Feasibility and Satisfaction With the Word Catheter in Treatment of Bartholin's Cyst and Abscess.

BACKGROUND/AIM: The Word catheter is a silicone device with a balloon system that may be inserted into a Bartholin's cyst or abscess in order to provide drainage and epithelization. The aim of this study was to evaluate the Word catheter as a therapy for Bartholin's cyst and abscess. Both patient and physician satisfaction, as well as the feasibility in an outpatient setting, were examined. PATIENTS AND METHODS: A total of 51 women with a Bartholin's cyst or abscess were given the option of Word catheter insertion in an outpatient setting between August 2013 and March 2018. Both the patients and the consulting physicians were asked to complete two questionnaires, before, during and after treatment, with a view to evaluating the overall pain level, any discomfort symptoms and sexual activity, as well as satisfaction levels. RESULTS: The insertion procedure seemed to constitute a short yet quite painful procedure. In most cases, the consulting physicians and the patients were content with the results. Nevertheless, dislodgement of the catheter or abscess recurrence were common. The removal of the Word catheter seemed to be short, painless, and uncomplicated. Most patients experienced pain and discomfort after catheter placement over the first days, with the symptoms fading over time. Sexual intercourse appeared to be negatively influenced. CONCLUSION: The Word catheter was frequently well tolerated for the treatment of Bartholin's cysts and abscesses, with few non-serious side-effects, however, it did interfere with sexual health. Nonetheless, it may not be possible to make general recommendations based on this exploratory study.

Primary results of the AGO-Zervix-1 Study: A prospective, randomized phase III study to compare the effects of paclitaxel and topotecan with those of cisplatin and topotecan in the treatment of patients with recurrent and persistent cervical cancer.

BACKGROUND: Before the era of immunotherapies and antibody-drug conjugates, there were limited chemotherapeutic options for patients with recurrent and metastatic cervical cancer. Combination therapies with cisplatin have shown some superiority over monotherapy. This study examined platinum-free treatment regimens, comparing a combination of topotecan and paclitaxel (TP) with topotecan and cisplatin (TC) in patients with recurrent or metastatic cervical cancer, with or without prior platinum-based treatment. METHODS: The AGO-Zervix-1 Study (NCT01405235) is a prospective, randomized phase III study in which patients were randomly assigned at a 1:1 ratio to treatment within the control arm with topotecan (0.75 mg/m2) on days 1-3 and cisplatin (50 mg/m2) on day 1 every 3 weeks and in the study arm topotecan (1.75 mg/m2) and paclitaxel (70 mg/m2) on days 1, 8, and 15 every 4 weeks or treatment. The primary study aim was overall survival; progression-free survival, toxicity, and quality of life were secondary aims. The interim and final analysis is here reported after recruitment of 173 of 312 planned patients. RESULTS: Median overall survival in the TP arm was 9.6 months, compared with 12.0 months in the TC arm (log-rank test, P = 0.33). Median progression-free survival rates were 4.4 months with TP and 4.2 months with TC (log-rank test, P = 0.47). Leukopenia and nausea/vomiting were more frequent in the cisplatin-containing arm. Otherwise, toxicity profiles were comparable. There were no differences in FACT-G-assessed quality of life. CONCLUSION: Platinum-based combination chemotherapy remains the standard of care chemotherapy regimen for patients with recurrent or metastatic cervical cancer.

Ureterocele as differential diagnosis of hydrosalpinx-an interesting case from the clinical practice.

Hydrosalpinx is a common condition in women of reproductive age that correlates with infertility. A ureterocele is a dilatation of the terminal ureter within the bladder and/or urethra that occurs seldomly in adults, but can sonographically be mistaken for a hydrosalpinx. We report of a 29-year-old patient (G2/P1) who was referred in our department with secondary infertility and suspicion of hydrosalpinx. Intraoperatively, no hydrosalpinx could be visualized. Postoperatively, an intravesical cystic mass was detected, alongside a second-degree urinary retention. Sonographically, a double kidney on the left side and an accentuated calyx system could be diagnosed. Ureteroceles seem to represent a rare but still possible differential diagnosis in suspected hydrosalpinx, given the similar sonographic presentation of both conditions.

Spatial expression of claudin 18.2 in matched primaries and metastases of tubo-ovarian carcinoma of all subtypes.

Physiologically, claudin 18 splice variant 2 (CLDN18.2) expression is restricted to the gastric epithelium, but its expression has been detected in solid cancers. Zolbetuximab, a chimeric IgG1 antibody targeting CLDN18.2, has demonstrated promising effects in patients suffering from CLDN18.2-positive, HER2-negative locally advanced gastric cancer and is currently being studied further. To date, little is known about CLDN18.2 expression in other histological subtypes of tubo-ovarian carcinoma (TOC) and their matching metastases.Using a cohort of all histological TOC subtypes, we investigated the immunohistochemical (IHC) CLDN18.2 expression in both TOCs (n = 536), their matching metastatic tissue (n = 385) and in 93 metastases without primary. Tissue microarrays comprised both the tumor center and periphery. IHC positivity was defined as biomarker expression of ≥ 75% in tumor cells with moderate-to-strong membranous staining.Overall CLDN18.2 positivity was 4.1% (21/515) in the TOC centers and 3.6% (18/498) in their peripheries. In primaries of mucinous tubo-ovarian carcinoma (MTOC), CLDN18.2 positivity rates were 45% (18/40) and 36.6% (15/41), respectively. Positivity rates for the corresponding metastases were 33% (4/12, center) and 27% (3/11, periphery). The expression was relatively homogenous throughout all tumor sites. With no expression in 99.5% of nonmucinous tumors, CLDN18.2 positivity was almost exclusively seen in the mucinous subtype.In tubo-ovarian carcinoma, CLDN18.2 expression was, with rare exceptions, restricted to the mucinous subtype. Among them, 33% of metastasized MTOCs presented with CLDN18.2 positivity. Hence, CLDN18.2 might display a promising target for personalized therapy in patients with advanced MTOC.

PD-L1 Expression and Silva Invasion Pattern in Villoglandular Adenocarcinoma of the Uterine Cervix.

Villoglandular adenocarcinoma (VGA) of the uterine cervix is a rare subtype of endocervical adenocarcinoma in young women. Between 2007 and 2020, all women with endocervical adenocarcinoma were retrospectively reviewed to find patients with VGA. Eight patients in whom pure VGA had been diagnosed were included. The mean age at initial diagnosis was 36.3 years (range 24-46). After surgical treatment, patients were followed up for 59 months (range 16-150). To date, all patients are alive with no evidence of disease. Neither lymph node involvement nor lymphovascular invasion was found. Furthermore, we examined the samples with a focus on morphological invasion pattern (Silva), stromal tumor-infiltrating lymphocytes (sTILs), and immunohistochemical programmed death ligand-1 (PD-L1) expression. PD-L1 expression was observed in 7/8 using the combined positive score (cutoff≥1%), 1/8 of VGAs using the tumor proportion score (cutoff≥1%), and 7/8 using the immune cell (cutoff≥1%). Using combined positive score and immune cell, PD-L1 expression was seen in 7/8 of pattern B and C tumors, with significantly higher expression in tumors with destructive-type patterns (P<0.05, A vs. B+C). Using tumor proportion score, no significant difference in PD-L1 expression was seen between VGAs with different invasion patterns. VGAs demonstrated twice higher sTILs in tumors with destructive-type invasion patterns. Our observations suggest that PD-L1 expression, tumor invasion patterns, and sTILs do not correlate with the excellent prognosis of pure VGA.

RANK and RANKL Expression in Tumors of Patients with Early Breast Cancer.

Introduction: The receptor activator of nuclear factor-κB (RANK) pathway was associated with the pathogenesis of breast cancer. Several studies attempted to link the RANK/RANKL pathway to prognosis; however, with inconsistent outcomes. We aimed to further contribute to the knowledge about RANK/RANKL as prognostic factors in breast cancer. Within this study, protein expression of RANK and its ligand, RANKL, in the tumor tissue was analyzed in association with disease-free survival (DFS) and overall survival (OS) in a study cohort of patients with early breast cancer. Patients and Methods: 607 samples of female primary and early breast cancer patients from the Bavarian Breast Cancer Cases and Controls Study were analyzed to correlate the RANK and RANKL expression with DFS and OS. Therefore, expression was quantified using immunohistochemical staining of a tissue microarray. H-scores were determined with the cut-off value of 8.5 for RANK and 0 for RANKL expression, respectively. Results: RANK and RANKL immunohistochemistry were assessed by H-score. Both biomarkers did not correlate (ρ = -0.04). According to molecular subtypes, triple-negative tumors and HER2-positive tumors showed a higher number of RANK-positive tumors (H-score ≥ 8.5), however, no subtype-specific expression of RANKL could be detected. Higher RANKL expression tended to correlate with a better prognosis. However, RANK and RANKL expression could not be identified as statistically significant prognostic factors within the study cohort. Conclusions: Tumor-specific RANK and RANKL expressions are not applicable as prognostic factors for DFS and OS, but might be associated with subtype-specific breast cancer progression.

Improving the Quality of Care for Cancer Patients through Oncological Second Opinions in a Comprehensive Cancer Center: Feasibility of Patient-Initiated Second Opinions through a Health-Insurance Service Point.

BACKGROUND: To improve the quality and cost-effectiveness of care, cancer patients can obtain a second medical opinion on their treatment. Validation of the diagnostic procedure (e.g., imaging), diagnosis, and treatment recommendation allows oncological therapy to be applied in a more targeted way, optimizing interdisciplinary care. This study describes patients who received second opinions at the Comprehensive Cancer Center for Erlangen-Nuremberg metropolitan area in Germany over a 6-year period, as well as the amount of time spent on second-opinion counseling. METHODS: This prospective, descriptive, single-center observational study included 584 male and female cancer patients undergoing gynecological, urologic, or general surgery who sought a second medical opinion. The extent to which the first opinion complied with standard guidelines was assessed solely descriptively. RESULTS: The first opinion was in accordance with the guidelines and complete in 54.5% of the patients, and guideline compliant but incomplete in 13.2%. The median time taken to form a second opinion was 225 min, and the cancer information service was contacted by patients an average of eight times. CONCLUSIONS: The initial opinion was guideline compliant and complete in every second case. Without a second opinion, the remaining patients would have been denied a guideline-compliant treatment recommendation. Obtaining a second opinion gives patients an opportunity to receive a guideline-compliant treatment recommendation and enables them to benefit from newer, individualized therapeutic approaches in clinical trials. Establishing patient-initiated second opinions via central contact points appears to be a feasible option for improving guideline compliance.

Feasibility of In Vivo Metal Artifact Reduction in Contrast-Enhanced Dedicated Spiral Breast Computed Tomography.

BACKGROUND: Radiopaque breast markers cause artifacts in dedicated spiral breast-computed tomography (SBCT). This study investigates the extent of artifacts in different marker types and the feasibility of reducing artifacts through a metal artifact reduction (MAR) algorithm. METHODS: The pilot study included 18 women who underwent contrast-enhanced SBCT. In total, 20 markers of 4 different types were analyzed for artifacts. The extent of artifacts with and without MAR was measured via the consensus of two readers. Image noise was quantitatively evaluated, and the effect of MAR on the detectability of breast lesions was evaluated on a 3-point Likert scale. RESULTS: Breast markers caused significant artifacts that impaired image quality and the detectability of lesions. MAR decreased artifact size in all analyzed cases, even in cases with multiple markers in a single slice. The median length of in-plain artifacts significantly decreased from 31 mm (range 11-51 mm) in uncorrected to 2 mm (range 1-5 mm) in corrected images (p ≤ 0.05). Artifact size was dependent on marker size. Image noise in slices affected by artifacts was significantly lower in corrected (13.6 ± 2.2 HU) than in uncorrected images (19.2 ± 6.8 HU, p ≤ 0.05). MAR improved the detectability of lesions affected by artifacts in 5 out of 11 cases. CONCLUSION: MAR is feasible in SBCT and improves the image quality and detectability of lesions.

Cytology and HPV Co-Testing for Detection of Vaginal Intraepithelial Neoplasia: A Retrospective Study.

(1) Background: Vaginal intraepithelial neoplasia (VaIN) is a rare premalignant disease caused by persistent human papillomavirus (HPV) infection. Diagnosing VaIN is challenging; abnormal cytology and positive HPV tests are usually the first signs, but published data on their accuracy for detecting it are rare and contradictory. The aim of this study is to compare the results of hrHPV and cytology co-testing with the histological findings of the vagina. (2) Methods: In the certified Dysplasia Unit at Erlangen University Hospital, cytology and HPV samples from the uterine cervix or vaginal wall after hysterectomy were obtained between 2015 and 2023 and correlated with histological findings in biopsies from the vaginal wall. Women without vaginal biopsy findings or concomitant cervical disease were excluded. (3) Results: In all, 279 colposcopies in 209 women were included. The histological results were: benign (n = 86), VaIN I/vLSIL (n = 116), VaIN II/vHSIL (n = 41), VaIN III/vHSIL (n = 33), and carcinoma (n = 3). Accuracy for detecting VaIN was higher in women with previous hysterectomies. Positive HPV testing during colposcopy increased the likelihood for VaIN II/III/vHSIL threefold. The detection rate for VaIN III/vHSIL was 50% after hysterectomy and 36.4% without hysterectomy. (4) Conclusions: Women with risk factors for VaIN, including HPV-16 infection or prior HPV-related disease, need careful work-up of the entire vaginal wall. Hysterectomy for HPV-related disease and a history of cervical intraepithelial neoplasia (CIN) also increased the risk for VaIN II/III/vHSIL.

Predicting mammographic density with linear ultrasound transducers.

BACKGROUND: High mammographic density (MD) is a risk factor for the development of breast cancer (BC). Changes in MD are influenced by multiple factors such as age, BMI, number of full-term pregnancies and lactating periods. To learn more about MD, it is important to establish non-radiation-based, alternative examination methods to mammography such as ultrasound assessments. METHODS: We analyzed data from 168 patients who underwent standard-of-care mammography and performed additional ultrasound assessment of the breast using a high-frequency (12 MHz) linear probe of the VOLUSON® 730 Expert system (GE Medical Systems Kretztechnik GmbH & Co OHG, Austria). Gray level bins were calculated from ultrasound images to characterize mammographic density. Percentage mammographic density (PMD) was predicted by gray level bins using various regression models. RESULTS: Gray level bins and PMD correlated to a certain extent. Spearman's ρ ranged from - 0.18 to 0.32. The random forest model turned out to be the most accurate prediction model (cross-validated R2, 0.255). Overall, ultrasound images from the VOLUSON® 730 Expert device in this study showed limited predictive power for PMD when correlated with the corresponding mammograms. CONCLUSIONS: In our present work, no reliable prediction of PMD using ultrasound imaging could be observed. As previous studies showed a reasonable correlation, predictive power seems to be highly dependent on the device used. Identifying feasible non-radiation imaging methods of the breast and their predictive power remains an important topic and warrants further evaluation. Trial registration 325-19 B (Ethics Committee of the medical faculty at Friedrich Alexander University of Erlangen-Nuremberg, Erlangen, Germany).

Image quality assessment using deep learning in high b-value diffusion-weighted breast MRI.

The objective of this IRB approved retrospective study was to apply deep learning to identify magnetic resonance imaging (MRI) artifacts on maximum intensity projections (MIP) of the breast, which were derived from diffusion weighted imaging (DWI) protocols. The dataset consisted of 1309 clinically indicated breast MRI examinations of 1158 individuals (median age [IQR]: 50 years [16.75 years]) acquired between March 2017 and June 2020, in which a DWI sequence with a high b-value equal to 1500 s/mm2 was acquired. From these, 2D MIP images were computed and the left and right breast were cropped out as regions of interest (ROI). The presence of MRI image artifacts on the ROIs was rated by three independent observers. Artifact prevalence in the dataset was 37% (961 out of 2618 images). A DenseNet was trained with a fivefold cross-validation to identify artifacts on these images. In an independent holdout test dataset (n = 350 images) artifacts were detected by the neural network with an area under the precision-recall curve of 0.921 and a positive predictive value of 0.981. Our results show that a deep learning algorithm is capable to identify MRI artifacts in breast DWI-derived MIPs, which could help to improve quality assurance approaches for DWI sequences of breast examinations in the future.

Evaluation of automated techniques for extraction of circulating cell-free DNA for implementation in standardized high-throughput workflows.

Analysis of circulating cell-free DNA (ccfDNA) is a suitable tool for detecting somatic mutations for the purpose of making decisions on treatment, monitoring treatment response, and predicting survival. High-throughput techniques for ccfDNA extraction are essential to implementing ccfDNA testing in the clinical setting. We set out to compare two automated techniques with regard to hands-on time, ccfDNA output and integrity, and circulating mitochondrial DNA (mtDNA). CcfDNA was isolated using the EZ1&2 ccfDNA field test kit (EZ2 kit, QIAGEN) and the Maxwell RSC ccfDNA plasma kit (Maxwell kit, Promega). DNA was extracted from plasma of 30 breast cancer patients enrolled in the iMODE-B (#325_19B; 12.10.2020) study. Real-time PCR, fluorescence-based detection and automated electrophoresis were used to assess ccfDNA concentrations. The ccfDNA yield was significantly higher when extracted with the EZ2 kit. The EZ2 kit enabled the isolation of a higher proportion of short fragments and a lower proportion of long fragments, resulting in lower DNA integrity. Significantly lower mtDNA quantities were detected in the Maxwell eluate than in the EZ2 eluate. Thus, decisions on which extraction method to use should proceed on the basis of the required input for downstream applications, the anticipated fragment size and minimum hands-on time.

Evaluation of a Wireless Localization System for Nonpalpable Breast Lesions - Feasibility and Cost-effectiveness in Everyday Clinical Routine.

BACKGROUND/AIM: Smaller, earlier-stage breast tumors are being found in breast cancer screening, and neoadjuvant chemotherapy is the gold standard when chemotherapy is indicated. Precise marking and localization of the tumor are thus becoming increasingly important. Wire-free localization techniques are under investigation in order to reduce presurgical radiography, pain, the risk of wire dislocation, and allow scheduling flexibility for patients and surgery departments. PATIENTS AND METHODS: This single-center observational study from June 2020 to October 2021 included 15 patients with mammographically or sonographically detected nonpalpable breast lesions. Radiofrequency identification (RFID) tags were placed preoperatively under ultrasound or radiologic guidance to localize lesions for planned surgery. All patients underwent breast conservation surgery, including one bilateral and one targeted axillary dissection. RESULTS: Histology identified two benign and 13 malignant lesions, including three ductal carcinomas in situ and 11 invasive breast cancers. Placement, control radiography, and handling of the RFID tag were feasible in everyday routine for different radiologists and surgeons and managed cost-effectively. All of the RFID tags were found in the specimen radiographs. CONCLUSION: The feasibility and cost-effectiveness of this non-wire localization method were demonstrated in this rather small cohort of patients. Further studies including larger numbers of patients are needed to confirm the method's accuracy.

Amniotic-Umbilical-to-Cerebral Ratio - A Novel Ratio Combining Doppler Parameters and Amniotic Fluid Volume to Predict Adverse Perinatal Outcome in SGA Fetuses At Term.

PURPOSE: Introduction of a novel ratio - the amniotic-umbilical-to-cerebral ratio (AUCR) - to predict adverse perinatal outcome in SGA fetuses at term and comparison of its predictive accuracy with established parameters. MATERIALS AND METHODS: This retrospective cohort study included 165 singleton pregnancies with SGA fetuses (birth weight < 10th percentile) at term. Cases with planned vaginal delivery and documented pulsatility indices (PI) of the umbilical artery (UA), middle cerebral artery (MCA), and single deepest pocket (SDP) were included. CPR was calculated as the ratio between MCA PI and UA PI, UCR as the ratio between UA PI and MCA PI. AUCR was defined as follows: SDP/(UA PI/MCA PI). Adverse perinatal outcomes were defined as operative intervention (OI), OI due to fetal distress, admission to the neonatal intensive care unit (NICU), and composite adverse perinatal outcome (CAPO). Associations between Doppler parameters and these outcomes were estimated using regression analyses. RESULTS: OI was statistically significantly associated with UCR, SDP, and AUCR, whereas no association was observed for UA PI, MCA PI, and CPR. Fetuses requiring OI due to fetal distress revealed a significantly higher UA PI and UCR as well as a lower MCA PI, CPR, and AUCR. With regard to NICU admission and CAPO, a significantly higher UA PI and lower CPR were found. Furthermore, a significant association was shown for SDP, UCR, and AUCR. AUCR achieved the best area under the curve for all outcome parameters. CONCLUSION: AUCR leads to an improvement in the prediction of unfavorable outcome in SGA fetuses at term. Furthermore, results of our study show that UCR might be superior to CPR.

Potential of spiral breast computed tomography to increase patient comfort compared to DM.

PURPOSE: To intra-individually compare patient comfort of spiral breast computed tomography (SBCT) versus digital mammography (DM). METHOD: This prospective IRB approved study included 79 patients undergoing both SBCT and DM for the assessment of BI-RADS 4 - 6 lesions. Following SBCT and DM patients answered a standardized questionnaire regarding "Overall patient comfort" and "Pain" on a 5-point Likert Scale. On the same Likert Scale, experienced radiologic technicians rated the workflow of the SBCT regarding patients' "Mobility", ease of patient "Positioning", patients' adherence to the examination ("Compliance") and expected image quality. Visibility of fibroglandular tissue in SBCT was independently rated by two breast radiologists on a 10-point Likert Scale. Subgroups stratified by menopausal status and body mass index (BMI) were analyzed. RESULTS: Patients reported significantly lower pain during SBCT (4.73 ± 0.57) compared to DM (4.09 ± 0.90; P < 0.01). This effect was independent from BMI. However, pain reduction by SBCT was most pronounced in premenopausal (SBCT vs. DM: 4.79 ± 0.50 vs. 3.89 ± 0.99) compared to postmenopausal patients (4.71 ± 0.77 vs. 4.20 ± 0.89). Overall patient comfort in premenopausal patients tended to be higher in SBCT compared to DM (P = 0.08). Radiologic technicians rated the SBCT procedure generally as positive (average: 4.62 ± 0.56). Coverage of fibroglandular tissue in SBCT was generally high (9.82 ± 0.43) and interrater agreement was good (κ = 0.77). CONCLUSIONS: Patients experience less pain during spiral breast computed tomography compared to DM, especially in premenopausal women. Imaging is feasible at a high level of anatomical breast coverage and without problems with the clinical workflow.

Influence of Family History of Breast or Ovarian Cancer on Pathological Complete Response and Long-Term Prognosis in Breast Cancer Patients Treated with Neoadjuvant Chemotherapy.

PURPOSE: In breast cancer, a pathological complete response (pCR) has been described as generally resulting in a favorable prognosis. However, there are subgroups, such as patients with a mutation in BRCA1 or BRCA2, in which the effect of pCR on the prognosis is suspected to be weaker. Patients with a family history of breast and/or ovarian cancer may therefore react differently in relation to pCR and prognosis, and this is investigated in this study. PATIENTS AND METHODS: Breast cancer patients were identified from a clinical breast cancer registry. The study subjects had been treated with neoadjuvant chemotherapy from 2001 to 2018 and their pathological and clinical information as well as medical family history were available. They were considered to have a positive family history if they had at least 1 first-degree relative with breast and/or ovarian cancer. Multivariate logistic regression analyses were performed to study the association between family history, pCR (ypT0; ypN0), and disease-free survival (DFS). RESULTS: Of 1,480 patients, 228 (15.4%) had a positive family history. The pCR rates were 24.9% in all patients, and 24.4% and 27.6% in those without/with a family history, respectively. Family history was not associated with a higher pCR rate (adjusted odds ratio [OR] 1.23; 95% confidence interval [CI] 0.85-1.76; p = 0.27) or a different disease-free survival (DFS; adjusted hazard ratio [HR] 1.15; 95% CI 0.88-1.52; p = 0.30). pCR did not affect the prognosis differently in relation to family history. CONCLUSIONS: In this retrospective analysis, family history was not associated with pCR and DFS. pCR improved survival, independently of family history.

Analysis of Oncological Second Opinions in a Certified University Breast and Gynecological Cancer Center Regarding Consensus between the First and Second Opinion and Conformity with the Guidelines.

INTRODUCTION: Oncological second opinions are becoming increasingly important in the era of complex treatments and established certified cancer centers. Oncological guidelines with the highest levels of evidence are available, but these can only be effective to the extent that they are implemented. Therefore, we analyzed the effects of second opinions with regard to their agreement with first opinions and conformity with guidelines. METHODS: In 164 patients with a diagnosis of breast cancer or gynecological malignancy who requested a second opinion, the first and second opinions, established at the interdisciplinary tumor conference, and conformity with the guidelines were evaluated. RESULTS: The first opinion was not in agreement with the guidelines in 34.8% (15.2% diagnosis, 12.8% surgical therapy, 13.4% systemic therapy, and 5.5% radiotherapy), and the recommendations were optimized in the second opinion in 56.7% (28.7% diagnosis, 15.9% surgical therapy, 30.5% systemic therapy, and 8.5% radiotherapy). CONCLUSIONS: Oncological second opinions showed significant effects and one-third of first opinions were not in conformity with the guidelines. In a significant proportion of cases, the existing treatment plan was changed or supplemented to allow modern and individualized treatment approaches.

Prognostic effect of low-level HER2 expression in patients with clinically negative HER2 status.

PURPOSE: Assessment of HER2 overexpression using immunohistochemistry (IHC) and/or in situ hybridisation (ISH) for the detection of HER2 amplifications is standard to identify patients for established HER2-directed treatments. Patients with lower HER2 expression levels have recently also become candidates for novel therapies targeting HER2. This study aimed to assess tumour and patient characteristics and prognosis in patients with advanced breast cancer (aBC), relative to low HER2 expression levels. METHODS: PRAEGNANT is a prospective aBC registry (NCT02338167), focusing on molecular biomarkers. Patients in all therapy lines receiving any kind of treatment are eligible. This analysis includes patients with conventionally HER2-negative aBC. Clinical outcome was compared in the groups with no (IHC score 0) or with low HER2 expression (IHC 1+, or IHC 2+/ISH negative). RESULTS: Low HER2 expression levels in triple-negative aBC patients did not influence progression-free survival. Overall survival appeared poorer in patients with IHC 2+ compared with patients with no HER2 expression in the unadjusted analysis (hazard ratio 2.24, 95% confidence interval 0.1.12-4.47). However, this effect was not maintained in the adjusted analysis. In HER2-negative, hormone receptor-positive patients, low HER2 expression appeared to have no effect on prognosis, neither progression-free survival nor overall survival. CONCLUSIONS: We could not demonstrate that HER2 expression at a low level and assessed in clinical routine can differentiate patients into prognostic groups. However, the prevalence of patients with a low expression makes this population interesting for clinical trials with potentially active treatments using HER2 as a target.

Detection of Microcalcifications in Spiral Breast Computed Tomography with Photon-Counting Detector Is Feasible: A Specimen Study.

The primary objective of the study was to compare a spiral breast computed tomography system (SBCT) to digital breast tomosynthesis (DBT) for the detection of microcalcifications (MCs) in breast specimens. The secondary objective was to compare various reconstruction modes in SBCT. In total, 54 breast biopsy specimens were examined with mammography as a standard reference, with DBT, and with a dedicated SBCT containing a photon-counting detector. Three different reconstruction modes were applied for SBCT datasets (Recon1 = voxel size (0.15 mm)3, smooth kernel; Recon2 = voxel size (0.05 mm)3, smooth kernel; Recon3 = voxel size (0.05 mm)3, sharp kernel). Sensitivity and specificity of DBT and SBCT for the detection of suspicious MCs were analyzed, and the McNemar test was used for comparisons. Diagnostic confidence of the two readers (Likert Scale 1 = not confident; 5 = completely confident) was analyzed with ANOVA. Regarding detection of MCs, reader 1 had a higher sensitivity for DBT (94.3%) and Recon2 (94.9%) compared to Recon1 (88.5%; p < 0.05), while sensitivity for Recon3 was 92.4%. Respectively, reader 2 had a higher sensitivity for DBT (93.0%), Recon2 (92.4%), and Recon3 (93.0%) compared to Recon1 (86.0%; p < 0.05). Specificities ranged from 84.7-94.9% for both readers (p > 0.05). The diagnostic confidence of reader 1 was better with SBCT than with DBT (DBT 4.48 ± 0.88, Recon1 4.77 ± 0.66, Recon2 4.89 ± 0.44, and Recon3 4.75 ± 0.72; DBT vs. Recon1/2/3: p < 0.05), while reader 2 found no differences. Sensitivity and specificity for the detection of MCs in breast specimens is equal for DBT and SBCT when a small voxel size of (0.05 mm)3 is used with an equal or better diagnostic confidence for SBCT compared to DBT.

Mammographic density and prognosis in primary breast cancer patients.

PURPOSE: Mammographic density (MD) is one of the strongest risk factors for breast cancer (BC). However, the influence of MD on the BC prognosis is unclear. The objective of this study was therefore to investigate whether percentage MD (PMD) is associated with a difference in disease-free or overall survival in primary BC patients. METHODS: A total of 2525 patients with primary, metastasis-free BC were followed up retrospectively for this analysis. For all patients, PMD was evaluated by two readers using a semi-automated method. The association between PMD and prognosis was evaluated using Cox regression models with disease-free survival (DFS) and overall survival (OS) as the outcome, and the following adjustments: age at diagnosis, year of diagnosis, body mass index, tumor stage, grading, lymph node status, hormone receptor and HER2 status. RESULTS: After median observation periods of 9.5 and 10.0 years, no influence of PMD on DFS (p = 0.46, likelihood ratio test (LRT)) or OS (p = 0.22, LRT), respectively, was found. In the initial unadjusted analysis higher PMD was associated with longer DFS and OS. The effect of PMD on DFS and OS disappeared after adjustment for age and was caused by the underlying age effect. CONCLUSIONS: Although MD is one of the strongest independent risk factors for BC, in our collective PMD is not associated with disease-free and overall survival in patients with BC.