A Novel, Cardiac-Derived Algorithm for Uterine Activity Monitoring in a Wearable Remote Device.

Background: Uterine activity (UA) monitoring is an essential element of pregnancy management. The gold-standard intrauterine pressure catheter (IUPC) is invasive and requires ruptured membranes, while the standard-of-care, external tocodynamometry (TOCO)'s accuracy is hampered by obesity, maternal movements, and belt positioning. There is an urgent need to develop telehealth tools enabling patients to remotely access care. Here, we describe and demonstrate a novel algorithm enabling remote, non-invasive detection and monitoring of UA by analyzing the modulation of the maternal electrocardiographic and phonocardiographic signals. The algorithm was designed and implemented as part of a wireless, FDA-cleared device designed for remote pregnancy monitoring. Two separate prospective, comparative, open-label, multi-center studies were conducted to test this algorithm. Methods: In the intrapartum study, 41 laboring women were simultaneously monitored with IUPC and the remote pregnancy monitoring device. Ten patients were also monitored with TOCO. In the antepartum study, 147 pregnant women were simultaneously monitored with TOCO and the remote pregnancy monitoring device. Results: In the intrapartum study, the remote pregnancy monitoring device and TOCO had sensitivities of 89.8 and 38.5%, respectively, and false discovery rates (FDRs) of 8.6 and 1.9%, respectively. In the antepartum study, a direct comparison of the remote pregnancy monitoring device to TOCO yielded a sensitivity of 94% and FDR of 31.1%. This high FDR is likely related to the low sensitivity of TOCO. Conclusion: UA monitoring via the new algorithm embedded in the remote pregnancy monitoring device is accurate and reliable and more precise than TOCO standard of care. Together with the previously reported remote fetal heart rate monitoring capabilities, this novel method for UA detection expands the remote pregnancy monitoring device's capabilities to include surveillance, such as non-stress tests, greatly benefiting women and providers seeking telehealth solutions for pregnancy care.

A New Practical Decision Rule to Better Differentiate BI-RADS 3 or 4 Breast Masses on Breast Ultrasound.

OBJECTIVES: The BI-RADS classification provides a standardized way to describe ultrasound findings in breast cancer diagnostics. However, there is little information regarding which BI-RADS descriptors are most strongly associated with malignancy, to better distinguish BI-RADS 3 (follow-up imaging) and 4 (diagnostic biopsy) breast masses. METHODS: Patients were recruited as part of an international, multicenter trial (NCT02638935). The trial enrolled 1294 women (6 excluded) categorized as BI-RADS 3 or 4 upon routine B-mode ultrasound examination. Ultrasound images were evaluated by three expert physicians according to BI-RADS. All patients underwent histopathological confirmation (reference standard). We performed univariate and multivariate analyses (chi-square test, logistic regression, and Krippendorff's alpha). RESULTS: Histopathologic evaluation showed malignancy in 368 of 1288 masses (28.6%). Upon performing multivariate analysis, the following descriptors were significantly associated with malignancy (P < .05): age ≥50 years (OR 8.99), non-circumscribed indistinct (OR 4.05) and microlobulated margin (OR 2.95), nonparallel orientation (OR 2.69), and calcification (OR 2.64). A clinical decision rule informed by these results demonstrated a 97% sensitivity and missed fewer cancers compared to three physician experts (range of sensitivity 79-95%) and a previous decision rule (sensitivity 59%). Specificity was 44% versus 22-83%, respectively. The inter-reader reliability of the BI-RADS descriptors and of the final BI-RADS score was fair-moderate. CONCLUSIONS: A patient should undergo a diagnostic biopsy (BI-RADS 4) instead of follow-up imaging (BI-RADS 3) if the patient is 50 years or older or exhibits at least one of the following features: calcification, nonparallel orientation of mass, non-circumscribed margin, or posterior shadowing.

Does conventional specimen radiography after neoadjuvant chemotherapy of breast cancer help to reduce the rate of second surgeries?

PURPOSE: This is the first study to systematically evaluate the diagnostic accuracy of intraoperative specimen radiography on margin level and its potential to reduce second surgeries in patients treated with neoadjuvant chemotherapy. METHODS: This retrospective study included 174 cases receiving breast conserving surgery (BCS) after neoadjuvant chemotherapy (NACT) of primary breast cancer. Conventional specimen radiography (CSR) was performed to assess potential margin infiltration and recommend an intraoperative re-excision of any radiologically positive margin. The histological workup of the specimen served as gold standard for the evaluation of the accuracy of CSR and the potential reduction of second surgeries by CSR-guided re-excisions. RESULTS: 1044 margins were assessed. Of 47 (4.5%) histopathological positive margins, CSR identified 9 correctly (true positive). 38 infiltrated margins were missed (false negative). This resulted in a sensitivity of 19.2%, a specificity of 89.2%, a positive predictive value (PPV) of 7.7%, and a negative predictive value (NPV) of 95.9%. The rate of secondary procedures was reduced from 23 to 16 with a number needed to treat (NNT) of CSR-guided intraoperative re-excisions of 25. In the subgroup of patients with cCR, the prevalence of positive margins was 10/510 (2.0%), PPV was 1.9%, and the NNT was 85. CONCLUSION: Positive margins after NACT are rare and CSR has only a low sensitivity to detect them. Thus, the rate of secondary surgeries cannot be significantly reduced by recommending targeted re-excisions, especially in cases with cCR. In summary, CSR after NACT is inadequate for intraoperative margin assessment but remains useful to document removal of the biopsy site clip.

Quality of life after simultaneously integrated boost with intensity-modulated versus conventional radiotherapy with sequential boost for adjuvant treatment of breast cancer: 2-year results of the multicenter randomized IMRT-MC2 trial.

BACKGROUND: We recently published 2-year results of the prospective, randomized IMRT-MC2 trial, showing non-inferior local control and cosmesis in breast cancer patients after conventionally fractionated intensity-modulated radiotherapy with simultaneously integrated boost (IMRT-SIB), compared to 3D-conformal radiotherapy with sequential boost (3D-CRT-seqB). Here, we report on 2-year quality of life results. PATIENTS AND METHODS: 502 patients were enrolled and randomized to IMRT-SIB (50.4 Gy in 1.8 Gy fractions with a 64.4 Gy SIB to the tumor bed) or to 3D-CRT-seqB (50.4 Gy in 1.8 Gy fractions, followed by a sequential boost of 16 Gy in 2 Gy fractions). For quality of life (QoL) assessment, patients completed the QLQ-C30 and QLQ-BR23 questionnaires at baseline, 6 weeks and 2 years after radiotherapy. RESULTS: Significant differences between treatment arms were seen 6 weeks after radiotherapy for pain (22.3 points for IMRT vs. 27.0 points for 3D-CRT-seqB; p = 0.033) and arm symptoms (18.1 points for IMRT vs. 23.6 points for 3D-CRT-seqB; p = 0.013), both favoring IMRT-SIB. Compared to baseline values, both arms showed significant improvement in global score (IMRT: p = 0.009; 3D-CRT: p = 0.001) after 2 years, with slight deterioration on the role (IMRT: p = 0.008; 3-D-CRT: p = 0.001) and social functioning (IMRT: p = 0.013, 3D-CRT: p = 0.001) as well as the future perspectives scale (IMRT: p = 0.003; 3D-CRT: p = 0.0034). CONCLUSION: This is the first randomized phase III trial demonstrating that IMRT-SIB was associated with slightly superior QoL compared to 3-D-CRT-seqB. These findings further support the clinical implementation of SIB in adjuvant breast cancer treatment.

First proof-of-concept evaluation of the FUSION-X-US-II prototype for the performance of automated breast ultrasound in healthy volunteers.

PURPOSE: The FUSION-X-US-II prototype was developed to combine 3D-automated breast ultrasound (ABUS) and digital breast tomosynthesis in a single device without decompressing the breast. We evaluated the technical function, feasibility of the examination workflow, image quality, breast tissue coverage and patient comfort of the ABUS device of the new prototype. METHODS: In this prospective feasibility study, the FUSION-X-US-II prototype was used to perform ABUS in 30 healthy volunteers without history of breast cancer. The ABUS images of the prototype were interpreted by a physician with specialization in breast diagnostics. Any detected lesions were measured and classified using BI-RADS® scores. Image quality was rated subjectively by the physician and coverage of the breast was measured. Patient comfort was evaluated by a questionnaire after the examination. RESULTS: One hundred and six scans were performed (61 × CC, 23 × ML, 22 × MLO) in 60 breasts. Image acquisition and processing by the prototype was fast and accurate. Breast coverage by ABUS was approximately 90.8%. Sixteen breast lesions (all benign, classified as BIRADS® 2) were identified. The examination was tolerated by all patients. CONCLUSION: The FUSION-X-US-II prototype allows a rapid ABUS scan with mostly high patient comfort. Technical developments resulted in an improvement of quality and coverage compared to previous prototype versions. The results are encouraging for a test of the prototype in a clinical setting in combination with tomosynthesis.

The Influence of Different Genres of Music on the Performance of Medical Students on Standardized Laparoscopic Exercises.

PURPOSE: Whether and how music influences the performance of surgical procedures such as laparoscopy is unclear and can be feasibly determined using laparoscopic box training tools under standardized conditions. The aim of this prospective study is to evaluate the effect of different genres of music on the performance of laparoscopic novices. METHODS: Between May 2018 and December 2018, n = 82 students (38 male, 44 female) from Heidelberg University Medical School performed 3 different laparoscopic exercises (A, B, C) from the "Luebecker Toolbox" with 2 repetitions each under standardized conditions. Time was recorded for each exercise. The students were assigned either to one of four groups, each of which was exposed to a compilation of music from 1 genre (hip hop, classical, rock, or mixed radio music), or to a fifth, control group, without exposure to music. The music was played at a constant sound pressure level of 70 decibels . Each group was compared with the others using a t-test for independent samples. RESULTS: Exposure to music generally led to better performance compared with the control group. Compared with exposure to mixed radio music or to rock, significantly better performance could be demonstrated for exposure to classical music in Exercise B, with an average exposure time of 127 s needed (± 21.4; p < 0.05). No significant differences could be demonstrated for Exercise A, though for classical music, best performance was possible with 120 s (±17.3) of exposure. In Exercise C, hip hop triggered significantly better performance than rock or radio music (p < 0.05). CONCLUSIONS: At an sound pressure level of 70 decibels, exposure to classical music or hip hop appears to have beneficial effects on training performance for surgical novices under standardized conditions.

Evaluation of the FUSION-X-US-II prototype to combine automated breast ultrasound and tomosynthesis.

OBJECTIVE: The FUSION-X-US-II prototype was developed to combine 3D automated breast ultrasound (ABUS) and digital breast tomosynthesis in a single device. We evaluated the performance of ABUS and tomosynthesis in a single examination in a clinical setting. METHODS: In this prospective feasibility study, digital breast tomosynthesis and ABUS were performed using the FUSION-X-US-II prototype without any change of the breast position in patients referred for clarification of breast lesions with an indication for tomosynthesis. The tomosynthesis and ABUS images of the prototype were interpreted independently from the clinical standard by a breast diagnostics specialist. Any detected lesion was classified using BI-RADS® scores, and results of the standard clinical routine workup (gold standard) were compared to the result of the separate evaluation of the prototype images. Image quality was rated subjectively and coverage of the breast was measured. RESULTS: One hundred one patients received both ABUS and tomosynthesis using the prototype. The duration of the additional ABUS acquisition was 40 to 60 s. Breast coverage by ABUS was approximately 80.0%. ABUS image quality was rated as diagnostically useful in 86 of 101 cases (85.1%). Thirty-three of 34 malignant breast lesions (97.1%) were identified using the prototype. CONCLUSION: The FUSION-X-US-II prototype allows a fast ABUS scan in combination with digital breast tomosynthesis in a single device integrated in the clinical workflow. Malignant breast lesions can be localized accurately with direct correlation of ABUS and tomosynthesis images. The FUSION system shows the potential to improve breast cancer screening in the future after further technical improvements. KEY POINTS: • The FUSION-X-US-II prototype allows the combination of automated breast ultrasound and digital breast tomosynthesis in a single device without decompression of the breast. • Image quality and coverage of ABUS are sufficient to accurately detect malignant breast lesions. • If tomosynthesis and ABUS should become part of breast cancer screening, the combination of both techniques in one device could offer practical and logistic advantages. To evaluate a potential benefit of a combination of ABUS and tomosynthesis in screening-like settings, further studies are needed.

Diagnostic accuracy of axillary staging by ultrasound in early breast cancer patients.

BACKGROUND: Axillary ultrasound (AUS) is a standard procedure in the preoperative clinical identification of axillary metastatic lymph node (LN) involvement. It guides decisions about local and systemic therapy for patients with early breast cancer (EBC). But there is only weak evidence on the diagnostic criteria and standard interpretation. The aim of this study was to assess the performance of AUS in the detection and exclusion of LN metastases. METHODS: In a retrospective single-center study, 611 consecutive EBC patients with 622 axillae underwent AUS +/- core needle biopsy (CNB) plus axillary surgery, i.e. sentinel lymph node biopsy and/or axillary lymph node dissection. For all patients, AUS image documentation of at least the most suspicious LN was saved during the initial diagnostic work-up. The diagnostic outcome measures were sensitivity, specificity, accuracy, Youden-index (YI), and diagnostic odds ratio (DOR) on the basis of the daily routine interpretation and on the basis of previously recommended diagnostic criteria by two blinded examiners. RESULTS: On the basis of the daily routine interpretation, AUS had a sensitivity (95 % CI) of 53.3 % (46.4-60.1), a specificity (95 % CI) of 93.6 % (90.8-95.8), an accuracy (95 % CI) of 79.7 % (76.4-82.8), a YI (95 % CI) of 0.47 (0.40 - 0.54), and a DOR (95 % CI) of 16.75 (10.37-27.05). Systematic application of previously recommended diagnostic criteria did not improve the diagnostic accuracy of routinely interpreted AUS. CONCLUSION: AUS performance alone is not sufficient to accurately identify or exclude axillary metastatic disease in unselected patients with EBC.

Intensity Modulated Radiation Therapy (IMRT) With Simultaneously Integrated Boost Shortens Treatment Time and Is Noninferior to Conventional Radiation Therapy Followed by Sequential Boost in Adjuvant Breast Cancer Treatment: Results of a Large Randomized Phase III Trial (IMRT-MC2 Trial).

PURPOSE: In the modern era, improvements in radiation therapy techniques have paved the way for simultaneous integrated boost irradiation in adjuvant breast radiation therapy after breast conservation surgery. Nevertheless, randomized trials supporting the noninferiority of this treatment to historical standards of care approach are lacking. METHODS: A prospective, multicenter, randomized phase 3 trial (NCT01322854) was performed to analyze noninferiority of conventional fractionated intensity modulated radiation therapy with simultaneous integrated boost (IMRT-SIB) to 3-D conformal radiation therapy with sequential boost (3-D-CRT-seqB) for breast cancer patients. Primary outcomes were local control (LC) rates at 2 and 5 years (noninferiority margin at hazard ratio [HR] of 3.5) as well as cosmetic results 6 weeks and 2 years after radiation therapy (evaluated via photo documentation calculating the relative breast retraction assessment [pBRA] score [noninferiority margin of 1.25]). RESULTS: A total of 502 patients were randomly assigned from 2011 to 2015. After a median follow-up of 5.1 years, the 2-year LC for the IMRT-SIB arm was noninferior to the 3-D-CRT-seqB arm (99.6% vs 99.6%, respectively; HR, 0.602; 95% CI, 0.123-2.452; P = .487). In addition, noninferiority was also shown for cosmesis after IMRT-SIB and 3-D-CRT-seqB at both 6 weeks (median pBRA, 9.1% vs 9.1%) and 2 years (median pBRA, 10.4% vs 9.8%) after radiation therapy (95% CI, -0.317 to 0.107 %; P = .332). Cosmetic assessment according to the Harvard scale by both the patient and the treating physician as well as late-toxicity evaluation with the late effects normal tissues- subjective, objective, management, analytic criteria, a score for the evaluation of long-term adverse effects in normal tissue, revealed no significant differences between treatment arms. In addition, there was no difference in overall survival rates (99.6% vs 99.6%; HR, 3.281; 95% CI: -0.748 to 22.585; P = .148) for IMRT-SIB and 3-D-CRT-seqB, respectively. CONCLUSIONS: To our knowledge, this is the first prospective trial reporting the noninferiority of IMRT-SIB versus 3-D-CRT-seqB with respect to cosmesis and LC at 2 years of follow-up. This treatment regimen considerably shortens adjuvant radiation therapy times without compromising clinical outcomes.

Adjuvant Radiation Therapy for Male Breast Cancer-A Rare Indication?

Due to its rarity, there are no randomized trials investigating the outcome of adjuvant radiotherapy in MBC. This study reports on patient and tumor characteristics of 41 consecutive MBC patients treated between 1990 and 2018 and on clinical outcomes after surgical resection of tumors and adjuvant radiotherapy of the chest wall or breast. Local control (LC), locoregional control (LRC), overall survival (OS), disease-free survival (DFS), and toxicity were evaluated. After a median follow-up of 80 months (95% CI: 14.6-213.8 months) there was only one recurrence, in a patient's locoregional lymph nodes 17 months after start of radiotherapy, resulting in an LC rate of 100% at 5 years and a 5-year LRC rate of 97.4% (standard deviation (SD): 0.025). Five-year DFS and OS rates were 64.6% (SD: 0.085) and 57.2% (SD: 0.082), respectively. Adjuvant radiotherapy was tolerated well without high-grade (CTCAE grade > II) adverse events. After tumor resection and adjuvant radiotherapy, LC and LRC rates in MBC patients are excellent and comparable to results found for female breast cancer (FBC) patients. However, as patients are often diagnosed with locally advanced, higher-risk tumors, distant recurrences remain the major failure pattern.

Wireless, remote solution for home fetal and maternal heart rate monitoring.

BACKGROUND: Access to prenatal care can be challenging due to physician shortages and rural geography. The multiple prenatal visits performed to collect basic fetal measurements lead to significant patient burden as well. The standard of care tools for fetal monitoring, external fetal heart rate monitoring with cardiotocography, as used today, must be applied by a medical professional in a healthcare setting. Novel tools to enable a remote and self-administered fetal monitoring solution would significantly alleviate some of the current barriers to care. OBJECTIVE: To compare maternal and fetal heart rate monitoring data obtained by 'Invu system' (a wireless, wearable, self-administered, fixed-location device containing passive electrical and acoustic sensors) to cardiotocography, toward a true remote fetal monitoring solution. MATERIALS AND METHODS: A prospective, open-label, multicenter study evaluated concurrent use of Invu and cardiotocography in pregnant women, aged 18 to 50 years, with singleton pregnancies ≥32+0 weeks' gestation (NCT03504189). Simultaneous recording sessions from Invu and cardiotocography lasted for ≥30 minutes. Data from the 8 electrical sensors and 4 acoustic sensors in the Invu belt were acquired, digitized, and sent wirelessly for analysis by an algorithm on cloud-based servers. The algorithm validates the data, preprocesses the data to remove noise, detects heartbeats independently from the two data sources (electrical and acoustic), and fuses the detected heartbeat arrays to calculate fetal heart rate (FHR) and maternal heart rate (MHR). The primary performance endpoint was Invu FHR limit of agreement within ± 10 beats per minute (bpm) of FHR measured with cardiotocography. RESULTS: A total of 147 women were included in the study analysis. The mean (SD) maternal age was 31.8 ±6.9 years, and the mean gestational age was 37.7 ±2.3 weeks. There was a highly significant correlation between FHR measurements from Invu and cardiotocography (r = 0.92; P<0.0001). The 95% limits of agreement for the difference, the range within which most differences between the two measurements will lie, were -8.84 bpm to 8.24 bpm. Invu measurements of MHR were also very similar to cardiotocography and were highly significantly correlated (r = 0.97; P<0.0001). No adverse events were reported during the study. CONCLUSION: Although captured by very different methods, the FHR and MHR outputs wirelessly obtained by the Invu system through passive methods were very similar to those obtained by the current standard of care. The limits of agreement for FHR measured by Invu were within a clinically acceptable ± 8 bpm of cardiotocography FHR. The Invu device uses passive technology to allow for safe, non-invasive and convenient monitoring of patients in the clinic and remotely. Further work should investigate how remote perinatal monitoring could best address some of the recent challenges seen with prenatal care and maternal and fetal outcomes. CLINICAL TRIAL INFORMATION: Registration date: April 20, 2018; First participant enrollment: February 28, 2018; ClinicalTrials.gov registration NCT03504189; https://clinicaltrials.gov/ct2/show/NCT03504189.

Acute toxicity of normofractionated intensity modulated radiotherapy with simultaneous integrated boost compared to three-dimensional conformal radiotherapy with sequential boost in the adjuvant treatment of breast cancer.

BACKGROUND: Intensity-modulated radiotherapy (IMRT) improves dose homogeneity and late toxicity compared to simple tangential techniques in adjuvant whole-breast radiotherapy for patients with breast cancer. Simultaneous-integrated boost (SIB) radiotherapy shortens the overall treatment time and improves dose homogeneity. However, prospective randomized trials regarding IMRT with SIB for adjuvant radiotherapy in breast cancer are lacking. METHODS: The IMRT-MC2 (MINT) trial is a phase III prospective randomized controlled trial comparing IMRT with SIB (Arm A: whole breast 28 × 1.8 Gy, Boost 28 × 2.3 Gy) to 3D-conformal radiotherapy with a sequential boost (Arm B: whole breast 28 × 1.8 Gy, boost 8 × 2 Gy) in patients with breast cancer after BCS. Indication for boost radiotherapy was defined as age < 70 years or age > 70 years with presence of additional risk factors. This is a retrospective analysis of acute toxicity at one of two trial sites. RESULTS: Five hundred two patients were randomized, of which 446 patients were eligible for this analysis. There was no statistically significant difference in terms of any grade radiation dermatitis between the two treatment arms at the end of treatment (p = 0.26). However, radiation dermatitis grade 2/3 (29.1% vs. 20.1 and 3.5% vs. 2.3%) occurred significantly more often in Arm A (p = 0.02). Breast/chest wall pain at the first follow-up visit was significantly more common in patients treated on Arm B (p = 0.02). CONCLUSIONS: Treatment on both arms was well tolerated, however there were some differences regarding radiodermatitis and breast pain. Further analyses are ongoing. TRIAL REGISTRATION: clinicaltrials.gov , NCT01322854 , registered 24th March 2011.

Fatigue following radiotherapy of low-risk early breast cancer - a randomized controlled trial of intraoperative electron radiotherapy versus standard hypofractionated whole-breast radiotherapy: the COSMOPOLITAN trial (NCT03838419).

BACKGROUND: Fatigue is one of the most common and distressing side-effects of breast cancer radiotherapy. According to current guidelines, accelerated partial breast irradiation (APBI) may be considered as an alternative treatment option for women with early-stage low-risk breast cancer. One method for APBI is single-dose intraoperative radiotherapy (IORT) applied directly to the tumor bed during breast conserving surgery (BCS). The COSMOPOLITAN trial therefore aims to analyze the intensity of fatigue following single-shot IORT with electrons (IOERT) compared to conventional hypofractionated whole breast irradiation (WBI) in low risk early breast cancer patients. METHODS: This trial is conducted as a multicenter, prospective, randomized, two-arm phase II study comparing the intensity of fatigue in early-stage breast cancer (cT1cN0cM0, tumor size < 2,5 cm, ER pos. Her2neu neg., age > 50 years) treated either with WBI or APBI after BCS. Secondary outcomes investigated are tumor control, overall survival (OS), disease-free survival (DFS), acute and chronic toxicity, quality of life (QoL) and cosmesis. A total of 202 patients will be randomized into two arms: Patients in arm A will receive WBI (40.05 Gy, 15 fractions) after surgical resection, while patients in arm B will receive IOERT (21 Gy to the 90%-isodose) during BCS. Fatigue will be assessed 12 weeks post surgery with the help of the Functional Assessment of Chronic Illness Therapy (FACIT) Fatigue Scale. DISCUSSION: The present trial aims to evaluate treatment response to compare single-shot intraoperative electron APBI to conventional WBI following BCS in early-stage low risk breast cancer patients. Fatigue is selected as the primary, patient-reported endpoint due its major clinical relevance. TRIAL REGISTRATION: The study is prospectively registered on February 12th, 2019: Clinicaltrials.gov, NCT03838419. "Intraoperative Electron Radiotherapy for Low-risk Early Breast Cancer (COSMOPOLITAN)". STUDY STATUS: Ongoing study. Start of recruitment was December 2019.

Prediction of pathological complete response in breast cancer patients during neoadjuvant chemotherapy: Is shear wave elastography a useful tool in clinical routine?

OBJECTIVE: To compare the validity of Shear Wave Elastography (SWE) for the preoperative assessment of pathological complete response (pCR) to standard clinical assessment in breast cancer patients undergoing neoadjuvant chemotherapy (NACT). MATERIALS AND METHODS: This prospective, consecutive clinical trial was conducted under routine clinical practice. Analysis included 134 patients. SWE served as index test, final pathology from surgical specimen as reference standard. PCR (ypT0) was defined as primary endpoint. Elasticity changes were compared for the pCR- vs. non-pCR group. To determine the validity of shear wave velocity (Vs), ROC analyses and diagnostic accuracy parameters were calculated and compared to the final standard clinical assessment by physical examination, mammography and B-mode ultrasound (ycT + vs. ycT0). RESULTS: Vs was significantly reduced in pCR and non-pCR groups during NACT (pCR: ΔVs(abs) = 3.90 m/s, p < 0.001; non-pCR: ΔVs(abs) = 3.10 m/s, p < 0.001). The pCR-group showed significant lower Vs for all control visits (t1,2,END: p < 0.001). ROC analysis of Vs yielded moderate AUCs for the total population (t0: 0.613, t1: 0.745, t2: 0.685, tEND: 0.718). Compared to standard clinical assessment, Vs(tEND) (cut-off: ≤3.35 m/s) was superior in sensitivity (79.6 % vs. 54.5 %), NPV (86.4 % vs. 77.5 %), FNR (20.4 % vs. 45.5 %), inferior in specificity (58.6 % vs. 77.5 %), PPV (46.3 % vs. 54.5 %), FPR (41.4 % vs. 22.5 %). CONCLUSION: SWE measures significant differences in tumour elasticity changes in pCR vs. non-pCR cases. SWE shows improved sensitivity compared to standard clinical assessment, high NPV and low FNR, but failed in specificity in order to predict pCR under routine conditions.

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.

Maternal-fetal attachment protects against postpartum anxiety: the mediating role of postpartum bonding and partnership satisfaction.

PURPOSE: Maternal mental disorders develop frequently during the perinatal period, and can have detrimental effects on the developing bond between a mother and her child. While depression has already been widely associated with bonding disorders, the link between anxiety disorders and maternal-fetal attachment has received only limited attention. This study aimed to explore the link between maternal-fetal attachment in the third trimester and postpartum anxiety, as previous research has suggested a potentially protective association. Additionally, we hypothesized a mediating influence of postpartum bonding and partnership satisfaction as additional measurements of attachment capacity. METHODS: Self-report questionnaires assessing maternal-fetal attachment, postpartum bonding, anxiety, depression, and partnership quality were completed at three time points: third trimester (T1, N = 324), first week postpartum (T2, N = 249), and 4 months postpartum (T3, N = 166). Conditional process analyses were used to test for mediation. RESULTS: A statistically significant negative correlation of maternal-fetal attachment was found with maternal anxiety postpartum. Overall, the analyses supported the mediation hypothesis. There was a significant, indirect effect of maternal-fetal attachment during pregnancy on state anxiety in the first week postpartum, mediated through postpartum bonding quality and partnership satisfaction. All three variables together accounted for 18.25% (state anxiety) or 30.35% (trait anxiety) of the variance in postpartum anxiety. CONCLUSIONS: Our results showed that a close maternal-fetal attachment buffers postpartum symptoms of anxiety, partially mediated through postpartum bonding and partnership satisfaction. Therefore, strengthening the maternal-fetal attachment and the partnership during pregnancy has the potential to reduce maternal postpartum symptoms of anxiety.

Psychometric validation of the Breast Cancer Treatment Outcome Scale (BCTOS-12): a prospective cohort study.

PURPOSE: The Breast Cancer Treatment Outcome Scale (BCTOS) is a questionnaire to evaluate the aesthetic and functional outcome after breast conserving surgery (BCS). The original BCTOS with its 22 items on three subscales was refined to a shorter, improved, and easier to administer patient-reported outcome measure, the BCTOS-12. The BCTOS-12 consists of 12 items on two distinct subscales, the Functional Status and the Aesthetic Status. The aim of this study was to validate the BCTOS-12 in a prospective cohort. METHODS: For this study, 239 breast cancer patients were included preoperatively, and 204 patients completed the BCTOS-12 and EORTC QLQ C30 BR23 shortly after their BCS, corresponding to a follow-up rate of 85%. The item-factor structure was examined by confirmatory factor analysis. The reliability was calculated by McDonald's Omega for estimating internal consistency. The convergent validity was assessed by Spearman's rank correlation coefficients between the related scales of the questionnaires. RESULTS: The BCTOS-12 showed a robust item-factor structure and a good internal consistency with McDonald's Omega of 0.89 for the Aesthetic Status and 0.90 for the Functional Status. A high convergent and divergent validity was indicated by correlations between the subscales of the EORTC QLQ C30 BR23 and the BCTOS-12. CONCLUSION: Overall, the results demonstrate a successful psychometric validation of the BCTOS-12. The BCTOS-12 is a refined, improved, and now validated, instrument. It can be used in clinical studies and routine management for the evaluation of the aesthetic and functional outcome after BCS.

Heterogeneous Responses of Axillary Lymph Node Metastases to Neoadjuvant Chemotherapy are Common and Depend on Breast Cancer Subtype.

BACKGROUND: The objective of this study was to analyze heterogeneous responses of axillary lymph node metastasis to neoadjuvant chemotherapy and to determine to what extent they differ between tumor subtypes (TN, HER2+, HR+/HER2-). METHODS: This retrospective, monocenter study included 72 consecutive, histologically node-positive breast cancers (cT1-4 cN1-3 cM0) diagnosed in the period from January 2015 to December 2016, who had received axillary lymph node dissection following neoadjuvant chemotherapy. All individual lymph node specimens were re-evaluated for the presence of tumor cells and chemotherapy effects to assess their response to neoadjuvant chemotherapy on an individual lymph node level according to the Sataloff classification. RESULTS: Heterogeneous axillary responses to neoadjuvant chemotherapy occurred in 47.2% of the included 72 patients. The partial response rate was significantly higher in HR+/HER2- tumors (74.2%) than in TN (28.6%) and HER2+ tumors (25.0%) (p < 0.001). The presence of at least one negative, completely responding lymph node in the axillary lymph node dissection specimen had a false-negative rate of 48.8% in predicting ypN0. It dropped below 10% if at least four completely responding negative lymph nodes were identified. CONCLUSIONS: Our study shows that axillary heterogeneous response rates differ significantly between tumor subtypes.

Adjuvant intensity modulated whole-abdominal radiation therapy for high-risk patients with ovarian cancer FIGO stage III: final results of a prospective phase 2 study.

BACKGROUND: To assess late toxicity, quality of life and oncological outcome after consolidative whole abdominal radiotherapy (WART) following cytoreductive surgery and carboplatin/paclitaxel chemotherapy in high risk patients with advanced ovarian cancer FIGO stage III using IMRT (Intensity modulated radiation therapy). METHODS: The OVAR-IMRT-02 study is a multi-center single-arm phase-II-trial. Twenty patients with optimally debulked ovarian cancer stage FIGO III with complete remission after chemotherapy were treated with intensity modulated WART. A total dose of 30 Gy in 20 fractions was applied to the entire peritoneal cavity. Primary endpoint was treatment tolerability; secondary objectives were acute and chronic toxicities, quality of life, rates of therapy disruption/abortion, progression-free survival (PFS) and overall survival (OS). RESULTS: All patients completed treatment and 10/20 patients (50%) reached the final study follow-up of 36 months. Late side effects consisted of °1-°2 lower limb edema (44.5%), with one patient (5.6%) showing °3 edema. Three patients (16.7%) showed elevated gamma-Glutamyltransferase. There were no severe late side effects regarding renal or hepatic function or any gastrointestinal toxicity greater than °2. During WART, mean global health status decreased by 18.1 points (95%-CI: 7.1-29.0), but completely normalized after 6 months. The same trend was observed for the function scale scores. Kaplan-Meier-estimated 1-, 2- and 3-year PFS was 74, 51 and 40%, respectively. 1-, 2- and 3-year OS was 89, 83 and 83%, respectively. CONCLUSIONS: Intensity modulated WART after aggressive surgery and carboplatin/paclitaxel chemotherapy is associated with an acceptable risk of acute and late toxicity and minor impact on long-term quality of life. Together with the promising results for PFS and OS, intensity modulated WART could offer a new therapeutic option for consolidation treatment of patients with advanced ovarian cancer. TRIAL REGISTRATION: The study is registered with ClinicalTrials.gov ( NCT01180504 ). Registered 12 August 2010 - retrospectively registered.

Second breast conserving therapy after ipsilateral breast tumor recurrence - a 10-year experience of re-irradiation.

PURPOSE: The aim of this study is to evaluate the efficacy and toxicity of post-operative partial breast re-irradiation with multi-catheter brachytherapy after second breast conserving therapy (BCT) in patients with small, low-risk ipsilateral breast tumor recurrence (IBTR). MATERIAL AND METHODS: Between 2008 and 2018, 19 consecutive patients with low-risk IBTR (max. rpT1 cN0 cM0, Her2 negative, preferably positive hormone receptor status) who refused mastectomy were treated with salvage lumpectomy, followed by post-operative partial breast re-irradiation with multi-catheter brachytherapy. Eight patients were irradiated using PDR brachytherapy (49.8-50.4 Gy in pulses of 0.5-0.7 Gy) and 11 patients using HDR brachytherapy (34.2 Gy in fractions of 3.8 Gy or 32 Gy in fractions of 4 Gy). All patients had undergone prior BCT for their primary tumor, followed by adjuvant whole breast radiotherapy. Local control (LC), locoregional control (LRC), overall survival (OS), disease-free survival (DFS) as well as toxicity were evaluated in the present study. RESULTS: After a median follow-up of 65 months following IBTR (18-120 months), only one second IBTR in 19 patients was diagnosed 77 months after re-irradiation, resulting in a LC rate of 100% at 5 years. DFS and OS rates were both 100% at 5 years following re-irradiation. Except for the above mentioned second IBTR, no regional or distant relapse was recorded. Regarding toxicity, 63% of patients developed adverse events (CTCAE grade ≤ 2), with fibrosis detected in 37% (7/19) of patients, necrosis in 11% (2/19), hyperpigmentation in 47% (9/19), and telangiectasia in 11% (2/19), respectively. No patient showed a high-grade (CTCAE grade ≥ 3) adverse event. CONCLUSIONS: In case of small, low-risk IBTR, adjuvant re-irradiation using multi-catheter brachytherapy is a feasible, safe, and effective treatment method after repeated lumpectomy, and an alternative to mastectomy.