Breast cancer (BC) is a heterogeneous disease in which estrogen receptor (ER) expression plays an important role in most tumors. A clinical dilemma may arise when a metastasis biopsy to determine the ER status cannot be performed safely or when ER heterogeneity is suspected between tumor lesions. Whole-body ER imaging, such as 16a-18 F-fluoro-17b-estradiol ( 18 F-FES) PET, may have added value in these situations. However, the role of this imaging technique in routine clinical practice remains to be further determined. Therefore, we assessed whether the physician's remaining clinical dilemma after the standard workup was solved by the 18 F-FES PET scan. Methods: This retrospective study included 18 F-FES PET scans of patients who had (or were suspected to have) ER-positive metastatic BC and for whom a clinical dilemma remained after the standard workup. The scans were performed at the University Medical Center of Groningen between November 2009 and January 2019. We investigated whether the physician's clinical dilemma was solved, defined either as solving the clinical dilemma through the 18 F-FES PET results or as basing a treatment decision directly on the 18 F-FES PET results. In addition, the category of the clinical dilemma was reported, as well as the rate of 18 F-FES-positive or -negative PET scans, and any correlation to the frequency of solved dilemmas was determined. Results: One hundred 18 F-FES PET scans were performed on 83 patients. The clinical dilemma categories were inability to determine the extent of metastatic disease or suspected metastatic disease with the standard workup (n 5 52), unclear ER status of the tumor (n 5 31), and inability to determine which primary tumor caused the metastases (n 5 17). The dilemmas were solved by 18 F-FES PET in 87 of 100 scans (87%). In 81 of 87 scans, a treatment decision was based directly on 18 F-FES PET results (treatment change, 51 scans; continuance, 30 scans). The frequency of solved dilemmas was not related to the clinical dilemma category (P 5 0.334). However, the frequency of solved dilemmas was related to whether scans were 18 F-FES-positive (n 5 63) or 18 F-FES-negative (n 5 37; P , 0.001). Conclusion: For various indications, the 18 F-FES PET scan can help to solve most clinical dilemmas that may remain after the standard workup. Therefore, the 18 F-FES PET scan has added value in BC patients who present the physician with a clinical dilemma.

Introduction: Breast cancer (BC) is a heterogeneous disease, in which estrogen receptor (ER) expression plays an important role in the majority of breast tumors. A clinical dilemma may arise when a metastasis biopsy to determine the ER status cannot be performed safely or when ER heterogeneity is suspected between tumor lesions. Whole-body ER imaging, such as 16α-[18F]-fluoro-17β-estradiol ([18F]-FES) positron emission tomography (PET), may have additional value in these situations. However, the role of this imaging technique in routine clinical practice remains to be further determined. Therefore, we assessed the value of [18F]-FES-PET in a large retrospective set of patients, by evaluating if the physicians’ clinical dilemma that remained after standard workup was solved by the [18F]-FES-PET scan. Methods: In this single center study, [18F]-FES-PET scans, performed in patients with (suspected) ER+ metastatic BC with remaining clinical dilemma after standard workup (such as computed tomography, [18F]-fluorodeoxyglucose ([18F]-FDG)-PET, bone scintigraphy, magnetic resonance imaging, or biopsy), performed at the UMCG between November 2009 and January 2019, were included. A whole-body [18F]-FES-PET scan was performed 60 min after ~200 MBq of [18F]-FES was injected intravenously. ER antagonists had to be discontinued at least 5 weeks before [18F]-FES-PET. Primary endpoint was the percentage of cases in which the referring physician’s clinical dilemma was solved based on the [18F]-FES-PET results. The dilemma was considered solved if 1) the [18F]-FES-PET provided a solution for the clinical dilemma (for example an extra metastatic site to biopsy), or 2) a treatment decision (to change or continue) was made based on the [18F]-FES-PET result. If the physician had doubts about the diagnosis after the [18F]-FES-PET examination, and additional workup was necessary for treatment decision-making, the dilemma was considered not solved. Secondary endpoints were type of clinical dilemma, and rate of [18F]-FES positive or negative PET scans (visual interpretation), related to frequency of solved dilemmas. Results: One hundred [18F]-FES-PET scans were performed in 83 patients. Clinical dilemma types were: 1) inability to determine extent of (suspected) metastatic disease with standard workup (n=52), 2) unclear disease ER status (n=31), and 3) inability to determine which primary tumor caused metastases (n=17). Dilemmas were solved by [18F]-FES-PET in 87/100 cases (87%). In these 87 cases, treatment was changed in 52 cases, and continued in 35 cases. The frequency of solved dilemmas was not related to the type of clinical dilemma. In contrast, the frequency of solved dilemmas was related to whether scans were [18F]-FES positive or negative. Out of the 63 [18F]-FES positive scans, the clinical dilemma was solved in 61 cases (97%); in 26 out of the 37 [18F]-FES negative scans (70%) the dilemma was solved (p<0.001). Conclusion: In this real life study of BC patients with a clinical dilemma after standard workup, we showed that [18F]-FES-PET solved the dilemma in the large majority of cases. Relevant treatment decisions were made based on the scan, particularly in ER+ disease. This indicates that the [18F]-FES-PET can be of value to solve clinical dilemmas in BC patients. Ultimately, this can support optimal treatment in these patients and potentially improve outcome. Prospective trials are currently ongoing to further assess this. Citation Format: Jorianne Boers, Naila Loudini, Celina L. Brunsch, Sylvia A. Koza, Erik F.J. de Vries, Andor W.J.M. Glaudemans, Geke A.P. Hospers, Carolina P. Schröder. Value of [18F]-FES-PET to solve clinical dilemmas in breast cancer patients: A retrospective study [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS3-05.

Neonates with congenital heart disease (CHD) display delayed brain development, predisposing them to impaired cerebrovascular autoregulation (CAR) and ischemic brain injury. For this paper, we analyzed the percentage of time with impaired CAR (%time impaired CAR) during the first 72 h after birth, the relation with clinical factors, and survival in 57 neonates with CHD. The primary outcome was a correlation coefficient of cerebral oxygenation (rcSO2) and mean arterial blood pressure (MABP, mmHg) for two hours on a daily basis. The %time impaired CAR ranged from 9.3% of the studied time on day one to 4.6% on day three. Variables associated with more %time impaired CAR were the use of inotropes (day 1, B = 19.5, 95%CI = 10.6–28.3; day 3, B = 11.5, 95%CI = 7.1–16), lower MABP (day 1, B = −0.6, 95%CI = −1.2–0.0), and dextro-transposition of the great arteries (dTGA) (16.2%) compared with other CHD types (2.0–5.0%; day 1, p = 0.022). Survival was not an associated variable. To summarize, impaired CAR was found in CHD neonates in up to 9.3% of the studied time. More evidence is necessary to evaluate an association with inotropes, dTGA, %time impaired CAR, and long-term outcome, further in larger cohorts.