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.

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.

Correlation of RANK and RANKL with mammographic density in primary breast cancer patients.

PURPOSE: The receptor activator of nuclear factor kappa B (RANK) and its ligand (RANKL) have been shown to promote proliferation of the breast and breast carcinogenesis. The objective of this analysis was to investigate whether tumor-specific RANK and RANKL expression in patients with primary breast cancer is associated with high percentage mammographic density (PMD), which is a known breast cancer risk factor. METHODS: Immunohistochemical staining of RANK and RANKL was performed in tissue microarrays (TMAs) from primary breast cancer samples of the Bavarian Breast Cancer Cases and Controls (BBCC) study. For RANK and RANKL expression, histochemical scores (H scores) with a cut-off value of > 0 vs 0 were established. PMD was measured in the contralateral, non-diseased breast. Linear regression models with PMD as outcome were calculated using common predictors of PMD (age at breast cancer diagnosis, body mass index (BMI) and parity) and RANK and RANKL H scores. Additionally, Spearman rank correlations (ρ) between PMD and RANK and RANKL H score were performed. RESULTS: In the final cohort of 412 patients, breast cancer-specific RANK and RANKL expression was not associated with PMD (P = 0.68). There was no correlation between PMD and RANK H score (Spearman's ρ = 0.01, P = 0.87) or RANKL H score (Spearman's ρ = 0.04, P = 0.41). RANK expression was highest in triple-negative tumors, followed by HER2-positive, luminal B-like and luminal A-like tumors, while no subtype-specific expression of RANKL was found. CONCLUSION: Results do not provide evidence for an association of RANK and RANKL expression in primary breast cancer with PMD.

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.

[Fusion of mammography and ultrasonography]. / Fusion von Mammographie und Ultraschall.

STANDARD RADIOLOGICAL PROCEDURES: Currently, the combination of mammography and sonography is the gold standard in breast diagnostics. If there are any uncertainties, further examinations such as breast magnetic resonance imaging (MRI) and, in studies, computer tomographic procedures can be used. These investigations are carried out separately. METHODICAL INNOVATION: The combination of different imaging techniques in fusion devices promises a significant improvement in breast diagnostics. Advantages of the new imaging technique include the simultaneous acquisition of different image modalities with a fixed breast, which allows better spatial localization of the region of interest (ROI). This can also reduce the time and investigator effort and compensate for the weaknesses of one imaging technique with the strengths of a second imaging technique. The current state of research and the history of the fusion of ultrasound and mammography in breast diagnostics are summarized.

Combination of an ultrafast TWIST-VIBE Dixon sequence protocol and diffusion-weighted imaging into an accurate easily applicable classification tool for masses in breast MRI.

OBJECTIVES: This study aimed to develop a tool for the classification of masses in breast MRI, based on ultrafast TWIST-VIBE Dixon (TVD) dynamic sequences combined with DWI. TVD sequences allow to abbreviate breast MRI protocols, but provide kinetic information only on the contrast wash-in, and because of the lack of the wash-out kinetics, their diagnostic value might be hampered. A special focus of this study was thus to maintain high diagnostic accuracy in lesion classification. MATERIALS AND METHODS: Sixty-one patients who received breast MRI between 02/2014 and 04/2015 were included, with 83 reported lesions (60 malignant). Our institute's standard breast MRI protocol was complemented by an ultrafast TVD sequence. ADC and peak enhancement of the TVD sequences were integrated into a generalised linear model (GLM) for malignancy prediction. For comparison, a second GLM was calculated using ADC and conventional DCE curve type. The resulting GLMs were evaluated for standard diagnostic parameters. For easy application of the GLMs, nomograms were created. RESULTS: The GLM based on peak enhancement of the TVD and ADC was as equally accurate as the GLM based on conventional DCE and ADC, with no significant differences (sensitivity, 93.3%/93.3%; specificity, 91.3%/87.0%; PPV, 96.6%/94.9%; NPV, 84.0%/83.3%; all, p ≥ 0.315). CONCLUSIONS: This study presents a method to integrate ultrafast TVD sequences into a breast MRI protocol, allowing a reduction of the examination time while maintaining diagnostic accuracy. A GLM based on the combination of TVD-derived peak enhancement and ADC provides high diagnostic accuracy, and can be easily applied using a nomogram. KEY POINTS: • Ultrafast TWIST-VIBE Dixon sequence protocols in combination with diffusion-weighted imaging allow to shorten breast MRI examinations, while diagnostic accuracy is maintained. • Integrating peak enhancement from the TWIST-VIBE Dixon sequence and the apparent diffusion coefficient into a generalised linear model provides a comprehensible image evaluation approach. • This approach is further facilitated by nomograms.

Breast MRI texture analysis for prediction of BRCA-associated genetic risk.

BACKGROUND: BRCA1/2 deleterious variants account for most of the hereditary breast and ovarian cancer cases. Prediction models and guidelines for the assessment of genetic risk rely heavily on criteria with high variability such as family cancer history. Here we investigated the efficacy of MRI (magnetic resonance imaging) texture features as a predictor for BRCA mutation status. METHODS: A total of 41 female breast cancer individuals at high genetic risk, sixteen with a BRCA1/2 pathogenic variant and twenty five controls were included. From each MRI 4225 computer-extracted voxels were analyzed. Non-imaging features including clinical, family cancer history variables and triple negative receptor status (TNBC) were complementarily used. Lasso-principal component regression (L-PCR) analysis was implemented to compare the predictive performance, assessed as area under the curve (AUC), when imaging features were used, and lasso logistic regression or conventional logistic regression for the remaining analyses. RESULTS: Lasso-selected imaging principal components showed the highest predictive value (AUC 0.86), surpassing family cancer history. Clinical variables comprising age at disease onset and bilateral breast cancer yielded a relatively poor AUC (~ 0.56). Combination of imaging with the non-imaging variables led to an improvement of predictive performance in all analyses, with TNBC along with the imaging components yielding the highest AUC (0.94). Replacing family history variables with imaging components yielded an improvement of classification performance of ~ 4%, suggesting that imaging compensates the predictive information arising from family cancer structure. CONCLUSIONS: The L-PCR model uncovered evidence for the utility of MRI texture features in distinguishing between BRCA1/2 positive and negative high-risk breast cancer individuals, which may suggest value to diagnostic routine. Integration of computer-extracted texture analysis from MRI modalities in prediction models and inclusion criteria might play a role in reducing false positives or missed cases especially when established risk variables such as family history are missing.

Analysis of motives and patient satisfaction in oncological second opinions provided by a certified university breast and gynecological cancer center.

PURPOSE: Second opinions in oncology are becoming increasingly important in an era of more complex treatments and a growing demand for information by patients. Therefore, we analyzed their effects and influencing factors like patients' motives, subjective extent of information and satisfaction with communications. METHODS: This prospective study evaluated second opinions for patients with breast cancer or gynecological malignancy. The patients received a questionnaire before and two months after, which inquired expectations, reasons, and satisfaction with the second opinion and the attending physicians. RESULTS: A total of 164 patients were included and the majority had breast cancer (75.0%). Receiving the second opinion made 89.7% feel better informed, their need for information decreased (from 75.3% to 39.2%, P < 0.0001), and satisfaction with doctor-patient communications increased (from 61.9 to 91.8%, P = 0.0002). There were various reasons for requesting a second opinion, e.g., the extremely stressful situation of a cancer diagnosis, hope for change in the treatment recommendation or dissatisfaction with the initial physicians. CONCLUSIONS: Second opinions can lead to significantly greater patient satisfaction, meeting the need for information and leading to better management of patients in the extremely stressful situation of a cancer diagnosis. Doctor-patient communications play a key role.

BRCA mutations and their influence on pathological complete response and prognosis in a clinical cohort of neoadjuvantly treated breast cancer patients.

PURPOSE: BRCA1/2 mutations influence the molecular characteristics and the effects of systemic treatment of breast cancer. This study investigates the impact of germline BRCA1/2 mutations on pathological complete response and prognosis in patients receiving neoadjuvant systemic chemotherapy. METHODS: Breast cancer patients were tested for a BRCA1/2 mutation in clinical routine work and were treated with anthracycline-based or platinum-based neoadjuvant chemotherapy between 1997 and 2015. These patients were identified in the tumor registry of the Breast Center of the University of Erlangen (Germany). Logistic regression and Cox regression analyses were performed to investigate the associations between BRCA1/2 mutation status, pathological complete response, disease-free survival, and overall survival. RESULTS: Among 355 patients, 59 had a mutation in BRCA1 or in BRCA2 (16.6%), 43 in BRCA1 (12.1%), and 16 in BRCA2 (4.5%). Pathological complete response defined as "ypT0; ypN0" was observed in 54.3% of BRCA1/2 mutation carriers, but only in 22.6% of non-carriers. The adjusted odds ratio was 2.48 (95% CI 1.26-4.91) for BRCA1/2 carriers versus non-carriers. Patients who achieved a pathological complete response had better disease-free survival and overall survival rates compared with those who did not achieve a pathological complete response, regardless of BRCA1/2 mutation status. CONCLUSIONS: BRCA1/2 mutation status leads to better responses to neoadjuvant chemotherapy in breast cancer. Pathological complete response is the main predictor of disease-free survival and overall survival, independently of BRCA1/2 mutation status.

Initial clinical results with a fusion prototype for mammography and three-dimensional ultrasound with a standard mammography system and a standard ultrasound probe.

BACKGROUND: Combinations *Equal contributors. of different imaging techniques in fusion devices appear to be associated with improvements in diagnostic assessment. PURPOSE: The aim of this study was to test the feasibility of using an automated standard three-dimensional (3D) ultrasound (US) device fused with standard mammography for the first time in breast cancer patients. MATERIAL AND METHODS: Digital mammograms and 3D automated US images were obtained in 23 patients with highly suspicious breast lesions. A recently developed fusion machine consisting of an ABVS 3D US transducer from an Acuson S2000 machine and a conventional Mammomat Inspiration device (both Siemens Healthcare GmbH, Erlangen, Germany) were used for the purpose. The feasibility of the examinations, imaging coverage, and patients' experience of the procedure were examined. RESULTS: In 15 out of 19 patients, the region of interest (ROI) with the tumor marked in the mammogram was visible on US. The examination was experienced positively by the patients, with no unexpected pain or injury. The examination was time-saving and well tolerated. CONCLUSION: In conclusion, we have shown initial clinical feasibility of an US/radiography fusion prototype with good localization and evaluation of the ROIs. The combined examination was well tolerated. The simultaneous evaluation with mammography and US imaging may be able to improve detection and reduce examiner-related variability.

Association between mammographic density and pregnancies relative to age and BMI: a breast cancer case-only analysis.

PURPOSE: Percentage mammographic density (PMD) is a major risk factor for breast cancer (BC). It is strongly associated with body mass index (BMI) and age, which are themselves risk factors for breast cancer. This analysis investigated the association between the number of full-term pregnancies and PMD in different subgroups relative to age and BMI. METHODS: Patients were identified in the breast cancer database of the University Breast Center for Franconia. A total of 2410 patients were identified, for whom information on parity, age, and BMI, and a mammogram from the time of first diagnosis were available for assessing PMD. Linear regression analyses were conducted to investigate the influence on PMD of the number of full-term pregnancies (FTPs), age, BMI, and interaction terms between them. RESULTS: As in previous studies, age, number of FTPs, and BMI were found to be associated with PMD in the expected direction. However, including the respective interaction terms improved the prediction of PMD even further. Specifically, the association between PMD and the number of FTPs differed in young patients under the age of 45 (mean decrease of 0.37 PMD units per pregnancy) from the association in older age groups (mean decrease between 2.29 and 2.39 PMD units). BMI did not alter the association between PMD and the number of FTPs. CONCLUSIONS: The effect of pregnancies on mammographic density does not appear to become apparent before the age of menopause. The mechanism that drives the effect of pregnancies on mammographic density appears to be counter-regulated by other influences on mammographic density in younger patients.

Semi-automated delineation of breast cancer tumors and subsequent materialization using three-dimensional printing (rapid prototyping).

OBJECTIVE: Three-dimensional (3D) printing has become widely available, and a few cases of its use in clinical practice have been described. The aim of this study was to explore facilities for the semi-automated delineation of breast cancer tumors and to assess the feasibility of 3D printing of breast cancer tumors. METHODS: In a case series of five patients, different 3D imaging methods-magnetic resonance imaging (MRI), digital breast tomosynthesis (DBT), and 3D ultrasound-were used to capture 3D data for breast cancer tumors. The volumes of the breast tumors were calculated to assess the comparability of the breast tumor models, and the MRI information was used to render models on a commercially available 3D printer to materialize the tumors. RESULTS: The tumor volumes calculated from the different 3D methods appeared to be comparable. Tumor models with volumes between 325 mm3 and 7,770 mm3 were printed and compared with the models rendered from MRI. The materialization of the tumors reflected the computer models of them. CONCLUSION: 3D printing (rapid prototyping) appears to be feasible. Scenarios for the clinical use of the technology might include presenting the model to the surgeon to provide a better understanding of the tumor's spatial characteristics in the breast, in order to improve decision-making in relation to neoadjuvant chemotherapy or surgical approaches. J. Surg. Oncol. 2017;115:238-242. © 2016 Wiley Periodicals, Inc.

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.

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.

Evaluation of ChatGPT's Potential in Tailoring Gynecological Cancer Therapies.

BACKGROUND/AIM: Demographic change and increasing complexity of therapy decisions lead to a growing burden on the healthcare system, necessitating efforts to simplify and enhance the efficiency of patient care. The present study evaluates ChatGPT's ability to provide therapy recommendations for gynecological malignancies that are both in line with the local guidelines and individually tailored to the patient. PATIENTS AND METHODS: Sixteen patients with endometrial, cervical, and ovarian cancer who were treated in the gynecological clinic of the University Hospital Erlangen from January 2022 to August 2023 were included in the analysis. Data collected within clinical routine care were communicated to the chat-based AI model ChatGPT (version 3.5). ChatGPT's performance generating treatment plans were evaluated using an answer scoring system and descriptive analysis. RESULTS: According to the answer scoring system [range: -1 point (minimum) to 2 points (maximum)], ChatGPT demonstrated a good potential in generating therapy recommendations with an average score of 0.75 points for patients with ovarian cancer, 0.7 points for cervical and 1.5 points for endometrial cancer patients. The most common deductions in points were about incomplete therapy recommendations, whereas contraindicated treatment modalities were rarely suggested. Individual patient characteristics were regularly considered by ChatGPT. ChatGPT reliably indicated aftercare and provided detailed information on preventive measures as well as supportive treatment. CONCLUSION: ChatGPT is a promising tool for the generation of therapy suggestions for gynecological carcinomas with high flexibility in response to individual patient differences. At the current state, however, ChatGPT is not suitable for replacing expert panels.

Clinical and Surgical Evaluation of Sentinel Node Biopsy in Patients with Early-Stage Endometrial Cancer and Atypical Hyperplasia.

Introduction: The medical and surgical treatment of endometrial cancer (EC) is evolving toward a more patient-centered and personalized approach. The role of laparoscopic sentinel node biopsy (SNB) for early-stage EC is unclear, and very few data are available for atypical endometrial hyperplasia (AEH). The present study investigated the effectiveness of SNB combined with laparoscopic hysterectomy in patients with early-stage EC and AEH. Patients and Methods: This was a retrospective, single-center cohort study for the period from January 2018 to December 2023. A total of 102 patients with atypical hyperplasia (n = 20) and early-stage EC (n = 82) findings on diagnostic curettage underwent pelvic sentinel node biopsy during the final operation. Results: Eleven patients (55%) who had initially been diagnosed with AEH were found to have EC in the final pathology report. No lymph node metastases were detected in patients who had initially been diagnosed with AEH; a 3.6% rate of positive SNBs was found in patients with EC. Changes in tumor grade occurred in 31.3% of the patients and changes in FIGO stage in 33%. Bilateral sentinel node (SN) mapping was successful in 94.1% of the patients. The postoperative outcomes were comparable to those of routine clinical practice without SNB. Conclusions: SNB can be safely offered to patients who have precursor lesions and early-stage EC without notably extending surgical times or increasing postoperative morbidity. This approach can be considered and is safe for patients diagnosed with AEH, but it appears to have a rather small impact on these patients.

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.

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.