Tool For Treatment Decisions Research Articles

Analysis of Healthcare Provider Practice Patterns from Individual Patient Cases Entered into an Online Treatment Decision Tool for Chronic Lymphocytic Leukemia (CLL)

BackgroundNew agent approvals and indications in CLL have changed treatment approaches and increased the complexity of managing CLL. Healthcare providers (HCPs), particularly those practicing in community settings with limited experience in caring for patients with CLL, can be challenged to make informed treatment decisions in this evolving treatment landscape. We report on an analysis of current CLL treatment patterns of HCPs using an online treatment decision tool developed by experienced CLL physicians from leading academic institutions and cancer centers (experts) to assist HCPs in their practice.MethodsSince 2016, CLL experts have developed and then twice updated (early 2016, late 2016, and 2017) an online treatment decision tool designed to provide specific recommendations for patient case scenarios entered by HCPs. For each iteration of the tool, 5 experts provided their treatment recommendations for hundreds of case variations based on key factors defined by the experts as those that guide treatment choices in their practice. Factors for newly diagnosed CLL included age, fitness (based on ECOG PS, CIRS, and renal function), cytogenetic abnormalities, and IGHV mutation status. Additional variables for patients with relapsed/refractory disease after first-line treatment included previous treatment, response duration, reason for switching therapy, burden of comorbidities, and disease-related symptoms. To use the tool, participating HCPs entered patient and disease factors along with their intended treatment plan for that case. When the entry of the case into the tool was completed, the 5 expert treatment recommendations for that specific patient case were shown, followed by a short survey designed to determine if the expert recommendations changed the HCPs' planned course of treatment. Our analysis includes a comparison of intended treatment of HCPs for 2198 cases entered into the tool (early 2016, n = 883; late 2016, n = 562; 2017, n = 753) with the expert recommendations for those patient cases.ResultsAlthough there was consensus among the experts (≥ 3 of 5 experts choosing the same treatment course) for 87% of cases included in the 2017 tool, there was substantial variation between the expert recommendations and the intended treatment of HCPs using the tool. In treatment-naive patients with del(17p) CLL in all 3 tool iterations, experts recommended ibrutinib as first-line therapy for 100% of cases regardless of any other variable, whereas only approximately 40% of HCPs planned to use ibrutinib for these patients.For young (< 65 years of age), fit patients with non-del(17p) CLL, the addition of IGHV mutation status as a factor in the late 2016 and 2017 tools changed expert recommendations. Experts recommended FCR for 60% (vs HCPs at 68%) and ibrutinib for 40% (vs HCPs at 14%) of cases with IGHV mutations. For cases without IGHV mutations, experts recommended FCR for 0% (vs HCPs at 53%), ibrutinib for 80% (vs HCPs at 18%), and BR for 20% (vs HCPs at 21%) of the cases. Similar treatment patterns are also seen with older or unfit patients with non-del(17p) CLL, where the expert recommended use of ibrutinib increased from early 2016 to 2017 (21% to > 65% of cases), whereas HCP use of ibrutinib remained consistent (15% to 20%).In patients with del(17p) CLL who progressed on first-line therapy, the approval of venetoclax changed treatment patterns among both experts and HCPs in the late 2016 and 2017 tools. In patient cases with del(17p) CLL who were discontinuing ibrutinib, experts consistently recommended venetoclax in 93% of cases (7% idelalisib + R for cases with intolerance to ibrutinib) vs HCPs using venetoclax for 59% and 69% of cases in late 2016 and 2017, respectively. For HCPs whose intended treatment differed from experts, 50% indicated that their treatment plan would change after using the tool (36% no/undecided and 14% reported barriers to change).ConclusionsPractice patterns between experts and HCPs differed substantially in their use of novel therapy for routine clinical practice. Expert recommendations in this online tool changed the intended treatment plan of HCPs using the tool and suggests that online treatment decision tools developed by respected experts can help optimize the care of patients with CLL. A full analysis of all cases entered into the tool, including a detailed report of expert and HCP practice trends, will be presented. DisclosuresCoutre:Gilead: Consultancy, Research Funding; Novartis: Consultancy, Research Funding; AbbVie: Consultancy, Research Funding; Janssen: Consultancy; Pharmacyclics LLC, an AbbVie Company: Consultancy, Research Funding; Celgene: Consultancy, Research Funding. Sharman:Novartis: Research Funding; Genentech: Research Funding; Gilead Sciences, Inc.: Consultancy, Honoraria, Research Funding, Speakers Bureau. Zelenetz:Amgen: Consultancy; Celgene: Consultancy.

Teratomatous Elements in Orchiectomy Specimens Are Associated with a Reduced Relapse-Free Survival in Metastasized Testicular Germ Cell Tumors

Introduction: The impact of teratomatous elements in orchiectomy specimens of metastasized testicular germ cell tumors (TGCT) regarding oncological outcome is still unclear. Methods: We performed a retrospective analysis including 146 patients with metastasized TGCT analysing patient characteristics. Results: Twenty-six (18%) of all patients showed teratomatous elements in the orchiectomy specimens. TGCT with teratomatous elements showed a significantly higher frequency of clinical-stage 2C-3 disease (73 vs. 49%, p = 0.031), visceral metastases (58 vs. 32%, p = 0.015), and poor prognosis (p = 0.011) than TGCT without teratomatous elements. Teratoma-containing TGCT revealed a significantly higher rate of post-chemotherapy retroperitoneal lymph node dissection (PC-RPLND, 54 vs. 32%, p = 0.041), with teratomatous elements being more often present in the PC-RPLND specimens (43 vs. 11%, p = 0.020) than nonteratoma-containing primaries. In the Kaplan-Meier estimates, the presence of teratomatous elements in orchiectomy specimens was associated with a significantly reduced relapse-free survival (RFS) (p = 0.049) during a median follow-up of 36 months (10–115.5). Conclusions: The presence of teratomatous elements in orchiectomy specimens is associated with an advanced tumor stage, worse treatment response as well as a reduced RFS in metastasized TGCT. Consequently, the presence of teratomatous elements might act as a reliable stratification tool for treatment decision in TGCT patients.

Gene expression-based outcome prediction in advanced stage classical Hodgkin lymphoma treated with BEACOPP

Classical Hodgkin Lymphoma (cHL) is a B cell-derived lymphoid malignancy, affecting 2.5–3/100,000 people per year. To date, in patients diagnosed with advanced cHL no reliable tool is able to—a priori—distinguish the subset of patients at high risk for relapse or refractory disease. Clinical risk indices for cHL, such as the International Prognostic Score (IPS), have not been successfully applied as a treatment decision tool in advanced stage cHL [1]. In this study we show, that a previously published gene expression-based predictor in advanced stage cHL patients treated with ABVD [2] does not prove prognostic in 401 BEACOPP-treated advanced stage cHL patients. Using transcriptome profiling, we identified however that three individual genes, PDGFRA, TNFRSF8 (encoding CD30) and CCL17 (encoding TARC), were significantly associated with progression-free survival (PFS) after multiple test correction in the BEACOPP-treated cohort, highlighting the potential of a modified gene expression profiling approach for pre-treatment risk assessment.

Elderly Glioma

Treatment of elderly glioma patients is a challenge in neurosurgery/neuro-oncology. The International Society of Geriatric Oncology(SIOG)recommends that elderly cancer patients undergo comprehensive geriatric assessment(CGA). The CGA score proved to be a significant predictor of mortality in this cohort, and it could be a useful treatment decision tool. Because of the rapid aging of Japan's population, clinical research focusing on elderly patients with cancer is urgently needed. The Japan Clinical Oncology Group(JCOG)has established a formal policy for research in geriatric cancers. Currently, the JCOG recommends that researchers perform CGA, including G8, to assess the tolerability of treatment for clinical trials in elderly cancer patients, including glioma. Under this policy, elderly cancer patients are categorized into three groups: fit, vulnerable, and frail. For "unfit" glioma/glioblastoma patients, physicians will need to conduct appropriately reduced treatment. Hypofractionated radiotherapy(40.05 Gy/15 fractions)has been an established treatment for elderly patients with glioblastoma. The concurrent and adjuvant temozolomide have reported to have a survival benefit for "fit" elderly patients. Subsequently, alternative hypofractionated radiotherapy, including 34 Gy/10 fractions and monotherapy with temozolomide against MGMT methylated glioblastomas, have been reported as non-inferior alternative treatments. Physicians also need to consider the adverse events associated with anticonvulsants.

Adjuvant chemotherapy in stage II and III colon cancer: the role of the \u201cbudding and TILs-(tumor-infiltrating lymphocytes) combination\u201d as tumor-host antagonists

PurposeTo analyze the influence of adjuvant chemotherapy on the combination of tumor budding and tumor-infiltrating lymphocytes (TILs) in stage II and III colon cancer and to elucidate its potential value for adjuvant treatment decisions.Methods306 patients with stage II and 205 patients with stage III colon cancer diagnosed between 2005 and 2016 who had undergone surgery in a curative setting were enrolled. Budding and TILs were assessed according to the criteria of the International Tumor Budding Consensus Conference (ITBCC) and the criteria of the International TILs Working Group (ITWG). Combinations of budding and TILs were analyzed, and the influence of adjuvant chemotherapy was assessed.ResultsIn stage II colon cancer, stratification into the four budding/TILs groups showed no significant differences in overall survival (OS) between the chemotherapy and the surgery-alone group, not even in cases with high-risk features. In stage III colon cancer, patients with low budding/high TILs benefited significantly from chemotherapy (p=0.005). Patients with high budding/low TILs as well as high budding/high TILs showed a trend to benefit from adjuvant treatment. However, no chemotherapy benefit was seen for the low budding/low TIL group.ConclusionsThe budding/TIL combination identified subgroups in stage II and III colon cancer with and without benefit from adjuvant treatment. The results this study suggest that the combination of budding and TILs as tumor-host antagonists might be an additional helpful tool in adjuvant treatment decisions in stage II and III colon cancer.

The Validity and Reliability of the Turkish Version of MacArthur Competence Assessment Tool for Treatment Decision: Correlates of Competence in Schizophrenia Patients.

Introduction:Informed consent is an indispensable condition of the clinical practice for the provision of health care. The main objective of this study is to translate the MacArthur competence assessment tool for treatment (MacCAT-T) into Turkish and evaluate the validity and reliability of the Turkish version in schizophrenia patients and healthy control subjects.Methods:In this cross-sectional study, 30 hospitalized schizophrenia patients and 25 healthy subjects were assessed with MacCAT-T, Mental Competence Evaluation Form for Assessment of Competency (MCEF), Positive and Negative Syndrome Scale, Beck Depression Inventory, Mini Mental State Examination, Wechsler Adult Intelligence Scale (WAIS) – Similarities subtest and the Schedule for Assessing the Three Components of Insight. Psychometric properties of MacCAT-T were examined by intra-class correlation coefficients and Cronbach’s alpha values.Results:Intra-class correlations ranged between 0.83 and 0.99 for four subscales of the tool. Cronbach alpha value of MacCAT-T was found 0.89. Severity of psychopathology and indices of insight were found to be negatively correlated with the subscales of the tool. WAIS-Similarities subtest scores were found to be positively correlated with understanding and reasoning subscales of MacCAT-T.Conclusion:The Turkish version of MacCAT-T is a valid and reliable instrument for Turkish patients. The severity of psychopathology, insight and executive functions were shown to be significantly related to the decision making capacity in patients with schizophrenia.

Evolving Treatment Patterns in Chronic Lymphocytic Leukemia Among Experts and Community Practitioners: Analysis of an Online Decision Support Tool

Evolving Treatment Patterns in Chronic Lymphocytic Leukemia Among Experts and Community Practitioners: Analysis of an Online Decision Support Tool

Antibiotic prescribing and non-prescribing in nursing home residents with signs and symptoms ascribed to urinary tract infection (ANNA): study protocol for a cluster randomized controlled trial

BackgroundAntibiotic overprescribing for suspected urinary tract infection (UTI) in nursing homes (NHs) is common. Typical clinical scenarios in which antibiotics are inappropriately prescribed include response to nonspecific signs and symptoms and/or a positive urine test in the absence of symptoms referable to the urinary tract. These and other scenarios for inappropriate antibiotic prescribing were addressed in a recent international Delphi study which resulted in the development of a decision tool for the empiric treatment of UTI in frail older adults. The aim of the current study is to implement this decision tool, by integrating it into the electronic health record (EHR) and providing education on its content and use, and to evaluate its effect on appropriate antibiotic prescribing. An additional aim is to evaluate the quality of the intervention and the implementation process.MethodsA cluster Randomized Controlled Trial (cRCT) is conducted in sixteen NHs and aims to include 897 residents diagnosed with suspected UTI. NHs in the intervention group use the EHR-integrated decision tool, and receive education for physicians and nursing staff; in the control group care as usual is provided. Data is collected through case report forms within the EHR at the day of diagnosis and at 3, 7, and 21 days thereafter. The primary outcome is appropriate antibiotic prescribing for suspected UTI at the day of diagnosis. Secondary outcomes include the course of symptoms, alternative diagnoses, treatment changes, complications, hospitalization, and mortality. Data on total antibiotic prescribing are additionally collected in the participating NHs 12 months before and during the study. Finally, the process evaluation combines cRCT data with questionnaires and qualitative interviews with NH professionals.DiscussionThis is the first cRCT to evaluate the recently developed, international decision tool for empiric treatment of suspected UTI in NH residents. Study findings will elucidate the effect of the intervention on appropriate antibiotic prescribing for suspected UTI, and provide insight into the applicability of the decision tool in NHs in general and in specific subgroups of NH residents. With this study we aim to contribute to antibiotic stewardship efforts in long-term care.Trial registrationThe ANNA study was registered at the Netherlands Trial Register on 26 February 2019, with identification number NTR NL7555.

Hereditary breast cancer: translation into clinical practice of recent American Society of Clinical Oncology, American Society of Radiation Oncology, and Society of Surgical Oncology recommendations.

Scientific acquisitions concerning the risk of breast cancer in the context of hereditary breast cancer syndrome are constantly evolving: alongside the BRCA1 and BRCA2 mutations, further ones have been identified, also associated with malignancies in different sites. Therefore, management of these clinical conditions requires a multidisciplinary and shared approach, based on constantly updated guidelines. The recent Expert Panel Consensus about management of hereditary breast cancer, chaired by the Society of Surgical Oncology with the American Society of Clinical Oncology and the American Society of Radiation Oncology, based on the evidences obtained by a systematic review of the literature, delineate accurate and novel directions towards an appropriate surgical, radiation, and systemic therapy management of breast cancer patients with specific germline mutations. These recent recommendations will provide to physicians an updated and useful tool in treatment decision making of these patients in daily practice.

Deep learning for risk prediction in patients with nasopharyngeal carcinoma using multi-parametric MRIs

BackgroundMagnetic resonance images (MRI) is the main diagnostic tool for risk stratification and treatment decision in nasopharyngeal carcinoma (NPC). However, the holistic feature information of multi-parametric MRIs has not been fully exploited by clinicians to accurately evaluate patients. ObjectiveTo help clinicians fully utilize the missed information to regroup patients, we built an end-to-end deep learning model to extract feature information from multi-parametric MRIs for predicting and stratifying the risk scores of NPC patients. MethodsIn this paper, we proposed an end-to-end multi-modality deep survival network (MDSN) to precisely predict the risk of disease progression of NPC patients. Extending from 3D dense net, this proposed MDSN extracted deep representation from multi-parametric MRIs (T1w, T2w, and T1c). Moreover, deep features and clinical stages were integrated through MDSN to more accurately predict the overall risk score (ORS) of individual NPC patient. ResultA total of 1,417 individuals treated between January 2012 and December 2014 were included for training and validating the end-to-end MDSN. Results were then tested in a retrospective cohort of 429 patients included in the same institution. The C-index of the proposed method with or without clinical stages was 0.672 and 0.651 on the test set, respectively, which was higher than the that of the stage grouping (0.610). ConclusionsThe C-index of the model which integrated clinical stages with deep features is 0.062 higher than that of stage grouping alone (0.672 vs 0.610). We conclude that features extracted from multi-parametric MRIs based on MDSN can well assist the clinical stages in regrouping patients.

Real World Evidence on Second-Line Palliative Chemotherapy in Advanced Pancreatic Cancer

Background: The outcome and tolerability of palliative second line chemotherapy for advanced pancreatic cancer (APC) in real life patients are largely unknown. Prognostic parameters for risk stratification and treatment guidance are lacking.Materials and Methods: A population based multicenter retrospective cohort study was conducted, covering all APC patients who received palliative second-line chemotherapy between 2011 and 2018 at any cancer center in the South East Region of Sweden. Primary outcome was overall survival after second-line therapy (OS2). Time to treatment failure after second-line therapy (TTF2), hematological toxicity, and unplanned hospitalizations were key secondary outcomes. A number of baseline potentially prognostic parameters were assessed.Results: A total of 509 patients received first-line palliative chemotherapy, and of these 167 (33%) received at least one dose of second-line therapy and formed the final study population. Median OS2 was 5.2 months (95% CI = 4.7–5.7) and median TTF2 was 1.9 months (1.5–2.2). OS2 and TTF2 were similar regardless regimen, including comparison of the two most common regimens (fluoropyrimidine monotherapy vs. fluoropyrimidine/oxaliplatin doublet). Multivariate analysis revealed that normal plasma albumin (≥35) and serum CA-19-9 above median (>1,550) were independent predictors for OS2 (HR = 0.21, p < 0.001 and HR = 2.03, p = 0.009) and TTF2 (HR = 0.22, p < 0.001 and HR = 2.03, p = 0.01), while ECOG performance status >1 was predictive for TTF2 (HR = 2.05, p = 0.032). Grade 3–4 hematological toxicity was registered in 17 patients (10%). 50 (30%) had at least one event of hospitalization.Conclusion: The real world outcome of second line palliative chemotherapy for refractory APC remains dismal. Baseline plasma albumin, serum CA-19-9, and performance status emerge as key prognostic factors, and should be further studied as tools for individualized treatment decisions.

Serum ceruloplasmin can predict liver fibrosis in hepatitis B virus-infected patients.

BACKGROUNDThe presence of significant liver fibrosis in hepatitis B virus (HBV)-infected individuals with persistently normal serum alanine aminotransferase (PNALT) levels is a strong indicator for initiating antiviral therapy. Serum ceruloplasmin (CP) is negatively correlated with liver fibrosis in HBV-infected individuals.AIMTo examine the potential value of serum CP and develop a noninvasive index including CP to assess significant fibrosis among HBV-infected individuals with PNALT.METHODSTwo hundred and seventy-five HBV-infected individuals with PNALT were retrospectively evaluated. The association between CP and fibrotic stages was statistically analyzed. A predictive index including CP [Ceruloplasmin hepatitis B virus (CPHBV)] was constructed to predict significant fibrosis and compared to previously reported models.RESULTSSerum CP had an inverse correlation with liver fibrosis (r = -0.600). Using CP, the areas under the curves (AUCs) to predict significant fibrosis, advanced fibrosis, and cirrhosis were 0.774, 0.812, and 0.853, respectively. The CPHBV model was developed using CP, platelets (PLT), and HBsAg levels to predict significant fibrosis. The AUCs of this model to predict significant fibrosis, advanced fibrosis, and cirrhosis were 0.842, 0.920, and 0.904, respectively. CPHBV was superior to previous models like the aspartate aminotransferase (AST)-to-PLT ratio index, Fibrosis-4 score, gamma-glutamyl transpeptidase-to-PLT ratio, Forn’s score, and S-index in predicting significant fibrosis in HBV-infected individuals with PNALT.CONCLUSIONCPHBV could accurately predict liver fibrosis in HBV-infected individuals with PNALT. Therefore, CPHBV can be a valuable tool for antiviral treatment decisions.

Researchers explore new prognostic, predictive tools for cancer: Easily attainable markers and measurements may help to better inform treatment decision making.

Researchers explore new prognostic, predictive tools for cancer: Easily attainable markers and measurements may help to better inform treatment decision making.

Sorafenib Resistance in Hepatocellular Carcinoma: The Relevance of Genetic Heterogeneity.

Despite advances in biomedicine, the incidence and the mortality of hepatocellular carcinoma (HCC) remain high. The majority of HCC cases are diagnosed in later stages leading to the less than optimal outcome of the treatments. Molecular targeted therapy with sorafenib, a dual-target inhibitor targeting the serine-threonine kinase Raf and the tyrosine kinases VEGFR/PDGFR, is at present the main treatment for advanced-stage HCC, either in a single or combinatory regimen. However, it was observed in a large number of patients that its effectiveness is hampered by drug resistance. HCC is highly heterogeneous, within the tumor and among individuals, and this influences disease progression, classification, prognosis, and naturally cellular susceptibility to drug resistance. This review aims to provide an insight on how HCC heterogeneity influences the different primary mechanisms of chemoresistance against sorafenib including reduced drug intake, enhanced drug efflux, intracellular drug metabolism, alteration of molecular targets, activation/inactivation of signaling pathways, changes in the DNA repair machinery, and negative balance between apoptosis and survival of the cancer cells. The diverse variants, mutations, and polymorphisms in molecules and their association with drug response can be a helpful tool in treatment decision making. Accordingly, the existence of heterogeneous biomarkers in the tumor must be considered to strengthen multi-target strategies in patient-tailored treatment.

Immunoscore as a parameter predicting time to recurrence and disease-free survival in T4N0 stage II colon cancer patients.

4105 Background: Risk assessment is particularly important to decide when to propose an adjuvant treatment for Stage II Colon Cancer (CC) patients. However, the current tumor risk features are imperfect and additional risk factors are needed to guide treatment decisions. The consensus Immunoscore is an alternative and powerful approach that could be used in the T4N0 Stage II colon cancer population. Immunoscore is an in vitro diagnostic test that predicts the risk of relapse in patients with CC by measuring the host immune response at the tumor site. Methods: From the international Immunoscore consortium study (n = 2681) (Pagès et al. The Lancet 2018), a subgroup analysis was performed on T4N0 Stage II colon cancer patients (n = 208). Results: In stage II T4N0, Int+Hi Immunoscore represented 65.4% of the population and low-Immunoscore only 34.6%. T4N0 patients with Int+Hi Immunoscore presented a significantly prolonged survival for TTR compared to low Immunoscore patients (5 years recurrence rate Int+Hi: 84.6% (78.3-91.5), Lo: 46.3% (35.1-61); unadjusted HR [Int+Hi vs Lo] = 0.21; (95% CI 0.11-0.4); P&lt; 0.0001), representing a restricted mean survival time (RMST) difference of 80.9 months (95% CI 51.1-110.6) ( P&lt; 0.0001). The DFS was significantly different between Int+Hi and Low Immunoscore (5 years recurrence rate Int+Hi: 70.5% (95% CI 62.7-79.1), Lo: 38.5% (95% CI 28.2-52.5); unadjusted HR [Int+Hi vs Lo] = 0.31; (95% CI 0.19-0.49); P&lt; 0.0001). Using restricted mean survival time (RMST) a significant ( P&lt; 0.0001) difference of 60.4 months (95% CI 32.6-88.1) was observed between the 2 groups Importantly, Cox multivariate analysis in Stage II T4N0 colon cancer patients, revealed that Immunoscore was the only remaining significant parameter (HR [Int+Hi vs Lo] = 0.15; (95% CI 0.05-0.46); P= 0.0009). In contrast, all other parameters, gender, sidedness, mucinous, grade, T-stage, VELIPI, MSI were not significant in multivariate analysis. Finally, Immunoscore showed the highest relative contribution to predict relapse (76.2% chi2 relative contribution), stronger than all the other parameters, MSI (16.1%), Grade (5%), sidedness (2%), gender (2%), VELIPI (1%). Conclusions: Immunoscore is the most powerful parameter to predict the risk in T4N0 population, and could be a good tool for adjuvant treatment decision in Stage II patients.

Treatment Motivations and Expectations in Patients with Actinic Keratosis: A German-Wide Multicenter, Cross-Sectional Trial.

Patient-centered motives and expectations of the treatment of actinic keratoses (AK) have received little attention until now. Hence, we aimed to profile and cluster treatment motivations and expectations among patients with AK in a nationwide multicenter, cross-sectional study including patients from 14 German skin cancer centers. Patients were asked to complete a self-administered questionnaire. Treatment motives and expectations towards AK management were measured on a visual analogue scale from 1–10. Specific patient profiles were investigated with subgroup and correlation analysis. Overall, 403 patients were included. The highest motivation values were obtained for the items “avoid transition to invasive squamous cell carcinoma” (mean ± standard deviation; 8.98 ± 1.46), “AK are considered precancerous lesions” (8.72 ± 1.34) and “treating physician recommends treatment” (8.10 ± 2.37; p < 0.0001). The highest expectation values were observed for the items “effective lesion clearance” (8.36 ± 1.99), “safety” (8.20 ± 2.03) and “treatment-related costs are covered by health insurance” (8.00 ± 2.41; p < 0.0001). Patients aged ≥77 years and those with ≥7 lesions were identified at high risk of not undergoing any treatment due to intrinsic and extrinsic motivation deficits. Heat mapping of correlation analysis revealed four clusters with distinct motivation and expectation profiles. This study provides a patient-based heuristic tool for a personalized treatment decision in patients with AK.

Electrochemical Microarray System for Acute Biomarker Detection Assessment for Point-of-Care (POC) Cancer Diagnosis

The research on biomarker detection has increased dramatically in recent years and many strategies has emerged. However, current methods for identifying specific biomarkers and small molecules for point of care (POC) diagnosis outcomes suffer shortcomings of limited specificity and complex procedure in the measurement and the lack of real-time analysis to establish a causal relationship between an individual's profile and impact on health. The goals of our research are 1) to provide researchers with a new tool to better assess the impacts of biomarkers and small molecules for the cancer diagnosis and treatment and 2) to provide individuals with an inexpensive benchtop device for rapid reporting of exposure data for personalized alerts and managed care services. To achieve these goals, we are exploring several key technologies and approaches that will enable implementation of a novel autonomous sensorarray microsystem for acute multi-analyte assessment, such as sulfatases, antibody/antigen and micro-RNA/RNA, with the sensitive real-time monitoring. Electrochemistry signals were classified and quantified during the bio-interactions on the designed electrode interface, exhibiting the excellent sensitivity and specificity for targeting biomarkers without adding signal media and label. This project would provide medical researchers and physicians with a much needed and currently non-existent tool for personal treatment assessment and decision, leading to more relevant disease regulation, intervention for individuals diagnosis, and ultimately improvement of overall public health.

Diffusion-Weighted-Imaging infarct volume measurement tools show discrepancies leading to diverging thrombectomy decisions

Background and purposeRecent clinical trials demonstrated the benefit of thrombectomy beyond 6h based on the automated measurement of infarct volume exclusively with the RAPID software. We aimed to compare eight tools commonly used for the measurement of infarct volume and see whether they would lead to similar thrombectomy decisions based on the Diffusion-weighted-imaging or computerized-tomography-perfusion Assessment with clinical mismatch in the triage of Wake-up and late-presenting strokes undergoing Neurointervention with Trevo (DAWN) trial imaging inclusion criteria. Materials and MethodsThe diffusion-weighted-imaging (DWI) infarct volume of 36 patients was measured with 3 automated tools (including RAPID) and 5 non-automated tools. The agreement for the measurements of DWI infarct volume and the resulting thrombectomy decisions were assessed with intraclass correlation coefficient (ICC) and Fleiss’ Kappa (K) statistics. ResultsThe correlation for the measurement of DWI infarct volume between all 9 tools was excellent (ICC>0.8). After dichotomization, agreement was substantial for any of the cut-points used in DAWN trial. Discrepancies involving at least one of the tools for thrombectomy decisions based on DAWN criteria occurred in one third of cases. Compared with RAPID, the use of any other tool for treatment decision based on DAWN criteria would have led to contradictory decisions in 6% to 19% of cases. ConclusionThere are several currently available tools for the measurement of DWI infarct volume with excellent correlation. Despite the high agreement demonstrated in our study, frequent discrepancies between measurements in some dichotomized configurations led to frequent diverging thrombectomy decisions when applying DAWN criteria.

Implications of the 21-gene recurrence score assay (Oncotype DX) on adjuvant treatment decisions in ER-positive early-stage breast cancer patients: experience of Kuwait Cancer Control Center

BackgroundThe Oncotype DX is a quantitative assay of the expression of 16 tumor-related genes and 5 reference genes that predicts the potential of adjuvant chemotherapy benefit in estrogen receptor (ER)-positive early breast cancer patients. The study aims to evaluate the impact of Oncotype DX as a tool for adjuvant treatment decision of ER-positive, HER2-negative, N0/N1 early-stage breast cancer patients and to determine which clinicopathological criteria derived the greatest advantage.ResultsA hundred patients at a median age of 50 years were included. TNM stage distribution was 34, 63, and 3 patients for stages I, II, and IIIA respectively. Fifty-four patients had luminal A and 46 had luminal B tumors. The recurrence score (RS) results were low, intermediate, and high risk in 54, 34, and 12 patients respectively. Before the test results, adjuvant chemoendocrine therapy (CET) was recommended for 46 patients while 54 were advised for endocrine therapy (ET). After getting the test results, 25 patients received CET (1, 12, and12 patients in the low-, intermediate-, and high-risk groups respectively) and 75 received ET. Treatment change was documented in 37 patients (8 patients from ET to CET and 29 from CET to ET; p = 0.001, McNemar test). Treatment change was significant among patients ≤ 50 years, luminal B tumors, stage II and IIIA disease, and node-positive disease.ConclusionOncotype DX testing resulted in significant changes in the adjuvant treatment decisions in ER-positive, HER2-negative early breast cancer particularly in the case of young, luminal B, N1, and stage II–IIIA disease.

Biomarkers of vascular disease in diabetes: the adipose-immune system cross talk.

Experimental and clinical studies aimed at investigating the mechanism(s) underlying vascular complications of diabetes indicate that a great number of molecules are involved in the pathogenesis of these complications. Most of these molecules are inflammatory mediators or markers generated by immune or adipose tissue. Some of them, i.e. resistin and sortilin, have been shown to be involved in the cross talk between adipocytes and inflammatory cells. This interaction is an attractive area of research, particularly in type 2 diabetes and obesity. Other proteins, such as adiponectin and visfatin, appear to be more promising as possible vascular markers. In addition, some molecules involved in calcium/phosphorus metabolism, such as klotho and FGF23, have an involvement in the pathogenesis of diabetic vasculopathy, which appears to be dependent on the degree of vascular impairment. Inflammatory markers are a promising tool for treatment decisions while measuring plasma levels of adipokines, sortilin, Klotho and FGF23 in adequately sized longitudinal studies is expected to allow a more precise characterization of diabetic vascular disease and the optimal use of personalized treatment strategies.