scholarly journals Matrix metalloproteinase 12 is an independent prognostic factor predicting postoperative relapse of conventional renal cell carcinoma - a short report

2021 ◽  
Author(s):  
Bence Beres ◽  
Maria Yusenko ◽  
Lehel Peterfi ◽  
Gyula Kovacs ◽  
Daniel Banyai
Keyword(s):  
Renal Cell ◽  
Cox Regression ◽  
Tissue Array ◽  
Short Report ◽  
Free Survival ◽  
Cox Regression Analysis ◽  
Conventional Renal Cell Carcinoma ◽  
Kaplan Meier ◽  
Matrix Metalloproteinase 12

Abstract Purpose Approximately 15% of clinically localised conventional renal cell carcinomas (cRCC) develop metastases within 5 years of follow-up. Sarcomatous cRCC is a highly malignant cancer of the kidney. The aim of our study was to identify biomarkers for estimating the postoperative progression of cRCCs. Methods Global microarray-based gene expression analysis of RCCs with and without sarcomatous changes revealed that a high MMP12 expression was associated with a sarcomatous histology. Additionally, we analysed MMP12 expression using a multi-tissue array comprising 736 cRCC patients without metastasis at the time of surgery. The median follow-up time was 66 ± 29 months. Results Immunohistochemistry revealed MMP12 expression in 187 of 736 cRCCs with good follow-up data. Subsequent Kaplan–Meier analysis revealed that patients with MMP12 positive tumours exhibited a significantly shorter tumour-free survival (p < 0.001). In multivariate Cox regression analysis a weak to strong MMP12 expression indicated a 2.4–2.8 times higher risk of postoperative tumour relapse (p < 0.001; p < 0.003, respectively). Conclusions MMP12 may serve as a biomarker to estimate postoperative cRCC relapse and as a possible target for penfluridol therapy.

scholarly journals Evaluation of pulse wave velocity for predicting major advanced cardiovascular events in patients with chronic myocardial infarction

2021 ◽  
Vol 42 (Supplement_1) ◽  
Author(s):  
Z Meiszterics ◽  
T Simor ◽  
R J Van Der Geest ◽  
N Farkas ◽  
B Gaszner
Keyword(s):  
Myocardial Infarction ◽  
Regression Analysis ◽  
Cardiovascular Events ◽  
Pulse Wave ◽  
Cox Regression ◽  
Event Free Survival ◽  
Free Survival ◽  
Cox Regression Analysis ◽  
Kaplan Meier

Abstract Introduction Increased aortic pulse wave velocity (PWV) as a strong predictor of major advanced cardiovascular events (MACE) has a prognostic relevance in patients after myocardial infarction (MI). Several non-invasive methods have been proposed for the assessment of arterial stiffness, but the PWV values show significant differences according to the applied techniques. Cardiac magnetic resonance imaging (CMR) provides an accurate method to measure PWV and infarct size in patients after MI. Purpose Calculated PWV values of CMR based phase-contrast (PC) and invasively validated oscillometric methods were compared in this prospective observational study. We aimed to evaluate the cut-off PWV values for each method, while MACE predicted and validated the prognostic value of high PWV in post-infarcted patients in a 6-year follow-up. Methods 3D aortic angiography and PC velocity imaging was performed using a Siemens Avanto 1,5 T CMR device. Oscillometric based Arteriograph (AG) was used to assess PWV using direct body surface distance measurements. The comparison between the two techniques was tested. Patients received follow-up for MACE comprising all-cause death, non-fatal MI, ischemic stroke, hospitalization for heart failure and coronary revascularization. Event-free survival was analysed using Kaplan-Meier plots and log-rank tests. Univariable and multivariable Cox regression analysis was performed to identify outcome predictors. Results 75 patients (56 male, 19 female, average age: 56±13 years) referred for CMR were investigated, of whom 50 had coronary artery disease (CAD) including 35 patients with previous MI developing ischaemic late gadolinium enhancement (LGE) pattern. AG and CMR derived PWV values were significantly correlated (rho: 0,343, p&lt;0,05), however absolute PWV values were significantly higher for AG (median (IQR): 10,4 (9,2–11,9) vs. 6,44 (5,64–7,5); p&lt;0,001). Bland Altman analysis showed an acceptable agreement with a mean difference of 3,7 m/s between the two measures. In patients with CAD significantly (p&lt;0,01) higher PWV values were measured by AG and CMR, respectively. During the median follow-up of 6 years, totally 69 MACE events occurred. Optimized PWV cut-off values for MACE prediction were calculated (CMR: 6,47 m/s; AG: 9,625 m/s) by receiver operating characteristic analysis. Kaplan-Meier analysis in both methods showed a significantly lower event-free survival in case of high PWV (p&lt;0,01, respectively). Cox regression analysis revealed PWV for both methods as a predictor of MACE (PWV CMR hazard ratio (HR): 2,6 (confidence interval (CI) 1,3–5,1), PWV AG HR: 3,1 (CI: 1,3–7,1), p&lt;0,005, respectively). Conclusions Our study showed good agreement between the AG and CMR methods for PWV calculation. Both techniques are feasible for MACE prediction in postinfarcted patients. However, different AG and CMR PWV cut-off values were calculated to improve risk stratification. FUNDunding Acknowledgement Type of funding sources: None. Agreement between the two methods Kaplan-Meier event curves for MACE

Long-term outcomes and determinants of restenosis after renal artery angioplasty in hypertensive patients with renovascular disease

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
A Roslawiecka ◽  
A Kablak-Ziembicka ◽  
R Badacz ◽  
P Pieniazek ◽  
D Rzeznik ◽  
...  
Keyword(s):  
Renal Function ◽  
Renal Artery ◽  
Cox Regression ◽  
Survival Curves ◽  
Free Survival ◽  
Cox Regression Analysis ◽  
Kaplan Meier ◽  
Stent Diameter

Abstract Introduction Restenosis (RS) following percutaneous angioplasty (PTA) of renal artery stenosis (RAS) might have an unfavorable impact on renal function and blood pressure (BP) outcomes. Aim To evaluate prevalence and predictors of RS in patients treated with PTA for RAS, and relationship between BP and renal function (RF) changes with RS. Material and methods We analyzed freedom from RS in 210 patients (64.6±12.8; range:20–85y.o.), who underwent 248 successful stent-assisted PTAs in RAS. The change in levels of serum creatinine (SCC), eGFR, systolic/diastolic BPs (SBP/DBP) were analyzed prior to PTA, at 6-, 12-months and final follow-up visits, and whenever RS was diagnosed. Results RS was identified in 30 (14.3%) patients and 36 (14.5%) lesions. The Kaplan-Meier RS-free survival curves in fibromuscular dysplasia, atherosclerosis and vasculitis were: 100% and 100%; 95.6 and 83.9%, while 71.4 and 39.7% at 1 and 7-years, respectively. Patients with RS, as compared to RS-free patients, presented with lesser response in changes of: SBP (1.4±17.6 vs −15.8±25.8mmHg; p=0.01), DBP (2.64±10.1 vs. −6.5±14.1mmHg; p=0.002), SCC (22.4±55.2 vs −3.6±43.9μmol/L; p=0.002) and eGFR (−1.85±18 vs. −5.34±19.5mmHg; p=0.045). In multivariate Cox regression analysis, independent predictors of RS occurred: lack of BP decrease (HR: 4.19, 95% CI: 1.67–10.3; p=0.002), lack of eGFR increase of less than ≤0.17 ml/min/1.73m2 (HR: 2.93, 95% CI: 1.08–7.91; p=0.033), stent diameter ≤5mm (HR: 2.76, 95% CI: 1.09–6.97; p=0.031) and vasculitis (HR: 5.61, 95% CI: 1.83–17.2; p=0.003). RS was treated in 24 patients with RS recurrence in 20%. Conclusions RS rate differs depending on RAS etiology. Lack of SBP/DBP and eGFR improvement, vasculitis, and stent diameter are associated with RS risk. Repeated PTA is effective, but recurrent RS occurs in 20% of cases. Kaplan-Meier RS-free survival curves Funding Acknowledgement Type of funding source: None

scholarly journals Primary versus Redo Urethroplasty: Results from a Single-Center Comparative Analysis

2020 ◽  
Vol 2020 ◽  
pp. 1-7
Author(s):  
Wesley Verla ◽  
Marjan Waterloos ◽  
Anne-Françoise Spinoit ◽  
Sarah Buelens ◽  
Elise De Bleser ◽  
...  
Keyword(s):  
Cox Regression ◽  
Lichen Sclerosus ◽  
University Hospital ◽  
Free Survival ◽  
Exact Test ◽  
Cox Regression Analysis ◽  
Kaplan Meier ◽  
Entire Patient Cohort ◽  
Definition Of

Objectives. To explore the differences between primary and redo urethroplasty and to directly compare according stricture-free survival (SFS). Materials and Methods. Data of all male patients who underwent urethroplasty at Ghent University Hospital were collected between 2000 and 2018. Exclusion criteria for this analysis were age <18 years and follow-up <1 year. Two patient groups were created for further comparison: the primary urethroplasty (PU) group (no previous urethroplasty) and redo urethroplasty (RU) group (≥1 previous urethroplasty), irrespective of prior endoscopic treatments. A comparison between groups was performed using the Mann–Whitney U test and Fisher’s Exact test. SFS was calculated using Kaplan–Meier statistics. A functional definition of failure, being the need for further urethral manipulation, was used. Uni- and multivariate Cox regression analyses were performed on the entire patient cohort. Results. 805 patients were included. Median (IQR) follow-up of the PU (n = 556) and RU (n = 249) groups was 87 (50–136) and 76 (40–133) months, respectively (p=0.1). The RU group involved more penile strictures (p<0.001), Lichen Sclerosus (p=0.016), failed hypospadias repair (p=0.004), multistage procedures (p<0.001), and definitive perineostomies (p=0.001). The 5- and estimated 10-year SFS was, respectively, 86% and 79% for the PU group and, respectively, 75% and 63% for the RU group (p<0.001). Prior urethroplasty (HR: 1.52; p=0.01) and diabetes (HR: 1.83; p=0.03) remained statistically significant in the multivariate Cox regression analysis. Conclusions. Several differences between primary and redo urethroplasties exist. Redo urethroplasty entails a distinct patient population to treat and is, in general, associated with lower stricture-free survival than primary urethroplasty, although more homogeneous series are required to corroborate these results. Prior urethroplasty and diabetes are independent risk factors for urethroplasty failure.

scholarly journals P-Cresyl Sulfate Is a Valuable Predictor of Clinical Outcomes in Pre-ESRD Patients

2014 ◽  
Vol 2014 ◽  
pp. 1-7 ◽  
Author(s):  
Cheng-Jui Lin ◽  
Chi-Feng Pan ◽  
Chih-Kuang Chuang ◽  
Fang-Ju Sun ◽  
Duen-Jen Wang ◽  
...  
Keyword(s):  
Clinical Outcomes ◽  
Cardiovascular Event ◽  
Cox Regression ◽  
Medical Center ◽  
Serum Biochemistry ◽  
Cox Regression Analysis ◽  
Kaplan Meier ◽  
Valuable Marker ◽  
Valuable Predictor

Background/Aims. Previous studies have reported p-cresyl sulfate (PCS) was related to endothelial dysfunction and adverse clinical effect. We investigate the adverse effects of PCS on clinical outcomes in a chronic kidney disease (CKD) cohort study.Methods. 72 predialysis patients were enrolled from a single medical center. Serum biochemistry data and PCS were measured. The clinical outcomes including cardiovascular event, all-cause mortality, and dialysis event were recorded during a 3-year follow-up.Results. After adjusting other independent variables, multivariate Cox regression analysis showed age (HR: 1.12,P=0.01), cardiovascular disease history (HR: 6.28,P=0.02), and PCS (HR: 1.12,P=0.02) were independently associated with cardiovascular event; age (HR: 0.91,P<0.01), serum albumin (HR: 0.03,P<0.01), and PCS level (HR: 1.17,P<0.01) reached significant correlation with dialysis event. Kaplan-Meier analysis revealed that patients with higher serum p-cresyl sulfate (>6 mg/L) were significantly associated with cardiovascular and dialysis event (log rankP=0.03, log rankP<0.01, resp.).Conclusion. Our study shows serum PCS could be a valuable marker in predicting cardiovascular event and renal function progression in CKD patients without dialysis.

scholarly journals Prognostic values, ceRNA network, and immune regulation function of SDPR in KRAS-mutant lung cancer

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Xiaoqing Luo ◽  
Shunli Peng ◽  
Sijie Ding ◽  
Qin Zeng ◽  
Rong Wang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Immune Checkpoint ◽  
Cox Regression ◽  
Tissue Array ◽  
Lung Cancers ◽  
Cox Regression Analysis ◽  
Immune Checkpoint Molecules ◽  
Cerna Network ◽  
Kaplan Meier ◽  
Infiltration Models

Abstract Background Serum Deprivation Protein Response (SDPR) plays an important role in formation of pulmonary alveoli. However, the functions and values of SDPR in lung cancer remain unknown. We explored prognostic value, expression pattern, and biological function of SDPR in non-small cell lung cancer (NSCLC) and KRAS-mutant lung cancers. Methods SDPR expression was evaluated by quantitative real-time PCR (RT-qPCR), immunohistochemistry (IHC), and Western blot on human NSCLC cells, lung adenocarcinoma tissue array, KRAS-mutant transgenic mice, TCGA and GEO datasets. Prognostic values of SDPR were evaluated by Kaplan–Meier and Cox regression analysis. Bioinformatics implications of SDPR including SDPR-combined transcription factors (TFs) and microRNAs were predicted. In addition, correlations between SDPR, immune checkpoint molecules, and tumor infiltration models were illustrated. Results SDPR expression was downregulated in tumor cells and tissues. Low SDPR expression was an independent factor that correlated with shorter overall survival of patients both in lung cancer and KRAS-mutant subgroups. Meanwhile, ceRNA network was constructed to clarify the regulatory and biological functions of SDPR. Negative correlations were found between SDPR and immune checkpoint molecules (PD-L1, TNFRSF18, TNFRSF9, and TDO2). Moreover, diversity immune infiltration models were observed in NSCLC with different SDPR expression and copy number variation (CNV) patterns. Conclusions This study elucidated regulation network of SDPR in KRAS-mutant NSCLC, and it illustrated correlations between low SDPR expression and suppressed immune system, unfolding a prognostic factor and potential target for the treatment of lung cancer, especially for KRAS-mutant NSCLC.

Pituitary surgery as alternative to dopamine agonists treatment for microprolactinomas, a cohort study

2021 ◽  
Author(s):  
Bertrand Baussart ◽  
Chiara Villa ◽  
Anne Jouinot ◽  
Marie-Laure Raffin-Sanson ◽  
Luc Foubert ◽  
...  
Keyword(s):  
Dopamine Agonists ◽  
Cox Regression ◽  
Disease Free Survival ◽  
Pituitary Surgery ◽  
Cerebrospinal Fluid Leakage ◽  
Neurosurgical Department ◽  
Free Survival ◽  
Kaplan Meier ◽  
Disease Free

Objective: Microprolactinomas are currently treated with dopamine agonists. Outcome information on microprolactinoma patients treated by surgery is limited. This study reports the first large series of consecutive non-invasive microprolactinoma patients treated by pituitary surgery and evaluates the efficiency and safety of this treatment. Design: Follow-up of a cohort of consecutive patients treated by surgery. Methods: Between January 2008 and October 2020, 114 adult patients with pure microprolactinomas were operated on in a single tertiary expert neurosurgical department, using an endoscopic endonasal transsphenoidal approach. Eligible patients were presenting a microprolactinoma with no obvious cavernous invasion on MRI. Prolactin was assayed before and after surgery. Disease-free survival was modeled using Kaplan-Meier representation. A cox regression model was used to predict remission. Results: Median follow-up was 18.2 months (range: 2.8 to 155). In this cohort, 14/114 (12%) patients were not cured by surgery, including 10 early surgical failures, and 4 late relapses occurring 37.4 months (33 to 41.8) after surgery. From Kaplan Meier estimates, 1-year and 5-year disease free survival were 90.9% (95% CI, 85.6%-96.4%) and 81% (95% CI,71.2%-92.1%) respectively. The preoperative prolactinemia was the only significant preoperative predictive factor for remission (P<0.05). No severe complication was reported, with no anterior pituitary deficiency after surgery, one diabetes insipidus, and one postoperative cerebrospinal fluid leakage properly treated by muscle plasty. Conclusions: In well selected microprolactinoma patients, pituitary surgery performed by an expert neurosurgical team is a valid first-line alternative treatment to dopamine agonists.

scholarly journals The impact of method of distal ureter management during radical nephroureterectomy on tumour recurrence

2014 ◽  
Vol 8 (11-12) ◽  
pp. 845 ◽  
Author(s):  
Anil Kapoor ◽  
Shawn Dason ◽  
Christopher B. Allard ◽  
Bobby Shayegan ◽  
Louis Lacombe ◽  
...  
Keyword(s):  
Cox Regression ◽  
Tumour Recurrence ◽  
Management Approach ◽  
Management Technique ◽  
Recurrence Free Survival ◽  
Radical Nephroureterectomy ◽  
Distal Ureter ◽  
Free Survival ◽  
Cox Regression Analysis

Introduction: Radical nephroureterectomy for upper tract urothelial carcinoma (UTUC) must include some form of distal ureter management to avoid high rates of tumour recurrence. It is uncertain which distal ureter management technique has the best oncologic outcomes. To determine which distal ureter management technique resulted in the lowest tumour recurrence rate, we analyzed a multiinstitutional Canadian radical nephroureterectomy database.Methods: We retrospectively analyzed patients who underwent radical nephroureterectomy with distal ureter management for UTUC between January 1990 and June 2010 at 10 Canadian tertiary hospitals. Distal ureter management approaches were divided into 3 categories: (1) extravesical tenting for ureteric excision without cystotomy (EXTRAVESICAL); (2) open cystotomy with intravesical bladder cuff excision (INTRAVESICAL); and (3) extravesical excision with endoscopic management of ureteric orifice (ENDOSCOPIC). Data available for each patient included demographic details, distal ureter management approach, pathology and operative details, as well as the presence and location of local or distant recurrence. Clinical outcomes included overall recurrence-free survival and intravesical recurrence-free survival. Survival analysis was performed with the Kaplan-Meier method. Multivariable Cox regression analysis was also performed.Results: A total of 820 patients underwent radical nephroureterectomy with a specified distal ureter management approach at 10 Canadian academic institutions. The mean patient age was 69.6 years and the median follow-up was 24.6 months. Of the 820 patients, 406 (49.5%) underwent INTRAVESICAL, 316 (38.5%) underwent EXTRAVESICAL, and 98 (11.9%) underwent ENDOSOPIC distal ureter management. Groups differed significantly in their proportion of females, proportion of laparoscopic cases, presence of carcinoma in situ and pathological tumour stage (p < 0.05). Recurrence-free survival at 5 years was 46.3%, 35.6%, and 30.1% for INTRAVESICAL, EXTRAVESICAL and ENDOSCOPIC, respectively (p < 0.05). Multivariable Cox regression analysis confirmed that INTRAVESICAL resulted in a lower hazard of recurrence compared to EXTRAVESICAL and ENDOSCOPIC. When looking only at intravesical recurrence-free survival (iRFS), a similar trend held up with INTRAVESICAL having the highest iRFS, followed by ENDOSCOPIC and then EXTRAVESICAL management (p < 0.05). At last follow-up, 406 (49.5%) patients were alive and free of disease.Conclusion: Open intravesical excision of the distal ureter (INTRAVESICAL) during radical nephroureterectomy was associated with improved overall and intravesical recurrence-free survival compared with extravesical and endoscopic approaches. These findings suggest that INTRAVESICAL should be considered the gold standard oncologic approach to distal ureter management during radical nephroureterectomy. Limitations of this study include its retrospective design, heterogeneous cohort, and limited follow-up.

scholarly journals Mortality in Patients with Diabetic Foot Ulcers: Causes, Risk Factors, and Their Association with Evolution and Severity of Ulcer

2020 ◽  
Vol 9 (9) ◽  
pp. 3009
Author(s):  
José Antonio Rubio ◽  
Sara Jiménez ◽  
José Luis Lázaro-Martínez
Keyword(s):  
Diabetic Foot ◽  
Cox Regression ◽  
Foot Ulcers ◽  
Diabetic Foot Ulcers ◽  
Cox Regression Analysis ◽  
Kaplan Meier ◽  
Hazard Ratios ◽  
History Of

Background: This study reviews the mortality of patients with diabetic foot ulcers (DFU) from the first consultation with a Multidisciplinary Diabetic Foot Team (MDFT) and analyzes the main cause of death, as well as the relevant clinical factors associated with survival. Methods: Data of 338 consecutive patients referred to the MDFT center for a new DFU during the 2008–2014 period were analyzed. Follow-up: until death or until 30 April 2020, for up to 12.2 years. Results: Clinical characteristics: median age was 71 years, 92.9% had type 2 diabetes, and about 50% had micro-macrovascular complications. Ulcer characteristics: Wagner grade 1–2 (82.3%), ischemic (49.2%), and infected ulcers (56.2%). During follow-up, 201 patients died (59.5%), 110 (54.7%) due to cardiovascular disease. Kaplan—Meier curves estimated a reduction in survival of 60% with a 95% confidence interval (95% CI), (54.7–65.3) at 5 years. Cox regression analysis adjusted to a multivariate model showed the following associations with mortality, with hazard ratios (HRs) (95% CI): age, 1.07 (1.05–1.08); HbA1c value < 7% (53 mmol/mol), 1.43 (1.02–2.0); active smoking, 1.59 (1.02–2.47); ischemic heart or cerebrovascular disease, 1.55 (1.15–2.11); chronic kidney disease, 1.86 (1.37–2.53); and ulcer severity (SINBAD system) 1.12 (1.02–1.26). Conclusion: Patients with a history of DFU have high mortality. Two less known predictors of mortality were identified: HbA1c value < 7% (53 mmol/mol) and ulcer severity.

Assessment of Losartan 50 mg on Survival of Post-Dialysis Euvolemic Hypertensive Patients: Findings from HELD Trial

2019 ◽  
Vol 48 (3) ◽  
pp. 233-242
Author(s):  
Raja Ahsan Aftab ◽  
Amer Hayat Khan ◽  
Azreen Syazril Adnan ◽  
Syed Azhar Syed Sulaiman ◽  
Tahir Mehmood Khan
Keyword(s):  
Cox Regression ◽  
Dialysis Session ◽  
Hypertensive Patients ◽  
Cox Regression Analysis ◽  
Probability Of Survival ◽  
End Point ◽  
Kaplan Meier ◽  
Significant Difference ◽  
Single Blind

Aims and objective: To estimate the effect of losartan 50 mg on survival of post-dialysis euvolemic hypertensive patients. Methodology: A single center, prospective, single-blind randomized trial was conducted to estimate the survival of post-dialysis euvolemic hypertensive patients when treated with lorsartan 50 mg every other day. Post-dialysis euvolemic assessment was done by a body composition monitor. Covariate Adaptive Randomization was used for allocation of participants to the standard or intervention arm, and the follow-up duration was twelve months. The primary end point was achieving targeted blood pressure (BP) of <140/90 mm Hg and maintaining for 4 weeks, whereas secondary end point was all cause of mortality. Pre-, intra-, and post-dialysis session BP measurements were recorded, and survival trends were analyzed using Kaplan-Meier analysis. Results: Of the total 229 patients, 96 (41.9%) were identified as post-dialysis euvolemic hypertensive. Final samples of 88 (40.1%) patients were randomized into standard (n = 44) and intervention arms (n = 44), and 36 (81.8%) patients in each arm completed a follow-up of 12 months. A total of eight patients passed away during the 12-month follow-up period (6 deaths among standard arm and 2 in intervention arm). However, the probability of survival between both arms was not significant (p = 0.13). Cox regression analysis revealed that chances of survival were higher among the patients in the intervention (OR 3.17) arm than the standard arm (OR 0.31); however, the survival was found not statistically significant. Conclusion: There was no statistical significant difference in 1 year survival of post-dialysis euvolemic hypertensive patients when treated with losartan 50 mg.

Intensive Versus Double Intensive Therapy in Untreated Multiple Myeloma: Updated Analysis of the Randomized Phase III Study HOVON 24 MM.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 948-948 ◽  
Author(s):  
Pieter Sonneveld ◽  
Bronno van der Holt ◽  
Christine Segeren ◽  
Edo Vellenga ◽  
Reinier Raymakers ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Cox Regression ◽  
Intensive Therapy ◽  
Elevated Serum ◽  
Intensive Treatment ◽  
Phase Iii ◽  
Remission Induction ◽  
Free Survival ◽  
Cox Regression Analysis

Abstract In 1995 HOVON started a prospective randomized multicenter trial to compare the efficacy of intensified treatment followed by myelo-ablative therapy and stem cell transplantation (PBSCT) with intensified treatment alone in patients with myeloma. We now report the results of a second analysis in 441 eligible patients with stage II (22%) and III (78%) disease. The median age was 55 years. Remission induction consisted of 3 courses of VAD. 63 patients with an HLA identical sibling were candidates for an allogeneic transplantation. After VAD, patients without donor were randomized to melphalan 140 mg/m2 divided in 2 doses of 70 mg/m2 (IDM) without PBSCT (arm A) or this regimen followed by myelo-ablation with cyclophosphamide (120 mg/kg) and TBI with PBSCT (arm B). Peripheral stem cells were mobilized by cyclophosphamide and G-CSF after VAD. Interferon-a -2a was given as maintenance therapy in both arms. Of 441 patients, 303 were eligible for randomization. Patient characteristics were not significantly different between the two arms. The median follow-up from randomization was 56 months. 81% of patients received both cycles of IDM (79% in arm A and 83% in arm B) and 79% of patients received myeloablative therapy followed by autologous PBSCT in arm B. The median duration of maintenance treatment was 12 (arm A) vs 7 months (arm B). The CR rate was better in Arm B (28% vs 13% , p=0.002), while overall response rate (PR + CR) was not different (90% vs 86% , p=0.23). Median event-free survival (EFS) from randomization was 22 (arm B) vs 20 months (arm A) (logrank p=0.016). Median progression-free survival (PFS) was significantly better in patients treated with double intensification (24 vs 23 months, logrank p=0.036). Time to Progression (TTP) was significantly worse in arm A (median 25 vs 33 months, logrank p=0.001). The difference for EFS, PFS and TTP became only evident after at least 4 years of follow-up. Overall survival (OS) was not different (55 months in arm A vs 50 in arm B, logrank p=0.38). Multivariate analysis showed that treatment arm A, higher age, hemoglobin < 6.21 mmol/l, stage 3 and elevated serum LDH were significant adverse prognostic factors for EFS. Cytogenetic analysis, available in 151 registered patients was abnormal in 37% (45% del 13/13q-, 51% abnormal 1p/q, 33% del 6q, 89% complex abnormalities). Cox regression analysis showed that 1p/q was an independent unfavourable prognostic factor for OS, EFS, PFS and TTP (p<0.001), calculated from start VAD. Del 13/13q- was highly correlated with 1p/q abnormalities. By combining B2M > 3 mg/L with del13/13q- and 1p/q, prognostic groups could be defined with a significant impact on OS (p<0.000002), EFS (p< 0.0002), PFS (p <0.00006) and TTP (p<0.0000002). Quality of Life analysis showed significant improvement of disease-related variables in double intensive treatment. In conclusion, in this trial second intensification by myeloablative treatment with cyclophosphamide/TBI when added to intensified chemotherapy alone resulted in a superior EFS, PFS and TTP, but not OS. The results of this trial indicate that double intensive treatment results in superior outcome, but not cure in multiple myeloma.

Sign in / Sign up

Export Citation Format

Share Document