PET Imaging for Response Assessment in Lymphoma: Potential and Limitations

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Fluorodeoxyglucose positron emission tomography (FDG-PET) is now considered the most accurate tool for the assessment of treatment response and prognosis in patients with Hodgkin lymphoma and aggressive non-Hodgkin lymphoma. This article discusses the potential and limitations of FDG-PET for response assessment in malignant lymphoma during chemotherapy (interim PET) and at the end of chemotherapy. Interim PET is used to predict the likelihood for a complete response at the end of such therapy. End-of-treatment PET aims to establish the completeness of response or the presence of residual viable tumor tissue. Until the results of ongoing clinical trials emerge over the next 5 years, interim PET should be considered investigational and should not be used for patient management outside of study protocols.

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Clinical background

HL and NHL are the most common hematologic malignancies in the United States; they account for 4% to 5% of all new cancer cases and are the fifth leading cause of cancer death in the United States.

Among HL, nodular sclerosis is the most common subtype in the United States and Western Europe, followed by mixed cellularity phenotype, lymphocyte-predominant subtype, and lymphocyte-depleted subtype. The international prognostic score is used for risk stratification.1 Treatment decisions for

Positron emission tomography imaging

FDG-PET is now widely used for the staging, restaging, and detection of recurrence in many patients with HL and NHL. It is also increasingly used for monitoring the response to chemotherapy in these patients. For meaningful clinical use, the specific lymphoma entity has to be FDG-avid. Although this information may be inferred from past studies,23, 24 it is clearly desirable to obtain a baseline scan to assess the extent of disease and to establish the degree and intensity of FDG uptake in

Background

Historically, imaging studies were obtained at baseline and after completion of therapy, for the purpose of staging and restaging. Investigators realized increasingly that a lack of complete normalization on structural imaging, either conventional radiograms53, 54 or CT,55 did not necessarily indicate the presence of residual viable tumor tissue. This led to the introduction of a category “complete response, unconfirmed” in the 1999 lymphoma response criteria.55 That is, clinicians presumed

Background

Early response assessment, although much en vogue nowadays, is not new. As early as 1986, Armitage and colleagues71 reported that “rapidly responding patients with DLBCL have more durable remissions.” They used conventional response criteria and chest radiograph and abdominal CT. With the advent of functional imaging, Front and colleagues72 used 67gallium scintigraphy for similar purpose and in 1999 published that a “negative test after one cycle of chemotherapy is a good early predictor of

Pediatric patients

In children and adolescents, HL and Burkitt's lymphoma, lymphoblastic, and DLBCL are the most common histopathologic subtypes. These tumors are generally FDG-avid. These considerations should also apply to PET response assessment in pediatric patients, but this needs to be proved in prospective studies.

Imaging with 18F fluorothymidine

This article is entirely focused on PET imaging with FDG. Among the many other PET radiotracers, the proliferation marker 18F fluorothymidine (FLT) seems particularly promising for treatment monitoring.84 FLT uptake depends on the activity of nucleoside transporters and the activity of the enzyme thymidine kinase 1.85 Thymidine kinase 1 activity correlates well with other indicators of cellular proliferation, and tumor FLT uptake correlates with the tissue proliferation marker ki-67.86 In

Open questions

Among several open questions regarding the use of FDG-PET in lymphoma response assessment, Box 2 offers some that may be of particular interest to oncologists and imaging physicians.

Summary

FDG-PET is currently the most accurate tool for the assessment of treatment response and prognosis in lymphoma; it is certainly more accurate than structural imaging or clinical indices. Unfortunately, many published studies suffer from suboptimal methodology and incomplete data reporting. In general, the data seem more consistent in HL than in aggressive NHL. A negative PET excludes residual disease with reasonably high certainty. In contrast, positive PET findings should always be confirmed

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