Hein Putter

Hein Putter
Leiden University Medical Centre | LUMC · Department of Medical Statistics and Bioinformatics

PhD

About

865
Publications
102,541
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44,349
Citations
Citations since 2017
328 Research Items
22832 Citations
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201720182019202020212022202301,0002,0003,0004,000
Introduction
Additional affiliations
February 2000 - present
Leiden University Medical Centre
April 1998 - January 2000

Publications

Publications (865)
Article
Background Prediction models for risk of cardiovascular events generally do not include young adults, and cardiovascular risk factors differ between women and men. Therefore, this study aimed to develop prediction models for first‐ever cardiovascular event risk in men and women aged 30 to 49 years. Methods and Results We included patients aged 30...
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From 2016 EBMT and JACIE developed an international risk-adapted benchmarking program of haematopoietic stem cell transplant (HSCT) outcome to provide individual EBMT Centers with a means of quality-assuring the HSCT process and meeting FACT-JACIE accreditation requirements relating to 1-year survival outcomes. Informed by previous experience from...
Article
Introduction In hormone receptor-positive, HER2-negative early-stage breast cancer (BC), cyclin-dependent kinases 4 and 6 inhibition (CDK4/6i) in combination with endocrine therapy (ET) could represent an alternative to neoadjuvant chemotherapy (NAC). Methods NEOLBC is a randomized phase II trial that tailored neoadjuvant therapy in postmenopausal...
Article
Introduction: Although optimising rectal cancer treatment has reduced local recurrence rates, many patients develop distant metastases (DM). The current study investigated whether a total neoadjuvant treatment strategy influences the development, location, and timing of metastases in patients diagnosed with high-risk locally advanced rectal cancer...
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Background In health research, several chronic diseases are susceptible to competing risks (CRs). Initially, statistical models (SM) were developed to estimate the cumulative incidence of an event in the presence of CRs. As recently there is a growing interest in applying machine learning (ML) for clinical prediction, these techniques have also bee...
Preprint
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Monitoring the quality of statistical processes has been of great importance, mostly in industrial applications. Control charts are widely used for this purpose, but often lack the possibility to monitor survival outcomes. Recently, inspecting survival outcomes has become of interest, especially in medical settings where outcomes often depend on ri...
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Multi-state models are used to describe how individuals transition through different states over time. The distribution of the time spent in different states, referred to as ‘length of stay’, is often of interest. Methods for estimating expected length of stay in a given state are well established. The focus of this paper is on the distribution of...
Article
Objectives: When introducing new techniques, attention must be paid to learning curve. Besides quantitative outcomes, qualitative factors of influence should be taken into consideration. This retrospective cohort study describes the quantitative learning curve of complex endovascular aortic repair (EVAR) in a non-high-volume academic center, and p...
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Background: The amount of stroma within the primary tumor is a prognostic parameter for colon cancer patients. This phenomenon can be assessed using the tumor-stroma ratio (TSR), which classifies tumors in stroma-low (≤50% stroma) and stroma-high (>50% stroma). Although the reproducibility for TSR determination is good, improvement might be expect...
Article
Objective: To analyze risk and patterns of locoregional failure (LRF) in patients of the RAPIDO trial at five years. Summary background data: Multimodality treatment improves local control in rectal cancer. Total neoadjuvant treatment (TNT) aims to improve systemic control while local control is maintained. At three years, LRF rate was comparabl...
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In studies of recurrent events, joint modeling approaches are often needed to allow for potential dependent censoring by a terminal event such as death. Joint frailty models for recurrent events and death with an additional dependence parameter have been studied for cases in which individuals are observed from the start of the event processes. Howe...
Article
Introduction The angiosome concept is defined as the anatomical territory of a source artery within all tissue layers. When applying this theory in vascular surgery, direct revascularization is preferred to achieve increased blood flow towards the targeted angiosome of the foot in patients with lower extremity arterial disease (LEAD). This study ev...
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BACKGROUND: The endometrial cancer molecular classification has been integrated into the 2020 World Health Organization (WHO) diagnostic classification and European treatment guidelines, and provides direction towards more effective and less toxic adjuvant treatment strategies for women with endometrial cancer. PRIMARY OBJECTIVES: The RAINBO progra...
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The purpose of this study was to evaluate the association between four distinct histopathological features: (1) tumor infiltrating lymphocytes, (2) mucinous differentiation, (3) tumor-stroma ratio, plus (4) tumor budding and two gene expression-based classifiers—(1) consensus molecular subtypes (CMS) plus (2) colorectal cancer intrinsic subtypes (C...
Conference Paper
Introduction/Background In 2021, the ESGO-ESTRO-ESP endometrial cancer (EC) guideline was updated and the molecular classification was added to the clinicopathological prognostic factors to classify women with EC in risk groups. The risk stratification is based on consensus of a multitude of studies investigating a variety of EC subgroups. To date,...
Conference Paper
Introduction/Background The EMBRACE Vaginal Morbidity sub-study prospectively evaluated physician-assessed vaginal changes and patient-reported-outcomes (PRO) on vaginal and sexual functioning problems, and sexual distress in the first 2 years after radio(chemo)therapy with image-guided adaptive brachytherapy for locally advanced cervical cancer....
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Introduction In older patients with breast cancer, the risk of dying from other causes than breast cancer strongly increases after the age of 70. The aim of this study was to assess contributions of breast cancer mortality versus other-cause mortality after locoregional or distant recurrence in a population-based cohort of older patients analysed b...
Article
The additive hazards model specifies the effect of covariates on the hazard in an additive way, in contrast to the popular Cox model, in which it is multiplicative. As non-parametric model, additive hazards offer a very flexible way of modeling time-varying covariate effects. It is most commonly estimated by ordinary least squares. In this paper we...
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Rapidly detecting problems in the quality of care is of utmost importance for the well-being of patients. Without proper inspection schemes, such problems can go undetected for years. Cumulative sum (CUSUM) charts have proven to be useful for quality control, yet available methodology for survival outcomes is limited. The few available continuous t...
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Background The challenging nature of performing surgery on a personal and professional level demands specific characteristics. Personality traits play an important role in the nature and behavior of humans, which are studied using the five-factor model. Therefore, we investigated the personality of 3 surgical generations. Methods Three distinct su...
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Background: Survival for rectal cancer patients has improved over the past decades. In parallel, long-term health-related quality of life (HRQoL) is gaining interest. This study focuses on the effect of complications following rectal cancer surgery on HRQoL and survival. Methods: The TME-trial (1996-1999) randomized patients with operable rectal...
Preprint
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Background Chronic anal fissure is a common benign anorectal disease with a high recurrence rate. Pelvic floor physical therapy has been proven effective in the short-term management in patients with chronic anal fissure and pelvic floor dysfunction (PAF-trial). The aim of this study was to determine the outcomes of the PAF-trial and fissure recurr...
Preprint
The purpose of this study was to evaluate the association between four distinct histopathological features, (1) tumor infiltrating lymphocytes, (2) mucinous differentiation, (3) tumor-stroma ratio, (4) tumor budding and two gene expression-based classifiers, (1) consensus molecular subtypes (CMS), (2) colorectal cancer intrinsic subtypes (CRIS). Al...
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Primary Plasma Cell Leukaemia (pPCL) is a rare and challenging malignancy. There is limited data regarding optimum transplant approaches. Therefore we undertook a retrospective analysis from 1998-2014 of 751 patients with Primary Plasma Cell Leukaemia (pPCL) undergoing one of four transplant strategies; single autologous transplant (single-auto), s...
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The most important outcome of many studies of haematopoietic cell transplants is survival. The statistical field that deals with such outcomes is survival analysis. Methods developed in this field are also applicable to other outcomes where the occurrence and timing are important. Analysis of such time-to-event outcomes has special challenges becau...
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Background: The optimal treatment strategy for postoperative pain following pancreatoduodenectomy remains unknown. The aim of this study was to investigate whether sublingual sufentanil tablet (SST) is a non-inferior analgesic compared to our standard-of-care (patient-controlled epidural analgesia [PCEA] or PCA morphine) in the treatment of pain f...
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In studies analyzing competing time-to-event outcomes, interest often lies in both estimating the effects of baseline covariates on the cause-specific hazards and predicting cumulative incidence functions. When missing values occur in these baseline covariates, they may be discarded as part of a complete-case analysis or multiply imputed. In the la...
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Objective To quantify prediction model performance in relation to data preparation choices when using electronic health records (EHR). Study Design and Setting Cox proportional hazards models were developed for predicting the first-ever main adverse cardiovascular events using Dutch primary care EHR data. The reference model was based on a 1-year...
Article
545 Background: The Breast Cancer Index (BCI) is a gene expression–based signature that stratifies patients based on the risk of overall (0-10y) and late (post-5y) distant recurrence (DR) and predicted the likelihood of benefit from extended endocrine therapy in MA.17, Trans-aTTom, IDEAL, and B-42 trials. The Clinical Treatment Score post-5 years (...
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Background: To develop a model for the prediction of the (most likely) effect of red blood cell (RBC) transfusion on subsequent organ functioning in nonbleeding critically ill patients with hemoglobin concentrations between 6 and 9 g/dL. Study design and methods: We conducted a retrospective cohort study using electronic health care data of nonb...
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Background and objectives: With the current advanced data-driven approach to health care, machine learning is gaining more interest. The current study investigates the added value of machine learning to linear regression in predicting anastomotic leakage and pulmonary complications after upper gastrointestinal cancer surgery. Methods: All patien...
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Background Anti-cancer drugs commonly adversely affect fertility and sexual function. Despite this, patients report a lack of counselling of these potential adverse effects. The aim was to determine Dutch oncologists’ knowledge about the adverse effects of various cancer drugs on fertility and sexual function. Methods A cross-sectional survey was...
Article
Purpose: For postmenopausal patients with breast cancer, previous subgroup analyses have shown a modest benefit from adjuvant bisphosphonate treatment. However, the efficacy of oral nitrogen-containing bisphosphonates such as ibandronate is unclear in this setting. TEAM-IIB investigates adjuvant ibandronate in postmenopausal women with estrogen re...
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Samenvatting In een placebogecontroleerde, multicenter, dubbelblind gerandomiseerde studie met 128 patiënten met bevestigde niersteenkolieken is onderzocht of placebo non-inferieur is aan continue infusie van butylscopolamine. De ene arm kreeg continue infusie van butylscopolamine, de andere arm placebo (zoutoplossing i.v.). De primaire uitkomstmaa...
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Background: In hemodialysis patients, implantable cardioverter-defibrillator (ICD) implantation may result in central venous stenosis (CVS) with associated symptoms, such as pain, edema of the ipsilateral arm, facial edema, and loss of dialysis access. However, literature concerning CVS in dialysis patients with a cardiac implantable electronic de...
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Introduction Anastomotic leakage (AL) is one of the major complications after colorectal surgery. Compromised tissue perfusion at the anastomosis site increases the risk of AL. Several cohort studies have shown that indocyanine green (ICG) combined with fluorescent near-infrared imaging is a feasible and reproducible technique for real-time intraop...
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Background and purpose The RAPIDO trial demonstrated a decrease in disease-related treatment failure (DrTF) and an increase in pathological complete responses (pCR) in locally advanced rectal cancer (LARC) patients receiving total neoadjuvant treatment (TNT) compared to conventional chemoradiotherapy. This study examines health-related quality of l...
Article
BACKGROUND AND AIMS Screening for celiac disease (CD) is recommended in children with affected first-degree relatives (FDR). However, the frequency of screening and at what age remain unknown. Aims:to detect variables influencing the risk of CD-development and develop and validate clinical prediction models to provide individualized screening advic...
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Multi-state models provide an extension of the usual survival/event-history analysis setting. In the medical domain, multi-state models give the possibility of further investigating intermediate events such as relapse and remission. In this work, a further extension is proposed using relative survival, where mortality due to population causes (i.e....
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Benchmarking is commonly used in many healthcare settings to monitor clinical performance, with the aim of increasing cost-effectiveness and safe care of patients. The funnel plot is a popular tool in visualizing the performance of a healthcare center in relation to other centers and to a target, taking into account statistical uncertainty. In this...
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Purpose: Near-infrared (NIR) fluorescence imaging using indocyanine green (ICG) is gaining popularity for the quantification of tissue perfusion, including foot perfusion in patients with lower extremity arterial disease (LEAD). However, the absolute fluorescence intensity is influenced by patient-and system-related factors limiting reliable and v...
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Background In diagnosing peripheral arterial disease (PAD), medial arterial calcification (MAC) hampers arterial compression and could lead to unreliable ankle brachial index (ABI), toe brachial index (TBI) and toe pressure (TP). Doppler ultrasonography (DUS) derived maximal systolic acceleration (ACCmax) might be more accurate to diagnose PAD. In...
Article
Background Patients with advanced endometrial cancer have a poor prognosis, and treatment options are limited. The investigator-initiated, multicenter, phase II DOMEC trial (NCT03951415) is the first trial to report data on efficacy and safety of combined treatment with PD-L1 and PARP inhibition for advanced endometrial cancer. Patients and method...
Article
Background: The evaluation of health-related quality of life (HRQoL) in clinical trials has become increasingly important because it addresses the impact of treatment from the patient's perspective. The primary aim of this study was to investigate the effect of postoperative chemotherapy and chemoradiotherapy (CRT) after neoadjuvant chemotherapy a...
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Background The Fine-Gray subdistribution hazard model is frequently used in the cardiovascular literature to estimate subject-specific probabilities of the occurrence of an event of interest over time in the presence of competing risks. A little-known limitation of this approach is that, for some subjects and for some time points, the sum of the su...
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The problem of dynamic prediction with time‐dependent covariates, given by biomarkers, repeatedly measured over time, has received much attention over the last decades. Two contrasting approaches have become in widespread use. The first is joint modeling, which attempts to jointly model the longitudinal markers and the event time. The second is lan...
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Background Assessing calibration—the agreement between estimated risk and observed proportions—is an important component of deriving and validating clinical prediction models. Methods for assessing the calibration of prognostic models for use with competing risk data have received little attention. Methods We propose a method for graphically asses...
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Liquid biopsy has emerged as a novel approach to tumor characterization, offering advantages in sample accessibility and tissue heterogeneity. However, as mutational analysis predominates, the tumor microenvironment has largely remained unacknowledged in liquid biopsy research. The current work provides an explorative transcriptomic characterizatio...
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Clofarabine is an active antileukemic drug for subgroups of patients with acute myeloid leukemia (AML). Multi-state models can provide additional insights to supplement the original intention-to-treat analysis of randomized controlled trials (RCT). We re-analyzed the HOVON102/SAKK30/09 phase III RCT for newly diagnosed AML patients, which randomize...
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The tumour-stroma ratio (TSR) and tumour budding (TB) are two high-risk factors with potential to be implemented in the next TNM classification. The aim of the current study was to evaluate the practical application of the two biomarkers based on reproducibility, independency and prognostic value. Patients diagnosed with stage II or III colon cance...
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Objective To identify the optimal estimated glomerular filtration rate (eGFR) at which to initiate dialysis in people with advanced chronic kidney disease. Design Nationwide observational cohort study. Setting National Swedish Renal Registry of patients referred to nephrologists. Participants Patients had a baseline eGFR between 10 and 20 mL/min...
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Background. Studies focusing on prediction models are widespread in medicine. There is a trend in applying machine learning (ML) by medical researchers and clinicians. Over the years, multiple ML algorithms have been adapted to censored data. However, the choice of methodology should be motivated by the real-life data and their complexity. Here, th...
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Objectives: The aim of this retrospective study was to assess the predictive performance of the American College of Surgeons (ACS) risk calculator for aortic aneurysm repair for the patient population of a Dutch tertiary referral hospital. Methods: This retrospective study included all patients who underwent elective endovascular or open aortic...
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Background Current prediction tools for breast cancer outcomes are not tailored to the older patient, in whom competing risk strongly influences treatment effects. We aimed to develop and validate a prediction tool for 5-year recurrence, overall mortality, and other-cause mortality for older patients (aged ≥65 years) with early invasive breast canc...
Article
Objectives: The utilization of liver allografts could be optimized if nonacceptance is predicted. This study aimed to evaluate the prognostic ability of an updated Discard Risk Index in Eurotransplant. Materials and methods: Potential deceased donors from January 2010 to December 2015 who had been reported to Eurotransplant were included in our...
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Aim To evaluate the prognostic value of tumor markers in a European cohort of patients with resectable gastric cancer. Methods We performed a post hoc analysis of the CRITICS trial, in which 788 patients received perioperative therapy. Association between survival and pretreatment CEA, CA 19-9, alkaline phosphatase, neutrophils, hemoglobin and lac...
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The best current biomarker strategies for predicting response to immune checkpoint inhibitor (ICI) therapy fail to account for interpatient variability in response rates. The histologic tumor–stroma ratio (TSR) quantifies intratumoral stromal content and was recently found to be predictive of response to neoadjuvant therapy in multiple cancer types...
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External beam radiation therapy (EBRT) with concurrent chemotherapy followed by brachytherapy is a very effective treatment for locally advanced cervical cancer (LACC). However, treatment-related toxicity is common and reduces the patient’s quality of life (QoL) and ability to complete treatment or undergo adjuvant therapies. Intensity modulated pr...
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Multi-state models are increasingly being used to model complex epidemiological and clinical outcomes over time. It is common to assume that the models are Markov, but the assumption can often be unrealistic. The Markov assumption is seldomly checked and violations can lead to biased estimation of many parameters of interest. This is a well known p...
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Introduction Radiotherapy techniques have developed from 3-dimensional conformal radiotherapy (3DCRT) to intensity-modulated radiotherapy (IMRT), with better sparing of the surrounding normal tissues. The current analysis aimed to investigate whether IMRT, compared to 3DCRT, resulted in fewer adverse events (AE) and patient-reported symptoms in the...
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Cancer diagnosis and treatment may influence reproductive planning and impact fertility in patients of reproductive age. Although guidelines have been established in the past decade, education, practice, and attitudes of medical oncologists regarding fertility preservation remain undecided. A nationwide survey was performed among members of the Dut...
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Background: Long-term use of statins is associated with a small reduced risk of colorectal cancer but their mechanism of action is not well understood. While they are generally believed to act on KRAS, we have previously proposed that they act via influencing the BMP pathway. The objective of this study was to look for associations between statin...