Page 12 - 18F-FDG PET as biomarker in aggressive lymphoma; technical and clinical validation

Chapter 1
Introduction lymphoma
Lymphoma is a malignant proliferative disease of lymphoid tissue. Historically, lymphoma has been divided into 2 types; Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL). HL was first described in a report by Thomas Hodgkin in 1832. The disease is characterized by the presence of Reed-Sternberg (RS) cells in pathological specimens. The RS cells originate from B lymphocytes and were later named after the pathologists Dorothy Reed Mendenhall and Carl Sternberg who discovered and described these multinuclear cells in their publications of 1902 and 1898, respectively. Young adults (<40 years) are most often affected with HL and the chance of curing HL patients is high (survival above 90%). However, survival rates for older patients (>60 years) are generally lower (median survival between 57% and 70%) [1].
NHL consists of a diverse group of lymphoma subtypes derived from (progenitors of ) B-cells, T-cells or NK-cells [2]. The entity has a wide clinical spectrum from (very) indolent subtypes until highly aggressive subtypes. Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of NHL, consisting of about 40% of all NHL, and has an aggressive clinical behavior [3]. DLBCL is the most prevalent hematologic malignancy, with about 1500 new diagnoses per year in the Netherlands [4]. The median age at diagnosis is 70 years at population level [3], but in recent randomized clinical trials the average age ranges between 60 and 65 years due to the study eligibility criteria [5-7]. Patients with DLBCL have a heterogeneous clinical presentation and prognosis.
Most DLBCL patients are treated with a chemotherapy combination of cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) [8] as first-line therapy. This chemotherapy scheme was introduced in the seventies and given in 3-week intervals. The therapeutic scheme changed after the introduction of the monoclonal anti-CD20 antibody rituximab [9]. This antibody targets the CD20 cell surface protein of mature B-cells (present in most B-cell lymphomas) and leads to apoptosis induction and cell death by different mechanisms (direct signalling, complement-mediated cytotoxicity and antibody-dependent cellular cytotoxicity). Survival of DLBCL has improved clearly after addition of rituximab to the CHOP scheme (R-CHOP) [10,11]. Current 5-year overall survival is 78% for patients <65, 64% for patients between 65 and 75 and 46% for patients above
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