Health-related quality of life and fear of progression in individuals with Li-Fraumeni syndrome.

Li-Fraumeni syndrome (LFS) is a rare autosomal dominant cancer predisposition syndrome associated with a highly elevated lifetime cancer risk. This and the recommended intense surveillance program represent a large psychological burden on families. In order to develop targeted psychosocial interventions, we conducted a needs assessment. Adults (≥18 years) with LFS were included via regular hospital visits and online support groups and newsletters. Individuals filled out a questionnaire addressing among others: fear of progression (FoP-questionnaire, short-form), health-related quality of life (HRQoL, Short-Form Health Survey-12), distress (National Comprehensive Cancer Network distress thermometer), perceived cancer risk, and aspects of surveillance adherence. Collecting data over a 14-month period (March 2020 - June 2021), 70 adults were recruited (female = 58, 82.9%; mean age = 41.53 years). With mean mental component scores (MCS) of 42.28 (SD = 10.79), and physical component scores (PCS) of 48.83 (SD = 10.46), HRQoL was low in 34.8% (physical) and 59.4% (mental) of individuals when applying a mean cut-off of 45.4 (PCS) and 47.5 (MCS) to indicate poor HRQoL. High levels of FoP and distress were present in 68.6% and 69.1% of the participants, respectively. Performing a multiple linear regression on MCS and PCS, no sociodemographic variable was shown to be significant. FoP (ß = -0.33, p < 0.05) and distress (ß = -0.34, p < 0.05) were significantly associated with MCS. Individuals in our sample were burdened more than expected, with the majority reporting low levels of (mental) HRQoL, high distress, and FoP. Psychosocial support is necessary to help individuals with LFS (survivors as well as "previvors") increase their HRQoL, as it is crucial to survival.

Medical students' knowledge on cancer predisposition syndromes and attitude toward eHealth.

PURPOSE: Individuals with cancer predisposition syndromes (CPS) inherit elevated cancer risks. Medical supply gaps for people at risk of CPS cause insufficient outreach and miss potential benefits of individualized care strategies. Increased awareness of CPS and progress in the eHealth sector are untapped sources of health care improvement for affected individuals. METHODS AND RESULTS: This study addressed German-speaking medical students with an online questionnaire in respect to their knowledge of CPS, their medical education, and perspectives. The study population (n = 404) reported interest in and knowledge of CPS, supported by a satisfactory and sustainable education for their prospective patient care. The next generation of doctors would implement eHealth to improve medical services. Skepticism about digitization was claimed by students. They were especially concerned about deterioration in the physician-patient relationship, data abuse, dependence on technology, and incorrect diagnoses. CONCLUSION: Due to increasing diagnosing of CPS and deeper knowledge, this topic is essential for the curriculum in medical schools. In particular, care providers need know-how on identifying patients at risk for a CPS, certain diagnostic and therapeutic steps, surveillance and prophylactic strategies to improve patients' outcomes. Education in medical school as well as implemented eHealth seems to have potential to meet this demand in an upcoming era of personalized medicine. What does this study add to the clinical work. Medical teaching on cancer predisposition syndromes should be expanded to improve knowledge and individualized and personalized healthcare.

Circulating cf-miRNA as a more appropriate surrogate liquid biopsy marker than cfDNA for ovarian cancer.

Ovarian cancer (OC) is an aggressive disease, primarily diagnosed in late stages with only 20% of patients surviving more than 5 years. Liquid biopsy markers have great potential to improve current diagnostic and prognostic methods. Here, we compared miRNAs and DNA methylation in matched plasma, whole blood and tissues as a surrogate marker for OC. We found that while both cfDNA and cf-miRNAs levels were upregulated in OC compared to patients with benign lesions or healthy controls, only cf-miRNA levels were an independent prognosticator of survival. Following on our previous work, we found members of the miR-200 family, miR-200c and miR-141 to be upregulated in both plasma and matched tissues of OC patients which correlated with adverse clinical features. We could also show that the upregulation of miR-200c and -141 correlated with promoter DNA hypomethylation in tissues, but not in plasma or matched whole blood samples. As cf-miRNAs are more easily obtained and very stable in blood, we conclude that they might serve as a more appropriate surrogate liquid biopsy marker than cfDNA for OC.

Health Behavior and Cancer Prevention among Adults with Li-Fraumeni Syndrome and Relatives in Germany-A Cohort Description.

Li-Fraumeni-syndrome (LFS) is a rare, highly penetrant cancer predisposition syndrome (CPS) caused by pathogenic variants (PVs) in TP53. Physical activity (PA) and a Mediterranean diet lead to cancer reduction or survival benefits and increased quality of life (QoL), but this is yet unstudied among LFS. TP53 PV carriers (PVC) and their relatives were questioned on dietary patterns (Mediterranean Diet Adherence Screener), PA (Freiburg Questionnaire), QoL (Short-form-Health-Survey-12), smoking, alcohol consumption and perception of cancer risk in a German bi-centric study from March 2020-June 2021. The study enrolled 70 PVC and 43 relatives. Women compared to men (6.49 vs. 5.38, p = 0.005) and PVC to relatives (6.59 vs. 5.51; p = 0.006) showed a healthier diet, associated with participation in surveillance (p = 0.04) and education (diet p = 0.02 smoking p = 0.0003). Women smoked less (2.91 vs. 5.91 packyears; p = 0.03), psychological well-being was higher among men (SF-12: males 48.06 vs. females 41.94; p = 0.004). PVC rated their own cancer risk statistically higher than relatives (72% vs. 38%, p < 0.001) however, cancer risk of the general population was rated lower (38% vs. 70%, p < 0.001). A relative's cancer-related death increased the estimated personal cancer risk (p = 0.01). The possibilities of reducing cancer through self-determined health behavior among PVC and relatives has not yet been exhausted. Educating families with a CPS on cancer-preventive behavior requires further investigation with regard to acceptance and real-life implementation.

A novel circulating miRNA panel for non-invasive ovarian cancer diagnosis and prognosis.

BACKGROUND: Ovarian cancer (OC) is an aggressive disease, primarily diagnosed in late stages with only 20% of patients surviving more than 5 years after diagnosis. There is a pending need to improve current diagnostics and prognostics. METHODS: In this study, we investigated total circulating cell-free microRNA (cf-miRNA) levels as well as a panel of cf-miRNAs in the plasma of OC patients (n = 100), patients with benign lesions (n = 45) and healthy controls (n = 99). RESULTS: High levels of cf-miRNAs correlated with unfavourable clinical features and were an independent prognosticator of patient survival. By mining NGS data, we identified a signature panel of seven individual cf-miRNAs which could distinguish controls from benign cases with an AUC of 0.77 and controls from cancer cases with an AUC of 0.87. Importantly, in combination with the current gold-standard marker, CA-125, the panel could predict early OC with an AUC of 0.93. CONCLUSION: Our findings highlight the potential of cf-miRNA levels as well as individual cf-miRNAs for OC diagnosis and prognosis that warrants further clinical evaluation.

Genotype-phenotype associations within the Li-Fraumeni spectrum: a report from the German Registry.

Li-Fraumeni syndrome (LFS) is a cancer predisposition syndrome caused by pathogenic TP53 variants. The condition represents one of the most relevant genetic causes of cancer in children and adults due to its frequency and high cancer risk. The term Li-Fraumeni spectrum reflects the evolving phenotypic variability of the condition. Within this spectrum, patients who meet specific LFS criteria are diagnosed with LFS, while patients who do not meet these criteria are diagnosed with attenuated LFS. To explore genotype-phenotype correlations we analyzed 141 individuals from 94 families with pathogenic TP53 variants registered in the German Cancer Predisposition Syndrome Registry. Twenty-one (22%) families had attenuated LFS and 73 (78%) families met the criteria of LFS. NULL variants occurred in 32 (44%) families with LFS and in two (9.5%) families with attenuated LFS (P value < 0.01). Kato partially functional variants were present in 10 out of 53 (19%) families without childhood cancer except adrenocortical carcinoma (ACC) versus 0 out of 41 families with childhood cancer other than ACC alone (P value < 0.01). Our study suggests genotype-phenotype correlations encouraging further analyses.

Consensus Recommendations of the German Consortium for Hereditary Breast and Ovarian Cancer.

Background: The German Consortium for Hereditary Breast and Ovarian Cancer (GC-HBOC) has established a multigene panel (TruRisk®) for the analysis of risk genes for familial breast and ovarian cancer. Summary: An interdisciplinary team of experts from the GC-HBOC has evaluated the available data on risk modification in the presence of pathogenic mutations in these genes based on a structured literature search and through a formal consensus process. Key Messages: The goal of this work is to better assess individual disease risk and, on this basis, to derive clinical recommendations for patient counseling and care at the centers of the GC-HBOC from the initial consultation prior to genetic testing to the use of individual risk-adapted preventive/therapeutic measures.

Assessing the influence of the menstrual cycle on APT CEST-MRI in the human breast.

PURPOSE: In fibroglandular breast tissue, conventional dynamic contrast-enhanced MR-mammography is known to be affected by water content changes during the menstrual cycle. Likewise, amide proton transfer (APT) chemical exchange saturation transfer (CEST)-MRI might be inherently prone to the menstrual cycle, as CEST signals are indirectly detected via the water signal. The purpose of this study was to investigate the influence of the menstrual cycle on APT CEST-MRI in fibroglandular breast tissue. METHOD: Ten healthy premenopausal women (19-34 years) were included in this IRB approved prospective study and examined twice during their menstrual cycle. Examination one and two were performed during the first half (day 2-8) and the second half (day 15-21) of the menstrual cycle, respectively. As a reference for the APT signal in malignant breast tumor tissue, previously reported data of nine breast cancer patients were included in this study. CEST-MRI (B1 = 0.7µT) was performed on a 7 T whole-body scanner followed by a multi-Lorentzian fit analysis. The APT signal was corrected for B0/B1-field inhomogeneities, fat signal contribution, and relaxation effects of the water signal and evaluated in the fibroglandular breast tissue. Intra-individual APT signal differences between examination one and two were compared using the Wilcoxon signed-rank test. The level of significance was set at p < 0.05. RESULTS: The APT signal showed no significant difference in the fibroglandular breast tissue of healthy premenopausal volunteers throughout the menstrual cycle (p = 1.00) (examination 1 vs. examination 2: mean and standard deviation = 3.24 ± 0.68%Hz vs. 3.30 ± 0.73%Hz, median and IQR = 3.36%Hz and 0.87%Hz vs. 3.38%Hz and 0.71%Hz). CONCLUSION: The present study provides an important basis for the clinical application of APT CEST-MRI as an additional contrast mechanism in MR-mammography, as menstrual cycle-related APT signal fluctuations seem to be negligible compared to the APT signal increase in breast cancer tissue.

Total circulating microRNA level as an independent prognostic marker for risk stratification in breast cancer.

BACKGROUND: Although breast cancer (BC) has a high survival rate, relapse events may occur which ultimately lead to aggressive disease. Circulating cell-free microRNAs (cf-miRNAs) are a promising minimally invasive biomarker with diagnostic and/or prognostic potential. Unfortunately, there is still no consensus as to a universal cf-miRNA biomarker in BC and there has been no clinical implementation until now. One major limitation is the technical variation with cf-miRNA isolation and specific quantification methods. METHODS: In this study, we assessed the total levels of cf-miRNAs as a potential prognostic marker for BC in 356 plasma samples from 250 BC patients. RESULTS: High levels of cf-miRNAs significantly correlated with unfavourable clinical features including tumour stage, load and the presence of metastasis at diagnosis. With more than 9 years of follow-up, we could show that global cf-miRNA levels significantly correlated with cancer relapse which was confirmed in multivariate cox regression analysis. Finally, for a subset of patients where the serial plasma was available, levels of cf-miRNAs increased in the plasma prior to clinical detection of progressive disease and were massively elevated in patients who died compared to those still alive at the last timepoint of measurement. CONCLUSIONS: This is the first study to suggest that total cf-miRNA levels in the blood can be used as an independent prognostic marker for BC.

Breast cancer characteristics and surgery among women with Li-Fraumeni syndrome in Germany-A retrospective cohort study.

BACKGROUND: Women with Li-Fraumeni syndrome (LFS) have elevated breast cancer (BC) risk. Optimal BC treatment strategies in this population are yet unknown. METHODS: BC subtypes and treatment were retrospectively investigated between December 2016 and January 2019 in a multicentre study. BC risks were evaluated according to the type of surgery. RESULTS: Thirty-five women of our study population (35/44; 79.5%) had developed 36 breast lesions at first diagnosis at a mean age of 34 years. Those breast lesions comprised 32 invasive BCs (89%), three ductal carcinoma in situ alone (8%) and one malignant phyllodes tumour (3%). BCs were mainly high-grade (18/32), of no special type (NST; 31/32), HER2-enriched (11/32) or luminal-B-(like)-type (10/32). Affected women (n = 35) received breast-conserving surgery (BCS, n = 17) or a mastectomy (ME, n = 18) including seven women with simultaneous contralateral prophylactic mastectomy (CPM) at first diagnosis. Nineteen women suffered 20 breast or locoregional axillary lesions at second diagnosis with mean age of 36. Median time between first and second diagnosis was 57 months; median time to contra- and ipsilateral recurrence depended on surgical strategies (BCS: 46 vs. unilateral ME: 93 vs. bilateral ME > 140 months). Women with a primary treatment of solitaire therapeutic ME suffered from contralateral BC earlier compared to those with therapeutic ME and CPM (median: 93 vs. >140 months). CONCLUSION: Aggressive BC subtypes occur among women with LFS. Surgical treatment, i.e. ME and CPM, may prolong time to a second BC diagnosis. Conclusion on long-term survival benefit is pending. Individual competing tumour risks and long-term outcomes need to be taken into consideration.

The shared frameshift mutation landscape of microsatellite-unstable cancers suggests immunoediting during tumor evolution.

The immune system can recognize and attack cancer cells, especially those with a high load of mutation-induced neoantigens. Such neoantigens are abundant in DNA mismatch repair (MMR)-deficient, microsatellite-unstable (MSI) cancers. MMR deficiency leads to insertion/deletion (indel) mutations at coding microsatellites (cMS) and to neoantigen-inducing translational frameshifts. Here, we develop a tool to quantify frameshift mutations in MSI colorectal and endometrial cancer. Our results show that frameshift mutation frequency is negatively correlated to the predicted immunogenicity of the resulting peptides, suggesting counterselection of cell clones with highly immunogenic frameshift peptides. This correlation is absent in tumors with Beta-2-microglobulin mutations, and HLA-A*02:01 status is related to cMS mutation patterns. Importantly, certain outlier mutations are common in MSI cancers despite being related to frameshift peptides with functionally confirmed immunogenicity, suggesting a possible driver role during MSI tumor evolution. Neoantigens resulting from shared mutations represent promising vaccine candidates for prevention of MSI cancers.

Emergency consultations in obstetrics: identification of decisive, contributing and associated factors.

PURPOSE: Psychosocial and biological factors influence the perception of physical changes during pregnancy. Some pregnant women present to the obstetric emergency department (ED) with diverse symptoms not requiring urgent medical action. These visits result in over-consultation, tying up resources and inflating health care expenses. This study outlines factors associated with multiple ED visits during pregnancy, measures the prevalence of anxiety and depression, and explores the choice of maternity clinic for delivery aiming to elucidate options for care strategies. METHODS: This prospective, cross-sectional, questionnaire-based bicentric study was performed in the obstetric outpatient departments of two university hospitals in Germany and recruited pregnant women between 12/2016 and 11/2017. The questionnaire included socio-demographics, obstetric history, anxiety (GAD-7), depression (PHQ-9), and health status (WHO-5, SF-12). RESULTS: This analysis included 496 women and showed that women with numerous ED visits were significantly younger (p < 0.0001), less educated (p = 0.0002), and more likely to be unemployed and single. Different prevalences for anxiety and depression were detected correlating with the number of ED visits although each showing only low effect sizes (0.024 resp. 0.015). CONCLUSIONS: Pregnant women attending the ED more often might benefit from health education, psychosomatic interventions, and social support to overcome their depression and anxiety to avoid non-urgent ED consultations. Further prospective studies are needed to support these findings.

Cancer surveillance and distress among adult pathogenic TP53 germline variant carriers in Germany: A multicenter feasibility and acceptance survey.

BACKGROUND: Li-Fraumeni syndrome (LFS) is a high-risk cancer predisposition syndrome caused by pathogenic germline variants of TP53. Cancer surveillance has noted a significant survival advantage in individuals with LFS; however, little is known about the feasibility, acceptance, and psychosocial effects of such a program. METHODS: Pathogenic TP53 germline variant carriers completed a 7-part questionnaire evaluating sociodemographics, cancer history, surveillance participation, reasons for nonadherence, worries, and distress adapted from the Cancer Worry Scale. Counselees' common concerns and suggestions were assessed in MAXQDA Analytics Pro 12. RESULTS: Forty-nine participants (46 females and 3 males), aged 40.0 ± 12.6 years, formed the study population; 43 (88%) had a personal cancer history (including multiple cancers in 10 [20%]). Forty-three individuals participated (88%) in surveillance during the study or formerly. Willingness to undergo surveillance was influenced by satisfaction with genetic testing and counseling (P = .019 [Fisher-Yates test]) but not by sociodemographics, cancer history, or distress level. Almost one-third of the participants reported logistical difficulties in implementing surveillance because of the high frequency of medical visits, scheduling difficulties, and the travel distance to their surveillance providers. Self-reported distress and perceived emotional burden for family members and partners were moderate (median for self-reported distress, 3.3; median for perceived emotional burden, 3.0). For both, the interquartile range was moderate to very high (2.7-3.7 and 3.0-3.7, respectively). CONCLUSIONS: Individuals with LFS require efficient counseling as well as an accessible, well-organized, interdisciplinary, standardized surveillance program to increase adherence and psychological coping.

Relaxation-compensated CEST (chemical exchange saturation transfer) imaging in breast cancer diagnostics at 7T.

PURPOSE: To investigate whether fat-corrected and relaxation-compensated amide proton transfer (APT) and guanidyl CEST-MRI enables the detection of signal intensity differences between breast tumors and normal-appearing fibroglandular tissue in patients with newly-diagnosed breast cancer. METHOD: Ten patients with newly-diagnosed breast cancer and seven healthy volunteers were included in this prospective IRB-approved study. CEST-MRI was performed on a 7 T-whole-body scanner followed by a multi-Lorentzian fit analysis. APT and guanidyl CEST signal intensities were quantified in the tumor and in healthy fibroglandular tissue after correction of B0/B1-field inhomogeneities, fat signal contribution, T1- and T2-relaxation; signal intensity differences of APT and guanidyl resonances were compared using Mann-Whitney-U-tests. Pearson correlations between tumor CEST signal intensities and the proliferation index Ki-67 were performed. RESULTS: APT CEST signal in tumor tissue (6.70 ±â€¯1.38%Hz) was increased compared to normal-appearing fibroglandular tissue of patients (3.56 ±â€¯0.54%Hz, p = 0.001) and healthy volunteers (3.70 ±â€¯0.68%Hz, p = 0.001). Further, a moderate positive correlation was found between the APT signal and the proliferation index Ki-67 (R2 = 0.367, r = 0.606, p = 0.11). Guanidyl CEST signal was also increased in tumor tissue (5.24 ±â€¯1.85%Hz) compared to patients' (2.42 ±â€¯0.45%Hz, p = 0.006) and volunteers' (2.36 ±â€¯0.54%Hz, p < 0.001) normal-appearing fibroglandular tissue and a positive correlation with the Ki-67 level was observed (R2 = 0.365, r = 0.604, p = 0.11). APT and guanidyl CEST signal in normal-appearing fibroglandular tissue was not different between patients and healthy volunteers (p = 0.88; p = 0.93). CONCLUSION: Relaxation-compensated and fat-corrected CEST-MRI allowed a non-invasive differentiation of breast cancer and normal-appearing breast tissue. Thus, this approach represents a contrast agent-free method that may help to increase diagnostic accuracy in MR-mammography.

The work and training situation for young physicians undergoing specialty training in gynecology and obstetrics in Germany: an assessment of the status quo.

PURPOSE: General conditions in the health-care system in Germany have changed dramatically in recent years. Factors affecting this include above all demographic change, rapid developments in diagnostic and therapeutic options, and the application of economic criteria to the health-care sector. This study aimed to establish the current status quo regarding conditions of work and training for young doctors in gynecology and obstetrics, analyze stress factors, and suggest potential improvements. METHODS: Between October 2015 and March 2016, a web-based survey was carried out among residents and members of the German Society for Gynecology and Obstetrics. The electronic questionnaire comprised 65 items on seven topics. Part of the survey included the short version of a validated model of professional gratification crises for analyzing psychosocial work-related stress. RESULTS: The analysis included a total of 391 complete datasets. Considerable negative findings in relation to psychosocial work pressure, time and organizational factors, quality of specialty training, and compatibility between work and family life and work and academic tasks were detected. A high level of psychosocial work pressure is associated with more frequent job changes, reduced working hours, poorer health among physicians, and a lower subjectively assessed quality of care. CONCLUSIONS: Greater efforts are needed from all the participants involved in patient care to achieve high-quality training and working conditions that allow physicians to work in a healthy and effective way. These aspects are all prerequisites for sustainably maximizing the resource "physician" and for ensuring high-quality patient care.

Breast cancer risk in BRCA1/2 mutation carriers and noncarriers under prospective intensified surveillance.

Comparably little is known about breast cancer (BC) risks in women from families tested negative for BRCA1/2 mutations despite an indicative family history, as opposed to BRCA1/2 mutation carriers. We determined the age-dependent risks of first and contralateral breast cancer (FBC, CBC) both in noncarriers and carriers of BRCA1/2 mutations, who participated in an intensified breast imaging surveillance program. The study was conducted between January 1, 2005, and September 30, 2017, at 12 university centers of the German Consortium for Hereditary Breast and Ovarian Cancer. Two cohorts were prospectively followed up for incident FBC (n = 4,380; 16,398 person-years [PY], median baseline age: 39 years) and CBC (n = 2,993; 10,090 PY, median baseline age: 42 years). Cumulative FBC risk at age 60 was 61.8% (95% CI 52.8-70.9%) for BRCA1 mutation carriers, 43.2% (95% CI 32.1-56.3%) for BRCA2 mutation carriers and 15.7% (95% CI 11.9-20.4%) for noncarriers. FBC risks were significantly higher than in the general population, with incidence rate ratios of 23.9 (95% CI 18.9-29.8) for BRCA1 mutation carriers, 13.5 (95% CI 9.2-19.1) for BRCA2 mutation carriers and 4.9 (95% CI 3.8-6.3) for BRCA1/2 noncarriers. Cumulative CBC risk 10 years after FBC was 25.1% (95% CI 19.6-31.9%) for BRCA1 mutation carriers, 6.6% (95% CI 3.4-12.5%) for BRCA2 mutation carriers and 3.6% (95% CI 2.2-5.7%) for noncarriers. CBC risk in noncarriers was similar to women with unilateral BC from the general population. Further studies are needed to confirm whether less intensified surveillance is justified in women from BRCA1/2 negative families with elevated risk.

[Work and Training of Young Doctors in Germany - a Comprehensive Analysis of Survey Results from Six Disciplines]. / Die Arbeits- und Weiterbildungssituation junger Ärztinnen und Ärzte in Deutschland ­ eine zusammenfassende Analyse von Befragungsergebnissen aus sechs Fachrichtungen.

OBJECTIVE: The working and training conditions of young physicians in Germany have changed over the last few years, as a result of far-reaching changes in the healthcare system. Therefore, Germany-wide surveys among young physicians of several disciplines were evaluated in a pooled analysis, in order to obtain a current interdisciplinary impression of conflicts in their daily work. MATERIAL AND METHODS: Data from web-based surveys from residents training in six disciplines were analyzed together retrospectively. One focus was a gratification crises model for the assessment of psychosocial workload. RESULTS: Data on 4041 participants were evaluated. In day-to-day work, young physicians were burdened with a high proportion of tasks that were not directly medical. Instruments of good subspecialty training, such as training contracts, curricula and regular feedback were associated with a lower psychosocial workload, which was generally significant among the participants. An economic influence on medical-professional decisions was subjectively clearly present among the participants. CONCLUSION: Many young doctors find the current work and training conditions in the medical work environment unsatisfactory. This might have consequences not only for the doctors themselves, but also for the patients they care for. A healthy work environment with health professionals in good health is therefore crucial and should be in everyone's interest.

Efficacy of intraoperative specimen radiography as margin assessment tool in breast conserving surgery.

PURPOSE: To explore the ability of intraoperative specimen radiography (SR) to correctly identify positive margins in patients receiving breast conserving surgery (BCS). To assess whether the reoperation rate can be reduced by using this method. METHODS: This retrospective study included 470 consecutive cases receiving BCS due to a primarily diagnosed breast cancer. SR was carried out in two planes, assessing the specimen regarding the presence of the lesion and its relation to all margins. If indicated, re-excision of selective orientations was advised. Under consideration of gross inspection and the SR-findings, it was up to the surgeon whether to perform re-resections. The recommendations for re-excision were, separately for each orientation, compared to the histopathological results, serving as gold standard. RESULTS: Intraoperative SR was performed in 470 cases, thus 2820 margins were assessed. Of those, 2510 (89.0%) were negative and 310 (11.0%) positive. SR identified 2179 (77.3%) margins correctly as negative, whereas 331 (11.7%) clear margins were misjudged as positive. Of 310 infiltrated margins, SR identified 114 (4.0%) correctly, whereas 196 (7.0%) infiltrated margins were missed. This resulted in a sensitivity/specificity of 36.8%/86.8% and PPV/NPV of 25.6%/91.8%. Through targeted re-resections positive margins could be reduced by 31.0% [310 to 214 (7.6%)]. On case level, the rate of secondary procedures could be reduced by 37.0% [from 162 to 102 (21.7%)]. CONCLUSIONS: SR is a helpful tool to identify infiltrated margins and to reduce the rate of secondary surgeries by recommending targeted re-excisions of according orientations in order to obtain a final negative margin status.