Automated immunostaining-free prediction of breast carcinoma ER and PR status, Ki67 count, patient therapy stratification index and quantification of prognostic quiescence burden in TNBC from pretreatment H&E stained histopathology images in breast cancer.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e12535-e12535
Author(s):  
Tathagata Dasgupta ◽  
Satabhisa Mukhopadhyay ◽  
Nicolas M Orsi ◽  
Michele Cummings ◽  
Angelene Berwick
Keyword(s):  
Low Cost ◽  
A Priori ◽  
Disease Recurrence ◽  
Mitotic Checkpoint ◽  
Luminal A ◽  
Slide Image ◽  
Luminal Type ◽  
Therapy Stratification ◽  
Pre Treatment ◽  
Stratification System

e12535 Background: Categorical combinations of ER, PR, HER2, and Ki67 levels are traditionally used to classify patients into luminal A and B-like subtypes in order to inform treatment choice. Accounting for nearly 70% of all breast malignancies, luminal cancer is heterogeneous, harboring subtypes with distinct molecular profiles and clinical outcomes. Although most patients with luminal-type disease respond well to endocrine therapy alone, some develop recurrences benefiting from additional cytotoxic therapy. Identifying such cases a priori remains a challenge but would enable patients to be spared the debilitating side-effects of ineffective chemotherapy. In this regard, the efficacy of chemotherapy and disease recurrence relate to (i) ER driven G1/S perturbations and/or (ii) quiescent cell populations arrested in the G0/G1 phase of cell cycle. This study aimed to develop a histopathology whole slide image (WSI)-based, low cost, rapid and automated approach to: (i) predict ER/PR/Ki67 status, (ii) quantify quiescence burden, (iii) develop a G1/S-based patient stratification system for luminal A/B patients, and (iv) achieve a quiescence burden-based stratification of TNBC patients. Methods: This investigation centered on the initial clinical validation of a novel, immunostaining-free technology which uses information extracted from pre-treatment hematoxylin and eosin (H&E) stained slide WSIs alone to achieve these aims. Unlike conventional artificial intelligence-based approaches, the underlying proprietary algorithm and its prediction criteria are based on deterministic, hard-coded observational relationships of continuous scales drawn from WSI morphological features. In this instance, these represent tumor-related biological pathway disruptions and mitotic checkpoint perturbations, where G1/S perturbations enable luminal subtype stratification, and G0/G1 perturbations reflect quiescence burden. Back projecting the algorithm’s quiescence burden output on to the original WSIs enables morphological patterns to be mapped to quiescence burden.

scholarly journals Towards Iron-Titanium Oxide Nanostructures from Ecuadorian Black Mineral Sands

Minerals ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 122
Author(s):  
Karina J. Lagos ◽  
Bojan A. Marinkovic ◽  
Alexis Debut ◽  
Karla Vizuete ◽  
Víctor H. Guerrero ◽  
...  
Keyword(s):  
Electron Microscopy ◽  
Titanium Oxide ◽  
Low Cost ◽  
Mineral Resources ◽  
Added Value ◽  
Secondary Phases ◽  
Hydrothermal Route ◽  
Oxide Nanostructures ◽  
Transmission Electron ◽  
Pre Treatment

Ecuadorian black mineral sands were used as starting material for the production of iron-titanium oxide nanostructures. For this purpose, two types of mineral processing were carried out, one incorporating a pre-treatment before conducting an alkaline hydrothermal synthesis (NaOH 10 M at 180 °C for 72 h), and the other prescinding this first step. Nanosheet-assembled flowers and nanoparticle agglomerates were obtained from the procedure including the pre-treatment. Conversely, nanobelts and plate-like particles were prepared by the single hydrothermal route. The nanoscale features of the product morphologies were observed by scanning electron microscopy (SEM) and transmission electron microscopy (TEM) analyses. The ilmenite and hematite molar fractions, within the ilmenite-hematite solid solution, in the as-synthetized samples were estimated by Brown’s approach using the computed values of unit-cell volumes from Le Bail adjustments of X-ray powder diffraction (XRPD) patterns. The resulting materials were mainly composed of Fe-rich ilmenite-hematite solid solutions (hematite molar contents ≥0.6). Secondary phases, which possibly belong to lepidocrocite-like or corrugated titanate structures, were also identified. The current study demonstrated the feasibility of employing Ecuadorian mineral resources as low-cost precursors to synthesize high-added-value nanostructures with promising applications in several fields.

scholarly journals Prognostic Relevance of Neutrophil to Lymphocyte Ratio (NLR) in Luminal Breast Cancer: A Retrospective Analysis in the Neoadjuvant Setting

Cells ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1685
Author(s):  
Antonino Grassadonia ◽  
Vincenzo Graziano ◽  
Laura Iezzi ◽  
Patrizia Vici ◽  
Maddalena Barba ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Disease Free Survival ◽  
Post Treatment ◽  
Neutrophil To Lymphocyte Ratio ◽  
Luminal Breast Cancer ◽  
Luminal A ◽  
Luminal B ◽  
Lymphocyte Ratio ◽  
Cell Counts ◽  
Pre Treatment

The neutrophil to lymphocyte ratio (NLR) is a promising predictive and prognostic factor in breast cancer. We investigated its ability to predict disease-free survival (DFS) and overall survival (OS) in patients with luminal A- or luminal B-HER2-negative breast cancer who received neoadjuvant chemotherapy (NACT). Pre-treatment complete blood cell counts from 168 consecutive patients with luminal breast cancer were evaluated to assess NLR. The study population was stratified into NLRlow or NLRhigh according to a cut-off value established by receiving operator curve (ROC) analysis. Data on additional pre- and post-treatment clinical-pathological characteristics were also collected. Kaplan–Meier curves, log-rank tests, and Cox proportional hazards models were used for statistical analyses. Patients with pre-treatment NLRlow showed a significantly shorter DFS (HR: 6.97, 95% CI: 1.65–10.55, p = 0.002) and OS (HR: 7.79, 95% CI: 1.25–15.07, p = 0.021) compared to those with NLRhigh. Non-ductal histology, luminal B subtype, and post-treatment Ki67 ≥ 14% were also associated with worse DFS (p = 0.016, p = 0.002, and p = 0.001, respectively). In a multivariate analysis, luminal B subtype, post-treatment Ki67 ≥ 14%, and NLRlow remained independent prognostic factors for DFS, while only post-treatment Ki67 ≥ 14% and NLRlow affected OS. The present study provides evidence that pre-treatment NLRlow helps identify women at higher risk of recurrence and death among patients affected by luminal breast cancer treated with NACT.

scholarly journals Unmet need of essential treatments for critical illness in Malawi

2021 ◽  
Author(s):  
Raphael Kazidule Kayambankadzanja ◽  
Carl Otto Schell ◽  
Isaac Mbingwani ◽  
Samson Kwazizira Mndolo ◽  
Markus Castegren ◽  
...  
Keyword(s):  
Critical Illness ◽  
Low Cost ◽  
A Priori ◽  
Unmet Need ◽  
Vital Signs ◽  
Lateral Position ◽  
Cross Sectional Study ◽  
Cross Sectional ◽  
Oropharyngeal Airway ◽  
Conscious Level

AbstractBackgroundCritical illness is common throughout the world and has been the focus of a dramatic increase in attention in the COVID-19 pandemic. Severely deranged vital signs can identify critical illness, are simple to check and treatments that aim to correct derangements are established, basic and low-cost. The aim of the study was to estimate the unmet need of essential treatments for severely deranged vital signs in all adults admitted to hospitals in Malawi.MethodsWe conducted a cross-sectional study with follow-up of adult hospitalized patients in Malawi. All in-patients aged ≥18 on single days Queen Elizabeth Central Hospital (QECH) and Chiradzulu District Hospital (CDH) were screened.. Patients with hypoxia (oxygen saturation <90%), hypotension (systolic blood pressure <90mmHg) and reduced conscious level (Glasgow Coma Score <9) were included in the study. The a-priori defined essential treatments were oxygen therapy for hypoxia, intravenous fluid for hypotension and an action to protect the airway for reduced consciousness (placing the patient in the lateral position, insertion of an oropharyngeal airway or endo-tracheal tube or manual airway protection).ResultsOf the 1135 hospital in-patients screened, 45 (4.0%) had hypoxia, 103 (9.1%) had hypotension, and 17 (1.5%) had a reduced conscious level. Of those with hypoxia, 40 were not receiving oxygen (88.9%). Of those with hypotension, 94 were not receiving intravenous fluids (91.3%). Of those with a reduced conscious level, nine were not receiving an action to protect the airway (53.0%).ConclusionThere was a large unmet need of essential treatments for critical illness in two hospitals in Malawi.

Dietary Phytochemicals in Cancer Signalling Pathways: Role of miRNA targeting

2021 ◽  
Vol 28 ◽  
Author(s):  
Ambreen Shoaib ◽  
Mohammad Tabish ◽  
Shafat Ali ◽  
Azher Arafah ◽  
Muneeb U Rehman ◽  
...  
Keyword(s):  
Low Cost ◽  
Notch Pathway ◽  
Disease Recurrence ◽  
Genetic Mutation ◽  
Health Condition ◽  
Carnosic Acid ◽  
Signalling Pathways ◽  
Dietary Phytochemicals ◽  
Different Types ◽  
Regulatory Effects

: Cancer is a multi-factorial health condition involving uncontrolled cell divisions. The disease has its roots in genetic mutation. This disease affects men, women, and even children. Chemotherapy, photodynamic, photothermal, and hormonal therapies have been used to treat this deadliest disease but a huge percentage of patients have chances of disease recurrence or resistance. Nowadays dysregulation in miRNAs is considered one of the key factors for the development and progression of different types of cancers as they control the expression of genes responsible for cell proliferation, growth, differentiation, and apoptosis. Dietary phytochemicals with anticancer properties have been gaining focus for cancer treatment since they are found more effective in targeting cancer via regulating miRNAs expression. These phytochemicals have no side effects and are readily available at a low cost. Several dietary phytochemicals with regulatory effects on the expression of miRNAs have been reported and include curcumin, diallyl disulphide, 3, 30-diindolylmethane, ellagic acid, genistein, indole-3-carbinol, quercetin, resveratrol, and sulforaphane. They exert their regulatory effects against different types of cancer either by upregulating or downregulating different cancer signalling pathways and inhibit its progression. Curcumin down-regulates SHH pathways, epigallocatechin-3-gallate regulates the Notch pathway, inhibits TGFβ1/SMAD signalling, resveratrol regulates the Wnt/β-catenin pathway, and carnosic acid-induced apoptosis in colon cancer cell via JAK2/STAT3 signalling pathway. The miRNAs are used for the treatment of cancer as essential modulators in cellular pathways. Therefore, identifying the miRNAs and their targets and counter them with specific phytochemicals provides a safe and effective mechanism for the treatment of cancer.

732 TUMOR INFILTRATING NEUTROPHILS ARE A POOR PROGNOSTIC MARKER FOR ESOPHAGEAL CANCER PATIENTS RECEIVING NEOADJUVANT CHEMORADIOTHERAPY

2021 ◽  
Vol 34 (Supplement_1) ◽  
Author(s):  
Carlos Cabalag ◽  
Owen Prall ◽  
John Ciciulla ◽  
Laurence Galea ◽  
Niko Thio ◽  
...  
Keyword(s):  
Immune Cell ◽  
Residual Disease ◽  
Neoadjuvant Chemoradiotherapy ◽  
Treatment Resistance ◽  
Tumor Infiltrating Lymphocytes ◽  
Disease Recurrence ◽  
Expression Of Genes ◽  
Inflammatory Chemokines ◽  
Pre Treatment ◽  
Immune Related Genes

Abstract   Significant advances have been made in our understanding of the tumor immune microenvironment (TIM) and tumor infiltrating lymphocytes (TILs). Nevertheless, there is little understanding of the changes in the TIM in response to neoadjuvant chemoradiotherapy (CRT). Thus, our aim was to investigate the changes in the TIM with neoadjuvant CRT in EC by assessing the immune cell infiltrate, the expression of immune related genes, and their association with treatment response and prognosis. Methods To decipher the effects of neoadjuvant CRT on the TIM, we obtained 58 paired pre-treatment and post neoadjuvant CRT treated EC specimens. TILs and tumor infiltrating neutrophils (TIN) were quantified in pre-treatment biopsies and surgical resection specimens following neoadjuvant CRT. To evaluate the immune transcriptomics, RNA was extracted from these specimens and gene expression was assessed using the Nanostring Platform based on the PanCancer Immune Profiling Panel. Immunohistochemistry (IHC) was performed to validate findings from the immune transcriptomics. Results TIL counts were not prognostic for disease specific survival (DSS). We observed higher expression of immune-suppressive inflammatory chemokines (TGFß-1 and IL-16) in post-neoadjuvant treated samples compared to pre-treatment biopsies. In samples collected after neoadjuvant CRT, low expression of genes related to anti-tumor T cell cytotoxic activity1 was significantly associated with disease recurrence. In patients with residual disease, multivariate analysis revealed a high neutrophil count, but not TIL count, was significantly associated with inferior DSS (HR 3.8 [1.3– 10.8]; p = 0.01). Conclusion In EC, the tumor microenvironment after neoadjuvant CRT remains largely immune-suppressive. We discovered that the presence of TINs in patients with residual disease post neoadjuvant CRT is an independent adverse prognostic factor. Collectively, our results suggest that an inflammatory pro-tumoral microenvironment associated with TINs may contribute to treatment resistance and progressive disease in EC.

Digital histological markers based on routine H&E slides to predict benefit from maintenance immunotherapy in esophagogastric adenocarcinoma.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e16074-e16074
Author(s):  
Quoc Dang Vu ◽  
Caroline Fong ◽  
Katharina von Loga ◽  
Shan E Ahmed Raza ◽  
Daniel Nava Rodrigues ◽  
...  
Keyword(s):  
Molecular Markers ◽  
Predictive Power ◽  
Low Cost ◽  
Predictive Biomarkers ◽  
Operating Characteristics ◽  
Treatment Benefit ◽  
Platinum Based Chemotherapy ◽  
Slide Image ◽  
Tumor Mutational Burden ◽  
Hematoxylin And Eosin

e16074 Background: Immune checkpoint inhibition (ICI) is an effective treatment for a subset of patients with inoperable esophagogastric (EG) adenocarcinoma. Robust predictive biomarkers are required to identify these patients and a variety of strategies including immunohistochemical staining of PD-L1 and tumor mutational burden (TMB) assessment have been employed. Here, we explore digital histological (dHis) markers based on routine hematoxylin and eosin (H&E) slides alone or in combination with molecular markers (PD-L1 and TMB) as predictive biomarkers of benefit from maintenance immunotherapy in patients with inoperable EG adenocarcinoma. Methods: We developed a deep learning based algorithm to construct novel digital histological (dHis) markers by summarizing the statistics of all different types of nuclei present in the tumor tissue sections, their morphological features and their colocalization across each of the whole slide image. The dHis markers were then input into a decision-tree based approach to test for prognostic and predictive power alone or in combination with molecular markers. We assessed two cohorts of patients randomized to surveillance (n=38) or maintenance durvalumab (n=35) after 18 weeks of first-line platinum-based chemotherapy in the PLATFORM trial (NCT02678182) according to the 12-week progression-free rate. We measured the accuracy as the area under the receiver operating characteristics curve (AUROC) to determine the prognostic and predictive power of each marker set. We conducted a stratified 3-fold cross-validation, repeated 5 times and report the overall AUROC results. Results: Molecular markers alone yielded an AUROC of 0.5581±0.0939 on the surveillance arm, 0.6671±0.1479 on the treatment arm, and 0.6376±0.0958 for both the arms. Digital histological markers alone yielded an AUROC of 0.8952±0.0638, 0.8995±0.0719 and 0.8488±0.0700 on surveillance, immunotherapy and both arms, respectively. When using these two sets of markers together for both arms, molecular markers offered a limited improvement (around 0.02). Patients with TMB in the highest tertile were associated with lower likelihood of having progressive disease 12 weeks after randomization. Interestingly, dHis markers from morphology of connective and inflammatory nuclei were highly predictive for treatment benefit. Conclusions: Preliminary results suggest digital histological markers offer significant improvement over PD-L1 and TMB markers alone for predicting benefit from immunotherapy in EG adenocarcinoma with the added advantages of scalable, rapid, low-cost and objective quantification on routine histology sections. We are further validating their effectiveness on a larger cohort. Clinical trial information: NCT02678182.

scholarly journals 128 Factors Associated with Cost Savings Following Use of a Pharmacogenetic Assay in Individuals with Mood and Anxiety Disorders

CNS Spectrums ◽  
2020 ◽  
Vol 25 (2) ◽  
pp. 281-282
Author(s):  
Alison M Edwards ◽  
Roy H Perlis ◽  
David S Krause
Keyword(s):  
Bipolar Disorder ◽  
Anxiety Disorders ◽  
Low Cost ◽  
A Priori ◽  
Cost Savings ◽  
Initial Study ◽  
Baseline Period ◽  
Cost Difference ◽  
Outpatient Visits ◽  
Mood And Anxiety Disorders

Abstract:Background:In a study conducted in the database of a large commercial healthcare insurer, we previously demonstrated that use of a commercial pharmacogenetic assay for individuals with mood disorders was associated with decreased resource utilization and cost in the 6 month period following use compared to propensity-score matched controls. We conducted a post hoc analysis to understand variables associated with high cost savings.Methods:The results and methods of the initial study have previously been described. Cases were individuals with mood and anxiety disorders who received a commercial pharmacogenetic assay (Genomind, King of Prussia PA) to inform pharmacotherapy. 817 tested individuals (cases) with mood and/or anxiety disorders were matched to 2745 controls. Overall costs were estimated to be $1,948 lower in the tested group. The differences were largely the result of lesser emergency room and inpatient utilization for cases. In the present analysis, cost difference for cases compared to their matched controls was rank ordered by decile. High cost savers were arbitrarily defined a priori as the top 20% of savers. Using multivariable modeling techniques, an ordinal logistic regression model was generated in which baseline or follow-up variables were statistically tested for independent associations with high, low, and no cost savings.Results:606 (74%) of cases were net cost savers compared to their controls (cost difference <0). High cost savers (n=121) saved on average $10,690 compared to their matched controls. They were statistically more likely to have been diagnosed with bipolar disorder (n=33/121) than low cost savers (n=57/485) or non-savers (n=31/211), and had a lower Charlson Comorbidity index. High cost savers had fewer mean number of antidepressants in the baseline period (mean=3.16) compared to non-savers (3.73) but more than low cost savers (2.72) (p<0.05 across groups). In a multivariable model, bipolar, count of antidepressants, outpatient visits, and inpatient visits were statistically associated with being a high cost saver; antidepressant count and all-cause inpatient and outpatient visits in the baseline period were inversely associated with cost savings.Conclusions:Use of a pharmacogenetic assay was associated with cost-savings in the database of a large commercial insurer. Patients with bipolar disorder were more likely to be high cost savers than individuals with other mood and anxiety disorders.Funding Acknowledgements:Genomind

scholarly journals A Molecular Stratification of Chilean Gastric Cancer Patients with Potential Clinical Applicability

Cancers ◽  
2020 ◽  
Vol 12 (7) ◽  
pp. 1863
Author(s):  
Mauricio P. Pinto ◽  
Miguel Córdova-Delgado ◽  
Ignacio N. Retamal ◽  
Matías Muñoz-Medel ◽  
M. Loreto Bravo ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Latin American ◽  
Epithelial To Mesenchymal Transition ◽  
Low Cost ◽  
Molecular Classification ◽  
The Cancer Genome Atlas ◽  
Mesenchymal Transition ◽  
Barr Virus ◽  
Clinical Applicability ◽  
Stratification System

Gastric cancer (GC) is a complex and heterogeneous disease. In recent decades, The Cancer Genome Atlas (TCGA) and the Asian Cancer Research Group (ACRG) defined GC molecular subtypes. Unfortunately, these systems require high-cost and complex techniques and consequently their impact in the clinic has remained limited. Additionally, most of these studies are based on European, Asian, or North American GC cohorts. Herein, we report a molecular classification of Chilean GC patients into five subtypes, based on immunohistochemical (IHC) and in situ hybridization (ISH) methods. These were Epstein–Barr virus positive (EBV+), mismatch repair-deficient (MMR-D), epithelial to mesenchymal transition (EMT)-like, and accumulated (p53+) or undetected p53 (p53−). Given its lower costs this system has the potential for clinical applicability. Our results confirm relevant molecular alterations previously reported by TCGA and ACRG. We confirm EBV+ and MMR-D patients had the best prognosis and could be candidates for immunotherapy. Conversely, EMT-like displayed the poorest prognosis; our data suggest FGFR2 or KRAS could serve as potential actionable targets for these patients. Finally, we propose a low-cost step-by-step stratification system for GC patients. To the best of our knowledge, this is the first Latin American report on a molecular classification for GC. Pending further validation, this stratification system could be implemented into the routine clinic

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