Clinicians' and Users' Views and Experiences of a Tele-Mental Health Service Implemented Alongside the Public Mental Health System during the COVID-19 Pandemic.

A tele-mental health model called Head to Health was implemented in the state of Victoria, Australia to address the crisis caused by the COVID-19 pandemic. It was a free centralized intake service that adopted a targeted approach with several novel elements, such as stepped care and telehealth. This study examines the views and experiences of clinicians and service users of the tele-mental health service in the Gippsland region of Victoria during the COVID-19 pandemic. Data from clinicians were obtained via an online 10-item open-ended survey instrument and from service users through semi-structured interviews. Data were obtained from 66 participants, including 47 clinician surveys and 19 service user interviews. Six categories emerged from the data. They were: 'Conditions where use of tele-mental health is appropriate', 'Conditions where tele-mental health may not be useful', 'Advantages of tele-mental health', 'Challenges in using tele-mental health', 'Client outcomes with tele-mental health', and 'Recommendations for future use'. This is one of a few studies where clinicians' and service users' views and experiences have been explored together to provide a nuanced understanding of perspectives on the efficacy of tele-mental health when it was implemented alongside public mental health services.

Cubic-wavelength mode volume photonic crystal nanobeam cavities in a monolithic CMOS platform.

We report on the design, fabrication, and experimental characterization of photonic crystal (PhC) nanobeam cavities with the smallest footprint, largest intrinsic quality factor, and smallest mode volume to be demonstrated to date in a monolithic CMOS platform. Two types of cavities were designed, with opposite spatial mode symmetries. The opposite mode symmetry, combined with evanescent coupling, allows the nanobeam cavities to be used in reflectionless topologies, desirable in complex photonic integrated circuits (PICs). The devices were implemented and fabricated in a 45 nm monolithic electronics-photonics CMOS platform optimized for silicon photonics (GlobalFoundries 45CLO) and do not require any post-processing. Quality factors exceeding 100 000 were measured for both devices, the highest, to the best of our knowledge, among fully cladded PhC nanobeam cavities in any silicon-on-insulator (SOI) platform. Additionally, the ability of the cavities to confine light into small mode volumes, of the order of (λ/n)3, was confirmed experimentally using near-field scanning optical microscopy (NSOM). These types of cavities are an important step toward realizing ultra-low energy active devices required for the next generation of integrated optical links beyond the current microring resonator-based links and other CMOS PICs.

Polarization-insensitive 1D grating coupler based on a zero-birefringence subwavelength corelet waveguide.

Grating coupler devices provide efficient, foundry-compatible vertical fiber-to-chip coupling solutions in integrated photonic platforms. However, standard grating coupler designs are highly polarization sensitive, which hinders their adoption. We present a new, to the best of our knowledge, type of 1D polarization-insensitive grating coupler (PIGC) that is based on a zero-birefringence subwavelength "corelet" waveguide. We demonstrate a PIGC for coupling in the telecommunications O-band in a 45-nm-node monolithic silicon-on-insulator (SOI) CMOS electronic-photonic platform, with measured insertion losses of 6.7 and 6.1 dB to transverse electric and transverse magnetic polarizations, respectively, and a ±1-dB polarization dependent loss bandwidth of 73 nm.

A Phase I Study of Apolizumab, an Anti-HLA-DR ß-chain Monoclonal Antibody, in Patients With Solid Tumor Malignancies.

BACKGROUND: Human leukocyte antigen (HLA)-DR, a member of the major histocompatibility complex class II antigen family, is a target for antibody-based therapeutics. Apolizumab (Hu1D10, Remitogen), a humanized IgG1 monoclonal anti-HLA-DR ß-chain antibody targets the antigen, 1D10, expressed on a wide variety of hematologic and solid tumor malignancies. In this Phase 1 trial, the maximum tolerated dose and dose-limiting toxicity of weekly apolizumab in patients with advanced solid tumor malignancies were determined. PATIENTS AND METHODS: Eligible patients with refractory solid tumors were initially screened for ID10 Ag on their tumor. Patients whose tumors expressed 1D10 were administered apolizumab 0.5, 1.0, 1.5, or 3.0 mg/kg intravenously over 90 minutes weekly for 4 consecutive weeks, followed by a 4-week break, and assessment of response. Patients whose disease had not progressed were offered additional treatment. RESULTS: Tumors from 75 patients were screened for 1D10 Ag of which 17 patients were positive and underwent treatment. The first 3 dose levels were well-tolerated. Dose-limiting toxicities of grade 3 infusion-related hypersensitivity reactions and grade 3 headache and hypertension occurred in 2 patients, respectively, at apolizumab 3.0 mg/kg. Four patients, 1 each with breast carcinoma, melanoma, renal cell carcinoma, and sarcoma had stable disease for a median of 15 weeks (range: 12 to 19 wk). CONCLUSION: Apolizumab can be administered safely at a maximum tolerated dose of 1.5 mg/kg for 4 consecutive weeks. Adverse events and limited clinical data in both hematologic and solid tumor malignancies resulted in discontinuation of clinical development of apolizumab. HLA-DR remains an interesting immunotherapeutic target.

Intracellular Signaling Pathways Mediating Tyrosine Kinase Inhibitor Cardiotoxicity.

Tyrosine kinase inhibitors (TKIs) are used to treat several cancers; however, a myriad of adverse cardiotoxic effects remain a primary concern. Although hypertension (HTN) is the most common adverse effect reported with TKI therapy, incidents of arrhythmias (eg, QT prolongation, atrial fibrillation) and heart failure are also prevalent. These complications warrant further research toward understanding the mechanisms of TKI-induced cardiotoxicity. Recent literature has given some insight into the intracellular signaling pathways that may mediate TKI-induced cardiac dysfunction. In this article, we discuss the cardiotoxic effects of TKIs on cardiomyocyte function, signaling, and possible treatments.

2021 White Paper on Recent Issues in Bioanalysis: ISR for Biomarkers, Liquid Biopsies, Spectral Cytometry, Inhalation/Oral & Multispecific Biotherapeutics, Accuracy/LLOQ for Flow Cytometry (Part 2 - Recommendations on Biomarkers/CDx Assays Development & Validation, Cytometry Validation & Innovation, Biotherapeutics PK LBA Regulated Bioanalysis, Critical Reagents & Positive Controls Generation).

The 15th edition of the Workshop on Recent Issues in Bioanalysis (15th WRIB) was held on 27 September to 1 October 2021. Even with a last-minute move from in-person to virtual, an overwhelmingly high number of nearly 900 professionals representing pharma and biotech companies, contract research organizations (CROs), and multiple regulatory agencies still eagerly convened to actively discuss the most current topics of interest in bioanalysis. The 15th WRIB included three Main Workshops and seven Specialized Workshops that together spanned 1 week in order to allow exhaustive and thorough coverage of all major issues in bioanalysis, biomarkers, immunogenicity, gene therapy, cell therapy and vaccines. Moreover, in-depth workshops on biomarker assay development and validation (BAV) (focused on clarifying the confusion created by the increased use of the term "context of use" [COU]); mass spectrometry of proteins (therapeutic, biomarker and transgene); state-of-the-art cytometry innovation and validation; and critical reagent and positive control generation were the special features of the 15th edition. This 2021 White Paper encompasses recommendations emerging from the extensive discussions held during the workshop, and is aimed to provide the bioanalytical community with key information and practical solutions on topics and issues addressed, in an effort to enable advances in scientific excellence, improved quality and better regulatory compliance. Due to its length, the 2021 edition of this comprehensive White Paper has been divided into three parts for editorial reasons. This publication (Part 2) covers the recommendations on ISR for Biomarkers, Liquid Biopsies, Spectral Cytometry, Inhalation/Oral & Multispecific Biotherapeutics, Accuracy/LLOQ for Flow Cytometry. Part 1A (Endogenous Compounds, Small Molecules, Complex Methods, Regulated Mass Spec of Large Molecules, Small Molecule, PoC), Part 1B (Regulatory Agencies' Inputs on Bioanalysis, Biomarkers, Immunogenicity, Gene & Cell Therapy and Vaccine) and Part 3 (TAb/NAb, Viral Vector CDx, Shedding Assays; CRISPR/Cas9 & CAR-T Immunogenicity; PCR & Vaccine Assay Performance; ADA Assay Comparability & Cut Point Appropriateness) are published in volume 14 of Bioanalysis, issues 9 and 11 (2022), respectively.

Determinants of long-term opioid prescribing in an urban population: A cross-sectional study.

BACKGROUND: Opioid prescribing has more than doubled in the UK between 1998 and 2016. Potential adverse health implications include dependency, falls and increased health expenditure. AIM: To describe the predictors of long-term opioid prescribing (LTOP) (≥3 opioid prescriptions in a 90-day period). DESIGN AND SETTING: A retrospective cross-sectional study in 41 general practices in South London. METHOD: Multi-level multivariable logistic regression to investigate the determinants of LTOP. RESULTS: Out of 320 639 registered patients ≥18 years, 2679 (0.8%) were identified as having LTOP. Patients were most likely to have LTOP if they had ≥5 long-term conditions (LTCs) (adjusted odds ratio [AOR] 36.5, 95% confidence interval [CI] 30.4-43.8) or 2-4 LTCs (AOR 13.8, CI 11.9-16.1) in comparison to no LTCs, were ≥75 years compared to 18-24 years (AOR 12.31, CI 7.1-21.5), were smokers compared to nonsmokers (AOR 2.2, CI 2.0-2.5), were female rather than male (AOR 1.9, CI 1.7-2.0) and in the most deprived deprivation quintile (AOR 1.6, CI 1.4-1.8) compared to the least deprived. In a separate model examining individual LTCs, the strongest associations for LTOP were noted for sickle cell disease (SCD) (AOR 18.4, CI 12.8-26.4), osteoarthritis (AOR 3.0, CI 2.8-3.3), rheumatoid arthritis (AOR 2.8, CI 2.2-3.4), depression (AOR 2.6, CI 2.3-2.8) and multiple sclerosis (OR 2.5, CI 1.4-4.4). CONCLUSION: LTOP was significantly higher in those aged ≥75 years, with multimorbidity or specific LTCs: SCD, osteoarthritis, rheumatoid arthritis, depression and multiple sclerosis. These characteristics may enable the design of targeted interventions to reduce LTOP.

Light- and Melanin Nanoparticle-Induced Cytotoxicity in Metastatic Cancer Cells.

Melanin nanoparticles are known to be biologically benign to human cells for a wide range of concentrations in a high glucose culture nutrition. Here, we show cytotoxic behavior at high nanoparticle and low glucose concentrations, as well as at low nanoparticle concentration under exposure to (nonionizing) visible radiation. To study these effects in detail, we developed highly monodispersed melanin nanoparticles (both uncoated and glucose-coated). In order to study the effect of significant cellular uptake of these nanoparticles, we employed three cancer cell lines: VM-M3, A375 (derived from melanoma), and HeLa, all known to exhibit strong macrophagic character, i.e., strong nanoparticle uptake through phagocytic ingestion. Our main observations are: (i) metastatic VM-M3 cancer cells massively ingest melanin nanoparticles (mNPs); (ii) the observed ingestion is enhanced by coating mNPs with glucose; (iii) after a certain level of mNP ingestion, the metastatic cancer cells studied here are observed to die-glucose coating appears to slow that process; (iv) cells that accumulate mNPs are much more susceptible to killing by laser illumination than cells that do not accumulate mNPs; and (v) non-metastatic VM-NM1 cancer cells also studied in this work do not ingest the mNPs, and remain unaffected after receiving identical optical energy levels and doses. Results of this study could lead to the development of a therapy for control of metastatic stages of cancer.

Is rapid scientific publication also high quality? Bibliometric analysis of highly disseminated COVID-19 research papers.

The impact of COVID-19 has underlined the need for reliable information to guide clinical practice and policy. This urgency has to be balanced against disruption to journal handling capacity and the continued need to ensure scientific rigour. We examined the reporting quality of highly disseminated COVID-19 research papers using a bibliometric analysis examining reporting quality and risk of bias (RoB) amongst 250 top scoring Altmetric Attention Score (AAS) COVID-19 research papers between January and April 2020. Method-specific RoB tools were used to assess quality. After exclusions, 84 studies from 44 journals were included. Forty-three (51%) were case series/studies, and only one was an randomized controlled trial. Most authors were from institutions based in China (n = 44, 52%). The median AAS and impact factor was 2015 (interquartile range [IQR] 1,105-4,051.5) and 12.8 (IQR 5-44.2) respectively. Nine studies (11%) utilized a formal reporting framework, 62 (74%) included a funding statement, and 41 (49%) were at high RoB. This review of the most widely disseminated COVID-19 studies highlights a preponderance of low-quality case series with few research papers adhering to good standards of reporting. It emphasizes the need for cautious interpretation of research and the increasingly vital responsibility that journals have in ensuring high-quality publications.

Phase I Study of Docetaxel and Temsirolimus in Refractory Solid Tumors.

INTRODUCTION: The mammalian target of rapamycin (mTOR) is a downstream mediator in the phosphatidylinositol 3-kinase/Akt signaling pathway, and plays a central role in cell proliferation, growth, differentiation, migration, and survival. Temsirolimus (CCI-779), a selective inhibitor of the mTOR, is an ester analog of rapamycin (sirolimus) with improved aqueous solubility and pharmacokinetic (PK) properties. Preclinical studies have confirmed additive and synergistic antitumor activity in cancer cell lines (breast, prostate cancer) with combinations of taxanes and mTOR inhibitors. We conducted a phase I open-label, dose-escalation study to determine the maximal tolerated dose (MTD) of docetaxel in combination with temsirolimus in patients with refractory solid tumors. PATIENTS AND METHODS: Eligible patients had a diagnosis of a refractory solid malignancy, measurable disease, and adequate organ function. Patients were sequentially enrolled in 4 dose level intravenous combinations of docetaxel and temsirolimus. Temsirolimus was administered weekly with docetaxel administered every 3 weeks. Laboratory data for tumor markers and radiologic imaging were conducted prestudy and then after every 2 cycles of the treatment. Radiologic response was assessed by Response Evaluation Criteria in Solid Tumors (RECIST) criteria. Blood samples for PK and pharmacodynamic analysis were planned to be drawn at MTD. Apart from the traditional 3+3 design, we also implemented Bayesian Optimal Interval design which uses isotonic regression method to select MTD. We proceeded with isotonic regression analysis by using 20% dose-limiting toxicity (DLT) rate as target. RESULTS: Twenty-six patients were treated in this study in 4 cohorts and dose levels. Fourteen males and 12 females were enrolled with a median age of 50 years (range of 27 to 72 y) and median Eastern Cooperative Oncology Group performance score of 1. Tumor histologies included pancreas (6), colon (5), rectum (3), gallbladder (2), non-small cell lung (2), endometrium (1), neuroendocrine (1), esophagus (1), stomach (1), pharynx (1), small intestine (1), and duodenum (1). Stable disease was observed in 2/4 (50%), 3/7 (43%), 4/10 (40%), and 3/5 (60%) patients in cohorts 1, 2, 3, and 4, respectively. Dose escalation in cohorts 2, 3, and 4 was complicated by DLTs such as grade 4 neutropenia and grade 3 diarrhea and an inability for patients to tolerate treatments during and beyond cycle 1 without dose reductions. Therefore, we could not determine an MTD or recommended phase II dose using the traditional 3+3 study analysis. Blood samples for PK and pharmacodynamic analysis were not collected since MTD was not determined. By using 20% DLT rate closest to the target, isotonic regression analysis showed identical estimated DLT rates in dose -1 (docetaxel 50 mg/m2 and temsirolimus 15 mg/m2) and dose level 1 (docetaxel 60mg/m2 and temsirolimus 15 mg/m2). CONCLUSIONS: Dose escalation of docetaxel and temsirolimus was limited by severe myelosuppressive toxicity in this phase I study. Most of the DLTs occurred after cycle 1 of therapy hence, we were unable to determine MTD or collect blood samples for PK and pharmacodynamic analysis. Our trial did not meet its objectives due to significant DLTs with this chemotherapy combination. Although our novel use of Bayesian Optimal Interval design using isotonic regression method to select MTD showed identical estimated DLT rates in dose levels 1 and -1, clinically our patients were not able to complete 2 cycles of this regimen without dose reductions due to myelosuppressive toxicity in either of these dose levels, and hence, escaped clinical validity. This combination regimen should not be studied further at the dose levels and schedules tested in our study.

Association of PET-based estradiol-challenge test for breast cancer progesterone receptors with response to endocrine therapy.

Estrogen receptor (ER) testing of breast cancer imperfectly predicts response to endocrine therapy (ET). We hypothesize that a brief estradiol challenge will increase tumor progesterone receptor (PgR) levels only in tumors with functional ER. In this prospective, phase 2, single-center, single-arm trial (NCT02455453), we report the association of response to ET with change in tumor uptake of the progestin analog, 21-[18F]fluorofuranylnorprogesterone (FFNP), before and after a one-day estradiol challenge. In 43 postmenopausal women with advanced ER+ breast cancer, we show a post-challenge increase in tumor FFNP uptake only in 28 subjects with clinical benefit from ET (responders), but not in 15 without clinical benefit (nonresponders) (p < 0.0001), indicating 100% sensitivity and specificity. We further show significantly longer survival (p < 0.0001) in the responding subjects. Our results demonstrate that change in tumor FFNP uptake after estradiol challenge is highly predictive of response to ET in women with ER+ breast cancer.

Prevalence of mental illness among parents of children receiving treatment within child and adolescent mental health services (CAMHS): a scoping review.

People affected by mental illness often come from families with patterns of mental illness that span across generations. Hence, child and adolescent mental health services (CAMHS) likely provide treatment to many children with parents who also experience mental illness. The aim of this scoping review was to: (1) identify the prevalence of mental illness among parents of children in CAMHS; (2) identify and appraise the methodologies that have been implemented to assess the prevalence of parental mental illness in CAMHS; (3) identify additional circumstances associated with families where both parent and child experience mental illness; and (4) present recommendations that have been made for CAMHS practice based on these findings. English language, peer-reviewed studies (2010-2018) that had investigated the mental health of parents in CAMHS were included in the review. Literature searching yielded 18 studies which were found to have utilised diverse methodologies to assess parental mental health. Overall, reported prevalence of parental mental illness ranged from 16 to 79%; however, a single study that was deemed to be comprehensive reported prevalence rates of 36% for mothers and 33% for fathers. Across studies, parent and child mental illness was found to be associated with additional adversities impacting family functioning and wellbeing. For children who receive treatment for mental illness, having a parent who also experiences mental illness is a frequent family circumstance that has implications for their prospects for recovery. Accordingly, the mental health of parents should be an important consideration within the mental health care CAMHS provide to children.

Extraordinary optical transmission in nano-bridged plasmonic arrays mimicking a stable weakly-connected percolation threshold.

Ultrasensitive sensors of various physical properties can be based on percolation systems, e.g., insulating media filled with nearly touching conducting particles. Such a system at its percolation threshold featuring the critical particle concentration, changes drastically its response (electrical conduction, light transmission, etc.) when subjected to an external stimulus. Due to the critical nature of this threshold, a given state at the threshold is typically very unstable. However, stability can be restored without significantly sacrificing the structure sensitivity by forming weak connections between the conducting particles. In this work, we employed nano-bridged nanosphere lithography to produce such a weakly connected percolation system. It consists of two coupled quasi-Babinet complementary arrays, one with weakly connected, and the other with disconnected metallic islands. We demonstrate via experiment and simulation that the physics of this plasmonic system is non-trivial, and leads to the extraordinary optical transmission at narrowly defined peaks sensitive to system parameters, with surface plasmons mediating this process. Thus, our system is a potential candidate for percolation effect based sensor applications. Promising detection schemes could be based on these effects.

Optical confinement in the nanocoax: coupling to the fundamental TEM-like mode.

The nanoscale coaxial cable (nanocoax) has demonstrated optical confinement in the visible and the near infrared. We report on a novel nanofabrication process which yields optically addressable, sub-µm diameter, and high aspect ratio metal-insulator-metal nanocoaxes made by atomic layer deposition of Pt and Al2O3. We observe sub-diffraction-limited optical transmission via the fundamental, TEM-like mode by excitation with a radially polarized optical vortex beam. Our experimental results are based on interrogation with a polarimetric imager. Finite element method numerical simulations support these results, and their uniaxial symmetry was exploited to model taper geometries with both an electrically large volume, (15λ)3, and a nanoscopic exit aperture, (λ/200)2.

Nano-bridged nanosphere lithography.

We develop nano-bridged nanosphere lithography (NB-NSL), a modification to the widely used conventional nanosphere lithography (NSL). Nano-bridges between polystyrene (PS) spheres of a pristine NSL template are controllably formed in a two-step process: (i) spin-coating of a dilute styrene solution on top of the template, followed by (ii) oxygen plasma etching of the template. We show that the nanobridge dimensions can be precisely tuned by controlling the pre-processing conditions and the plasma etching time. The resulting lithography templates feature control over the shape and size of the apertures, which determine the morphology of the final nano-island arrays after material deposition and template removal. The unique advantage of NB-NSL is that PS particle templates based on a single PS particle diameter can be utilized for the fabrication of a variation of nano-island shapes and sizes, whereas conventional NSL yields only bowtie-shaped nano-islands, with their size being predetermined by the PS particle diameter of the template.

Facile fabrication and formation mechanism of aluminum nanowire arrays.

Anodized alumina membranes (AAMs) have proven effective at making vertically-oriented and well-ordered metal nanowire arrays, which are useful in plasmonics and electrochemistry. Here, we produced Al nanowires via directed AAM pore nucleation: a patterned oxide mask on a flat Al surface directed where pores did and did not form, the pores acting to oxidize Al around the sites without pores. This left Al nanowires embedded in the AAM, and produced freestanding Al nanowires after etching the AAM. The nanowire tops had two distinct contours, smooth bowls and flat rough surfaces-suggesting that nanowires with bowl tops result from slow pore development relative to pattern-nucleated pores, not pore blockage as prior literature suggests. The observed low porosity of ∼2%, as opposed to the more typical 10%, suggests pore nucleation in the electrolyte employed may need greater local variations in electric field or pH, possibly explaining the electrolyte's peculiar ability to make Al nanowires. Finally, a soft nano-imprint lithography process was developed here to pattern the mask without damaging the stamp, avoiding a stamp degradation problem in previous work that utilized hard nano-imprint lithography.

Impact of parental mental illness on children's HoNOSCA results in a regional child and adolescent mental health service.

Use of routine outcome measures are frequently used to ascertain improvement in children's symptomology, this study examined whether living with a parent with a mental illness impacted outcome measures. The study examined 134 children attending a Child and Adolescent Mental Health Service (CAMHS). The majority lived with a parent reporting mental illness. Routine HoNOSCA and CGAS outcome measures were collected over a 6-month period. Children of parents with a mental illness scored higher on most outcome measures. All children improved on most variables over the 6 months of CAMHS intervention with children of parents with mental illness showing greater improvement compared to other children on behaviour but less improvement on all other variables. They did not, however, improve as much on education-related factors and showed lower improvement in overall functioning. Younger children with a parent with a mental illness improved least in the area of behaviour. This study highlighted the need for greater use and integration of measures where children live with a parent who has a mental illness. Findings suggest parental mental illness impacted on overall child outcomes, and this influence remained irrespective of clinical intervention. The common occurrence of parental mental illness, where children also have a mental illness, indicates focusing on a wider set of outcome measures for more effective intervention. Analysis of a larger cohort sample is warranted.

Predictors of Locoregional Recurrence After Failure to Achieve Pathologic Complete Response to Neoadjuvant Chemotherapy in Triple-Negative Breast Cancer.

BACKGROUND: This study evaluated factors predictive of locoregional recurrence (LRR) in women with triple-negative breast cancer (TNBC) treated with neoadjuvant chemotherapy who do not experience pathologic complete response (pCR). METHODS: This is a single-institution retrospective review of women with TNBC treated with neoadjuvant chemotherapy, surgery, and radiation therapy in 2000 through 2013. LRR was estimated between patients with and without pCR using the Kaplan-Meier method. Patient-, tumor-, and treatment-specific factors in patients without pCR were analyzed using the Cox proportional hazards method to evaluate factors predictive of LRR. Log-rank statistics were then used to compare LRR among these risk factors. RESULTS: A total of 153 patients with a median follow-up of 48.6 months were included. The 4-year overall survival and LRR were 70% and 15%, respectively, and the 4-year LRR in patients with pCR was 0% versus 22.0% in those without (P<.001). In patients without pCR, lymphovascular space invasion (LVSI; hazard ratio, 3.92; 95% CI, 1.64-9.38; P=.002) and extranodal extension (ENE; hazard ratio, 3.32; 95% CI, 1.35-8.15; P=.009) were significant predictors of LRR in multivariable analysis. In these patients, the 4-year LRR with LVSI was 39.8% versus 15.0% without (P<.001). Similarly, the 4-year LRR was 48.1% with ENE versus 16.1% without (P=.002). In patients without pCR, the presence of both LVSI and ENE were associated with an even further increased risk of LRR compared with patients with either LVSI or ENE alone and those with neither LVSI nor ENE in the residual tumor (P<.001). CONCLUSIONS: In patients without pCR, the presence of LVSI and ENE increases the risk of LRR in TNBC. The risk of LRR is compounded when both LVSI and ENE are present in the same patient. Future clinical trials are warranted to lower the risk of LRR in these high-risk patients.

Treatment response as predictor for brain metastasis in triple negative breast cancer: A score-based model.

BACKGROUND: Triple negative breast cancer (TNBC) has worse prognosis than other subtypes of breast cancer, and many patients develop brain metastasis (BM). We developed a simple predictive model to stratify the risk of BM in TNBC patients receiving neo-adjuvant chemotherapy (NAC), surgery, and radiation therapy (RT). METHODS: Patients with TNBC who received NAC, surgery, and RT were included. Cox proportional hazards method was used to evaluate factors associated with BM. Significant factors predictive for BM on multivariate analysis (MVA) were used to develop a risk score. Patients were divided into three risk groups: low, intermediate, and high. A receiver operating characteristic (ROC) curve was drawn to evaluate the value of the risk group in predicting BM. This predictive model was externally validated. RESULTS: A total of 160 patients were included. The median follow-up was 47.4 months. The median age at diagnosis was 49.9 years. The 2-year freedom from BM was 90.5%. Persistent lymph node positivity, HR 8.75 (1.76-43.52, P = 0.01), and lack of downstaging, HR 3.46 (1.03-11.62, P = 0.04), were significant predictors for BM. The 2-year rate of BM was 0%, 10.7%, and 30.3% (P < 0.001) in patients belonging to low-, intermediate-, and high-risk groups, respectively. Area under the ROC curve was 0.81 (P < 0.001). This model was externally validated (C-index = 0.79). CONCLUSIONS: Lack of downstaging and persistent lymph node positivity after NAC are associated with development of BM in TNBC. This model can be used by the clinicians to stratify patients into the three risk groups to identify those at increased risk of developing BM and potentially impact surveillance strategies.