Specificity For Diagnosis Of Cancer Research Articles

Predictive value of abnormal blood tests for detecting cancer in primary care patients with nonspecific abdominal symptoms: A population-based cohort study of 477,870 patients in England.

Identifying patients presenting with nonspecific abdominal symptoms who have underlying cancer is a challenge. Common blood tests are widely used to investigate these symptoms in primary care, but their predictive value for detecting cancer in this context is unknown. We quantify the predictive value of 19 abnormal blood test results for detecting underlying cancer in patients presenting with 2 nonspecific abdominal symptoms. Using data from the UK Clinical Practice Research Datalink (CPRD) linked to the National Cancer Registry, Hospital Episode Statistics and Index of Multiple Deprivation, we conducted a population-based cohort study of patients aged ≥30 presenting to English general practice with abdominal pain or bloating between January 2007 and October 2016. Positive and negative predictive values (PPV and NPV), sensitivity, and specificity for cancer diagnosis (overall and by cancer site) were calculated for 19 abnormal blood test results co-occurring in primary care within 3 months of abdominal pain or bloating presentations. A total of 9,427/425,549 (2.2%) patients with abdominal pain and 1,148/52,321 (2.2%) with abdominal bloating were diagnosed with cancer within 12 months post-presentation. For both symptoms, in both males and females aged ≥60, the PPV for cancer exceeded the 3% risk threshold used by the UK National Institute for Health and Care Excellence for recommending urgent specialist cancer referral. Concurrent blood tests were performed in two thirds of all patients (64% with abdominal pain and 70% with bloating). In patients aged 30 to 59, several blood abnormalities updated a patient's cancer risk to above the 3% threshold: For example, in females aged 50 to 59 with abdominal bloating, pre-blood test cancer risk of 1.6% increased to: 10% with raised ferritin, 9% with low albumin, 8% with raised platelets, 6% with raised inflammatory markers, and 4% with anaemia. Compared to risk assessment solely based on presenting symptom, age and sex, for every 1,000 patients with abdominal bloating, assessment incorporating information from blood test results would result in 63 additional urgent suspected cancer referrals and would identify 3 extra cancer patients through this route (a 16% relative increase in cancer diagnosis yield). Study limitations include reliance on completeness of coding of symptoms in primary care records and possible variation in PPVs if extrapolated to healthcare settings with higher or lower rates of blood test use. In patients consulting with nonspecific abdominal symptoms, the assessment of cancer risk based on symptoms, age and sex alone can be substantially enhanced by considering additional information from common blood test results. Male and female patients aged ≥60 presenting to primary care with abdominal pain or bloating warrant consideration for urgent cancer referral or investigation. Further cancer assessment should also be considered in patients aged 30 to 59 with concurrent blood test abnormalities. This approach can detect additional patients with underlying cancer through expedited referral routes and can guide decisions on specialist referrals and investigation strategies for different cancer sites.

Enhancing decision-making in breast cancer diagnosis for women through the application of nano beta open sets

Nano topology is a modern type of topology based on rough sets, introducing nano open sets and their properties. This study explores the new properties of nano-β-open sets and nano-closures in nano topological space, providing some equivalent definitions, theorems, and lemmas for illustration. The effectiveness of incorporating nano β-open sets in medical decision-making is demonstrated in diagnosing breast cancer in two cases for women. Results indicated that utilizing nano open sets enhanced the accuracy, sensitivity, and specificity of cancer diagnosis. Additionally, an algorithm has been developed to aid clinicians in diagnosing breast cancer infections. The overarching objective is to provide physicians with a valuable tool to make informed decisions and reach optimal conclusions in patient care.

Altered serum metabolome as an indicator of paraneoplasia or concomitant cancer in patients with rheumatic disease

ObjectivesA timely diagnosis is imperative for curing cancer. However, in patients with rheumatic musculoskeletal diseases (RMDs) or paraneoplastic syndromes, misleading symptoms frequently delay cancer diagnosis. As metabolic remodelling characterises both...

Abstract 311: Development of cludin-3 specific human monoclonal antibody(ABN501) as therapeutic anti-tumor agents

Abstract The tight junctions of epithelial tissues, that most malignant tumors are derived from, are associated in cell-cell interactions. Among the tight junction proteins, claudin-3 (CLDN3) is overexpressed in many types of solid cancers, such as breast, ovarian, colorectal, and gastric cancers. Although CLDN3 can be potential therapeutic target due to the overexpression in various types of cancers, high homology with other CLDN family members is a hurdle to develop antibodies specifically targeting CLDN3. In this study, human IgG1 monoclonal antibody (ABN501) against CLDN3 was developed by scFv phage display using CLDN3-overexpressing stable cells and CLDN3-embedded lipoparticles as antigens. It was confirmed that ABN501 specifically bound to human and mouse CLDN3 without cross-reactivity to other CLDN family members. Sub-nanomolar affinity in binding kinetics of ABN501 was measured in CLDN3 expressing cell lines. We observed the antibody-dependent cytotoxicity (ADCC) activity of ABN501 with human NK cells expressing CD16a (NK-92MI-CD16a), in various cancer cell lines according to CLDN3 expression levels. We also confirmed that ABN501 specifically targeted CLDN3-expressing tumors in biodistribution assay using fluorescence-conjugated ABN501. In addition, ABN501 showed anti-tumor effects when treated with NK-92MI-CD16a in xenograft mice bearing CLDN3 expressing tumors. Taken these results together, we suggest that ABN501, specifically recognizing to CLDN3, can be used as therapeutic agents for CLDN3 positive cancer, and developed in many different forms to treat cancers with its specificity for cancer diagnosis, antibody-drug conjugates, and chimeric antigen receptor (CAR) immunotherapy. Citation Format: Hong-Seok Choi, Euni Sim, Na Young Kim, Yong Jin Lee, Sae Hyung Lee, Hayeon Park, Hobin Yang, Jiwon Jo, Myeung-Ryun Seo, Heegeon Park, Ji-Hye Lee, Sungyoul Hong, Young Kee Shin, Jun-Young Choi. Development of cludin-3 specific human monoclonal antibody(ABN501) as therapeutic anti-tumor agents [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 311.

Multiplex measurement of twelve tumor markers using a GMR multi-biomarker immunoassay biosensor

Tumor markers play an important role in the early diagnosis and therapeutic effect monitoring of tumors. Combined detection of multiple tumor markers is a realistic way of improving the sensitivity and specificity of cancer diagnosis. To achieve this, we studied and designed a giant magneto resistance (GMR) multi-biomarker immunoassay biosensor that can simultaneously detect twelve kinds of tumor markers by integrating a GMR sensor chip, a microfluidic device, a magnetic nano-beads label, and a double antibody sandwich immunoassay method. As a proof of concept, the proposed immunosensor was utilized to detect 12 tumor markers (AFP, CEA, CYFRA21-1, NSE, SCC, PG I, PG II, CA19-9, total PSA, free PSA, free-β-hCG, Tg) and to screen patients with lung cancer, liver cancer, digestive tract cancer, prostatic cancer, etc. The immunosensor showed excellent sensitivity, accuracy, precision and stability. Designed as a POCT device, the immunosensor also allows for portability, able to perform rapid detection wherever necessary. As a multi-analyte assay, it provides significant advantages over single-analyte tests in terms of cost per test, labor and convenience. The system's ability to simultaneously measure the concentration of multiple markers in serum samples with excellent sensitivity and accuracy allows the immunosensor to be used for early tumor diagnosis.

The diagnosis of cancer in thyroid fine needle aspiration biopsy. Surgery, repeat biopsy or specimen consultation?

Fine needle aspiration biopsy (FNA) is the only diagnostic method that allows a preoperative diagnosis of thyroid carcinoma. An unequivocal diagnosis of a malignant change is achievable only in cases in which all cytological criteria of carcinoma are met. The aim of the study was to evaluate the necessity of repeat thyroid FNA in patients with papillary thyroid carcinoma verified on consultative examination (CE). We analyzed cytology reports of thyroid FNA and CE that resulted in the diagnosis of papillary carcinoma. Evaluation of the correlation of the cytological diagnosis with the histopathology report was based on data obtained after the surgery. Between 2010 and 2015 in the Institute of Oncology (IO) there were 184 cancers diagnosed on CE or in thyroid FNA performed primarily in IO. Additionally, 74 patients were subjected to repeat biopsy after confirmation of cancer in CE. Histopathological diagnosis of cancer was obtained in 62 (100%) cases that were doubly confirmed with cytological examination. The remaining 12 patients were operated on outside the institute. From 110 FNA primarily performed in the IO, histopathological verification was achievable in 92 cases, from which 92 (100%) provided a confirmation of cancer, and the remaining 18 patients were operated on outside the institute. High (100%) specificity of cancer diagnosis in FNA established primarily and verified on CE (second independent assessment) indicates that repeat FNA in order to confirm the diagnosis is unnecessary.

Cancer and Diverticulitis of the Sigmoid Colon. Differentiation with Computed Tomography Versus Magnetic Resonance Imaging: Preliminary Experiences

Both colon cancer and diverticular disease are common in the Western world. A challenge when patients present with clinical findings is that both diseases can present with symptoms that may mimic the other. To determine whether magnetic resonance imaging (MRI) could be helpful to differentiate between diverticulitis and cancer of the sigmoid colon compared to the differentiation offered by evaluation of multidetector computed tomography (CT) in a clinical situation. Thirty patients were consecutively included. Fifteen patients were under work-up for a recently diagnosed sigmoid cancer and 15 patients had recently been treated in hospital due to first-time acute sigmoid diverticulitis. All patients underwent CT, T2- weighted MRI and diffusion-weighted MRI. Anonymized examinations were retrospectively presented in random order to one experienced radiologist. With contrast-enhanced CT, the sensitivity and specificity for diagnosis of cancer and diverticulitis were 66.7% (10/15) and 93.3% (14/15), respectively. Using T2-weighted and diffusion-weighted MR images, the sensitivity and specificity for diagnosis of cancer and diverticulitis were 100% (14/14) and 100% (14/14), respectively. MRI provides information that may contribute to improve the differentiation between sigmoid cancer and diverticulitis that is offered by CT. These encouraging results need to be confirmed in a larger study.

Multiparametric Analysis of Cell-Free DNA in Melanoma Patients

Cell-free DNA in blood (cfDNA) represents a promising biomarker for cancer diagnosis. Total cfDNA concentration showed a scarce discriminatory power between patients and controls. A higher specificity in cancer diagnosis can be achieved by detecting tumor specific alterations in cfDNA, such as DNA integrity, genetic and epigenetic modifications.The aim of the present study was to identify a sequential multi-marker panel in cfDNA able to increase the predictive capability in the diagnosis of cutaneous melanoma in comparison with each single marker alone. To this purpose, we tested total cfDNA concentration, cfDNA integrity, BRAFV600E mutation and RASSF1A promoter methylation associated to cfDNA in a series of 76 melanoma patients and 63 healthy controls. The chosen biomarkers were assayed in cfDNA samples by qPCR. Comparison of biomarkers distribution in cases and controls was performed by a logistic regression model in both univariate and multivariate analysis. The predictive capability of each logistic model was investigated by means of the area under the ROC curve (AUC). To aid the reader to interpret the value of the AUC, values between 0.6 and 0.7, between 0.71 and 0.8 and greater than 0.8 were considered as indicating a weak predictive, satisfactory and good predictive capacity, respectively. The AUC value for each biomarker (univariate logistic model) was weak/satisfactory ranging between 0.64 (BRAFV600E) to 0.85 (total cfDNA). A good overall predictive capability for the final logistic model was found with an AUC of 0.95. The highest predictive capability was given by total cfDNA (AUC:0.86) followed by integrity index 180/67 (AUC:0.90) and methylated RASSF1A (AUC:0.89).An approach based on the simultaneous determination of three biomarkers (total cfDNA, integrity index 180/67 and methylated RASSF1A) could improve the diagnostic performance in melanoma.

An optimal tumor marker group-coupled artificial neural network for diagnosis of lung cancer

Background Epidemiological statistics has shown that there are approximately 1.2 million new cases of lung cancer diagnosed every year and the death rate of these patients is 17.8%. Earlier diagnosis is key to promote the five-year survival rate of these cancer patients. Some tumor markers have been found to be valuable for earlier diagnosis, but a single marker has limitation in its sensitivity and specificity of cancer diagnosis. To improve the efficiency of diagnosis, several distinct tumor marker groups are combined together using a mathematical evaluation model, called artificial neural network (ANN). Lung cancer markers have been identified to include carcinoembryonic antigen, carcinoma antigen 125, neuron specific enolase, β 2-microglobulin, gastrin, soluble interleukin-6 receptor, sialic acid, pseudouridine, nitric oxide, and some metal ions. Methods These tumor markers were measured through distinct experimental procedures in 50 patients with lung cancer, 40 patients with benign lung diseases, and 50 cases for a normal control group. The most valuable were selected into an optimal tumor marker group by multiple logistic regression analysis. The optimal marker group-coupled ANN model was employed as an intelligent diagnosis system. Results We have presented evidence that this system is superior to a traditional statistical method, its diagnosis specificity significantly improved from 72.0% to 100.0% and its accuracy increased from 71.4% to 92.8%. Conclusions The ANN-based system may provide a rapid and accurate diagnosis tool for lung cancer.

Multi-modality CADx: ROC Study of the Effect on Radiologists' Accuracy in Characterizing Breast Masses on Mammograms and 3D Ultrasound Images

To investigate the effect of a computer-aided diagnosis (CADx) system on radiologists' performance in discriminating malignant and benign masses on mammograms and three-dimensional (3D) ultrasound (US) images. Our dataset contained mammograms and 3D US volumes from 67 women (median age, 51; range: 27-86) with 67 biopsy-proven breast masses (32 benign and 35 malignant). A CADx system was designed to automatically delineate the mass boundaries on mammograms and the US volumes, extract features, and merge the extracted features into a multi-modality malignancy score. Ten experienced readers (subspecialty academic breast imaging radiologists) first viewed the mammograms alone, and provided likelihood of malignancy (LM) ratings and Breast Imaging and Reporting System assessments. Subsequently, the reader viewed the US images with the mammograms, and provided LM and action category ratings. Finally, the CADx score was shown and the reader had the opportunity to revise the ratings. The LM ratings were analyzed using receiver-operating characteristic (ROC) methodology, and the action category ratings were used to determine the sensitivity and specificity of cancer diagnosis. Without CADx, readers' average area under the ROC curve, A(z), was 0.93 (range, 0.86-0.96) for combined assessment of the mass on both the US volume and mammograms. With CADx, their average A(z) increased to 0.95 (range, 0.91-0.98), which was borderline significant (P = .05). The average sensitivity of the readers increased from 98% to 99% with CADx, while the average specificity increased from 27% to 29%. The change in sensitivity with CADx did not achieve statistical significance for the individual radiologists, and the change in specificity was statistically significant for one of the radiologists. A well-trained CADx system that combines features extracted from mammograms and US images may have the potential to improve radiologists' performance in distinguishing malignant from benign breast masses and making decisions about biopsies.

A diagnostic evaluation of serum human telomerase reverse transcriptase mRNA as a novel tumor marker for gynecologic malignancies

Human telomerase reverse transcriptase (hTERT) and epidermal growth factor receptor (EGFR) play an important role in many cancers including gynecological cancers. We previously reported the usefulness of a quantitative highly sensitive detection method for hTERT mRNA in the serum of cancer patients. By this method, we attempted to elucidate the diagnostic evaluation of serum hTERT mRNA for gynecologic malignancies. In 174 female patients with gynecological lesions (47 with ovarian lesions, 63 with uterine lesions, 2 with malignancies in other gynecological lesions, and 62 benign lesions) and 20 healthy individuals, we measured serum hTERT mRNA and EGFR mRNA by using the newly developed real-time quantitative RT-PCR. We examined their sensitivity and specificity in cancer diagnosis, clinical significance in comparison with conventional tumor markers, and their correlations with the clinical parameters by using multivariate analyses. Serum hTERT mRNA showed higher values in patients with gynecologic cancers than in those with benign diseases and healthy individuals. The hTERT mRNA level independently correlated with the presence of cancers (P=0.004 for both ovarian and uterine cancer) and clinical stage (P<0.001). The sensitivity and specificity of hTERT mRNA in cancer diagnosis was 74.4% and 74.1%, respectively. The hTERT mRNA level showed a significant correlation with CA125 by Pearson's relative test (P=0.035) and with histological findings in ovarian cancer by the Friedman test (P<0.004). EGFR mRNA did not display any differences between the diseases. hTERT mRNA is useful for diagnosing gynecologic cancer and is superior to conventional tumor markers. Therefore, serum hTERT mRNA is a novel and available biomarker for gynecologic malignancies.