Healthy Lifestyle and Social Network Prolong Disability-Free Survival in Older Adults With Diabetes

Abstract Aim We aimed to estimate the extent to which diabetes shortens disability-free survival, and identify which factors may prolong disability-free survival in older adults with diabetes. Methods A total of 2,216 disability-free participants aged ≥60 were followed up to 15 years. Diabetes was ascertained through antidiabetic drug use, medical records, or HbA1c ≥ 6.5%. Disability-free survival was defined as the survival until the occurrence of disability. Data on behaviours (healthy vs. unhealthy), leisure activities (active vs. inactive), and social network (moderate-to-rich vs. poor) were collected at baseline. A favourable (vs. unfavourable) lifestyle profile was defined as the presence of at least one of healthy behaviours, active engagement in leisure activities, and/or moderate-to-rich social network. Data were analysed with Cox regression and Laplace regression. Results During the follow-up, 1,345 (60.7%) participants developed disability/death. Diabetes was related to the outcome (HR 1.29, 95% CI 1.06–1.57), and shortened 2.15 (1.02–3.27) years of median disability-free survival. Additionally, disability-free survival (95% CI) was shortened by 3.29 (1.21–5.36), 3.92 (2.08–5.76) and 1.66 (0.06–3.28) years for participants with diabetes plus unhealthy behaviours, inactive leisure activities, or poor social network, respectively (reference: no diabetes plus healthy behaviours, leisure activities, or moderate-to-rich social network). Among participants with diabetes, a favourable profile led to a non-significant HR of 1.19 (0.93–1.56) for disability/death and prolonged disability-free survival by 3.26 (2.33–4.18) years than those with unfavourable profile. Conclusions Healthy lifestyle and/or moderate-to-rich social network attenuates the risk of diabetes on disability/death and prolongs disability-free survival in people with diabetes by 3 years.

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The Framingham risk score is associated with incident frailty, or is it?

BMC Geriatrics ◽

10.1186/s12877-021-02387-4 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Hui Shi ◽

Mei-Ling Ge ◽

Birong Dong ◽

Qian-Li Xue

Keyword(s):

Older Adults ◽

Risk Score ◽

Cox Regression ◽

Activity Level ◽

Cvd Risk ◽

Frailty Phenotype ◽

Frailty Status ◽

Adverse Health Outcomes ◽

Comorbidity Burden

Abstract Backgrounds Cardiovascular disease (CVD) risk factors are individually associated with frailty. This study examined whether Framingham CVD risk score (FRS) as an aggregate measure of CVD risk is associated with incident frailty among Chinese older adults. Methods This study used data from the China Health and Retirement Longitudinal Study. A sample of 3,618 participants aged 60 to 95 years and without CVD at baseline were followed for four years. FRS was calculated at baseline. Frailty status was defined as not-frail (0–2 criteria) or frail (3–5 criteria) based on the physical frailty phenotype consisting of five binary criteria (weakness, slowness, exhaustion, low activity level, and weight loss). After excluding subjects who were frail (n = 248) at baseline, discrete-time Cox regression was used to evaluate the relationship between FRS and incident frailty. Results During a median follow-up of 4.0 years, 323 (8 %) participants developed CVD and 318 (11 %) subjects had frailty onset. Higher FRS was associated with greater risk of incident frailty (HR: 1.03, 95 % CI: 1.00 to 1.06) after adjusting for education, marital status, obesity, comorbidity burden, and cognitive function. This association however was no longer significant (HR: 1.00, 95 % CI: 0.97 to 1.03) after additionally adjusting for age. These findings remained essentially unchanged after excluding subjects with depression (n = 590) at baseline or incident CVD (n = 323) during the 4-year follow-up. Conclusions The FRS was not independently associated with incident frailty after adjusting for chronological age. More research is needed to assess the clinical utility of the FRS in predicting adverse health outcomes other than CVD in older adults.

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FRI0181 ORGAN DAMAGE FREE SURVIVAL IN SOUTHERN CHINESE PATIENTS WITH ACTIVE LUPUS NEPHRITIS

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2020-eular.2552 ◽

2020 ◽

Vol 79 (Suppl 1) ◽

pp. 674.1-674

Author(s):

C. C. Mok ◽

C. S. Sin ◽

K. C. Hau ◽

T. H. Kwan

Keyword(s):

Lupus Nephritis ◽

Regression Model ◽

Cox Regression ◽

Organ Damage ◽

Renal Survival ◽

Cox Regression Model ◽

Free Survival ◽

Renal Response

Background:The goals of treatment of lupus nephritis (LN) are to induce remission, retard the progression of chronic kidney disease, prevent organ complications and ultimately reduce mortality. Previous cohort studies of LN have mainly focused on the risk of mortality and development of end stage renal failure (ESRF) (renal survival). The cumulative frequency of LN patients who survive without organ damage, which correlates better with the balance between treatment efficacy and toxicity, as well as quality of life, has not been well studied.Objectives:To study the organ damage free survival and its predictive factors in patients with active LN.Methods:Consecutive patients who fulfilled ≥4 ACR/SLICC criteria for SLE and with biopsy proven active LN between 2003 and 2018 were retrospectivey analyzed. Those with organ damage before LN onset were excluded. Data on renal parameters and treatment regimens were collected. Complete renal response (CR) was defined as normalization of serum creatinine (SCr), urine P/Cr (uPCR) <0.5 and inactive urinary sediments. Partial renal response (PR) was defined as ≥50% reduction in uPCR and <25% increase in SCr. Organ damage of SLE was assessed by the ACR/SLICC damage index (SDI). The cumulative risk of having any organ damage or mortality since LN was studied by Kaplan-Meier’s analysis. Factors associated with a poor outcome were studied by a forward stepwise Cox regression model, with entry of covariates with p<0.05 and removal with p>0.10.Results:273 LN patients were identified but 64 were excluded (organ damage before LN onset). 211 LN patients were studied (92% women; age at SLE 30.4±13.5 years; SLE duration at LN 1.9±3.1years). 47 (22%) patients had nephrotic syndrome and 60 (29%) were hypertensive. Histological LN classes was: III/IV±V (75.1%), I/II (7.8%) and pure V (17.1%) (histologic activity and chronicity score 7.0±4.2 and 1.8±1.5, respectively). Induction regimens were: prednisolone (33.1±17.5mg/day) in combination with intravenous cyclophosphamide (CYC) (21.4%; 1.0±0.2g per pulse), oral CYC (8.6%; 96.4±37.8mg/day), azathioprine (AZA) (14.3%; 78.6±25.2mg/day), mycophenolate mofetil (MMF) (22.8%; 1.9±0.43g/day) and tacrolimus (TAC) (17.1%; 4.3±1.1mg/day). After a follow-up of 8.6±5.4 years, 94(45%) patient developed organ damage (SDI≥1) and 21(10%) patients died. The commonest organ damage was renal (36.3%) and musculoskeletal (17.9%), and the causes of death were: infection (38.1%), malignancy (19.0%), cardiovascular events (9.5%) and ESRF complications (9.5%). At last visit, 114 (55%) patients survived without any organ damage. The cumulative organ damage free survival at 5, 10 and 15 years after renal biopsy was 73.5%, 59.6% and 48.3%, respectively. The 5, 10 and 15-year renal survival rate were 95.2%, 92.0% and 84.1% respectively. In a Cox regression model, nephritic relapse (HR 3.72[1.78-7.77]), proteinuric relapse (HR 2.30[1.07-4.95]) and older age (HR 1.89[1.05-3.37]) were associated with either organ damage or mortality, whereas CR (HR 0.25[0.12-0.50]) at month 12 were associated with organ damage free survival. Baseline SCr, uPCR and histological LN classes were not significantly associated with a poor outcome. Among patients with class III/IV LN, the long-term organ damage free survival were not significantly different in users of MMF (reference) from CYC (IV/oral) (HR 1.45[0.76- 2.75]) or TAC (HR 1.03[0.26-1.62]) as induction therapy.Conclusion:Organ damage free survival is achieved in 55% of patients with active LN upon 9 years of follow-up. CYC/MMF/TAC based induction regimens did not differ for the long-term outcome of LN. Targeting complete renal response and preventing renal relapses remain important goals of LN treatment.Acknowledgments:NILDisclosure of Interests:None declared

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FAS and Subsequent Therapies in Pancreatic Neuroendocrine Tumors

Neuroendocrinology ◽

10.1159/000514339 ◽

2021 ◽

Author(s):

Jane E. Rogers ◽

Michael Lam ◽

Daniel M. Halperin ◽

Cecile G. Dagohoy ◽

James C. Yao ◽

...

Keyword(s):

Neuroendocrine Tumors ◽

Cox Regression ◽

Progression Free Survival ◽

Pancreatic Neuroendocrine Tumors ◽

Free Survival ◽

Prior Therapy ◽

Well Differentiated ◽

Grade 3 ◽

Line Of Therapy

We evaluated outcomes of treatment with 5-fluorouracil (5-FU), doxorubicin, and streptozocin (FAS) in well-differentiated pancreatic neuroendocrine tumors (PanNETs) and its impact on subsequent therapy (everolimus or temozolomide). Advanced PanNET patients treated at our center from 1992 to 2013 were retrospectively reviewed. Patients received bolus 5-FU (400 mg/m2), streptozocin (400 mg/m2) (both IV, days 1-5) and doxorubicin (40 mg/m2 IV, day 1) every 28 days. Overall response rate (ORR) was assessed using RECIST version 1.1. Of 243 eligible patients, 220 were evaluable for ORR, progression-free survival (PFS), and toxicity. Most (90%) had metastatic, nonfunctional PanNETs; 14% had prior therapy. ORR to FAS was 41% (95% confidence interval [CI]: 36-48%). Median follow-up was 61 months. Median PFS was 20 (95% CI: 15-23) months; median overall survival (OS) was 63 (95% CI: 60-71) months. Cox regression analyses suggested improvement with first-line vs subsequent lines of FAS therapy. Main adverse events ≥ grade 3 were neutropenia (10%) and nausea/vomiting (5.5%). Dose reductions were required in 32% of patients. Post-FAS everolimus (n=108; 68% second line) had a median PFS of 10 (95% CI: 8-14) months. Post-FAS temozolomide (n=60; 53% > fourth line) had an ORR of 13% and median PFS of 5.2 (95% CI: 4-12) months. In this largest reported cohort of PanNETs treated with chemotherapy, FAS demonstrated activity without significant safety concerns. FAS did not appear to affect subsequent PFS with everolimus; this sequence is being evaluated prospectively. Responses were noted with subsequent temozolomide-based regimens although PFS was possibly limited by line of therapy.

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

Acta Endocrinologica ◽

10.1530/eje-21-0293 ◽

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.

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Animal protein intake is inversely associated with mortality in older adults: the InCHIANTI study

The Journals of Gerontology Series A ◽

10.1093/gerona/glab334 ◽

2021 ◽

Author(s):

Tomás Meroño ◽

Raúl Zamora-Ros ◽

Nicole Hidalgo-Liberona ◽

Montserrat Rabassa ◽

Stefania Bandinelli ◽

...

Keyword(s):

Older Adults ◽

Total Energy ◽

Cardiovascular Mortality ◽

Protein Intake ◽

Cox Regression ◽

Clinical Information ◽

Community Dwelling ◽

Animal Protein ◽

Plant Protein

Abstract Background In general, plant protein intake was inversely associated with mortality in studies in middle-aged adults. Our aim was to evaluate the long-term associations of animal and plant protein intake with mortality in older adults. Methods A prospective cohort study including 1,139 community-dwelling older adults (mean age 75 years, 56% women) living in Tuscany, Italy, followed for 20 years (InCHIANTI study) was analyzed. Dietary intake by food frequency questionnaires and clinical information were assessed five times during the follow-up. Protein intakes were expressed as percentages of total energy. Time-dependent Cox regression models adjusted for confounders were used to assess the association between plant and animal protein intake, and mortality. Results During the 20-years of follow up (mean: 12y), 811 deaths occurred (292 of cardiovascular- and 151 of cancer-related causes). Animal protein intake was inversely associated with all-cause (HR per 1% of total energy from protein increase, 95%CI: 0.96, 0.93-0.99) and cardiovascular mortality (HR per 1% of total energy from protein increase, 95%CI: 0.93, 0.87-0.98). Plant protein intake showed no association with any of the mortality outcomes, but an interaction with baseline hypertension was found for all-cause and cardiovascular mortality (p<0.05). Conclusions Animal protein was inversely associated with all-cause and cardiovascular mortality in older adults. Further studies are needed to provide recommendations on dietary protein intake for older adults.

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

Canadian Urological Association Journal ◽

10.5489/cuaj.1985 ◽

2014 ◽

Vol 8 (11-12) ◽

pp. 845 ◽

Cited By ~ 17

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.

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

Cellular Oncology ◽

10.1007/s13402-021-00650-9 ◽

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.

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Predictors of three-month mortality among hospitalized older adults in Togo

10.21203/rs.3.rs-38973/v2 ◽

2020 ◽

Author(s):

Fifonsi Adjidossi GBEASOR-KOMLANVI ◽

Martin Kouame TCHANKONI ◽

Akila Wimima BAKOUBAYI ◽

Matthieu Yaovi LOKOSSOU ◽

Arnold SADIO ◽

...

Keyword(s):

Older Adults ◽

Hospital Mortality ◽

Cox Regression ◽

Sub Saharan Africa ◽

Mortality Data ◽

Kaplan Meier ◽

All Cause Mortality ◽

Hospitalized Older Adults ◽

Sub Saharan

Abstract Background: Assessing hospital mortality and its predictors is important as some of these can be prevented through appropriate interventions. Few studies have reported hospital mortality data among older adults in sub-Saharan Africa. The objective of this study was to assess the mortality and associated factors among hospitalized older adults in Togo.Methods: We conducted a prospective cohort study from February 2018 to September 2019 among patients ≥50 years admitted in medical and surgical services of six hospitals in Togo. Data were recorded during hospitalization and through telephone follow-up survey within 90 days after admission. The main outcome was all-cause mortality at 3 months. Survival curves were estimated using the Kaplan-Meier method and Cox regression analyses were performed to assess predictors of mortality.Results: The median age of the 650 older adults included in the study period was 61 years, IQR: [55-70] and at least one comorbidity was identified in 59.7% of them. The all-cause mortality rate of 17.2% (95%CI: 14.4-20.4) and the majority of death (93.7%) occurred in hospital. Overall survival rate was 85.5% and 82.8% after 30 and 90 days of follow-up, respectively. Factors associated with 3-month mortality were the hospital level in the health pyramid, hospitalization service, length of stay, functional impairment, depression and malignant diseases.Conclusion: Togolese health system needs to adjust its response to an aging population in order to provide the most effective care.

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Pré-implantation de l’Accompagnement-citoyen personnalisé d’intégration communautaire (APIC): Adaptabilité, collaboration et financement, les déterminants d’une implantation réussie

Canadian Journal on Aging / La Revue canadienne du vieillissement ◽

10.1017/s0714980819000059 ◽

2019 ◽

Vol 38 (03) ◽

pp. 315-327

Author(s):

Laurie Piché ◽

Sophie Arsenault ◽

Mathilde Leblanc ◽

Nathalie Croteau ◽

Mélanie Levasseur

Keyword(s):

Older Adults ◽

Action Research ◽

Social Participation ◽

Research Study ◽

Scientific Evidence ◽

Leisure Activities ◽

Economic Context ◽

New Knowledge ◽

Facilitators And Barriers

ABSTRACTThis study aimed to identify the facilitators and barriers to as well as the feasibility of Implementing Personalized Citizen Assistance for social participation (IPCA) in older adults with disabilities living in the community. The IPCA is a three-hour, weekly follow-up achieved by trained and supervised non-professional assistants that aims to increase engagement in social and leisure activities of people living with disabilities. An action research study was conducted with 16 people from the community. The adaptability of the IPCA, the presence of scientific evidence, the acknowledgement of a need for such an intervention, as well as expertise and collaboration, were the main facilitators in implementation of the IPCA. Meanwhile, funding, associated with an unfavorable political and economic context, was a barrier. Overall, the majority of the participants perceived that the IPCA could be offered in the community by volunteers. This new knowledge will facilitate the implementation of IPCA or other similar interventions.

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

Blood ◽

10.1182/blood.v104.11.948.948 ◽

2004 ◽

Vol 104 (11) ◽

pp. 948-948 ◽

Cited By ~ 6

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.

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