Abstract
614
Introduction: Imaging using PET/CT with FDG is the gold standard for initial staging for malignant lymphoma. This sequence is well established for Hodgkin lymphoma, aggressive lymphomas and follicular lymphoma but lacks sensitivity for marginal zone lymphoma (MZL), irrespectively of the different MZL subsets e.g. mucosa-associated lymphoid tissue (MALT), and nodal marginal lymphoma (NMZL), splenic marginal zone lymphoma (sMZL) and extranodal marginal zone lymphoma (eNMZL). Limited disease of MZL (Stage I/II) are commonly treated by irradiation. Extensive disease (Stage III/IV) is either followed by watch and wait if clinically asymptomatic and or treated with anti-CD20 directed immune chemotherapy if clinically prudent.Hence, better diagnostic procedures are highly warranted to improve the accuracy of the Ann Arbor staging in MZL for Stage adapted treatment of MZL patients.
Methods: We included 21 patients (age, 50 -85 years) with newly diagnosed, pathologically confirmed MZL (15 MALT, 5 NMZL, 1 sMZL). Patients´ characteristics are summarized in Table 1. The staging workup included whole-body imaging with [18F]FDG and [68Ga]Pentixafor-PET/CT and bone marrow biopsy. All patients with MALT MZL were further subject to gastric endoscopy and colonoscopy with tissue biopsies. If a lesion was 18F]FDG-negative but positive on [68Ga]Pentixafor-PET/CT, additional tissue samples were acquired in some patients to confirm MZL infiltration by immunohistochemistry. [68Ga]Pentixafor was administered on a compassionate use basis in compliance with §37 of the Declaration of Helsinki and The German Medicinal Products Act, AMG §13 2b and in accordance with the responsible regulatory body (Regierung von Oberfranken, Bavaria, Germany). All subjects gave written informed consent prior to [68Ga]Pentixafor PET/CT.PET/CT imaging [68Ga]Pentixafor and [18F]FDG were prepared as previously described [1]. All PET scans were performed on a dedicated PET/CT scanner (Siemens Biograph mCT 64; Siemens Medical Solutions, Germany) within two weeks (range, 4-18 days, median 13 d) using standard protocols.PET-positive lesions were visually determined as focally increased tracer retention.
Results: From 05/2017 to 09/2018 twenty-one patients with newly diagnosed MZL were staged by dual-tracer PET/CT and bone marrow biopsy. 9 patients suffered from limited disease, in the remaining 12 extensive disease was recorded. 12 patients were missed by FDG-PET whereas only 1 patient with minimal gastral infiltration and low proliferation index was not detected by [68Ga]Pentixafor-PET/CT. All cases with bone marrow infiltration could be detected by CXCR4-directed PET (3/3), but none by [18F]FDG-PET. [18F]FDG also missed al patients with intestinal involvement of the lymphoma whereas 2/3 patients were true positive (confirmed by biopsy) on [68Ga]Pentixafor-PET. 14/15 patients with MALT Lymphoma were CXCR4 positive in all lesions. In contrast, only 6/15 MALT patients could be detected with [18F]FDG. In the group of NMZL 5/5 patients demonstrated CXCR4 PET positivity and only 3/5 were [18F]FDG-positive. In the single case of sMZL, CXCR4-directed PET was positive and [18F]FDG-PET negative . Taken together, 95.2% of lesions of MZL patients were positive on [68Ga]Pentixafor-PET/CT in contrast to 42.9% of lesions detected by [18F]FDG. In addition, CXCR4-dorected PET revealed bone marrow (in 3/3 cases) and GI tract involvement (in 2/3 cases) that was missed by [18F]FDG/PET. Key result 95.2% of MZL patients revealed positive lesions on CXCR4-directed PET/CT as compared to only 42.9% on [18F]FDG PET/CT including nodal and extranodal involvement like GI tract and bone marrow. Our preliminary results imply that [68Ga]Pentixafor-PET/CT may be useful for more accurate staging of MZL, potentially resulting in better stage-adapted treatment decisions. These pilot data have to be confirmed in larger patient cohorts.