Frédéric Amant's research while affiliated with Netherlands Cancer Institute and other places

Publications (585)

Article
Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO...
Article
Oncogenic rearrangements in the anaplastic lymphoma kinase (ALK) gene account for 5% of non-small cell lung cancer (NSCLC) cases. ALK inhibitors have markedly improved the outcome of metastatic ALK-positive NSCLC (ALK+ mNSCLC) by increasing long-term overall survival. Although a diagnosis of NSCLC during pregnancy or the peripartum period is rare,...
Article
Objectives In patients with an ovarian mass, a risk of malignancy assessment is used to decide whether referral to an oncology hospital is indicated. Risk assessment strategies do not perform optimally, resulting in either referral of patients with a benign mass or patients with a malignant mass not being referred. This process may affect the psych...
Conference Paper
Objectives The primary objective of the CONTESSA/NEOCON-F trial (NCT04016389) is to assess the feasibility of preserving fertility in women with FIGO 2018 stage IB2 cervical cancer by administering neo-adjuvant chemotherapy (NACT) followed by fertility sparing surgery (FSS). Methods This ongoing multi-center, phase II clinical trial will accrue 90...
Article
Since antineoplastic agents are frequently used in cancer therapy and able to affect the patient's DNA, it is important to know the genotoxic consequences on non-cancerous tissue. Therefore, we aimed to characterize the genotoxic profile of antineoplastic drugs belonging to different classes, using the cytokinesis-block micronucleus cytome assay in...
Article
Importance: Patients with low-grade (ie, grade 1-2) endometrial cancer (EC) are characterized by their favorable prognosis compared with patients with high-grade (ie, grade 3) EC. With the implementation of molecular profiling, the prognostic relevance of tumor grading might lose attention. As most patients present with low-grade EC and have an ex...
Presentation
Introduction/Background Current ESGO guidelines recommend secondary cytoreductive surgery (SCS) followed by chemotherapy in case of first recurrent epithelial ovarian cancer and a platinum-free interval (TFIp) of >6 months as it is the best strategy to prolong progression free survival (PFS) and overall survival (OS). Two prediction models have bee...
Conference Paper
Introduction/Background It is unknown if future fertility is compromised by the administration of chemotherapy during pregnancy. The aim of this study was to identify if chemotherapy affects the maternal ovaries during pregnancy, whether these effects depend on type of chemotherapy and duration of exposure, and if pregnancy protects against chemoth...
Conference Paper
Introduction/Background Resistance to platinum-based chemotherapy represents a major challenge for the management of many cancer patients, particularly those with epithelial ovarian cancer. Despite improved knowledge of the molecular determinants of platinum resistance, lack of clinical applicability still limits exploitation of many potential targ...
Conference Paper
Introduction/Background The malignancy rate of adnexal masses in pregnancy is 0.2–3.8/100.000 cases. Even though malignant ovarian cancer diagnoses in pregnancy are uncommon, awareness is crucial to obtain an adequate oncological treatment and a good obstetrical outcome. Methodology Using the INCIP (International Network on Cancer, Infertility and...
Conference Paper
Introduction/Background Following the increasing evidence on fetal safety, over time more pregnant women are receiving cancer treatment, including chemotherapy, in order to safeguard maternal prognosis. To evaluate current clinical practice obstetric and neonatal outcomes of women registered by the International Network on Cancer, Infertility and P...
Conference Paper
Introduction/Background Endometrial cancer (EC) is the most common gynaecological malignancy in developed countries. Currently, the extent of the surgical staging depends on a pre-operative risk assessment, but it is relatively inaccurate. This leads to an incorrect risk estimation of metastases at the diagnosis. Furthermore, the relation between t...
Conference Paper
Introduction/Background The optimal management of FIGO 2018 stage IB2 cervical cancer patients who desire to preserve fertility is unknown. Therefore, the CONTESSA/NEOCON-F trial (NCT04016389) aims to evaluate a promising, new fertility-sparing treatment: neoadjuvant chemotherapy (NACT) followed by fertility-sparing surgery (FSS). Methodology This...
Article
Full-text available
Background: Uterine leiomyosarcoma (uLMS) are rare and malignant tumors that arise in the myometrium cells and whose diagnosis is based on histopathological features. Identifying diagnostic biomarkers for uLMS is a challenge due to molecular heterogeneity and the scarcity of samples. In vivo and in vitro models for uLMS are urgently needed. Knocko...
Article
Background Chemotherapy crosses the placenta, however, it remains unclear to what extent it affects fetal growth. The current literature suggests up to 21% of the offspring of women receiving chemotherapy are small for gestational age (SGA, birth weight <10th percentile). Limiting research to birth weights only might misjudge fetal growth restricti...
Article
Full-text available
Purpose It is unknown if future fertility is compromised by the administration of chemotherapy during pregnancy. The aim of this study was to identify if chemotherapy affects the maternal ovaries during pregnancy and whether these effects depend on type of chemotherapy and duration of exposure. Methods Pregnant 8-week-old female BL6 mice were expo...
Article
Cancer during pregnancy threatens the lives of mother and foetus and its incidence is rising, making it an emerging medical challenge. Evidence on the direct impact of cancer therapies on neonatal outcomes resulted in general guidelines for maternal treatment that safeguards foetal development. Less focus has been placed on indirect factors, in pre...
Article
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A phase II study (PRIMMO) of patients with pretreated persistent/recurrent/metastatic cervical or endometrial cancer is presented. Patients received an immunomodulatory five-drug cocktail (IDC) consisting of low-dose cyclophosphamide, aspirin, lansoprazole, vitamin D, and curcumin starting 2 weeks before radioimmunotherapy. Pembrolizumab was admini...
Article
Full-text available
Resistance to platinum-based chemotherapy represents a major clinical challenge for many tumors, including epithelial ovarian cancer. Patients often experience several response-relapse events, until tumors become resistant and life expectancy drops to 12–15 months. Despite improved knowledge of the molecular determinants of platinum resistance, the...
Article
Background Most physicians encounter pregnant women with cancer incidentally, leading to a lack of expertise or confidence to inform and treat these patients based on the most recent guidelines and expert opinions. In the Netherlands, a national multidisciplinary tumour board for cancer, infertility and pregnancy (CIP-MDT) was founded in December 2...
Article
Background A diagnosis of breast cancer during pregnancy (PrBC) does not impact prognosis if standard treatment is offered. However, caution is warranted as gestational changes in pharmacokinetics may lead to reduced chemotherapy concentration. Methods Survival of PrBC patients treated with chemotherapy during pregnancy was compared to non-pregnan...
Article
Full-text available
Background: Cell-free DNA (cfDNA) analysis holds great promise for non-invasive cancer screening, diagnosis, and monitoring. We hypothesized that mining the patterns of cfDNA shallow whole-genome sequencing datasets from patients with cancer could improve cancer detection. Methods: By applying unsupervised clustering and supervised machine learn...
Article
Full-text available
Background With the aim of obtaining more uniformity and quality in the treatment of corpus uteri cancer in Belgium, the EFFECT project has prospectively collected detailed information on the real-world clinical care offered to 4063 Belgian women with primary corpus uteri cancer. However, as data was collected on a voluntary basis, data may be inco...
Article
Although overall rare, the most frequently diagnosed cancer during pregnancy is breast cancer. While treatment for pregnant patients should adhere to treatment guidelines for non-pregnant patients, there exist specific considerations concerning diagnosis, staging, oncological treatment and obstetrical care. Imaging and staging are preferably perfor...
Article
Full-text available
Background and purpose Radiotherapy during pregnancy is rarely administered due to lack of data and practical challenges. This is the first detailed report of proton therapy as cancer treatment for a pregnant patient with nasopharyngeal carcinoma. Materials and methods Pencil beam scanning proton therapy was prescribed to a pregnant patient to a t...
Article
Full-text available
The distinguishing of uterine leiomyosarcomas (ULMS) and uterine leiomyomas (ULM) before the operation and histopathological evaluation of tissue is one of the current challenges for clinicians and researchers. Recently, a few new and innovative methods have been developed. However, researchers are trying to create different scales analyzing availa...
Article
Little is known about infant’s safety of chemotherapy during breastfeeding where evidence is limited to few case reports. This lack of knowledge has led to a general tendency to advice against breastfeeding during cytotoxic therapy despite the overwhelming benefits that breastfeeding offers to both the mother and their children. In this case series...
Preprint
Background Cell-free DNA (cfDNA) analysis holds great promise for non-invasive cancer screening, diagnosis and monitoring. We hypothesized that mining the patterns of big datasets of shallow whole genome sequencing cfDNA from cancer patients could improve cancer detection. Methods By applying unsupervised clustering and supervised machine learning...
Article
Full-text available
Transient receptor potential (TRP) channels excel in cellular sensing as they allow rapid ion influx across the plasma membrane in response to a variety of extracellular cues. Recently, a distinct TRP mRNA expression signature was observed in stromal cells (ESC) and epithelial cells (EEC) of the endometrium, a tissue in which cell phenotypic plasti...
Chapter
This authoritative textbook provides a much-needed guide for postgraduate trainees preparing for the European Board and College of Obstetrics and Gynaecology (EBCOG) Fellowship examination. Published in association with EBCOG, it fully addresses the competencies defined by the EBCOG curriculum and builds the clinical practice related to these compe...
Article
Immunotherapy has greatly improved outcomes for subgroups of patients with cancer. As indications keep expanding, there is an unmet need to gain a better understanding of the effect of these therapies on pregnancy and fertility. During pregnancy, substantial adaptations occur in the maternal immune system to maintain protection against pathogens wh...
Article
Full-text available
Endometrial cancer (EC) is the most common gynaecologic malignancy in developed countries. The main challenge in EC management is to correctly estimate the risk of metastases at diagnosis and the risk to develop recurrences in the future. Risk stratification determines the need for surgical staging and adjuvant treatment. Detection of occult, micro...
Article
Introduction: Lymphoma (LYM) diagnosed during pregnancy is an uncommon occurrence. There are significant ethical and management challenges that involve maternal and fetal risks associated with delayed intervention vs antenatal therapy. Moreover, there are a scarcity of available data regarding relapsed/refractory LYM occurring during pregnancy, whi...
Article
Objective To assess the association between loss of lumbar skeletal muscle mass and density during neoadjuvant chemotherapy (NACT) and postoperative complications after interval cytoreductive surgery (CRS) in older patients with ovarian cancer. Materials and methods This multicenter, retrospective cohort study included patients aged 70 years and o...
Article
Full-text available
Endometrial cancer is the most common gynecological malignancy in high- and middle-income countries. Although the overall prognosis is relatively good, high-grade endometrial cancers have a tendency to recur. Recurrence needs to be prevented since the prognosis for recurrent endometrial cancer is dismal. Treatment tailored to tumor biology is the o...
Conference Paper
Full-text available
Introduction/Background* Insights in how to select older patients who can benefit from standard care and patients that need adjusted treatment are necessary. This study aims to determine the predictive value of lumbar skeletal muscle mass and density, measured on a computed tomography (CT) scan, for postoperative outcomes in older women with advanc...
Article
Full-text available
Endometriosis, polycystic ovary syndrome (PCOS) and uterine fibroids have been proposed as endometrial cancer risk factors; however, disentangling their relationships with endometrial cancer is complicated due to shared risk factors and comorbidities. Using genome-wide association study (GWAS) data, we explored the relationships between these non-c...
Article
Background In young women, a breast cancer diagnosis after childbirth increases the risk for metastasis and death. Studies in rodents suggest that post-weaning mammary gland involution contributes to the poor prognosis of postpartum breast cancers. However, this association has not been investigated in humans, mainly because of missing information...
Article
Full-text available
Postpartum breast cancer (PPBC) – which according to new data, can extend to 5-10 years after the birth - are estimated to represent 35-55% of all cases of breast cancer in women younger than 45 years. Increasing clinical evidence indicates that PPBC represents a high-risk form of breast cancer in young women with an approximately 2-fold increased...
Article
Cancer is diagnosed in 1 in 1000 to 1500 pregnancies. Most frequently encountered malignancies during pregnancy are breast cancer, hematological cancer, cervical cancer and malignant melanoma. Maternal cancer is associated with an increased risk of IUGR and preterm labor, especially in patients with systemic disease or those receiving chemotherapy...
Article
Full-text available
Endometrial carcinomas (EC) are the sixth most common cancer in women worldwide and the most prevalent in the developed world. ECs have been historically sub-classified in two major groups, type I and type II, based primarily on histopathological characteristics. Notwithstanding the usefulness of such classification in the clinics, until now it fai...
Preprint
Full-text available
Transient Receptor Potential (TRP) channels excel in cellular sensing as they allow rapid ion influx across the plasma membrane in response to a variety of extracellular cues. Recently, a distinct TRP expression signature was observed in stromal cells (ESC) and epithelial cells (EEC) of the endometrium, a tissue in which cell phenotypic plasticity...
Preprint
Full-text available
We have performed genetic correlation and Mendelian randomization analyses using publicly available genome-wide association study (GWAS) data to identify endometrial cancer risk factors. These and previously established risk factors of endometrial cancer were then included in a multi-trait Bayesian GWAS analysis to detect endometrial cancer suscept...
Article
Full-text available
Background Premenopausal women with early hormone-receptor positive (HR+) breast cancer receive 5–10 years of adjuvant endocrine therapy (ET) during which pregnancy is contraindicated and fertility may wane. The POSITIVE study investigates the impact of temporary ET interruption to allow pregnancy. Methods POSITIVE enrolled women with stage I-III...
Article
Full-text available
Triple-Negative Breast Cancer (TNBC) is the most aggressive breast cancer subtype, characterized by limited treatment options and higher relapse rates than hormone-receptor-positive breast cancers. Chemotherapy remains the mainstay treatment for TNBC, and platinum salts have been explored as a therapeutic alternative in neo-adjuvant and metastatic...
Article
Full-text available
PURPOSE Many patients and physicians remain concerned about the potential detrimental effects of pregnancy after breast cancer (BC) in terms of reproductive outcomes and maternal safety. This systematic review and meta-analysis aimed at providing updated evidence on these topics. METHODS A systematic literature review was conducted to identify stu...
Article
Full-text available
Importance Chemotherapy during the first trimester of pregnancy should be avoided owing to the risk of congenital malformations. However, the precise gestational age at which chemotherapy can be initiated safely remains unclear. Objective To assess congenital malformation rates associated with gestational age at initiation of chemotherapy among pr...
Article
Full-text available
Objective: To determine the predictive value of lumbar skeletal muscle mass and density for postoperative outcomes in older women with advanced stage ovarian cancer. Methods: A multicenter, retrospective cohort study was performed in women ≥ 70 years old receiving surgery for primary, advanced stage ovarian cancer. Skeletal muscle mass and density...
Article
Full-text available
Cancer during pregnancy has been associated with (pathologically) small for gestational age offspring, especially after exposure to chemotherapy in utero. These infants are most likely growth restricted, but sonographic results are often lacking. In view of the paucity of data on underlying pathophysiological mechanisms, the objective was to summar...
Article
Purpose of review: Although chemotherapeutics are considered as genotoxins for decades, their exact mutagenic impact on the genome of cancerous and normal cells of cancer patients was unknown for a long time. However, this knowledge is necessary to understand the long-term side effects of chemotherapy. A particular condition represents pregnant ca...
Preprint
Triple-Negative Breast Cancer (TNBC) is the most aggressive breast cancer subtype, characterized by both limited treatment options and higher relapse rates than hormone-receptor-positive breast cancers. Chemotherapy remains the mainstay treatment for TNBC, and platinum salts have been explored as a therapeutic alternative in neo-adjuvant and metast...
Article
515 Background: Overall a diagnosis of breast cancer during pregnancy (BCP) appears not to impact maternal prognosis if standard treatment is offered. However, caution is warranted as gestational changes in pharmacokinetics with respect to the distribution, metabolism and excretion of drugs may lead to reduced chemotherapy concentration in pregnant...
Article
Breast cancer diagnosed within 10 years following childbirth is defined as postpartum breast cancer (PPBC) and is highly metastatic. Interactions between immune cells and other stromal cells within the involuting mammary gland are fundamental in facilitating an aggressive tumor phenotype. The MNK1/2–eIF4E axis promotes translation of prometastatic...
Article
Full-text available
Triple-negative breast cancer (TNBC) is a cancer subtype critically dependent upon excessive activation of Wnt pathway. The anti-mycobacterial drug clofazimine is an efficient inhibitor of canonical Wnt signaling in TNBC, reducing tumor cell proliferation in vitro and in animal models. These properties make clofazimine a candidate to become first t...
Article
Full-text available
Background Implausible false positive results in non-invasive prenatal testing (NIPT) have been occasionally associated with the detection of occult maternal malignancies. Hence, there is a need for approaches allowing accurate prediction of whether the NIPT result is pointing to an underlying malignancy, as well as for organized programs ensuring...
Article
Full-text available
The onset of immune checkpoint blockade (ICB) therapy over the last decade has transformed the therapeutic landscape in oncology. ICB has shown unprecedented clinical activity and durable responses in a variety of difficult-to-treat cancers. However, despite these promising long-term responses, a majority of patients fail to respond to single-agent...
Article
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Data on the long-term neurodevelopmental outcomes of children exposed to hematological maternal cancer with or without treatment during pregnancy are lacking. A total of 57 children, of whom 33 males and 24 females, prenatally exposed to hematological malignancies and its treatment, were invited for neuropsychological and physical examinations at 1...
Article
The article focuses on fertility-sparing management during pregnancy and obstetrical management after fertility-sparing surgery. Over the years, more women in developed countries tend to delay childbirth to a later age, which leads to cervical cancer more often diagnosed during pregnancy. The advances in our understanding of prognosis and treatment...
Article
Full-text available
Data on the use of Granulocyte colony-stimulating factor (G-CSF) in pregnant cancer patients are scarce. The International Network of Cancer, Infertility and Pregnancy (INCIP) reviewed data of pregnant patients treated with chemotherapy and G-CSF, and their offspring. Among 2083 registered patients, 42 pregnant patients received G-CSF for the follo...
Article
Full-text available
Breast cancers that occur in young women up to 5 to 10 years' postpartum are associated with an increased risk for metastasis and death compared with breast cancers diagnosed in young, premenopausal women during or outside pregnancy. Given the trend to delay childbearing, this frequency is expected to increase. The (immuno)biology of postpartum bre...
Article
Full-text available
Cancer during pregnancy is increasingly diagnosed due to the trend of delaying pregnancy to a later age and probably also because of increased use of non-invasive prenatal testing for fetal aneuploidy screening with incidental finding of maternal cancer. Pregnant women pose higher challenges in imaging, diagnosis, and staging of cancer. Physiologic...
Article
Full-text available
As the incidence of cancer in pregnancy has been increasing in recent decades, more specialists are confronted with a complex oncologic-obstetric decision-making process. With the establishment of (inter)national registries, including the International Network on Cancer, Infertility and Pregnancy, and an increasing number of smaller cohort studies,...
Article
Full-text available
Fertility-sparing surgery (FSS) is increasingly being offered to women with a gynecological malignancy who wish to preserve fertility. In this systematic review, we evaluate the best evidence currently available on oncological and reproductive outcome after FSS for early stage cervical cancer, epithelial ovarian cancer, and endometrial cancer. An e...
Conference Paper
Background: Pregnancy-related issues are a priority for young breast cancer (BC) patients. Increasing evidence has shown that pregnancy after prior BC diagnosis is feasible. Nevertheless, few BC survivors conceive following anticancer treatment completion and many physicians remain concerned about the potentially detrimental effects of pregnancy af...
Article
Full-text available
Triple-negative breast cancer (TNBC) is the most aggressive breast cancer subtype, lacking effective therapy. Many TNBCs show remarkable response to carboplatin-based chemotherapy, but often develop resistance over time. With increasing use of carboplatin in the clinic, there is a pressing need to identify vulnerabilities of carboplatin-resistant t...