Carla M.L. van Herpen's research while affiliated with Radboud University Medical Centre (Radboudumc) and other places
What is this page?
This page lists the scientific contributions of an author, who either does not have a ResearchGate profile, or has not yet added these contributions to their profile.
It was automatically created by ResearchGate to create a record of this author's body of work. We create such pages to advance our goal of creating and maintaining the most comprehensive scientific repository possible. In doing so, we process publicly available (personal) data relating to the author as a member of the scientific community.
If you're a ResearchGate member, you can follow this page to keep up with this author's work.
If you are this author, and you don't want us to display this page anymore, please let us know.
It was automatically created by ResearchGate to create a record of this author's body of work. We create such pages to advance our goal of creating and maintaining the most comprehensive scientific repository possible. In doing so, we process publicly available (personal) data relating to the author as a member of the scientific community.
If you're a ResearchGate member, you can follow this page to keep up with this author's work.
If you are this author, and you don't want us to display this page anymore, please let us know.
Publications (184)
Drug resistance is a perpetual problem in cancer therapy with many underlying mechanisms. Alterations in drug transport over the cancer cell membrane can severely alter intratumoral drug exposure, contributing to resistance. Here, we present the somatic mutational landscape of 48 ATP-binding cassette and 416 solute carrier transporter genes in a co...
The use of anticancer drugs targeting specific molecular tumor characteristics is rapidly increasing in clinical practice, but selecting patients to benefit from these remains a challenge. It has been suggested that organoid cultures would be ideally suited to test drug responses in vitro. Here we describe and characterize in depth a case of ETV6-N...
Purpose:
For prostate-specific membrane antigen-directed radioligand therapy (PSMA-RLT), [177Lu]Lu-PSMA-617 and [177Lu]Lu-PSMA-I&T are the currently preferred compounds. Recent preclinical studies suggested ~30x higher kidney absorbed dose for [177Lu]Lu-PSMA-I&T compared to [177Lu]Lu-PSMA-617, which may lead to an increased risk of kidney toxicity...
In this phase 1 open-label study, we assessed the relative bioavailability of a prototype tablet formulation of TAK-931, a cell division cycle 7 kinase inhibitor, in reference to the current powder-in-capsule (PIC) formulation in patients with advanced solid tumors for whom no effective standard treatment was available. Adult patients were randomiz...
Purpose:
Watchful waiting (WW) can be considered for patients with metastatic clear cell renal cell carcinoma (mccRCC) with good or intermediate prognosis, especially those with <2 International Metastatic RCC Database Consortium criteria and ≤2 metastatic sites (referred to as watch and wait ("W&W")-criteria). The IMPACT-RCC study objective was t...
Gallbladder cancer (GBC) is a rare, highly aggressive malignancy with a 5-year survival rate of 5–10% in advanced cases, highlighting the need for more effective therapies. The aim of this study was to identify potentially actionable therapeutic targets for GBC. Specimens and clinicopathological data of 642 GBC patients, diagnosed between 2000 and...
Objective:
Three-dimensional organoid cell cultures have been established for a variety of human cancers. For most rare cancers, including salivary gland cancer (SGC), these models are lacking, despite the great unmet need to study cancer biology in these diseases. Therefore, we aimed to develop patient-derived organoid (PDO) models for different...
Introduction: Salivary gland cancer (SGC) is a rare cancer for which systemic treatment options are limited. Therefore, it is important to characterize its genetic landscape in search for actionable aberrations, such as NTRK gene fusions. This research aimed to identify these actionable aberrations by combining NGS-based analysis of RNA (gene fusio...
Aim:
This study examined whether anthropometric and body composition parameters such as body surface area (BSA), lean body mass (LBM), and total body weight (TBW) are correlated with docetaxel clearance and exposure by analyzing area under the curve (AUC). In addition, LBM, TBW, and a fixed dose were compared to BSA as dosing parameters for dose i...
(1) Background: Studies examining the psychosocial impact of living long term on systemic treatment in advanced cancer patients are scarce. This scoping review aimed to answer the research question “What has been reported about psychosocial factors among patients living with advanced cancer receiving life-long systemic treatment?”, by synthesizing...
Introduction
Fucosyl-GM1 is a monosialoganglioside with limited expression in healthy tissues and high expression on small cell lung cancer (SCLC) cells. BMS-986012 is a nonfucosylated, first-in-class, fully human immunoglobulin G1 monoclonal antibody that binds to fucosyl-GM1.
Methods
CA001-030 is a phase 1/2, first-in-human study of BMS-986012 a...
Background:
Larotrectinib is the first tumour-agnostic therapy that has been approved by the European Medicines Agency. Tumour-agnostic therapies are indicated for a multitude of tumour types. The economic models supporting reimbursement submissions of tumour-agnostic therapies are complex because of the multitude of indications per model.
Object...
4504
Background: C, a multitargeted receptor tyrosine kinase inhibitor (TKI), promotes an immune-permissive environment that may enhance response to immune checkpoint inhibitors (ICIs). COSMIC-021, a multicenter phase 1b study, is evaluating C + A (anti‒PD-L1 therapy) in various solid tumors (NCT03170960). C + A demonstrated encouraging clinical ac...
Nephrotoxicity is a common and dose-limiting side effect of platinum compounds, which often manifests as acute kidney injury or hypomagnesemia. This study aimed to investigate the genetic risk loci for platinum-induced nephrotoxicity. Platinum-treated brain tumor and head–neck tumor patients were genotyped with genome-wide coverage. The data regard...
Background: In the PINCH study we performed 89Zr-DFO-durvalumab (anti-PD-L1) PET/CT in patients with recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN) prior to monotherapy durvalumab treatment. The primary aims were to assess safety and feasibility of 89Zr-DFO-durvalumab PET-imaging and predict disease control rate during...
Purpose: For prostate-specific membrane antigen directed radioligand therapy (PSMA-RLT), [¹⁷⁷Lu]Lu‑PSMA‑617 and [¹⁷⁷Lu]Lu-PSMA-I&T are the currently preferred compounds. Recent preclinical studies suggested ~30x higher kidney absorbed dose for [¹⁷⁷Lu]Lu-PSMA-I&T compared to [¹⁷⁷Lu]Lu-PSMA-617, which may lead to an increased risk of kidney toxicity....
Introduction
Epidemiological discrepancies exist between rare and common cancers. The aim of this population-based study was to compare rare versus common adult solid cancers in the Netherlands, by providing incidence, prevalence and survival rates, evaluating trends in survival and comparing individual entities within domains and families.
Method...
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.
Experimental design:
This is a phase Ib/II, open-label study of ribociclib + binimetinib in patie...
Aim
In the registration trial, cabozantinib exposure ≥ 750 ng/mL correlated to improved tumor size reduction, response rate and progression free survival (PFS) in patients with metastatic renal cell cancer (mRCC). Because patients in routine care often differ from patients in clinical trials, we explored the cabozantinib exposure–response relations...
Purpose:
Patients with rare cancers (incidence less than 6 cases per 100,000 persons per year) commonly have less treatment opportunities and are understudied at the level of genomic targets. We hypothesized that rare cancer patients benefit from approved anti-cancer drugs outside their label similar to common cancers.
Patients and methods:
In t...
Aims
Salivary gland neoplasms are rare and are characterised by overlapping histopathological aspects. Therefore, the assessment of the correct histopathological diagnosis can be challenging. This study evaluated the frequency of pathology consultations and revisions for salivary gland neoplasms during routine clinical practice in the Netherlands....
Aim: In our study we examined whether anthropometric and body composition parameters, i.e. body surface area (BSA), lean body mass (LBM) and total body weight (TBW), are correlated with docetaxel clearance and exposure. In addition, LBM, TBW and a fixed dose were compared to BSA as dosing parameters for dose individualisation of docetaxel. Methods:...
Background
Patients with rare cancers face challenges in the diagnostic and treatment phase, and in access to clinical expertise. Since studies on health care experiences of these patients in comparison to patients with more common cancers are scarce, we aimed to explore these differences.
Methods
Data were cross-sectionally collected among (forme...
Aim
Because the tyrosine kinases c-MET and vascular endothelial growth factor receptors (VEGFR) are often overexpressed in salivary gland cancer (SGC), this study evaluated the efficacy and safety of cabozantinib in patients with recurrent/metastatic (R/M) SGC.
Patients and methods
A single-centre phase II study was conducted. Patients with immuno...
BACKGROUND & AIMS
Patients who receive chemoradiotherapy or bioradiotherapy (CRT/BRT) for locally advanced head and neck squamous cell carcinoma (LAHNSCC) often experience high toxicity rates interfering with oral intake, causing tube feeding (TF) dependency. International guidelines recommend gastrostomy insertion when the expected use of TF excee...
Background: Salivary duct carcinoma (SDC), one subtype of the 22 different salivary gland cancers, is a rare malignancy. Risk factors for the development of salivary gland cancer and SDC are largely unknown, although pollution has been described as one of the risk factors. In other cancers, especially in lung cancer, the carcinogenicity of chromium...
Background
In the TAX 323 (EORTC 24971) phase III trial enrolling patients with unresectable locoregionally advanced squamous cell carcinoma of the head and neck (LA-SCCHN), the addition of docetaxel (T) to cisplatin and 5-fluorouracil (PF)-based induction chemotherapy prior to definite radiotherapy significantly improved progression-free survival...
Cabozantinib is registered in fixed 60 mg dose. However, 46-62% of patients in the registration studies needed a dose reduction due to toxicity. Improved clinical efficacy has been observed in renal cell carcinoma patients (RCC) with a cabozantinib exposure >750 μg/L. In this study we explored the cabozantinib exposure in patients with different tu...
Background
Patients with incurable cancer face complex medical decisions. Their family caregivers play a prominent role in shared decision making processes, but we lack insights into their experiences. In this study, we explored how bereaved family caregivers experienced the shared decision making process.
Methods
We performed a qualitative interv...
Objective
Patients with rare cancers may experience different unmet needs than those with common cancer. The objective of this systematic review was to (1) investigate unmet supportive care needs of rare cancer patients throughout the disease trajectory and (2) identify predictive factors for these unmet needs.
Methods
PubMed, PsycINFO and CINAHL...
Patients suffering from recurrent or metastatic (R/M) salivary duct carcinoma (SDC) are often treated with combined androgen blockade (CAB). However, CAB frequently fails, resulting in a worse prognosis. Therefore, biomarkers that can predict treatment failure are urgently needed. mRNA from 76 R/M androgen receptor (AR)-positive SDC patients treate...
Background
Cabozantinib is approved for treatment of renal cell cancer (RCC) in a starting dose of 60 mg. However, in the registration studies dose reductions were needed in 46-62% of patients due to toxicity. Improved clinical efficacy of cabozantinib was observed in RCC patients with an average exposure of > 750 ug/L. Data about cabozantinib phar...
Cancer immunotherapies have induced long-lasting responses in cancer patients including those with melanoma and head and neck squamous cell carcinoma (HNSCC). However, the majority of treated patients does not achieve clinical benefit from immunotherapy because of systemic tumor-induced immunosuppression. Monocytic myeloid-derived suppressor cells...
A cancer is considered rare when the annual cancer incidence is less than 6 per 100,000 inhabitants. In absolute numbers more than 500,000 patients per year are diagnosed with a rare cancer, and 4,300,000 rare cancer patients are prevalent in Europe. The definition is widely adopted among the different scientific international societies like ESMO a...
6071
Background: Patients suffering from recurrent or metastatic (R/M) salivary duct carcinoma (SDC) are often treated with combined androgen blockade (CAB). This treatment however frequently fails (response rates: 18-53%), resulting in a worse prognosis. Therefore, biomarkers that have prognostic value and can predict treatment response are urgent...
6040
Background: Patients who receive chemoradiation or bioradiation (CRT/BRT) for locally advanced head and neck squamous cell carcinoma (LAHNSCC) often experience high toxicity rates, which may interfere with oral intake, leading to (temporary) tube feeding (TF) dependency. International guidelines recommend gastrostomy insertion when the expecte...
Background
The mTOR inhibitor everolimus used in cancer has immune-modulating effects, potentially contributing to an antitumor response but also leading to pulmonary toxicity. We studied the association of immunological cell subsets with antitumor response and pulmonary toxicity in breast cancer patients treated with everolimus plus exemestane.
M...
Merkel cell carcinoma (MCC) is a rare neuroendocrine tumor of the skin mainly seen in the elderly. Its incidence is rising due to ageing of the population, increased sun exposure, and the use of immunosuppressive medication. Additionally, with the availability of specific immunohistochemical markers, MCC is easier to recognize. Typically, these tum...
Introduction
A better understanding of the molecular, genetic and immunological characteristics of cancer and the introduction of new systemic treatment regimens in the last decades, has led to better treatment outcomes and increased survival rates for patients with previously short lived cancers. However, there is no uniform description to refer t...
Co‐treatment with gastric acid suppressants (GAS) in patients taking anticancer drugs that exhibit pH‐dependant absorption may lead to decreased drug exposure and may hamper drug efficacy. In this study we investigated wheter a one‐hour time interval between subsequent intake of pazopanib and GAS could mitigate this negative effect on drug exposure...
Lessons learned:
Afatinib and selumetinib can be combined in continuous and intermittent dosing schedules, albeit at lower doses than approved for monotherapy. Maximum tolerated dose for continuous and intermittent schedules is afatinib 20 mg once daily and selumetinib 25 mg b.i.d. Because the anticancer activity was limited, further development o...
Background Patients with rare cancers face challenges in the diagnostic and treatment phase, and in access to clinical expertise. Since studies on health care experiences of these patients in comparison to patients with more common cancers are scarce, we aimed to explore these differences.
Methods Data were cross-sectionally collected among (former...
Objectives
Salivary duct carcinoma (SDC) is a rare and aggressive subtype of salivary gland cancer. Androgen receptor (AR) (96%) and HER2 (29–46%) expression, and a high propensity for regional lymph node metastases are hallmarks of the disease. We hypothesized that c-MET, E-cadherin, PSMA tumor and PSMA neovascular expression may be prognostic fac...
Background
Nivolumab, a programmed death (PD) 1 inhibitor, has been approved as second line treatment for advanced renal-cell carcinoma (RCC) in Europe since 2016. We investigated toxicity and efficacy of nivolumab as well as potential predictive biomarkers in the Dutch population.
Methods
A retrospective, multicenter study of the Dutch national r...
We report a case of a patient with concurrent myotonic dystrophy and recurrent pleomorphic adenoma and hypothesize the association between both diseases. A 58-year-old man with classic myotonic dystrophy type 1 was diagnosed with pleomorphic adenoma. Appropriate treatment was commenced. Massive recurrences occurred within 15, 28 and 22 months respe...
Adenoid cystic carcinoma is a rare cancer that arises from secretory glands. Metastases are mainly seen in the lungs and bones. Cardiac metastases are extremely rare; only 1 case has previously been described. In this patient, cardiac metastases were suspected based on CT imaging. Tumor imaging by Ga-prostate-specific membrane antigen (PSMA)-11 PET...
Background:
Timely and efficient diagnostic workup of patients with head and neck cancer (HNC) is challenging. This observational study describes the implementation of an optimized multidisciplinary oncological diagnostic workup for patients with HNC and its impact on diagnostic and treatment intervals, survival, costs, and patient satisfaction....
6529
A phase II study on the efficacy and toxicity of cabozantinib in recurrent/metastatic salivary gland cancer patients. Background: Because c-MET and VEGFR are often overexpressed in salivary gland cancer (SGC), this study evaluated the efficacy and safety of cabozantinib in recurrent/metastatic (R/M) SGC pts. Methods: A single center, single ar...
5079
Background: In metastatic clear cell renal cell carcinoma (mccRCC), the number of International Metastatic Database Consortium (IMDC) risk factors plus metastatic sites may identify patients with rapid or slow disease progression in a period of watchful waiting (WW) (median WW of 8.4 vs 22.2 months; Rini et al. Lancet Oncol. 2016). We aimed to...
3573
Background: Immune checkpoint inhibitors (ICI) targeting programmed cell death protein-1/ligand-1 (PD-1/PD-L1) have shown activity in R/M squamous cell carcinoma of the head and neck (SCCHN). Positron-emission-tomography (PET) with ⁸⁹ Zr-labeled anti-PD-L1 antibodies could aid in predicting response to ICI. We present the dose-finding results...
3613
Background: Mutations in the KRAS gene result in a constitutively activated RAS-RAF-MEK-ERK (MAPK) pathway. In KRAS mutant tumors, the anti-tumor activity of MEK inhibitors is limited due to intrinsic resistance caused by feedback activation of upstream epidermal growth factor receptors (HER). This upstream activation not only reactivates MAPK...
Aim:
Sunitinib is an oral tyrosine kinase inhibitor approved for the treatment of renal cell carcinoma (RCC) and gastrointestinal stromal tumor (GIST). Due to large interpatient pharmacokinetic variability and an established exposure-response and exposure-toxicity relationship in clinical trial patients, Therapeutic Drug Monitoring (TDM) seems pro...
Objective
An increased interval between symptomatic disease and treatment may negatively influence oncologic and/or functional outcomes in head and neck cancer (HNC). This systematic review aims to provide insight into the effects of time to treatment intervals on oncologic and functional outcomes in oral cavity, pharyngeal, and laryngeal cancer....
In cancer, the primary tumour’s organ of origin and histopathology are the strongest determinants of its clinical behaviour, but in 3% of cases a patient presents with a metastatic tumour and no obvious primary. Here,as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, we train a deep learning classifier to predict canc...
Background:
Extracorporeally induced whole-body hyperthermia (eWBH) might be a beneficial treatment in cancer patients. Objectives of this pig study were to assess thermal distribution, (patho-)physiological effects, and safety of eWBH with a new WBH device.
Methods:
Fourteen healthy adult pigs were anesthetized, mechanically ventilated, and can...
Rationale: Treatment options for recurrent and/or metastatic (R/M) adenoid cystic carcinoma (ACC) and salivary duct carcinoma (SDC), major subtypes of salivary gland cancer, are limited. Both tumors often show overexpression of prostate-specific membrane antigen (PSMA). In prostate cancer, PSMA-ligands labeled with 68Ga or 177Lu are used for imagin...
Background:
Methotrexate in recurrent or metastatic (R/M) squamous cell carcinoma of the head and neck (SCCHN) has limited progression-free survival (PFS) benefit. We hypothesized that adding cetuximab to methotrexate improves PFS.
Methods:
In the phase-Ib-study, patients with R/M SCCHN received methotrexate and cetuximab as first-line treatment...
Androgen deprivation therapy (ADT) is first‐line palliative treatment in androgen receptor positive (AR+) salivary duct carcinoma (SDC), and response rates are 17.6‐50.0%. We investigated potential primary ADT resistance mechanisms for their predictive value of clinical benefit from ADT in a cohort of recurrent/metastatic SDC patients receiving pal...
Purpose
Knowledge of caregivers’ burden and fatigue before and after patients’ treatment for locally advanced head and neck cancer is scarce. Therefore, we aimed to explore caregivers’ fatigue and burden in relation to patients’ fatigue, distress, and quality of life.
Methods
For caregivers, burden and fatigue were assessed. For patients, fatigue...
Metastatic cancer is a major cause of death and is associated with poor treatment efficacy. A better understanding of the characteristics of late-stage cancer is required to help adapt personalized treatments, reduce overtreatment and improve outcomes. Here we describe the largest, to our knowledge, pan-cancer study of metastatic solid tumour genom...
The rapidly evolving landscape of immune-oncology is promising, but also leaves many yet unanswered questions. Recent clinical studies have demonstrated feasibility of PD-1/PD-L1 imaging to visualize PD-L/PD-L1 expression in clinical studies. These emerging noninvasive, whole-body and quantitative tools serve to improve our understanding of the dyn...
Salivary gland cancer (SGC) is a rare malignancy consisting of 22 subtypes with different genetic, histological and clinical characteristics. This rarity and heterogeneity makes systemic treatment of recurrent or metastatic (R/M) disease challenging. Use of chemotherapy is scarcely studied and chemotherapy at best has moderate effects. New therapeu...
Background
Inflammatory bowel disease (IBD) patients are at increased risk for developing extra-intestinal malignancies, mainly due to immunosuppressive medication. The risk of developing head and neck cancer in immunosuppressed transplant patients is increased. The relation between IBD patients and laryngeal cancer (LC) remains unclear. We aimed (...
Objectives:
The recent PANTAP trial showed that administration of prophylactic antibiotics in locally advanced head and neck carcinoma (LAHNC) patients treated with chemoradiotherapy reduced fever, hospitalization and costs. The current study describes the effect of prophylactic antibiotics on health-related quality of life (HRQoL), another second...
![A Violin plot of actual distribution of [⁸⁹Zr]Zr-DFO-girentuximab and...](publication/333654392/figure/fig4/AS:941400774422538@1601458843202/A-Violin-plot-of-actual-distribution-of-ZrZr-DFO-girentuximab-and-FFDG-SUVmax-in_Q320.jpg)
Purpose:
The main objective of this preliminary analysis of the IMaging PAtients for Cancer drug selecTion (IMPACT)-renal cell cancer (RCC) study is to evaluate the lesion detection of baseline contrast-enhanced CT, [89Zr]Zr-DFO-girentuximab-PET/CT and [18F]FDG-PET/CT in detecting ccRCC lesions in patients with a good or intermediate prognosis met...
In metastatic colorectal cancer, RAS and BRAF mutations cause resistance to anti‐EGFR therapies, such as cetuximab. Heterogeneity in RAS and BRAF mutations might explain non‐response in a subset of patients receiving cetuximab. Analyzing mutations in plasma‐derived circulating tumor DNA (ctDNA) could provide a more comprehensive overview of the mut...
Background
Everolimus-related interstitial lung disease (ILD) (also: pneumonitis) poses a difficulty for physicians, as it is hard to discriminate ILD from other causes of respiratory symptoms and to decide on safe treatment continuation.
Objective
We investigated the capability of pulmonary function tests (PFT), plasma biomarkers, everolimus phar...
In metastatic breast cancer (MBC), expression of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor-2 (HER2) guides treatment selection. In case of bone-only metastatic disease, ER, PR, and HER2 status assessment may be hampered by decalcification. We aimed to determine the optimal decalcification method,...
Background:
Patients with head and neck cancer (HNC) are vulnerable to fear of cancer recurrence (FCR) and psychiatric morbidity. We investigated the prevalence of high FCR and demographic, clinical, psychological, and psychiatric factors associated with high FCR prior to the s