New guidelines for assessing lymphoma response to treatment

An international team of cancer specialists and imaging experts has developed standardized guidelines for assessing lymphoma response to treatment.

The guidelines will provide clinicians worldwide with uniform criteria to compare and interpret clinical trials of lymphoma treatments and should facilitate the development of new therapies.

The new guidelines developed by the International Harmonization Project (IHP) build on criteria for treatment response assessment of non-Hodgkin's lymphoma published in 1999 by an international working group (IWG) of clinicians, radiologists and pathologists. Although the IWG criteria have been widely adopted by clinicians and regulatory agencies and used to approve several treatments, recent advances, including increased use of positron emission tomography (PET) scans and immunohistochemistry in lymphoma response assessment, prompted the IHP to substantially revise the criteria.

The IHP recommendations aim to standardize the parameters used in clinical trials for lymphoma and incorporate the new technologies. In addition, the revised guidelines cover all lymphomas. The recommendations appear in the Jan. 22 online issue of the Journal of Clinical Oncology. Bruce Cheson, M.D., professor of medicine at the Lombardi Comprehensive Cancer Center at Georgetown University Hospital, is senior author of the paper and led the IHP effort.

Integration of PET represents a major change in the guidelines. Malik Juweid, M.D., associate professor of radiology at the UI Roy J. and Lucille A. Carver College of Medicine and a member of the UI Holden Comprehensive Cancer Center, was co-chair of the IHP committee that developed the recommendations for performing and interpreting PET scans in response assessment of lymphoma. The imaging committee, which included world-renowned PET imaging experts from the United States, Europe and Australia, was co-chaired by Sigrid Stroobants from University Hospital Gasthuisberg in Leuven, Belgium.

"This is the first time that standardized guidelines have been recommended on an international level," Juweid said. "These revised criteria for response assessment of lymphoma are unique in that they are the first for any cancer type to formally integrate functional imaging with PET into the more conventional response assessment using clinical, laboratory and radiological measures."

Juweid is a co-author and principal imaging author of the paper outlining the IHP recommendations. He also is senior author of a second paper in the Jan. 22 online issue of the Journal of Clinical Oncology, which details the integration of PET into lymphoma response assessment.

PET is a non-invasive imaging technique that uses radioactivity emitted from injected tracer chemicals to measure and image biological activity. The most commonly used PET radiotracer is fluorodeoxyglucose (FDG), a radiolabeled form of glucose, which is consumed more avidly by tumors than by normal tissue.

In contrast to conventional computed tomography (CT) or magnetic resonance imaging (MRI), PET is able to distinguish between viable tumor and non-cancerous scar tissue that is often left behind after successful treatment of lymphoma. Incorporation of PET imaging into response assessment means that doctors can more accurately determine the nature of any residual mass and essentially rule out persistent cancer within the mass if the scan is PET-negative. This approach will allow researchers to accurately assess how well anti-lymphoma drugs work even when there is a residual mass at the tumor site following treatment.

Adoption of the revised guidelines is expected to have major implications for patient management, says Juweid.

"Many patients with either diffuse large B-cell lymphoma (DLBCL), which is the most common subtype of lymphoma, or Hodgkin's disease, who were previously considered in partial response to treatment based on the conventional assessment, will now be considered in complete response if their PET scan is negative. Such patients can be safely observed and are expected to have an excellent outcome," Juweid said.

In contrast, Juweid added, the smaller fraction of such patients who are PET-positive after treatment should undergo a biopsy to evaluate the PET-positive lesion unless there already is other compelling clinical and/or biochemical suspicion of persistent disease. If the biopsy is positive, these patients can rapidly be considered for salvage therapy.

The revised guidelines cover the use of PET for assessing all types of lymphoma. For two potentially curable types of lymphoma, DLBCL and Hodgkin's disease, the guidelines recommend that PET always be used to assess post-treatment response. PET also is strongly recommended prior to treatment to determine extent of disease for these lymphomas.

For the other 30 or so other subtypes of lymphoma, most of which are less common, the guidelines offer recommendations for when PET is useful and when it is not, and if PET is used in those cases, what criteria should be fulfilled.

The guidelines also address when a scan should be performed and recommend that PET obtained for response assessment at therapy conclusion be done preferably six to eight weeks after completion of chemotherapy and eight to twelve weeks after radiation. Timing is important because inflammation, which is present in the early weeks following treatment of the tumor, can cause false positive PET scans.

Juweid added that adherence to the guidelines could improve medical practice by minimizing inappropriate practice variation, which should improve patient care.