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”

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

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

Patient-Reported Outcome Measures may optimize shared decision-making for cancer risk management in BRCA mutation carriers

Purpose: The aim of this study was to compare patient-reported outcomes (PROs) of BRCA1/2 mutation carriers, either after bilateral prophylactic mastectomy (BPM) or during breast surveillance, to improve shared decision-making in their cancer risk management. Methods: Unaffected BRCA1/2 mutation carriers at least one year after BPM followed by immediate breast reconstruction (BPM-IBR) or one year under surveillance were eligible. After informed consent, the Hospital Anxiety and Depression Scale (HADS) and BREAST-Q were administered and compared between the different strategies. PROs were also compared to available normative data. Results: Ninety-six participants were analyzed in this study and showed significant differences between strategies in age, age at genetic testing, and time since BPM or starting breast surveillance. All HADS scores were below 8 suggesting no signs of anxiety or depression in both groups. Higher mean ‘Q-physical well-being’ scores were reported by the surveillance group (81.78 [CI 76.99–86.57]) than the BPM group (76.96 [CI 73.16 – 80.75]; p = 0.011). Overall, for both questionnaires better scores were seen when compared to age-matched normative data. Conclusions: No signs of anxiety or depression were seen in the surveillance or BPM-IBR group. Slightly better mean BREAST-Q scores were seen for the surveillance group in comparison to BPM-IBR, except for ‘Q-psychological well-being’. The difference in ‘Q-physical well-being’ was significantly worse for BPM-IBR. Approaches to obtain longitudinal PROs and reference values should be explored in the future, which could add value to shared decision-making in regards to breast cancer risk management in this specific patient population

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

Extent of ductal carcinoma in situ according to breast cancer subtypes: a population-based cohort study

Ductal carcinoma in situ (DCIS) is a precursor of invasive breast carcinoma (IBC). The DCIS component is often more extensive than the invasive component, which affects local control. The aim of our study was to analyze features of DCIS within different IBC subtypes, which may contribute to the optimization of personalized approaches for patients with IBC. Patients with IBC reported according to the synoptic reporting module in the Netherlands between 2009 and 2015 were included. Data extraction included characteristics of the invasive component and, if present, several features of the DCIS component. Resection margin status analyses were restricted to patients undergoing breast-conserving surgery (BCS). Differences between subtypes were tested by a Chi-square test, spearman’s Rho test or a one-way ANOVA test. Overall, 36.937 cases of IBC were included. About half of the IBCs (n = 16.014; 43.4 %) were associated with DCIS. Her2+ IBC (irrespective of ER status) was associated with a higher prevalence of adjacent DCIS, a larger extent of DCIS and a higher rate of irradicality of the DCIS component as compared to ER+/Her2− and triple-negative subtypes (P < 0.0001 for all variables). The prevalence of DCIS in triple-negative IBC on the other hand was lowest. In this large population-based cohort study, we showed significant differences between the prevalence and extent of DCIS according to IBC subtypes, which is also reflected in the resection margin status in patients treated with BCS. Our data provide important information regarding the optimization of local therapy according to IBC subtypes