Stage Information for Adult Hodgkin Lymphoma
Note: Some citations in the text of this section are followed by a level of
evidence. The PDQ editorial boards use a formal ranking system to help the
reader judge the strength of evidence linked to the reported results of a
therapeutic strategy. (Refer to the PDQ summary on Levels of Evidence for more
information.)
Clinical staging
for patients with Hodgkin lymphoma (HL) includes a history, physical examination, laboratory studies (including
sedimentation rate), and thoracic and abdominal/pelvic computerized tomographic
(CT) scans.[1]
Positron emission tomography (PET) scans, sometimes combined with CT scans, have replaced gallium scans and lymphangiography for clinical staging.[2-4] The use of PET scans to assess response and define the use or avoidance of further treatment is under clinical evaluation.[5-9] A prospective multinational study of 260 newly diagnosed patients with HL obtained PET scans at baseline and after two cycles (four doses) of ABVD (doxorubicin plus bleomycin plus vinblastine plus dacarbazine); with a median follow-up of 2.2 years, the 2-year progression-free survival was 12.8% with a positive PET scan after two cycles and 95% with a negative PET scan after two cycles (P < .0001).[8] In a prospective trial of BEACOPP-based therapy—which includes the drugs bleomycin, etoposide, doxorubicin hydrochloride, cyclophosphamide, vincristine sulfate, procarbazine, and prednisone— for previously untreated patients with advanced-stage HL, patients with residual abnormalities measuring 2.5 cm or more received a PET scan at the end of therapy.[10] A negative PET scan predicted no progression or relapse within 1 year for 94% of patients (confidence interval, 91%–97%). Whether consolidation with radiation therapy can be omitted for PET-negative patients must await overall survival data at 5 years. Only further prospective studies can assess whether improved outcomes can be achieved by altering the therapeutic strategy based on PET scan results.
Bone marrow involvement occurs in 5% of patients; biopsy is indicated
in the presence of constitutional B symptoms or anemia, leukopenia, or
thrombocytopenia. Staging laparotomy is no longer recommended; it
should be considered only when the results will allow substantial reduction in
treatment. It should not be done in patients who require chemotherapy. If the laparotomy is required for treatment decisions, the risks
of potential morbidity should be considered.[11-14] The staging classification
that is currently used for HL was adopted in 1971 at the Ann
Arbor Conference [15] with some modifications 18 years later from the Cotswolds
meeting.[1]
Subclassification of stage
Stages I, II, III, and IV adult HL can be subclassified into A
and B categories: B for those with defined general symptoms and A for those
without B symptoms. The B designation is given to patients with any of the
following symptoms:
- Unexplained loss of more than 10% of body weight in the 6 months before
diagnosis.
- Unexplained fever with temperatures above 38°C.
- Drenching night sweats. (Refer to the PDQ summary on Fever, Sweats, and Hot Flashes for more information.)
[Note: The most significant B symptoms are fevers and weight loss. Night
sweats alone do not confer an adverse prognosis. Pruritus as a systemic
symptom remains controversial and is not considered a B symptom in the Ann
Arbor staging system. (For more information on Pruritus, refer to the PDQ summary of the same name.) This symptom is hard to define quantitatively and
uniformly, but when it is recurrent, generalized, and otherwise unexplained, and
when it ebbs and flows parallel to disease activity, it may be the equivalent
of a B symptom.]
The designation E is used when well-localized extranodal lymphoid malignancies
arise in or extend to tissues beyond, but near, the major lymphatic aggregates.
Stage IV refers to disease that is diffusely spread throughout an extranodal
site, such as the liver. If pathologic proof of involvement of one or more
extralymphatic sites has been documented, the symbol for the site of
involvement, followed by a plus sign (+), is listed.
Sites are identified by the following notations:
N = nodes |
H = liver |
L = lung |
M = bone marrow |
S = spleen |
P = pleura |
O = bone |
D = skin |
Current practice is to assign a clinical stage (CS) based on the findings of
the clinical evaluation and a pathologic stage (PS) based on the findings of
invasive procedures.
For example, a patient who has disease in the chest and neck, systemic
symptoms, and a negative lymphangiogram might be found at laparotomy to have
involvement of the spleen, liver, and bone marrow. Thus, the precise stage of
such a patient would be CS IIB, PS IVB (S+)(H+)(M+).
Stage I
Stage I adult HL is characterized by the involvement of a single lymph node
region (I) or localized involvement of a single extralymphatic organ or site
(IE).
Stage II
Stage II adult HL is characterized by the involvement of two or more lymph node
regions on the same side of the diaphragm (II) or localized involvement of a
single associated extralymphatic organ or site and its regional lymph node(s)
with or without involvement of other lymph node regions on the same side of the
diaphragm (IIE). Note: The number of lymph node regions involved may be
indicated by a subscript.
Stage III
Stage III adult HL is characterized by the involvement of lymph node regions
on both sides of the diaphragm (III), which may also be accompanied by
localized involvement of an associated extralymphatic organ or site (IIIE), by
involvement of the spleen (IIIS), or by involvement of both (IIIE + S). Stage
III disease may be subdivided by anatomic distribution of abdominal involvement
or by extent of splenic involvement. Stage III (1) indicates involvement that
is limited to the upper abdomen above the renal vein. Stage III (2) indicates
involvement of pelvic and/or para-aortic nodes. Five or more visible splenic
nodules on a cut section constitutes extensive splenic involvement. Zero to four
nodules is classified as minimal splenic disease.
Stage IV
Stage IV adult HL is characterized by disseminated (multifocal)
involvement of one or more extralymphatic organs, with or without associated
lymph node involvement, or isolated extralymphatic organ involvement with
distant (nonregional) nodal involvement.
Massive mediastinal disease has been defined by the Cotswolds meeting as a
thoracic ratio of maximum transverse mass diameter of 33% or more of the internal transverse thoracic diameter measured at the T5/6
intervertebral disc level on chest radiography.[1] Some investigators have
designated a lymph node mass measuring 10 cm or more in greatest
dimension as massive disease.[16] Other investigators use a measurement of the
maximum width of the mediastinal mass divided by the maximum intrathoracic
diameter.[17]
Many investigators and many new clinical trials employ a clinical staging system that divides patients into four major groups that are also useful for the practicing physician:[18]
-
Early favorable: Clinical stage I or II without any risk factors.
-
Early unfavorable: Clinical stage I or II with one or more of the following risk factors:
- Large mediastinal mass (>33% of the thoracic width on the CXR, ≥10 cm on CT scan).
- Extranodal involvement.
- Elevated ESR (>30 mm/hr for B stage, >50 mm/hr for A stage).
- Three or more lymph node areas' involvement.
- B symptoms.
-
Advanced favorable: Clinical stage III or IV with zero to three adverse risk factors listed below. Patients with advanced favorable disease have a 60% to 80% freedom-from-progression at 5 years from treatment with first-line chemotherapy.[19][Level of evidence: 3iiiDiii]
-
Advanced unfavorable: Clinical stage III or IV with four or more adverse risk factors listed below.[19] Patients with advanced unfavorable disease showed a 42% to 51% freedom-from-progression at 5 years from treatment with first-line chemotherapy.[19][Level of evidence: 3iiiDiii]. For patients with advanced-stage HL, the International Prognostic Factors Project has
developed an International Prognostic Index with a prognostic score that is based on seven adverse factors:[19]
- Albumin level of less than 4.0 g/dL.
- Hemoglobin level of less than 10.5 g/dL.
- Male sex.
- Age of 45 years or older.
- Stage IV disease.
- White blood cell
(WBC) count of at least 15,000/mm3.
- Absolute lymphocytic
count of less than 600/mm3 or a lymphocyte count that was less than 8% of the total WBC count.
References
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Lister TA, Crowther D, Sutcliffe SB, et al.: Report of a committee convened to discuss the evaluation and staging of patients with Hodgkin's disease: Cotswolds meeting. J Clin Oncol 7 (11): 1630-6, 1989.
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Jerusalem G, Beguin Y, Fassotte MF, et al.: Whole-body positron emission tomography using 18F-fluorodeoxyglucose compared to standard procedures for staging patients with Hodgkin's disease. Haematologica 86 (3): 266-73, 2001.
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Naumann R, Beuthien-Baumann B, Reiss A, et al.: Substantial impact of FDG PET imaging on the therapy decision in patients with early-stage Hodgkin's lymphoma. Br J Cancer 90 (3): 620-5, 2004.
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Munker R, Glass J, Griffeth LK, et al.: Contribution of PET imaging to the initial staging and prognosis of patients with Hodgkin's disease. Ann Oncol 15 (11): 1699-704, 2004.
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Weihrauch MR, Re D, Scheidhauer K, et al.: Thoracic positron emission tomography using 18F-fluorodeoxyglucose for the evaluation of residual mediastinal Hodgkin disease. Blood 98 (10): 2930-4, 2001.
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Hutchings M, Loft A, Hansen M, et al.: FDG-PET after two cycles of chemotherapy predicts treatment failure and progression-free survival in Hodgkin lymphoma. Blood 107 (1): 52-9, 2006.
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Dann EJ, Bar-Shalom R, Tamir A, et al.: Risk-adapted BEACOPP regimen can reduce the cumulative dose of chemotherapy for standard and high-risk Hodgkin lymphoma with no impairment of outcome. Blood 109 (3): 905-9, 2007.
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Gallamini A, Hutchings M, Rigacci L, et al.: Early interim 2-[18F]fluoro-2-deoxy-D-glucose positron emission tomography is prognostically superior to international prognostic score in advanced-stage Hodgkin's lymphoma: a report from a joint Italian-Danish study. J Clin Oncol 25 (24): 3746-52, 2007.
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Advani R, Maeda L, Lavori P, et al.: Impact of positive positron emission tomography on prediction of freedom from progression after Stanford V chemotherapy in Hodgkin's disease. J Clin Oncol 25 (25): 3902-7, 2007.
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Kobe C, Dietlein M, Franklin J, et al.: Positron emission tomography has a high negative predictive value for progression or early relapse for patients with residual disease after first-line chemotherapy in advanced-stage Hodgkin lymphoma. Blood 112 (10): 3989-94, 2008.
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Dietrich PY, Henry-Amar M, Cosset JM, et al.: Second primary cancers in patients continuously disease-free from Hodgkin's disease: a protective role for the spleen? Blood 84 (4): 1209-15, 1994.
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Carbone PP, Kaplan HS, Musshoff K, et al.: Report of the Committee on Hodgkin's Disease Staging Classification. Cancer Res 31 (11): 1860-1, 1971.
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Bradley AJ, Carrington BM, Lawrance JA, et al.: Assessment and significance of mediastinal bulk in Hodgkin's disease: comparison between computed tomography and chest radiography. J Clin Oncol 17 (8): 2493-8, 1999.
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Jost LM, Stahel RA; ESMO Guidelines Task Force.: ESMO Minimum Clinical Recommendations for diagnosis, treatment and follow-up of Hodgkin's disease. Ann Oncol 16 (Suppl 1): i54-5, 2005.
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