The impact of prostate cancer (PC) margin extent (ME) at radical prostatectomy (RP) on biochemical relapse-free survival (bRFS).

2018 ◽  
Vol 36 (6_suppl) ◽  
pp. 83-83
Author(s):  
Steven Neema Seyedin ◽  
Sarah L Mott ◽  
Anthony N Snow ◽  
James Kyle Russo ◽  
John Watkins
Keyword(s):  
Risk Stratification ◽  
Multivariable Analysis ◽  
Surgical Margin ◽  
Recurrence Risk ◽  
Disease Recurrence ◽  
Accurate Estimation ◽  
Clinicopathologic Factor ◽  
Pathology Reports ◽  
The Impact

83 Background: Surgical margin involvement (M+) by PC at RP is associated with suboptimal bRFS; however, the interaction of M+ with coincident high-risk clinicopathologic and treatment factors obscures accurate estimation of recurrence risk. The objective of this study is to determine whether ME permits risk stratification. Methods: Retrospective analysis of clinicopathologic factor association with bRFS. Eligible patients underwent RP alone for clinically localized PC. Patients with metastatic disease, PSA > 30 at diagnosis, pathologic involvement of seminal vesicles or lymph nodes at RP, insufficient follow-up, or receipt of pre-RP or adjuvant therapy were excluded. Slides from RP specimens with close or positive margins were re-reviewed by study pathologists blinded to outcome. Results: From 2002-2010, 667 patients were eligible for analysis. The median age was 61 yrs (range, 43-76), and all had cT1-2 disease (83% T1c), with median PSA 5.6 (0.9-28.0; 85% ≤10). Robot-assisted RP was employed in 141 cases (21%). Two hundred ten patients (31%) had M+, with single maximal ME 3mm (0.1-23), and cumulative ME 4mm (0.1-34). At median follow-up of 102 months (13-184), 149 patients (22%) had recurrence, with estimated 8-year bRFS rates of 85%/56% for M-/+ patients (p < 0.01). Multivariable analysis identified PSA, Gleason score (GS), extraprostatic extension, and M+ as associated with bRFS. Specific to patients with involved margins, the combination of ME and GS permitted recurrence risk stratification, with a low-risk subset identified (GS≤6 and ME < 3mm; Table). Conclusions: The current investigation suggests that GS6 patients with maximal or cumulative ME < 3mm appear to have favorable early 8-year bRFS following RP. GS6 patients with wider ME and GS ≥7 with any extent M+ appear to have suboptimal bRFS. RP pathology reports should include ME details, in order to more precisely estimate risk of subsequent disease recurrence. [Table: see text]

The Efficacy of Etoposide-Based Therapy in Adult Secondary Hemophagocytic Lymphohistiocytosis

2021 ◽  
pp. 1-9
Author(s):  
Leonard Naymagon ◽  
Douglas Tremblay ◽  
John Mascarenhas
Keyword(s):  
Hemophagocytic Lymphohistiocytosis ◽  
Proportional Hazards ◽  
Multivariable Analysis ◽  
Cox Proportional Hazards ◽  
Rank Test ◽  
Kaplan Meier ◽  
Hazard Ratios ◽  
Significant Difference ◽  
The Impact

Data supporting the use of etoposide-based therapy in hemophagocytic lymphohistiocytosis (HLH) arise largely from pediatric studies. There is a lack of comparable data among adult patients with secondary HLH. We conducted a retrospective study to assess the impact of etoposide-based therapy on outcomes in adult secondary HLH. The primary outcome was overall survival. The log-rank test was used to compare Kaplan-Meier distributions of time-to-event outcomes. Multivariable Cox proportional hazards modeling was used to estimate adjusted hazard ratios (HRs) with 95% confidence intervals (CIs). Ninety adults with secondary HLH seen between January 1, 2009, and January 6, 2020, were included. Forty-two patients (47%) received etoposide-based therapy, while 48 (53%) received treatment only for their inciting proinflammatory condition. Thirty-three patients in the etoposide group (72%) and 32 in the no-etoposide group (67%) died during follow-up. Median survival in the etoposide and no-etoposide groups was 1.04 and 1.39 months, respectively. There was no significant difference in survival between the etoposide and no-etoposide groups (log-rank <i>p</i> = 0.4146). On multivariable analysis, there was no association between treatment with etoposide and survival (HR for death with etoposide = 1.067, 95% CI: 0.633–1.799, <i>p</i> = 0.8084). Use of etoposide-based therapy was not associated with improvement in outcomes in this large cohort of adult secondary HLH patients.

scholarly journals Anastomotic Ulcers After Ileocolic Resection for Crohn’s Disease Are Common and Predict Recurrence

2019 ◽  
Vol 26 (7) ◽  
pp. 1050-1058 ◽  
Author(s):  
Robert P Hirten ◽  
Ryan C Ungaro ◽  
Daniel Castaneda ◽  
Sarah Lopatin ◽  
Bruce E Sands ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Multivariable Analysis ◽  
Disease Recurrence ◽  
Ileocolic Resection ◽  
Anastomotic Ulcer ◽  
Endoscopic Recurrence ◽  
Academic Center ◽  
Endoscopic Remission ◽  
The Impact

Abstract Background Crohn’s disease recurrence after ileocolic resection is common and graded with the Rutgeerts score. There is controversy whether anastomotic ulcers represent disease recurrence and should be included in the grading system. The aim of this study was to determine the impact of anastomotic ulcers on Crohn’s disease recurrence in patients with prior ileocolic resections. Secondary aims included defining the prevalence of anastomotic ulcers, risk factors for development, and their natural history. Methods We conducted a retrospective cohort study of patients undergoing an ileocolic resection between 2008 and 2017 at a large academic center, with a postoperative colonoscopy assessing the neoterminal ileum and ileocolic anastomosis. The primary outcome was disease recurrence defined as endoscopic recurrence (&gt;5 ulcers in the neoterminal ileum) or need for another ileocolic resection among patients with or without an anastomotic ulcer in endoscopic remission. Results One hundred eighty-two subjects with Crohn’s disease and an ileocolic resection were included. Anastomotic ulcers were present in 95 (52.2%) subjects. No factors were associated with anastomotic ulcer development. One hundred eleven patients were in endoscopic remission on the first postoperative colonoscopy. On multivariable analysis, anastomotic ulcers were associated with disease recurrence (adjusted hazard ratio [aHR] 3.64; 95% CI, 1.21–10.95; P = 0.02). Sixty-six subjects with anastomotic ulcers underwent a second colonoscopy, with 31 patients (79.5%) having persistent ulcers independent of medication escalation. Conclusion Anastomotic ulcers occur in over half of Crohn’s disease patients after ileocolic resection. No factors are associated with their development. They are associated with Crohn’s disease recurrence and are persistent.

scholarly journals Prognostic Significance of Tumor Response at the End of Therapy in Group III Rhabdomyosarcoma: A Report From the Children's Oncology Group

2009 ◽  
Vol 27 (22) ◽  
pp. 3705-3711 ◽  
Author(s):  
David A. Rodeberg ◽  
Julie A. Stoner ◽  
Andrea Hayes-Jordan ◽  
Simon C. Kao ◽  
Suzanne L. Wolden ◽  
...  
Keyword(s):  
Alternative Therapy ◽  
Prognostic Significance ◽  
Complete Response ◽  
Disease Recurrence ◽  
Radiographic Measurement ◽  
Clinical Group ◽  
Group Iii ◽  
Best Response ◽  
Pathology Reports ◽  
The Impact

Purpose Some patients with rhabdomyosarcoma (RMS) achieve less than a complete response (CR) despite receiving all planned therapy. We assessed the impact of best response at the completion of all therapy on patient outcome. Patients and Methods We studied 419 clinical group III participants who completed all protocol therapy without developing progressive disease for Intergroup Rhabdomyosarcoma Study (IRS) IV. Response (complete resolution [CR], partial response [PR; ≥ 50% decrease], or no response [NR; < 50% decrease and < 25% increase]) was determined by radiographic measurement and categorized by the best response. Results At the end of therapy, 341 participants (81%) achieved a best response of CR and 78 (19%) had a best response of PR/NR. Five-year failure-free survival was similar for participants achieving CR (80%) and PR/NR (78%). After adjustment for age, nodal status, primary site, and histology, there was no significant indication of lower risk of failure (hazard ratio [HR], 0.77; 95% CI, 0.46 to 1.27; P = .3) nor death (HR, 0.63; 95% CI, 0.36 to 1.09; P = .1) for CR versus PR/NR participants. Seventeen participants with a best response of PR/NR had surgical procedures; eight (50%) of 16 with available pathology reports had residual viable tumor and only three achieved a complete resection. Resection of residual masses was not associated with improved outcome. Conclusion CR status at the end of protocol therapy in clinical group III participants was not associated with a reduction of disease recurrence and death. Aggressive alternative therapy may not be warranted for RMS patients with a residual mass at the end of planned therapy.

scholarly journals Risk stratification and prognostic value of CMR in DCM; parametric mapping and GLS- value beyond EF and LGE?

2021 ◽  
Vol 22 (Supplement_1) ◽  
Author(s):  
P Brown ◽  
A Dimarco ◽  
J Bradley ◽  
G Nucifora ◽  
C Miller ◽  
...  
Keyword(s):  
Risk Stratification ◽  
Prognostic Value ◽  
Nyha Class ◽  
Univariate Analysis ◽  
Multivariable Analysis ◽  
Youden Index ◽  
Private Company ◽  
Parametric Mapping ◽  
Selection For

Abstract Funding Acknowledgements Type of funding sources: Private company. Main funding source(s): Dr Pamela Brown was suppoerted by funding from Alliance Medical. Background; Arrhythmia risk stratification and device implantation in dilated cardiomyopathy (DCM) poses significant challenges and as demonstrated by the DANISH trial appears to have reached the asymptote of clinical efficacy. A body of evidence now demonstrates that risk stratification of and device selection for DCM patients may be enhanced by inclusion of patients" LGE-status. Furthermore, it has been suggested that CMR based parametric mapping and strain analysis may further advance risk stratification. Methods; 703 patients with DCM undergoing clinically indicated CMR scans and prospectively enrolled into the UHSM-CMR study (NCT02326324) between 03/2015-12/2018 were analysed. Multivariable Cox proportional hazard models and Youden index driven C-statistics were used to assess additive prognostic value of GLS, T1 and ECV mapping on the combined endpoint of cardiovascular death, cardiac transplantation, LVAD  insertion  or hospitalisation for heart failure in models incorporating NHYA class, EF and LGE status. Additionally. the value of GLS, T1, and ECV on predicting significant arrhythmic events (SAV) (ventricular arrhythmia (VA), resuscitated cardiac arrest (rCA) or sudden cardiac death (SCD)) was assessed. Results; Patients (mean age 59, 66% male, 60% ≥NYHA II, mean EF 42%, mean GLS -12%, mean ECV 27%) were on good medical therapy (beta blocker 74%%, ACE 79%, MRA 38%, Entresto 5%, CRT 23%). Mean follow-up was 21 months; the combined endpoint occurred in 34 patients (5%). On univariate analysis NYHA class (HR 2.44 (1.67-3.57), p &lt; 0.001), ECV (HR 1.14 (1.05-1.22), p &lt; 0.001), GLS% (HR 1.14 (1.07-1.21) p &lt; 0.001,) T1 (HR 1.06 (1.005-1.1), p = 0.03), RVEF (HR 0.95 (0.93-0.98), p &lt; 0.001), LVEF (HR 0.92 (0.9-0.95), p &lt; 0.001) were all significantly associated with outcome. On multivariate analysis only EF and NYHA class was associated with outcome. SAV occurred as the first manifestation of disease or during follow up in 27 patients (4%). At univariate analysis LGE, ECV, GLS, EF and NYHA class were all associated with SAV. However, on multivariable analysis only EF, LGE  and ECV (HR 1.11 (1.01-1.22), p = 0.03) but not GLS remained independently predictive in a model already incorporating EF, NYHA and LGE. Conclusion Optimally treated DCM populations have very low event rates. CMR based assessment of fibrosis status/burden with both LGE and ECV assessment has the potential to enhance patient selection for ICD therapy. Whilst GLS is increasingly recognised as a sensitive imaging biomarker of early disease detection it provides no additive value,  likely because of it’s high co-linearity with EF, in models already containing EF, NYHA class and LGE status.

scholarly journals The Diagnostic and Prognostic Utility of Contemporary Cardiac Magnetic Resonance in Suspected Acute Myocarditis

Diagnostics ◽  
2022 ◽  
Vol 12 (1) ◽  
pp. 156
Author(s):  
Jakub Lagan ◽  
Christien Fortune ◽  
David Hutchings ◽  
Joshua Bradley ◽  
Josephine H. Naish ◽  
...  
Keyword(s):  
Magnetic Resonance ◽  
Volume Fraction ◽  
Acute Myocarditis ◽  
Multivariable Analysis ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Ventricular Ejection Fraction ◽  
Parametric Mapping ◽  
The Impact

Cardiovascular magnetic resonance (CMR) is used to investigate suspected acute myocarditis, however most supporting data is retrospective and few studies have included parametric mapping. We aimed to investigate the utility of contemporary multiparametric CMR in a large prospective cohort of patients with suspected acute myocarditis, the impact of real-world variations in practice, the relationship between clinical characteristics and CMR findings and factors predicting outcome. 540 consecutive patients we recruited. The 113 patients diagnosed with myocarditis on CMR performed within 40 days of presentation were followed-up for 674 (504–915) days. 39 patients underwent follow-up CMR at 189 (166–209) days. CMR provided a positive diagnosis in 72% of patients, including myocarditis (40%) and myocardial infarction (11%). In multivariable analysis, male sex and shorter presentation-to-scan interval were associated with a diagnosis of myocarditis. Presentation with heart failure (HF) was associated with lower left ventricular ejection fraction (LVEF), higher LGE burden and higher extracellular volume fraction. Lower baseline LVEF predicted follow-up LV dysfunction. Multiparametric CMR has a high diagnostic yield in suspected acute myocarditis. CMR should be performed early and include parametric mapping. Patients presenting with HF and reduced LVEF require closer follow-up while those with normal CMR may not require it.

Abstract 17492: Extent and Pattern of Late Gadolinium Enhancement Predict Arrhythmic Events in Patients With Nonischemic Dilated Cardiomyopathy

Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Dong Geum Shin ◽  
Hye-Jeong Lee ◽  
Junbeom Park ◽  
Young Jin Kim ◽  
Jae-Sun Uhm ◽  
...  
Keyword(s):  
Late Gadolinium Enhancement ◽  
Ventricular Arrhythmia ◽  
Dilated Cardiomyopathy ◽  
Cardiac Death ◽  
Primary Outcome ◽  
Multivariable Analysis ◽  
Gadolinium Enhancement ◽  
Nonischemic Dilated Cardiomyopathy ◽  
The Impact

Background: Late gadolinium enhancement (LGE) by cardiac MR (CMR) has been related to adverse clinical outcomes in patients with nonischemic dilated cardiomyopathy (NIDC). But, a statistically significant association between LGE and arrhythmic risk in NIDC has not been demonstrated consistently. This study evaluated the impact of the presence, location and pattern of LGE on arrhythmic risk prediction in NICM. Methods: This study included 365 patients (54±15years) with NICM who underwent CMR. The extent, location and pattern of LGE were categorized. We analyzed for the primary outcome of ventricular arrhythmia (VA) including sustained or nonsustained ventricular tachycardia (VT), appropriate implantable cardioverter-defibrillator (ICD) intervention and ventricular fibrillation (VF). Cardiac death and hospitalization for heart failure (HF) were evaluated as secondary outcomes. Results: LGE was seen in 267 (73 %) patients. During median follow-up of 44±36 months, patients with LGE had higher incidence of cardiac death (15 % vs. 2 %, p<0.001), hospitalization for HF (40 % vs. 15 %, p<0.001) and VA (14% vs. 6%, p=0.03). In multivariable analysis, the presence of LGE (HR 2.78; 95% CI 1.10-7.02; p=0.03) was the independent predictor of arrhythmias. Patients with extensive LGE had higher VA (32% vs. 10%, p<0.001) with lower cumulative survival free of VA than those without extensive LGE (p=0.001). The frequent LGE location was as follows: LV septum 64%, LV-RV junction 42% and inferior 10%. VA was lower in patients with than without localized LGE limited to LV-RV junction (21% vs. 46%, p=0.005). Interestingly, while the incidence of ventricular arrhythmia was higher in patients with transmural LGE (29% vs. 10%, p=0.003), it was lower in those with patch LGE (2% vs. 16%, p=0.02) than the other patients. Conclusions: In patients with NICM, the LGE was an independent prognostic predictor of VA. Extensive LGE and specific location of LGE was related with the arrhythmic events.

4070Clinical impact of mitral regurgitation before or following transcatheter aortic valve replacement in patients with aortic stenosis: a nationwide multivariable analysis

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
L Fauchier ◽  
A Bernard ◽  
A Bisson ◽  
T Lacour ◽  
J Herbert ◽  
...  
Keyword(s):  
Transcatheter Aortic Valve Replacement ◽  
Independent Predictor ◽  
Multivariable Analysis ◽  
Total Mortality ◽  
Transcatheter Aortic Valve ◽  
Mortality Hazard ◽  
History Of ◽  
The Impact ◽  
Mortality Hazard Ratio

Abstract Patients undergoing transcatheter aortic valve replacement (TAVR) may have concomitant mitral regurgitation (MR). The impact of MR at baseline or after TAVR on subsequent prognosis remains to be more precisely determined. We analysed the impact of MR before or after TAVR on prognosis in the systematic analysis of patients treated with TAVR at a nationwide level. Methods Based on the French administrative hospital-discharge database, the study collected information for all consecutive patients with aortic stenosis treated with transfemoral TAVR in France between 2008 and 2018. Cox regression was used for the analysis of predictors of events during follow-up. Results A total of 47,872 patients with transfemoral TAVR were included in the analysis (mean age 83±7 years). Moderate/severe MR was present at baseline (MRb) in 9.5% of the patients. Few patients (1.6%) revealed moderate/severe MR post-TAVR (MRpt). Mean follow-up was 1.31±1.61 years. MRb was associated with an increased cardiovascular mortality (Hazard ratio 1.29, 95% CI 1.20–1.39) and total mortality (Hazard ratio 1.15, 95% CI 1.10–1.21). However, MRb was not an independent predictor in multivariable analysis, neither for cardiovascular mortality (adjusted HR 1.06, 95% CI 0.98–1.14) nor for total mortality (adjusted HR 1.01, 95% CI 0.96–1.07). MRpt was not a predictor of cardiovascular or total mortality. Older age, male sex, history of pulmonary edema/cardiogenic shock, atrial fibrillation, myocardial infarction, diabetes, renal failure, liver disease, pulmonary disease, previous cancer and anemia at baseline independently predicted mortality during follow-up. All of them (but history of cancer) were also independent predictor of cardiovascular death. Conclusion Baseline MR was associated with increased cardiovascular and totality mortality following TAVR but was not an independent predictor of any of them. By contrast, several other predictors of cardiovascular and total mortality were identified. This suggests that MR should not be directly considered to establish the strategy for TAVR decision or for avoiding TAVR-related futility.

Recurrence prediction for breast phyllodes tumours: validation of the Singapore nomogram in Korean women

2020 ◽  
pp. jclinpath-2020-207093
Author(s):  
Jung Eun Choi ◽  
Su Hwan Kang ◽  
Puay Hoon Tan ◽  
Young Kyung Bae
Keyword(s):  
Univariate Analysis ◽  
Surgical Margin ◽  
Recurrence Risk ◽  
Margin Status ◽  
Positive Surgical Margin ◽  
Free Survival ◽  
Recurrence Prediction ◽  
Malignant Grade ◽  
Pathology Reports ◽  
Phyllodes Tumours

AimThe Singapore nomogram was developed to predict recurrence risk of phyllodes tumours (PTs) of the breast based on histological features of stromal atypia, stromal mitoses, stromal overgrowth and surgical margin status. We aimed to validate the utility of the Singapore nomogram in a Korean PT cohort.MethodsOne hundred and twenty-four patients with Korean PT who underwent surgical resection between 1996 and 2015 were included in this study. Pathology reports and slides were reviewed to obtain histopathologic features and acquire Singapore nomogram scores. The probability of concordance between predicted and observed survivals by means of the Singapore nomogram was evaluated using a concordance index (C-index).ResultsOf the 124 cases, 57 (46%) were diagnosed as benign, 50 (40.3%) as borderline and 17 (13.7%) as malignant. Recurrences occurred in 25 (20.2%) patients. Univariate analysis showed PTs with higher stromal mitotic counts, marked stromal cellularity, stromal overgrowth, positive surgical margin, marked stromal atypia or a malignant grade presented higher risks of recurrence. Multivariate analysis showed stromal mitoses and surgical margin status independently predicted recurrence-free survival. Patients with high nomogram scores were at greater risk of recurrence (HR=1.05, 95% CI: 1.02 to 1.07, p<0.001) with a C-index of 0.762.ConclusionThe Singapore nomogram provided a useful means of predicting PT outcomes in a Korean PT cohort.

scholarly journals Post-operative neck ultrasound and risk stratification in differentiated thyroid cancer patients with initial lymph node involvement

2014 ◽  
Vol 170 (6) ◽  
pp. 837-846 ◽  
Author(s):  
Charlotte Lepoutre-Lussey ◽  
Dina Maddah ◽  
Jean-Louis Golmard ◽  
Gilles Russ ◽  
Frédérique Tissier ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Risk Stratification ◽  
Predictive Value ◽  
Cumulative Incidence ◽  
Recurrence Risk ◽  
Lymph Node Involvement ◽  
American Thyroid Association ◽  
Intermediate Risk ◽  
Sensitivity Specificity

ObjectiveCervical ultrasound (US) scan is a key tool for detecting metastatic lymph nodes (N1) in patients with papillary thyroid cancer (PTC). N1-PTC patients are stratified as intermediate-risk and high-risk (HR) patients, according to the American Thyroid Association (ATA) and European Thyroid Association (ETA) respectively. The aim of this study was to assess the value of post-operative cervical US (POCUS) in local persistent disease (PD) diagnosis and in the reassessment of risk stratification in N1-PTC patients.DesignRetrospective cohort study.MethodsBetween 1997 and 2010, 638 N1-PTC consecutive patients underwent a systematic POCUS. Sensitivity, specificity, negative predictive value (NPV), and positive predictive value (PPV) of POCUS for the detection of PD were evaluated and a risk reassessment using cumulative incidence functions was carried out.ResultsAfter a median follow-up of 41.6 months, local recurrence occurred in 138 patients (21.6%), of which 121 were considered to have PD. Sensitivity, specificity, NPV, and PPV of POCUS for the detection of the 121 PD were 82.6, 87.4 95.6, and 60.6% respectively. Cumulative incidence of recurrence at 5 years was estimated at 26% in ETA HR patients, 17% in ATA intermediate-risk patients, and 35% in ATA HR patients respectively. This risk fell to 9, 8, and 11% in the above three groups when the POCUS result was normal and to <6% when it was combined with thyroglobulin results at ablation.ConclusionPOCUS is useful for detecting PD in N1-PTC patients and for stratifying individual recurrence risk. Its high NPV could allow clinicians to tailor follow-up recommendations to individual needs.

Survival in Patients with Newly Diagnosed Myeloma Undergoing Therapy with Lenalidomide and Dexamethasone: Impact of High-Risk Cytogenetic Risk Status on Outcome

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 95-95 ◽  
Author(s):  
Prashant Kapoor ◽  
Shaji Kumar ◽  
Rafael Fonseca ◽  
Martha Q. Lacy ◽  
Thomas E Witzig ◽  
...  
Keyword(s):  
High Risk ◽  
Risk Stratification ◽  
Plasma Cell ◽  
Risk Groups ◽  
Newly Diagnosed ◽  
High Risk Patients ◽  
Risk Patients ◽  
The Impact ◽  
Standard Risk

Abstract Background: Multiple myeloma (MM) is a heterogeneous disease with very divergent outcomes that are dictated in a large part by specific cytogenetic abnormalities, as well as other prognostic factors such as the proliferative rate of marrow plasma cells. Prognostic systems incorporating these factors have shown clinical utility in identifying high-risk patients, and are increasingly being utilized for treatment decision-making. However, the prognostic relevance of these factors may change with the application of novel therapies. The objective of this study was to determine the impact of risk-stratification (incorporating plasma cell metaphase cytogenetics, interphase fluorescent in-situ hybridization (FISH) and the slide-based plasma cell labeling index (PCLI)) in a cohort of patients with newly diagnosed MM treated initially with lenalidomide + dexamethasone (Rev-Dex). Methods: From March 2004 to November 2007, 100 consecutive patients treated with Rev (25mg/day) on days 1 through 21 of a 4-week cycle in combination with dexamethasone as initial therapy for newly diagnosed myeloma, were identified. High-risk MM was defined as presence of any one or more of the following: hypodiploidy, monoallelic loss of chromosome 13 or its long arm (by metaphase cytogenetics only), deletion of p53 (locus 17p13) or PCLI ≥ 3% or immunoglobulin heavy chain (IgH) translocations, t(4;14) (p16.3;q32) or t(14;16)(q32;q23) on FISH. PFS and OS survival estimates were created using the Kaplan Meier method, and compared by log-rank tests. Results: The median estimated follow-up of the entire cohort (N=100) was 36 months. The median PFS was 31 months; the median OS has not been reached. The 2- and 3-year OS estimates were 93% and 83%, respectively. 16% patients were deemed high-risk by at least one of the 3 tests (cytogenetics, FISH or PCLI). Response rates (PR or better) were 81% versus 89% in the high-risk and standard risk groups, respectively, P=NS; corresponding values for CR plus VGPR rates were 38% and 45% respectively. The median PFS was 18.5 months in high-risk patients compared to 37 months in the standard-risk patients (n=84), P<0.001(Figure). Corresponding values for TTP were 18.5 months and 36.5 months, respectively, P=<0.001. OS was not statistically significant between the two groups; 92% 2-year OS was noted in both the groups. Overall, 95 patients had at least one of the 3 tests to determine risk, while 55 patients could be adequately stratified based on the availability of all the 3 tests, or at least one test result that led to their inclusion in the high-risk category. The significant difference in PFS persisted even when the analysis was restricted to the 55 patients classified using this stringent criterion; 18.5 months vs. 36.5 months in the high-risk and standard- risk groups respectively; P<0.001. In a separate analysis, patients who underwent SCT before the disease progression were censored on the date of SCT to negate its effect, and PFS was still inferior in the high-risk group (p=0.002). Conclusion: The TTP and PFS of high-risk MM patients are inferior to that of the standard-risk patients treated with Rev-Dex, indicating that the current genetic and proliferation-based risk-stratification model remains prognostic with novel therapy. However, the TTP, PFS, and OS obtained in high-risk patients treated with Rev-Dex in this study is comparable to overall results in all myeloma patients reported in recent phase III trials. In addition, no significant impact of high-risk features on OS is apparent so far. Longer follow-up is needed to determine the impact of risk stratification on the OS of patients treated with Rev-Dex. Figure Figure

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