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.
View Article and Find Full Text PDFPredicting 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.
View Article and Find Full Text PDFBackground: 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.
View Article and Find Full Text PDFUniversal 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).
View Article and Find Full Text PDFBackground: Exercise is a promising intervention to alleviate cognitive problems in breast cancer patients, but studies on mechanisms underlying these effects are lacking.
Purpose: Investigating whether an exercise intervention can affect cerebral blood flow (CBF) in cognitively impaired breast cancer patients and to determine if CBF changes relate to memory function.
Study Type: Prospective.
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.
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.
Purpose: Detection of 11 pathogenic variants in the gene in endometrial cancer (EC) is critically important to identify women with a good prognosis and reduce overtreatment. Currently, status is determined by DNA sequencing, which can be expensive, relatively time-consuming, and unavailable in hospitals without specialized equipment and personnel. This may hamper the implementation of -testing in clinical practice.
View Article and Find Full Text PDFBackground: Risk-assessment of endometrial cancer (EC) is based on clinicopathological factors and molecular subgroup. It is unclear whether adding hormone receptor expression, L1CAM expression or CTNNB1 status yields prognostic refinement.
Methods: Paraffin-embedded tumour samples of women with high-risk EC (HR-EC) from the PORTEC-3 trial (n = 424), and a Dutch prospective clinical cohort called MST (n = 256), were used.
Background: Endometrial cancer can be molecularly classified into POLE, mismatch repair deficient (MMRd), p53 abnormal (p53abn), and no specific molecular profile (NSMP) subgroups. We aimed to develop an interpretable deep learning pipeline for whole-slide-image-based prediction of the four molecular classes in endometrial cancer (im4MEC), to identify morpho-molecular correlates, and to refine prognostication.
Methods: This combined analysis included diagnostic haematoxylin and eosin-stained slides and molecular and clinicopathological data from 2028 patients with intermediate-to-high-risk endometrial cancer from the PORTEC-1 (n=466), PORTEC-2 (n=375), and PORTEC-3 (n=393) randomised trials and the TransPORTEC pilot study (n=110), the Medisch Spectrum Twente cohort (n=242), a case series of patients with POLE endometrial cancer in the Leiden Endometrial Cancer Repository (n=47), and The Cancer Genome Atlas-Uterine Corpus Endometrial Carcinoma cohort (n=395).
Purpose: Describes the relevance of -various classification methods for ipsilateral breast tumour recurrence (IBTR) as either true recurrence (TR) or new primary (NP) on both disease-specific survival (DSS) and distant metastasis-free survival (DMFS).
Method: Two hundred and thirty-four of 4359 women undergoing breast-conserving therapy experienced IBTR. We compared the impact of four known classification methods and two newly created classification methods.
Purpose: To investigate the effect of the timing of radiation therapy after breast-conserving surgery in relation to distant metastasis-free survival and disease-specific survival.
Methods: The analysis was performed in relation to 4189 women all undergoing breast-conserving therapy (BCT). Three groups were defined with respect to lymph node status and the use of adjuvant systemic therapy (AST).
Lymphovascular space invasion (LVSI) occurs in a minority of endometrial cancer (EC) cases, and the extent of LVSI is an important risk factor for recurrence and/or metastases. Our aim was to improve the reproducibility of measuring clinically meaningful LVSI by performing a quantitative analysis of the correlation between LVSI and the risk of pelvic lymph node recurrence in EC. EC samples from PORTEC-1 and PORTEC-2 trials were retrieved and used to collect quantitative data, including the number of LVSI-positive vessels per H&E-stained slide.
View Article and Find Full Text PDFBackground: Standard screening of endometrial cancer (EC) for Lynch syndrome (LS) is gaining traction; however, the prognostic impact of an underlying hereditary etiology is unknown. We established the prevalence, prognosis, and subsequent primary cancer incidence of patients with LS-associated EC in relation to sporadic mismatch repair deficient (MMRd)-EC in the large combined Post Operative Radiation Therapy in Endometrial Carcinoma-1, -2, and -3 trial cohort.
Methods: After MMR-immunohistochemistry, MLH1-promoter methylation testing, and next-generation sequencing, tumors were classified into 3 groups according to the molecular cause of their MMRd-EC.
Optimum risk stratification in early-stage endometrial cancer combines clinicopathologic factors and the molecular endometrial cancer classification defined by The Cancer Genome Atlas (TCGA). It is unclear whether analysis of intratumoral immune infiltrate improves this. We developed a machine-learning, image-based algorithm to quantify density of CD8 and CD103 immune cells in tumor epithelium and stroma in 695 stage I endometrioid endometrial cancers from the PORTEC-1 and -2 trials.
View Article and Find Full Text PDFPurpose: The aim of this study is to evaluate the prognostic value of the Mitotic Activity Index (MAI) in combination with the human epidermal growth factor receptor (Her2) for distant metastases-free survival (DMFS) and disease-specific survival (DSS) in breast cancer and compare it with the immunohistochemically (IHC) profile types.
Methods: Analyses were based on 2.923 breast-conserving breast cancer specimens with known MAI, Her2 status, and hormone receptor status, resulting in 2.
Introduction: After treatment with chemotherapy, many patients with breast cancer experience cognitive problems. While limited interventions are available to improve cognitive functioning, physical exercise showed positive effects in healthy older adults and people with mild cognitive impairment. The Physical Activity and Memory study aims to investigate the effect of physical exercise on cognitive functioning and brain measures in chemotherapy-exposed patients with breast cancer with cognitive problems.
View Article and Find Full Text PDFThe utilization rate of RT increased from 64.4% in 2011 to 70.3% in 2015.
View Article and Find Full Text PDFBackground: The aim of this study was to analyze the distant metastases-free survival (DMFS), and disease-specific survival (DSS) after breast-conserving therapy (BCT) in older patients with breast cancer in a large, population-based, single-center cohort study with long-term follow-up.
Material And Methods: Analyses were based on 1,425 women aged 65 years and older with breast cancer treated with BCT. Patients were divided in three age categories: 65 - 70 years, 71 - 75 years, and >75 years.
Objective: The aim of this study was to analyse the efficacy of breast-conserving therapy (BCT) for women with primary DCIS in a population-based setting.
Methods: Data were used from five Radiotherapy centres in The Netherlands from 2000 to 2010, all treated with BCT. Of all the cases, 59.
Ann Surg
August 2019
Objective: To investigate the effects of different types of surgery on breast cancer prognosis in germline BRCA1/BRCA2 mutation carriers compared with noncarriers.
Summary Of Background Data: Although breast-conserving therapy (breast-conserving surgery followed by radiotherapy) has been associated with more local recurrences than mastectomy, no differences in overall survival have been found in randomized trials performed in the general breast cancer population. Whether breast-conservation can be safely offered to BRCA1/2 mutation carriers is debatable.
Background: The Dutch guidelines advise to start radiation therapy (RT) within 5 weeks following breast-conserving surgery (BCS). However, much controversy exists regarding timing of RT. This study investigated its effect on 10-year disease-free survival (DFS) in a Dutch population-based cohort.
View Article and Find Full Text PDFBackground: The primary aim of the study was to investigate prognosis and long-term survival in young breast cancer patients with a BRCA1 or BRCA2 germline mutation compared with noncarriers. The secondary aim was to investigate whether differences in survival originate from associations with tumor characteristics, second cancers, and/or treatment response.
Methods: We established a cohort of invasive breast cancer patients diagnosed younger than age 50 years in 10 Dutch hospitals between 1970 and 2003.
Purpose: To investigate whether the Geriatric 8 (G8) and the Timed Get Up and Go Test (TGUGT) and clinical and demographic patient characteristics were associated with acute toxicity of radiation therapy and noncompliance in elderly cancer patients being irradiated with curative intent.
Methods And Materials: Patients were eligible if aged ≥65 years and diagnosed with breast, non-small cell lung, prostate, head and neck, rectal, or esophageal cancer, and were referred for curative radiation therapy. We recorded acute toxicity and noncompliance and identified potential predictors, including the G8 and TGUGT.