Publications by authors named "Carien Creutzberg"

Purpose: To compare the cost-effectiveness of a nurse-led sexual rehabilitation intervention with standard care in women treated with external beam radiotherapy, with or without brachytherapy, for gynaecological cancers.

Methods: Eligible women were randomly assigned to the intervention (n = 112) or standard care (n = 117). Primary endpoint was sexual functioning at 12-months post-radiotherapy, assessed by the Female Sexual Function Index (FSFI).

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Of the 4 molecular subtypes of endometrial cancer (EC), p53-abnormal (p53abn) EC is associated with abundant copy number alterations and the worst clinical outcome. Patients with p53abn EC have the highest risk of disease recurrence and death, independent of tumor grade and histologic subtype. Currently, all invasive p53abn ECs are considered high risk, and no prognostic biomarkers have yet been found that can aid in clinical management.

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Background: The European Organization of Research and Treatment of Cancer (EORTC) has recently developed and validated a patient-reported outcome measure (PROM) for sexual health (SH) in cancer patients. Here, we present results from a secondary analysis of the EORTC QLQ-SH22 validation study. The objective was to investigate the impact of cancer treatment on SH over the disease trajectory into survivorship in patients who underwent curative treatment.

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Incorporation of pathological and (not mandatory) molecular features into the new FIGO 2023 staging system has generated some controversy. Several validations have been published recently that demonstrated the higher prognostic precision of FIGO 2023 compared to the previous FIGO 2009 scheme. In the present article, the authors want to respond to some concerns that were raised by some pathologists and clinicians.

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Bone marrow (BM) damage due to chemoradiotherapy can increase BM fat in cervical cancer patients. Water-fat magnetic resonance (MR) scans were performed on a phantom and a healthy female volunteer to validate proton density fat fraction accuracy, reproducibility, and repeatability across different vendors, field strengths, and protocols. Phantom measurements showed a high accuracy, high repeatability, and excellent reproducibility.

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Article Synopsis
  • Recent research on the HER2-targeted therapy trastuzumab-deruxtecan has led to a study examining HER2-low status in over 800 advanced endometrial cancer (EC) cases, which typically have a poor prognosis despite numerous treatment options.
  • The study found that 17.2% of tumors were HER2-low, with higher frequencies in recurrent or metastatic EC (35.6%) and primary stage IV EC (29.9%), indicating HER2 status is present across various EC classifications without independent prognostic value.
  • The findings suggest that a significant portion of high-risk and metastatic EC cases exhibit HER2 overexpression, emphasizing the importance of broad HER2 testing and potential treatment opportunities for diverse patient groups.
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Article Synopsis
  • The GCIG Endometrial Cancer Consensus Conference was held in Incheon, South Korea, aimed at creating consensus statements to improve future clinical trials in endometrial cancer.
  • Representatives from 33 member groups developed 18 statements across four key topics, focusing on treatment strategies and trial methodologies, including consideration for low-resource settings.
  • For the first time, the conference included patient advocates and early-career investigators, resulting in a high consensus rate on the statements, reinforcing progress in global clinical research for endometrial cancer.
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Objectives: Sexuality is an important dimension of health-related quality of life (HRQOL) in cancer patients. Studies evidence that most patients report impairments of their sexual health related to their disease or its treatment. The Quality of Life Group of the European Organization for the Research and Treatment of Cancer (EORTC) developed a patient reported outcome measure assessing multidimensional aspects of sexual health.

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Article Synopsis
  • The FIGO 2023 staging system for endometrial cancer introduces significant updates that include nonanatomic factors (lymphovascular space invasion and histology) and molecular classification, marking a shift from the 2009 system.
  • These changes aim to enhance prognosis accuracy and help identify specific treatment-relevant subgroups for patients in early-stage disease.
  • The new system reflects advancements in our understanding of endometrial cancer's biology and focuses on integrating anatomical and tumor biology factors for personalized treatment recommendations.
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Background: Evidence on the optimal follow-up schedule after endometrial cancer is lacking. The study aim was to compare satisfaction with care between women who received reduced follow-up care and women who received usual guideline-directed follow-up care for three years after surgery.

Methods: The ENSURE (ENdometrial cancer SURvivors' follow-up carE) trial was a non-inferiority randomized controlled multicenter trial in 42 hospitals in the Netherlands.

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Background: The multicentre randomised SPARC trial evaluated the efficacy of a nurse-led sexual rehabilitation intervention on sexual functioning, distress, dilator use, and vaginal symptoms after radiotherapy for gynaecological cancers.

Methods: Eligible women were randomised to the rehabilitation intervention or care-as-usual. Four intervention sessions were scheduled over 12 months, with concurrent validated questionnaires and clinical assessments.

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Predicting distant recurrence of endometrial cancer (EC) is crucial for personalized adjuvant treatment. The current gold standard of combined pathological and molecular profiling is costly, hampering implementation. Here we developed HECTOR (histopathology-based endometrial cancer tailored outcome risk), a multimodal deep learning prognostic model using hematoxylin and eosin-stained, whole-slide images and tumor stage as input, on 2,072 patients from eight EC cohorts including the PORTEC-1/-2/-3 randomized trials.

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Background: Numerous studies have shown that older women with endometrial cancer have a higher risk of recurrence and cancer-related death. However, it remains unclear whether older age is a causal prognostic factor, or whether other risk factors become increasingly common with age. We aimed to address this question with a unique multimethod study design using state-of-the-art statistical and causal inference techniques on datasets of three large, randomised trials.

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Embracing the complex and diverse nature of the heterogenous group of malignancies that are included under the umbrella of "endometrial cancer" (EC) to better align prognosis with treatment recommendations, requires a more comprehensive staging system. Our goal at the development of the new FIGO staging was to provide 1) high accuracy in the predictive prognosis for a patient with EC, which is the genuine purpose of a staging system, and 2) identification of distinct treatment relevant subgroups. Since the publication of the 2009 staging system by the International Federation of Gynecology and Obstetrics (FIGO) 14  years ago (1, 2), our understanding of the biology and natural history of EC has undergone a radical transformation.

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Universal tumor screening in endometrial carcinoma (EC) is increasingly adopted to identify individuals at risk of Lynch syndrome (LS). These cases involve mismatch repair-deficient (MMRd) EC without MLH1 promoter hypermethylation (PHM). LS is confirmed through the identification of germline MMR pathogenic variants (PV).

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Background: Uveal melanoma (UM) is a rare intraocular tumor with a dismal prognosis once metastasized. This study provides a nationwide overview and time trends of patients diagnosed with primary UM in the Netherlands between 1989 and 2019.

Methods: A retrospective population-based cohort study based on patients with primary UM from the database of the Netherlands Cancer Registry (NCR), linked with the national population registry Statistics Netherlands on inhabitants' cause of death.

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Purpose: Women with locally advanced cervical cancer (LACC) undergoing primary platinum-based chemoradiotherapy and brachytherapy often experience toxicities. Normal-tissue complication probability (NTCP) models quantify toxicity risk and aid in optimizing radiation therapy to minimize side effects. However, it is unclear which predictors to include in an NTCP model.

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Purpose: The clinical significance of the p53-abnormal (p53abn) molecular subtype in stage I low-grade endometrioid endometrial carcinoma (EEC) is debated. We aimed to review pathologic and molecular characteristics, and outcomes of stage I low-grade p53abn EEC in a large international cohort.

Experimental Design: Previously diagnosed stage I p53abn EC (POLE-wild-type, mismatch repair-proficient) low-grade EEC from Canadian retrospective cohorts and PORTEC-1&2 trials were included.

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Hodgkin lymphoma (HL) has become 1 of the most curable cancers. Therefore, rigorous assessment of health-related quality of life (HRQoL) and symptom burden of these patients is essential to support informed clinical decisions. The European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Group previously developed the EORTC Quality of Life Questionnaire (QLQ) Hodgkin Lymphoma 27.

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Introduction: Many advances in the understanding of the pathologic and molecular features of endometrial cancer have occurred since the FIGO staging was last updated in 2009. Substantially more outcome and biological behavior data are now available regarding the several histological types. Molecular and genetic findings have accelerated since the publication of The Cancer Genome Atlas (TCGA) data and provide improved clarity on the diverse biological nature of this collection of endometrial cancers and their differing prognostic outcomes.

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Purpose: The molecular classification of endometrial cancer (EC) has proven to have prognostic value and is predictive of response to adjuvant chemotherapy. Here, we investigate its predictive value for response to external beam radiotherapy (EBRT) and vaginal brachytherapy (VBT) in early-stage endometrioid EC (EEC).

Methods: Data of the randomized PORTEC-1 trial (n = 714) comparing pelvic EBRT with no adjuvant therapy in early-stage intermediate-risk EC and the PORTEC-2 trial (n = 427) comparing VBT with EBRT in early-stage high-intermediate-risk EC were used.

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The European Society of Gynaecological Oncology (ESGO), the European Society for Radiotherapy and Oncology (ESTRO), and the European Society of Pathology (ESP) jointly published comprehensive evidence-based guidelines on all relevant issues of diagnosis and treatment in endometrial carcinoma in a multidisciplinary setting. In order to improve their implementation, a free downloadable easy-to-use mobile app was developed.Two interactive decision tools were created for (1) helping users to identify the recommended surgical steps, especially in terms of nodal staging approach based on the pre-operatively assumed risk group (tool #1), and (2) to facilitate prognostic risk group allocation and adjuvant treatment decision-making after primary surgery integrating both clinicopathological and molecular markers (if known) (tool #2).

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Background: As part of its mission to improve the quality of care for women with gynecological cancers across Europe, the European Society of Gynaecological Oncology (ESGO) first published in 2017 evidence-based guidelines for the management of patients with vulvar cancer.

Objective: To update the ESGO guidelines based on the new evidence addressing the management of vulvar cancer and to cover new topics in order to provide comprehensive guidelines on all relevant issues of diagnosis and treatment of vulvar cancer.

Methods: The ESGO Council nominated an international development group comprised of practicing clinicians who provide care to vulvar cancer patients and have demonstrated leadership through their expertize in clinical care and research, national and international engagement and profile as well as dedication to the topics addressed to serve on the expert panel (18 experts across Europe).

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