An international group of leading hematologists and oncologists has released revised recommendations for the initial evaluation, staging, and assessment of response to treatment of Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL) based on a workshop at the 11th International Conference on Malignant Lymphoma held in June 2011 in Lugano, Switzerland.
Known as the Lugano Classification, these recommendations update the 2007 International Working Group Guidelines for response. The updates reflect the current state of knowledge and incorporate lessons learned through major international lymphoma clinical trials. The Lugano recommendations are summarized here.
Diagnosis and Evaluation
Review of morphology, immunohistochemistry, and flow cytometry by an experienced pathologist and molecular studies, where appropriate, are used to make the diagnosis of lymphoma. Incisional or excisional biopsy are preferred over fine-needle aspirate, which is inadequate for initial diagnosis.
However, a core-needle biopsy is acceptable if the others are not available and is also used to document relapse. If patients give permission, extra tissue should be taken stored for future research.1
Patient evaluation includes comprehensive history, including assessment of fever, chills, night sweats, or unexplained weight loss; measurement of accessible nodes and assessment of organomegaly by physical examination and CT imaging; and laboratory tests needed to assess prognostic variables.1
Updates to Staging Recommendations
Staging defines the location and extent of disease and provides prognostic information or a baseline for comparison of response or progression.1 Several changes from the Ann Arbor criteria appear in the Lugano Classification, starting with the addition of fluorodeoxyglucose (FDG) positron emission tomography (PET)–computed tomography (CT) to standard staging for FDG-avid lymphomas.
Chest radiographs are no longer required because they are less accurate than CT.1 A comparison of the Ann Arbor and Lugano criteria for staging appears in Table 1.
There are substantial modifications to the Ann Arbor criteria in the terms used to describe the distribution of disease extent. Ann Arbor used a subclassification A/B within staging based on the presence of fever (101.5ºF or higher), weight loss more than 10% over the previous 6 months, and drenching night sweats.
|Table 1. Revised Staging Criteria for Primary Nodal Lymphomas: Lugano Classification|
|Lugano1||Ann Arbor2 †|
|Involvement||Extranodal Status (E)|
|I||1 node or group of adjacent nodes||Single extranodal lesion w/o nodal involvement||1 node area or lymphoid organ Located in only in 1 area of a single organ outside of lymph system|
|II||2 or more nodal groups on same side of diaphragm||Stage I or II by nodal extent with limited, contiguous, extranodal involvement||2 or more nodal groups on same side of diaphragm Lymphoma extends to a nearby organ or group of nodes on same side of diaphragm|
|II bulky*||Stage II with “bulky” disease||Not applicable|
|III||Nodes on both sides of diaphragm; nodes above diaphragm with spleen involvement||Not applicable||Nodes on both sides of diaphragm; spread into area or organ near nodes or into spleen|
|IV||Additional noncontiguous extralymphatic involvement||Not applicable||Additional noncontiguous extralymphatic involvement Metastasis to bone marrow, liver, central nervous system, or pleura|
| Extent of disease is determined by FDG-PET for avid disease and by CT for nonavid histologies.
*Treatment of stage II bulky disease as limited or advanced is determined by histology and prognostic factors. In Ann Arbor, bulky disease is defined as chest tumors ≥1/3 the width of the chest, or tumors outside of chest that are ≥10 cm across.
†In the Ann Arbor classification, each stage may be assigned A or B. B is used to denote presence of symptoms of unexplained weight loss (>10%), unexplained fever (≥101.5ºF), or drenching night sweats, and indicates more advanced disease. In the Lugano update, A/B are used only for HL.
Patients with these symptoms were classified as “B,” which generally indicated more advanced disease. In the Lugano Classification, the A and B are dropped for NHL, because symptoms are not consistently or reliably reported and, importantly, do not drive treatment decisions in this setting.1,2 Use of A and B is retained for patients with HL, where it has prognostic value and factors into treatment.1
In both NHL and HL, the largest tumor measurement on CT is recorded and used to replace the “X” used in Ann Arbor to indicate bulky disease.1
In the new recommendation, bulk is considered a negative prognostic factor, that—because its definition is specific to disease, stage, and treatment—is left open ended for NHL.1,2 In the Ann Arbor criteria, a single nodal mass10 cm or larger or more than 1/3 the transthoracic diameter at any level of thoracic vertebrae, as determined by CT, defined bulky disease for NHL and HL; the new recommendation retains that definition for HL only.1,2
Finally, the new recommendations remove the requirement for bone marrow biopsy in routine staging of HL and most diffuse large B-cell lymphomas, provided that PET-CT is performed. Bone marrow biopsy may be required for patients with diffuse large B-cell lymphoma if necessary to determine patient management.1
Updates to Treatment Decision Making
The new recommendations categorize patients as having limited (stages I and II, nonbulky) or advanced (stage III or IV) disease for the purpose of treatment decisions (see Table 1).
Determination of stage II bulky disease as limited or advanced disease is based on histology and a number of prognostic factors specific to the individual patient setting.1