From Barrett's Esophagus towards Adenocarcinoma: Genetic and Clinical studies

Esophageal adenocarcinoma is a highly aggressive disease from which more than 80% of patients die within 5 years after diagnosis. Worldwide almost 400,000 new patients are diagnosed annually. Herewith esophageal cancer ranks eighth on the list of most common cancers, and sixth on the list of cancer mortality causes 1. More than 90% of esophageal cancers are either squamous cell carcinomas or adenocarcinomas 2. Esophageal cancer incidence has been rapidly increasing in Western Europe and the USA 3-5. This could be mainly ascribed to an increase in the rate of esophageal adenocarcinoma, which by now equals or even exceeds the rate of esophageal squamous cell carcinomas. Esophageal cancer incidence in the Netherlands is 10.2/100,000 for men and 3.2/100,000 for women with around 900 newly diagnosed patients annually 6. Adenocarcinomas of the gastric cardia and of the esophagus, commonly located in the distal esophagus, have several similarities. They show a parallel increase in incidence. Moreover, they show similarities in epidemiological and histomorphological features as well as in patterns of comorbidity 7-9. This thesis mainly deals with molecular biological aspects of adenocarcinomas of the distal esophagus and its precursor lesion, Barrett’s esophagus, but also includes work on adenocarcinomas of the gastric cardia. Adenocarcinomas from the distal third of the esophagus plus adenocarcinomas of the gastric cardia are in this thesis altogether mentioned by the description “gastro-esophageal junction (GEJ) adenocarcinomas”

Health-related Quality of Life using the EQ-5D-5L:normative utility scores in a Dutch female population

PURPOSE: Normative utility scores represent the health related quality of life of the general population, are of utmost importance in cost-effectiveness studies and should reflect relevant sexes and age groups. The aim of this study was to estimate EQ-5D-5L normative utility scores in a population of Dutch females, stratified by age, and to compare these scores to those of female populations of three other countries. METHODS: Dutch women completed the EQ-5D-5L online between January and July 2020. Mean normative utilities were computed using the Dutch EQ-5D-5L value set, stratified by age, tested for differences using the Kruskall–Wallis test, and compared to normative utility scores of female populations elsewhere. Additionally, to support the use of the Dutch EQ-5D-5L data in other settings, normative utility scores were also calculated by applying the value sets of Germany, United Kingdom and USA. RESULTS: Data of 9037 women were analyzed and the weighted mean utility score was 0.911 (SD 0.155, 95% CI 0.908–0.914). The mean normative utility scores differed between age groups, showing lower scores in older females. Compared to other normative utility scores of female populations, Dutch mean utilities were consistently higher except for age groups 18–24 and 25–34. With the three country-specific value sets, new age-specific mean normative utility scores were provided. CONCLUSION: This study provides mean normative utility scores of a large cohort of Dutch females per age group, which were found to be lower in older age groups. Utility scores calculated with three other value sets were made available. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s11136-022-03271-3

Machine learning with PROs in breast cancer surgery; caution: Collecting PROs at baseline is crucial

As high breast cancer survival rates are achieved nowadays, irrespective of type of surgery performed, prediction of long-term physical, sexual, and psychosocial outcomes is very important in treatment decision-making. Patient-reported outcomes (PROs) can help facilitate this shared decision-making. Given the significance of more personalized medicine and the growing trend on the application of machine learning techniques, we are striving to develop an algorithm using machine learning techniques to predict PROs in breast cancer patients treated with breast surgery. This short communication describes the bottlenecks in our attempt to predict PROs

Omitting re-excision for focally positive margins after breast-conserving surgery does not impair disease-free and overall survival

Purpose: In contrast to other countries, the Dutch breast cancer guideline does not recommend re-excision for focally positive margins after breast-conserving surgery (BCS) in invasive tumor and does recommend whole-breast irradiation including boost. We investigated whether omitting re-excision as compared to performing re-excision affects prognosis with a retrospective population-based cohort study. Methods: The total cohort included 32,119 women with primary BCS for T1–T3 breast cancer diagnosed between 2003 and 2008 from the nationwide Netherlands cancer registry. The subcohort included 10,433 patients in whom the resection margins were registered. Outcome measures were 5-year ipsilateral breast tumor recurrence (IBTR) rate, 5-year disease-free survival (DFS) rate, and 10-year overall survival (OS) rate. Results: In the total cohort, 25,878 (80.6%) did not have re-excision, 2368 (7.4%) had re-excision by BCS, and 3873 (12.1%) had re-excision by mastectomy. Five-year IBTR rates were 2.1, 2.8, and 2.9%, respectively (p = 0.001). In the subcohort, 7820 (75.0%) had negative margins without re-excision, 492 (4.7%) had focally positive margins without re-excision, 586 (5.6%) had focally positive margins and underwent re-excision, and 1535 (14.7%) had extensively positive margins and underwent re-excision. Five-year IBTR rate was 2.3, 2.9, 1.1, and 2.9%, respectively (p = 0.099). Compared to omitting re-excision, performing re-excision for focally positive margins was associated with lower risk of IBTR (adjusted HR 0.30, 95% CI 0.11–0.82), but not with DFS (adjusted HR 0.83 95% CI 0.59–1.17) nor with OS (adjusted HR 1.17 95% CI 0.87–1.59). Conclusion: Omitting re-excision in breast cancer patients for focally positive margins after BCS does not impair DFS and OS, provided that whole-breast irradiation including boost is given

A preliminary prediction model for potentially guiding patient choices between breast conserving surgery and mastectomy in early breast cancer patients; a Dutch experience

Purpose: To guide early stage breast cancer patients to choose between breast conserving surgery (BCS) and mastectomy (MST) considering the predicted cosmetic result and quality of life (QoL). Methods: A decision model was built to compare QoL after BCS and MST. Treatment could result in BCS with good cosmesis, BCS with poor cosmesis, MST only, and MST with breast reconstruction. QoL for these treatment outcomes were obtained from a previous study and the literature and translated into EuroQoL-5D derived utilities. Chance of good cosmesis after BCS was predicted based on tumor location and tumor/breast volume ratio. The decision model determined whether the expected QoL was superior after BCS or MST based on chance of good cosmesis. Results: The mean utility for the treatments such as BCS with good cosmesis, BCS with poor cosmesis, MST only, and MST with breast reconstruction were 0.908, 0.843, 0.859, and 0.876, respectively. BCS resulted in superior QoL compared to MST in patients with a chance of good cosmesis above 36%. This 36% threshold is reached in case the tumor is located in the upper lateral, lower lateral, upper medial, lower medial, and central quadrant of the breast with a tumor/breast volume ratio below 21.6, 4.1, 15.1, 3.2, and 14.7, respectively. Conclusions: BCS results in superior QoL in patients with tumors in the upper breast quadrants or centrally and a tumor/breast volume ratio below 15. MST results in superior QoL in patients with tumors in the lower breast quadrants and a tumor/breast volume ratio above 4

Breast and Tumour Volume Measurements in Breast Cancer Patients Using 3-D Automated Breast Volume Scanner Images

Background: The resection volume in relation to the breast volume is known to influence cosmetic outcome following breast-conserving therapy. It was hypothesised that three-dimensional ultrasonography (3-D US) could be used to preoperatively assess breast and tumour volume and show high association with histopathological measurements. Methods: Breast volume by the 3D-US was compared to the water displacement method (WDM), mastectomy specimen weight, 3-D MRI and three different calculations for breast volume on mammography. Tumour volume by the 3-D US was compared to the histopathological tumour volume and 3-D MRI. Relatedness was based on the intraclass correlation coefficient (ICC) with corresponding 95% confidence interval (95% CI). Bland–Altman plots were used to graphically display the agreement for the different assessment techniques. All measurements were performed by one observer. Results: A total of 36 patients were included, 20 and 23 for the evaluation of breast and tumour volume (ductal invasive carcinomas), respectively. 3-D US breast volume showed ‘excellent’ association with WDM, ICC 0.92 [95% CI (0.80–0.97)]. 3-D US tumour volume showed a ‘excellent’ association with histopathological tumour volume, ICC 0.78 [95% CI (0.55–0.91)]. Bland–Altman plots showed an increased overestimation in lager tumour volumes measured by 3-D MRI compared to histopathological volume. Conclusions: 3-D US showed a high association with gold standard WDM for the preoperative assessment of breast volume and the histopathological measurement of tumour volume. 3-D US is an patient-friendly preoperative available technique to calculate both breast volume and tumour volume. Volume measurements are promising in outcome prediction of intended breast-conserving treatment

Opportunities for personalised follow-up care among patients with breast cancer: A scoping review to identify preference-sensitive decisions

Abstract Introduction Current follow‐up arrangements for breast cancer do not optimally meet the needs of individual patients. We therefore reviewed the evidence on preferences and patient involvement in decisions about breast cancer follow‐up to explore the potential for personalised care. Methods Studies published between 2008 and 2017 were extracted from MEDLINE, PsycINFO and EMBASE. We then identified decision categories related to content and form of follow‐up. Criteria for preference sensitiveness and patient involvement were compiled and applied to determine the extent to which decisions were sensitive to patient preferences and patients were involved. Results Forty‐one studies were included in the full‐text analysis. Four decision categories were identified: “surveillance for recurrent/secondary breast cancer; consultations for physical and psychosocial effects; recurrence‐risk reduction by anti‐hormonal treatment; and improving quality of life after breast cancer.” There was little evidence that physicians treated decisions about anti‐hormonal treatment, menopausal symptoms, and follow‐up consultations as sensitive to patient preferences. Decisions about breast reconstruction were considered as very sensitive to patient preferences, and patients were usually involved. Conclusion Patients are currently not involved in all decisions that affect them during follow‐up, indicating a need for improvements. Personalised follow‐up care could improve resource allocation and the value of care for patients

From Multiple Quality Indicators of Breast Cancer Care Toward Hospital Variation of a Summary Measure

Objectives: To improve quality in breast cancer care, large numbers of quality indicators are collected per hospital, but benchmarking remains complex. We aimed to assess the validity of indicators, develop a textbook outcome summary measure, and compare case-mix adjusted hospital performance. Methods: From a nationwide population-based registry, all 79 690 nonmetastatic breast cancer patients surgically treated between 2011 and 2016 in 91 hospitals in The Netherlands were included. Twenty-one indicators were calculated and their construct validity tested by Spearman's rho. Between-hospital variation was expressed by interquartile range (IQR), and all valid indicators were included in the summary measure. Standardized scores (observed/expected based on case mix) were calculated as above (>100) or below (<100) expected. The textbook outcome was presented as a continuous and all-or-none score. Results: The size of between-hospital variation varied between indicators. Sixteen (76%) of 21 quality indicators showed construct validity, and 13 were included in the summary measure after excluding redundant indicators that showed collinearity with others owing to strong construct validity. The median all-or-none textbook outcome score was 49% (IQR 42%-54%) before and 49% (IQR 48%-51%) after case-mix adjustment. From the total of 91 hospitals, 3 hospitals were positive (3%) and 9 (10%) were negative outlier