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

ABSTRACT: 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: 1^st magnetic resonance imaging P=0.028/P=0.048; 2^nd magnetic resonance imaging P=0.008/P=0.024). Focal infiltration pattern itself seemed to be an additional adverse prognostic factor for overall survival (2^nd 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.

SUBMITTER: Mosebach J

PROVIDER: S-EPMC5792278 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature

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

Mosebach Jennifer J Shah Sofia S Delorme Stefan S Hielscher Thomas T Goldschmidt Hartmut H Schlemmer Heinz-Peter HP Schönland Stefan S Hegenbart Ute U Hillengass Jens J

Haematologica 20171207 2

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 surviva ...[more]

PMID: 29217779

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Project description:OBJECTIVES:Whole-body MRI (WB-MRI) is recommended by the International Myeloma Working Group for all patients with asymptomatic myeloma and solitary plasmacytoma and by the UK NICE guidance for all patients with suspected myeloma. Some centres unable to offer WB-MRI offer low-dose whole-body CT (WB-CT). There are no studies comparing interobserver agreement and disease detection of contemporary WB-MRI (anatomical imaging and DWI) versus WB-CT. Our primary aim is to compare the interobserver agreement between WB-CT and WB-MRI in the diagnosis of myeloma. METHODS:Consecutive patients with newly diagnosed myeloma imaged with WB-MRI and WB-CT were prospectively reviewed. For each body region and modality, two experienced and two junior radiologists scored disease burden with final scores by consensus. Intraclass correlation coefficients (ICC), median scores, Wilcoxon signed-rank test and Spearman's correlation coefficients were calculated. RESULTS:There was no significant difference in overall observer scores between WB-MRI and WB-CT (p?=?0.87). For experienced observers, interobserver agreement for WB-MRI was superior to WB-CT overall and for each region, without overlap in whole-skeleton confidence intervals (ICC 0.98 versus 0.77, 95%CI 0.96-0.99 versus 0.45-0.91). For inexperienced observers, although there is a trend for a better interobserver score for the whole skeleton on WB-MRI (ICC 0.95, 95%CI 0.72-0.98) than on WB-CT (ICC 0.72, 95%CI 0.34-0.88), the confidence intervals overlap. CONCLUSIONS:WB-MRI offers excellent interobserver agreement which is superior to WB-CT for experienced observers. Although the overall burden was similar across both modalities, patients with lower disease burdens where MRI could be advantageous are not included in this series. KEY POINTS:• Whole-body MRI is recommended by the International Myeloma Working Group for patients with multiple myeloma and solitary plasmacytoma and by the NICE guidance for those with suspected multiple myeloma. • Some centres unable to offer whole-body MRI (WB-MRI) offer low-dose whole-body CT (WB-CT). • This prospective study demonstrates that contemporary WB-MRI (with anatomical sequences and DWI) provides better interobserver agreement in assessing myeloma disease burden for the whole skeleton and across any individual body region in myeloma patients when compared with low-dose whole-body CT.

Project description:UnlabelledApproximately 30% of rheumatoid arthritis patients achieve inadequate response to anti-TNF biologics. Attempts to identify molecular biomarkers predicting response have met with mixed success. This may be attributable, in part, to the variable and subjective disease assessment endpoints with large placebo effects typically used to classify patient response. Sixty-one patients with active RA despite methotrexate treatment, and with MRI-documented synovitis, were randomized to receive infliximab or placebo. Blood was collected at baseline and genome-wide transcription in whole blood was measured using microarrays. The primary endpoint in this study was determined by measuring the transfer rate constant (Ktrans) of a gadolinium-based contrast agent from plasma to synovium using MRI. Secondary endpoints included repeated clinical assessments with DAS28(CRP), and assessments of osteitis and synovitis by the RAMRIS method. Infliximab showed greater decrease from baseline in DCE-MRI Ktrans of wrist and MCP at all visits compared with placebo (P<0.001). Statistical analysis was performed to identify genes associated with treatment-specific 14-week change in Ktrans. The 256 genes identified were used to derive a gene signature score by averaging their log expression within each patient. The resulting score correlated with improvement of Ktrans in infliximab-treated patients and with deterioration of Ktrans in placebo-treated subjects. Poor responders showed high expression of activated B-cell genes whereas good responders exhibited a gene expression pattern consistent with mobilization of neutrophils and monocytes and high levels of reticulated platelets. This gene signature was significantly associated with clinical response in two previously published whole blood gene expression studies using anti-TNF therapies. These data provide support for the hypothesis that anti-TNF inadequate responders comprise a distinct molecular subtype of RA characterized by differences in pre-treatment blood mRNA expression. They also highlight the importance of placebo controls and robust, objective endpoints in biomarker discovery.Trial registrationClinicalTrials.gov NCT01313520.

Dataset Information

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

Publications

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

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