Association of Elevated Circulating Proteasome Levels at Diagnosis with Poor Outcome in Multiple Myeloma

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 5140-5140
Author(s):  
Peter Liebisch ◽  
Stephan Sixt ◽  
Hagen S Bachmann ◽  
Ulrich H Frey ◽  
Juergen Peters ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Observation Interval ◽  
Prognostic Significance ◽  
Progression Free Survival ◽  
Ubiquitin Proteasome System ◽  
University Hospital ◽  
Rank Test ◽  
Healthy Controls ◽  
Serum Samples ◽  
Poor Outcome

Abstract Background: The proteasome is a proteolytic complex for intracellular degradation of ubiquitinated proteins which are involved in cell cycle regulation and apoptosis. A constitutively increased proteasome activity has been found in myeloma cells. Recent studies have shown that inhibition of the ubiquitin-proteasome system can be successfully used as a targeted therapy in multiple myeloma (MM). Recent data suggest a significant correlation between circulating proteasome levels (CPL) and outcome in patients with MM. Therefore, we investigated CPL in 110 patients in order to assess the role of CPL in MM. Experimental design: CPL were measured in serum samples from healthy controls (N=10) as well as from patients with monoclonal gammopathies of undetermined significance (N=27), indolent MM (N=15) and symptomatic MM (N=68) using enzyme-linked immunoabsorbent assay (ELISA) techniques detecting circulating 20S proteasome components. All serum samples were collected at the University Hospital in Ulm at time of diagnosis. Results: The median CPL were 123.5 ng/mL (range, 95–185 ng/mL) in healthy controls, 180 ng/mL (range, 100–485 ng/mL) in patients with MGUS (N=27) or indolent MM (N=15), and 227.5 ng/mL (range, 100–985 ng/mL) in patients with symptomatic MM (N=70). The CPL of patients with symptomatic MM were significantly elevated compared with healthy donors (p=0.0017) and to persons with asymptomatic gammopathies (p=0.046). While CPL were also significantly higher in the MGUS/indolent MM cohort as compared to controls (p=0.03), CPL in MGUS and indolent MM were comparable. Using ROC analysis in the symptomatic MM cohort patients with CPL >150ng/mL (N=50) had a significantly shorter progression-free survival (PFS) time than patients (N=18) with CPL<150 ng/mL levels (median PFS: 40 versus 57 months, log rank test p=0.026). Of note, all six patients who died in the observation interval had CPL >150ng/mL. Conclusions: Here we demonstrate that increased CPL at diagnosis correlates with poor outcome in symptomatic MM patients. Evaluation of the prognostic significance of CPL in a larger cohort of uniformly treated patients with symptomatic MM is currently under way. This data will be presented at the meeting.

Longitudinal whole body MRI (wbMRI) in monoclonal gammopathy of undetermined significance (MGUS) and smoldering multiple myeloma.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 8590-8590
Author(s):  
Maximilian Merz ◽  
Barbara Wagner-Gund ◽  
Kai Neben ◽  
Anthony D. Ho ◽  
Hartmut Goldschmidt ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Prognostic Significance ◽  
Progression Free Survival ◽  
Whole Body ◽  
Rank Test ◽  
Focal Lesions ◽  
Patients At Risk ◽  
Initial Work

8590 Background: The detection of bone marrow focal lesions (FLs) by MRI at the initial work up has prognostic significance in multiple myeloma (MM), smoldering MM as well as MGUS. Currently, there are no data available on the predictive relevance of new FLs or FLs increasing in size in longitudinally performed wbMRIs for the follow-up of sMM and MGUS. Methods: We retrospectively analyzed 87 patients (sMM n=65; MGUS n=22) that received at least 2 (up to 5) wbMRIs for follow-up. The date of progression into MM requiring systemic therapy was defined as event for the analysis of progression free survival (PFS). Radiological progressive disease (rPD) was defined as the appearance of novel FLs or increase in size of preexisting FLs. Kaplan-Meier plots of PFS for patients with rPD and patients without rPD were analyzed using the log-rank test for significant differences. Results: Median follow-up was 61 months (9.8-101) with a median time between follow-up wbMRIs of 15.8 months (1-73). Progression from sMM/MGUS into MM was found in 28 patients (sMM 40%; MGUS 9%). Using wbMRI, rPD was found in 21 patients (sMM 32%; MGUS 0%). Of all patients, 76% (n=16) with rPD and 16% (n= 9) without rPD progressed into MM during the observation period. Analysis of Kaplan Meyer plots for PFS revealed a highly significant shorter PFS for patients with rPD (32 months) compared to patients with radiological stable disease in wbMRI (PFS not reached; p<0.0001). New appearance or progression of diffuse bone marrow infiltration was not associated with a shorter PFS (not reached; p>0.05). Conclusions: In our study, the appearance of novel FLs or progression of preexisting FLs was highly predictive for progression from sMM into MM requiring systemic treatment. We conclude that wbMRI is effective for the longitudinal follow-up of patients with sMM and MGUS and identifies a group of patients at risk for progression into MM.

Prognostic significance of t(11;14) expression by FISH in patients with newly diagnosed multiple myeloma in the era of novel therapies.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e19525-e19525
Author(s):  
Miguel Gonzalez Velez ◽  
Ricardo Daniel Parrondo ◽  
Tracy Andrews ◽  
Narjust Duma ◽  
Joshua Ryan Richter ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Cox Regression ◽  
Prognostic Significance ◽  
Progression Free Survival ◽  
Autologous Stem Cell Transplant ◽  
Cell Transplant ◽  
Novel Therapies ◽  
Newly Diagnosed ◽  
Seer Data ◽  
Worse Prognosis

e19525 Background: Rearrangements of the immunoglobulin heavy chain (IGH) on chromosome 14 are identified by FISH in about 15-20% of patients (pts) with newly diagnosed multiple myeloma (MM). Historically there is variation on the significance on prognosis of these rearrangements: typically, t(4;14), t(14;16) and t(14;20) have high risk (HR), and t(11;14) have standard risk (SR). A recent study (Kaufman et al, Leukemia. 2016 30:633-9) suggests that t(11;14) may confer a worse prognosis We report the prognostic significance of t(11;14) in a single-institution MM cohort. Methods: 87 pts with t(11;14) by CD 138 selected FISH at diagnosis were identified, pts without symptomatic MM were excluded. Cox regression was used for statistical analysis. Progression free survival (PFS), and overall survivals (OS) from diagnosis and post autologous stem cell transplant (ASCT) were analyzed by Kaplan-Meier. Results: Median age at diagnosis was 62 years, 45 pts (52%) were male, and 24 pts (27%) had ISS 3. All pts received either a proteasome inhibitor or an immunomodulatory agent, and 42 (48%) received triplet treatment as induction. Sixty-nine (79%) pts had ASCT, and overall response rate (ORR, partial response or better) post ASCT was 73%. For pts with HR FISH (defined as t(14;16), p53 del, 1q21 gain or 1p del) compared to SR FISH, the ORR post ASCT was 70% vs 77% (p = 0.67). OS from diagnosis was 93% at 3 years, 74% at 4 years and 51% at 5 years. Seven patients (8%) developed plasma cell leukemia, and there was no association between HR and SR FISH (p = 0.66). In multivariate analysis, ISS stage was an independent risk factor for mortality; pts with stage 3 had 7.3 times (CI: 1.16-36.4) and 5.7 times (CI: 1.63-20.0) the risk of mortality than pts with stage 1 and 2. Having an ASCT reduced mortality by 87% (CI: 0.04-0.41). Conclusions: Despite the use of novel therapies the OS at 5 years of our pts with MM was not significantly improved compared to SEER data from 1992-2013 (51% vs 48.5%). Pts with t(11;14) who had ASCT had increased survival compared to those who did not. Our results suggest that t(11;14) may confer a worse prognosis. Further prospective studies evaluating the risk of t(11;14) are warranted.

scholarly journals Extracellular Vesicle-Based Detection of Pancreatic Cancer

2021 ◽  
Vol 9 ◽  
Author(s):  
Yesim Verel-Yilmaz ◽  
Juan Pablo Fernández ◽  
Agnes Schäfer ◽  
Sheila Nevermann ◽  
Lena Cook ◽  
...  
Keyword(s):  
High Sensitivity ◽  
Roc Curves ◽  
Serum Levels ◽  
Extracellular Vesicle ◽  
Ductal Adenocarcinoma ◽  
Rank Test ◽  
Healthy Controls ◽  
Precursor Lesions ◽  
Healthy Individuals ◽  
Serum Samples

Due to a grim prognosis, there is an urgent need to detect pancreatic ductal adenocarcinoma (PDAC) prior to metastasis. However, reliable diagnostic imaging methods or biomarkers for PDAC or its precursor lesions are still scarce. ADAM8, a metalloprotease-disintegrin, is highly expressed in PDAC tissue and negatively correlates with patient survival. The aim of our study was to determine the ability of ADAM8-positive extracellular vesicles (EVs) and cargo microRNAs (miRNAs) to discriminate precursor lesions or PDAC from healthy controls. In order to investigate enrichment of ADAM8 on EVs, these were isolated from serum of patients with PDAC (n = 52), precursor lesions (n = 7) and healthy individuals (n = 20). Nanoparticle Tracking Analysis and electron microscopy indicated successful preparation of EVs that were analyzed for ADAM8 by FACS. Additionally, EV cargo analyses of miRNAs from the same serum samples revealed the presence of miR-720 and miR-451 by qPCR and was validated in 20 additional PDAC samples. Statistical analyses included Wilcoxon rank test and ROC curves. FACS analysis detected significant enrichment of ADAM8 in EVs from patients with PDAC or precursor lesions compared to healthy individuals (p = 0.0005). ADAM8-dependent co-variates, miR-451 and miR-720 were also diagnostic, as patients with PDAC had significantly higher serum levels of miR-451 and lower serum levels of miR-720 than healthy controls and reached high sensitivity and specificity (AUC = 0.93 and 1.00, respectively) to discriminate PDAC from healthy control. Thus, detection of ADAM8-positive EVs and related cargo miR-720 and miR-451 may constitute a specific biomarker set for screening individuals at risk for PDAC.

scholarly journals The Prognostic Value of Whole-Blood PSMB5, CXCR4, POMP and RPL5 mRNA Expression in Patients with Multiple Myeloma Treated with Bortezomib

2021 ◽  
Author(s):  
Paweł Robak ◽  
Dariusz Jarych ◽  
Damian Mikulski ◽  
Izabela Dróżdż ◽  
Edyta Węgłowska ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Mrna Expression ◽  
Molecular Mechanisms ◽  
Multiple Drug Resistance ◽  
Mrna Level ◽  
Proteasome Inhibitors ◽  
Progression Free Survival ◽  
High Expression ◽  
Multiple Drug ◽  
Healthy Controls

Proteasome inhibitors, like bortezomib, play a key role in the treatment of multiple myeloma (MM); however, most patients eventually relapse and eventually show multiple drug resistance, and the molecular mechanisms of this resistance remain unclear. The present study examines the expression of previously-described genes that may influence resistance to bortezomib treatment at the mRNA level (ABCB1, CXCR4, MAF, MARCKS, POMP, PSMB5, RPL5, TXN and XBP1). mRNA expression was determined in 73 MM patients treated with bortezomib-based regimens (30 bortzomib-sensitive and 43 bortezomib-refractory patients) and 11 healthy controls. RPL5 was significantly down-regulated in multiple myeloma patients as compared with healthy controls. Moreover, POMP was significantly up-regulated in MM patients refractory to bortezomib-based treatment. In multivariate analysis, high expression of PSMB5 and CXCR and autologous stem cell transplantation were independent predictors of progression-free survival, and high expression of POMP and RPL5 was associated with shorter overall survival.

scholarly journals Multiple Myeloma Patients with Lenalidomide-Associated Skin Rash Have a Favorable Prognosis

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 4532-4532 ◽  
Author(s):  
Ayumi Kojima ◽  
Yuka Tanaka ◽  
Yuta Kimura ◽  
Daisuke Tsuchimoto ◽  
Rina Etani ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
Skin Rash ◽  
Research Funding ◽  
Kinase Inhibitors ◽  
Performance Status ◽  
Progression Free Survival ◽  
Rank Test ◽  
Free Survival ◽  
The Relationship

Abstract Background: Lenalidomide, one of the immunomodulatory drugs, is an important component of treatment for multiple myeloma. Lenalidomide inhibits the proliferation of tumor cells via antiangiogenesis, induces apoptosis and acts directly on the immune system and tumor microenvironment. Immunomodulatory effects of lenalidomide notably stimulate the production of cytokines and activation of T-cells and natural killer cells. Skin rash is a frequent adverse event of lenalidomide. Some studies have shown a correlation between the efficacy of anti-cancer agents such as tyrosine kinase inhibitors and the development of skin rash. However, the relationship between the development of lenalidomide-associated skin rash and its efficacy is unclear. We conducted a retrospective survey to clarify whether development of skin rash correlates with the efficacy of lenalidomide. Materials and Methods: All patients with multiple myeloma who received lenalidomide at 9 hospitals in Japan from July 2009 to December 2015 were serially registered. The chart review was performed for all identified patients to obtain the following information; age, sex, performance status at the initiation of lenalidomide, International Staging System (ISS) classification, prior chemotherapy regimen, tumor response, development of skin rash and clinical outcomes. A log-rank test was used to assess the relationship between the presence of skin rash and survival. A two-sided p < 0.05 was considered statistically significant. This study received approval from the appropriate ethics committees. Results: We identified 215 patients (92 women and 123 men), with a median age was 69 years (range, 39-86 years). Types of myeloma were as follows: 139 patients of IgG, 43 of IgA, and 29 of Bence-Jones protein. ISS was available for 204 patients, and of these, 63, 73, and 68 patients were classified as ISS stage I, II, and III, respectively. The median number of prior therapies was 2 (range, 0-6); 161 (74.9%) and 46 patients (21.4%) had previously received bortezomib and thalidomide, respectively. Fifty patients (23.3%) had undergone previous autologous stem cell transplantation. Sixty-five patients (30.2%) developed a skin rash after lenalidomide initiation, and the median time to onset of skin rash was 12 days. The patients with and without skin rash were similar with respect to age, type of myeloma, and ISS. The median follow-up of survivors was 28.9 months (range, 1.7-80.3 months). The progression-free survival and overall survival were better in patients who had skin rash than in those who did not (p = 0.009 and p = 0.033, respectively) (Figures A and B). Conclusions: In this study, the progression-free survival and overall survival among patients with skin rash during lenalidomide therapy was significantly superior to the patients without skin rash. Lenalidomide-associeated skin rash in patients with multiple myeloma may be a predictive factor of their clinical outcome. Figure Figure. Disclosures Nagai: Takeda: Honoraria, Research Funding; Janssen: Research Funding; Mundipharma KK: Research Funding.

Massively parallel sequencing (MPS) of circulating DNA in patients with metastatic colorectal cancer (mCRC): Prognostic significance and early changes during chemotherapy (CT).

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 11015-11015 ◽  
Author(s):  
Jeanne Tie ◽  
Isaac Kinde ◽  
Hui-Li Wong ◽  
Joseph James McKendrick ◽  
Peter Gibbs ◽  
...  
Keyword(s):  
Massively Parallel Sequencing ◽  
Prognostic Significance ◽  
Predictive Biomarkers ◽  
Progression Free Survival ◽  
Circulating Tumor Dna ◽  
Rank Test ◽  
Cancer Center ◽  
Circulating Dna ◽  
Plasma Samples ◽  
Mutational Status

11015 Background: Prognostic and predictive biomarkers in mCRC are urgently needed. Circulating tumor cells are a promising blood biomarker, but are detectable in only a minority of pts. Recently, analysis of circulating tumor DNA (ctDNA) has shown promise as a liquid biopsy, reflecting the evolving mutational status of the tumor. Here we explored baseline ctDNA as a prognostic marker, and early changes in ctDNA as a marker of CT response. Methods: Serial plasma samples and CEA were collected at baseline (D1), day 3 (D3) and cycle 2 day 1 (C2D1) from 40 mCRC pts receiving standard combination CT. Restaging scans performed at 8 weeks were centrally assessed using RECIST criteria. Samples were analyzed at Johns Hopkins Kimmel Cancer Center. Initially tumor tissue was analyzed for hotspot mutations in TP53, APC, KRAS, BRAF, PIK3CA and FBXW7. The same mutation was queried and quantified in plasma using a MPS platform (Safe-SeqS). Log-rank test was used to compare survival curves and Wilcoxon matched pairs test was used to compare paired plasma samples. Results: Preliminary data is available on 19 pts in this ongoing study. Using our initial panel at least 1 mutation was found in 16 of 19 (84.2%) tumors (7 KRAS, 3 TP53, 3 BRAF, 2 APC and 1 PIK3CA), with matching ctDNA found for each pt. For the remaining 3 cases a further panel of mutations is being analyzed. Median D1 cell free DNA (cfDNA) and ctDNA levels were 1.98 ng/ul (0.15 – 57.18) and 523 mutant fragments (frag)/ml (0.4 – 109,876), respectively. Pts with D1 cfDNA of ≥ 2.5 compared with < 2.5 had shorter median overall survival (OS; 6.9 v 12.2 months, p = 0.0086), with a trend for shorter progression-free survival (PFS; 3.6 v 8.2 months, p = 0.3477). A surge of ctDNA level from D1 to D3 was typically observed (median increase: 91.2 frag/ml, p = 0.0313), followed by a drop (median decrease from D1 to C2D1: 208.8 frag/ml, p = 0.0098). All pts with a decrease in ctDNA at C2D1 had a reduction in tumor size at 8 weeks. Conclusions: In all cases of mCRC where tumor mutation was identified, matching ctDNA was detected in plasma. Circulating DNA is a promising marker of prognosis. Early changes in DNA levels may be a useful marker of tumor response.

Monokine Induced by Interferon-γ (MIG) Serum Levels Are a Marker of Disease Load and Correlate with Prognosis in Multiple Myeloma.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 5040-5040
Author(s):  
Martin Schreder ◽  
Gudrun Koch ◽  
Daniel Heintel ◽  
Kathrin Strasser-Weippl ◽  
Katrin Frischmuth ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
Prognostic Significance ◽  
Serum Levels ◽  
Interferon Γ ◽  
Serum Samples ◽  
Myeloma Cells ◽  
Autocrine Loop ◽  
Protein Levels

Abstract Background and Aims: Monokine-induced by interferon-γ (MIG) is a chemokine that is produced by monocytes and macrophages in response to interferon-γ and acts as a chemoattractant mainly to T-lymphocytes in inflammatory processes. MIG has also been suggested to act in an autocrine loop to stimulate tumour cells through its receptor CXCR3, which is known to be expressed in myeloma cells. However, it is presently unclear if MIG is of biologic significance in myeloma in vivo. We have recently shown that multiple myeloma oncogene 1 (MUM1) expression in myeloma cells correlates with prognosis in this disease (Heintel D et al., ASH 2005), and MUM1 was found to upregulate MIG gene expression in B cell malignancies (Uranishi M et al., Leukemia 2005). This led us to evaluate the potential prognostic significance of MIG serum levels in a series of well characterized myeloma patients. Methods: 105 newly diagnosed multiple myeloma patients (median age 69.3 years, range 39.4–90.5) were enrolled. 18 patients presented with Durie/Salmon stage I disease, 9 had stage II and 78 had stage III. MIG serum levels were determined by a commercially available ELISA (R&D Systems). Serum samples from 17 MGUS patients and 37 age-matched healthy volunteers were used as controls. Results: MIG serum levels were elevated in multiple myeloma patients (median 161.3 pg/ml, range 9.37–1966.0) compared to MGUS patients (median 92.7 pg/ml, range 6.29–1303.1) and healthy controls (median 106.2 pg/ml, range 51.0–390.6). For analysis of myeloma cases, a cut-off level for MIG of 200pg/ml (=95th percentile of MIG in controls) was chosen to identify low and high MIG expressers. Using the cut-off as defined above, 63 patients with low MIG serum levels and 42 high MIG expressers were identified in a population of 105 myeloma patients. MIG serum levels in myeloma patients showed strong correlations with several markers of tumour load including low albumin and high β2-microglobulin. Interestingly, no correlation was found with C-reactive protein levels, indicating that MIG is not associated with an inflammatory response in myeloma. Median survival was significantly shorter in patients with high MIG serum levels compared to patients with low MIG expression (median not reached vs. 17.0 months, p&lt;0.001; see figure). Conclusions: MIG serum levels correlate with markers of disease burden in myeloma and high MIG levels are associated with a poor outcome in this disease. Overall Survival: low vs. high MIG serum levels Overall Survival: low vs. high MIG serum levels

A Functional Promoter Polymorphism (−8C>G) of the Proteasome Subunit α6 Gene Is Associated with Multiple Myeloma and Poor Outcome Independent of Circulating Proteasome Serum Levels.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 1668-1668
Author(s):  
Hagen S Bachmann ◽  
Juergen Novotny ◽  
Stephan Sixt ◽  
Peter Liebisch ◽  
Ulrich Frey ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Prognostic Factor ◽  
Genetic Model ◽  
University Hospital ◽  
20S Proteasome ◽  
Genotype Distribution ◽  
Healthy Controls ◽  
Α Subunit ◽  
Dominant Genetic Model

Abstract Introduction: The proteasome system plays a crucial role in several malignant diseases, especially in multiple myeloma (MM). Recently, the serum 20S circulating proteasome level (CPL) was shown to be an independent prognostic factor in MM. A single nucleotide polymorphism (SNP) −8C&gt;G in PSMA6, one of seven α-subunit genes of the 20S proteasome, was currently demonstrated to be associated with myocardial infarction. Additionally, it has been shown that PSMA6 expression is genotype-dependently altered e.g. in human B cells, whereas the G allele is associated with a 1.8 fold higher expression. Demonstrating the extensive role of the proteasome system in MM we investigated the role of the novel SNP in our cohort of 116 patients with MM. Methods: DNA-samples of 116 patients with MM, all treated at the University Hospital Essen, and 125 healthy controls were genotyped for PSMA6 −8C&gt;G. CPL of 70 patients were studied by an anti-20S proteasome enzyme-linked immunoabsorbant assay (ELISA). PSMA6 −8C&gt;G genotypes were correlated with patients’ survival and CPL. Results: Patients’ genotype distribution (69 CC, 44 CG, 3 GG) and genotype distribution of healthy controls (90 CC, 31 CG, 4 GG) were consistent with Hardy-Weinberg equilibrium. Genotypes were significantly associated with MM in a dominant genetic model (CC vs. CG+GG), with an odds ratio of 1.75 (95% confidence interval (CI): 1.02–3.00, p=0.043). Kaplan-Meier curves revealed a significant association of PSMA6 −8C&gt;G with 5-year survival (p=0.014). Median survival time was 43 months for the GG genotype and 50 months for the CG genotype. It was not reached within follow-up by the CC genotype (CC 5-year survival rate 61.2%). Following hazard ratios (HR) were calculated: CC vs. CG: 2.007, 95%CI 1.11–3.63, p=0.022; CC vs. GG: 2.515, 95%CI 0.58–10.86, p=0.217 and in the dominant genetic model CC vs. CG+GG: 2.038, 95%CI 1.14–3.65, p=0.017. In multivariate analysis the GG/GC genotypes were independent prognostic factors (HR 2.1, p=0.014). To proove if the detected effect of individual PSMA6 genotypes was dependent or independent from CPL, ELISA experiments were performed. There was no detectable difference in CPL between the genotypes. Mean CPL was 255 ng/mL for CC homozygous and 205 ng/mL for G allele carriers (p=0.718). Conclusions: These results suggest the PSMA6 −8C&gt;A polymorphism as a survival prognosticator as well as indicator of a high risk group within patients with MM. PSMA6 genotypes were not associated with CPL. Therefore, the SNP is independent of this known prognostic factor and could lead to additional prognostic information for MM patients.

Long-Term Outcomes of Autologous Transplantation in Multiple Myeloma: Prognostic Significance of Complete Response.

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 3126-3126
Author(s):  
Marta Krejci ◽  
Roman Hajek ◽  
Zdenek Adam ◽  
Ludek Pour ◽  
Lenka Zahradova ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Prognostic Significance ◽  
Progression Free Survival ◽  
Complete Response ◽  
Advisory Committees ◽  
Term Survival ◽  
Free Survival ◽  
Different Response

Abstract Abstract 3126 Background: Autologous stem cell transplantation (ASCT) after high-dose melphalan 200mg/m2 has got an important role in the treatment of symptomatic multiple myeloma (MM). The prognostic significance of achieving complete response (CR) after ASCT was cause of great debate for a long time. Some studies have shown the strong prognostic significance of achieving CR in MM, but other studies have failed to correlation between strength of the response and outcome. Aim: In this report we describe the long-term outcome of cohort 232 MM patients (pts) after ASCT with aim to establish the actual prognosis for the different response categories and to analyse other factors that might predict for long-term survival. Methods: We evaluated 232 pts with newly diagnosed symptomatic MM who received ASCT as a part of the first-line treatment between 1995 and 2005, median follow-up from ASCT was 131 months (range 61–195). Results: Following ASCT, overall response rate was 90% (202/232), 23% (52/232) of pts were in complete remission (CR), very good partial response (VGPR) was achieved in 45% of pts (100/232), partial response (PR) in 22% of pts (50/232), minimal response (MR) or stable disease (SD) in 10% of pts (22/232). Median progression-free survival (PFS) and overall survival (OS) from ASCT were 30.8 and 71.9 months, respectively. Progression-free survival at 12 years after ASCT in different response categories was 41% for pts with CR, 11% for pts with VGPR and 10% for pts with PR. Overall survival at 12 years after ASCT was 51% for pts with CR, 22% for pts with VGPR and 20% for pts with PR. The achievement of CR after ASCT was independent factor for long-term survival, significance differences in OS and PFS were found between CR and non-CR groups (P under 0.001 and P under 0.001, respectively). On multivariate analysis, the other factors associated with significantly better OS were ISS stage under III (P = 0.002), no presence of renal impairment (P = 0.008), age under 60 years (P = 0.001), no presence of deletion 1q21 (P = 0.029) and lenalidomide treatment in the post-transplant relapse (P = 0.002). Conclusion: The achievement of complete response after ASCT in multiple myeloma is the most important prognostic factor, even after long-term follow-up. The relapse rate is low in patients who remained in CR after 12 years from ASCT. A long-term complete remission should be a goal of treatment. Disclosures: Hajek: Merck: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen Cilag: Honoraria.

scholarly journals [F-18] FDG-PET/CT parameters as predictors of outcome in inoperable NSCLC patients

2015 ◽  
Vol 49 (4) ◽  
pp. 320-326 ◽  
Author(s):  
Antonio Nappi ◽  
Rosj Gallicchio ◽  
Vittorio Simeon ◽  
Anna Nardelli ◽  
Alessandra Pelagalli ◽  
...  
Keyword(s):  
Fdg Pet ◽  
Prognostic Significance ◽  
Standardized Uptake Value ◽  
Progression Free Survival ◽  
Rank Test ◽  
Metabolic Tumour Volume ◽  
Nodal Involvement ◽  
Pet Ct ◽  
Fdg Pet Ct ◽  
Nsclc Patients

Abstract Background. We evaluated the prognostic significance of standardized uptake value (SUVmax), metabolic tumour volume (MTV), and total lesion glycolysis (TLG) in [F-18] FDG PET/CT findings in patients with inoperable non-small-cell lung cancer (NSCLC). Patients and methods. One hundred and three patients (mean age, 65.6 ± 16 years) underwent [F-18] FDG PET/CT before the chemotherapy. The SUVmax value, the MTV (cm3; 42% threshold) and the TLG (g) were registered. The patients were followed up to 18 months thereafter (range 12-55 months). Failure to respond without progression, progression and/or disease-related death constituted surrogate end-points. The optimal SUVmax, MTV and TLG cut-off to predict the patients’ outcome were estimated. PET/CT results were then related to disease outcome (progression free survival; PFS). Results. The Kaplan-Meier survival analysis for SUVmax showed a significant shorter PFS in patients presenting with lower values as compared to those with higher (p < 0.05, log-rank test). MTV and TLG were not suitable for predicting PFS apart from the subset of patients with mediastinal nodal involvement. Conclusions. Despite the availability of new tools for the quantitative assessment of disease activity on PET/CT, the SUVmax rather than MTV and TLG remains the only predictor for PFS in NSCLC patients. MTV holds a value only when concomitant nodal involvement occurs.

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