Personalized survivorship care: Routine breast cancer risk assessment in the gynecologic oncology clinic.

INTRODUCTION: Gynecologic and breast cancers share several risk factors. Breast cancer risk assessment tools can identify those at elevated risk and allow for enhanced breast surveillance and chemoprevention, however such tools are underutilized. We aim to evaluate the use of routine breast cancer risk assessment in a gynecologic oncology clinic. METHODS: A patient-facing web-based tool was used to collect personal and family history and run four validated breast cancer risk assessment models (Tyrer-Cuzick (TC), Gail, BRCAPRO, and Claus) in a gynecologic oncology clinic. We evaluated completion of the tools and identification of patients at elevated risk for breast cancer using the four validated models. RESULTS: A total of 99 patients were included in this analysis. The BRCAPRO model had the highest completion rate (84.8%), followed by the TC model (74.7%), Gail model (74.7%), and the Claus model (52.1%). The TC model identified 21.6% of patients completing the model as having ≥20% lifetime risk of breast cancer, compared to 6.8% by the Gail model, and 0% for both the BRCAPRO and Claus models. The Gail model identified 52.5% of patients as having ≥1.67% 5-year risk of breast cancer. Among patients identified as high-risk for breast cancer and eligible for screening, 9/9 (100%) were referred to a high-risk breast clinic. CONCLUSION: Among patients that completed the TC breast cancer risk assessment in a gynecologic oncology clinic, approximately 1 in 5 were identified to be at significantly elevated lifetime risk for breast cancer. The gynecologic oncologist's office might offer a convenient and feasible setting to incorporate this risk assessment into routine patient care, as gynecologic oncologists often have long-term patient relationships and participate in survivorship care.

Evaluating Healthcare Professionals' Knowledge, Attitudes, Practices and Education Interest in LGBTQ2 + Cancer Care.

The lesbian, gay, bisexual, transgender, queer/questioning and two-spirited, plus (LGBTQ2 +) community experiences cancer-related health disparities and inequities. Our objective was to assess LGBTQ2 + knowledge, attitudes, practices and education interest of healthcare professionals (HCPs), identify opportunities to improve care and inform the development of an HCP education curriculum. This was a mixed methods quality improvement study conducted within a tertiary academic cancer centre. An email was sent to all gynaecologic oncology disease site staff (n = 92) with a secure link to an online survey. We measured respondents' sociodemographic characteristics and LGBTQ2 + knowledge, attitudes, practice behaviours and education interest. Open comments explored HCP experiences and reservations caring for LGBTQ2 + patients and suggestions to improve care. Seventy-five out of ninety-two (82%) HCPs completed the survey, with 7% identifying as LGBTQ2 + . HCPs reported feeling less comfortable (88% vs. 80%, p = 0.031) and knowledgeable (44% vs. 27%, p < 0.001) caring for transgender patients compared to LGBQ2 + patients. Most (76%) were unaware whether LGBTQ2 + -specific patient educational materials existed within their institution. Almost all (92% strongly agreed/agreed) were interested in receiving LGBTQ2 + -specific education. Two themes emerged from analysis of open comments: (i) HCPs are concerned of offending LGBTQ2 + individuals because of their lack of knowledge and (ii) HCPs desire LGBTQ2 + -specific health training, specifically in asking pronouns and caring for transgender patients. HCPs report competency gaps in caring for LGBTQ2 + patients with cancer but desire education. In response, we recommend institutions develop an educational curriculum for HCPs improve communication and inclusivity in cancer care.

Predicting Regional Lymph Node Recurrence in the Modern Age of Tumor-Positive Sentinel Node Melanoma: The Role of the First Postoperative Ultrasound.

BACKGROUND: The Multicenter Selective Lymphadenectomy Trial II (MSLT-II) led to a change in the management of tumor-positive sentinel lymph nodes (SLNs) from completion node dissection (CLND) to nodal observation. This study aimed to evaluate prognostic factors for predicting sentinel node basin recurrence (SNBR) using data from MSLT-II trial participants. METHODS: In MSLT-II, 1076 patients were treated with observation. Patients were included in the current study if they had undergone a post-sentinel node basin ultrasound (PSNB-US) within 4 months after surgery. The study excluded patients with positive SLN by reverse transcription-polymerase chain reaction (RT-PCR) or incomplete SLN pathologic data. Primary tumor, patient, PSNB-US, and SLN characteristics were evaluated. Multivariable regression analyses were performed to determine independent prognostic factors associated with SNBR. RESULTS: The study enrolled 737 patients: 193 (26.2%) patients with SNBR and 73 (9.9%) patients with first abnormal US. The patients with an abnormal first US were more likely to experience SNBR (23.8 vs. 5.0%). In the multivariable analyses, increased risk of SNBR was associated with male gender (adjusted hazard ratio [aHR], 1.38; 95% confidence interval [CI], 1.00-1.9; p = 0.049), increasing Breslow thickness (aHR, 1.10; 95% CI, 1.01-1.2; p = 0.038), presence of ulceration (aHR, 1.93; 95% CI, 1.42-2.6; p < 0.001), sentinel node tumor burden greater than 1 mm (aHR, 1.91; 95% CI, 1.10-3.3; p = 0.022), lymphovascular invasion (aHR, 1.53; 95% CI, 1.00-2.3; p = 0.048), and presence of abnormal PSNB-US (aHR, 4.29; 95% CI, 3.02-6.1; p < 0.001). CONCLUSIONS: The first postoperative US together with clinical and pathologic factors may play an important role in predicting SNBR.

Effects of obesity and acute resistance exercise on skeletal muscle angiogenic communication pathways.

NEW FINDINGS: What is the central question of this study? Do obesity and acute resistance exercise alter the regulation of muscle intercellular communication pathways consistent with inadequate compensatory angiogenesis in response to muscle loading present in individuals with obesity? What is the main finding and its importance? Obesity is associated with differences in both pro- and anti-angiogenic signalling consistent with lower muscle capillarization. Acute resistance exercise increases the release of skeletal muscle small extracellular vesicles independent of body mass. These results identify new cellular factors associated with impaired angiogenesis in obesity and the positive effects of acute resistance exercise in lean and obese skeletal muscle. ABSTRACT: Obesity (OB) impairs cell-to-cell communication signalling. Small extracellular vesicles (EVs), which include exosomes, are released by skeletal muscle and participate in cell-to-cell communication, including the regulation of angiogenesis. Resistance exercise (REx) increases muscle fibre size and capillarization. Although obesity increases muscle fibre size, there is an inadequate increase in capillarization such that capillary density is reduced. It was hypothesized that REx-induced angiogenic signalling and EV biogenesis would be lower with obesity. Sedentary lean (LN) and OB subjects (n = 8 per group) performed three sets of single-leg knee-extension REx at 80% of maximum. Muscle biopsies were obtained at rest, 15 min and 3 h postexercise and analysed for angiogenic and EV biogenesis mRNA and protein. In OB subjects, muscle fibre size was ∼20% greater and capillary density with type II fibres ∼25% lower compared with LN subjects (P < 0.001). In response to REx, the increase in VEGF mRNA (pro-angiogenic) was similar (3-fold) between groups, while thrombospondin-1 (TSP-1) mRNA (anti-angiogenic) increased ∼2.5-fold in OB subjects only (P = 0.010). miR-130a (pro-angiogenic) was ∼1.4-fold (P = 0.011) and miR-503 (anti-angiogenic) ∼1.8-fold (P = 0.017) greater in OB compared with LN subjects at all time points. In both groups, acute REx decreased the EV surface protein Alix by ∼50%, consistent with the release of exosomes (P = 0.016). Acute REx appears to induce the release of skeletal muscle small EVs independent of body mass. However, with obesity there is predominantly impaired angiogenic signalling, consistent with inadequate angiogenesis in response to basal muscle hypertrophy.

Postoperative CT scans after resection of brain metastases: neurosurgical routine or added value?

BACKGROUND: Metastasis is the most common brain tumor in adults. It is the standard of care at most North American centers to obtain an early postoperative imaging after their resection. However, the necessity of this practice in the absence of a new postoperative deficit remains unclear. METHODS: We retrospectively reviewed our surgical cohort of patients who underwent resection of brain metastases from July 2018 to June 2019. We collected demographic data and reviewed results of routine postoperative CT scans and neurological morbidities to examine the diagnostic and therapeutic yield of an early postoperative scan. In addition, we performed a systematic review of the topic. RESULTS: Our review included 130 patients, all of whom underwent gross total resection of one or more brain metastases. On postoperative CT, none had unexpected findings such as cavity hematoma or new ischemia; no changes in management resulted from postoperative imaging. One patient required a higher dose of dexamethasone on postoperative day 4 for delayed hemiparesis and aphasia due to cerebral edema. Three additional patients underwent a wound washout for delayed infection during a subsequent admission. Our systematic review identified three additional studies; in a combined cohort of 450 patients (including our own), no patients had clinically actionable findings on routine postoperative CT. CONCLUSIONS: Following resection of brain metastases, a routine postoperative CT scan has low diagnostic yield and did not change patient management in any cases examined in this work.

Skeletal muscle IGF-1 is lower at rest and after resistance exercise in humans with obesity.

PURPOSE: Obesity is associated with numerous changes in skeletal muscle including greater muscle mass and muscle fiber cross sectional area (FCSA), yet fasted muscle protein synthesis is lower. Activation of the IGF-1/Akt/mTOR pathway is critical for muscle mass maintenance, muscle hypertrophy, and muscle protein regulation. Resistance exercise (RE) increases muscle mass, FCSA, and IGF-1. Persons with obesity have greater skeletal muscle mass and larger skeletal muscle fiber cross sectional area. The IGF-1/Akt/mTOR pathway is critical for the regulation of skeletal muscle mass. Our study found men and women with obesity have lower skeletal muscle IGF-1 mRNA and protein and higher expression of miR-206 an epigenetic regulator of IGF-1, at rest and following an acute bout of resistance exercise. Despite this, Akt mediated signaling was maintained and maintenance of phosphorylation does not appear to be accounted for by compensatory pathways. Our findings suggest a possible negative feedback mechanism via increased miR-206 and in turn decreased IGF-1 to limit further skeletal muscle hypertrophy in persons with obesity. The current work investigated if: (1) obesity dysregulates basal skeletal muscle IGF-1 pathways; and (2) obesity augments the muscle IGF-1 pathway responses to acute RE. METHODS: Eight sedentary (no self-reported physical activity), lean (LN) and eight sedentary subjects with obesity (OB) had vastus lateralis biopsies taken at rest, and 15 min and 3 h post-acute RE for the measurement of the IGF-1 pathway and muscle FCSA. RESULTS: Type II FCSA was larger in OB vs. LN. Skeletal muscle IGF-1 mRNA and IGF-1 protein were lower in OB vs. LN at rest and post-exercise. Acute RE increased IGF-1 protein similarly in both groups. The expression of miR-206, a post-transcriptional inhibitor of IGF-1 expression, was higher in OB vs. LN and linked with lower IGF-1 mRNA (r = - 0.54). CONCLUSION: In spite of greater muscle FCSA, muscle IGF-1 expression was lower in obesity suggesting negative feedback may be limiting muscle mass expansion in obesity.

Benefits and Harms of Intensive Blood Pressure Treatment in Adults Aged 60 Years or Older: A Systematic Review and Meta-analysis.

BACKGROUND: Recent guidelines recommend a systolic blood pressure (SBP) goal of less than 150 mm Hg for adults aged 60 years or older, but the balance of benefits and harms is unclear in light of newer evidence. PURPOSE: To systematically review the effects of more versus less intensive BP control in older adults. DATA SOURCES: Multiple databases through January 2015 and MEDLINE to September 2016. STUDY SELECTION: 21 randomized, controlled trials comparing BP targets or treatment intensity, and 3 observational studies that assessed harms. DATA EXTRACTION: Two investigators extracted data, assessed study quality, and graded the evidence using published criteria. DATA SYNTHESIS: Nine trials provided high-strength evidence that BP control to less than 150/90 mm Hg reduces mortality (relative risk [RR], 0.90 [95% CI, 0.83 to 0.98]), cardiac events (RR, 0.77 [CI, 0.68 to 0.89]), and stroke (RR, 0.74 [CI, 0.65 to 0.84]). Six trials yielded low- to moderate-strength evidence that lower targets (≤140/85 mm Hg) are associated with marginally significant decreases in cardiac events (RR, 0.82 [CI, 0.64 to 1.00]) and stroke (RR, 0.79 [CI, 0.59 to 0.99]) and nonsignificantly fewer deaths (RR, 0.86 [CI, 0.69 to 1.06]). Low- to moderate-strength evidence showed that lower BP targets do not increase falls or cognitive impairment. LIMITATION: Data relevant to frail elderly adults and the effect of multimorbidity are limited. CONCLUSION: Treatment to at least current guideline standards for BP (<150/90 mm Hg) substantially improves health outcomes in older adults. There is less consistent evidence, largely from 1 trial targeting SBP less than 120 mm Hg, that lower BP targets are beneficial for high-risk patients. Lower BP targets did not increase falls or cognitive decline but are associated with hypotension, syncope, and greater medication burden. PRIMARY FUNDING SOURCE: U.S. Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Quality Enhancement Research Initiative. (PROSPERO 2015: CRD42015017677).

Reproducibility of Assessment of Lepidic (Noninvasive) Patterns in Lung Adenocarcinoma With Cytokeratin Immunostain Compared With Hematoxylin and Eosin and the Proposed New International Association for the Study of Lung Cancer (IASLC) Algorithm.

Introduction: Lepidic growth is considered noninvasive in lung nonmucinous adenocarcinoma, whereas other patterns are invasive. Considerable interobserver variability in assessing "invasion" has been reported. We assessed the utility of cytokeratin 7 (CK7) stain and recently proposed International Association for the Study of Lung Cancer criteria to improve assessment of noninvasion in lung adenocarcinoma. Methods: Four pathologists (two staff, two trainees) assessed 158 hematoxylin and eosin (HE)- and CK7-stained slides of 108 pT1N0-2 nonmucinous lung adenocarcinoma cases. Scoring took place in four rounds. First, sections were independently scored for percentage of noninvasive or probable noninvasive and invasive or probable invasive patterns. Second, after a consensus scoring algorithm for CK7 was formulated, the slides were rescored. Subsequent third-round scoring was conducted only on HE slides using the 2023 International Association for the Study of Lung Cancer proposed criteria, and fourth-round scoring on both HE and CK7 slides simultaneously. Intraclass correlation coefficient (ICC) was calculated for each round. Recurrence-free survival was assessed using Cox proportional hazards regression methods. Results: In the first two rounds, interobserver concordance was consistently higher with CK7 (ICC range = 0.44-0.6) than HE (range = 0.24-0.49) scores. The IASLC proposed algorithm improved ICC of HE scores to 0.60 (95% confidence interval: 0.52-0.67), and round 4 HE and CK7 combined improved ICC to 0.75 (95% confidence interval: 0.70-0.80). Continuous measures of averaged noninvasive and probable noninvasive scores on HE were associated with improved recurrence-free survival (hazard ratio: 0.83-0.86). Conclusions: CK7 staining consistently increased interobserver concordance in assessment of invasive versus noninvasive patterns than HE. Combining CK7 with the 2023 IASLC criteria for morphologic features of invasion may further improve the interobservers' concordance for the recognition of lepidic growth in nonmucinous lung adenocarcinoma.

Multiparametric MRI radiomics for predicting disease-free survival and high-risk histopathological features for tumor recurrence in endometrial cancer.

Background: Current preoperative imaging is insufficient to predict survival and tumor recurrence in endometrial cancer (EC), necessitating invasive procedures for risk stratification. Purpose: To establish a multiparametric MRI radiomics model for predicting disease-free survival (DFS) and high-risk histopathologic features in EC. Methods: This retrospective study included 71 patients with histopathology-proven EC and preoperative MRI over a 10-year period. Clinicopathology data were extracted from health records. Manual MRI segmentation was performed on T2-weighted (T2W), apparent diffusion coefficient (ADC) maps and dynamic contrast-enhanced T1-weighted images (DCE T1WI). Radiomic feature (RF) extraction was performed with PyRadiomics. Associations between RF and histopathologic features were assessed using logistic regression. Associations between DFS and RF or clinicopathologic features were assessed using the Cox proportional hazards model. All RF with univariate analysis p-value < 0.2 were included in elastic net analysis to build radiomic signatures. Results: The 3-year DFS rate was 68% (95% CI = 57%-80%). There were no significant clinicopathologic predictors for DFS, whilst the radiomics signature was a strong predictor of DFS (p<0.001, HR 3.62, 95% CI 1.94, 6.75). From 107 RF extracted, significant predictive elastic net radiomic signatures were established for deep myometrial invasion (p=0.0097, OR 4.81, 95% CI 1.46, 15.79), hysterectomy grade (p=0.002, OR 5.12, 95% CI 1.82, 14.45), hysterectomy histology (p=0.0061, OR 18.25, 95% CI 2.29,145.24) and lymphovascular space invasion (p<0.001, OR 5.45, 95% CI 2.07, 14.36). Conclusion: Multiparametric MRI radiomics has the potential to create a non-invasive a priori approach to predicting DFS and high-risk histopathologic features in EC.

Real-World Treatment Patterns and Clinical Outcomes among Patients Receiving CDK4/6 Inhibitors for Metastatic Breast Cancer in a Canadian Setting Using AI-Extracted Data.

Cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) are widely used in patients with hormone receptor-positive (HR+)/human epidermal growth factor receptor 2 negative (HER2-) advanced/metastatic breast cancer (ABC/MBC) in first line (1L), but little is known about their real-world use and clinical outcomes long-term, in Canada. This study used Pentavere's previously validated artificial intelligence (AI) to extract real-world data on the treatment patterns and outcomes of patients receiving CDK4/6i+endocrine therapy (ET) for HR+/HER2- ABC/MBC at Sinai Health in Toronto, Canada. Between 1 January 2016 and 1 July 2021, 48 patients were diagnosed with HR+/HER2- ABC/MBC and received CDK4/6i + ET. A total of 38 out of 48 patients received CDK4/6i + ET in 1L, of which 34 of the 38 (89.5%) received palbociclib + ET. In 2L, 12 of the 21 (57.1%) patients received CDK4/6i + ET, of which 58.3% received abemaciclib. In 3L, most patients received chemotherapy (10/12, 83.3%). For the patients receiving CDK4/6i in 1L, the median (95% CI) time to the next treatment was 42.3 (41.2, NA) months. The median (95% CI) time to chemotherapy was 46.5 (41.4, NA) months. The two-year overall survival (95% CI) was 97.4% (92.4, 100.0), and the median (range) follow-up was 28.7 (3.4-67.6) months. Despite the limitations inherent in real-world studies and a limited number of patients, these AI-extracted data complement previous studies, demonstrating the effectiveness of CDK4/6i + ET in the Canadian real-world 1L, with most patients receiving palbociclib as CDK4/6i in 1L.

A T2-weighted MRI-based radiomic signature for disease-free survival in locally advanced cervical cancer following chemoradiation: An international, multicentre study.

INTRODUCTION: To develop and validate a T2-weighted magnetic resonance imaging (MRI)-based radiomic signature associated with disease-free survival (DFS) in locally advanced cervical cancer. MATERIALS AND METHODS: The study comprised a training dataset of 132 patients (93 Norwegian; 39 The Cancer Imaging Archive (TCIA) and an independent validation Canadian dataset of 199 patients with FIGO stage IB-IVA cervical cancer treated with chemoradiation. Radiomic features were extracted using PyRadiomics. A radiomic signature was developed based on a multivariable radiomic prognostic model for DFS built using the training dataset, with minimal redundancy maximum relevancy feature selection method. Univariate and multivariable Cox regression analyses were then conducted to examine the association of the derived radiomic signature with DFS. RESULTS: A radiomic signature was prognostic for DFS in the training cohort (Norwegian hazard ratio [HR] 5.54, p = 0.002; TCIA HR 3.59, p = 0.04). The radiomic signature remained independently associated with DFS (HR 3.70, p = 0.004) when adjusted for stage and tumor volume. The radiomic signature was also prognostic for DFS in the validation cohort, both on univariate analysis (HR 2.22, p = 0.003), and multivariable analysis adjusted for stage and tumor volume (HR 1.84, p = 0.04). The 4-year DFS rates of patients with radiomic signature score > 0 vs ≤ 0 were 48.2 % vs 87.9 %, and 56.4 % vs 80.8 % for training and validation cohorts respectively. CONCLUSION: An MRI-based radiomic signature can be used as a prognostic biomarker for DFS in patients with locally advanced cervical cancer undergoing chemoradiation.

Oropharyngeal Cancer Staging Health Record Extraction Using Artificial Intelligence.

Importance: Accurate, timely, and cost-effective methods for staging oropharyngeal cancers are crucial for patient prognosis and treatment decisions, but staging documentation is often inaccurate or incomplete. With the emergence of artificial intelligence in medicine, data abstraction may be associated with reduced costs but increased efficiency and accuracy of cancer staging. Objective: To evaluate an algorithm using an artificial intelligence engine capable of extracting essential information from medical records of patients with oropharyngeal cancer and assigning tumor, nodal, and metastatic stages according to American Joint Committee on Cancer eighth edition guidelines. Design, Setting, and Participants: This retrospective diagnostic study was conducted among a convenience sample of 806 patients with oropharyngeal squamous cell carcinoma. Medical records of patients with staged oropharyngeal squamous cell carcinomas who presented to a single tertiary care center between January 1, 2010, and August 1, 2020, were reviewed. A ground truth cancer stage dataset and comprehensive staging rule book consisting of 135 rules encompassing p16 status, tumor, and nodal and metastatic stage were developed. Subsequently, 4 distinct models were trained: model T (entity relationship extraction) for anatomical location and invasion state, model S (numerical extraction) for lesion size, model M (sequential classification) for metastasis detection, and a p16 model for p16 status. For validation, results were compared against ground truth established by expert reviewers, and accuracy was reported. Data were analyzed from March to November 2023. Main Outcomes and Measures: The accuracy of algorithm cancer stages was compared with ground truth. Results: Among 806 patients with oropharyngeal cancer (mean [SD] age, 63.6 [10.6] years; 651 males [80.8%]), 421 patients (52.2%) were positive for human papillomavirus. The artificial intelligence engine achieved accuracies of 55.9% (95% CI, 52.5%-59.3%) for tumor, 56.0% (95% CI, 52.5%-59.4%) for nodal, and 87.6% (95% CI, 85.1%-89.7%) for metastatic stages and 92.1% (95% CI, 88.5%-94.6%) for p16 status. Differentiation between localized (stages 1-2) and advanced (stages 3-4) cancers achieved 80.7% (95% CI, 77.8%-83.2%) accuracy. Conclusion and Relevance: This study found that tumor and nodal staging accuracies were fair to good and excellent for metastatic stage and p16 status, with clinical relevance in assigning optimal treatment and reducing toxic effect exposures. Further model refinement and external validation with electronic health records at different institutions are necessary to improve algorithm accuracy and clinical applicability.

Real-World Outcomes of Patients with Advanced Epidermal Growth Factor Receptor-Mutated Non-Small Cell Lung Cancer in Canada Using Data Extracted by Large Language Model-Based Artificial Intelligence.

Real-world evidence for patients with advanced EGFR-mutated non-small cell lung cancer (NSCLC) in Canada is limited. This study's objective was to use previously validated DARWENTM artificial intelligence (AI) to extract data from electronic heath records of patients with non-squamous NSCLC at University Health Network (UHN) to describe EGFR mutation prevalence, treatment patterns, and outcomes. Of 2154 patients with NSCLC, 613 had advanced disease. Of these, 136 (22%) had common sensitizing EGFR mutations (cEGFRm; ex19del, L858R), 8 (1%) had exon 20 insertions (ex20ins), and 338 (55%) had EGFR wild type. One-year overall survival (OS) (95% CI) for patients with cEGFRm, ex20ins, and EGFR wild type tumours was 88% (83, 94), 100% (100, 100), and 59% (53, 65), respectively. In total, 38% patients with ex20ins received experimental ex20ins targeting treatment as their first-line therapy. A total of 57 patients (36%) with cEGFRm received osimertinib as their first-line treatment, and 61 (39%) received it as their second-line treatment. One-year OS (95% CI) following the discontinuation of osimertinib was 35% (17, 75) post-first-line and 20% (9, 44) post-second-line. In this real-world AI-generated dataset, survival post-osimertinib was poor in patients with cEGFR mutations. Patients with ex20ins in this cohort had improved outcomes, possibly due to ex20ins targeting treatment, highlighting the need for more effective treatments for patients with advanced EGFRm NSCLC.

Rate of pachymeningeal failure following adjuvant WBRT vs SRS in patients with brain metastases.

Background: Stereotactic radiosurgery (SRS) has supplanted whole brain radiotherapy (WBRT) as standard-of-care adjuvant treatment following surgery for brain metastasis (BrM). Concomitant with the adoption of adjuvant SRS, a new pattern of failure termed "Pachymeningeal failure" (PMF) has emerged. Methods: We reviewed a prospective registry of 264 BrM patients; 145 and 119 were treated adjuvantly with WBRT and SRS, respectively. The Cox proportional hazards model was used to identify variables correlating to outcomes. Outcomes were calculated using the cumulative incidence (CI) method. Univariate (UVA) and multivariate analyses (MVA) were done to identify factors associated with PMF. Results: CI of PMF was 2 % and 18 % at 12 months, and 2 % and 23 % at 24 months for WRBT and SRS, respectively (p < 0.001). The CI of classic leptomeningeal disease (LMD) was 3 % and 4 % at 12 months, and 6 % and 6 % at 24 months for WBRT and SRS, respectively (P = 0.67). On UVA, adjuvant SRS [HR 9.75 (3.43-27.68) (P < 0.001)]; preoperative dural contact (PDC) [HR 6.78 (1.64-28.10) (P = 0.008)]; GPA score [HR 1.64 (1.11-2.42) (P = 0.012)]; and lung EGFR/ALK status [HR 3.11 (1.02-9.45) (P = 0.045)]; were associated with PMF risk. On MVA, adjuvant SRS [HR 8.15 (2.69-24.7) (P < 0.001)]; and PDC [HR 6.28 (1.51-26.1) (P = 0.012)] remained associated with PMF. Conclusions: Preoperative dural contact and adjuvant SRS instead of adjuvant WBRT were associated with an increased risk of PMF. Strategies to improve pachymeningeal radiation coverage to sterilize at risk pachymeninges should be investigated.

Genomic Characterization and Clinical Outcomes of Patients with Peritoneal Metastases from the AACR GENIE Biopharma Collaborative Colorectal Cancer Registry.

Peritoneal metastases (PM) are common in metastatic colorectal cancer (mCRC). We aimed to characterize patients with mCRC and PM from a clinical and molecular perspective using the American Association of Cancer Research Genomics Evidence Neoplasia Information Exchange (GENIE) Biopharma Collaborative (BPC) registry. Patients' tumor samples underwent targeted next-generation sequencing. Clinical characteristics and treatment outcomes were collected retrospectively. Overall survival (OS) from advanced disease and progression-free survival (PFS) from start of cancer-directed drug regimen were estimated and adjusted for the left truncation bias. A total of 1,281 patients were analyzed, 244 (19%) had PM at time of advanced disease. PM were associated with female sex [OR: 1.67; 95% confidence interval (CI): 1.11-2.54; P = 0.014] and higher histologic grade (OR: 1.72; 95% CI: 1.08-2.71; P = 0.022), while rectal primary tumors were less frequent in patients with PM (OR: 0.51; 95% CI: 0.29-0.88; P < 0.001). APC occurred less frequently in patients with PM (N = 151, 64% vs. N = 788, 79%) while MED12 alterations occurred more frequently in patients with PM (N = 20, 10% vs. N = 32, 4%); differences in MED12 were not significant when restricting to oncogenic and likely oncogenic variants according to OncoKB. Patients with PM had worse OS (HR: 1.45; 95% CI: 1.16-1.81) after adjustment for independently significant clinical and genomic predictors. PFS from initiation of first-line treatment did not differ by presence of PM. In conclusion, PM were more frequent in females and right-sided primary tumors. Differences in frequencies of MED12 and APC alterations were identified between patients with and without PM. PM were associated with shorter OS but not with PFS from first-line treatment. SIGNIFICANCE: Utilizing the GENIE BPC registry, this study found that PM in patients with colorectal cancer occur more frequently in females and right-sided primary tumors and are associated with worse OS. In addition, we found a lower frequency of APC alterations and a higher frequency in MED12 alterations in patients with PM.

University campus breastfeeding, knowledge, and perceptions of support: An exploratory study.

Breastfeeding is often considered principally a biological issue but success is impacted by the socio-ecological environment of the lactating parent. Identifying current attitudes towards breastfeeding is essential in the effort toward normalizing breastfeeding in communities, including university campuses. The study explored campus community knowledge, awareness, and attitudes about breastfeeding, including available resources and applicable laws on two university campuses in the southern United States. This cross-sectional, self-reporting study utilized the Iowa Infant Feeding Attitude Scale and an adaptation of the Breastfeeding Behavior Questionnaire to survey a convenience sample. Results revealed decreased awareness of protective laws, availability of private lactation space, and insufficient public appreciation of breastfeeding's unique advantages to both lactating parent and infant as barriers to breastfeeding. These findings will help develop additional breastfeeding strategies to improve university campus community breastfeeding initiatives.

Evolving management of early stage pancreatic adenocarcinoma in older patients.

BACKGROUND: Due to the aging population, the number of older patients diagnosed with pancreatic ductal adenocarcinoma (PDAC) will continue to rise. STUDY DESIGN: Utilizing the NCDB from 2010 to 2016, patients with early stage, clinically node negative PDAC who were ≥70 years old and had a Whipple were identified. Multivariable logistic regressions were used to determine independent factors for R0 resection and NAT. Cox-proportional-hazards regression analyses examined for the impact of NAT on the risk of death. RESULTS: Of 5086 patients, 51.7% received upfront surgery + adjuvant therapy (UFS + AT), followed by 29.9% UFS only, and the remainder NAT. NAT significantly improved OS compared to a combined cohort of those that had UFS ± AT. NAT retained its independent survival benefit when compared to only patients that had UFS + AT. CONCLUSION: For older patients diagnosed with early stage PDAC, NAT was associated with improved R0 resection rates and a significant survival benefit when compared to the current standard of care.