Leiden University Scholarly Publications

Hendriks, L.E.; Kerr, K.M.; Menis, J.; Mok, T.S.; Nestle, U.; Passaro, A.; ... ; ESMO Guidelines Committee 2023

Oncogene-addicted metastatic non-small-cell lung cancer: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up

Article / Letter to editor

open access

• •This ESMO Clinical Practice Guideline provides key recommendations and algorithms for managing oncogene-addicted mNSCLC.
• •ESMO-MCBS scores are given to describe the levels of evidence for treatment...

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• •This ESMO Clinical Practice Guideline provides key recommendations and algorithms for managing oncogene-addicted mNSCLC.
• •ESMO-MCBS scores are given to describe the levels of evidence for treatment choices.
• •ESCAT scores are given to describe the evidence level for genomic alterations as biomarkers for using targeted therapies.
• •Recommendations are based on available scientific data and the authors’ collective expert opinion.
• •In clinical practice, all recommendations provided need to be discussed with patients in a shared decision-making approach

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Ruschoff, J.H.; Haberecker, M.; Tsourti, Z.; Nackaerts, K.; Perrot, M. de; Brcic, L.; ... ; Consortium, E.M. 2022

Correction to: Expression of phosphorylated ribosomal protein S6 in mesothelioma patients-correlation with clinico-pathological characteristics and outcome: results from the European Thoracic Oncology Platform (ETOP) Mesoscape project

Article / Letter to editor

open access

Felip, E.; Smit, E.F.; Molina-Vila, M.A.; Dafni, U.; Massuti, B.; Berghmans, T.; ... ; ETOP 12-17 ALERT-Lung Collaborator 2022

Alectinib for the treatment of pretreated RET-rearranged advanced NSCLC: results of the ETOP ALERT-lung trial

Article / Letter to editor

open access

Background: Alectinib, a highly selective next generation ALK-inhibitor, has exhibited potent anti-tumour activity in RET-rearranged NSCLC in the preclinical stage. Methods: ALERT-lung is a single... Show moreBackground: Alectinib, a highly selective next generation ALK-inhibitor, has exhibited potent anti-tumour activity in RET-rearranged NSCLC in the preclinical stage. Methods: ALERT-lung is a single-arm, phase II trial evaluating the activity of alectinib for the treatment of pretreated RET-rearranged advanced NSCLC. Alectinib was administered orally, 600 mg, twice per day until progression, refusal or unacceptable toxicity (treatment could continue beyond progression, if patient was deriving clinical benefit). Patient recruitment closed prematurely due to discouraging results for alectinib in a phase I/II study in the same indication. Results: All 14 patients who enrolled until the premature accrual closure, received at lease one dose of alectinib. Among them, median age was 61 years, majority (71 %) was female, never smokers, of ECOG PS 1. No objective response (complete or partial response) was recorded. Of the 13 evaluable patients, three (23 %) achieved and maintained disease stabilisation for 24 weeks. Up to 31 March 2021 (median follow-up 15.9 months), 12 PFS-events (92 %) were observed, with median PFS of 3.7 months (95 % C.I.: 1.8 - 7.3 months). Overall, three deaths (23 %) were reported. Seven patients (50 %) experienced grade = 3 adverse events, while three discontinued treatment due to erythema multiforme of grade 3, related to alectinib. No treatment-related serious adverse event was reported. Conclusions: Accrual into our trial was terminated early in response to other reports of limited activity of alectinib in patients with RET-fusion NSCLC and the emergence of more potent selective RET-inhibitors. Also in our trial, alectinib did not show the expected potential for anti-tumour activity in NSCLC. Show less

Scherpereel, A.; Antonia, S.; Bautista, Y.; Grossi, F.; Kowalski, D.; Zalcman, G.; ... ; Baas, P. 2022

First-line nivolumab plus ipilimumab versus chemotherapy for the treatment of unresectable malignant pleural mesothelioma: patient-reported outcomes in CheckMate 743

Article / Letter to editor

open access

Objective: In CheckMate 743 (NCT02899299), nivolumab + ipilimumab significantly prolonged overall survival in patients with unresectable malignant pleural mesothelioma (MPM). We present patient... Show moreObjective: In CheckMate 743 (NCT02899299), nivolumab + ipilimumab significantly prolonged overall survival in patients with unresectable malignant pleural mesothelioma (MPM). We present patient-reported outcomes (PROs). Materials and Methods: Patients (N = 605) were randomized to nivolumab + ipilimumab or chemotherapy. Changes in disease-related symptom burden and health-related quality of life (HRQoL) were evaluated descriptively using the Lung Cancer Symptom Scale (LCSS)-Mesothelioma (Meso) average symptom burden index (ASBI), LCSS-Meso 3-item global index (3-IGI), 3-level EuroQol 5-dimensional (EQ-5D-3L) visual analog score (VAS), and EQ-5D-3L utility index. PROs were assessed at baseline and every 2 (nivolumab + ipilimumab) or 3 weeks (chemotherapy) through 12 weeks, every 6 weeks through 12 months, every 12 weeks thereafter, and at specified follow-ups. Mixed-effect model repeated measures (MMRM) and time to deterioration analyses were conducted. Results: Completion rates were generally > 80%. LCSS-Meso ASBI mean changes from baseline trended to improve over time with nivolumab + ipilimumab and deteriorate with chemotherapy, but did not meet clinically important difference thresholds [& PLUSMN;10 score change]. EQ-5D-3L VAS mean scores improved over time with nivolumab + ipilimumab; by week 60, patients had scores consistent with United Kingdom normal population values. MMRM analyses favored nivolumab + ipilimumab for all individual symptoms except cough. Nivolumab + ipilimumab delayed time to definitive deterioration in HRQoL (hazard ratio 0.52 [95% confidence interval 0.36-0.74]) and showed a trend in symptom delay versus chemotherapy. Conclusions: Nivolumab + ipilimumab decreased the risk of deterioration in disease-related symptoms and HRQoL versus chemotherapy and maintained QoL in patients with unresectable MPM. Show less

Aar, L.P.E. van der; Peters, S.; Becht, A.I.; Crone, E.A.M. 2021

Better self-concept, better future choices? Behavioral and neural changes after a naturalistic self-concept training program for adolescents

Article / Letter to editor

open access

A large number of adolescents experience difficulty when choosing a suitable higher education program that matches their self-views. Stimulating self-concept development could help adolescents to... Show moreA large number of adolescents experience difficulty when choosing a suitable higher education program that matches their self-views. Stimulating self-concept development could help adolescents to increase their chances of finding a suitable major. We addressed this issue by examining the effects of a naturalistic self-concept training within a gap year context on behavioral and neural correlates of self-evaluations, as well as the long-term effects for future educational decision-making. In total, 38 adolescents/young adults (ages 16-24 years) participated in a 4-wave longitudinal study, with lab visits before, during, and after the training, including behavioral assessments and fMRI. During fMRI-scanning, they rated themselves on positive and negative traits in academic, (pro)social, and physical domains, and additionally filled out questionnaires related to self-esteem and self-concept clarity. Results showed that the positivity of domain-specific self-evaluations, self-esteem, and self-concept clarity increased during the training. Second, participants with lower medial PFC activity during self-evaluation before training showed larger self-esteem increases over the year. Moreover, mPFC activity increased after training for the evaluation of positive but not negative traits. Furthermore, individual differences in the rate of change (slope) in self-concept clarity and social self-evaluations positively predicted social adjustment to college and academic performance 6 months after training. Together, these findings suggest that self-concept can be modulated in late adolescents, with an important role of the medial PFC in relation to enhanced positive self-evaluations, and self-concept clarity as a predictor of future educational outcomes. Show less

Peters, S.; Cruijsen, R. van der; Aar, L.P.E. van der; Spaans, J.P.; Becht, A.I.; Crone, E.A.M. 2021

Social media use and the not-so-imaginary audience: behavioral and neural mechanisms underlying the influence on self-concept

Article / Letter to editor

open access

We investigated behavioral and neural mechanisms in the relation between social media use (SMU) and selfconcept, as well as longitudinal developmental outcomes. Adolescents and young adults (N =... Show moreWe investigated behavioral and neural mechanisms in the relation between social media use (SMU) and selfconcept, as well as longitudinal developmental outcomes. Adolescents and young adults (N = 150, 11?21 years old at T1) rated themselves on 60 traits in the academic, physical and prosocial domain, and also indicated how they thought peers would judge them (reflected-peer-judgements). Longitudinal questionnaires (1-and 2 year follow-up) were collected to assess positive (prosocial behavior, self-concept clarity) and negative (clinical symptoms) long-term outcomes. Results indicated that heavier self-reported SMU was linked with lower difference scores between self judgements and reflected-peer-judgements. Lower SMU was related to more positive ratings from self judgements vs. reflected-peer-judgements. SMU was also associated with less positive self-concept, particularly in the academic domain (boys and girls) and physical domain (girls). Neurally, increased SMU was linked to heightened mPFC-activity during self-judgements compared to reflected-peer-judgements, and increased activity during physical compared to academic and prosocial self-judgements. Longitudinal analyses indicated no evidence for long-term effects of social media use, self/reflected-peer-difference scores and mPFC-activity on clinical symptoms, prosocial behavior or self-concept clarity. This study highlights the complex relationship between social media use and wellbeing and future research is needed to confirm the lack of long-term effects. Show less

McCormick, E.M.; Peters, S.; Crone, E.A.; Telzer, E.H. 2021

Longitudinal network re-organization across learning and development

Article / Letter to editor

open access

While it is well understood that the brain experiences changes across short-term experience/learning and long-term development, it is unclear how these two mechanisms interact to produce... Show moreWhile it is well understood that the brain experiences changes across short-term experience/learning and long-term development, it is unclear how these two mechanisms interact to produce developmental outcomes. Here we test an interactive model of learning and development where certain learning-related changes are constrained by developmental changes in the brain against an alternative development-as-practice model where outcomes are determined primarily by the accumulation of experience regardless of age. Participants (8-29 years) participated in a three-wave, accelerated longitudinal study during which they completed a feedback learning task during an fMRI scan. Adopting a novel longitudinal modeling approach, we probed the unique and moderated effects of learning, experience, and development simultaneously on behavioral performance and network modularity during the task. We found nonlinear patterns of development for both behavior and brain, and that greater experience supported increased learning and network modularity relative to naive subjects. We also found changing brain-behavior relationships across adolescent development, where heightened network modularity predicted improved learning, but only following the transition from adolescence to young adulthood. These results present compelling support for an interactive view of experience and development, where changes in the brain impact behavior in context-specific fashion based on developmental goals. Show less

McCormick, E.M.; Peters, S.; Crone, E.A.M.; Telzer, E.H. 2021

Longitudinal network re-organization across learning and development

Article / Letter to editor

open access

While it is well understood that the brain experiences changes across short-term experience/learning and long-term development, it is unclear how these two mechanisms interact to produce... Show moreWhile it is well understood that the brain experiences changes across short-term experience/learning and long-term development, it is unclear how these two mechanisms interact to produce developmental outcomes. Here we test an interactive model of learning and development where certain learning-related changes are constrained by developmental changes in the brain against an alternative development-as-practice model where outcomes are determined primarily by the accumulation of experience regardless of age. Participants (8–29 years) participated in a three-wave, accelerated longitudinal study during which they completed a feedback learning task during an fMRI scan. Adopting a novel longitudinal modeling approach, we probed the unique and moderated effects of learning, experience, and development simultaneously on behavioral performance and network modularity during the task. We found nonlinear patterns of development for both behavior and brain, and that greater experience supported increased learning and network modularity relative to naïve subjects. We also found changing brain-behavior relationships across adolescent development, where heightened network modularity predicted improved learning, but only following the transition from adolescence to young adulthood. These results present compelling support for an interactive view of experience and development, where changes in the brain impact behavior in context-specific fashion based on developmental goals. Show less

Becht, A.I.; Klapwijk, E.T.; Wierenga, L.M.; Cruijsen, R. van der; Spaans, J.; Aar, L. van der; ... ; Crone, E.A. 2020

Longitudinal associations between structural prefrontal cortex and nucleus accumbens development and daily identity formation processes across adolescence

Article / Letter to editor

open access

2020-12-31T00:00:00Z

15.92 years) were followed across three waves, covering 4 years. Self-reported daily educational identity and structural brain data of lateral prefrontal cortex (lPFC)/anterior cingulate cortex ... Show more15.92 years) were followed across three waves, covering 4 years. Self-reported daily educational identity and structural brain data of lateral prefrontal cortex (lPFC)/anterior cingulate cortex (ACC), medial PFC, and nucleus accumbens (NAcc) was collected across three waves. All hypotheses were pre-registered. Latent class growth analyses confirmed 2 identity subgroups: an identity synthesis class (characterized by strong commitments, and low uncertainty), and an identity moratorium class (high daily identity uncertainty). Latent growth curve models revealed, on average, delayed maturation of the lateral PFC/ACC and medial PFC and stable NAcc. Yet, adolescents in identity moratorium showed lower levels and less decline in NAcc gray matter volume. Lateral PFC/ACC and medial PFC trajectories did not differ between identity subgroups. Exploratory analyses revealed that adolescents with higher baseline levels and delayed maturation of lateral PFC/ACC and medial PFC gray matter volume, surface area, and cortical thickness reported higher baseline levels and stronger increases of in-depth exploration. These results provide insight into how individual differences in brain development relate to fluctuations in educational identity development across adolescence and young adulthood. Show less

Thunnissen, E.; Kerr, K.M.; Dafni, U.; Bubendorf, L.; Finn, S.P.; Soltermann, A.; ... ; European Thoracic Oncology 2020

Programmed death-ligand 1 expression influenced by tissue sample size. Scoring based on tissue microarrays' and cross-validation with resections, in patients with, stage I-III, non-small cell lung carcinoma of the European Thoracic Oncology Platform Lungscape cohort

Article / Letter to editor

metadata only

PD-L1, as assessed by immunohistochemistry, is a predictive biomarker for immuno-oncology treatment in lung cancer. Different scoring methods have been used to assess its status, resulting in a... Show morePD-L1, as assessed by immunohistochemistry, is a predictive biomarker for immuno-oncology treatment in lung cancer. Different scoring methods have been used to assess its status, resulting in a wide range of positivity rates. We use the European Thoracic Oncology Platform Lungscape non-small cell lung carcinoma cohort to explore this issue. PD-L1 expression was assessed via immunohistochemistry on tissue microarrays (up to four cores per case), using the DAKO 28-8 immunohistochemistry assay, following a two-round external quality assessment procedure. All samples were analyzed under the same protocol. Cross-validation of scoring between tissue microarray and whole sections was performed in 10% randomly selected samples. Cutoff points considered: >= 1, 50 (primarily), and 25%. At the two external quality assessment rounds, tissue microarray scoring agreement rates between pathologists were: 73% and 81%. There were 2008 cases with valid immunohistochemistry tissue microarray results (50% all cores evaluable). Concordant cases at 1, 25, and 50% were: 85, 91, and 93%. Tissue microarray core results were identical for 70% of cases. Sensitivity of the tissue microarray method for 1, 25, and 50% was: 80, 78, and 79% (specificity: 90, 95, 98%). Complete agreement between tissue microarrays and whole sections was achieved for 60% of the cases. Highest sensitivity rates for 1% and 50% cutoffs were detected for higher number of cores. Underestimation of PD-L1 expression on small samples is more common than overestimation. We demonstrated that classification of PD-L1 on small biopsy samples does not represent the overall expression of PD-L1 in all non-small cell cancer carcinoma cases, although the majority of cases are 'correctly' classified. In future studies, sampling more and larger biopsies, recording the biopsy size and tumor load may permit further refinement, increasing predictive accuracy. Show less