Baseline and on Treatment Biodistribution Variability of 18 F-FLT Uptake in Patients With Advanced Melanoma: Brief Communication.

Purpose: This prospective study evaluates the biodistribution of 18 F-FLT PET in patients with advanced melanoma before and after treatment with BRAF/MEK inhibitors.

Patients And Methods: Eighteen BRAF-positive unresectable stage IIIc or IV melanoma patients referred for 18 F-FLT PET/CT before (BL) and during (D14) BRAF/MEK inhibition were included. 18 F-FLT accumulation in the liver, bone marrow, blood, and muscle was quantified.

Focused Ultrasound-Enhanced Liquid Biopsy: A Promising Diagnostic Tool for Brain Tumor Patients.

The performance of minimally invasive molecular diagnostic tools in brain tumors, such as liquid biopsy, has so far been limited by the blood-brain barrier (BBB). The BBB hinders the release of brain tumor biomarkers into the bloodstream. The use of focused ultrasound in conjunction with microbubbles has been shown to temporarily open the BBB (FUS-BBBO).

The Predictive Value of FDG PET/CT for Determining Progression-Free Survival in Advanced Stage III-IV BRAF -Mutated Melanoma Patients Treated With Targeted Therapy-What Can Be Learned From Progression?

Purpose: The aims of this study were to investigate whether (early) PERCIST response monitoring with 18 F-FDG PET/CT is predictive for progression-free survival (PFS) in unresectable stage III or IV melanoma patients treated with BRAF/MEK inhibitor (MEKi) and to define dissemination patterns at progression with a lesion-based evaluation in direct comparison to baseline to improve our understanding of 18 F-FDG PET/CT during BRAF/MEKi.

Patients And Methods: This prospective multicenter single-arm study included 70 patients with unresectable stage III/IV BRAF -mutated melanoma who underwent contrast-enhanced CT and 18 F-FDG PET/CT at baseline and 2 and 7 weeks during treatment with vemurafenib plus cobimetinib and at progression if possible. Tumor response assessment was done with RECIST1.

Efficacy and Safety of Panitumumab in Patients With RAF/RAS-Wild-Type Glioblastoma: Results From the Drug Rediscovery Protocol.

Background: The prognosis of malignant primary high-grade brain tumors, predominantly glioblastomas, is poor despite intensive multimodality treatment options. In more than 50% of patients with glioblastomas, potentially targetable mutations are present, including rearrangements, altered splicing, and/or focal amplifications of epidermal growth factor receptor (EGFR) by signaling through the RAF/RAS pathway. We studied whether treatment with the clinically available anti-EGFR monoclonal antibody panitumumab provides clinical benefit for patients with RAF/RAS-wild-type (wt) glioblastomas in the Drug Rediscovery Protocol (DRUP).

Limited clinical activity of palbociclib and ribociclib monotherapy in advanced cancers with cyclin D-CDK4/6 pathway alterations in the Dutch DRUP and Australian MoST trials.

The Dutch Drug Rediscovery Protocol (DRUP) and the Australian Cancer Molecular Screening and Therapeutic (MoST) Program are similar nonrandomized, multidrug, pan-cancer trial platforms that aim to identify signals of clinical activity of molecularly matched targeted therapies or immunotherapies outside their approved indications. Here, we report results for advanced or metastatic cancer patients with tumors harboring cyclin D-CDK4/6 pathway alterations treated with CDK4/6 inhibitors palbociclib or ribociclib. We included adult patients that had therapy-refractory solid malignancies with the following alterations: amplifications of CDK4, CDK6, CCND1, CCND2 or CCND3, or complete loss of CDKN2A or SMARCA4.

Prevalence and Predictors of Physician-Patient Discordance in Prognostic Perceptions in Advanced Cancer.

Background: Discordance between physicians' and patients' prognostic perceptions in advanced cancer care threatens informed medical decision-making and end-of-life preparation, yet this phenomenon is poorly understood. We sought to: (1) describe the extent and direction of prognostic discordance, patients' prognostic information preferences in cases of prognostic discordance, and physicians' awareness of prognostic discordance; and (2) examine which patient, physician, and caregiver factors predict prognostic discordance.

Materials And Methods: Oncologists and advanced cancer patients (median survival ≤12 months; n = 515) from 7 Dutch hospitals completed structured surveys in a cross-sectional study.

Dabrafenib plus trametinib in BRAFV600E-mutated rare cancers: the phase 2 ROAR trial.

BRAFV600E alterations are prevalent across multiple tumors. Here we present final efficacy and safety results of a phase 2 basket trial of dabrafenib (BRAF kinase inhibitor) plus trametinib (MEK inhibitor) in eight cohorts of patients with BRAFV600E-mutated advanced rare cancers: anaplastic thyroid carcinoma (n = 36), biliary tract cancer (n = 43), gastrointestinal stromal tumor (n = 1), adenocarcinoma of the small intestine (n = 3), low-grade glioma (n = 13), high-grade glioma (n = 45), hairy cell leukemia (n = 55) and multiple myeloma (n = 19). The primary endpoint of investigator-assessed overall response rate in these cohorts was 56%, 53%, 0%, 67%, 54%, 33%, 89% and 50%, respectively.

Attitudes Toward Striving for Quality and Length of Life Among Patients With Advanced Cancer and a Poor Prognosis.

Purpose: When deliberating palliative cancer treatment, insight into patients' attitudes toward striving for quality of life (QL) and length of life (LL) may facilitate goal-concordant care. We investigated the (1) attitudes of patients with advanced cancer toward striving for QL and/or LL and whether these change over time, and (2) characteristics associated with these attitudes (over time).

Methods: We performed a secondary analysis of a randomized controlled trial on improving shared decision making (SDM), without differentiation between intervention arms.

Characteristics of patients with advanced cancer preferring not to know prognosis: a multicenter survey study.

Background: For some patients with advanced cancer not knowing prognosis is essential. Yet, in an era of informed decision-making, the potential protective function of unawareness is easily overlooked. We aimed to investigate 1) the proportion of advanced cancer patients preferring not to know prognosis; 2) the reasons underlying patients' prognostic information preference; 3) the characteristics associated with patients' prognostic information preference; and 4) the concordance between physicians' perceived and patients' actual prognostic information preference.

Complications, compliance, and undertreatment do not explain the relationship between cognition and survival in diffuse glioma patients.

Background: Cognitive deficits occur in all different grades of glioma. In a recent study, we found these deficits to be independently, and possibly causally, related to survival in diffuse gliomas. In this study, we investigated whether the relationship between cognition and survival was mediated by three different factors: undertreatment, complications of treatment, and compliance.

Phase Ib/II Trial of Ribociclib in Combination with Binimetinib in Patients with NRAS-mutant Melanoma.

Purpose: Enhanced MAPK pathway signaling and cell-cycle checkpoint dysregulation are frequent in NRAS-mutant melanoma and, as such, the regimen of the MEK inhibitor binimetinib and the selective CDK4/6 inhibitor ribociclib is a rational combination.

Patients And Methods: This is a phase Ib/II, open-label study of ribociclib + binimetinib in patients with NRAS-mutant melanoma (NCT01781572). Primary objectives were to estimate the MTD/recommended phase II dose (RP2D) of the combination (phase Ib) and to characterize combination antitumor activity at the RP2D (phase II).

Added Value of Cognition in the Prediction of Survival in Low and High Grade Glioma.

Diffuse gliomas, which are at WHO grade II-IV, are progressive primary brain tumors with great variability in prognosis. Our aim was to investigate whether pre-operative cognitive functioning is of added value in survival prediction in these patients. In a retrospective cohort study of patients undergoing awake craniotomy between 2010 and 2019 we performed pre-operative neuropsychological assessments in five cognitive domains.

Dabrafenib plus trametinib in patients with BRAF-mutant low-grade and high-grade glioma (ROAR): a multicentre, open-label, single-arm, phase 2, basket trial.

Background: Effective treatments are needed to improve outcomes for high-grade glioma and low-grade glioma. The activity and safety of dabrafenib plus trametinib were evaluated in adult patients with recurrent or progressive BRAF mutation-positive high-grade glioma and low-grade glioma.

Methods: This study is part of an ongoing open-label, single-arm, phase 2 Rare Oncology Agnostic Research (ROAR) basket trial at 27 community and academic cancer centres in 13 countries (Austria, Belgium, Canada, France, Germany, Italy, Japan, the Netherlands, Norway, South Korea, Spain, Sweden, and the USA).

Evaluation of the Khorana, PROTECHT, and 5-SNP scores for prediction of venous thromboembolism in patients with cancer.

Background: The Khorana score is a validated tool to identify cancer patients at higher risk of venous thromboembolism (VTE).

Objective: We compared its predictive performance to that of the clinical PROTECHT and the polygenic 5-SNP scores in patients who participated in the Dutch CPCT-02 study.

Patients/methods: Data on VTE and its risk factors were retrospectively collected for 2729 patients with advanced stage solid tumors planned for systemic cancer treatment.

Impact of depatuxizumab mafodotin on health-related quality of life and neurological functioning in the phase II EORTC 1410/INTELLANCE 2 trial for EGFR-amplified recurrent glioblastoma.

Background: In the EORTC 1410/INTELLANCE 2 randomised, phase II study (NCT02343406), with the antibody-drug conjugate depatuxizumab mafodotin (Depatux-M, ABT-414) in patients with recurrent EGFR-amplified glioblastoma, the primary end-point (overall survival) was not met, and the drug had ocular dose-limiting toxicity. This study reports results from the prespecified health-related quality of life (HRQoL) and neurological deterioration-free survival (NDFS) exploratory analysis.

Patients And Methods: Patients (n = 260) were randomised 1:1:1 to receive either Depatux-M 1.

[Revised guideline 'Brain metastases': More treatment options].

The guideline on brain metastasis from the Netherlands Society of Neurology has been updated. Important changes have been made, particularly with regard to treatment of brain metastases. Treatment of patients with brain metastases is complex and requires a multidisciplinary approach to formulate an optimal, individualized treatment plan.

Cognitive impairments are independently associated with shorter survival in diffuse glioma patients.

Background: Diffuse gliomas (WHO grade II-IV) are progressive primary brain tumors with great variability in prognosis. Cognitive deficits are of important prognostic value for survival in diffuse gliomas. Until now, few studies focused on domain-specific neuropsychological assessment and rather used MMSE as a measure for cognitive functioning.

Effect of a Skills Training for Oncologists and a Patient Communication Aid on Shared Decision Making About Palliative Systemic Treatment: A Randomized Clinical Trial.

Background: Palliative systematic treatment offers uncertain and often limited benefits, and the burden can be high. Hence, treatment decisions require shared decision making (SDM). This trial examined the independent and combined effect of an oncologist training and a patient communication aid on SDM.

Phase 1 study of the pan-HER inhibitor dacomitinib plus the MEK1/2 inhibitor PD-0325901 in patients with KRAS-mutation-positive colorectal, non-small-cell lung and pancreatic cancer.

Background: Mutations in KRAS result in a constitutively activated MAPK pathway. In KRAS-mutant tumours existing treatment options, e.g.

Efficacy and Tolerability of Tremelimumab in Locally Advanced or Metastatic Urothelial Carcinoma Patients Who Have Failed First-Line Platinum-Based Chemotherapy.

Purpose: Patients with advanced urothelial carcinoma who fail platinum-containing chemotherapy (treatment fails) have a poor prognosis and limited treatment options. Recent approvals of immune-checkpoint inhibitors confirmed the value of immunomodulatory therapy in urothelial carcinoma. Tremelimumab is a selective human immunoglobulin G2 (IgG2) monoclonal antibody against cytotoxic T-lymphocyte-associated antigen 4 with demonstrated durable response rate in metastatic melanoma.

Molecular tools for the pathologic diagnosis of central nervous system tumors.

Molecular diagnostics currently has a crucial role in neuro-oncological patient care. (Epi)genetic assays testing for point mutations, copy number variations, gene fusions, translocations, and methylation status are of main diagnostic interest in neuro-oncology. Multiple assays have been developed for this purpose, ranging from single gene tests to high-throughput, integrated techniques enabling detection of multiple genetic aberrations in a single workflow.

Phase I Study of BI 853520, an Inhibitor of Focal Adhesion Kinase, in Patients with Advanced or Metastatic Nonhematologic Malignancies.

Background: Overexpression/activation of focal adhesion kinase (FAK) in human malignancies has led to its evaluation as a therapeutic target. We report the first-in-human phase I study of BI 853520, a novel, potent, highly selective FAK inhibitor.

Objective: Our objectives were to identify the maximum tolerated dose (MTD), and to evaluate safety, pharmacokinetics (PK), pharmacodynamics (PD), biomarker expression, and preliminary activity.

Randomized, Open-Label, Crossover Studies Evaluating the Effect of Food and Liquid Formulation on the Pharmacokinetics of the Novel Focal Adhesion Kinase (FAK) Inhibitor BI 853520.

Background: BI 853520 is a potent inhibitor of focal adhesion kinase and is currently under clinical development for the treatment of non-hematological malignancies.

Objective: The objective of this study was to evaluate the effect of food and liquid dispersion on the pharmacokinetics of BI 853520 in two open-label, crossover substudies.

Patients And Methods: Sixteen patients with advanced solid tumors were enrolled in each substudy.

Pharmacokinetic Effects and Safety of Olaparib Administered with Endocrine Therapy: A Phase I Study in Patients with Advanced Solid Tumours.

Introduction: The PARP inhibitor olaparib is efficacious as monotherapy and has potential application in combination with endocrine therapy for the treatment of breast cancer. This phase I study assessed the safety and pharmacokinetic (PK) profiles of olaparib combined with tamoxifen, anastrozole or letrozole in patients with advanced solid tumours.

Methods: During part A, PK profiles were assessed in three consecutive treatment periods: (1) olaparib (tablet) 300 mg bid, days 1-5 followed by a 4-day washout; (2) cohort 1, tamoxifen 60 mg loading dose qd days 10-13, 20 mg qd days 14-26; cohort 2, anastrozole 1 mg qd days 10-19; cohort 3, letrozole 2.

Training for Medical Oncologists on Shared Decision-Making About Palliative Chemotherapy: A Randomized Controlled Trial.

Background: Systemic treatment for advanced cancer offers uncertain and sometimes limited benefit, while the burden can be high. This study examines the effect of shared decision-making (SDM) training for medical oncologists on observed SDM in standardized patient assessments.

Materials And Methods: A randomized controlled trial comparing training with standard practice was conducted.