Whole-body magnetic resonance imaging plus serological follow-up for early identification of progression in smouldering myeloma patients to prevent development of end-organ damage.

The definition of multiple myeloma (MM) was updated in 2014, with the intent to enable earlier treatment and thereby avoid appearance of end-organ damage at progression from smouldering multiple myeloma (SMM) to MM. The purpose of this study was to investigate to which extent the development of end-organ damage at progression to MM was reduced under the updated guidelines. In this prospective observational cohort study (ClinicalTrials.gov Identifier: NCT01374412), between 2014 and 2020, 96 SMM patients prospectively underwent whole-body magnetic resonance imaging (wb-MRI) and serological follow-up at baseline and every 6 months thereafter. A total of 22 patients progressed into MM during follow-up, of which seven (32%) showed SLiM-criteria only but no end-organ damage. Four (57%) of the seven patients who progressed by SLiM-criteria only progressed with >1 focal lesion (FL) or a growing FL, and three (43%) due to serum free light-chain-ratio ≥100. Fifteen (68%) out of 22 patients who progressed still suffered from end-organ damage at progression. The updated disease definition reduced the proportion of SMM patients suffering from end-organ damage at progression to MM by one third. wb-MRI is an important tool for detection of SMM patients who progress to MM without end-organ damage.

Multiple Myeloma Guidelines and Their Recent Updates: Implications for Imaging. / Leitlinien zum multiplen Myelom und ihre aktuellen Anpassungen: Konsequenzen für die Bildgebung.

BACKGROUND: In 2014, the diagnostic criteria for multiple myeloma were updated, leading to revised recommendations for imaging modalities and definition of therapy response. This review provides an overview of the current definitions of monoclonal plasma cell disease, diagnostic options, and changes relevant to radiologists. METHOD: A pubmed search regarding the multiple myeloma guidelines was conducted, and results were filtered considering publications of international associations and expert reviews. Recommendations by the International Myeloma Working Group (IMWG), the National Comprehensive Cancer Network (NCCN, USA), the European Society for Medical Oncology (ESMO), and the European Myeloma Network are acknowledged. RESULTS AND CONCLUSION: Conventional skeletal survey is to be replaced by cross-sectional imaging techniques. For initial diagnostics of bone lesions or bone marrow involvement defining multiple myeloma, whole-body low-dose CT and whole-body MRI are recommended. Two or more focal bone marrow lesions suspicious for myeloma on MRI will now define symptomatic disease even in the case of intact mineralized bone. Follow-up imaging is not clearly specified so far. New guidelines concerning the definitions of minimal residual disease include the assessment of focal lesions before and after treatment using 18F-FDG-PET/CT, with the potential to redefine the role of PET/CT in the diagnostics of multiple myeloma. KEY POINTS: · Whole-body low-dose CT is recommended by international reference organizations for detecting lytic bone lesions.. · Focal myeloma lesions detected on whole-body MRI will indicate symptomatic multiple myeloma requiring therapy, even in the absence of damage to mineralized bone.. · The IMWG recommends using cross-sectional imaging in the initial work-up: whole-body low-dose CT, MRI, or PET/CT, depending on availability and resources.. · The diagnostic potential of 18F-FDG-PET/CT is highlighted by its inclusion in the definition of minimal residual disease after therapy; implementation in Germany is uncertain due to limited access in the daily routine.. CITATION FORMAT: · Mosebach J, Thierjung H, Schlemmer H et al. Multiple Myeloma Guidelines and Their Recent Updates: Implications for Imaging. Fortschr Röntgenstr 2019; 191: 998 - 1009.

Prognostic significance of tumor burden assessed by whole-body magnetic resonance imaging in multiple myeloma patients treated with allogeneic stem cell transplantation.

Allogeneic stem cell transplantation is a therapeutic option under dispute but nonetheless chosen with increasing frequency for patients suffering from multiple myeloma in Europe. To study possible predictors of survival, 79 patients were investigated using whole-body magnetic resonance imaging to assess the visible tumor burden before and after allogeneic stem cell transplantation. Statistical analysis of clinical and imaging parameters included Cox regression models and distribution of survival time estimates (Kaplan-Meier method). Log rank test was used to determine the prognostic impact of the presence of focal lesions on survival. A higher tumor burden according to the lesion count was associated with a shorter overall survival (univariable/multivariable Cox regression: 1st magnetic resonance imaging P=0.028/P=0.048; 2nd magnetic resonance imaging P=0.008/P=0.024). Focal infiltration pattern itself seemed to be an additional adverse prognostic factor for overall survival (2nd MRI P=0.048), although no definite cut-off could be defined. Kaplan-Meier estimates at 60 months of follow up show a significant difference (Log rank P=0.04) for overall survival rates between patients with focal infiltration (32%) and those without (75%). Since this subgroup of patients may benefit from maintenance therapy, adoptive immunotherapy, or local interventions, whole-body imaging is an appropriate and highly recommendable diagnostic approach for detection of prognostically relevant lesions before and after treatment.

Application of (18)F-FDG PET and diffusion weighted imaging (DWI) in multiple myeloma: comparison of functional imaging modalities.

Aim of this prospective study was to assess the sensitivity of positron emission tomography (PET) and diffusion-weighted imaging (DWI) in detecting multiple myeloma (MM) lesions, using the well-established morphologic modalities magnetic resonance imaging (MRI) and computed tomography (CT) as the standard of reference (RS). The study included 24 MM patients (15 newly diagnosed, 9 pre-treated). All underwent (18)F-FDG PET/CT and wholebody DWI. The findings in PET and DWI were compared to matching imaging findings in combined non-enhanced T1w, fat-saturated T2w (TIRM)- MRI, and low-dose CT. Patient-based analysis revealed that 15/24 patients (10 primary MM, 5 pre-treated) had myeloma lesions according to our RS. PET was positive in 13/24 patients (11 primary MM, 2 pre-treated) and DWI in 18/24 patients (12 primary MM, 6 pre-treated). Lesion-based analysis demonstrated 128 MM lesions, of which PET depicted 60/128 lesions (sensitivity 47%), while DWI depicted 99/128 lesions (sensitivity 77%). Further analysis including only the 15 untreated MM patients revealed a sensitivity of 90% for both PET and DWI and an overall concordance of PET and DWI of 72%. In conclusion, DWI was more sensitive than (18)F-FDG PET in detecting myeloma lesions in a mixed population of primary and pre-treated MM patients. However, (18)F-FDG PET and DWI demonstrated equivalent sensitivities in the sub-population of primary, untreated MM patients. This higher sensitivity of DWI in pre-treated patients may be due to the fact that (18)F-FDG PET becomes negative earlier in the course of treatment in contrary to MRI, in which already treated lesions can remain visible.

Comparison of (18)F-FDG PET/CT and PET/MRI in patients with multiple myeloma.

PET/MRI represents a promising hybrid imaging modality with several potential clinical applications. Although PET/MRI seems highly attractive in the diagnostic approach of multiple myeloma (MM), its role has not yet been evaluated. The aims of this prospective study are to evaluate the feasibility of (18)F-FDG PET/MRI in detection of MM lesions, and to investigate the reproducibility of bone marrow lesions detection and quantitative data of (18)F-FDG uptake between the functional (PET) component of PET/CT and PET/MRI in MM patients. The study includes 30 MM patients. All patients initially underwent (18)F-FDG PET/CT (60 min p.i.), followed by PET/MRI (120 min p.i.). PET/CT and PET/MRI data were assessed and compared based on qualitative (lesion detection) and quantitative (SUV) evaluation. The hybrid PET/MRI system provided good image quality in all cases without artefacts. PET/MRI identified 65 of the 69 lesions, which were detectable with PET/CT (94.2%). Quantitative PET evaluations showed the following mean values in MM lesions: SUVaverage=5.5 and SUVmax=7.9 for PET/CT; SUVaverage=3.9 and SUVmax=5.8 for PET/MRI. Both SUVaverage and SUVmax were significantly higher on PET/CT than on PET/MRI. Spearman correlation analysis demonstrated a strong correlation between both lesional SUVaverage (r=0.744) and lesional SUVmax (r=0.855) values derived from PET/CT and PET/MRI. Regarding detection of myeloma skeletal lesions, PET/MRI exhibited equivalent performance to PET/CT. In terms of tracer uptake quantitation, a significant correlation between the two techniques was demonstrated, despite the statistically significant differences in lesional SUVs between PET/CT and PET/MRI.

Increased nuclear Olig1-expression in the pregenual anterior cingulate white matter of patients with major depression: a regenerative attempt to compensate oligodendrocyte loss?

BACKGROUND: Structural and functional oligodendrocyte deficits as well as impaired myelin integrity have been described in affective disorders and schizophrenia, and may disturb the connectivity between disease-relevant brain regions. Olig1, an oligodendroglial transcription factor, might be important in this context, but has not been systematically studied so far. METHODS: Nissl- and Olig1-stained oligodendrocytes were quantified in the pregenual anterior cingulate (pACC)/dorsolateral prefrontal cortex (DLPFC), and adjacent white matter of patients with major depressive disorder (MDD, n = 9), bipolar disorder (BD, n = 8), schizophrenia (SZ, n = 13), and matched controls (n = 16). Potential downstream effects of increased Olig1-expression were analyzed. Antidepressant drug effects on Olig1-expression were further explored in OLN-93 oligodendrocyte cultures. RESULTS: Nissl-stainings of both white matter regions showed a 19-27% reduction of total oligodendrocyte densities in MDD and BD, but not in SZ. In contrast, nuclear Olig1-immunoreactivity was elevated in MDD in the pACC-adjacent white matter (left: p = 0.008; right: p = 0.018); this effect tended to increase with antidepressant dosage (r = 0.631, p = 0.069). This reactive increase of Olig1 was confirmed by partly dose-dependent effects of imipramine and amitriptyline in oligodendrocyte cultures. Correspondingly, MBP expression in the pACC-adjacent white matter tended to increase with antidepressant dosage (r = 0.637, p = 0.065). Other tested brain regions showed no diagnosis-dependent differences regarding Olig1-immunoreactivity. CONCLUSIONS: Since nuclear Olig1-expression marks oligodendrocyte precursor cells, its increased expression along with reduced total oligodendrocyte densities (Nissl-stained) in the pACC-adjacent white matter of MDD patients might indicate a (putatively medication-boosted) regenerative attempt to compensate oligodendrocyte loss.