Clinical outcomes of melanoma brain metastases treated with nivolumab and ipilimumab alone versus nivolumab and ipilimumab with stereotactic radiosurgery.

PURPOSE: Upfront dual checkpoint blockade with immune checkpoint inhibitors (ICI) has demonstrated efficacy for treating melanoma brain metastases (MBM) in asymptomatic patients. Whether the combination of stereotactic radiosurgery (SRS) with dual checkpoint blockade improves outcomes over dual-checkpoint blockade alone is unknown. We evaluated clinical outcomes of patients with MBM receiving ICI with nivolumab and ipilimumab, with and without SRS. METHODS: 49 patients with 158 MBM receiving nivolumab and ipilimumab for untreated MBM between 2015 and 2022 were identified at our institution. Patient and tumor characteristics including age, Karnofsky Performance Status (KPS), presence of symptoms, cancer history, MBM burden, and therapy course were recorded. Outcomes measured from initiation of MBM-directed therapy included overall survival (OS), local control (LC), and distant intracranial control (DIC). Time-to-event analysis was conducted with the Kaplan-Meier method. RESULTS: 25 patients with 74 MBM received ICI alone, and 24 patients with 84 MBM received concurrent SRS. Median follow-up was 24 months. No differences in age (p = 0.96), KPS (p = 0.85), presence of symptoms (p = 0.79), prior MBM (p = 0.68), prior MBM-directed surgery (p = 0.96) or SRS (p = 0.68), MBM size (p = 0.67), or MBM number (p = 0.94) were seen. There was a higher rate of nivolumab and ipilimumab course completion in the SRS group (54% vs. 24%; p = 0.029). The SRS group received prior immunotherapy more often than the ICI alone group (54% vs. 8.0%; p < 0.001). There was no significant difference in 1-year OS (72% vs. 71%, p = 0.20) and DIC (63% v 51%, p = 0.26) between groups. The SRS group had higher 1-year LC (92% vs. 64%; p = 0.002). On multivariate analysis, LC was improved with combination therapy (AHR 0.38, p = 0.01). CONCLUSION: In our analysis, patients who received SRS with nivolumab and ipilimumab had superior LC without increased risk of toxicity or compromised immunotherapy treatment completion despite the SRS cohort having higher rates of prior immunotherapy. Further prospective study of combination nivolumab and ipilimumab with SRS is warranted.

The Society for Cardiovascular Magnetic Resonance Registry at 150,000.

BACKGROUND: Cardiovascular magnetic resonance (CMR) is increasingly utilized to evaluate expanding cardiovascular conditions. The Society for Cardiovascular Magnetic Resonance (SCMR) Registry is a central repository for real-world clinical data to support cardiovascular research, including those relating to outcomes, quality improvement, and machine learning. The SCMR Registry is built on a regulatory-compliant, cloud-based infrastructure that houses searchable content and Digital Imaging and Communications in Medicine images. The goal of this study is to summarize the status of the SCMR Registry at 150,000 exams. METHODS: The processes for data security, data submission, and research access are outlined. We interrogated the Registry and presented a summary of its contents. RESULTS: Data were compiled from 154,458 CMR scans across 20 United States sites, containing 299,622,066 total images (∼100 terabytes of storage). Across reported values, the human subjects had an average age of 58 years (range 1 month to >90 years old), were 44% (63,070/145,275) female, 72% (69,766/98,008) Caucasian, and had a mortality rate of 8% (9,962/132,979). The most common indication was cardiomyopathy (35,369/131,581, 27%), and most frequently used current procedural terminology code was 75561 (57,195/162,901, 35%). Macrocyclic gadolinium-based contrast agents represented 89% (83,089/93,884) of contrast utilization after 2015. Short-axis cines were performed in 99% (76,859/77,871) of tagged scans, short-axis late gadolinium enhancement (LGE) in 66% (51,591/77,871), and stress perfusion sequences in 30% (23,241/77,871). Mortality data demonstrated increased mortality in patients with left ventricular ejection fraction <35%, the presence of wall motion abnormalities, stress perfusion defects, and infarct LGE, compared to those without these markers. There were 456,678 patient-years of all-cause mortality follow-up, with a median follow-up time of 3.6 years. CONCLUSION: The vision of the SCMR Registry is to promote evidence-based utilization of CMR through a collaborative effort by providing a web mechanism for centers to securely upload de-identified data and images for research, education, and quality control. The Registry quantifies changing practice over time and supports large-scale real-world multicenter observational studies of prognostic utility.

Tucatinib and stereotactic radiosurgery in the management of HER2 positive breast cancer brain metastases.

PURPOSE: HER2-positive breast cancer has a high risk of brain metastasis. Stereotactic radiosurgery (SRS) is standard of care for limited brain metastases. Tucatinib, a HER2-targeted tyrosine kinase inhibitor, has demonstrated intracranial efficacy in the HER2-CLIMB Trial. However, it is unknown whether tucatinib with SRS is safe or effective. METHODS: A retrospective analysis of HER2-positive breast cancer treated with SRS and tucatinib for brain metastases management was performed. All patients received tucatinib and SRS for the management of active brain metastases. The primary endpoint was local and distant brain tumor control. Secondary endpoints were intracranial progression free survival (CNS-PFS), systemic PFS, overall survival (OS), and neurotoxicity. RESULTS: A total of 135 lesions treated with SRS over 39 treatment sessions in 22 patients were identified. Median follow-up from tucatinib initiation was 20.8 months. Local brain control was 94% at 12-months and 81% at 24-months. Distant brain control was 39% at 12-months and 26% at 24-months. Median survival was 21.2 months, with 12- and 24-month OS rates of 84% and 50%, respectively. Median CNS-PFS was 11.3 months, with 12- and 24-month CNS-PFS rates of 44.9% at both time points. Median systemic PFS was not reached, with 12- and 24-month systemic PFS rates of 86% and 57%, respectively. Symptomatic radiation necrosis occurred in 6 (4%) lesions. No additional unexpected toxicities were noted. CONCLUSIONS: SRS in combination with tucatinib, capecitabine, and trastuzumab appears to be a safe and feasible treatment for HER2 + brain metastases. Further prospective evaluation of potential synergistic effects is warranted.

The presentation of brain metastases in melanoma, non-small cell lung cancer, and breast cancer and potential implications for screening brain MRIs.

PURPOSE: This study assessed the presentation and institutional outcomes treating brain metastases (BM) of breast cancer (BC), non-small cell lung cancer (NSCLC), and melanoma origin. METHODS: Patients with brain metastases treated between 2014 and 2019 with primary melanoma, NSCLC, and BC were identified. Overall survival (OS) was calculated from dates of initial BM diagnosis using the Kaplan-Meier method. RESULTS: A total of 959 patients were identified including melanoma (31%), NSCLC (51%), and BC (18%). Patients with BC were younger at BM diagnosis (median age: 57) than NSCLC (65) and melanoma patients (62, p < 0.0001). Breast cancer patients were more likely to present with at least 5 BM (27%) than NSCLC (14%) and melanoma (13%), leptomeningeal disease (23%, 6%, and 6%, p = 0.0004) and receive whole brain radiation therapy (WBRT) (58%, 37%, and 22%, p < 0.0001). There were no differences in surgical resection (24%, 24%, and 29%, p = 0.166). Median OS was shorter for BC patients (9.9, 10.3, and 13.7 months, p = 0.0006). CONCLUSION: Breast cancer patients were more likely to be younger, present with advanced disease, require WBRT, and have poorer OS than NSCLC and melanoma patients. Further investigation is needed to determine which BC patients are at sufficient risk for brain MRI screening.

Evolving management of HER2+ breast cancer brain metastases and leptomeningeal disease.

Patients with human epidermal growth factor receptor 2 (HER2)-positive breast cancer are at a particularly high risk of breast cancer brain metastasis (BCBM) and leptomeningeal disease (LMD). Improvements in systemic therapy have translated to improved survival for patients with HER2-positive BCBM and LMD. However, the optimal management of these cases is rapidly evolving and requires a multidisciplinary approach. Herein, a team of radiation oncologists, medical oncologists, neuro-oncologists, and breast surgeon created a review of the evolving management of HER2-positive BCBM and LMD. We assess the epidemiology, diagnosis, and evolving treatment options for patients with HER2-positive BCBM and LMD, as well as the ongoing prospective clinical trials enrolling these patients. The management of HER2-positive BCBM and LMD represents an increasingly common challenge that involves the coordination of local and systemic therapy. Advances in systemic therapy have resulted in an improved prognosis, and promising targeted therapies currently under prospective investigation have the potential to further benefit these patients.

Pan-cancer prediction of radiotherapy benefit using genomic-adjusted radiation dose (GARD): a cohort-based pooled analysis.

BACKGROUND: Despite advances in cancer genomics, radiotherapy is still prescribed on the basis of an empirical one-size-fits-all paradigm. Previously, we proposed a novel algorithm using the genomic-adjusted radiation dose (GARD) model to personalise prescription of radiation dose on the basis of the biological effect of a given physical dose of radiation, calculated using individual tumour genomics. We hypothesise that GARD will reveal interpatient heterogeneity associated with opportunities to improve outcomes compared with physical dose of radiotherapy alone. We aimed to test this hypothesis and investigate the GARD-based radiotherapy dosing paradigm. METHODS: We did a pooled, pan-cancer analysis of 11 previously published clinical cohorts of unique patients with seven different types of cancer, which are all available cohorts with the data required to calculate GARD, together with clinical outcome. The included cancers were breast cancer, head and neck cancer, non-small-cell lung cancer, pancreatic cancer, endometrial cancer, melanoma, and glioma. Our dataset comprised 1615 unique patients, of whom 1298 (982 with radiotherapy, 316 without radiotherapy) were assessed for time to first recurrence and 677 patients (424 with radiotherapy and 253 without radiotherapy) were assessed for overall survival. We analysed two clinical outcomes of interest: time to first recurrence and overall survival. We used Cox regression, stratified by cohort, to test the association between GARD and outcome with separate models using dose of radiation and sham-GARD (ie, patients treated without radiotherapy, but modelled as having a standard-of-care dose of radiotherapy) for comparison. We did interaction tests between GARD and treatment (with or without radiotherapy) using the Wald statistic. FINDINGS: Pooled analysis of all available data showed that GARD as a continuous variable is associated with time to first recurrence (hazard ratio [HR] 0·98 [95% CI 0·97-0·99]; p=0·0017) and overall survival (0·97 [0·95-0·99]; p=0·0007). The interaction test showed the effect of GARD on overall survival depends on whether or not that patient received radiotherapy (Wald statistic p=0·011). The interaction test for GARD and radiotherapy was not significant for time to first recurrence (Wald statistic p=0·22). The HR for physical dose of radiation was 0·99 (95% CI 0·97-1·01; p=0·53) for time to first recurrence and 1·00 (0·96-1·04; p=0·95) for overall survival. The HR for sham-GARD was 1·00 (0·97-1·03; p=1·00) for time to first recurrence and 1·00 (0·98-1·02; p=0·87) for overall survival. INTERPRETATION: The biological effect of radiotherapy, as quantified by GARD, is significantly associated with time to first recurrence and overall survival for patients with cancer treated with radiation. It is predictive of radiotherapy benefit, and physical dose of radiation is not. We propose integration of genomics into radiation dosing decisions, using a GARD-based framework, as the new paradigm for personalising radiotherapy prescription dose. FUNDING: None. VIDEO ABSTRACT.

Trastuzumab Emtansine (T-DM1) and stereotactic radiation in the management of HER2+ breast cancer brain metastases.

BACKGROUND: Due to recent concerns about the toxicity of trastuzumab emtansine (T-DM1) with stereotactic radiation, we assessed our institutional outcomes treating HER2-positive breast cancer brain metastases (BCBM) with T-DM1 and stereotactic radiation. METHODS: This is a single institution series of 16 patients with HER2-positive breast cancer who underwent 18 stereotactic sessions to 40 BCBM from 2013 to 2019 with T-DM1 delivered within 6 months. The Kaplan-Meier method was used to calculate overall survival (OS), local control (LC), distant intracranial control (DIC), and systemic progression-free survival (sPFS) from the date of SRS. A neuro-radiologist independently reviewed follow-up imaging. RESULTS: One patient had invasive lobular carcinoma, and 15 patients had invasive ductal carcinoma. All cases were HER2-positive, while 10 were hormone receptor (HR) positive. Twenty-four lesions were treated with stereotactic radiosurgery (SRS) to a median dose of 21 Gy (14-24 Gy). Sixteen lesions were treated with fractionated stereotactic radiation (FSRT) with a median dose of 25 Gy (20-30Gy) delivered in 3 to 5 fractions. Stereotactic radiation was delivered concurrently with T-DM1 in 19 lesions (48%). Median follow up time was 13.2 months from stereotactic radiation. The 1-year LC, DIC, sPFS, and OS were 75, 50, 30, and 67%, respectively. There was 1 case of leptomeningeal progression and 1 case (3%) of symptomatic radionecrosis. CONCLUSIONS: We demonstrate that stereotactic radiation and T-DM1 is well-tolerated and effective for patients with HER2-positive BCBM. An increased risk for symptomatic radiation necrosis was not noted in our series.

Capecitabine and stereotactic radiation in the management of breast cancer brain metastases.

BACKGROUND: Little is known about the safety and efficacy of concurrent capecitabine and stereotactic radiotherapy in the setting of breast cancer brain metastases (BCBM). METHODS: Twenty-three patients with BCBM underwent 31 stereotactic sessions to 90 lesions from 2005 to 2019 with receipt of capecitabine. The Kaplan-Meier method was used to calculate overall survival (OS), local control (LC), and distant intracranial control (DIC) from the date of stereotactic radiation. Imaging was independently reviewed by a neuro-radiologist. RESULTS: Median follow-up from stereotactic radiation was 9.2 months. Receptor types of patients treated included triple negative (n = 7), hormone receptor (HR)+/HER2- (n = 7), HR+/HER2+ (n = 6), and HR-/HER2+ (n = 3). Fourteen patients had stage IV disease prior to BCBM diagnosis. The median number of brain metastases treated per patient was 3 (1 to 12). The median dose of stereotactic radiosurgery (SRS) was 21 Gy (range: 15-24 Gy) treated in a single fraction and for lesions treated with fractionated stereotactic radiation therapy (FSRT) 25 Gy (24-30 Gy) in a median of 5 fractions (range: 3-5). Of the 31 stereotactic sessions, 71% occurred within 1 month of capecitabine. No increased toxicity was noted in our series with no cases of radionecrosis. The 1-year OS, LC, and DIC were 46, 88, and 30%, respectively. CONCLUSIONS: In our single institution experience, we demonstrate stereotactic radiation and capecitabine to be a safe treatment for patients with BCBM with adequate LC. Further study is needed to determine the potential synergy between stereotactic radiation and capecitabine in the management of BCBM.

Breast cancer subtype predicts clinical outcomes after stereotactic radiation for brain metastases.

PURPOSE: We investigated the prognostic ability of tumor subtype for patients with breast cancer brain metastases (BCBM) treated with stereotactic radiation (SRT). METHODS: This is a retrospective review of 181 patients who underwent SRT to 664 BCBM from 2004 to 2019. Patients were stratified by subtype: hormone receptor (HR)-positive, HER2-negative (HR+/HER2-), HR-positive, HER2-positive (HR+/HER2+), HR-negative, HER2-positive (HR-/HER2+), and triple negative (TN). The Kaplan-Meier method was used to calculate overall survival (OS), local control (LC), and distant intracranial control (DIC) from the date of SRT. Multivariate analysis (MVA) was conducted using the Cox proportional hazards model. RESULTS: Median follow up from SRT was 11.4 months. Of the 181 patients, 47 (26%) were HR+/HER2+, 30 (17%) were HR-/HER2+, 60 (33%) were HR+/HER2-, and 44 (24%) were TN. Of the 664 BCBMs, 534 (80%) received single fraction stereotactic radiosurgery (SRS) with a median dose of 21 Gy (range 12-24 Gy), and 130 (20%) received fractionated stereotactic radiation therapy (FSRT), with a median dose of 25 Gy (range 12.5-35 Gy) delivered in 3 to 5 fractions. One-year LC was 90%. Two-year DIC was 35%, 23%, 27%, and 16% (log rank, p = 0.0003) and 2-year OS was 54%, 47%, 24%, and 12% (log rank, p < 0.0001) for HR+/HER2+, HR-/HER2+, HR+/HER2-, and TN subtypes, respectively. On MVA, the TN subtype predicted for inferior DIC (HR 1.62, 95% CI 1.00-2.60, p = 0.049). The modified breast-Graded Prognostic Assessment (GPA) significantly predicted DIC and OS (both p < 0.001). CONCLUSIONS: Subtype is prognostic for OS and DIC for patients with BCBM treated with SRT.

Procedural Risks of Carotid Intervention in 19,000 Patients.

BACKGROUND: Randomized controlled trials (RCTs) show that carotid endarterectomy (CEA) and carotid stenting (CAS) reduce long-term stroke risk in symptomatic and asymptomatic patients with carotid artery stenosis. Historical RCTs may not represent contemporary practice and administrative datasets may estimate procedural risks more reliably. We studied procedural risks after carotid intervention in a novel, international administrative data set of 18,997 patients admitted to 28 hospitals across 7 countries. METHODS: Symptomatic and asymptomatic patients undergoing CEA (n = 16,220) and CAS (n = 2,777) between 2011 and 2015 were studied retrospectively. The primary outcome was in-hospital death within seven days. The secondary outcome was the proportion of patients whose length of hospital stay (LOS) exceeded 2 days. We also describe the rate of computerized tomography brain imaging within 2 days of CEA and CAS (proxy for stroke) as procedural strokes were not reliably recorded. RESULTS: In symptomatic patients after CEA, mortality was 0.2% [5/2,118] (95% confidence interval: 0.1-0.5), and 57.0% [628/1,101] (54.1-60.0) had prolonged LOS. In asymptomatic patients after CEA, mortality was 0.1% [21/14,102] (0.1-0.2), and 28.5% [2,864/10,039] (27.7-29.4) had prolonged LOS. In symptomatic patients after CAS, mortality was 3.3% [10/307] (1.3-5.2), and 64.3% [144/224] (58.0-70.5) had prolonged LOS. In asymptomatic patients after CAS, mortality was 0.7% [18/2,470] (0.4-1.1), and 27.5% [601/2,187] (25.6-29.4) had prolonged LOS. After CEA, 8.1% [89/1,101] (6.5-9.7) symptomatic patients and 2.1% [207/10,039] (1.8-2.3) asymptomatic patients underwent brain imaging. After CAS, 7.1% [16/224] (4.0-10.7) symptomatic patients and 3.2% [71/2,187] (2.5-4.0) asymptomatic patients underwent brain imaging. CONCLUSIONS: Death and LOS after CEA and CAS were higher in symptomatic than asymptomatic patients. Symptomatic patients undergoing CAS had particularly increased risk of death. This may be partly explained by case selection, with more comorbid patients preferentially undergoing CAS. While RCTs effectively compare long-term efficacy of CEA versus CAS, administrative datasets can provide reliable estimates of contemporary procedural risks.

Miliary breast cancer brain metastasis: a rare and aggressive form of central nervous system metastasis.

Although breast cancer brain metastasis is an increasingly common occurrence, relatively little is known about miliary brain metastases, a rare subtype that presents unique diagnostic and management challenges. The present study from Bashour et al. proposes the first objective diagnostic imaging criteria, enabling improved future study.

Management of brain metastases in breast cancer: a review of current practices and emerging treatments.

PURPOSE: Breast cancer brain metastases (BCBM) are becoming an increasingly common diagnosis due to improved systemic control and more routine surveillance imaging. Treatment continues to require a multidisciplinary approach managing systemic and intracranial disease burden. Although, improvements have been made in the diagnosis and management of BCBM, brain metastasis patients continue to pose a challenge for practitioners. METHODS: In this review, a group of medical oncologists, radiation oncologists, radiologists, breast surgeons, and neurosurgeons specializing in the treatment of breast cancer reviewed the available published literature and compiled a comprehensive review on the current state of BCBM. RESULTS: We discuss the pathogenesis, epidemiology, diagnosis, treatment options (including systemic, surgical, and radiotherapy treatment modalities), and treatment response evaluation for BCBM. Furthermore, we discuss the ongoing prospective trials enrolling BCBM patients and their biologic rationale. CONCLUSIONS: BCBM management is an increasing clinical concern. Multidisciplinary management combining the strengths of surgical, systemic, and radiation treatment modalities with prospective trials incorporating knowledge from the basic and translational sciences will ultimately lead to improved clinical outcomes for BCBM patients.

High-dose intensity-modulated chemoradiotherapy in vulvar squamous cell carcinoma: Outcome and toxicity.

INTRODUCTION: To evaluate clinical outcomes, pattern of failure, and toxicity after high-dose intensity-modulated radiation therapy (IMRT) for advanced vulvar cancer. METHODS: In this IRB approved retrospective study, the charts of women with histologically confirmed, non-metastatic vulvar cancer consecutively treated at our institution from 2012 to 2018 were reviewed to identify patients that received high-dose IMRT with curative intent. The treatment compliance, toxicities, and patterns of failure were investigated. Actuarial local, regional and distant recurrence and survival were estimated using Kaplan-Meier method and compared using log rank test. RESULTS: Twenty-six patients were identified, 23 were unresectable, and 3 refused surgery. Fifteen patients (58%) had inguinal node metastases; 10(38%) had pelvic node metastases. Elective surgical staging of groins was performed in 9-patients. Median tumor dose was 65.4Gy. Concurrent platinum-based chemotherapy was administered in 22(84.6%) patients. Complete response (CR) was achieved in 21/26 (80.7%) patients. Five patients had persistent disease following treatment and one sustained recurrence 5-months following radiotherapy. All persistent or recurrent disease occurred inside the irradiated volume. Median follow-up was 19 months (3-52 months). Actuarial 1-year local, regional and distant controls were 72.4%, 85.4%, and 86%, respectively. One and 2-year overall survivals were 91% and 62%, respectively. Complete response at 3-months was a strong predictor for overall survival (1-yr OS 73% vs 27%, HR 7.1 (95% CI 1.2-44); p = 0.01). Lymph node metastases adversely affected overall survival (2-yr OS 49% vs. 83%, p = 0.09). Grade 3-4 late urinary and soft-tissue toxicity was seen in 5 patients. Tumor doses >66 Gy (p = 0.03) and prior pelvic radiotherapy (p = 0.002) predicted grade 3-4 toxicity. CONCLUSION: High-dose IMRT for vulvar cancer achieves high rates of local control with acceptable dose dependent long-term toxicity.

Modeling precision genomic-based radiation dose response in rectal cancer.

Aim: Genomic-based risk stratification to personalize radiation dose in rectal cancer. Patients & methods: We modeled genomic-based radiation dose response using the previously validated radiosensitivity index (RSI) and the clinically actionable genomic-adjusted radiation dose. Results: RSI of rectal cancer ranged from 0.19 to 0.81 in a bimodal distribution. A pathologic complete response rate of 21% was achieved in tumors with an RSI <0.31 at a minimal genomic-adjusted radiation dose of 29.76 when modeling RxRSI to the commonly prescribed physical dose of 50 Gy. RxRSI-based dose escalation to 55 Gy in tumors with an RSI of 0.31-0.34 could increase pathologic complete response by 10%. Conclusion: This study provides a theoretical platform for development of an RxRSI-based prospective trial in rectal cancer.

A Machine Learning Approach to Model Interdependencies between Dynamic Response and Crack Propagation.

Accurate damage detection in engineering structures is a critical part of structural health monitoring. A variety of non-destructive inspection methods has been employed to detect the presence and severity of the damage. In this research, machine learning (ML) algorithms are used to assess the dynamic response of the system. It can predict the damage severity, damage location, and fundamental behaviour of the system. Fatigue damage data of aluminium and ABS under coupled mechanical loads at different temperatures are used to train the model. The model shows that natural frequency and temperature appear to be the most important predictive features for aluminium. It appears to be dominated by natural frequency and tip amplitude for ABS. The results also show that the position of the crack along the specimen appears to be of little importance for either material, allowing simultaneous prediction of location and damage severity.

Health Education Programs Challenges in Rural Communities: Experiences of Health Educators and Healthcare Authorities.

BACKGROUND: Health education is one of the main areas of primary health care and it is improbable that health promotion will succeed without it. However, studies show that there are some problems when implementing health education programs in rural communities. This study was carried out to illuminate the barriers to health education using Ardabil's health center manager's and health educators' experiences. METHODS: This was a qualitative study using the content analysis approach. Twenty-seven health educators and managers were selected to participate in the study considering the maximum variation. Purposive sampling technique was used to select study participants. Data were collected through semi-structured interviews and focus group discussions. Data analysis was done using a six-stage thematic analysis framework. RESULTS: During the data analysis, four themes were apparent as barriers to health education in rural communities included: inefficient management skills, lack of responsibility among health personnel, inadequate policies, and poor inter-sectoral cooperation. CONCLUSIONS: It seems that changing job descriptions of health workers, reviewing health priorities, increasing lobbying activities are mechanisms that can help overcome barriers to health education in the rural communities.

Trends in use of bilateral prophylactic mastectomy vs high-risk surveillance in unaffected carriers of inherited breast cancer syndromes in the Inherited Cancer Registry (ICARE).

PURPOSE: Awareness of inherited breast cancer has increased bilateral prophylactic mastectomy (BPM) among unaffected genetic mutation carriers, yet many still choose surveillance. We aimed to identify differences among women electing BPM vs high-risk surveillance. METHODS: Participants from an IRB-approved database recruited from 11/2000 to 01/2017 with a deleterious/pathogenic, variant suspected deleterious, or likely pathogenic mutation in ≥ 1 of 11 genes with increased risk for breast cancer (per 2017 NCCN guidelines) were identified. Participants with breast cancer and males were excluded. Sociodemographic and clinical data were collected. The BPM and high-risk surveillance groups were compared using Wilcoxon, Fisher's Exact, and Pearson's Chi-Square analyses. RESULTS: A total of 304 unaffected genetic mutation carriers were identified; 22 men were excluded. 113/282 (40%) underwent BPM. There was no significant difference in age, race, marital status, high school graduates, family history of breast cancer, breast biopsies, chemoprevention use, or understanding implications of genetic mutation carriage. BPM participants were more likely to have a prior pregnancy (p = 0.0005), college education (p = 0.04), income > $50,000/year (p = 0.01), first-degree relative with breast cancer (p = 0.04), higher total number of relatives with breast cancer (p = 0.01), and rate of risk-reducing salpingo-oophorectomy (p = < 0.0001). The high-risk surveillance group was more likely to have a history of ovarian cancer (p = 0.009) and cancer worry (p = < 0.0001). CONCLUSIONS: BPM is a common but not universal choice among unaffected genetic carriers of inherited breast cancer syndromes. Parity, education, income, ovarian cancer history, first-degree relatives with breast cancer, and cancer worry play significant roles in these decisions.

Correction to: Non-contrast MRI for breast screening: preliminary study on detectability of benign and malignant lesions in women with dense breasts.

In the original version of the article, the image of Figure 2 was erroneously duplicated as Figure 4. The correct version of Figure 4 is given below. The original article has been corrected.

Non-contrast MRI for breast screening: preliminary study on detectability of benign and malignant lesions in women with dense breasts.

PURPOSE: The importance of breast cancer screening has long been known. Unfortunately, there is no imaging modality for screening women with dense breasts that is both sensitive and without concerns regarding potential side effects. The purpose of this study is to explore the possibility of combined diffusion-weighted imaging and turbo inversion recovery magnitude MRI (DWI + TIRM) to overcome the difficulty of detection sensitivity and safety. METHODS: One hundred and seventy-six breast lesions from 166 women with dense breasts were retrospectively evaluated. The lesion visibility, area under the curve (AUC), sensitivity and specificity of cancer detection by MG, DWI + TIRM, and clinical MRI were evaluated and compared. MG plus clinical MRI served as the gold standard for lesion detection and pathology served as the gold standard for cancer detection. RESULTS: Lesion visibility of DWI + TIRM (96.6%) was significantly superior to MG (67.6%) in women with dense breasts (p < 0.001). There was no significant difference compared with clinical MRI. DWI + TIRM showed higher accuracy (AUC = 0.935) and sensitivity (93.68%) for breast cancer detection than MG (AUC = 0.783, sensitivity = 46.32%), but was comparable to clinical MRI (AUC = 0.944, sensitivity = 93.68%). The specificity of DWI + TIRM (83.95%) was lower than MG (98.77%), but higher than clinical MRI (77.78%). CONCLUSIONS: DWI combined with TIRM could be a safe, sensitive, and practical alternative for screening women with dense breasts.

Breast leptomeningeal disease: a review of current practices and updates on management.

PURPOSE: Leptomeningeal disease (LMD) is an advanced metastatic disease presentation portending a poor prognosis with minimal treatment options. The advent and widespread use of new systemic therapies for metastatic breast cancer has improved systemic disease control and extended survival; however, as patients live longer, the rates of breast cancer LMD are increasing. METHODS: In this review, a group of medical oncologists, radiation oncologists, radiologists, breast surgeons, and neurosurgeons specializing in treatment of breast cancer reviewed the available published literature and compiled a comprehensive review on the current state of breast cancer LMD. RESULTS: We discuss the pathogenesis, epidemiology, diagnosis, treatment options (including systemic, intrathecal, surgical, and radiotherapy treatment modalities), and treatment response evaluation specific to breast cancer patients. Furthermore, we discuss the controversies within this unique clinical setting and identify potential clinical opportunities to improve upon the diagnosis, treatment, and treatment response evaluation in the management of breast LMD. CONCLUSIONS: We recognize the shortcomings in our current understanding of the disease and explore the future role of genomic/molecular disease characterization, technological innovations, and ongoing clinical trials attempting to improve the prognosis for this advanced disease state.