The Bone Resorption Marker Serum-ICTP and the Circulating Proteasome Levels Separate ISS-Stages 1–3 and Are the Most Powerful Prognostic Factors for Overall Survival in Newly Diagnosed Symptomatic Multiple Myeloma.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 1475-1475
Author(s):  
Christian Jakob ◽  
Peter Liebisch ◽  
Karl Egerer ◽  
Jan Sterz ◽  
Martin Kaiser ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
Prognostic Factors ◽  
Bone Resorption ◽  
Hazard Ratio ◽  
Bone Resorption Marker ◽  
Type I ◽  
Newly Diagnosed ◽  
Normal Value ◽  
Cox Regression Analysis

Abstract Prognostic markers are important to identify high-risk patients in Multiple Myeloma (MM). Several prognostic models have been published, including parameters of tumor burden and cytogenetics. Recently the International Staging System (ISS) for Multiple Myeloma, which includes beta2-microglobulin (beta2-MG) and albumin, has been introduced for newly diagnosed patients with symptomatic MM. We previously reported about the prognostic significance of circulating proteasome levels (cProteasomes) in MM patients (Jakob et al., Blood 2007). In the present study we investigated the prognostic relevance of the bone resorption marker carboxy-terminal telopeptide of type-I collagen (ICTP) and cProteasome levels in comparison to the classical prognostic factors (beta2-MG), albumin, deletion 13q14 and type of chemotherapy (high-dose-therapy versus conventional dose chemotherapy) in 92 patients with newly diagnosed active MM. ICTP and cProteasome were significantly elevated parallel to ISS stages (P<0.001). ICTP (cut off: normal value), cProteasome levels (cut off: median value) and a combined ICTP-cProteasome score (1: ICTP < normal value and cProteasome < median; 2: one of both parameters elevated; 3: both parameters elevated) were significant univariate prognostic factors for overall survival in active MM (P<0.001, P=0.002 and P<0.001, respectively). Survival rates at 5-yrs were 95%, 66% and 27% in the groups of patients with ICTP-cProteasome score 1, 2 and 3, respectively. In a further analysis ICTP alone and the combined ICTP-cProteasome score significantly separated each of the three ISS stages into two distinct groups with a better versus worse prognosis. In a multivariate Cox regression analysis, including beta2-MG, albumin, deletion 13q14, type of chemotherapy, cProteasome levels and ICTP, ICTP was the parameter with the strongest prognostic power (P<0.001, hazard-ratio: 7.9) and cProteasomes (P=0.011, hazard-ratio: 3). Our study underlines that the activity of myeloma bone disease, as reflected by the collagen-I degradation product ICTP, has a major impact on the prognosis of symptomatic MM. This result is in line with published data showing a positive feedback between myeloma cells and osteoclasts, i.e. a vicious cycle. The inclusion of the bone resorption marker ICTP and cProteasome levels into multivariate models add substantial prognostic information on overall survival in newly diagnosed active MM.

Prognostic Value of Syndecan-1 in Multiple Myeloma and its Relationship with Other Prognostic Factors.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 2402-2402 ◽  
Author(s):  
Shaji Kumar ◽  
Emily Blood ◽  
Martin M. Oken ◽  
Philip R. Greipp
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
Prognostic Factors ◽  
Bone Disease ◽  
Prognostic Value ◽  
Progression Free Survival ◽  
Type I ◽  
Newly Diagnosed ◽  
Clinical Markers ◽  
Free Survival

Abstract Background: Syndecan-1 (CD138) is a heparan sulfate bearing proteoglycan found on various epithelial cells as well as on B lineage cells depending on its stage of development. Syndecan-1 (CD138) is abundantly expressed by plasma cells, especially myeloma cells. The extra cellular domain along with the heparan sulfate side chains can be cleaved off the cell surface and can be detected in the serum as soluble syndecan. Syndecan possibly plays a multifunctional role in the biology of myeloma. It has been shown to be an independent prognostic factor in patients with multiple myeloma. It has also been shown to promote myeloma cell growth through different mechanisms. Its expression has also been suggested to correlate with bone disease in MM. Methods: In this study we studied serum levels of soluble syndecan in newly diagnosed MM patients enrolled in the Eastern Cooperative Oncology Group (ECOG) E9486 and its associated correlative laboratory clinical trial E9487. We evaluated the prognostic value of syndecan in MM and its relationship to other known prognostic factors for this disease. In addition, syndecan levels were correlated with clinical and laboratory markers of bone disease. Results: A total of 501 patients were studied and the median serum syndecan-1 was 158 ng/mL. Syndecan levels correlated positively with other prognostic factors and markers of tumor burden such as β2-microglobulin (correlation coefficient 0.3; P <0.00001), labeling index (0.25; <0.0001), creatinine (0.23; <0.0001), soluble IL6 receptor (0.3; <0.0001), BM plasma cell percentage (0.16; <0.0006), and disease stage (P=0.0007). Significant differences in the overall and progression free survival was found between two groups of patient separated using the median value as cut-off. The High syndecan group had a median overall survival of 36.3 months compared to 49.3 months for the low syndecan group (P < 0.0001). Similarly, the high syndecan group had progression free survival of 25.4 months compared to 33.5 months for the low syndecan group (P < 0.0001). In a proportional hazards model including syndecan-1 as well as labeling index, β2M, Platelet count, IL-6R, syndecan-1 retained its prognostic value for overall survival (HR 1.3, P = 0.021). Syndecan levels were correlated with various bone markers including C-terminal telopeptide of type I collagen (ICTP), osteocalcin (OC), C-terminal type I procollagen (PICP), bone-specific alkaline phosphatase (BAP), and tartrate resistant alkaline phosphatase (TRAP) and were found to correlate only with ICTP (0.25, P < 0.0001). No correlation was found between clinical markers of bone disease including presence of lytic lesions, osteoporosis and pathologic fractures on X-rays or bone pain. Conclusion: In this large study, we once again confirm the prognostic value of serum syndecan-1 levels in large group of patients with newly diagnosed myeloma. Syndecan-1 level correlates with other disease markers. Syndecan levels also correlated with ICTP, a marker of bone turnover, though no strong correlation was found between syndecan levels and clinical markers of myeloma bone disease. The biological basis of these finding needs further evaluation.

TIMP-1 and TIMP-2 Levels Are Directly Correlated with Neoangiogenesis and Are Prognostic Factors in Multiple Myeloma Patients.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 4866-4866
Author(s):  
Luciana Correa Oliveira de Oliveira ◽  
Juliana Alves Uzuelli ◽  
Ana Paula Alencar de Lima Lange ◽  
Barbara Amelia Aparecida Santana-Lemos ◽  
Marcia Sueli Baggio ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Overall Survival ◽  
Prognostic Factors ◽  
Bone Disease ◽  
Cox Regression ◽  
Conflicts Of Interest ◽  
Newly Diagnosed ◽  
Significant Difference ◽  
The Impact

Abstract Abstract 4866 Background Multiple myeloma (MM) is an incurable malignant disease, characterized by increased angiogenesis in the bone marrow (BM) microenvironment and aberrant BM metabolism. Matrix metalloproteinases (MMP) are a family of zinc-dependent endopeptidases implicated in tumour progression, invasion, metastasis and angiogenesis, via proteolytic degradation of extracellular matrix. MMPs are inhibited by tissue inhibitors of metalloproteinase (TIMP). Although recent studies have implicated MMP 9 in MM bone disease, little is known about the role of the TIMPs. Objectives a) to compare levels of sRANKL, OPG, MMP-2, MMP-9, TIMP-1, TIMP-2, VEGF, bFGF, microvessel density (MVD) between newly diagnosed MM patients and healthy controls; b) to determine the association of these molecules with disease progression, bone disease and neoangiogenesis and c) to evaluate the impact of these variables on survival. Patients and Methods As of July 2009 38 newly diagnosed and untreated multiple myeloma patients were enrolled in the study. The median age was 61years-old (range 39-91) with 24 (63%) males. Patients were diagnosed and categorized according The International Myeloma Working Group criteria and ISS, respectively. Bone involvement was graded according to standard X-ray: patients with no lesions, or with one/ two bones involved or diffuse osteoporosis were classified as low score, whereas patients with lesions in more than two bones or presence of bone fracture were classified as high score. MMP-2 and MMP-9 were determined by PAGE gelatin zymography from plasma as previously described. MMP-9, TIMP-1 and TIMP-2, OPG and sRANKL concentrations were measured by ELISA. The levels of VEGF, bFGF were obtained using cytometric bead array. Ten healthy volunteers were used as controls. Bone marrow MVD measured in hotspots was evaluated in 26 out of 38 patients at diagnosis and 15 patients with Hodgkin Lymphoma stage IA and IIA (used as controls) by staining immunohistochemically for CD34. Comparisons among groups were analyzed by ANOVA and the correlation by the Spearman's correlation coefficient. Cox regression were performed for overall survival (OS) analysis. Results Patients with MM had elevated TIMP-1, TIMP-2 and OPG values compared with controls. No significant difference was found between plasma sRANKL, pro-MMP2, pro-MMP9 and MMP-9 levels. We found that plasma TIMP-1 levels correlated positively with bFGF, VEGF, MVD, beta-2 microglobulin (B2M) and OPG (r: 0.514, p=0,001, r: 0.350, p=0,031; r: 0.610, p<0.0001; r: 0.760, p<0.0001 and r: 0.701, p<0.0001, respectively) and TIMP-2 levels with bFGF, DMV, B2M and OPG (r: 0.512, p=0.002; r: 0.595, p<0.0001; r: 0.587, p<0.0001 and r: 0.552, p<0.0001, respectively). TIMP-1 and TIMP-2 levels correlated with the ISS stage (p<0.0001, p=0.006, respectively). The only variables that correlated with clinical bone disease staging were hemoglobin, B2M and albumin levels, whereas TIMP-1, TIMP-2, bFGF, VEGF and OPG correlated with DMV. On the univariate analyses, age, gender, proMMP2, TIMP-1, TIMP-2, creatinine, B2M and MVD were significantly associated with overall survival. In Cox regression model, TIMP-1, TIMP-2 and B2M levels remained to be significantly associated with OS. In conclusion, our results suggest that TIMP-1 and TIMP-2 levels are strongly associated with neoangiogenesis and are independent prognostic factors in MM. Disclosures No relevant conflicts of interest to declare.

Front-line daratumumab-VTd versus standard-of-care in ASCT-eligible multiple myeloma: matching-adjusted indirect comparison

Immunotherapy ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 143-154
Author(s):  
Philippe Moreau ◽  
Benjamin Hebraud ◽  
Thierry Facon ◽  
Xavier Leleu ◽  
Cyrille Hulin ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
Indirect Comparison ◽  
Standard Of Care ◽  
Hazard Ratio ◽  
Newly Diagnosed ◽  
Front Line ◽  
Adjusted Indirect Comparison ◽  
Matching Adjustment

Aim: To compare daratumumab plus standard-of-care (SoC; bortezomib/thalidomide/dexamethasone [VTd]) and VTd alone with other SoC for transplant-eligible newly diagnosed multiple myeloma. Patients & methods: We conducted an unanchored matching-adjusted indirect comparison of progression-free and overall survival (PFS/OS) with D-VTd/VTd versus bortezomib/lenalidomide/dexamethasone (VRd), bortezomib/cyclophosphamide/dexamethasone (VCd) and bortezomib/dexamethasone (Vd). Results: After matching adjustment, significant improvements in PFS were estimated for D-VTd versus VRd (hazard ratio [HR]: 0.47 [95% CI: 0.33–0.69]), VCd (HR: 0.35 [95% CI: 0.21–0.58]) and Vd (HR: 0.42 [95% CI: 0.28–0.63]). OS was significantly longer with D-VTd versus VRd (HR: 0.31 [95% CI: 0.16–0.57]), VCd (HR: 0.35 [95% CI: 0.14–0.86]) and Vd (HR: 0.38 [95% CI: 0.18–0.77]). No significant PFS/OS differences were seen for VTd versus other SoC. Conclusion: This analysis supports front-line daratumumab for transplant-eligible newly diagnosed multiple myeloma.

Superior Rate of Complete Response with up-Front Velcade-Thalidomide-Dexamethasone Versus Thalidomide-Dexamethasone in Newly Diagnosed Multiple Myeloma Is Not Affected by Adverse Prognostic Factors, Including High-Risk Cytogenetic Abnormalities.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 1662-1662
Author(s):  
Michele Cavo ◽  
Nicoletta Testoni ◽  
Carolina Terragna ◽  
Giulia Marzocchi ◽  
Sandra Durante ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Multivariate Analysis ◽  
Prognostic Factors ◽  
High Risk ◽  
Light Chain ◽  
Complete Response ◽  
Phase Iii ◽  
Newly Diagnosed ◽  
Cox Regression Analysis

Abstract Complete response (CR) is an important objective of autologous stem-cell transplantation (ASCT) in multiple myeloma (MM). In comparison with conventional induction treatments, newer combinations of novel agents may effect increased rates of CR and near CR (nCR), a benefit potentially translating into even higher frequencies of CR/nCR after ASCT and improved clinical outcome. We designed a phase III study to detect an increase in CR+nCR rates from 10–15% with conventional Thalidomide-Dexamethasone (TD) to 20–30% with Velcade added to TD (VTD) in newly diagnosed MM. Both TD and VTD were given as three 21-day cycles in preparation for double ASCT. In the present analysis, CR+nCR rates by the two induction treatments were examined in relationship to baseline prognostic variables in 399 evaluable pts aged ≤65 years, of whom 199 randomized to VTD and 200 to TD. All analyses were intent to treat. In comparison with TD, VTD effected higher rates of CR+nCR (12% vs 33%, P&lt;0.001) and of ≥very good partial response (VGPR) (30% vs 61%, P&lt;0.001). By univariate analysis, superiority of VTD to TD was maintained across all sub-group analyses according to standard prognostic factors, including β2-m, albumin, stage (ISS), Hb, PLTs, bone marrow PC, M protein isotype, LDH, CRP. In particular, the rates of CR+nCR with VTD vs TD in pts with standard poor prognostic factors were as follows: ISS stage 3 (23.5% vs 6%, P=0.03), Hb&lt;10 g/dL (24% vs 4%, P=0.002), PLTs&lt;150.000/μL (35% vs 4%, P=0.009), bone marrow PC ≥50% (31% vs 13%, P&lt;0.001), IgA isotype (63% vs 15%, P&lt;0.001), LDH &gt;190 U/L (33% vs 9%, P&lt;0.001), CRP ≥8 mg/L (29% vs 10%, P=0.004). We next examined CR+nCRs by treatment arms in relationship to cytogenetics (FISH data available in 93% to 99% of all pts). Superior CR+nCR rates were effected by VTD vs TD in the presence of high-risk cytogenetics, including del(13) (39% vs 10%, P&lt;0.001), t(4;14) (39.5% vs 10%, P=0.002), combined t(4;14) and del(13) (32% vs 0%, P=0.001), and del(17p) (28.5% vs 0%, P=0.03). Remarkably, when examined in the context of the VTD arm, high-quality response rates were significantly higher for pts carrying del(13) and t(4;14) vs those who lacked these abnormalities [del(13): CR+nCR:39% vs 24%, P=0.03; ≥VGPR: 71% vs 48%, P=0.001] [t(4;14): ≥VGPR:79% vs 55%, P=0.007)]. An opposite trend was noted for pts in the TD arm, whose probability to attain ≥VGPR was adversely affected by the presence of del(13) (P=0.07) and del(17p) (P=0.03). Variables associated with achievement of CR+nCR in the two arms that retained statistical significance when assessed by multivariate Cox regression analysis included randomization to VTD (P&lt;0.001), light chain only subtype (P&lt;0.001), IgA isotype (P&lt;0.001) and Hb&gt;10 g/dL (P=0.01). In the VTD arm, a positive correlation was observed with del(13) (P=0.006) and t(4;14) (P=0.02). Response to first ASCT with melphalan 200 mg/m2 could be evaluated in 297 pts, of whom 145 randomized to VTD and 152 to TD. Randomization to VTD was closely associated with increased CR+nCR rates (54% vs 29% with TD, P&lt;0.001) and remained statistically significant (P&lt;0.001) also in the multivariate analysis. Additional factors predicting for superior post-ASCT CR+nCR rates in the multivariate setting included light chain only subtype (P&lt;0.001) and IgA isotype (P=0.005). We conclude that randomization to up-front VTD was the strongest and independent factor associated with increased rates of CR+nCR before ASCT. Superiority of VTD to TD pertained in both low-risk and high-risk sub-groups, including the traditionally unfavorable sub-groups carrying del(13), t(4,14) and del(17p). Remarkably, in the VTD arm improved postinduction CR+nCR rates were significantly associated with the presence of del(13) and t(4;14) in the multivariate analysis. Benefit from VTD vs TD as primary induction therapy translated into significantly improved CR+nCR rates after the first ASCT and remained statistically significant when assessed by multivariate analysis.

Prognostic Value of Bone Marrow Angiogenesis in Newly Diagnosed Multiple Myeloma: A Comparison with Conventional Prognostic Factors.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 5111-5111
Author(s):  
Shaji Kumar ◽  
Jessica L. Haug ◽  
Linda Wellik ◽  
Thomas E. Witzig ◽  
John A. Lust ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Overall Survival ◽  
Multivariate Analysis ◽  
Prognostic Factors ◽  
Prognostic Value ◽  
Staging System ◽  
Continuous Variable ◽  
Newly Diagnosed ◽  
Grade Group

Abstract Background: Abnormally increased tumor associated neovasculature plays an important role in tumor progression in solid tumors and hematological malignancies. In multiple myeloma (MM) bone marrow angiogenesis, measured in terms of microvessel density (MVD), has prognostic value, and appear to increase with disease progression from monoclonal gammopathy of undetermined significance to relapsed MM. We have shown that MVD has prognostic value in patients with newly diagnosed MM including patients undergoing upfront high dose therapy and stem cell transplantation, but comparison with other known prognostic factors has been limited by sample size. It is also not known whether the MVD adds prognostic value once the recently described International Staging System (ISS) is applied. The goal of this study was to determine the prognostic effect of bone marrow MVD in newly diagnosed MM relative to the ISS and other known prognostic factors. Methods: We studied 400 patients with newly diagnosed MM seen at the Mayo Clinic between March of 1988 and December 2001. Sections from bone marrow biopsy blocks from the time of initial diagnosis were studied by immunohistochemistry using antibodies against CD34 antigen to high light the endothelial cells. Under low power (100X); three areas with maximum number of microvessels (hotspots) were identified. Each of these areas was further studied at 400X magnification and the number of microvessels per high power field counted. The average of the three readings was taken as the MVD for the sample. In addition, the samples were graded as low, intermediate or high by using a visual estimate as previously described. Additional clinical data was extracted from medical records. Some of the patients have been included in previous studies related to angiogenesis. Results: A total of 400 patients in whom a bone marrow biopsy from within 30 days of diagnosis was available were studied. The pts were followed for a median of 37 months (Range: 1 month to 16.5 years) and 318 pts (80%) had died at the time of this analysis. The median MVD for the entire group was 14.7 (Range 0–168). The median overall survival for the three groups according to the MVD grade was lower for the high grade group (31.9 months) compared to the intermediate grade group (37.2 months) and the low grade group (not reached); P &lt;0.029, log rank test. We examined this group of patients for other factors prognostic for overall survival. Factors significant on univariate analysis included ISS stage, platelet count (&lt;150 vs. &gt;= 150 X 106/L), and plasma cell labeling index (&lt;1 vs &gt;=1). In a multivariate analysis using these variables and MVD as a continuous variable, high MVD and the ISS staging system were significantly associated with poorer survival (Table). Conclusion: In this large group of pts with newly diagnosed MM, we confirm the prognostic value of increased bone marrow angiogenesis. We examined the MVD as a continuous variable in the multivariate analysis for a closer evaluation of this measure in this comparison. More importantly, the prognostic value appears to be independent of the ISS and other major prognostic factors. The resultsof this study reinforces the biological relevance of this finding in MM. HR 95% CI P value MVD 1.006 (1.001, 1.011) 0.0279 ISS Stage I 0.37 (0.25, 0.56) &lt;0.001 ISS Stage II 0.58 (0.41, 0.83) 0.0025

scholarly journals Development of a Medicare Health Outcomes Survey Deficit-Accumulation Frailty Index and Its Application to Older Patients With Newly Diagnosed Multiple Myeloma

2018 ◽  
pp. 1-13 ◽  
Author(s):  
Hira S. Mian ◽  
Tanya M. Wildes ◽  
Mark A. Fiala
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
Standard Deviation ◽  
Health Outcomes ◽  
Older Patients ◽  
Frailty Index ◽  
Hazard Ratio ◽  
Newly Diagnosed ◽  
Increased Risk ◽  
The Mean

Purpose To develop a frailty index using the Rockwood Accumulation of Deficits approach for the Medicare Health Outcomes Survey (MHOS) and apply it in a subset of older patients with newly diagnosed multiple myeloma. Methods Data from 2,692,361 patients without cancer, > 66 years of age, in SEER-MHOS linked databases between 1998 and 2009 were analyzed. A frailty index was constructed, resulting in a 25-item scale; cutoff values were created for individuals classified as frail. This frailty index was then applied to 305 patients with newly diagnosed myeloma in the database to predict overall survival. Results In the derivation cohort of patients without cancer, the median age was 74 years and the mean frailty index was 0.23 (standard deviation, 0.17). Among patients without cancer, each 10% increase in frailty index (approximately three to four more deficits) was associated with a 40% increased risk for death (adjusted hazard ratio, 1.397; 95% CI, 1.396 to 1.399; P < .001). In the cohort of patients with newly diagnosed myeloma, the median age was 76 years and the mean frailty index was 0.28 (standard deviation, 0.17). Each 10% increase in frailty index was associated with a 16% increased risk for death (adjusted hazard ratio, 1.159; 95% CI, 1.080 to 1.244; P < .001). Fifty-three percent of patients with multiple myeloma were considered frail. The estimated median overall survival of patients considered frail was 26.8 months, compared with 43.7 months ( P = .015) for those who were not. Conclusion The MHOS-based frailty index was prognostic for patients with multiple myeloma in predicting overall survival.

Incorporation of the Bone Marker Carboxy-Terminal Telopeptide of Type-1 Collagen (ICTP) into a Combined ISS-ICTP Score Improves the Prognostic Significance of the ISS in Newly Diagnosed Symptomatic Multiple Myeloma and Identifies a Very Low Risk Group Which Has No Benefit from High-Dose Therapy

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 2721-2721
Author(s):  
Christian Jakob ◽  
Peter Liebisch ◽  
Ulrike Heider ◽  
Martin Kaiser ◽  
Jan Sterz ◽  
...  
Keyword(s):  
Overall Survival ◽  
Prognostic Factor ◽  
Bone Resorption ◽  
Risk Group ◽  
Risk Groups ◽  
Low Risk ◽  
High Dose ◽  
Bone Resorption Marker ◽  
Newly Diagnosed ◽  
Reference Limit

Abstract The prognosis of patients with newly diagnosed symptomatic multiple myeloma (MM) has been improved, but the outcome is still highly variable. Several prognostic markers, including parameters of tumor burden and cytogenetics were adopted to identify high-risk patients. Recently the International Staging System (ISS), including the parameters β2-microglobulin (β2M) and albumin, was introduced for patients with symptomatic MM. In previous studies the bone resorption marker carboxy-terminal telopeptide of type-1 collagen (ICTP) was identified as a sensitive and specific marker of increased bone resorption and as a strong prognostic factor for overall survival (OS) in MM. Since bone disease is a hallmark of MM, we investigated the prognostic impact of the bone resorption marker ICTP in combination with ISS, β2M, albumin and deletion of chromosome 13 (del(13q14)) and high-dose therapy (HDT) in 100 patients with newly diagnosed symptomatic MM. β2M alone, albumin alone, ISS, del(13q14) and ICTP were significant prognostic factors for overall survival. In contrast to ICTP, lytic bone lesions were not an independent prognostic factor for OS (P=0.289). In a multivariate analysis, ICTP was the most powerful prognostic factor (log rank P&lt;0.001, hazard-ratio: 9-fold increase). Furthermore ICTP clearly separated two subgroups with a good and a worse prognosis within each of the three ISS stages (ISS I: P=0.027, ISS II: P=0.022, ISS III: P=0.013). A combined ISS-ICTP score, including β2M (cut off: 3.5 mg/l), albumin (cut off: &lt; 3.5 g/dl) and ICTP (cut off: reference limit) significantly (P&lt;0.001) separated four risk groups with a 5-year overall survival rate of 94% in the very low risk group, 65% in the low risk group, 46% in the intermediate risk group and 22% in the high risk group, respectively. In the very low risk group, there was no significant survival benefit with highdose therapy (P=0.24), while HDT was a favorable prognostic factor in ISS-ICTP risk groups 1–3 (P=0.037, P=0.011 and P=0.012) and in ISS stages I–III (P=0.026, P=0.001 and P=0.052). These data demonstrate that the inclusion of the bone resorption marker ICTP adds to the prognostic value of ISS and may have clinical implications for selection of HDT in frontline treatment strategies in newly diagnosed MM. Table: Comparison between ISS and combined ISS-ICTP score in newly diagnosed symptomatic MM. Combined ISS-ICTP Score ISS Risk factors† (group) Patients (%) 5-yr OS (%) Stage* Patients (%) 5-yr OS (%) 0 (very low) 21 94 1 (low) 38 64 I 38 72 2 (intermediate) 26 46 II 35 62 3 (high) 15 22 III 27 35 † risk factors: β2M ≥3.5 mg/l&#x2028; Albumin &lt;3.5 g/dl&#x2028; ICTP &gt;reference limit * ISS I:&#x2028; ISS II:&#x2028; ISS III: β2M &lt;3.5 mg/l,&#x2028; Albumin ≥3.5 g/dl&#x2028; not stage I or III&#x2028; β2M ≥5.5 mg/l

Prognostic nomogram to predict overall survival for patients with perihilar cholangiocarcinoma: A population-based study of SEER database (Preprint)

2020 ◽  
Author(s):  
Chendong Wang
Keyword(s):  
Overall Survival ◽  
Prognostic Factors ◽  
Staging System ◽  
Tnm Staging ◽  
Survival Outcome ◽  
Perihilar Cholangiocarcinoma ◽  
Cox Regression Analysis ◽  
Calibration Curves ◽  
Tnm Staging System ◽  
Net Benefits

BACKGROUND Perihilar cholangiocarcinoma (pCCA) is a highly aggressive malignancy with poor prognosis. Accurate prediction is of great significance for patients’ survival outcome. OBJECTIVE The present study aimed to propose a prognostic nomogram for predicting the overall survival (OS) for patients with pCCA. METHODS We conducted a retrospective analysis in a total of 940 patients enrolled from the Surveillance, Epidemiology, and End Results (SEER) program and developed a nomogram based on the prognostic factors identified from the cox regression analysis. Concordance index (C-index), risk group stratification and calibration curves were adopted to test the discrimination and calibration ability of the nomogram with bootstrap method. Decision curves were also plotted to evaluate net benefits in clinical use against TNM staging system. RESULTS On the basis of multivariate analysis, five independent prognostic factors including age, summary stage, surgery, chemotherapy, together with radiation were selected and entered into the nomogram model. The C-index of the model was significantly higher than TNM system in the training set (0.703 vs 0.572, P<0.001), which was also proved in the validation set (0.718 vs 0.588, P<0.001). The calibration curves for 1-, 2-, and 3-year OS probabilities exhibited good agreements between the nomogram-predicted and the actual observation. Decision curves displayed that the nomogram obtained more net benefits than TNM staging system in clinical context. The OS curves of two distinct risk groups stratified by nomogram-predicted survival outcome illustrated statistical difference. CONCLUSIONS We established and validated an easy-to-use prognostic nomogram, which can provide more accurate individualized prediction and assistance in decision making for pCCA patients.

scholarly journals Comparative survival analysis using the International Stratification Score (ISS) in newly-diagnosed multiple myeloma in the Uruguayan population

2021 ◽  
Author(s):  
David Israel Garrido ◽  
Virginia Bove ◽  
Victoria Matosas ◽  
Eloisa Riva
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
Latin America ◽  
Survival Analysis ◽  
Hematologic Malignancy ◽  
Staging System ◽  
Newly Diagnosed ◽  
Hematopoietic Stem ◽  
Survival Estimation ◽  
Real Practice

Background and aims. Multiple myeloma is a frequent hematologic malignancy, in which the International Stratification Score (ISS) is widely used to estimate the overall survival. However, there are no studies in Latin America evaluating its performance. This study aims to describe the ISS performance in the overall survival estimation for newly diagnosed multiple myeloma patients in Uruguay. Methods. This is a retrospective registry‐based survival analysis through the Grupo Uruguayo de Mieloma Múltiple (GUMMA) database, including newly diagnosed multiple myeloma patients from January 2001 until May 2019. Results. 249 patients were included, 51.81% males and an average age of 63.49 years. According to ISS and Durie-Salmon score (DSS), 47.79% and 82.3% were ISS III and DSS III, respectively. Also, 32.3% were DSS B. Auto hematopoietic stem cell transplantation was performed in 31.73% of patients, and bortezomib was used in 44.18% as frontline therapy. The overall survival was 80% for ISS1, 64.9% ISS2, and 48.6% ISS3 (Log-Rank; p <0.01). The average overall survival was 116.5 months for ISS 1, 77.6 months for ISS 2, and 57.8 months for ISS 3. The hazard ratio between ISS II and ISS I was 2.42 (95% CI 1.10-5.33; p<0.05), and 3.94 (95% CI 1.88-8.26; p<0.05) between ISS III and ISS II. Conclusion. The ISS staging system allows an adequate stratification of patients according to overall survival in the real-practice setting. However, considering the relevance of the new cytogenetic advances, it is necessary to increase the availability and quality of iFISH in Latin America.

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