Diagnosis of ruptured breast implants through high-resolution ultrasound combined with real-time elastography.

BACKGROUND: Implant rupture as a late complication of breast implant surgery is often a silent phenomenon that is difficult to diagnose. Sonoelastography is a new ultrasound-based technique that allows assessment of tissue elasticity. OBJECTIVES: This study was undertaken to evaluate elastographic findings in normal and ruptured breast implants. METHODS: This prospective study included 28 implants in 16 patients, all of whom underwent high-resolution ultrasound and real-time elastography. The diagnosis of implant rupture was confirmed by surgery. RESULTS: Implant rupture was diagnosed in 5 out of 28 implants (17.9%). In those patients with ruptured implants, 3 had no symptoms, 1 presented with pain, and 1 complained of ipsilateral axillary lymph node swelling. Implants with a homogenous anechoic interior were considered to be intact. Ultrasound findings indicating implant rupture included multiple parallel echogenic lines in the implant interior in 2 cases and a mix of hyperechoic and hypoechoic masses in 3 cases. The feasibility of real-time elastography of implants was demonstrated in all cases. Elastograms of intact implants revealed a typical blue-green-red pattern familiar from cystic lesions. In all 5 ruptured implants, elastography revealed yellow-green figures without typical layering. CONCLUSIONS: To the authors' knowledge this is the first series to combine high-resolution ultrasound with real-time elastography for the diagnosis of implant rupture. Since there are distinct differences between elastograms of intact and ruptured implants, addition of real-time elastography to conventional ultrasound may improve implant surveillance and obviate the need for magnetic resonance imaging.

Effects of prenatal Doppler ultrasound on the retina of the chick embryo in ovo.

Currently, the effect of prenatal ultrasound on foetal development is intensively discussed and the guidelines for prenatal diagnostics have been changed. However, data supporting these concerns are scarce. Therefore, we used an established in ovo model of the chicken embryo to investigate cell proliferation and apoptosis within the retina. A total of 21 chicken eggs were fenestrated on Day 5 and allocated to either the control (n = 8) or exposition group (n = 13). The exposition group was treated with pulsed-wave Doppler ultrasound (PWD) for 10 min while controls remained without treatment. After subsequent incubation (6-48 h), the eggs were sacrificed, and chicken embryos were examined morphologically (HE-staining) and immunohistochemically. Counting of apoptotic and proliferating cells per retina was performed using antibodies specific for phospho-histone-H3 and active caspase-3 in combination with a biotin-labelled secondary antibody and peroxidase conjugated avidin-biotin complex for chromogenic detection. Due to a rather low number of specimens at each time point after ultrasound exposition, we neglected the effects of incubation time and focused on treatment effects. This approach revealed that the median number of proliferating cells is reduced after 10 min of exposure to PWD (569 vs. 766), while the number of apoptotic cells is fairly comparable between groups (5 vs. 6). Our data contribute to a better understanding of prenatal US on foetal development by suggesting that PWD could have an impact on the number of proliferating cells in the developing chicken retina and therefore justify further investigations.

Taxane-Induced Neuropathy and Its Ocular Effects-A Longitudinal Follow-up Study in Breast Cancer Patients.

A common severe neurotoxic side effect of breast cancer (BC) therapy is chemotherapy-induced peripheral neuropathy (CIPN) and intervention is highly needed for the detection, prevention, and treatment of CIPN at an early stage. As the eye is susceptible to neurotoxic stimuli, the present study aims to determine whether CIPN signs in paclitaxel-treated BC patients correlate with ocular changes by applying advanced non-invasive biophotonic in vivo imaging. Patients (n = 14, 10 controls) underwent monitoring sessions after diagnosis, during, and after therapy (T0-T3). Monitoring sessions included general anamnesis, assessment of their quality of life, neurological scores, ophthalmological status, macular optical coherence tomography (OCT), and imaging of their subbasal nerve plexus (SNP) by large-area confocal laser-scanning microscopy (CLSM). At T0, no significant differences were detected between patients and controls. During treatment, patients' scores significantly changed while the greatest differences were found between T0 and T3. None of the patients developed severe CIPN but retinal thickenings could be detected. CLSM revealed large SNP mosaics with identical areas while corneal nerves remained stable. The study represents the first longitudinal study combining oncological examinations with advanced biophotonic imaging techniques, demonstrating a powerful tool for the objective assessment of the severity of neurotoxic events with ocular structures acting as potential biomarkers.

Patient-reported outcomes for the Intergroup Sentinel Mamma study (INSEMA): A randomised trial with persistent impact of axillary surgery on arm and breast symptoms in patients with early breast cancer.

Background: In clinically node-negative breast cancer patients, the INSEMA trial (NCT02466737) assessed the non-inferiority of avoiding sentinel lymph node biopsy (SLNB) or axillary lymph node dissection (ALND). Here we present patient-reported outcomes (PROs) as a secondary endpoint. Methods: PROs were assessed for patients with no axillary surgery, SLNB alone, and ALND. Quality of life (QoL) questionnaire EORTC QLQ-C30 and its breast cancer module (BR23) were used at baseline (pre-surgery) and 1, 3, 6, 12, and 18 months after surgery. The QoL scores were compared using repeated measures mixed models based on the safety set. Findings: Between 2015 and 2019, 5502 patients were recruited for the first randomization, and 5154 were included in the intent-to-treat set (4124 SLNB versus 1030 no SLNB). In the case of one to three macrometastases after SLNB, 485 patients underwent second randomization (242 SLNB alone versus 243 ALND). Questionnaire completion response remained high throughout the trial: over 70% at all time points for the first randomization. There were significant differences for the BRBS (breast symptoms) and BRAS (arm symptoms) scores favoring the no SLNB group in all post-baseline assessments. Patients in the SLNB group showed significantly and clinically relevant higher scores for BRAS (differences in mean values ≥5.0 points at all times), including pain, arm swelling, and impaired mobility in all postoperative visits, with the highest difference at one month after surgery. Scoring of the QLQ-C30 questionnaire revealed no relevant differences between the treatment groups, although some comparisons were statistically significant. Interpretation: This is one of the first randomized trials investigating the omission of SLNB in clinically node-negative patients and the first to report comprehensive QoL data. Patients with no SLNB benefitted regarding arm symptoms/functioning, while no relevant differences in other scales were seen. Funding: Supported by German Cancer Aid (Deutsche Krebshilfe, Bonn, Germany), Grant No. 110580 and Grant No. 70110580 to University Medicine Rostock.

Deep learning to predict breast cancer sentinel lymph node status on INSEMA histological images.

BACKGROUND: Sentinel lymph node (SLN) status is a clinically important prognostic biomarker in breast cancer and is used to guide therapy, especially for hormone receptor-positive, HER2-negative cases. However, invasive lymph node staging is increasingly omitted before therapy, and studies such as the randomised Intergroup Sentinel Mamma (INSEMA) trial address the potential for further de-escalation of axillary surgery. Therefore, it would be helpful to accurately predict the pretherapeutic sentinel status using medical images. METHODS: Using a ResNet 50 architecture pretrained on ImageNet and a previously successful strategy, we trained deep learning (DL)-based image analysis algorithms to predict sentinel status on hematoxylin/eosin-stained images of predominantly luminal, primary breast tumours from the INSEMA trial and three additional, independent cohorts (The Cancer Genome Atlas (TCGA) and cohorts from the University hospitals of Mannheim and Regensburg), and compared their performance with that of a logistic regression using clinical data only. Performance on an INSEMA hold-out set was investigated in a blinded manner. RESULTS: None of the generated image analysis algorithms yielded significantly better than random areas under the receiver operating characteristic curves on the test sets, including the hold-out test set from INSEMA. In contrast, the logistic regression fitted on the Mannheim cohort retained a better than random performance on INSEMA and Regensburg. Including the image analysis model output in the logistic regression did not improve performance further on INSEMA. CONCLUSIONS: Employing DL-based image analysis on histological slides, we could not predict SLN status for unseen cases in the INSEMA trial and other predominantly luminal cohorts.

Radiopaque tissue transfer and X-ray system versus standard specimen radiography for intraoperative margin assessment in breast-conserving surgery: randomized clinical trial.

BACKGROUND: Reduction of positive margin rate (PMR) in breast-conserving surgery (BCS) of non-palpable breast cancer remains a challenge. The efficacy of intraoperative specimen radiography (SR) is unclear. This randomized trial evaluated whether the PMR was reduced by the use of devices that allow precise localization of the affected margins. METHODS: Patients with microcalcification-associated breast cancer undergoing planned BCS were enrolled. Study participants were randomized to receive either SR with radiopaque tissue transfer and X-ray system (KliniTrayTM) or the institutional standard procedure (ISO). In all patients with a radiological margin less than 5 mm, an immediate re-excision was conducted. The primary outcome was the PMR. Risk factors for positive margins and the effect of immediate re-excision on final surgery were secondary analyses. RESULTS: Among 122 randomized patients, 5 patients were excluded due to the extent of primary surgery and 117 were available for analysis. Final histopathology revealed a PMR of 31.7 per cent for the KliniTrayTM group and 26.3 per cent for the ISO group (P = 0.127). Independent factors for positive margins were histological tumour size more than 30 mm (adjusted OR (aOR) 10.73; 95 per cent c.i. 3.14 to 36.75; P < 0.001) and specimen size more than 50 mm (aOR 6.65; 95 per cent c.i. 2.00 to 22.08; P = 0.002). Immediate re-excision due to positive SR led to an absolute risk reduction in positive margins of 13.6 per cent (from 42.7 to 29.1 per cent). CONCLUSION: Specimen orientation with a radiopaque tissue transfer and X-ray system did not decrease the PMR in patients with microcalcification-associated breast cancer; however, SR and immediate re-excision proved to be helpful in the reduction of PMR. REGISTRATION NUMBER: DRKS00011527 (https://www.drks.de).

Radiological Underestimation of Tumor Size as a Relevant Risk Factor for Positive Margin Rate in Breast-Conserving Therapy of Pure Ductal Carcinoma In Situ (DCIS).

Background: Radiological underestimation of the actual tumor size is a relevant problem in reaching negative margins in ductal carcinoma in situ (DCIS) associated with microcalcifications in breast-conserving therapy (BCT). The aim of this study is to evaluate whether the radiological underestimation of tumor size has an influence on the histopathological margin status. Methods: Patients who underwent BCT with preoperatively diagnosed pure DCIS were included (pooled analysis of two trials). Multiple factors were analysed regarding radiological underestimation ≥10 mm. Radiological underestimation was defined as mammographic minus histological tumor size in mm. Results: Positive margins occurred in 75 of 189 patients. Radiological underestimation ≥10 mm was an independent influencing factor (OR 5.80; 95%CI 2.55−13.17; p < 0.001). A radiological underestimation was seen in 70 patients. The following parameters were statistically significant associated with underestimation: pleomorphic microcalcifications (OR 3.77; 95%CI 1.27−11.18), clustered distribution patterns (OR 4.26; 95%CI 2.25−8.07), and mammographic tumor sizes ≤20 mm (OR 7.47; 95%CI 3.49−15.99). Only a mammographic tumor size ≤20 mm was an independent risk factor (OR 6.49; 95%CI 2.30−18.26; p < 0.001). Grading, estrogen receptor status, and comedo necrosis did not influence the size estimation. Conclusion: Radiological underestimation is an independent risk factor for positive margins in BCT of DCIS associated with microcalcifications predominantly occurring in mammographic small tumors.

Assessment of dynamic corneal nerve changes using static landmarks by in vivo large-area confocal microscopy-a longitudinal proof-of-concept study.

Background: The purpose of the present proof-of-concept study was to use large-area in vivo confocal laser scanning microscopy (CLSM) mosaics to determine the migration rates of nerve branching points in the human corneal subbasal nerve plexus (SNP). Methods: Three healthy individuals were examined roughly weekly over a total period of six weeks by large-area in vivo confocal microscopy of the central cornea. An in-house developed prototype system for guided eye movement with an acquisition time of 40 s was used to image and generate large-area mosaics of the SNP. Kobayashi-structures and nerve entry points (EPs) were used as fixed structures to enable precise mosaic registration over time. The migration rate of 10 prominent nerve fiber branching points per participant was tracked and quantified over the longitudinal period. Results: Total investigation times of 10 minutes maximum per participant were used to generate mosaic images with an average size of 3.61 mm2 (range: 3.18-4.42 mm2). Overall mean branching point migration rates of (46.4±14.3), (48.8±15.5), and (50.9±13.9) µm/week were found for the three participants with no statistically significant difference. Longitudinal analyses of nerve branching point migration over time revealed significant time-dependent changes in migration rate only in participant 3 between the last two measurements [(63.7±12.3) and (43.0±12.5) µm/week, P<0.01]. Considering individual branching point dynamics, significant differences in nerve migration rate from the mean were only found in a few exceptions. Conclusions: The results of this proof-of-concept study have demonstrated the feasibility of using in vivo confocal microscopy to study the migration rates of corneal subbasal nerves within large areas of the central human cornea (>1 mm2). The ability to monitor dynamic changes in the SNP opens a window to future studies of corneal nerve health and regenerative capacity in a number of systemic and ocular diseases. Since corneal nerves are considered part of the peripheral nervous system, this technique could also offer an objective diagnostic tool and biomarker for disease- or treatment-induced neuropathic changes.

In Vivo Monitoring of Corneal Dendritic Cells in the Subbasal Nerve Plexus during Trastuzumab and Paclitaxel Breast Cancer Therapy-A One-Year Follow-Up.

Paclitaxel and trastuzumab have been associated with adverse effects including chemotherapy-induced peripheral neuropathy (CIPN) or ocular complications. In vivo confocal laser scanning microscopy (CLSM) of the cornea could be suitable for assessing side effects since the cornea is susceptible to, i.e., neurotoxic stimuli. The study represents a one-year follow-up of a breast cancer patient including large-area in vivo CLSM of the subbasal nerve plexus (SNP), nerve function testing, and questionnaires during paclitaxel and trastuzumab therapy. Six monitoring sessions (one baseline, four during, and one after therapy) over 58 weeks were carried out. Large-area mosaics of the SNP were generated, and identical regions within all sessions were assigned. While corneal nerve morphology did not cause alterations, the number of dendritic cells (DCs) showed dynamic changes with a local burst at 11 weeks after baseline. Simultaneously, paclitaxel treatment was terminated due to side effects, which, together with DCs, returned to normal levels as the therapy progressed. Longitudinal in vivo CLSM of the SNP could complement routine examinations and be helpful to generate a comprehensive clinical picture. The applied techniques, with corneal structures acting as biomarkers could represent a diagnostic tool for the objective assessment of the severity of adverse events and the outcome.

Axillary lymph node dissection in early-stage invasive breast cancer: is it still standard today?

Evaluation of axillary lymph node status by sentinel lymph node biopsy (SLNB) and complete axillary lymph node dissection (ALND) are an inherent part of breast cancer treatment. Increased understanding of tumor biology has changed the prognostic and therapeutic impact of lymph node status. Non-invasive imaging techniques like axillary ultrasound, FDG-PET, or MRI revealed moderate sensitivity and high specificity in evaluation of lymph node status. Therefore, they are not sufficient for lymph node staging. Otherwise, the impact of remaining micrometastases and even macrometastases for prognosis and treatment decisions is overestimated. Considering tumor biology, the distinction of axillary metastases in isolated tumor cells (ITC, pN0(i+)); micrometastases (pN1mi), and macrometastases (pN1a) is not comprehensible. Increasing data support the thesis that remaining axillary metastases neither increase the axillary recurrence rate nor decrease overall survival. It is doubtful that axillary tumor cells are capable to complete the complex multistep metastatic process. If applied, axillary metastases are sensitive to systemic treatment and are targeted by postoperative tangential breast irradiation. Therefore, the controversy about the clinical relevance of tumor cell clusters or micrometastases in SLN is a sophisticated but not contemporary discussion. Currently, there is no indication for axillary surgery in elderly patients with favorable tumors and clinically tumor-free lymph nodes. Nonetheless, a rational and evidence-based approach to the management of clinically and sonographically N0 patients with planned breast-conserving surgery and limited tumor size is needed now.

The Clinical Relevance of Target Lymph Node Biopsy after Primary Systemic Therapy in Initially Node-Positive Breast Cancer Patients.

PURPOSE: To assess the impact of the removal of the target lymph node (TLN) on therapy after the completion of primary systemic therapy (PST) in initially node-positive breast cancer patients. METHODS: Pooled data analysis of participants of the prospective CLIP- and TATTOO-study at the University of Rostock was performed. RESULTS: A total of 75 patients were included; 63 of them (84.0%) converted to clinically node-negative after PST. Both TLN and sentinel lymph node (SLN) were identified in 41 patients (51.2%). In five out of 63 patients (7.9%), the TLN was metastatic after PST and the SLN was either tumor-free or not detected. Axillary lymph node dissection (ALND) was conducted in all five patients. In one patient, systemic therapy recommendation was influenced by the TLN; adjuvant radiotherapy was influenced by the TLN in zero patients. For patients with fewer than three removed SLNs, the FNR was 28.6% for the SLN biopsy alone and 7.1% for targeted axillary dissection (TAD). CONCLUSIONS: Removal of the TLN in addition to the SLN after PST has only minimal impact on the type of adjuvant systemic therapy and radiotherapy. However, the extent of axillary surgery was relevantly affected and FNR was improved by TAD.

Targeted Removal of Axillary Lymph Nodes After Carbon Marking in Patients with Breast Cancer Treated with Primary Chemotherapy.

In breast cancer patients who have received primary chemotherapy and then no longer have any suspicious lymph nodes clinically and/or on imaging, marking of initially suspicious axillary lymph nodes with targeted removal has recently been discussed and practised both in Germany and internationally as an alternative to complete axillary lymph node dissection. Tattooing of the suspicious lymph nodes with a highly purified carbon suspension is currently being investigated in clinical studies. Compared with other techniques, the advantages of this method are the high rate of intraoperative lymph node detection, avoidance of an immediately preoperative localisation procedure and the low costs. The practical aspects of lymph node tattooing and the current data regarding this method will be described.

Lost clips after targeted lymph node biopsy in breast cancer patients: Follow-up of the CLIP-study.

INTRODUCTION: Clipping and selective removal of axillary lymph nodes in breast cancer patients presenting with initially node-positive disease and achieving a nodal downstaging after primary systemic therapy is a less invasive method for axillary staging. An imaging guided localization and successful extirpation of these clipped lymph nodes is not possible in all patients. To date no follow-up data regarding patients with lost clips are available. MATERIAL AND METHODS: The oncological outcome of all participants of the CLIP-study and the results of postoperative axillary imaging in those patients with unproven clip resection are presented. RESULTS: A total of thirty patients were included into the pilot study. In ten of these patients (33%) the removal of the clipped axillary lymph node could not be verified by intraoperative radiograph. Postoperative imaging did not find lost clips in eight of these ten patients (80%). The lost clip was detected in two patients after surgery (20%), by mammography in one patient during routine follow-up and by computed tomography scan in one patient before radiotherapy. After a median follow-up of 40 months, 26 (87%) patients were still alive. Seven patients (23%) developed distant recurrent disease. No local or axillary recurrences were observed. CONCLUSION: Lost clips were detected by postoperative imaging only in a minority of patients. The impact of lost clips on axillary recurrences in breast cancer patients is still unclear and should be further clarified in larger, multicentric trials.

Prevalence, Clinical Significance and Risk Factors for Developing Scar Pain and Sensibility Disorders in Breast Cancer Patients after Breast-Conserving Therapy and Mastectomy.

INTRODUCTION: The aim of this study was to gather information on the prevalence and risk factors for scar pain and sensibility disorders after breast cancer surgery, as only limited information of these complaints are available. MATERIAL AND METHODS: A clinical cohort study using a non-validated questionnaire was conducted among women who presented to routine follow-up at the Breast Cancer Center Rostock, Germany. The subjects were informed that the subjective perception and sensation were in the foreground and that the questionnaire had to be filled out independently according to the current feeling. RESULTS: Overall 175 patients could be evaluated. The prevalence of scar pain was 30.8% after breast conserving therapy (BCT) and 34.5% after mastectomy. Following BCT 87.5%, respectively 81.8% of women after mastectomy were very satisfied or satisfied with the scarring. Sensory disorders were increased in the mastectomy group (p = 0.001). Scar pain after previous surgery was a risk factor to develop sensory disorders after BCT (p = 0.008) and mastectomy (p = 0.029). For patients receiving mastectomy, sensory disorders after previous breast surgeries increased the risk for sensory disorders (p = 0.029). Smoking was a risk factor for sensory disorders after mastectomy (p = 0.048). Multivariate analysis could not confirm any of the risk factors. CONCLUSION: This study demonstrated a high satisfaction with scarring after breast surgery and a low level of scar pain. A lack of postoperative information, as well as a low level of actually performed scar care after surgery were observed. Increased focus should be on improved information on postoperative scare care.

Burst of Corneal Dendritic Cells during Trastuzumab and Paclitaxel Treatment.

During breast cancer therapy, paclitaxel and trastuzumab are both associated with adverse effects such as chemotherapy-induced peripheral neuropathy and other systemic side effects including ocular complications. Corneal nerves are considered part of the peripheral nervous system and can be imaged non-invasively by confocal laser scanning microscopy (CLSM) on the cellular level. Thus, in vivo CLSM imaging of structures of the corneal subbasal nerve plexus (SNP) such as sensory nerves or dendritic cells (DCs) can be a powerful tool for the assessment of corneal complications during cancer treatment. During the present study, the SNP of a breast cancer patient was analyzed over time by using large-scale in vivo CLSM in the course of paclitaxel and trastuzumab therapy. The same corneal regions could be re-identified over time. While the subbasal nerve morphology did not alter significantly, a change in dendritic cell density and an additional local burst within the first 11 weeks of therapy was detected, indicating treatment-mediated corneal inflammatory processes. Ocular structures such as nerves and dendritic cells could represent useful biomarkers for the assessment of ocular adverse effects during cancer therapy and their management, leading to a better visual prognosis.

The Significance of Preoperative Computed Tomography for Predicting Optimal Cytoreduction in Advanced Ovarian Cancer.

Introduction Optimal cytoreduction is the most important prognostic factor in advanced ovarian cancer. Although staging and assessment of operability are made by exploratory surgery, preoperative computed tomography (CT) of the abdomen is regarded as standard. The aim of this study was to examine various CT parameters with regard to prediction of optimal cytoreduction. Patients and Methods The retrospective study included 131 patients with ovarian cancer newly diagnosed between 2010 and 2014. Of these, n = 36 with FIGO stage I to IIB were excluded from the study. A preoperative abdominal CT was available for n = 75 of the 95 patients with FIGO stage IIC to IV. The CT scans underwent blinded review. The 11 evaluated CT parameters were examined by means of χ 2 test and logistic regression analysis with regard to the endpoints of macroscopic residual tumour and residual tumour > 1 cm. Survival analyses used the Kaplan-Meier method and log rank test. Results Of 75 patients, 28 (37.3%) had complete tumour resection and 26 (34.7%) had residual tumour ≤ 1 cm. Residual tumours > 1 cm were found in 21 (28%) patients, five of which were not resectable. Overall survival with residual tumour > 1 cm differed significantly from the group with no macroscopic residual tumour (p = 0.003) and with residual tumour ≤ 1 cm (p = 0.04). The CT parameters tumour foci in the diaphragm, mesocolon, greater omentum and peritoneum as well as ascites correlated with macroscopic residual tumour. In the multivariate logistic regression analysis only the CT parameter intraparenchymal liver metastasis was statistically significant with regard to prediction of suboptimal tumour resection (> 1 cm) (OR 8.04; 95% CI 1.57 - 42.4; p = 0.0134). The sensitivity, specificity, PPV and NPV were 37.5, 89.7, 66.7 and 72.2%. Conclusion Although risk parameters for suboptimal tumour reduction can be identified by CT of the abdomen, surgical exploration with histological confirmation of the diagnosis is essential because of the poor diagnostic accuracy.

Central Review of Radiation Therapy Planning Among Patients with Breast-Conserving Surgery: Results from a Quality Assurance Process Integrated into the INSEMA Trial.

PURPOSE: After publication of the radiation field design in the American College of Surgeons Oncology Group Z0011 trial, a radiation therapy quality assurance review was integrated into the Intergroup-Sentinel-Mamma (INSEMA) trial. We aimed to investigate the role of patient characteristics, extent of axillary surgery, and radiation techniques for dose distribution in ipsilateral axillary levels. METHODS AND MATERIALS: INSEMA (NCT02466737) has randomized 5542 patients who underwent breast-conserving surgery. Of these, 276 patients from 108 radiation therapy facilities were included in the central review, using the planning records of the first 3 patients treated at each site. RESULTS: Of the 276 patients, 41 had major deviations (ie, no axillary contouring or submission of insufficient records) leading to exclusion. A total of 235 (85.1%) radiation therapy planning records were delineated according to the INSEMA protocol, including 9 (3.8%) cases with minor deviations. At least 25% of INSEMA patients were unintentionally treated with ≥95% of the prescribed breast radiation dose in axillary level I. Approximately 50% of patients were irradiated with a median radiation dose of more than 85% of prescription dose in level I. Irradiated volumes and applied doses were significantly lower in levels II and III compared with level I. However, 25% of patients still received a median radiation dose of ≥75% of prescription dose to level II. Subgroup analysis revealed a significant association between incidental radiation dose in the axilla and obesity. Younger age, boost application, and fractionation schedule showed no impact on axillary dose distribution. CONCLUSIONS: Assuming ≥80% of prescribed breast dose as the optimal dose for curative radiation of low-volume disease in axillary lymph nodes, at least 50% of reviewed INSEMA patients received an adequate dose in level I, even with contemporary 3-dimensional techniques. Dose coverage was much less in axillary levels II and III, and far below therapeutically relevant doses.

Benign Breast Disease in Women.

BACKGROUND: Most clinical breast changes in women are benign; in only 3% to 6% of cases are they due to breast cancer. How- ever, there is a lack of up-to-date, evidence-based treatment recommendations for the various benign differential diagnoses. METHODS: Selective literature search of PubMed from 1985 to May 2019, including current national (AWMF, Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften [Association of Scientific Medical Societies in Germany]) and inter- national guidelines. RESULTS: Mastalgia and fibrocystic changes are common (around 50% of all women over the age of 30). Fibroadenomas occur in 25% of women; they are the most common benign tumors of the breast and do not require treatment. With most benign breast changes the risk of dedifferentiation is very low. However, it is important in the differential diagnosis to distinguish between such benign changes and breast cancer or changes that carry a risk of malignancy. Complex cysts, for example, carry a risk of malig- nancy of 23% to 31%, papillary lesions 16% , and radial scars 7%. Where there is doubt, histological confirmation should be sought by means of percutaneous biopsy. CONCLUSION: Benign breast changes can be definitively distinguished from malignant lesions through the selective use of avail- able diagnostic investigations and interdisciplinary collaboration. When lesions of uncertain malignant potential are found (B3 in the biopsy classification), complete excision is indicated. Prospective studies on the early diagnosis of breast cancer in lesions carrying a risk of malignancy are desirable.

Oncologic Outcome of Patients with (Low-Risk) Endometrial Carcinoma Undergoing Laparotomy versus Minimally Invasive Hysterectomy: A Retrospective Analysis.

BACKGROUND: Patients with endometrial carcinoma (EC) frequently are obese and have various secondary diseases. We investigated the oncologic safety and complication rates of early-stage EC treated with laparotomy (LAP) versus minimally invasive hysterectomy (MIH). A secondary study aim was the evaluation of risk factors for relapse and complications. METHODS: Data from the Cancer Registry Rostock, Germany, and the medical records of women diagnosed with type 1 EC between January 2005 and December 2014 were retrospectively evaluated. The baseline characteristics were analyzed with the χ2 test and Fisher's exact test. Multivariate analysis with the Cox proportional-hazards model and logistic regression were performed to identify prognostic factors for time to event and risk factors for complications. Kaplan-Meier analysis was performed for disease-free and overall survival. RESULTS: Of 350 evaluated patients, 242 underwent traditional LAP; on 108 patients, MIH was performed. The median follow-up period in the LAP group and the MIH group was 82 ± 31.1 and 71.1 ± 33.6 months, respectively (p = 0.10). The median time to event was 40.3 ± 28.1 months in the LAP group and 38.0 ± 27.5 months in the MIH group (p = 0.476). Significantly longer surgery times (p < 0.001) and more complications (p < 0.001) were observed in the LAP group. Disease-free survival after MIH was not significantly different from that after LAP (log-rank p = 0.052). Multimorbidity remained as the single risk factor for event/recurrence (p = 0.019) in multivariate analysis. CONCLUSIONS: MIH for early-stage EC may be an oncologically safe approach when compared to LAP, and its complication rates are lower; therefore, MIH represents the preferred approach for this patient cohort.

How important is the axillary nodal status for adjuvant treatment decisions at a breast cancer multidisciplinary tumor board? A survival analysis.

BACKGROUND: Tumor board recommendations for breast cancer are mainly based on patient characteristics and prognostic tumor parameters. In the era of potential avoidance of axillary surgery we evaluate the impact of pathologic nodal status for adjuvant treatment decisions. METHODS: Postoperative tumor board records of 207 patients over a 1-year period were rediscussed without knowledge of pathologic nodal status. Differences were classified as major (chemotherapy and/or radiotherapy: present/absent) or minor (different chemotherapeutic protocols) discrepancies. The survival rates among subgroups were calculated using Adjuvant! Online tool. RESULTS: The tumor board without information of pathologic nodal status resulted in treatment changes in 72 of the 207 patients studied (34.8%). Major discrepancies were observed in 37 patients (17.9%). The survival rates were not significantly different due to a balanced overtreatment and undertreatment in this subgroup. Lymphovascular invasion (LVI) was an independent parameter used to predict the subgroup with major discrepancies (P = .001; RR = 4.9 [95% CI, 1.9-12.7]). CONCLUSIONS: The knowledge of pathologic nodal status is important for postoperative chemotherapy and postmastectomy radiotherapy indications. There is a risk for one-third of all patients when avoiding axillary surgery to get an adjuvant therapy that differs from the current guidelines especially in carcinomas with present LVI.