Faculty Bibliography

OBJECTIVES/OBJECTIVE:The aim of this study was to compare F-fluorodeoxyglucose (FDG) positron emission tomography (PET)/magnetic resonance (MR) (with and without diffusion-weighted imaging [DWI]) to F-FDG PET/computed tomography (CT), with regard to the assessment of nodal and extranodal involvement, in patients with Hodgkin lymphoma and non-Hodgkin lymphoma, without restriction to FDG-avid subytpes. MATERIALS AND METHODS/METHODS:Patients with histologically proven lymphoma were enrolled in this prospective, institutional review board-approved study. After a single F-FDG injection, patients consecutively underwent F-FDG PET[Fraction Slash]CT and F-FDG PET/MR on the same day for staging or restaging. Three sets of images were analyzed separately: F-FDG PET/CT, F-FDG PET/MR without DWI, and F-FDG PET/MR with DWI. Region-based agreement and examination-based sensitivity and specificity were calculated for F-FDG PET/CT, F-FDG PET/MR without DWI, and F-FDG PET/MR DWI. Maximum and mean standardized uptake values (SUVmax, SUVmean) on F-FDG PET/CT and F-FDG PET/MR were compared and correlated with minimum and mean apparent diffusion coefficients (ADCmin, ADCmean). RESULTS:Thirty-four patients with a total of 40 examinations were included. Examination-based sensitivities for F-FDG PET/CT, F-FDG PET/MR, and F-FDG PET/MR DWI were 82.1%, 85.7%, and 100%, respectively; specificities were 100% for all 3 techniques; and accuracies were 87.5%, 90%, and 100%, respectively. F-FDG PET/CT was false negative in 5 of 40 examinations (all with mucosa-associated lymphoid tissue lymphoma), and F-FDG PET/MR (without DWI) was false negative in 4 of 40 examinations. Region-based percentages of agreement were 99% (κ, 0.95) between F-FDG PET/MR DWI and F-FDG PET/CT, 99.2% (κ, 0.96) between F-FDG PET/MR and F-FDG PET/CT, and 99.4% (κ, 0.97) between F-FDG PET/MR DWI and F-FDG PET/MR. There was a strong correlation between F-FDG PET/CT and F-FDG PET/MR for SUVmax (r = 0.83) and SUVmean (r = 0.81) but no significant correlation between ADCmin and SUVmax (F-FDG PET/CT: r = 0.46, P = 0.65; F-FDG PET/MR: r = 0.64, P = 0.53) or between ADCmean and SUVmean (respectively, r = -0.14, P = 0.17 for the correlation with PET/CT and r = -0.14, P = 0.14 for the correlation with PET/MR). CONCLUSIONS:F-FDG PET/MR and F-FDG PET/CT show a similar diagnostic performance in lymphoma patients. However, if DWI is included in the F-FDG PET/MR protocol, results surpass those of F-FDG PET/CT because of the higher sensitivity of DWI for mucosa-associated lymphoid tissue lymphomas.

PURPOSE/OBJECTIVE:To determine whether in patients with extranodal marginal zone B-cell lymphoma of the mucosa-associated lymphoid tissue lymphoma (MALT), delayed-time-point 2-F-fluoro-2-deoxy-d-glucose-positron emission tomography (F-FDG-PET) performs better than standard-time-point F-FDG-PET. MATERIALS AND METHODS/METHODS:Patients with untreated histologically verified MALT lymphoma, who were undergoing pretherapeutic F-FDG-PET/computed tomography (CT) and consecutive F-FDG-PET/magnetic resonance imaging (MRI), using a single F-FDG injection, in the course of a larger-scale prospective trial, were included. Region-based sensitivity and specificity, and patient-based sensitivity of the respective F-FDG-PET scans at time points 1 (45-60 minutes after tracer injection, TP1) and 2 (100-150 minutes after tracer injection, TP2), relative to the reference standard, were calculated. Lesion-to-liver and lesion-to-blood SUVmax (maximum standardized uptake values) ratios were also assessed. RESULTS:F-FDG-PET at TP1 was true positive in 15 o f 23 involved regions, and F-FDG-PET at TP2 was true-positive in 20 of 23 involved regions; no false-positive regions were noted. Accordingly, region-based sensitivities and specificities were 65.2% (confidence interval [CI], 45.73%-84.67%) and 100% (CI, 100%-100%) for F-FDG-PET at TP1; and 87.0% (CI, 73.26%-100%) and 100% (CI, 100%-100%) for F-FDG-PET at TP2, respectively. FDG-PET at TP1 detected lymphoma in at least one nodal or extranodal region in 7 of 13 patients, and F-FDG-PET at TP2 in 10 of 13 patients; accordingly, patient-based sensitivity was 53.8% (CI, 26.7%-80.9%) for F-FDG-PET at TP1, and 76.9% (CI, 54.0%-99.8%) for F-FDG-PET at TP2. Lesion-to-liver and lesion-to-blood maximum standardized uptake value ratios were significantly lower at TP1 (ratios, 1.05 ± 0.40 and 1.52 ± 0.62) than at TP2 (ratios, 1.67 ± 0.74 and 2.56 ± 1.10; P = 0.003 and P = 0.001). CONCLUSIONS:Delayed-time-point imaging may improve F-FDG-PET in MALT lymphoma.

BACKGROUND:The immunomodulatory drugs (IMiDs) thalidomide and lenalidomide have both been tested for treatment of mucosa-associated lymphoid tissue (MALT) lymphoma, with lenalidomide, in particular, showing promising activity. However, long-term results are missing. Because of the late-onset remissions registered in individual patients, we have systemically analyzed the patients treated with IMiDs at our institution for long-term results. METHODS:Within the present retrospective analysis, we identified 25 patients who had been treated with lenalidomide (n = 18) or thalidomide (n = 7) and were available for long-term assessments of outcome. All patients were followed up according to a standardized follow-up protocol. RESULTS:Of the 25 patients, 7 (28%) experienced delayed-onset responses without further treatment (thalidomide, n = 2; lenalidomide, n = 5). In 4 patients (16%), the initial outcome switched to a better result (partial remission [PR] to complete remission [CR], n = 1; stable disease [SD] to PR, n = 1; SD to CR, n = 1; and PD to CR, n = 1) after a median time of 19.5 months (range, 10.9-32.0). Furthermore, 2 patients showed ongoing shrinkage of the target lesion for 47.4+ and 43.5+ months, respectively, and 1 patient had durable disease stabilization for 16.2+ months. The median time to the best response for all responding patients (13 of 25; 53%) was 7.3 months (interquartile range [IQR], 5.6-22.5). After a median follow-up of 46 months (IQR, 32.0-58.5), 23 of 25 patients (92%) were alive. CONCLUSION/CONCLUSIONS:Our findings suggest that late-onset remissions might be a common phenomenon in the use of IMiDs for the treatment of MALT lymphoma. Thus, sufficient follow-up time after treatment before the initiation of further therapy appears crucial to assess the full effect of therapy and avoid unnecessary overtreatment. IMPLICATIONS FOR PRACTICE/CONCLUSIONS:The immunomodulatory drugs (IMiDs) thalidomide and lenalidomide have been tested for the treatment of mucosa-associated lymphoid tissue (MALT) lymphoma, with lenalidomide showing promising activity. However, long-term results are missing. The present findings suggest that late-onset remissions and delayed responses could be a common phenomenon with IMiD use for MALT lymphoma. Using a standardized restaging protocol to ensure concise follow-up data, these findings suggest it is of major importance to ensure a sufficient follow-up time after treatment with these compounds and before initiation of further treatment lines, because nearly one third of treated patients showed further improvement during prolonged follow-up.

The European Society for Medical Oncology (ESMO) and the American Society of Clinical Oncology (ASCO) are publishing a new edition of the ESMO/ASCO Global Curriculum (GC) thanks to contribution of 64 ESMO-appointed and 32 ASCO-appointed authors. First published in 2004 and updated in 2010, the GC edition 2016 answers to the need for updated recommendations for the training of physicians in medical oncology by defining the standard to be fulfilled to qualify as medical oncologists. At times of internationalisation of healthcare and increased mobility of patients and physicians, the GC aims to provide state-of-the-art cancer care to all patients wherever they live. Recent progress in the field of cancer research has indeed resulted in diagnostic and therapeutic innovations such as targeted therapies as a standard therapeutic approach or personalised cancer medicine apart from the revival of immunotherapy, requiring specialised training for medical oncology trainees. Thus, several new chapters on technical contents such as molecular pathology, translational research or molecular imaging and on conceptual attitudes towards human principles like genetic counselling or survivorship have been integrated in the GC. The GC edition 2016 consists of 12 sections with 17 subsections, 44 chapters and 35 subchapters, respectively. Besides renewal in its contents, the GC underwent a principal formal change taking into consideration modern didactic principles. It is presented in a template-based format that subcategorises the detailed outcome requirements into learning objectives, awareness, knowledge and skills. Consecutive steps will be those of harmonising and implementing teaching and assessment strategies.

The purpose of our study was to determine the value of different hybrid imaging combinations for the detection of focal and diffuse bone marrow infiltration in lymphoma. Patients with histologically proven lymphoma, who underwent both [18F]-FDG-PET/CT and whole-body MRI (including T1- and diffusion-weighted [DWI] sequences) within seven days, and a subsequent bone marrow biopsy, were retrospectively included. Three hybrid imaging combinations were evaluated: (1) [18F]-FDG-PET/CT; (2) [18F]-FDG-PET/T1; and (3) [18F]-FDG-PET/DWI. The presence of focal or diffuse bone marrow infiltration was assessed by two rater teams. Sensitivity, specificity, and accuracy for the detection of overall, focal, and diffuse bone marrow involvement were compared between the three hybrid imaging combinations. Overall, lymphomatous bone marrow involvement was found in 16/60 patients (focal, 8; diffuse, 8). Overall sensitivity, specificity, and accuracy were 81.3%, 95.5%, and 91.7% for [18F]-FDG-PET/CT; 81.3%, 97.7%, and 93.3% for [18F]-FDG-PET/T1; and 81.3%, 95.5%, and 91.7% for [18F]-FDG-PET/DWI. No statistically significant differences between the three imaging combinations were observed, based on overall bone marrow involvement, focal involvement, or diffuse involvement. The sensitivity of all three imaging combinations for detecting diffuse bone marrow involvement was only moderate (62.5% for all three combinations). Although the combination of [18F]-FDG-PET and T1-weighted MRI generally showed the best diagnostic performance for the detection of bone marrow involvement in lymphoma, it was not significantly superior to the two other hybrid imaging combinations. Since the sensitivity of all imaging combinations for the detection of diffuse bone marrow involvement was only moderate, bone marrow biopsy cannot be replaced by imaging as yet.

OBJECTIVES/OBJECTIVE:Gender-related aspects have been investigated in a variety of tumor entities including results on sex-specific differences in non-Hodgkin lymphoma. However, there are no data on gender differences in mucosa-associated lymphoid tissue (MALT) lymphoma. METHODS:We have analyzed 327 patients treated between 1999 and 2015 with a median follow-up time of 55.2 months. RESULTS:There was a female predominance, with 197 female (60.2%) and 130 male patients (39.8%, female-to-male ratio 1.5). The mean age was comparable between female and male patients (61.2 vs. 61.7 years, p = 0.777). Female patients less frequently had gastric MALT lymphoma (31.5 vs. 39.2%), but this was not statistically significant (p = 0.149). Extragastric manifestations were equally distributed, except for parotid (p = 0.003) and breast lymphoma (n = 8, 100% female) showing a female predominance. This was most likely related to a higher rate of active autoimmune disorders in women (35.6 vs. 11.0%, p < 0.001). β2-Microglobulin elevation at diagnosis occurred more often in female patients (42.8 vs. 26.0%; p = 0.008). However, this did not translate into a worse progression-free survival for female (56.0 months, 95% CI 30.1-81.9) versus male patients (49.0 months, 95% CI 25.4-72.5, p = 0.433). Overall survival did not differ between groups. CONCLUSION/CONCLUSIONS:Our data show surprisingly little differences between female and male patients with MALT lymphoma. Both sexes appeared to have well-balanced clinical features and an identical prognosis.

PURPOSE/OBJECTIVE:To determine the value of diffusion-weighted MRI (DWI-MRI) for treatment response assessment in 2-[18F]fluoro-2-deoxy-D-glucose (FDG)-avid lymphoma. EXPERIMENTAL DESIGN/METHODS:Patients with FDG-avid Hodgkin (HL) or non-Hodgkin lymphoma (NHL) at pretherapeutic 18F-FDG-PET/CT, who had also undergone pretherapeutic whole-body DWI-MRI, were included in this prospective study. Depending on the histologic lymphoma subtype, patients received different systemic treatment regimens, and follow-up DWI-MRI and 18F-FDG-PET/CT were performed at one or more time points, depending on the clinical course. For each follow-up DWI-MRI, region-based rates of agreement, and rates of agreement in terms of treatment response (complete remission, partial remission, stable disease, or progressive disease), relative to the corresponding 18F-FDG-PET/CT, were calculated. RESULTS:Sixty-four patients were included: 10 with HL, 22 with aggressive NHL, and 32 with indolent NHL. The overall region-based agreement of DWI-MRI with 18F-FDG-PET/CT was 99.4%. For the 51 interim examinations (performed after 1-3 therapy cycles), region-based agreement of DWI-MRI with 18F-FDG-PET/CT was 99.2%, and for the 48 end-of-treatment examinations, agreement was 99.8%. No significant differences, in terms of region-based agreement between DWI-MRI and 18F-FDG-PET/CT, were observed between the three lymphoma groups (HL, aggressive NHL, indolent NHL; P = 0.25), or between interim and end-of-treatment examinations (P = 0.21). With regard to treatment response assessment, DWI-MRI agreed with 18F-FDG-PET/CT in 99 of 102 follow-up examinations (97.1%), with a κ value of 0.94 (P < 0.0001). CONCLUSIONS:In patients with FDG-avid lymphoma, DWI-MRI may be a feasible alternative to 18F-FDG-PET/CT for follow-up and treatment response assessment.