

In a recent study, Jerusalem et al (5) compared FDG PET to CT in the post-treatment evaluation of 54 patients with Hodgkin's disease or intermediate/high grade non-Hodgkin's lymphoma. Residual masses were seen in 24 subjects on post-treatment CT. Six patients (5/24 with a residual mass on CT and 1/30 without a residual post-treatment mass) had a positive post-treatment FDG-PET study. Disease relapse was seen in all six patients with a positive FDG-PET study, 5/19 patients (26%) with residual masses on CT but negative FDG-PET and 3/29 patients (10%) with both a negative CT and FDG-PET. Evidence of active tumor on FDG-PET post-treatment was shown to have a higher predictive value for relapse than the presence of a residual mass on CT imaging with a positive predictive value of 100% versus 42%.

Gallium-67 SPECT versus FDG PET

Gallium-67 scintigraphy is currently the standard technique to assess tumor viability in the post-treatment evaluation of lymphoma. In patients with pre-treatment gallium avid disease, it is valuable in monitoring treatment response, determining if a residual mass contains active tumor cells, and in evaluating for recurrence. Gallium uptake in tumor after radiation and chemotherapy is proportionate to the number of residual neoplasitc cells in animal models. A significant difference in disease free survival is seen in patients with positive versus negative gallium scans after treatment. No significant difference in survival is seen between patients with positive versus negative CT scans after treatment (6) .Gallium scintigraphy has no utility in pre-treatment staging as sensitivity of lesion detection varies greatly depending on anatomic site.

FDG in studies to date appears to be more sensitive than gallium in detecting viable tumor as illustrated in the index case (7). Pre-treatment scans required in all patients to determine if the tumor is gallium avid may not be necessary with FDG PET.

Positron tomography has inherently greater sensitivity and resolution than conventional gamma camera SPECT, allowing more accurate lesion detection. Less patient preparation and time are necessary for FDG PET than for gallium scans. With PET imaging the patient is required to fast for 6 hours before administration of tracer and is imaged at approximately one hour after injection. In gallium scanning tracer administration and patient imaging are separated by several days in order to allow background clearance of tracer.

References

1 Freedman, A.S. & Nadler, L. M. (1998). Harrison's principles of internal medicine (13th ed.). (pp.695-711). New York: McGraw-Hill.

2 Maisey, M. M., Wahl, R. L., Barrington S. F., (1999). Atlas of clinical positron emission tomography. (Pp. 51-74). London: Arnold.

3 Delbeke, K. Oncological applications of FDG PET Imaging: brain tumors, colorectal cancer, lymphoma and melanoma. J Nucl Med 1999; 40:591-603.

4 Hoh CK, Glaspy J, Rosen P, Dahlbom M, Lee S J, Kunkel L, Hawkin R A, Maddahi J, Phelps M E. Whole-body FDG-PET imaging for staging of Hodgkin's disease and lymphoma. J. Nucl Med 1997;38(3):343-8.

5 Jerusalem G, Beguin Y, Fassotte, M F, Najjar F, Paulus P, Rigo P, Fillet G. Whole -body positron emission tomography using 18F-fluorodeoxyglucose for posttreatment evaluation in Hodgkin's disease and non-Hodgkin's lymphoma has higher diagnostic and prognostic value than classical computed tomography scan imaging. Blood 1999 Jul 15;94(2):429-33.

6 Front D, Israel O. The role of Ga-67 scintigraphy in evaluating the results of therapy of lymphoma patients. Seminars in Nuc Med 1995 Jan;25:60-71.

7 Paul, R. Comparison of Fluorine-18-2-fluorodeoxyglucose and gallium-67 citrate imaging for detection of lymphoma. J Nucl Med 28: 288-292, 1987.

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J. Anthony Parker, MD PhD, Tony_Parker@CareGroup.Harvard.edu