Prognostic value of radiologic and pathological response in colorectal cancer liver metastases upon systemic induction treatment: subgroup analysis of the CAIRO5 trial.

Background: RECIST may not be optimal for assessing treatment response with current systemic regimens. We evaluated RECIST, morphologic, and pathologically documented response (pathological response) in patients with initially unresectable colorectal cancer liver-only metastases (CRLM).

Patients And Methods: Four hundred and eighty-nine patients from the phase III CAIRO5 trial were included who were treated with FOLFOX/FOLFIRI/FOLFOXIRI and bevacizumab or panitumumab.

Cancer treatment monitoring using cell-free DNA fragmentomes.

Circulating cell-free DNA (cfDNA) assays for monitoring individuals with cancer typically rely on prior identification of tumor-specific mutations. Here, we develop a tumor-independent and mutation-independent approach (DELFI-tumor fraction, DELFI-TF) using low-coverage whole genome sequencing to determine the cfDNA tumor fraction and validate the method in two independent cohorts of patients with colorectal or lung cancer. DELFI-TF scores strongly correlate with circulating tumor DNA levels (ctDNA) (r = 0.

Neurocognition and academic achievement among bereaved children in the Generation R Cohort.

Childhood bereavement is an adverse event, yet children demonstrate considerable variability in health outcomes. Bereaved children are at risk of lower lifelong educational attainment, though the contribution of neurocognitive performance is yet to be investigated. Using data from the population-based Generation R Study wherein nearly 10,000 pregnant mothers were recruited between 2002 and 2006, we estimated the association of bereavement by age 10 years with four subtests of cognitive function and academic achievement at 13 years.

The Association Between Trajectories of Self-reported Psychotic Experiences and Continuity of Mental Health Care in a Longitudinal Cohort of Adolescents and Young Adults.

Background And Hypothesis: Young people (YP) with psychotic experiences (PE) have an increased risk of developing a psychiatric disorder. Therefore, knowledge on continuity of care from child and adolescent (CAMHS) to adult mental health services (AMHS) in relation to PE is important. Here, we investigated whether the self-reported trajectories of persistent PE were associated with likelihood of transition to AMHS and mental health outcomes.

Hepatic arterial infusion pump chemotherapy combined with systemic chemotherapy for borderline resectable and unresectable colorectal liver metastases: phase II feasibility study.

Background: Hepatic arterial infusion pump chemotherapy combined with systemic chemotherapy (HAIP-SYS) for liver-only colorectal liver metastases (CRLMs) has shown promising results but has not been adopted worldwide. This study evaluated the feasibility of HAIP-SYS in the Netherlands.

Methods: This was a single-arm phase II study of patients with CRLMs who received HAIP-SYS consisting of floxuridine with concomitant systemic FOLFOX or FOLFIRI.

Extrahepatic perfusion and incomplete hepatic perfusion after hepatic arterial infusion pump implantation: incidence and clinical implications.

Introduction: This study investigates the incidence of extrahepatic perfusion and incomplete hepatic perfusion at intraoperative methylene blue testing and on postoperative nuclear imaging in patients undergoing hepatic arterial infusion pump (HAIP) chemotherapy.

Methods: The first 150 consecutive patients who underwent pump implantation in the Netherlands were included. All patients underwent surgical pump implantation with the catheter in the gastroduodenal artery.

Maternal Migration, Prenatal Stress and Child Autistic Traits: Insights From a Population-Based Cohort Study.

Objective: There is emerging evidence for an increased prevalence of autism in children of mothers with a migration background. To date, the mechanisms underlying this relationship are poorly understood. We investigated whether prenatal stress exposure mediates the association between maternal migration and child autistic traits, assessing first- and second-generation migrant mothers in the Netherlands and their children.

Childhood Adversity and Incident Psychotic Experiences in Early Adulthood: Cognitive and Psychopathological Mediators.

Background And Hypothesis: Childhood adversity is often described as a potential cause of incident psychotic experiences, but the underlying mechanisms are not well understood. We aimed to examine the mediating role of cognitive and psychopathological factors in the relation between childhood adversity and incident psychotic experiences in early adulthood.

Study Design: We analyzed data from the Avon Longitudinal Study of Parents and Children, a large population-based cohort study.

Risk of Psychosis Among Individuals Who Have Presented to Hospital With Self-harm: A Prospective Nationwide Register Study in Sweden.

Background And Hypothesis: Recent research showed that young people who presented to hospital with self-harm in Finland had a significantly elevated risk of later psychosis. We investigated the prospective relationship between hospital presentation for self-harm and risk of psychosis in an unprecedentedly large national Swedish cohort.

Study Design: We used inpatient and outpatient healthcare registers to identify all individuals born between 1981 and 1993 who were alive and living in Sweden on their 12th birthday and who presented to hospital one or more times with self-harm.

Survival of Patients with Deficient Mismatch Repair Versus Proficient Mismatch Repair Metastatic Colorectal Cancer Receiving Curative-Intent Local Treatment of Metastases in a Nationwide Cohort.

Background: It is unclear whether curative-intent local therapy of metastases is of similar benefit for the biological distinct subgroup of patients with deficient mismatch repair (dMMR) metastatic colorectal cancer (mCRC) compared with proficient mismatch repair (pMMR) mCRC.

Patients And Methods: In this nationwide study, recurrence-free (RFS) and overall survival (OS) were analyzed in patients with dMMR versus pMMR mCRC who underwent curative-intent local treatment of metastases between 2015 and 2018. Subgroup analyses were performed for resection of colorectal liver metastases (CRLM) and cytoreductive surgery ± hyperthermic intraperitoneal chemotherapy (CRS ± HIPEC).

First-line systemic treatment strategies in patients with initially unresectable colorectal cancer liver metastases (CAIRO5): an open-label, multicentre, randomised, controlled, phase 3 study from the Dutch Colorectal Cancer Group.

Background: Patients with initially unresectable colorectal cancer liver metastases might qualify for local treatment with curative intent after reducing the tumour size by induction systemic treatment. We aimed to compare the currently most active induction regimens.

Methods: In this open-label, multicentre, randomised, phase 3 study (CAIRO5), patients aged 18 years or older with histologically confirmed colorectal cancer, known RAS/BRAF mutation status, WHO performance status of 0-1, and initially unresectable colorectal cancer liver metastases were enrolled at 46 Dutch and one Belgian secondary and tertiary centres.

Child Neuropsychological Functioning and Interpersonal Callousness as Predictors of Externalising Behaviour in Early Adolescence: A Prospective Population-based Study.

Externalizing problems are a key predictor of individual functioning in adulthood. Therefore, identifying possible risk factors for externalising problems is valuable for optimising prevention and treatment programmes. Previous research has shown that (domains of) neuropsychological functioning predict externalising problems later in life.

Intersurgeon Variability in Local Treatment Planning for Patients with Initially Unresectable Colorectal Cancer Liver Metastases: Analysis of the Liver Expert Panel of the Dutch Colorectal Cancer Group.

Background: Consensus on resectability criteria for colorectal cancer liver metastases (CRLM) is lacking, resulting in differences in therapeutic strategies. This study evaluated variability of resectability assessments and local treatment plans for patients with initially unresectable CRLM by the liver expert panel from the randomised phase III CAIRO5 study.

Methods: The liver panel, comprising surgeons and radiologists, evaluated resectability by predefined criteria at baseline and 2-monthly thereafter.

The role of tumour biological factors in technical anatomical resectability assessment of colorectal liver metastases following induction systemic treatment: An analysis of the Dutch CAIRO5 trial.

Background: Large inter-surgeon variability exists in technical anatomical resectability assessment of colorectal cancer liver-only metastases (CRLM) following induction systemic therapy. We evaluated the role of tumour biological factors in predicting resectability and (early) recurrence after surgery for initially unresectable CRLM.

Methods: 482 patients with initially unresectable CRLM from the phase 3 CAIRO5 trial were selected, with two-monthly resectability assessments by a liver expert panel.

Mapping gene by early life stress interactions on child subcortical brain structures: A genome-wide prospective study.

Background: Although it is well-established that both genetics and the environment influence brain development, they are typically examined separately. Here, we aimed to prospectively investigate the interactive effects of genetic variants-from a genome-wide approach-and early life stress (ELS) on child subcortical brain structures, and their association with subsequent mental health problems.

Method: Primary analyses were conducted using data from the Generation R Study ( = 2257), including genotype and cumulative prenatal and postnatal ELS scores (encompassing life events, contextual risk, parental risk, interpersonal risk, direct victimisation).

BILATERAL DIFFUSE UVEAL MELANOCYTIC PROLIFERATION MISTAKEN FOR NIVOLUMAB-INDUCED VOGT-KOYANAGI-HARADA DISEASE-LIKE SYNDROME.

Background/purpose: To describe a case of bilateral diffuse uveal melanocytic proliferation (BDUMP) that was mistaken for nivolumab-induced Vogt-Koyanagi-Harada disease-like syndrome.

Methods: We present the case of a 58-year-old white man with metastatic renal clear cell carcinoma for which he was palliatively treated with IV nivolumab immunotherapy. The patient developed subacute onset of blurry vision and gray spots in the visual fields of both eyes, macular subretinal fluid, thickening of the retinal pigment epithelium, and swollen optic nerve heads.

Predicting early extrahepatic recurrence after local treatment of colorectal liver metastases.

Background: Patients who develop early extrahepatic recurrence (EHR) may not benefit from local treatment of colorectal liver metastases (CRLMs). This study aimed to develop a prediction model for early EHR after local treatment of CRLMs using a national data set.

Methods: A Cox regression prediction model for EHR was developed and validated internally using data on patients who had local treatment for CRLMs with curative intent.

A Prospective Cohort Study on the Intergenerational Transmission of Childhood Adversity and Subsequent Risk of Psychotic Experiences in Adolescence.

Background And Hypothesis: Previous studies have shown a robust relationship between childhood adversity and subsequent psychotic symptoms. However, the role of familial risk factors underlying this relationship remains largely unclear. Here, we tested whether offspring childhood adversity and postnatal maternal psychopathology mediated the relationship between maternal childhood adversity and offspring psychotic experiences.

Metastatic Colorectal Cancer Treatment Response Evaluation by Ultra-Deep Sequencing of Cell-Free DNA and Matched White Blood Cells.

Purpose: Circulating tumor DNA (ctDNA) has the potential to guide therapy selection and monitor treatment response in patients with metastatic cancer. However, germline and clonal hematopoiesis-associated alterations can confound identification of tumor-specific mutations in cell-free DNA (cfDNA), often requiring additional sequencing of tumor tissue. The current study assessed whether ctDNA-based treatment response monitoring could be performed in a tumor tissue-independent manner by combining ultra-deep targeted sequencing analyses of cfDNA with patient-matched white blood cell (WBC)-derived DNA.

Help-Seeking Undocumented Migrants in the Netherlands: Mental Health, Adverse Life Events, and Living Conditions.

Undocumented migrants are a particularly vulnerable group regarding (mental) health, living conditions, and restricted access to health care. The aim and objective of the study was to examine the prevalence and correlates of mental health problems in a help-seeking population of undocumented migrants. Observational study was performed by integrating cross-sectional questionnaire data with retrospective electronic patient record data.