Assessment of Waldeyer's ring in pediatric and adolescent Hodgkin lymphoma patients-Importance of multimodality imaging: Results from the EuroNet-PHL-C1 trial.

BACKGROUND: In the EuroNet Pediatric Hodgkin Lymphoma (EuroNet-PHL) trials, decision on Waldeyer's ring (WR) involvement is usually based on clinical assessment, that is, physical examination and/or nasopharyngoscopy. However, clinical assessment only evaluates mucosal surface and is prone to interobserver variability. Modern cross-sectional imaging technology may provide valuable information beyond mucosal surface, which may lead to a more accurate WR staging. PATIENTS, MATERIALS, AND METHODS: The EuroNet-PHL-C1 trial recruited 2102 patients, of which 1752 underwent central review including reference reading of their cross-sectional imaging data. In 14 of 1752 patients, WR was considered involved according to clinical assessment. In these 14 patients, the WR was re-assessed by applying an imaging-based algorithm considering information from 18 F-fluorodeoxyglucose positron emission tomography, contrast-enhanced computed tomography, and/or magnetic resonance imaging. For verification purposes, the imaging-based algorithm was applied to 100 consecutive patients whose WR was inconspicuous on clinical assessment. RESULTS: The imaging-based algorithm confirmed WR involvement only in four of the 14 patients. Of the remaining 10 patients, four had retropharyngeal lymph node involvement and six an inconspicuous WR. Applying the imaging-based algorithm to 100 consecutive patients with physiological appearance of their WR on clinical assessment, absence of WR involvement could be confirmed in 99. However, suspicion of WR involvement was raised in one patient. CONCLUSIONS: The imaging-based algorithm was feasible and easily applicable at initial staging of young patients with Hodgkin lymphoma. It increased the accuracy of WR staging, which may contribute to a more individualized treatment in the future.

Inter-Reader Reliability of Early FDG-PET/CT Response Assessment Using the Deauville Scale after 2 Cycles of Intensive Chemotherapy (OEPA) in Hodgkin's Lymphoma.

PURPOSE: The five point Deauville (D) scale is widely used to assess interim PET metabolic response to chemotherapy in Hodgkin lymphoma (HL) patients. An International Validation Study reported good concordance among reviewers in ABVD treated advanced stage HL patients for the binary discrimination between score D1,2,3 and score D4,5. Inter-reader reliability of the whole scale is not well characterised. METHODS: Five international expert readers scored 100 interim PET/CT scans from paediatric HL patients. Scans were acquired in 51 European hospitals after two courses of OEPA chemotherapy (according to the EuroNet-PHL-C1 study). Images were interpreted in direct comparison with staging PET/CTs. RESULTS: The probability that two random readers concord on the five point D score of a random case is only 42% (global kappa = 0.24). Aggregating to a three point scale D1,2 vs. D3 vs. D4,5 improves concordance to 60% (kappa = 0.34). Concordance if one of two readers assigns a given score is 70% for score D1,2 only 36% for score D3 and 64% for D4,5. Concordance for the binary decisions D1,2 vs. D3,4,5 is 67% and 86% for D1,2,3 vs D4,5 (kappa = 0.36 resp. 0.56). If one reader assigns D1,2,3 concordance probability is 92%, but only 64% if D4,5 is called. Discrepancies occur mainly in mediastinum, neck and skeleton. CONCLUSION: Inter-reader reliability of the five point D-scale is poor in this interobserver analysis of paediatric patients who underwent OEPA. Inter-reader variability is maximal in cases assigned to D2 or D3. The binary distinction D1,2,3 versus D4,5 is the most reliable criterion for clinical decision making.

Evaluation of diffusion-weighted MRI for pretherapeutic assessment and staging of lymphoma: results of a prospective study in 140 patients.

PURPOSE: To determine the value of diffusion-weighted MRI (DWI-MRI) for pretherapeutic imaging of fluorodeoxyglucose (FDG)-avid lymphoma and lymphoma with variable FDG avidity. EXPERIMENTAL DESIGN: Treatment-naïve patients with lymphoma who were referred for whole-body staging were included in this prospective study. Group A included patients with FDG-avid lymphoma (e.g., Hodgkin, diffuse large B-cell, and follicular lymphoma), whereas Group B included patients with lymphoma of variable FDG avidity [e.g., extranodal marginal zone B-cell lymphoma of the mucosa-associated lymphoid tissue (MALT)]. All patients underwent DWI-MRI and 18F-FDG- positron emission tomography/computed tomography (PET/CT). Region-based sensitivity and agreement with Ann Arbor staging, relative to the reference standard, were calculated for DWI-MRI, and, in Group B, also 18F-FDG-PET/CT and contrast-enhanced (CE-) CT. RESULTS: In Group A (100 patients), DWI-MRI had a region-based sensitivity of 97%, and with regard to staging, agreed with the reference standard in 94 of 100 patients (κ, 0.92). In Group B (40 patients; 38 MALT lymphomas and 2 small lymphocytic lymphomas/chronic lymphocytic leukemias), DWI-MRI, 18F-FDG-PET/CT, and CE-CT had region-based sensitivities of 94.4%, 60.9%, and 70.7%, respectively. With regard to staging in Group B, DWI-MRI, 18F-FDG-PET/CT, and CE-CT agreed with the reference standard in 37 of 40, 26 of 40, and 24 of 40 patients, with κ values of 0.89, 0.52, and 0.43, respectively. CONCLUSIONS: In patients with FDG-avid lymphoma, DWI-MRI seems to be only slightly inferior to 18F-FDG-PET/CT with regard to pretherapeutic regional assessment and staging. In patients with lymphoma subtypes that show a variable FDG avidity (e.g., MALT lymphoma), DWI-MRI seems to be superior to both 18F-FDG-PET/CT and CE-CT.

Assessment of disease dissemination in gastric compared with extragastric mucosa-associated lymphoid tissue lymphoma using extensive staging: a single-center experience.

PURPOSE: Molecular data and preliminary clinical findings have suggested mucosa-associated lymphoid tissue (MALT) lymphoma as a multifocal disease in a high percentage of patients. We report our findings with an extensive staging routine applied in patients diagnosed with MALT lymphoma at our institution. PATIENTS AND METHODS: A total of 140 consecutive patients (61 with gastric and 79 with extragastric MALT lymphoma) underwent staging according to a standardized protocol. Staging included gastroscopy with multiple biopsies, endosonography of the upper GI tract, computed tomography of thorax and abdomen, lymph node sonography, colonoscopy with multiple biopsies, otorhinolaryngologic assessment, magnetic resonance imaging of salivary and lacrimal glands, and bone marrow biopsy. All lesions suggestive of lymphoma involvement were subjected to biopsy, if accessible, and biopsies were evaluated for MALT lymphoma-specific genetic aberrations by means of reverse transcriptase polymerase chain reaction and/or fluorescent in situ hybridization. RESULTS: Fifteen (25%) of 61 patients with gastric MALT lymphoma had multiorgan involvement, with dissemination beyond the GI tract in six patients. By contrast, significantly more patients with extragastric MALT lymphoma had dissemination to another MALT organ (37 of 79 patients, 46%; P = .045). Nine of these 37 patients had dissemination to the stomach. Only three (2%) of 140 patients had bone marrow involvement. Multifocality was significantly associated with t(11;18)(q21;q21) in gastric lymphomas (P = .045) and with trisomy 18 in extragastric lymphomas (P = .011). CONCLUSION: Our findings suggest that MALT lymphoma frequently presents as a multifocal disease. Extragastric MALT lymphomas are significantly more prone to dissemination than gastric MALT lymphomas.