scholarly journals A computational model of MGUS progression to Multiple Myeloma identifies optimum screening strategies and their effects on mortality

2017 ◽  
Author(s):  
Philipp M. Altrock ◽  
Jeremy Ferlic ◽  
Tobias Galla ◽  
Michael H. Tomasson ◽  
Franziska Michor
Keyword(s):  
Multiple Myeloma ◽  
Computational Modeling ◽  
Risk Reduction ◽  
Disease Prevalence ◽  
Modeling Framework ◽  
Populations At Risk ◽  
Screening Strategies ◽  
Specific Mortality ◽  
Progression Risk

ABSTRACTRecent advances uncovered therapeutic interventions that might reduce the risk of progression of premalignant diagnoses, such as from Monoclonal Gammopathy of Undetermined Significance (MGUS) to multiple myeloma (MM). It remains unclear how to best screen populations at risk and how to evaluate the ability of these interventions to reduce disease prevalence and mortality at the population level. To address these questions, we developed a computational modeling framework. We used individual-based computational modeling of MGUS incidence and progression across a population of diverse individuals, to determine best screening strategies in terms of screening start, intervals, and risk-group specificity. Inputs were life tables, MGUS incidence and baseline MM survival. We measured MM-specific mortality and MM prevalence following MGUS detection from simulations and mathematical precition modeling. We showed that our framework is applicable to a wide spectrum of screening and intervention scenarios, including variation of the baseline MGUS to MM progression rate and evolving MGUS, in which progression increases over time. Given the currently available progression risk-point estimate of 61% risk, starting screening at age 55 and follow-up screening every 6yrs reduced total MM prevalence by 19%. The same reduction could be achieved with starting age 65 and follow-up every 2yrs. A 40% progression risk reduction per MGUS patient per year would reduce MM-specific mortality by 40%. Generally, age of screening onset and frequency impact disease prevalence, progression risk reduction impacts both prevalence and disease-specific mortality, and screeenign would generally be favorable in high-risk individuals. Screening efforts should focus on specifically identified groups of high lifetime risk of MGUS, for which screening benefits can be significant. Screening low-risk MGUS individuals would require improved preventions.

scholarly journals Computational Model of Progression to Multiple Myeloma Identifies Optimum Screening Strategies

2018 ◽  
pp. 1-12 ◽  
Author(s):  
Philipp M. Altrock ◽  
Jeremy Ferlic ◽  
Tobias Galla ◽  
Michael H. Tomasson ◽  
Franziska Michor
Keyword(s):  
Multiple Myeloma ◽  
Computational Modeling ◽  
Risk Reduction ◽  
Disease Prevalence ◽  
Modeling Framework ◽  
Populations At Risk ◽  
Screening Strategies ◽  
Specific Mortality ◽  
Progression Risk

Purpose Recent advances have uncovered therapeutic interventions that might reduce the risk of progression of premalignant diagnoses, such as monoclonal gammopathy of undetermined significance (MGUS) to multiple myeloma (MM). It remains unclear how to best screen populations at risk and how to evaluate the ability of these interventions to reduce disease prevalence and mortality at the population level. To address these questions, we developed a computational modeling framework. Materials and Methods We used individual-based computational modeling of MGUS incidence and progression across a population of diverse individuals to determine best screening strategies in terms of screening start, intervals, and risk-group specificity. Inputs were life tables, MGUS incidence, and baseline MM survival. We measured MM-specific mortality and MM prevalence after MGUS detection from simulations and mathematic modeling predictions. Results Our framework is applicable to a wide spectrum of screening and intervention scenarios, including variation of the baseline MGUS to MM progression rate and evolving MGUS, in which progression increases over time. Given the currently available point estimate of progression risk reduction to 61% risk, starting screening at age 55 years and performing follow-up screening every 6 years reduced total MM prevalence by 19%. The same reduction could be achieved with starting screening at age 65 years and performing follow-up screening every 2 years. A 40% progression risk reduction per patient with MGUS per year would reduce MM-specific mortality by 40%. Specifically, screening onset age and screening frequency can change disease prevalence, and progression risk reduction changes both prevalence and disease-specific mortality. Screening would generally be favorable in high-risk individuals. Conclusion Screening efforts should focus on specifically identified groups with high lifetime risk of MGUS, for which screening benefits can be significant. Screening low-risk individuals with MGUS would require improved preventions.

scholarly journals Assessing the prognostic utility of smoldering multiple myeloma risk stratification scores applied serially post diagnosis

2021 ◽  
Vol 11 (11) ◽  
Author(s):  
Alissa Visram ◽  
S. Vincent Rajkumar ◽  
Prashant Kapoor ◽  
Angela Dispenzieri ◽  
Martha Q. Lacy ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
High Risk ◽  
Risk Stratification ◽  
Baseline Risk ◽  
Risk Category ◽  
High Risk Patients ◽  
Smoldering Multiple Myeloma ◽  
Risk Patients ◽  
Progression Risk

AbstractThe Mayo-2018 smoldering multiple myeloma (SMM) risk score is used routinely in the clinical setting but has only been validated at diagnosis. In SMM patients, the progression risk decreases over time. However, the utility of applying risk stratification models after diagnosis is unknown. We retrospectively studied 704 SMM patients and applied the Mayo 2018 and IMWG-2020 risk stratification models at annual landmark timepoints up to 5 years post diagnosis. The Mayo-2018 and IMWG-2020 models reliably stratified patients based on progression risk when applied post diagnosis. The respective 2-year progression risk in Mayo-2018 high risk patients versus IMWG-2020 intermediate-high risk patients was 51% versus 62% at the 1-year landmark and 47% versus 45% at the 4-year landmark. We showed that patients categorized at Mayo-2018 high-risk at follow-up had a similar risk of progression if the baseline risk assessment was low-intermediate versus high-risk (HR 1.04, 95% CI 0.46–2.36, p = 0.931 at 5-year landmark). Patients migrating to a higher risk category during follow up had a higher progression risk compared to patients with stable/decreased risk categorization. Our findings support the use of these risk scores post-diagnosis and suggest that patients evolving to a high-risk category may benefit from early intervention therapeutic approaches.

Audio Stories as Incidental Language Teachers

2020 ◽  
pp. 1-12 ◽  
Author(s):  
Ute Ritterfeld ◽  
Timo Lüke
Keyword(s):  
Language Learning ◽  
Low Socioeconomic Status ◽  
Language Teachers ◽  
Control Group ◽  
Low Socioeconomic ◽  
Migrant Families ◽  
Populations At Risk ◽  
Grammatical Skills ◽  
Entertainment Value

Abstract. Audio stories offer a unique blend of narrative entertainment with language learning opportunities as a user’s enjoyment is dependent on their processing of the linguistic content. A total of 138 third- and fourth-graders from low socioeconomic status and migrant families recruited from a metropolitan area in Germany participated in a randomized pre–post follow-up intervention study with a control group. Children listened to a tailored crime story of approximately 90 min over a period of 3 days within the classroom setting. Entertainment value for the age group was established in a pilot study. Outcome variables included semantic and grammatical skills in German and were administered before (pretest), shortly after intervention (posttest), and 2 weeks later (follow-up). We used nonverbal intelligence, reading, comprehension skills, age and sex as control variables. Results indicate a strong positive effect of media reception on language skills. The effectiveness of the intervention is discussed with reference to different linguistic domains, entertainment value, and compensatory effects in populations at risk of language learning deficits.

scholarly journals Associations between Amplification (1q) and Prior Cancer in a Real-World De Novo Myeloma Cohort

2021 ◽  
Author(s):  
Elizabeth B Lamont ◽  
Andrew J Yee ◽  
Stuart L Goldberg ◽  
David S Siegel ◽  
Andrew D Norden
Keyword(s):  
Real World ◽  
Fluorescent In Situ Hybridization ◽  
De Novo ◽  
Chromosome 1 ◽  
Second Malignancies ◽  
Cancer History ◽  
Screening Strategies ◽  
Cytogenetic Testing

Abstract Genomic biomarkers inform treatment in multiple myeloma (MM) making patient clinical data a potential window into MM biology. We evaluated de novo MM patients for associations between specific MM cytogenetic patterns and prior cancer history. Analyzing a MM real-world dataset (RWD), we identified a cohort of 1,769 patients with fluorescent in-situ hybridization (FISH) cytogenetic testing at diagnosis. Fully 241 patients (0.14) had histories of prior cancer(s). Amplification of the long arm of chromosome 1 [amp(1q)] varied by prior cancer history (0.31 with prior cancer vs 0.24 without; p = .02). No other MM translocations, amplifications, or deletions were associated with prior cancers. Amp(1q) and cancer history remained strongly associated in a logistic regression adjusting for patient demographic and disease attributes. The results merit follow-up regarding carcinogenic treatment effects and screening strategies for second malignancies. Broadly the findings suggest analyses of patient-level phenotypic-genomic RWD may accelerate cancer research through hypothesis generating studies.

scholarly journals Accuracy of upper endoscopies with random biopsies to identify patients with gastric premalignant lesions who can safely be exempt from surveillance

2021 ◽  
Vol 24 (3) ◽  
pp. 680-690
Author(s):  
Michiel C. Mommersteeg ◽  
Stella A. V. Nieuwenburg ◽  
Wouter J. den Hollander ◽  
Lisanne Holster ◽  
Caroline M. den Hoed ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
High Risk ◽  
Low Risk ◽  
Premalignant Lesions ◽  
High Risk Patients ◽  
European Guidelines ◽  
Progression Of Disease ◽  
Risk Patients ◽  
Progression Risk

Abstract Introduction Guidelines recommend endoscopy with biopsies to stratify patients with gastric premalignant lesions (GPL) to high and low progression risk. High-risk patients are recommended to undergo surveillance. We aimed to assess the accuracy of guideline recommendations to identify low-risk patients, who can safely be discharged from surveillance. Methods This study includes patients with GPL. Patients underwent at least two endoscopies with an interval of 1–6 years. Patients were defined ‘low risk’ if they fulfilled requirements for discharge, and ‘high risk’ if they fulfilled requirements for surveillance, according to European guidelines (MAPS-2012, updated MAPS-2019, BSG). Patients defined ‘low risk’ with progression of disease during follow-up (FU) were considered ‘misclassified’ as low risk. Results 334 patients (median age 60 years IQR11; 48.7% male) were included and followed for a median of 48 months. At baseline, 181/334 (54%) patients were defined low risk. Of these, 32.6% were ‘misclassified’, showing progression of disease during FU. If MAPS-2019 were followed, 169/334 (51%) patients were defined low risk, of which 32.5% were ‘misclassified’. If BSG were followed, 174/334 (51%) patients were defined low risk, of which 32.2% were ‘misclassified’. Seven patients developed gastric cancer (GC) or dysplasia, four patients were ‘misclassified’ based on MAPS-2012 and three on MAPS-2019 and BSG. By performing one additional endoscopy 72.9% (95% CI 62.4–83.3) of high-risk patients and all patients who developed GC or dysplasia were identified. Conclusion One-third of patients that would have been discharged from GC surveillance, appeared to be ‘misclassified’ as low risk. One additional endoscopy will reduce this risk by 70%.

scholarly journals Iceland screens, treats, or prevents multiple myeloma (iStopMM): a population-based screening study for monoclonal gammopathy of undetermined significance and randomized controlled trial of follow-up strategies

2021 ◽  
Vol 11 (5) ◽  
Author(s):  
Sæmundur Rögnvaldsson ◽  
Thorvardur Jon Love ◽  
Sigrun Thorsteinsdottir ◽  
Elín Ruth Reed ◽  
Jón Þórir Óskarsson ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Early Treatment ◽  
Monoclonal Gammopathy ◽  
Controlled Trial ◽  
Participation Rate ◽  
Population Based ◽  
Early Therapy ◽  
Screening Study ◽  
Undetermined Significance

AbstractMonoclonal gammopathy of undetermined significance (MGUS) precedes multiple myeloma (MM). Population-based screening for MGUS could identify candidates for early treatment in MM. Here we describe the Iceland Screens, Treats, or Prevents Multiple Myeloma study (iStopMM), the first population-based screening study for MGUS including a randomized trial of follow-up strategies. Icelandic residents born before 1976 were offered participation. Blood samples are collected alongside blood sampling in the Icelandic healthcare system. Participants with MGUS are randomized to three study arms. Arm 1 is not contacted, arm 2 follows current guidelines, and arm 3 follows a more intensive strategy. Participants who progress are offered early treatment. Samples are collected longitudinally from arms 2 and 3 for the study biobank. All participants repeatedly answer questionnaires on various exposures and outcomes including quality of life and psychiatric health. National registries on health are cross-linked to all participants. Of the 148,704 individuals in the target population, 80 759 (54.3%) provided informed consent for participation. With a very high participation rate, the data from the iStopMM study will answer important questions on MGUS, including potentials harms and benefits of screening. The study can lead to a paradigm shift in MM therapy towards screening and early therapy.

Cause-specific mortality in insulin-treated diabetic patients: A 20-year follow-up

2008 ◽  
Vol 80 (1) ◽  
pp. 16-23 ◽  
Author(s):  
Shelagh I. Dawson ◽  
Jinny Willis ◽  
Christopher M. Florkowski ◽  
Russell S. Scott
Keyword(s):  
Diabetic Patients ◽  
Specific Mortality

scholarly journals Multiple myeloma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up

2013 ◽  
Vol 24 ◽  
pp. vi133-vi137 ◽  
Author(s):  
P. Moreau ◽  
J. San Miguel ◽  
H. Ludwig ◽  
H. Schouten ◽  
M. Mohty ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Clinical Practice ◽  
Clinical Practice Guidelines ◽  
Practice Guidelines
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